專利名稱：治療和診斷肺癌的組合物和方法
技術(shù)領(lǐng)域：
本發(fā)明總地涉及癌癥如肺癌的治療和診斷。本發(fā)明更特別涉及包含至少一部分肺腫瘤蛋白的多肽，以及編碼這種多肽的多核苷酸。這種多肽和多核苷酸可用于診斷和治療肺癌的藥物組合物如疫苗，和其它組合物中。發(fā)明背景肺癌是美國男性和女性癌癥死亡的主要原因，1994年報(bào)道了估計(jì)172,000個(gè)新病例。不考慮診斷時(shí)疾病病期，所有肺癌患者的五年存活率僅為13％。這與疾病仍限于局部時(shí)就被查出的病例中46％的五年存活率形成對比。然而，僅有16％的肺癌在疾病播散前被發(fā)現(xiàn)。
早期檢測困難，因?yàn)槌３？床坏脚R床癥狀，直至疾病已經(jīng)達(dá)到進(jìn)展階段。目前，使用胸部X線，分析痰中所含細(xì)胞的類型和支氣管纖維鏡檢查來輔助診斷。治療方案由癌癥的類型和分期來決定，包括手術(shù)、放射治療和/或化療。盡管對疾病的治療進(jìn)行了大量研究，肺癌仍難以治療。
因此，本領(lǐng)域仍需要用于肺癌的改進(jìn)疫苗、治療方法和診斷技術(shù)。發(fā)明概述一方面，本發(fā)明提供了包含選自下組的序列的多核苷酸組合物(a)SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583提供的序列；(b)SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583提供的序列的互補(bǔ)物；
(c)由SEQ ID N0217-390，392，394，396，398-420，422-424，428-433和440-583提供的序列中至少20個(gè)連續(xù)殘基組成的序列；(d)在中等嚴(yán)格條件下，與SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583提供的序列雜交的序列；(e)與SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583的序列具有至少75％同一性的序列；(f)與SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583的序列具有至少90％同一性的序列和(g)SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583提供的序列的簡并變異體。
在一個(gè)優(yōu)選實(shí)施方案中，所測肺腫瘤樣本中至少大約20％，更優(yōu)選至少大約30％，最優(yōu)選至少大約50％表達(dá)本發(fā)明的多核苷酸組合物，其水平比正常組織高至少大約2倍，優(yōu)選至少大約5倍，最優(yōu)選至少大約10倍。
本發(fā)明在另一個(gè)方面提供了包含由上述多核苷酸序列編碼的氨基酸序列的多肽組合物。
在具體實(shí)施方案中，本發(fā)明提供了包含選自SEQ ID NO391，393，395，397，421，425-427，434-439和584-587所示序列的氨基酸序列的多肽組合物。
在某些優(yōu)選實(shí)施方案中，本發(fā)明的多肽和/或多核苷酸具有免疫原性，即它們能夠引起免疫應(yīng)答，特別是體液和/或細(xì)胞免疫應(yīng)答，如本文進(jìn)一步描述。
本發(fā)明進(jìn)一步提供了所公開的多肽和/或多核苷酸序列的片段、變異體和/或衍生物，其中片段、變異體和/或衍生物優(yōu)選其免疫原活性水平為SEQ ID NOs391，393，395，397，421，425-427，434-439和584-587所示多肽序列或由SEQ ID NOs217-390，392，394，396，398-420，422-424，428-433和440-583所示多核苷酸序列編碼的多肽序列的免疫原活性水平的至少大約50％，優(yōu)選至少大約70％和更優(yōu)選至少大約90％。
本發(fā)明進(jìn)一步提供了編碼上述多肽的多核苷酸、包含這種多核苷酸的表達(dá)載體和用這種表達(dá)載體轉(zhuǎn)化或轉(zhuǎn)染的宿主細(xì)胞。
在其它方面中，本發(fā)明提供了包括如上所述的多肽或多核苷酸和生理學(xué)可接受載體的藥物組合物。
本發(fā)明的相關(guān)方面中，提供藥物組合物如疫苗組合物用于預(yù)防或治療應(yīng)用。這種組合物通常包括本發(fā)明的免疫原性多肽或多核苷酸和免疫刺激劑，如佐劑。
本發(fā)明進(jìn)一步提供了藥物組合物，包括(a)與本發(fā)明的多肽特異性結(jié)合的抗體或其抗原結(jié)合片段，或其片段；和(b)生理學(xué)可接受載體。
在其它方面中，本發(fā)明提供了藥物組合物，包括(a)表達(dá)上述多肽的抗原呈遞細(xì)胞和(b)藥學(xué)可接受載體或賦形劑。示例的抗原呈遞細(xì)胞包括樹突細(xì)胞、巨噬細(xì)胞、單核細(xì)胞、成纖維細(xì)胞和B細(xì)胞。
在相關(guān)的方面中，提供了藥物組合物，包括(a)表達(dá)上述多肽的抗原呈遞細(xì)胞和(b)免疫刺激劑。
在其它方面，本發(fā)明進(jìn)一步提供了包括至少一種上述多肽的融合蛋白，以及編碼這種融合蛋白的多核苷酸，典型地以藥物組合物的形式，如疫苗組合物，包括生理學(xué)可接受載體和/或免疫刺激劑。融合蛋白可以包括多個(gè)免疫原性多肽或其部分/變異體，如這里所述，并可以進(jìn)一步包括一個(gè)或多個(gè)利于多肽表達(dá)、純化和/或免疫原性的多肽片段。
在進(jìn)一步的方面中，本發(fā)明提供了刺激患者免疫應(yīng)答，優(yōu)選人類患者T細(xì)胞應(yīng)答的方法，包括給予這里所述的藥物組合物?；颊呖梢灶净挤伟?，這種情況下，該方法用于治療疾病，或可以預(yù)防性地治療被認(rèn)為具有患這種疾病風(fēng)險(xiǎn)的患者。
在其它方面中，本發(fā)明提供了抑制患者癌癥發(fā)展的方法，包括給患者施用上述藥物組合物。所述患者可以患有肺癌，此時(shí)該方法用于治療疾病，或被認(rèn)為具有患此病風(fēng)險(xiǎn)的患者可以進(jìn)行預(yù)防性治療。
在其它方面中，本發(fā)明進(jìn)一步提供了從生物樣本中去除腫瘤細(xì)胞的方法，包括使生物樣本接觸與本發(fā)明的多肽特異性反應(yīng)的T細(xì)胞，其中接觸步驟在足以允許從樣本中去除表達(dá)所述蛋白的細(xì)胞的條件下實(shí)施足夠長時(shí)間。
在相關(guān)方面中，提供了抑制患者癌癥發(fā)展的方法，包括給患者施用如上所述處理的生物樣本。
在其它方面中，進(jìn)一步提供了刺激和/或擴(kuò)充對本發(fā)明多肽特異性的T細(xì)胞的方法，包括使T細(xì)胞接觸下列一個(gè)或多個(gè)物質(zhì)(i)上述的多肽；(ii)編碼這種多肽的多核苷酸；和/或(iii)表達(dá)這種多肽的抗原呈遞細(xì)胞；接觸的條件和時(shí)間足以允許刺激和/或擴(kuò)充T細(xì)胞。也提供了包括如上所述制備的T細(xì)胞的分離的T細(xì)胞群。
在進(jìn)一步的方面中，本發(fā)明提供了抑制患者癌癥發(fā)展的方法，包括給患者施用有效量的上述T細(xì)胞群。
本發(fā)明進(jìn)一步提供了抑制患者癌癥發(fā)展的方法，包括以下步驟(a)將從患者分離的CD4+和/或CD8+T細(xì)胞與下列一種或多種物質(zhì)共同培養(yǎng)(i)至少包括這里公開的多肽的免疫原性部分的多肽；(ii)編碼這種多肽的多核苷酸；和(iii)表達(dá)這種多肽的抗原呈遞細(xì)胞；和(b)給患者施用有效量的增殖T細(xì)胞，從而抑制患者癌癥的進(jìn)展。增殖細(xì)胞可以但勿需在給予患者前進(jìn)行克隆。
在進(jìn)一步的方面中，本發(fā)明提供了確定患者存在或不存在癌癥，優(yōu)選肺癌的方法，包括(a)使從患者得到的生物樣本接觸與如上列舉的多肽結(jié)合的結(jié)合劑；(b)檢測樣本中與結(jié)合劑結(jié)合的多肽的量；和(c)比較多肽的量和預(yù)確定的截?cái)嘀?，從而確定患者存在或不存在癌癥。在優(yōu)選的實(shí)施方案中，結(jié)合劑是抗體，更優(yōu)選單克隆抗體。
在其它方面中，本發(fā)明還提供了監(jiān)測患者癌癥進(jìn)展的方法。這種方法包括以下步驟(a)使從患者得到的生物樣本在第一時(shí)間點(diǎn)接觸與如上列舉的多肽結(jié)合的結(jié)合劑；(b)檢測樣本中與結(jié)合劑結(jié)合的多肽的量；(c)用從患者得到的生物樣本在隨后的時(shí)間點(diǎn)重復(fù)步驟(a)和(b)；和(d)比較步驟(c)中檢測的多肽量和步驟(b)中檢測的量，從而監(jiān)測患者癌癥的進(jìn)展。
在其它方面中，本發(fā)明進(jìn)一步提供了確定患者存在或不存在癌癥的方法，包括以下步驟(a)使從患者得到的生物樣本接觸與編碼本發(fā)明多肽的多核苷酸雜交的寡核苷酸；(b)檢測樣本中與寡核苷酸雜交的多核苷酸優(yōu)選mRNA的水平；和(c)比較與寡核苷酸雜交的多核苷酸水平和預(yù)確定的截?cái)嘀?，從而確定患者存在或不存在癌癥。在某些實(shí)施方案中，使用例如至少一條與編碼如上列舉的多肽的多核苷酸或這種多核苷酸的互補(bǔ)物雜交的寡核苷酸引物，通過聚合酶鏈?zhǔn)椒磻?yīng)檢測mRNA的量。在其它實(shí)施方案中，利用與編碼如上列舉的多肽的多核苷酸或這種多核苷酸的互補(bǔ)物雜交的寡核苷酸探針，使用雜交技術(shù)檢測mRNA的量。
在相關(guān)方面，提供了監(jiān)測患者癌癥進(jìn)展的方法，包括以下步驟(a)使從患者得到的生物樣本接觸與編碼本發(fā)明多肽的多核苷酸雜交的寡核苷酸；(b)檢測樣本中與寡核苷酸雜交的多核苷酸的量；(c)用在后來的時(shí)間點(diǎn)從患者得到的生物樣本重復(fù)步驟(a)和(b)；和(d)比較步驟(c)中檢測的多核苷酸量和步驟(b)中檢測的量，從而監(jiān)測患者癌癥的進(jìn)展。
在進(jìn)一步的方面中，本發(fā)明提供了與上述的多肽結(jié)合的抗體，例如單克隆抗體，以及包括這種抗體的診斷試劑盒。也提供了包含一種或多種上述寡核苷酸探針或引物的診斷試劑盒。
參考下列詳細(xì)描述，本發(fā)明的這些和其它方面將變得明顯。這里公開的所有參考文獻(xiàn)以其整體引入作為參考，正如每篇被單獨(dú)引入一樣。序列標(biāo)識SEQ ID NO1是L363C1.cons的cDNA測定序列SEQ ID NO2是L263C2.cons的cDNA測定序列SEQ ID NO3是L263C2c的cDNA測定序列SEQ ID NO4是L263C1.cons的cDNA測定序列SEQ ID NO5是L263C1b的cDNA測定序列SEQ ID NO6是L164C2.cons的cDNA測定序列SEQ ID NO7是L164C1.cons的cDNA測定序列SEQ ID NO8是L366C1a的cDNA測定序列SEQ ID NO9是L260C1.cons的cDNA測定序列SEQ ID NO10是L163C1c的cDNA測定序列SEQ ID NO11是L163C1b的cDNA測定序列SEQ ID NO12是L255C1.cons的cDNA測定序列SEQ ID NO13是L255C1b的cDNA測定序列SEQ ID NO14是L355C1.cons的cDNA測定序列SEQ ID NO15是L366C1.cons的cDNA測定序列SEQ ID NO16是L163C1a的cDNA測定序列SEQ ID NO17是LT86-1的cDNA測定序列SEQ ID NO18是LT86-2的cDNA測定序列SEQ ID NO19是LT86-3的cDNA測定序列SEQ ID NO20是LT86-4的cDNA測定序列SEQ ID NO21是LT86-5的cDNA測定序列SEQ ID NO22是LT86-6的cDNA測定序列SEQ ID NO23是LT86-7的cDNA測定序列SEQ ID NO24是LT86-8的cDNA測定序列SEQ ID NO25是LT86-9的cDNA測定序列SEQ ID NO26是LT86-10的cDNA測定序列SEQ ID NO27是LT86-11的cDNA測定序列SEQ ID NO28是LT86-12的cDNA測定序列SEQ ID NO29是LT86-13的cDNA測定序列SEQ ID NO30是LT86-14的cDNA測定序列SEQ ID NO31是LT86-15的cDNA測定序列SEQ ID NO32是LT86-1的預(yù)測氨基酸序列SEQ ID NO33是LT86-2的預(yù)測氨基酸序列SEQ ID NO34是LT86-3的預(yù)測氨基酸序列SEQ ID NO35是LT86-4的預(yù)測氨基酸序列SEQ ID NO36是LT86-5的預(yù)測氨基酸序列SEQ ID NO37是LT86-6的預(yù)測氨基酸序列SEQ ID NO38是LT86-7的預(yù)測氨基酸序列SEQ ID NO39是LT86-8的預(yù)測氨基酸序列SEQ ID NO40是LT86-9的預(yù)測氨基酸序列SEQ ID NO41是LT86-10的預(yù)測氨基酸序列SEQ ID NO42是LT86-11的預(yù)測氨基酸序列SEQ ID NO43是LT86-12的預(yù)測氨基酸序列SEQ ID NO44是LT86-13的預(yù)測氨基酸序列SEQ ID NO45是LT86-14的預(yù)測氨基酸序列SEQ ID NO46是LT86-15的預(yù)測氨基酸序列SEQ ID NO47是(dT)12AG引物SEQ ID NO48是引物SEQ ID NO49是L86S-3的5’cDNA測定序列SEQ ID NO50是L86S-12的5’cDNA測定序列SEQ ID NO51是L86S-16的5’cDNA測定序列SEQ ID NO52是L86S-25的5’cDNA測定序列SEQ ID NO53是L86S-36的5’cDNA測定序列SEQ ID NO54是L86S-40的5’cDNA測定序列SEQ ID NO55是L86S-46的5’cDNA測定序列SEQ ID NO56是L86S-3的預(yù)測氨基酸序列SEQ ID NO57是L86S-12的預(yù)測氨基酸序列SEQ ID NO58是L86S-16的預(yù)測氨基酸序列SEQ ID NO59是L86S-25的預(yù)測氨基酸序列SEQ ID NO60是L86S-36的預(yù)測氨基酸序列SEQ ID NO61是L86S-40的預(yù)測氨基酸序列SEQ ID NO62是L86S-46的預(yù)測氨基酸序列SEQ ID NO63是L86S-30的5’cDNA測定序列SEQ ID NO64是L86S-41的5’cDNA測定序列SEQ ID NO65是從LT86-95’末端的推測氨基酸序列SEQ ID NO66是LT86-4的延伸cDNA測定序列SEQ ID NO67是LT86-4的預(yù)測延伸氨基酸序列SEQ ID NO68是LT86-20的5’cDNA測定序列SEQ ID NO69是LT86-21的3’cDNA測定序列SEQ ID NO70是LT86-22的5’cDNA測定序列SEQ ID NO71是LT86-26的5’cDNA測定序列SEQ ID NO72是LT86-27的5’cDNA測定序列SEQ ID NO73是LT86-20的預(yù)測氨基酸序列SEQ ID NO74是LT86-21的預(yù)測氨基酸序列SEQ ID NO75是LT86-22的預(yù)測氨基酸序列SEQ ID NO76是LT86-26的預(yù)測氨基酸序列SEQ ID NO77是LT86-27的預(yù)測氨基酸序列SEQ ID NO78是L86S-12的延伸cDNA測定序列SEQ ID NO79是L86S-36的延伸cDNA測定序列SEQ ID NO80是L86S-46的延伸cDNA測定序列SEQ ID NO81是L86S-12的預(yù)測延伸氨基酸序列SEQ ID NO82是L86S-36的預(yù)測延伸氨基酸序列SEQ ID NO83是L86S-46的預(yù)測延伸氨基酸序列SEQ ID NO84是L86S-6的5’cDNA測定序列SEQ ID NO85是L86S-11的5’cDNA測定序列SEQ ID NO86是L86S-14的5’cDNA測定序列SEQ ID NO87是L86S-29的5’cDNA測定序列SEQ ID NO88是L86S-34的5’cDNA測定序列SEQ ID NO89是L86S-39的5’cDNA測定序列SEQ ID NO90是L86S-47的5’cDNA測定序列SEQ ID NO91是L86S-49的5’cDNA測定序列SEQ ID NO92是L86S-51的5’cDNA測定序列SEQ ID NO93是L86S-6的預(yù)測氨基酸序列SEQ ID NO94是L86S-11的預(yù)測氨基酸序列SEQ ID NO95是L86S-14的預(yù)測氨基酸序列SEQ ID NO96是L86S-29的預(yù)測氨基酸序列SEQ ID NO97是L86S-34的預(yù)測氨基酸序列SEQ ID NO98是L86S-39的預(yù)測氨基酸序列SEQ ID NO99是L86S-47的預(yù)測氨基酸序列SEQ ID NO100是L86S-49的預(yù)測氨基酸序列SEQ ID NO101是L86S-51的預(yù)測氨基酸序列SEQ ID NO102是SLT-T1的DNA測定序列SEQ ID NO103是SLT-T2的5’cDNA測定序列SEQ ID NO104是SLT-T3的5’cDNA測定序列SEQ ID NO105是SLT-T5的5’cDNA測定序列SEQ ID NO106是SLT-T7的5’cDNA測定序列SEQ ID NO107是SLT-T9的5’cDNA測定序列SEQ ID NO108是SLT-T10的5’cDNA測定序列SEQ ID NO109是SLT-T11的5’cDNA測定序列SEQ ID NO110是SLT-T12的5’cDNA測定序列SEQ ID NO111是SLT-T1的預(yù)測氨基酸序列SEQ ID NO112是SLT-T2的預(yù)測氨基酸序列SEQ ID NO113是SLT-T3的預(yù)測氨基酸序列SEQ ID NO114是SLT-T10的預(yù)測氨基酸序列SEQ ID NO115是SLT-T12的預(yù)測氨基酸序列SEQ ID NO116是SALT-T3的5’cDNA測定序列SEQ ID NO117是SALT-T4的5’cDNA測定序列SEQ ID NO118是SALT-T7的5’cDNA測定序列SEQ ID NO119是SALT-T8的5’cDNA測定序列SEQ ID NO120是SALT-T9的5’cDNA測定序列SEQ ID NO121是SALT-T3的預(yù)測氨基酸序列SEQ ID NO122是SALT-T4的預(yù)測氨基酸序列SEQ ID NO123是SALT-T7的預(yù)測氨基酸序列SEQ ID NO124是SALT-T8的預(yù)測氨基酸序列SEQ ID NO125是SALT-T9的預(yù)測氨基酸序列SEQ ID NO126是PSLT-1的cDNA測定序列SEQ ID NO127是PSLT-2的cDNA測定序列SEQ ID NO128是PSLT-7的cDNA測定序列SEQ ID NO129是PSLT-13的cDNA測定序列SEQ ID NO130是PSLT-27的cDNA測定序列SEQ ID NO131是PSLT-28的cDNA測定序列SEQ ID NO132是PSLT-30的cDNA測定序列SEQ ID NO133是PSLT-40的cDNA測定序列SEQ ID NO134是PSLT-69的cDNA測定序列SEQ ID NO135是PSLT-71的cDNA測定序列SEQ ID NO136是PSLT-73的cDNA測定序列SEQ ID NO137是PSLT-79的cDNA測定序列SEQ ID NO138是PSLT-03的cDNA測定序列SEQ ID NO139是PSLT-09的cDNA測定序列SEQ ID NO140是PSLT-011的cDNA測定序列SEQ ID NO141是PSLT-041的cDNA測定序列SEQ ID NO142是PSLT-62的cDNA測定序列SEQ ID NO143是PSLT-6的cDNA測定序列SEQ ID NO144是PSLT-37的cDNA測定序列SEQ ID NO145是PSLT-74的cDNA測定序列SEQ ID NO146是PSLT-010的cDNA測定序列SEQ ID NO147是PSLT-012的cDNA測定序列SEQ ID NO148是PSLT-037的cDNA測定序列SEQ ID NO149是SAL-3的5’cDNA測定序列SEQ ID NO150是SAL-24的5’cDNA測定序列SEQ ID NO151是SAL-25的5’cDNA測定序列SEQ ID NO152是SAL-33的5’cDNA測定序列SEQ ID NO153是SAL-50的5’cDNA測定序列SEQ ID NO154是SAL-57的5’cDNA測定序列SEQ ID NO155是SAL-66的5’cDNA測定序列SEQ ID NO156是SAL-82的5’cDNA測定序列SEQ ID NO157是SAL-99的5’cDNA測定序列SEQ ID NO158是SAL-104的5’cDNA測定序列SEQ ID NO159是SAL-109的5’cDNA測定序列SEQ ID NO160是SAL-5的5’cDNA測定序列SEQ ID NO161是SAL-8的5’cDNA測定序列SEQ ID NO162是SAL-12的5’cDNA測定序列SEQ ID NO163是SAL-14的5’cDNA測定序列SEQ ID NO164是SAL-16的5’cDNA測定序列SEQ ID NO165是SAL-23的5’cDNA測定序列SEQ ID NO166是SAL-26的5’cDNA測定序列SEQ ID NO167是SAL-29的5’cDNA測定序列SEQ ID NO168是SAL-32的5’cDNA測定序列SEQ ID NO169是SAL-39的5’cDNA測定序列SEQ ID NO170是SAL-42的5’cDNA測定序列SEQ ID NO171是SAL-43的5’cDNA測定序列SEQ ID NO172是SAL-44的5’cDNA測定序列SEQ ID NO173是SAL-48的5’cDNA測定序列SEQ ID NO174是SAL-68的5’cDNA測定序列SEQ ID NO175是SAL-72的5’cDNA測定序列SEQ ID NO176是SAL-77的5’cDNA測定序列SEQ ID NO177是SAL-86的5’cDNA測定序列SEQ ID NO178是SAL-88的5’cDNA測定序列SEQ ID NO179是SAL-93的5’cDNA測定序列SEQ ID NO180是SAL-100的5’cDNA測定序列SEQ ID NO181是SAL-105的5’cDNA測定序列SEQ ID NO182是SAL-3的預(yù)測氨基酸序列SEQ ID NO183是SAL-24的預(yù)測氨基酸序列SEQ ID NO184是SAL-25的第一預(yù)測氨基酸序列SEQ ID NO185是SAL-25的第二預(yù)測氨基酸序列SEQ ID NO186是SAL-33的預(yù)測氨基酸序列SEQ ID NO187是SAL-50的第一預(yù)測氨基酸序列SEQ ID NO188是SAL-57的預(yù)測氨基酸序列SEQ ID NO189是SAL-66的第一預(yù)測氨基酸序列SEQ ID NO190是SAL-66的第二預(yù)測氨基酸序列SEQ ID NO191是SAL-82的預(yù)測氨基酸序列SEQ ID NO192是SAL-99的預(yù)測氨基酸序列SEQ ID NO193是SAL-104的預(yù)測氨基酸序列SEQ ID NO194是SAL-5的預(yù)測氨基酸序列SEQ ID NO195是SAL-8的預(yù)測氨基酸序列SEQ ID NO196是SAL-12的預(yù)測氨基酸序列SEQ ID NO197是SAL-14的預(yù)測氨基酸序列SEQ ID NO198是SAL-16的預(yù)測氨基酸序列SEQ ID NO199是SAL-23的預(yù)測氨基酸序列SEQ ID NO200是SAL-26的預(yù)測氨基酸序列SEQ ID NO201是SAL-29的預(yù)測氨基酸序列SEQ ID NO202是SAL-32的預(yù)測氨基酸序列SEQ ID NO203是SAL-39的預(yù)測氨基酸序列SEQ ID NO204是SAL-42的預(yù)測氨基酸序列SEQ ID NO205是SAL-43的預(yù)測氨基酸序列SEQ ID NO206是SAL-44的預(yù)測氨基酸序列SEQ ID NO207是SAL-48的預(yù)測氨基酸序列SEQ ID NO208是SAL-68的預(yù)測氨基酸序列SEQ ID NO209是SAL-72的預(yù)測氨基酸序列SEQ ID NO210是SAL-77的預(yù)測氨基酸序列SEQ ID NO211是SAL-86的預(yù)測氨基酸序列SEQ ID NO212是SAL-88的預(yù)測氨基酸序列SEQ ID NO213是SAL-93的預(yù)測氨基酸序列SEQ ID NO214是SAL-100的預(yù)測氨基酸序列SEQ ID NO215是SAL-105的預(yù)測氨基酸序列SEQ ID NO216是SAL-50的第二預(yù)測氨基酸序列SEQ ID NO217是SSLT-4的cDNA測定序列SEQ ID NO218是SSLT-9的cDNA測定序列SEQ ID NO219是SSLT-10的cDNA測定序列SEQ ID NO220是SSLT-12的cDNA測定序列SEQ ID NO221是SSLT-19的cDNA測定序列SEQ ID NO222是SSLT-31的cDNA測定序列SEQ ID NO223是SSLT-38的cDNA測定序列SEQ ID NO224是LT4690-2的cDNA測定序列SEQ ID NO225是LT4690-3的cDNA測定序列SEQ ID NO226是LT4690-22的cDNA測定序列SEQ ID NO227是LT4690-24的cDNA測定序列SEQ ID NO228是LT4690-37的cDNA測定序列SEQ ID NO229是LT4690-39的cDNA測定序列SEQ ID NO230是LT4690-40的cDNA測定序列SEQ ID NO231是LT4690-41的cDNA測定序列SEQ ID NO232是LT4690-49的cDNA測定序列SEQ ID NO233是LT4690-55的3’cDNA測定序列SEQ ID NO234是LT4690-55的5’cDNA測定序列SEQ ID NO235是LT4690-59的cDNA測定序列SEQ ID NO236是LT4690-63的cDNA測定序列SEQ ID NO237是LT4690-71的cDNA測定序列SEQ ID NO238是2LT-3的cDNA測定序列SEQ ID NO239是2LT-6的cDNA測定序列SEQ ID NO240是2LT-22的cDNA測定序列SEQ ID NO241是2LT-25的cDNA測定序列SEQ ID NO242是2LT-26的cDNA測定序列SEQ ID NO243是2LT-31的cDNA測定序列SEQ ID NO244是2LT-36的cDNA測定序列SEQ ID NO245是2LT-42的cDNA測定序列SEQ ID NO246是2LT-44的cDNA測定序列SEQ ID NO247是2LT-54的cDNA測定序列SEQ ID NO248是2LT-55的cDNA測定序列SEQ ID NO249是2LT-57的cDNA測定序列SEQ ID NO250是2LT-58的cDNA測定序列SEQ ID NO251是2LT-59的cDNA測定序列SEQ ID NO252是2LT-62的cDNA測定序列SEQ ID NO253是2LT-63的cDNA測定序列SEQ ID NO254是2LT-65的cDNA測定序列SEQ ID NO255是2LT-66的cDNA測定序列SEQ ID NO256是2LT-70的cDNA測定序列SEQ ID NO257是2LT-73的cDNA測定序列SEQ ID NO258是2LT-74的cDNA測定序列SEQ ID NO259是2LT-76的cDNA測定序列SEQ ID NO260是2LT-77的cDNA測定序列SEQ ID NO261是2LT-78的cDNA測定序列SEQ ID NO262是2LT-80的cDNA測定序列SEQ ID NO263是2LT-85的cDNA測定序列SEQ ID NO264是2LT-87的cDNA測定序列SEQ ID NO265是2LT-89的cDNA測定序列SEQ ID NO266是2LT-94的cDNA測定序列SEQ ID NO267是2LT-95的cDNA測定序列SEQ ID NO268是2LT-98的cDNA測定序列SEQ ID NO269是2LT-100的cDNA測定序列SEQ ID NO270是2LT-103的cDNA測定序列SEQ ID NO271是2LT-105的cDNA測定序列SEQ ID NO272是2LT-107的cDNA測定序列SEQ ID NO273是2LT-108的cDNA測定序列SEQ ID NO274是2LT-109的cDNA測定序列SEQ ID NO275是2LT-118的cDNA測定序列SEQ ID NO276是2LT-120的cDNA測定序列SEQ ID NO277是2LT-121的cDNA測定序列SEQ ID NO278是2LT-122的cDNA測定序列SEQ ID NO279是2LT-124的cDNA測定序列SEQ ID NO280是2LT-126的cDNA測定序列SEQ ID NO281是2LT-127的cDNA測定序列SEQ ID NO282是2LT-128的cDNA測定序列SEQ ID NO283是2LT-129的cDNA測定序列SEQ ID NO284是2LT-133的cDNA測定序列SEQ ID NO285是2LT-137的cDNA測定序列SEQ ID NO286是LT4690-71的cDNA測定序列SEQ ID NO287是LT4690-82的cDNA測定序列SEQ ID NO288是SSLT-74的全長cDNA測定序列SEQ ID NO289是SSLT-78的cDNA測定序列SEQ ID NO290是SCC1-8的cDNA測定序列SEQ ID NO291是SCC1-12的cDNA測定序列SEQ ID NO292是SCC1-336的cDNA測定序列SEQ ID NO293是SCC1-344的cDNA測定序列SEQ ID NO294是SCC1-345的cDNA測定序列SEQ ID NO295是SCC1-346的cDNA測定序列SEQ ID NO296是SCC1-348的cDNA測定序列SEQ ID NO297是SCC1-350的cDNA測定序列SEQ ID NO298是SCC1-352的cDNA測定序列SEQ ID NO299是SCC1-354的cDNA測定序列SEQ ID NO300是SCC1-355的cDNA測定序列SEQ ID NO301是SCC1-356的cDNA測定序列SEQ ID NO302是SCC1-357的cDNA測定序列SEQ ID NO303是SCC1-501的cDNA測定序列SEQ ID NO304是SCC1-503的cDNA測定序列SEQ ID NO305是SCC1-513的cDNA測定序列SEQ ID NO306是SCC1-516的cDNA測定序列SEQ ID NO307是SCC1-518的cDNA測定序列SEQ ID NO308是SCC1-519的cDNA測定序列SEQ ID NO309是SCC1-522的cDNA測定序列SEQ ID NO310是SCC1-523的cDNA測定序列SEQ ID NO311是SCC1-525的cDNA測定序列SEQ ID NO312是SCC1-527的cDNA測定序列SEQ ID NO313是SCC1-529的cDNA測定序列SEQ ID NO314是SCC1-530的cDNA測定序列SEQ TD NO315是SCC1-531的cDNA測定序列SEQ ID NO316是SCC1-532的cDNA測定序列SEQ ID NO317是SCC1-533的cDNA測定序列SEQ ID NO318是SCC1-536的cDNA測定序列SEQ ID NO319是SCC1-538的cDNA測定序列SEQ ID NO320是SCC1-539的cDNA測定序列SEQ ID NO321是SCC1-541的cDNA測定序列SEQ ID NO322是SCC1-542的cDNA測定序列SEQ ID NO323是SCC1-546的cDNA測定序列SEQ ID NO324是SCC1-549的cDNA測定序列SEQ ID NO325是SCC1-551的cDNA測定序列SEQ ID NO326是SCC1-552的cDNA測定序列SEQ ID NO327是SCC1-554的cDNA測定序列SEQ ID NO328是SCC1-558的cDNA測定序列SEQ ID NO329是SCC1-559的cDNA測定序列SEQ ID NO330是SCC1-561的cDNA測定序列SEQ ID NO331是SCC1-562的cDNA測定序列SEQ ID NO332是SCC1-564的cDNA測定序列SEQ ID NO333是SCC1-565的cDNA測定序列SEQ ID NO334是SCC1-566的cDNA測定序列SEQ ID NO335是SCC1-567的cDNA測定序列SEQ ID NO336是SCC1-568的cDNA測定序列SEQ ID NO337是SCC1-570的cDNA測定序列SEQ ID NO338是SCC1-572的cDNA測定序列SEQ ID NO339是SCC1-575的cDNA測定序列SEQ ID NO340是SCC1-576的cDNA測定序列SEQ ID NO341是SCC1-577的cDNA測定序列SEQ ID NO342是SCC1-578的cDNA測定序列SEQ ID NO343是SCC1-582的cDNA測定序列SEQ ID NO344是SCC1-583的cDNA測定序列SEQ ID NO345是SCC1-586的cDNA測定序列SEQ ID NO346是SCC1-588的cDNA測定序列SEQ ID NO347是SCC1-590的cDNA測定序列SEQ ID NO348是SCC1-591的cDNA測定序列SEQ ID NO349是SCC1-592的cDNA測定序列SEQ ID NO350是SCC1-593的cDNA測定序列SEQ ID NO351是SCC1-594的cDNA測定序列SEQ ID NO352是SCC1-595的cDNA測定序列SEQ ID NO353是SCC1-596的cDNA測定序列SEQ ID NO354是SCC1-598的cDNA測定序列SEQ ID NO355是SCC1-599的cDNA測定序列SEQ ID NO356是SCC1-602的cDNA測定序列SEQ ID NO357是SCC1-604的cDNA測定序列SEQ ID NO358是SCC1-605的cDNA測定序列SEQ ID NO359是SCC1-606的cDNA測定序列SEQ ID NO360是SCC1-607的cDNA測定序列SEQ ID NO361是SCC1-608的cDNA測定序列SEQ ID NO362是SCC1-610的cDNA測定序列SEQ ID NO363是克隆DMS79T1的cDNA測定序列SEQ ID NO364是克隆DMS79T2的cDNA測定序列SEQ ID NO365是克隆DMS79T3的cDNA測定序列SEQ ID NO366是克隆DMS79T5的cDNA測定序列SEQ ID NO367是克隆DMS79T6的cDNA測定序列SEQ ID NO368是克隆DMS79T7的cDNA測定序列SEQ ID NO369是克隆DMS79T9的cDNA測定序列SEQ ID NO370是克隆DMS79T10的cDNA測定序列SEQ ID NO371是克隆DMS79T11的cDNA測定序列SEQ ID NO372是克隆128T1的cDNA測定序列SEQ ID NO373是克隆128T2的cDNA測定序列SEQ ID NO374是克隆128T3的cDNA測定序列SEQ ID NO375是克隆128T4的cDNA測定序列SEQ ID NO376是克隆128T5的cDNA測定序列SEQ ID NO377是克隆128T7的cDNA測定序列SEQ ID NO378是克隆128T9的cDNA測定序列SEQ ID NO379是克隆128T10的cDNA測定序列SEQ ID NO380是克隆128T11的cDNA測定序列SEQ ID NO381是克隆128T12的cDNA測定序列SEQ ID NO382是克隆NCIH69T3的cDNA測定序列SEQ-ID NO383是克隆NCIH69T5的cDNA測定序列SEQ ID NO384是克隆NCIH69T6的cDNA測定序列SEQ ID NO385是克隆NCIH69T7的cDNA測定序列SEQ ID NO386是克隆NCIH69T9的cDNA測定序列SEQ ID NO387是克隆NCIH69T10的cDNA測定序列SEQ ID NO388是克隆NCIH69T11的cDNA測定序列SEQ ID NO389是克隆NCIH69T12的cDNA測定序列SEQ ID NO390是128T1的全長cDNA序列SEQ ID NO391是128T1的氨基酸序列SEQ ID NO392是2LT-128的全長cDNA序列SEQ ID NO393是2LT-128的氨基酸序列SEQ ID NO394是克隆SCC1-542的延伸cDNA序列SEQ ID NO395是對應(yīng)于SEQ ID NO394的氨基酸序列SEQ ID NO396是克隆SCC1-593的延伸cDNA序列SEQ ID NO397是對應(yīng)于SEQ ID NO396的氨基酸序列SEQ ID NO398是55508.1的cDNA測定序列SEQ ID NO399是55509.1的cDNA測定序列SEQ ID NO400是54243.1的cDNA測定序列SEQ ID NO401是54251.1的cDNA測定序列SEQ ID NO402是54252.1的cDNA測定序列SEQ ID NO403是54253.1的cDNA測定序列SEQ ID NO404是55518.1的cDNA測定序列SEQ ID NO405是54258.1的cDNA測定序列SEQ ID NO406是54575.1的cDNA測定序列SEQ ID NO407是54577.1的cDNA測定序列SEQ ID NO408是54584.1的cDNA測定序列SEQ ID NO409是55521.1的cDNA測定序列SEQ ID NO410是54589.1的cDNA測定序列SEQ ID NO411是54592.1的cDNA測定序列SEQ ID NO412是55134.1的cDNA測定序列SEQ ID NO413是55137.1的cDNA測定序列SEQ ID NO414是55140.1的cDNA測定序列SEQ ID NO415是55531.1的cDNA測定序列SEQ ID NO416是55532.1的cDNA測定序列SEQ ID NO417是54621.1的cDNA測定序列SEQ ID NO418是55548.1的cDNA測定序列SEQ ID NO419是54623.1的cDNA測定序列SEQ ID NO420是L39的cDNA測定序列SEQ ID NO421是L39的預(yù)測氨基酸序列SEQ ID NO422是SCC2-29的cDNA測定序列SEQ ID-NO423是SCC2-36的cDNA測定序列SEQ ID NO424是SCC2-60的cDNA測定序列SEQ ID NO425是SCC2-29的預(yù)測氨基酸序列SEQ ID NO426是SCC2-36的預(yù)測氨基酸序列SEQ ID NO427是SCC2-60的預(yù)測氨基酸序列SEQ ID NO428是克隆20129的延伸cDNA序列，所述克隆也即SEQ ID NO238中的2LT-3SEQ ID NO429是克隆20347的延伸cDNA序列，所述克隆也即SEQ ID NO242中的2LT-26SEQ ID NO430是克隆21282的延伸cDNA序列，所述克隆也即SEQ ID NO249中的2LT-57SEQ ID NO431是克隆21283的延伸cDNA序列，所述克隆也即SEQ ID NO250中的2LT-58SEQ ID NO432是克隆21484的延伸cDNA序列，所述克隆也即SEQ ID NO268中的2LT-98SEQ ID NO433是克隆21871的延伸cDNA序列，所述克隆也即SEQ ID NO279中的2LT-124SEQ ID NO434是由SEQ ID NO428編碼的氨基酸序列SEQ ID NO435是由SEQ ID NO429編碼的氨基酸序列SEQ ID NO436是由SEQ ID NO430編碼的氨基酸序列SEQ ID NO437是由SEQ ID NO431編碼的氨基酸序列SEQ ID NO438是由SEQ ID NO432編碼的氨基酸序列SEQ ID NO439是由SEQ ID NO433編碼的氨基酸序列SEQ ID NO440是克隆19A4的cDNA測定序列SEQ ID NO441是克隆14F10的全長cDNA測定序列SEQ ID NO442是克隆20E10的5’cDNA測定序列SEQ ID NO443是克隆55153的第一cDNA測定序列SEQ ID NO444是克隆55153的第二cDNA測定序列SEQ ID NO445是克隆55154的第一cDNA測定序列SEQ ID NO446是克隆55154的第二cDNA測定序列SEQ ID NO447是克隆55155的cDNA測定序列SEQ ID NO448是克隆55156的第一cDNA測定序列SEQ ID NO449是克隆55156的第二cDNA測定序列SEQ ID NO450是克隆55157的第一cDNA測定序列SEQ ID NO451是克隆55157的第二cDNA測定序列SEQ ID NO452是克隆55158的cDNA測定序列SEQ ID NO453是克隆55159的cDNA測定序列SEQ ID NO454是克隆55161的第一cDNA測定序列SEQ ID NO455是克隆55161的第二cDNA測定序列SEQ ID NO456是克隆55162的第一cDNA測定序列SEQ ID NO457是克隆55162的第二cDNA測定序列SEQ ID NO458是克隆55163的第一cDNA測定序列SEQ ID NO459是克隆55163的第二cDNA測定序列SEQ ID NO460是克隆55164的第一cDNA測定序列SEQ ID NO461是克隆55164的第二cDNA測定序列SEQ ID NO462是克隆55165的第一cDNA測定序列SEQ ID NO463是克隆55165的第二cDNA測定序列SEQ ID NO464是克隆55166的第一cDNA測定序列SEQ ID NO465是克隆55166的第二cDNA測定序列SEQ ID NO466是克隆55167的第一cDNA測定序列SEQ ID NO467是克隆55167的第二cDNA測定序列SEQ ID NO468是克隆55168的第一cDNA測定序列SEQ ID NO469是克隆55168的第二cDNA測定序列SEQ ID NO470是克隆55169的第一cDNA測定序列SEQ ID NO471是克隆55169的第二cDNA測定序列SEQ ID NO472是克隆55170的第一cDNA測定序列SEQ ID NO473是克隆55170的第二cDNA測定序列SEQ ID NO474是克隆55171的cDNA測定序列SEQ ID NO475是克隆55172的cDNA測定序列SEQ ID NO476是克隆55173的cDNA測定序列SEQ ID NO477是克隆55174的第一cDNA測定序列SEQ ID NO478是克隆55174的第二cDNA測定序列SEQ ID NO479是克隆55175的cDNA測定序列SEQ ID NO480是克隆55176的cDNA測定序列SEQ ID NO481是重疊群525的cDNA測定序列SEQ ID NO482是重疊群526的cDNA測定序列SEQ ID NO483是重疊群527的cDNA測定序列SEQ ID NO484是重疊群528的cDNA測定序列SEQ ID NO485是重疊群529的cDNA測定序列SEQ ID NO486是重疊群530的cDNA測定序列SEQ ID NO487是重疊群531的cDNA測定序列SEQ ID NO488是重疊群532的cDNA測定序列SEQ ID NO489是重疊群533的cDNA測定序列SEQ ID NO490是重疊群534的cDNA測定序列SEQ ID NO491是重疊群535的cDNA測定序列SEQ ID NO492是重疊群536的cDNA測定序列SEQ ID NO493是重疊群537的cDNA測定序列SEQ ID NO494是重疊群538的cDNA測定序列SEQ ID NO495是重疊群539的cDNA測定序列SEQ ID NO496是重疊群540的cDNA測定序列SEQ ID NO497是重疊群541的cDNA測定序列SEQ ID NO498是重疊群542的cDNA測定序列SEQ ID NO499是重疊群543的cDNA測定序列SEQ ID NO500是重疊群544的cDNA測定序列SEQ ID NO501是重疊群545的cDNA測定序列SEQ ID NO502是重疊群546的cDNA測定序列SEQ ID NO503是重疊群547的cDNA測定序列SEQ ID NO504是重疊群548的cDNA測定序列SEQ ID NO505是重疊群549的cDNA測定序列SEQ ID NO506是重疊群550的cDNA測定序列SEQ ID NO507是重疊群551的cDNA測定序列SEQ ID NO508是重疊群552的cDNA測定序列SEQ ID NO509是重疊群553的cDNA測定序列SEQ ID NO510是重疊群554的cDNA測定序列SEQ ID NO511是重疊群555的cDNA測定序列SEQ-ID NO512是克隆57207的cDNA測定序列SEQ ID NO513是克隆57209的cDNA測定序列SEQ ID NO514是克隆57210的cDNA測定序列SEQ ID NO515是克隆57211的cDNA測定序列SEQ ID NO516是克隆57212的cDNA測定序列SEQ ID NO517是克隆57213的cDNA測定序列SEQ ID NO518是克隆57215的cDNA測定序列SEQ ID NO519是克隆57219的cDNA測定序列SEQ ID NO520是克隆57221的cDNA測定序列SEQ ID NO521是克隆57222的cDNA測定序列SEQ ID NO522是克隆57223的cDNA測定序列SEQ ID NO523是克隆57225的cDNA測定序列SEQ ID NO524是克隆57227的cDNA測定序列SEQ ID NO525是克隆57228的cDNA測定序列SEQ ID NO526是克隆57229的cDNA測定序列SEQ ID NO527是克隆57230的cDNA測定序列SEQ ID NO528是克隆57231的cDNA測定序列SEQ ID NO529是克隆57232的cDNA測定序列SEQ ID NO530是克隆57233的cDNA測定序列SEQ ID NO531是克隆57234的cDNA測定序列SEQ ID NO532是克隆57235的cDNA測定序列SEQ ID NO533是克隆57236的cDNA測定序列SEQ ID NO534是克隆57237的cDNA測定序列SEQ ID NO535是克隆57238的cDNA測定序列SEQ ID NO536是克隆57239的cDNA測定序列SEQ ID NO537是克隆57240的cDNA測定序列SEQ ID-NO538是克隆57242的cDNA測定序列SEQ ID NO539是克隆57243的cDNA測定序列SEQ ID NO540是克隆57245的cDNA測定序列SEQ ID NO541是克隆57248的cDNA測定序列SEQ ID NO542是克隆57249的cDNA測定序列SEQ ID NO543是克隆57250的cDNA測定序列SEQ ID NO544是克隆57251的cDNA測定序列SEQ ID NO545是克隆57253的cDNA測定序列SEQ ID NO546是克隆57254的cDNA測定序列SEQ ID NO547是克隆57255的cDNA測定序列SEQ ID NO548是克隆57257的cDNA測定序列SEQ ID NO549是克隆57258的cDNA測定序列SEQ ID NO550是克隆57259的cDNA測定序列SEQ ID NO551是克隆57261的cDNA測定序列SEQ ID NO552是克隆57262的cDNA測定序列SEQ ID NO553是克隆57263的cDNA測定序列SEQ ID NO554是克隆57264的cDNA測定序列SEQ ID NO555是克隆57265的cDNA測定序列SEQ ID NO556是克隆57266的cDNA測定序列SEQ ID NO557是克隆57267的cDNA測定序列SEQ ID NO558是克隆57268的cDNA測定序列SEQ ID NO559是克隆57269的cDNA測定序列SEQ ID NO560是克隆57270的cDNA測定序列SEQ ID NO561是克隆57271的cDNA測定序列SEQ ID NO562是克隆57272的cDNA測定序列SEQ ID NO563是克隆57274的cDNA測定序列SEQ ID NO564是克隆57275的cDNA測定序列’SEQ ID NO565是克隆57277的cDNA測定序列SEQ ID NO566是克隆57280的cDNA測定序列SEQ ID NO567是克隆57281的cDNA測定序列SEQ ID NO568是克隆57282的cDNA測定序列SEQ ID NO569是克隆57283的cDNA測定序列SEQ ID NO570是克隆57285的cDNA測定序列SEQ ID NO571是克隆57287的cDNA測定序列SEQ ID NO572是克隆57288的cDNA測定序列SEQ ID NO573是克隆57289的cDNA測定序列SEQ ID NO574是克隆57290的cDNA測定序列SEQ ID NO575是克隆57292的cDNA測定序列SEQ ID NO576是克隆57295的cDNA測定序列SEQ ID NO577是克隆57296的cDNA測定序列SEQ ID NO578是克隆57297的cDNA測定序列SEQ ID NO579是克隆57299的cDNA測定序列SEQ ID NO580是克隆57301的cDNA測定序列SEQ ID NO581是克隆57302的cDNA測定序列SEQ ID NO582是肺腫瘤特異性T細(xì)胞受體β鏈的cDNA測定序列SEQ ID NO583是肺腫瘤特異性T細(xì)胞受體α鏈的cDNA測定序列SEQ ID NO584是由SEQ ID NO583編碼的氨基酸序列SEQ ID NO585是由SEQ ID NO582編碼的氨基酸序列SEQ ID NO586是由14F10的5’末端編碼的氨基酸序列SEQ ID NO587是SEQ ID NO586中所述包含的T細(xì)胞表位的氨基酸序列。發(fā)明詳述本發(fā)明總地涉及組合物及其在癌癥特別是肺癌的治療和診斷中的應(yīng)用。如下進(jìn)一步的描述，本發(fā)明的示例組合物包括但不限于多肽，特別是免疫原性多肽，編碼這種多肽的多核苷酸，抗體和其它結(jié)合劑，抗原呈遞細(xì)胞(APCs)和免疫系統(tǒng)細(xì)胞(如T細(xì)胞)。
除非有反向特別指示，本發(fā)明的實(shí)踐將采用本領(lǐng)域技術(shù)內(nèi)的病毒學(xué)、免疫學(xué)、微生物學(xué)、分子生物學(xué)和重組DNA技術(shù)的常規(guī)方法，其中許多在下面進(jìn)行描述作為示例。這種技術(shù)在文獻(xiàn)中有完整解釋。參見例如Sambrook等，Molecular CloningA Laboratory Manual(第二版，1989)；Maniatis等，Molecular CloningALaboratory Manual(1982)；DNA CloningA PracticalApproach，vol.I & II(D.Glover主編)；OligonucleotideSynthesis(N.Gait主編，1984)；Nucleic Acid Hybridization(B.Hames & S.Higgins主編，1985)；Transcription andTranslation(B.Hames & S.Higgins主編，1984)；Animal CellCulture(R.Freshney主編，1986)；Perbal，A Practical Guideto Molecular Cloning(1984)。
這里引用的所有出版物、專利和專利申請，無論前述或后述，在此都以其完整形式引入作為參考。
如本說明書和所附權(quán)利要求中的使用，單數(shù)形式的“一(個(gè))”和“這(個(gè))”包括復(fù)數(shù)引用，除非內(nèi)容清楚指出不是這樣。多肽組合物這里使用的術(shù)語“多肽”使用其常規(guī)意思，即作為一序列的氨基酸。多肽不限于特定長度的產(chǎn)物；因此，肽、寡肽和蛋白都包括在多肽的定義中，這種術(shù)語在這里可以互換使用，除非特別指明。這個(gè)術(shù)語也不指或排除多肽的表達(dá)后修飾，例如，糖基化、乙?；?、磷酸化等等，以及本領(lǐng)域所知的其它修飾，包括自然發(fā)生和非自然發(fā)生的。多肽可以是完整蛋白或其子序列。本發(fā)明內(nèi)容中特別感興趣的多肽是包含表位即抗原決定簇的氨基酸序列，所述表位實(shí)質(zhì)上產(chǎn)生多肽的免疫原特性并能夠激發(fā)免疫應(yīng)答。
本發(fā)明特別示例的多肽包括那些由SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583中任何一個(gè)所示的多核苷酸序列編碼的多肽，或在中等嚴(yán)格條件下或可供選擇地在高度嚴(yán)格條件下，與SEQ ID NOs217-390，392，394，396，398-420，422-424，428-433和440-583中任何一個(gè)所示的多核苷酸序列雜交的序列所編碼的多肽。本發(fā)明的某些其它示例多肽包括如SEQID NO391，393，395，397，421，425-427，434-439和584-587中任何一個(gè)所示的氨基酸序列。
本發(fā)明的多肽有時(shí)在這里是指肺腫瘤蛋白或肺腫瘤多肽，表示它們的鑒定至少部分基于其在肺腫瘤樣本中的表達(dá)水平增加。因此，“肺腫瘤多肽”或肺腫瘤蛋白”一般是指本發(fā)明的多肽序列，或編碼這種多肽的多核苷酸序列，它們在相當(dāng)大部分的肺腫瘤樣本中表達(dá)，例如占所檢測的肺腫瘤樣本的優(yōu)選高于大約20％，更優(yōu)選大約高于30％，最優(yōu)選高于大約50％或更多，其水平比正常組織中表達(dá)水平高至少兩倍，優(yōu)選至少五倍，如采用這里提供的代表試驗(yàn)所測定。本發(fā)明的肺腫瘤多肽序列，基于其在腫瘤細(xì)胞中表達(dá)水平的增加，在作為診斷標(biāo)記以及治療靶中特別有用，如下進(jìn)一步描述。
在某些優(yōu)選實(shí)施方案中，本發(fā)明的多肽是免疫原性的，即它們在免疫測定(如ELISA或T細(xì)胞刺激試驗(yàn))中可檢測到地與來自肺癌患者的抗血清和/或T細(xì)胞發(fā)生反應(yīng)?？梢允褂帽绢I(lǐng)域技術(shù)人員熟知的技術(shù)實(shí)施免疫原性的篩選。例如，可以使用如Harlow和Lane，AntibodiesA Labora-tory Manual，Cold Spring HarborLaboratory，1988中描述的方法進(jìn)行這種篩選。在一個(gè)示例的實(shí)施例中，多肽可以固定在固相支持體上并接觸患者血清以允許血清中的抗體與固定的多肽結(jié)合。然后可以去除未結(jié)合的血清并使用例如125I標(biāo)記的蛋白A檢測結(jié)合的抗體。
如本領(lǐng)域技術(shù)人員將認(rèn)識到的，這里公開的多肽的免疫原性部分也包含在本發(fā)明中。這里所用的“免疫原性部分”是本發(fā)明免疫原性多肽的片段，其本身可與識別多肽的B細(xì)胞和/或T細(xì)胞表面抗原受體發(fā)生免疫學(xué)反應(yīng)(即特異性結(jié)合)。免疫原性部分通?？梢允褂檬熘夹g(shù)來鑒定，例如Paul，F(xiàn)undamental Immunology，3rd ed.，243-247(Raven Press，1993)和這里引用的參考文獻(xiàn)所總結(jié)的。這種技術(shù)包括篩選多肽與抗原特異性抗體、抗血清和/或T細(xì)胞系或克隆反應(yīng)的能力。這里使用的抗血清和抗體如果它們與抗原特異性結(jié)合(即它們在ELISA或其它免疫測定中與蛋白反應(yīng)，且不與無關(guān)蛋白發(fā)生可檢測到的反應(yīng))，則是抗原特異性的”。
在一個(gè)優(yōu)選實(shí)施方案中，本發(fā)明多肽的免疫原性部分是與抗血清和/或T細(xì)胞以基本不低于全長多肽的反應(yīng)性(如在ELISA和/或T細(xì)胞反應(yīng)性測定中)的水平發(fā)生反應(yīng)的部分。優(yōu)選，免疫原性部分的免疫原性水平是全長多肽免疫原性的至少大約50％，優(yōu)選至少大約70％和最優(yōu)選大于大約90％。在有些情況下，所鑒定的優(yōu)選的免疫原性部分具有的免疫原性水平高于相應(yīng)的全長多肽，如具有高于大約100％或150％或更高的免疫原性。
在某些其它實(shí)施方案中，示例的免疫原性部分可以包括已缺失N末端前導(dǎo)序列和/或跨膜結(jié)構(gòu)域的肽。其它示例的免疫原性部分相對于成熟蛋白，將含有小的N和/或C末端缺失(如1-30個(gè)氨基酸，優(yōu)選5-15個(gè)氨基酸)。
在另一個(gè)實(shí)施方案中，本發(fā)明的多肽組合物還可以包括一種或多種與針對本發(fā)明多肽而產(chǎn)生的T細(xì)胞和/或抗體發(fā)生免疫學(xué)反應(yīng)的多肽，特別是具有這里公開的氨基酸序列的多肽，或其免疫原性片段或變異體。
在本發(fā)明的另一個(gè)實(shí)施方案中，提供的多肽包含一種或多種能夠引發(fā)與這里描述的一種或多種多肽發(fā)生免疫學(xué)反應(yīng)的T細(xì)胞和/或抗體的多肽，或一種或多種由這里公開的多核苷酸序列中包含的連續(xù)核酸序列，或其免疫原性片段或變異體，或與這些序列的一個(gè)或多個(gè)在中等至高度嚴(yán)格條件下雜交的一個(gè)或多個(gè)核酸序列所編碼的多肽。
在另一個(gè)方面，本發(fā)明提供了多肽片段，包括這里列舉的多肽組合物，例如SEQ ID NO391，393，395，397，421，425-427，434-439和584-587列舉的那些多肽或由SEQ ID NO217-390，392，394，396，398-420，422-424，428-433和440-583的序列中列舉的多核苷酸序列編碼的那些多肽中至少大約5，10，15，20，25，50或100個(gè)連續(xù)氨基酸，或更多，包括所有中間長度。
在另一個(gè)方面，本發(fā)明提供了這里描述的多肽組合物的變異體。本發(fā)明通常包括的多肽變異體典型地顯示出與這里列舉的多肽序列沿其長度具有至少大約70％，75％，80％，85％，90％，91％，92％，93％，94％，95％，96％，97％，98％或99％或更高的同一性(如下所確定)。
在一個(gè)優(yōu)選實(shí)施方案中，本發(fā)明提供的多肽片段和變異體和與這里特別列舉的全長多肽反應(yīng)的抗體和/或T細(xì)胞發(fā)生免疫學(xué)反應(yīng)。
在另一個(gè)優(yōu)選實(shí)施方案中，本發(fā)明提供的多肽片段和變異體顯示出的免疫原性水平是這里特別列舉的全長多肽序列所顯示出的免疫原性的至少大約50％，優(yōu)選至少大約70％，最優(yōu)選至少大約90％或更高。
這里使用的術(shù)語多肽“變異體”是由一個(gè)或多個(gè)置換、缺失、添加和/或插入而典型不同于這里特別公開的多肽的多肽。這種變異體可以自然發(fā)生或可以合成產(chǎn)生，例如通過修飾一個(gè)或多個(gè)上述本發(fā)明的多肽序列并如這里所述和/或使用本領(lǐng)域熟知的大量技術(shù)中任何一種來評價(jià)其免疫原性。
例如，本發(fā)明多肽的某些示例變異體包括已去除了一個(gè)或多個(gè)部分，如N末端前導(dǎo)序列或跨膜結(jié)構(gòu)域的那些。其它示例變異體包括其中一小部分(如1-30個(gè)氨基酸，優(yōu)選5-15個(gè)氨基酸)已經(jīng)從成熟蛋白的N和/或C末端去除的那些。
在很多情況下，變異體含有保守置換?！氨Ｊ刂脫Q”是氨基酸被具有相似性能的另一個(gè)氨基酸置換，使得肽化學(xué)領(lǐng)域的技術(shù)人員預(yù)計(jì)該多肽的二級結(jié)構(gòu)和親水性基本不改變。如上所述，可以在本發(fā)明的多核苷酸和多肽結(jié)構(gòu)中進(jìn)行修飾，并仍得到一個(gè)編碼具有期望特性如免疫原特性的變異體或衍生多肽的功能性分子。當(dāng)期望改變多肽的氨基酸序列而產(chǎn)生等同物，或甚至本發(fā)明多肽的改進(jìn)的免疫原性變異體或部分時(shí)，本領(lǐng)域技術(shù)人員通常會根據(jù)表1改變DNA編碼序列的一個(gè)或多個(gè)密碼子。
例如，蛋白結(jié)構(gòu)中某些氨基酸可以被其它氨基酸置換，而不明顯喪失與如抗體的抗原結(jié)合區(qū)或底物分子上的結(jié)合位點(diǎn)這樣的結(jié)構(gòu)相互作用結(jié)合的能力。由于是蛋白的相互作用能力和性質(zhì)限定了蛋白的生物功能活性，可以對蛋白序列及其基礎(chǔ)的DNA編碼序列進(jìn)行某些氨基酸序列置換，而得到類似性能的蛋白。因此預(yù)期可在公開的組合物的肽序列中，或相應(yīng)的編碼所述肽的DNA序列中進(jìn)行各種改變，而不明顯喪失其生物實(shí)用性或活性。表1

在進(jìn)行這種改變時(shí)，可以考慮氨基酸的親水指數(shù)。賦予蛋白質(zhì)相互作用生物功能的親水氨基酸指數(shù)的重要性是本領(lǐng)域通常所知的(Kyte和Doolittle，1982，這里引入作為參考)。已接受氨基酸的相對親水特性有助于所得蛋白的二級結(jié)構(gòu)，其依次限定蛋白與其它分子如酶、底物、受體、DNA、抗體、抗原等等的相互作用?；谄涫杷院碗姾商匦?，每個(gè)氨基酸分別指定了親水指數(shù)(Kyte和Doolittle，1982)。這些值是異亮氨酸(+4.5)；纈氨酸(+4.2)；亮氨酸(+3.8)；苯丙氨酸(+2.8)；半胱氨酸/胱氨酸(+2.5)；蛋氨酸(+1.9)；丙氨酸(+1.8)；甘氨酸(-0.4)；蘇氨酸(-0.7)；絲氨酸(-0.8)；色氨酸(-0.9)；酪氨酸(-1.3)；脯氨酸(-1.6)；組氨酸(-3.2)；谷氨酸(-3.5)；谷氨酰胺(-3.5)；天冬氨酸(-3.5)；天冬酰胺(-3.5)；賴氨酸(-3.9)和精氨酸(-4.5)。
本領(lǐng)域已知某些氨基酸可以被其它具有相似親水指數(shù)或分值的氨基酸置換并仍產(chǎn)生具有相似生物活性的蛋白，即仍得到生物功能等同的蛋白。在進(jìn)行這種改變時(shí)，優(yōu)選親水指數(shù)在±2以內(nèi)的氨基酸的置換，特別優(yōu)選±1以內(nèi)的，甚至更優(yōu)選±0.5以內(nèi)的氨基酸。本領(lǐng)域也理解基于親水性可以有效進(jìn)行類似氨基酸的置換。美國專利4,554,101(這里以其完整形式特別引入作為參考)，陳述由其相鄰氨基酸的親水性控制的蛋白最大局部平均親水性與蛋白的生物性質(zhì)有關(guān)。
美國專利4,554,101詳述氨基酸殘基具有下列親水性值精氨酸(+3.0)；賴氨酸(+3.0)；天冬氨酸(+3.0±1)；谷氨酸(+3.0±1)；絲氨酸(+0.3)；天冬酰胺(+0.2)；谷氨酰胺(+0.2)；甘氨酸(0)；蘇氨酸(-0.4)；脯氨酸(-0.5±1)；丙氨酸(-0.5)；組氨酸(-0.5)；半胱氨酸(-1.0)；蛋氨酸(-1.3)；纈氨酸(-1.5)；亮氨酸(-1.8)；異亮氨酸(-1.8)；酪氨酸(-2.3)；苯丙氨酸(-2.5)；色氨酸(-3.4)。已理解氨基酸可以置換為另一個(gè)具有相似親水性值的氨基酸并仍得到生物等同物，特別是免疫學(xué)等同蛋白。在這種改變中，優(yōu)選親水性值在±2以內(nèi)的氨基酸的置換，特別優(yōu)選±1以內(nèi)的，甚至更優(yōu)選±0.5以內(nèi)的氨基酸。
如上面概括的，氨基酸置換因此通?；诎被醾?cè)鏈取代基的相對相似性，例如，它們的疏水性、親水性、電荷、大小等等?？紤]到各種前述特性的示范置換是本領(lǐng)域技術(shù)人員熟知的并包括精氨酸和賴氨酸；谷氨酸和天冬氨酸；絲氨酸和蘇氨酸；谷氨酰胺和天冬酰胺；和纈氨酸、亮氨酸和異亮氨酸。
此外，可以進(jìn)一步修飾任何多核苷酸來增加在體內(nèi)的穩(wěn)定性。可能的修飾包括但不限于在5’和/或3’末端添加側(cè)翼序列；在骨架中使用硫代磷酸或2’O-甲基，而不是磷酸二酯酶連接；和/或夾雜非常規(guī)堿基例如肌苷、queosine和wybutosine，以及乙酰基、甲基、硫代和其它修飾形式的腺嘌呤、胞苷、鳥嘌呤、胸腺嘧啶和尿苷。
可以基于殘基的極性、電荷、溶解度、疏水性、親水性和/或兩親性的相似性進(jìn)行氨基酸置換。例如，帶負(fù)電荷氨基酸包括天冬氨酸和谷氨酸；帶正電荷氨基酸包括賴氨酸和精氨酸；和具有相似親水性值的帶有不帶電荷極性頭基的氨基酸包括亮氨酸、異亮氨酸和纈氨酸；甘氨酸和丙氨酸；天冬酰胺和谷氨酰胺；和絲氨酸、蘇氨酸、苯丙氨酸和酪氨酸?？梢源肀Ｊ馗淖兊钠渌被峤M包括(1)ala，pro，gly，glu，asp，gln，asn，ser，thr；(2)cys，ser，tyr，thr；(3)val，ile，leu，met，ala，phe；(4)lys，arg，his；和(5)phe，tyr，trp，his。變異體也可以或可選擇地含有非保守改變。在優(yōu)選的實(shí)施方案中，變異多肽由于五個(gè)或更少氨基酸的置換、缺失或添加而不同于天然序列。變異體也可以(或可供選擇)被修飾，例如通過缺失或添加對多肽的免疫原性、二級結(jié)構(gòu)和親水性影響最小的氨基酸。
如上指出，多肽可以包括在蛋白的N末端的信號(或前導(dǎo))序列，其在共同翻譯時(shí)或在翻譯后指導(dǎo)蛋白轉(zhuǎn)移。多肽也可以與接頭或其它序列結(jié)合，以易于多肽的合成、純化或鑒定(如聚-His)，或增強(qiáng)多肽與固相支持體的結(jié)合。例如，多肽可以結(jié)合免疫球蛋白Fc區(qū)。
當(dāng)比較多肽序列時(shí)，如果如下所述進(jìn)行對比作最大對應(yīng)時(shí)兩個(gè)序列的氨基酸序列是相同的，則稱兩個(gè)序列“等同”。兩個(gè)序列之間的比較典型地是通過在對比窗口中比較序列以鑒定和比較局部區(qū)域的序列相似性來進(jìn)行。這里使用的“對比窗口”是指至少大約20個(gè)連續(xù)位點(diǎn)的片段，通常30至大約75，40至大約50，其中將兩個(gè)序列最佳比對后，序列可以與相同數(shù)目連續(xù)位點(diǎn)的參考序列進(jìn)行比較。
序列比較的最佳比對可以使用生物信息軟件Lasergene程序組的Megalign程序(DNASTAR，Inc.，Madison，WI)進(jìn)行，使用默認(rèn)參數(shù)。這個(gè)程序包含幾個(gè)比對方案，在下列參考文獻(xiàn)中描述Dayhoff，M.O.(1978)A model of evolutionary change in proteins-Matrices for detecting distant relationships.In Dayhoff，M.O.(ed.)Atlas of Protein Sequence and Structure，NationalBiomedical Research Foundation，Washington DC Vol.5，Suppl.3，pp.345-358；Hein J.(1990)Unified Approach toAlignment and Phylogenes 626-645頁Methods in Enzymology183卷，Academic Press，Inc.，San Diego，CA；Higgins，D.G.和Sharp，P.M.(1989)CABIOS 5151-153；Myers，E.W.和Muller W.(1988)，CABIOS 411-17；Robinson，E.D.(1971)Comb.Theor 11105；Santou，N.Nes，M.(1987)Mol.Biol.Evol.4406-425；Sneath，P.H.A.和Sokal，R.R.(1973)Numerical Taxonomy-the Principles and Practice ofNuyrierical Taxonomy，F(xiàn)reeman Press，San Francisco，CA；Wilbur，W.J.和Lipman，D.J.(1983)Proc.Natl.Acad.，Sci.USA 80726-730。
可供選擇地，實(shí)施序列比較的最佳比對可以通過Smith和Waterman(1981)Add.APL.Math 2482的局部同一性算法，Needleman和Wunsch(1970)J Mol.Biol.48443的同一性比對算法，Pearson和Lipman(1988)Proc.Natl.Acad.Sci.USA852444的檢索相似性法，這些算法的計(jì)算機(jī)化實(shí)施(Wisconsin-遺傳學(xué)軟件包中的GAP，BESTFIT，BLAST，F(xiàn)ASTA，和TFASTA，Genetics Computer Group(GCG)，575 Science Dr.，Madison，WI)，或通過視察。
一個(gè)適合確定序列同一性和序列相似性百分比的優(yōu)選算法例是BLAST和BLAST 2.0算法，分別在Altschul等(1977)Nucl.AcidsRes.253389-3402和Altschul等(1990)J.Mol.215403-410中描述?？梢允褂肂LAST和BLAST 2.0，例如用這里描述的參數(shù)，以確定本發(fā)明多核苷酸和多肽的序列同一性百分比。進(jìn)行BLAST分析的軟件通過National Center for Biotechnology Information公眾可以得到。對于氨基酸序列，可使用計(jì)分矩陣計(jì)算累積值。當(dāng)累積比對值從其最大得到值下降數(shù)量X；由于一個(gè)或多個(gè)負(fù)分值殘基比對的累積，累積值達(dá)到零或以下；或到達(dá)兩個(gè)序列中任何一個(gè)的末尾時(shí)，每個(gè)方向上字擊的延伸停止。BLAST算法參數(shù)W，T和X決定比對的敏感性和速度。
在一個(gè)優(yōu)選方法中，“序列同一性百分比”由在至少20個(gè)位點(diǎn)的對比窗口中比較兩個(gè)最佳比對的序列來決定，其中對比窗口中的多肽序列部分與兩個(gè)序列最佳比對的參考序列(不包含添加或缺失)相比，可以包含百分之20或更少的添加或缺失(即缺口)，通常百分之5至15，或百分之10至12。百分比的計(jì)算通過確定兩個(gè)序列中出現(xiàn)相同氨基酸殘基的位點(diǎn)數(shù)以得到匹配位點(diǎn)數(shù)，匹配位點(diǎn)數(shù)除以參考序列的位點(diǎn)總數(shù)(即窗口大小)，結(jié)果乘以100得到序列同一性百分比。
在其它示例實(shí)施方案中，多肽可以是融合多肽，其包括這里所述的多種多肽，或包括至少一種這里所述的多肽和一種無關(guān)序列，例如已知的腫瘤蛋白。融合配偶體可以例如協(xié)助提供T輔助表位(免疫學(xué)融合配偶體)，優(yōu)選人識別的T輔助表位，或可以協(xié)助蛋白以比天然重組蛋白更高的產(chǎn)量表達(dá)(表達(dá)增強(qiáng)子)。某些優(yōu)選融合配偶體同時(shí)是免疫學(xué)和表達(dá)增強(qiáng)融合配偶體?？梢赃x擇其它融合配偶體以增加多肽的溶解度或使多肽定向于期望的細(xì)胞內(nèi)區(qū)室。融合蛋白配偶體還包括親和標(biāo)記，其有利于多肽的純化。
通?？梢圆捎脴?biāo)準(zhǔn)技術(shù)制備融合蛋白，包括化學(xué)結(jié)合。優(yōu)選融合多肽作為重組多肽表達(dá)，使表達(dá)體系中產(chǎn)物水平相對于非融合多肽有所增加。簡言之，可以分開裝配編碼多肽成分的DNA序列，并連接到適當(dāng)?shù)谋磉_(dá)載體中。將編碼一個(gè)多肽成分的DNA序列3’端，用或不用肽接頭，與編碼第二個(gè)多肽成分的DNA序列5’端連接，使得序列的閱讀框架同相。這允許翻譯為保留兩個(gè)成分多肽的生物活性的單一融合多肽。
可以使用肽接頭序列以足以確保每個(gè)肽折疊成其二級和三級結(jié)構(gòu)的距離分隔第一個(gè)和第二個(gè)多肽成分。使用本領(lǐng)域熟知的標(biāo)準(zhǔn)技術(shù)將這種肽接頭序列引入融合多肽。合適的肽接頭序列可以基于下列因素選擇(1)其采用靈活的延伸構(gòu)象的能力；(2)其不采用與第一和第二個(gè)多肽上的功能表位相互作用的二級結(jié)構(gòu)的能力；和(3)缺乏可能與多肽功能表位反應(yīng)的疏水性或帶電荷殘基。優(yōu)選的肽接頭序列包括Gly，Asn和Ser殘基。其它近中性氨基酸，例如Thr和Ala也可以用于接頭序列中?？梢杂行в米鹘宇^的氨基酸序列包括那些在Maratea等，Gene 4039-46，1985；Murphy等，Proc.Natl.Acad.Sci.USA 838258-8262，1986；美國專利4,935,233和美國專利4,751,180中公開的序列。接頭序列長度通常可以從1至大約50個(gè)氨基酸。當(dāng)?shù)谝缓偷诙€(gè)多肽具有可用于分隔功能域并防止空間干擾的非必需N末端氨基酸區(qū)時(shí)，不需要接頭序列。
結(jié)合的DNA序列可操作連接合適的轉(zhuǎn)錄或翻譯調(diào)控元件。負(fù)責(zé)DNA表達(dá)的調(diào)控元件僅位于編碼第一個(gè)多肽的DNA序列的5’端。類似地，終止翻譯所需的終止密碼子和轉(zhuǎn)錄終止信號也僅在編碼第二個(gè)多肽的DNA序列的3’端出現(xiàn)。
融合多肽可以包括這里所述的多肽以及無關(guān)的免疫原性蛋白，例如能夠引發(fā)記憶應(yīng)答的免疫原性蛋白。這種蛋白的例子包括破傷風(fēng)、肺結(jié)核和肝炎蛋白(參見如Stoute等，New Engl.J.Med.，33686-91，1997)。
在一個(gè)優(yōu)選的實(shí)施方案中，免疫融合配偶體來自分枝桿菌屬，例如來自結(jié)核分枝桿菌的Ra12片段。Ra12組合物及其在增強(qiáng)異源多核苷酸/多肽序列的表達(dá)和/或免疫原性中的使用方法在美國專利申請60/158,585中描述，其內(nèi)容在這里以完整形式引入作為參考文獻(xiàn)。簡言之，Ra12是指結(jié)核分枝桿菌MTB32A核酸的子序列的多核苷酸區(qū)。MTB32A是結(jié)核分枝桿菌毒力株和無毒株的基因編碼的分子量32KD的絲氨酸蛋白酶。MTB32A核苷酸序列和氨基酸序列已經(jīng)公開(例如，美國專利申請60/158,585；也見，Skeiky等，Infectionand Immun.(1999)673998-4007，在此引入作為參考文獻(xiàn))。MTB32A編碼序列的C末端片段以高水平表達(dá)并在整個(gè)純化過程中保持為可溶性多肽。而且，Ra12可以增強(qiáng)與其融合的異源免疫原性多肽的免疫原性。一個(gè)優(yōu)選的Ra12融合多肽包括對應(yīng)MTB32A的氨基酸殘基192至323的14kD C末端片段。其它優(yōu)選的Ra12多核苷酸通常包括編碼Ra12多肽一部分的至少大約15個(gè)連續(xù)的核苷酸，至少大約30個(gè)核苷酸，至少大約60個(gè)核苷酸，至少大約100個(gè)核苷酸，至少大約200個(gè)核苷酸，或至少大約300個(gè)核苷酸。Ra12多核苷酸可以包括天然序列(即編碼Ra12多肽或其一部分的內(nèi)源性序列)或可以包括這種序列的變異體。Ra12多核苷酸變異體可以包含一個(gè)或多個(gè)置換、添加、缺失和/或插入，使得編碼的融合多肽的生物活性相對于含有天然Ra12多肽的融合多肽基本上不降低。優(yōu)選變異體顯示出與編碼天然Ra12多肽或其一部分的多核苷酸序列至少大約70％的同一性，更優(yōu)選至少大約80％的同一性和最優(yōu)選至少大約90％的同一性。
在其它優(yōu)選的實(shí)施方案中，免疫融合配偶體來自蛋白D-革蘭氏陰性細(xì)菌流感嗜血桿菌B的表面蛋白(WO 91/18926)。優(yōu) 選，蛋白D衍生物包括大約該蛋白的前三分之一(如最前的N末端100-110個(gè)氨基酸)，并且蛋白D衍生物可以脂化。在某些優(yōu)選的實(shí)施方案中，脂蛋白D融合配偶體的最前109個(gè)殘基包含在N末端，為多肽提供另外的外源T細(xì)胞表位和增加在大腸桿菌中的表達(dá)水平(因此起表達(dá)增強(qiáng)子的作用)。脂類尾部確保抗原向抗原呈遞細(xì)胞的最佳呈遞。其它融合配偶體包括來自流感病毒的非結(jié)構(gòu)蛋白，NS1(血凝素)。典型地，使用N末端81個(gè)氨基酸，盡管可以使用包括T輔助表位的不同片段。
在另一個(gè)實(shí)施方案中，免疫融合配偶體是已知的蛋白LYTA，或其一部分(優(yōu)選C末端部分)。LYTA來自肺炎鏈球菌，它合成稱為酰胺酶LYTA的N-乙?；?L-丙氨酸酰胺酶(由LytA基因編碼；Gene 43265-292，1986)。LYTA是特異性降解肽聚糖骨架中某些鍵的自溶素。LYTA蛋白C末端域負(fù)責(zé)與膽堿或一些膽堿類似物如DEAE的親和性。這個(gè)性能已被利用開發(fā)有效表達(dá)融合蛋白的大腸桿菌C-LYTA表達(dá)質(zhì)粒。在氨基末端含有C-LYTA片段的雜合蛋白的純化已經(jīng)有描述(見Biotechnology 10795-798，1992)。在一個(gè)優(yōu)選的實(shí)施方案中，LYTA的重復(fù)部分可以摻入融合多肽。發(fā)現(xiàn)重復(fù)部分在C末端區(qū)殘基178處開始。特別優(yōu)選的重復(fù)部分摻入殘基188-305。
另一個(gè)示例的實(shí)施方案包括融合多肽和編碼它們的多核苷酸，其中融合配偶體包括能夠指導(dǎo)多肽到內(nèi)體/溶酶體區(qū)室的引導(dǎo)信號，如美國專利5,633,234中所述。本發(fā)明的免疫多肽，當(dāng)與這個(gè)引導(dǎo)信號融合，將更高效與MHC II類分子結(jié)合并因此增強(qiáng)對多肽特異性的CD4+T細(xì)胞的體內(nèi)刺激。
使用任何各種熟知的合成和/或重組技術(shù)制備本發(fā)明的多肽，后者在下進(jìn)一步描述。通常小于大約150個(gè)氨基酸的多肽、其部分和其它變異體可以用合成裝置使用本領(lǐng)域普通技術(shù)人員熟知的技術(shù)而產(chǎn)生。在一個(gè)示例的實(shí)施例中，使用任何商業(yè)可獲得的固相技術(shù)合成這種多肽，如Merrifield固相合成方法，其中氨基酸循序添加到增長的氨基酸鏈。見Merrifield，J.Am.Chem.Soc.852149-2146，1963。多肽自動合成裝置可從供應(yīng)商通過商業(yè)購得，例如PerkinElmer/Applied BioSystems Division(Foster City，CA)，并可以根據(jù)制造商的用法說明進(jìn)行操作。
通常，本發(fā)明的多肽組合物(包括融合多肽)是分離的?！胺蛛x的”多肽是從其原始環(huán)境中分出的。例如，天然存在的蛋白或多肽如果與天然系統(tǒng)中部分或所有共存物質(zhì)分開的話便是分離的。優(yōu)選這種多肽還可以被純化，如，至少大約90％純，更優(yōu)選至少大約95％純和最優(yōu)選至少大約99％純。多核苷酸組合物在其它方面，本發(fā)明提供了多核苷酸組合物。使用的術(shù)語“DNA”和“多核苷酸”這里基本上可以互換，是指已經(jīng)從特定物種總基因組DNA分離出來的DNA分子。這里使用的“分離”是指基本上與其它編碼序列分離的多核苷酸，該DNA分子不合大部分的無關(guān)編碼DNA，例如大染色體片段或其它功能基因或多肽編碼區(qū)。當(dāng)然，這是指如原始分離的DNA分子，且不排除后來人工添加到片段上的基因或編碼區(qū)。
如本領(lǐng)域技術(shù)人員會理解的，本發(fā)明的多核苷酸組合物可以包括基因組序列，基因組外和質(zhì)粒編碼的序列，和表達(dá)或可以適應(yīng)于表達(dá)蛋白、多肽、肽等等的更小的改造基因片段。這種片段可以是天然分離的，或人工合成修飾的。
如本領(lǐng)域技術(shù)人員也將認(rèn)識到的，本發(fā)明的多核苷酸可以是單鏈(編碼或反義)或雙鏈，且可以是DNA(基因組、cDNA或合成的)或RNA分子。RNA分子可以包括HnRNA分子，它含有內(nèi)含子并與DNA分子一一對應(yīng)，和mRNA分子，它不含有內(nèi)含子。另外的編碼或非編碼序列可以，但不是必需，在本發(fā)明的多核苷酸中出現(xiàn)，多核苷酸可以，但不是必需，與其它分子和/或支持材料連接。
多核苷酸可以包括天然序列(即編碼本發(fā)明多肽/蛋白或其一部分的內(nèi)源性序列)或可以包括編碼變異體或衍生物的序列，優(yōu)選這種序列的免疫原性變異體或衍生物。
因此，根據(jù)本發(fā)明的另一個(gè)方面，提供的多核苷酸組合物包括部分或全部下列多核苷酸序列SEQ ID NO217-390，392，394，396，398-420 422-424，428-433和440-583任何一個(gè)所列舉的多核苷酸序列，SEQ ID NO217-390，392，394；396，398-420 422-424，428-433和440-583任何一個(gè)所列舉的多核苷酸序列的互補(bǔ)物，SEQID NO217-390，392，394，396，398-420 422-424，428-433和440-583任何一個(gè)所列舉的多核苷酸序列的簡并變異體。在某些優(yōu)選的實(shí)施方案中，這里列舉的多核苷酸序列編碼免疫原性多肽，如上所述。
在其它相關(guān)實(shí)施方案中，本發(fā)明提供了具有與這里公開的SEQ IDNO217-390，392，394，396，398-420 422-424，428-433和440-583序列具有相當(dāng)大同一性的多核苷酸變異體，例如使用這里描述的方法與本發(fā)明的多核苷酸序列相比(如使用標(biāo)準(zhǔn)參數(shù)進(jìn)行BLAST分析，如下所述)包括至少70％序列同一性，優(yōu)選至少75％，80％，85％，90％，95％，96％，97％，98％或99％或更高同一性。本領(lǐng)域技術(shù)人員將認(rèn)識到考慮到密碼子簡并性、氨基酸相似性、閱讀框架定位等等，可以適當(dāng)調(diào)整這些值以確定兩個(gè)核苷酸序列編碼的蛋白的相應(yīng)同一性。
典型地，多核苷酸變異體將含有一個(gè)或多個(gè)置換、添加、缺失和/或插入，優(yōu)選使得該變異體多核苷酸編碼的多肽的免疫原性相對于這里特別列舉的多核苷酸序列編碼的多肽基本上不降低。術(shù)語“變異體”也應(yīng)該理解為包含異種來源的同源基因。
在另外的實(shí)施方案中，本發(fā)明提供了多核苷酸片段，其包括各種長度的等同于或互補(bǔ)于一個(gè)或多個(gè)這里公開的序列的連續(xù)一段序列。例如，本發(fā)明提供的多核苷酸包括一個(gè)或多個(gè)這里公開的序列中至少大約10，15，20，30，40，50，75，100，150，200，300，400，500或1000或更多連續(xù)核苷酸以及它們之間的所有中間長度。很容易理解，在本文中，“中間長度”是指引用值之間的任何長度，例如16，17，18，19，等；21，22，23，等；30，31，32等；50，51，52，53等；100，101，102，103，等，150，151，152，153等；包括200-500；500-1,000間的所有整數(shù)等等。
在本發(fā)明的另一個(gè)實(shí)施方案中，提供的多核苷酸組合物能夠在中等至高度嚴(yán)格條件下與這里提供的多核苷酸序列或其片段或其互補(bǔ)序列雜交。雜交技術(shù)是分子生物學(xué)領(lǐng)域熟知的。為了闡明，檢測本發(fā)明多核苷酸與其它多核苷酸雜交的合適的中等嚴(yán)格條件包括在5×SSC，0.5％SDS，1.0mM EDTA(pH8.0)溶液中預(yù)洗；在50℃-60℃，5×SSC雜交過夜；隨后在65℃洗滌兩次，20分鐘，用各含0.1％SDS的2×，0.5×和0.2×SSC。本領(lǐng)域技術(shù)人員將理解雜交的嚴(yán)格性可很容易操縱，例如改變雜交溶液的鹽含量和/或進(jìn)行雜交的溫度。例如，在另一個(gè)實(shí)施方案中，合適的高度嚴(yán)格雜交條件包括上述的那些，除外雜交溫度升高，例如到60-65℃或65-70℃。
在某些優(yōu)選的實(shí)施方案中，上述多核苷酸，例如多核苷酸變異體、片段和雜交序列，編碼與這里特別列舉的多肽序列發(fā)生免疫交叉反應(yīng)的多肽。在其它優(yōu)選的實(shí)施方案中，這種多核苷酸編碼的多肽具有這里特別列舉的多肽序列的至少大約50％。優(yōu)選至少大約70％，和更優(yōu)選至少大約90％的免疫原性水平。
本發(fā)明的多核苷酸或其片段，不論編碼序列本身的長度，可以與其它DNA序列結(jié)合，例如啟動子、聚腺苷酸化信號、另外的限制性酶切位點(diǎn)、多克隆位點(diǎn)、其它編碼片段等等，使得它們的整個(gè)長度可以顯著變化。因此預(yù)期可以使用幾乎任何長度的核酸片段，總長度優(yōu)選由制備的容易程度和在期望的重組DNA方案中的使用來限制。例如，總長度大約10,000，大約5000，大約3000，大約2,000，大約1,000，大約500，大約200，大約100，大約50個(gè)堿基對等等(包括所有中間長度)的示例多核苷酸片段預(yù)期對本發(fā)明眾多實(shí)施有用。
當(dāng)比較多核苷酸序列時(shí)，如果最大對應(yīng)比對時(shí)兩個(gè)序列中的核苷酸序列是相同的，則兩個(gè)序列被稱為“等同”，如下所述。兩個(gè)序列之間的比較典型地是通過在對比窗口中比較序列以鑒定和比較局部區(qū)域的序列相似性來進(jìn)行。這里使用的“對比窗口”是指至少大約20個(gè)連續(xù)位點(diǎn)的片段，通常30至大約75，40至大約50，其中兩個(gè)序列最佳排列后，序列可以與相同數(shù)目連續(xù)位點(diǎn)的參考序列進(jìn)行比較。
用于比較的序列最佳比對可以使用生物信息軟件Lasergene程序組的Megalign程序(DNASTAR，Inc.，Madison，WI)進(jìn)行，使用默認(rèn)參數(shù)。這個(gè)程序包含幾個(gè)比對方案，在下列參考文獻(xiàn)中有所描述Dayhoff，M.O.(1978)A model of evolutionary change inproteins-Matrices for detecting distant relationships.InDayhoff，M.O.(ed.)Atlas of Protein Sequence andStructure，National Biomedical Research Foundation，Washington DC Vol.5，Suppl.3，pp.345-358；Hein J.(1990)Unified Approach to Alignment and Phylogenes 626-645頁Methods in Enzymology 183卷，Academic Press，Inc.，SanDiego，CA；Higgins，D.G.和Sharp，P.M.(1989)CABIOS 5151-153；Myers，E.W.和Muller W.(1988)CABIOS 411-17；Robinson，E.D.(1971)Comb.Theor 11105；Santou，N.Nes.M.(1987)Mol.Biol.Evol.4406-425；Sneath，P.H.A和Sokal，R.R.(1973)Numerical Taxonomy-the Principles and Practice of NumericalTaxonomy，F(xiàn)reeman Press，San Francisco，CA；Wilbur，W.J.和Lipman，D.J.(1983)Proc.Natl.Acad.，Sci.USA 80726-730。
可供選擇地，用于比較的序列最佳比對的實(shí)施可以通過Smith和Waterman(1981)Add.APL.Math 2482的局部同一性算法，Needleman和Wunsch(1970)J Mol.Biol.48443的同一性比對算法，Pearson和Lipman(1988)Proc.Natl.Acad.Sci.USA852444的相似性檢索法，這些算法的計(jì)算機(jī)化實(shí)施(Wisconsin-遺傳學(xué)軟件包中GAP，BESTFIT，BLAST，F(xiàn)ASTA，和TFASTA，Genetics Computer Group(GCG)，575 Science Dr.，Madison，WI)或通過視察。
適合確定序列同一性和序列相似性百分比的算法的一個(gè)優(yōu)選例子是BLAST和BLAST 2.0算法，分別在Altschul等(1977)Nucal.Acids Res.253389-3402和Altschul等(1990)J.Mol.Biol.215403-410中描述?？梢允褂肂LAST和BLAST 2.0，例如用這里描述的參數(shù)，以確定本發(fā)明多核苷酸的序列同一性百分比。進(jìn)行BLAST分析的軟件通過National Center for BiotechnologyInformation公眾可以得到。在一個(gè)示例實(shí)施例中，對于核苷酸序列，可以使用參數(shù)M(一對匹配殘基的賞分值；通常＞0)和N(不匹配殘基的罰分值；通常＜0)計(jì)算累積分值。當(dāng)累積比對值從其最大得到值下降了數(shù)量X；由于累積了一個(gè)或多個(gè)負(fù)分值殘基比對，累積值達(dá)到零或以下；或到達(dá)兩個(gè)序列中任何一個(gè)的末尾時(shí)，每個(gè)方向上的字擊延伸停止。BLASTN算法參數(shù)W，T和X決定比對的敏感性和速度。BLAST程序(對于核苷酸序列)用11的字長度(W)，和10的期望值(E)作為默認(rèn)值，和BLOSUM62計(jì)分矩陣(見Henikoff和Henikoff(1989)Proc.Natl.Acad.Sci.USA 8910915)比對，(B)為50，期望值(E)為10，M＝5，N＝-4并比較兩條鏈。
優(yōu)選，“序列同一性百分比”由在至少20個(gè)位點(diǎn)的對比窗口中比較兩個(gè)最佳比對的序列來決定，其中對比窗口中多核苷酸序列部分與兩個(gè)序列最佳比對的參考序列(不包含添加或缺失)相比，可以包含百分之20或更少的添加或缺失(即缺口)，通常百分之5至15，或百分之10至12。百分比的計(jì)算通過確定兩個(gè)序列中出現(xiàn)相同核酸堿基的位點(diǎn)數(shù)以得到匹配位點(diǎn)數(shù)，匹配位點(diǎn)數(shù)除以參考序列的位點(diǎn)總數(shù)(即窗口大小)，結(jié)果乘以100得到序列同一性百分比。
本領(lǐng)域普通技術(shù)人員將領(lǐng)會到，遺傳密碼的簡并性結(jié)果是有許多核苷酸序列編碼這里所述的多肽。這些多核苷酸中有些與任何天然基因的核苷酸序列具有最小的同源性。然而，由于密碼子使用差異而不同的多核苷酸特別包含在本發(fā)明中。進(jìn)一步，包含這里提供的多核苷酸序列的等位基因在本發(fā)明的范圍內(nèi)。等位基因是由于一個(gè)或多個(gè)突變例如核苷酸缺失、添加和/或置換而改變的內(nèi)源性基因。所得的mRNA和蛋白可以但不是必需發(fā)生結(jié)構(gòu)或功能改變。使用標(biāo)準(zhǔn)技術(shù)可以鑒定等位基因(例如雜交、擴(kuò)增和/或數(shù)據(jù)庫序列比較)。
因此，在本發(fā)明的另一個(gè)實(shí)施方案中，采用誘變方法，例如定點(diǎn)誘變，制備這里描述的多肽的免疫原性變異體和/或衍生物。使用這個(gè)方法，通過誘變編碼它們的多核苷酸進(jìn)行對多肽序列的特異性修飾。這些技術(shù)提供了制備和檢測序列變異體的直接方法，例如，通過將一個(gè)或多個(gè)核苷酸序列改變導(dǎo)入多核苷酸而引入一個(gè)或多個(gè)前述考慮因素。
定點(diǎn)誘變可以產(chǎn)生突變體，通過使用編碼期望突變的DNA序列的特異性寡核苷酸序列，以及足夠數(shù)量的相鄰核苷酸以提供足夠大小的引物序列和順序復(fù)雜性，在被橫越的缺失連接處兩側(cè)形成穩(wěn)定的雙螺旋?？梢栽谒x多核苷酸序列中利用突變來提高、改變、降低、修飾或改變多核苷酸本身的性能，和/或改變編碼的多肽的性能、活性、組成、穩(wěn)定性，或一級序列。
在本發(fā)明的某些實(shí)施方案中，發(fā)明者預(yù)計(jì)誘變所公開的多核苷酸序列會改變編碼的多肽的一個(gè)或多個(gè)性能，例如多肽疫苗的免疫原性。定點(diǎn)誘變技術(shù)是本領(lǐng)域熟知的，并廣泛用于產(chǎn)生多肽和多核苷酸的變異體。例如，常常使用定點(diǎn)誘變改變DNA分子的特定部分。在這種實(shí)施方案中，使用長度通常包含大約14至大約25個(gè)核苷酸左右的引物，其中大約5至大約10個(gè)殘基在待改變的序列的連接處兩側(cè)。
本領(lǐng)域技術(shù)人員將領(lǐng)會到，定點(diǎn)誘變技術(shù)常常使用以單鏈和雙鏈形式存在的噬菌體載體。用于定點(diǎn)誘變中的典型載體包括載體例如M13噬菌體。這些噬菌體容易從商業(yè)上獲得，且其使用通常是本領(lǐng)域技術(shù)人員熟知的。雙鏈質(zhì)粒也被常規(guī)用于定點(diǎn)誘變，排除將感興趣基因從質(zhì)粒轉(zhuǎn)移到噬菌體的步驟。
通常，這里的定點(diǎn)誘變的實(shí)施是通過首先得到單鏈載體或使雙鏈載體的兩條鏈解鏈，載體在其序列中包括編碼期望肽的DNA序列。制備含有期望突變序列的寡核苷酸引物，通常通過合成方法。然后，這個(gè)引物與單鏈載體退火，并加入DNA聚合酶例如大腸桿菌聚合酶IKlenow片段，以完成含有突變鏈的合成。因此，形成了異源雙鏈，其中一條鏈編碼原始未突變序列，第二條鏈含有期望的突變。然后將這個(gè)異源雙鏈載體用于轉(zhuǎn)化適當(dāng)?shù)募?xì)胞，例如大腸桿菌細(xì)胞，選擇包括含突變序列重排的重組載體的克隆。
使用定點(diǎn)誘變制備編碼所選肽的DNA片段的序列變異體，提供了產(chǎn)生潛在有用的物種的方法，并不意味著限制有其它方法可以獲得肽和編碼它們的DNA序列的序列變異體。例如，可以用誘變劑，例如羥胺，處理編碼期望的肽序列的重組載體得到序列變異體。有關(guān)這些方法和方案的具體細(xì)節(jié)在Maloy等，1994；Segal，1976；Prokop和Bajpai，1991；Kuby，1994；和Maniatis等，1982的教導(dǎo)中找到，為了那個(gè)目的將每篇引入這里作為參考。
這里使用的術(shù)語“寡核苷酸定向誘變步驟”是指模板依賴性過程和載體介導(dǎo)的增殖，導(dǎo)致特定核酸分子的濃度相對于其最初的濃度增加，或可檢測信號濃度增加，如擴(kuò)增。這里使用的術(shù)語“寡核苷酸定向誘變步驟”旨在指包括引物分子的模板依賴性延伸的過程。術(shù)語模板依賴性過程是指RNA或DNA分子的核酸合成，其中新合成的核酸鏈的序列由熟知的堿基互補(bǔ)配對規(guī)則指定(見，例如Watson，1987)。典型地，載體介導(dǎo)的方法包括將核酸片段導(dǎo)入DNA或RNA載體，載體的克隆擴(kuò)增，和回收擴(kuò)增的核酸片段。美國專利4,237,224提供了這種方法學(xué)的實(shí)例，這里以其完整形式特別引入作為參考。
在另一個(gè)產(chǎn)生本發(fā)明的多肽變異體的方法中，可以使用如美國專利5,837,458所述的遞推序列重組。在這個(gè)方法中，反復(fù)循環(huán)實(shí)施重組和篩選或選擇以“發(fā)展”具有例如增強(qiáng)的免疫原性的本發(fā)明的各多核苷酸變異體。
在本發(fā)明的其它實(shí)施方案中，這里提供的多核苷酸序列可以有利地用作核酸雜交的探針或引物。由此預(yù)計(jì)包括具有與這里公開的長15個(gè)核苷酸的連續(xù)序列序列相同的序列或與之互補(bǔ)的長度至少大約15個(gè)核苷酸的連續(xù)序列的序列區(qū)的核酸片段將特別有用。更長的連續(xù)的等同或互補(bǔ)序列，例如，大約20，30，40，50，100，200，500，1000(包括所有中間長度)和甚至高達(dá)全長序列的序列也將用于某些實(shí)施方案。
這種核酸探針與感興趣序列特異性雜交的能力將使它們能夠用于檢測給定樣本中互補(bǔ)序列的存在。然而也可預(yù)想其它用途，例如將序列信息用于制備突變種引物，或用于制備其它遺傳結(jié)構(gòu)的引物。
具有由10-14，15-20，30，50，或甚至100-200個(gè)核苷酸左右的連續(xù)核苷酸段(也包括中間長度)組成的序列區(qū)的多核苷酸分子，與這里公開的多核苷酸序列等同或互補(bǔ)，特別考慮在如DNA印跡和RNA印跡中用作為雜交探針。這將使得基因產(chǎn)物或其片段可在多種類型細(xì)胞中且也可以在各種細(xì)菌細(xì)胞中進(jìn)行分析。片段的總大小，以及互補(bǔ)段的大小，將最終依賴于特定核酸片段的期望用途或應(yīng)用。更小的片段將通常用于雜交方案中，其中連續(xù)互補(bǔ)區(qū)的長度可以變化，例如在大約15和大約100個(gè)核苷酸之間，但根據(jù)期望檢測的互補(bǔ)序列長度，可以使用更長的連續(xù)互補(bǔ)段。
使用長度為大約15-25個(gè)核苷酸的雜交探針允許形成既穩(wěn)定又有選擇性的雙螺旋分子。盡管為了增加雜交的穩(wěn)定性和選擇性，通常優(yōu)選具有連續(xù)互補(bǔ)序列跨越長度大于15個(gè)堿基的分子，并因此提高所得到的特異雜交分子的質(zhì)量和程度。人們通常會優(yōu)選設(shè)計(jì)具有15至25個(gè)連續(xù)核苷酸的基因互補(bǔ)段的核酸分子，或期望的話甚至更長。
雜交探針可以選自這里公開的任何序列的任何部分。所需要的只是瀏覽這里列舉的序列，或希望利用作為探針或引物的長度從大約15-25個(gè)核苷酸到包括全長序列的序列的任何連續(xù)部分。探針和引物序列的選擇可以受各種因素的控制。例如，可以希望使用來自趨向于全序列末端的引物。
可以很容易地制備小的多核苷酸段或片段，例如通過化學(xué)方法直接合成片段，如使用自動寡核苷酸合成儀普通進(jìn)行的。而且，片段也可以通過應(yīng)用核酸復(fù)制技術(shù)，例如美國專利4,683,202(這里引入作為參考)的PCRTM技術(shù)，通過將所選序列導(dǎo)入重組載體用于產(chǎn)生重組體，和通過分子生物學(xué)領(lǐng)域技術(shù)人員通常所知的其它重組DNA技術(shù)而獲得。
可以使用本發(fā)明的核苷酸序列，因?yàn)樗鼈兙哂信c完整基因或感興趣的基因片段的互補(bǔ)段選擇性形成雙螺旋分子的能力。根據(jù)預(yù)想的應(yīng)用，人們通常會期望利用不同的雜交條件獲得探針對靶序列的不同選擇性程度。對于需要高選擇性的應(yīng)用，人們通常會期望利用相對嚴(yán)格的條件形成雜種，例如，會選擇相對低的鹽和/或高的溫度條件，例如提供從大約0.02M至大約0.15M的鹽濃度，從大約50℃至大約70℃的溫度。這種選擇性條件容忍極少的，如果有的話，探針和模板或靶鏈間的錯(cuò)配，將特別適合分離相關(guān)序列。
當(dāng)然，對于有些應(yīng)用，例如，期望利用與基礎(chǔ)模板雜交的突變引物鏈制備突變體時(shí)，為了允許形成異源雙鏈典型地需要較不嚴(yán)格的(嚴(yán)格性降低)的雜交條件。在這些情況下，可以期望利用例如從大約0.15M至大約0.9M鹽的鹽條件，溫度范圍從大約20℃至大約55℃。因此能很容易鑒定交叉雜交種，其相對于對照雜交出現(xiàn)陽性雜交信號。在任何情況下，通?？深I(lǐng)會到添加增加量的甲酰胺可以使條件更為嚴(yán)格，它以與溫度增加相同的模式使雜種雙鏈不穩(wěn)定。因此，雜交條件可很容易操縱，而這通常將是一種取決于期望的結(jié)果而選擇的方法。
根據(jù)本發(fā)明的另一個(gè)實(shí)施方案，提供了包括反義寡核苷酸的多核苷酸組合物。已經(jīng)證明了反義寡核苷酸是有效的且定向的蛋白合成抑制劑，并且因此提供了通過抑制引起疾病的蛋白合成來治療疾病的治療方法。反義寡核苷酸抑制蛋白合成的功效已經(jīng)很好地被證實(shí)。例如，多聚半乳糖醛酸酶和毒蕈堿2型乙酰膽堿受體的合成可被針對其各自的mRNA序列的反義寡核苷酸抑制(美國專利5,739,119和美國專利5,759,829)。此外，反義抑制的例子已經(jīng)在核內(nèi)蛋白細(xì)胞周期蛋白，多重耐藥基因(MDG1)，ICAM-1，E-選擇素，STK-1，紋狀體GABAA受體和人EGF中得到證實(shí)(Jaskulski等，Science.1988 Jun10；240(4858)1544-6；Vasanthakumar和Ahmed，CancerCommun.1989；1(4)225-32；Peris等，Brain Res MolBrain Res.1998 Juh 15；57(2)310-20；美國專利5,801,154；美國專利5,789,573；美國專利5,718,709和美國專利5,610,288)。也描述了反義構(gòu)建體抑制和可用于治療多種異常細(xì)胞增殖，例如癌癥(美國專利5,747,470；美國專利5,591,317和美國專利5,783,683)。
因此，在某些實(shí)施方案中，本發(fā)明提供了寡核苷酸序列，其包括全部或部分能夠特異性結(jié)合這里描述的多核苷酸序列或其互補(bǔ)物的任何序列。在一個(gè)實(shí)施方案中，反義寡核苷酸包括DNA或其衍生物。在另一個(gè)實(shí)施方案中，寡核苷酸包括RNA或其衍生物。在第三個(gè)實(shí)施方案中，寡核苷酸是包括硫代磷酸修飾骨架的經(jīng)修飾DNA。在第四個(gè)實(shí)施方案中，寡核苷酸序列包括肽核酸或其衍生物。在每種情況下，優(yōu)選組合物包括與這里公開的多核苷酸的一個(gè)或多個(gè)部分互補(bǔ)和更優(yōu)選基本互補(bǔ)，和甚至更優(yōu)選完全互補(bǔ)的序列區(qū)。選擇對給定基因序列特異性的反義組合物是基于所選靶序列的分析和二級結(jié)構(gòu)的確定，Tm，結(jié)合能和相對穩(wěn)定性。反義組合物可以基于其相對不形成會降低或禁止與宿主細(xì)胞中目的mRNA特異性結(jié)合的二聚體、發(fā)夾或其它二級結(jié)構(gòu)的能力來選擇。非常優(yōu)選的mRNA的靶區(qū)是位于或接近AUG翻譯起始密碼子，和基本上與mRNA 5’區(qū)互補(bǔ)的那些序列。這些二級結(jié)構(gòu)分析和靶位點(diǎn)選擇考慮可以使用例如OLIGO引物分析軟件V.4和/或BLASTN2.0.5算法軟件(Altschul等，Nucleic Acids Res.1997，25(17)3389-402)來實(shí)施。
也可以考慮采用使用短肽載體，稱為MPG(27個(gè)殘基)的反義送遞方法。MPG肽含有來自HIV gp41和來自SV40 T抗原的核定位序列親水區(qū)的融合序列的疏水區(qū)(Morris等，Nucleic Acids Res.1997Jul 15；25(14)2730-6)。已經(jīng)證明幾個(gè)MPG肽分子包被反義寡核苷酸并可在小于1小時(shí)內(nèi)以相對高的效率(90％)遞送至培養(yǎng)的哺乳動物細(xì)胞中。此外，與MPG的相互作用強(qiáng)烈增加寡核苷酸對核酸酶的穩(wěn)定性和穿過質(zhì)膜的能力。
根據(jù)本發(fā)明的另一個(gè)實(shí)施方案，這里描述的多核苷酸組合物用于涉及和制備核酶分子以用于抑制本發(fā)明的腫瘤多肽和蛋白在腫瘤細(xì)胞中的表達(dá)。核酶是以位點(diǎn)特異性方式切割核酸的RNA-蛋白復(fù)合體。核酶具有具備內(nèi)切核酸酶活性的特異性催化區(qū)(Kim和Cech，ProcNatl Acad Sci U S A.1987 Dec；84(24)8788-92；Forster和Symons，Cell.1987 Apr 24；49(2)211-20)。例如，大量核酶以高度特異性加速磷酸酯轉(zhuǎn)移反應(yīng)，常常僅切割寡核苷酸底物中幾個(gè)磷酸酯之一(Cech等，Cell.1981 Dec；27(3 Pt 2)487-96；Michel和Westhof，J Mol Biol.1990 Dec 5；216(3)585-610；Reinhold-Hurek和Shub，Nature.1992 May 14；357(6374)173-6)。這個(gè)特異性要求在化學(xué)反應(yīng)前底物通過特異性堿基配對相互作用結(jié)合核酶的內(nèi)部引導(dǎo)序列(“IGS”)。
現(xiàn)在已知天然發(fā)生的酶性RNA的六個(gè)基本變種。每種可以在生理?xiàng)l件下催化RNA磷酸二酯鍵在運(yùn)輸中(因此可切割其它RNA分子)的水解。通常，酶性核酸通過先結(jié)合靶RNA而發(fā)揮作用。這種結(jié)合發(fā)生在酶性核酸的靶結(jié)合部分，它與切割靶RNA的所述分子的酶性部分接近。因此，酶性核酸首先識別并接著通過堿基互補(bǔ)配對結(jié)合靶RNA，一旦結(jié)合到正確位點(diǎn)，即發(fā)揮酶促作用切割靶DNA。這種靶RNA的策略性切割將破壞其指導(dǎo)編碼蛋白的合成的能力。酶性核酸結(jié)合和切割其RNA靶后，它被那個(gè)RNA釋放出來去搜尋其它目標(biāo)并能重復(fù)結(jié)合和切割新的目標(biāo)。
核酶的酶學(xué)性質(zhì)比許多技術(shù)有優(yōu)勢，例如反義技術(shù)(其中核酸分子僅結(jié)合核酸目標(biāo)阻斷其翻譯)，因?yàn)橹委熕匦璧暮嗣笣舛鹊陀诜戳x寡核苷酸的濃度。這個(gè)優(yōu)點(diǎn)反映了核酶進(jìn)行酶促作用的能力。因此，單一核酶分子能夠切割許多靶RNA分子。而且，核酶是高度特異性抑制劑，其抑制特異性不僅僅依賴于結(jié)合靶RNA的堿基配對機(jī)制，而且還依賴于靶RNA切割的機(jī)制。接近切割位點(diǎn)的單一錯(cuò)配或堿基置換可以完全消除核酶的催化活性。反義分子中類似的錯(cuò)配不能阻止其作用(Woolf等，Proc Natl Acad Sci U S A.1992 Aug 15；89(16)7305-9)。因此，核酶作用的特異性高于結(jié)合相同RNA位點(diǎn)的反義寡核苷酸。
酶性核酸分子可以形成錘頭狀、發(fā)夾狀、肝炎Γ病毒、I組內(nèi)含子或RNA酶P RNA(與RNA指導(dǎo)序列有關(guān))或鏈孢霉屬VS RNA基元。錘頭狀基元的例子在Rossi等.Nucleic Acids Res.1992 Sep11；20(17)4559-65中描述。發(fā)夾狀基元的例子記載在Hampel等(歐洲專利申請公開號EP 0360257)，Hampel和Tritz，Biochemistry 1989 Jun 13；28(12)4929-33；Hampel等，NucleicAcids Res.1990 Jan 25；18(2)299-304和美國專利5,631,359。肝炎Γ病毒基元在Perrotta和Been，Biochemi stry.1992 Dec 1；31(47)11843-52中描述；RNA酶P基元的例子在Guerrier-Takada等，Cell.1983 Dec；35(3 Pt 2)849-57中描述；鏈孢霉屬VS RNA核酶基元在Collins(Saville和Collins，Cell.1990 May18；61(4)685-96；Saville和Collins，Proc Natl AcadSci USA.1991 Oct 1；88(19)8826-30；Collins和Olive，Biochemistry.1993 Mar 23；32(11)2795-9)中描述；而I組內(nèi)含子在(美國專利4,987,071)中描述。在本發(fā)明的酶性核酸分子中重要的是它具有與一個(gè)或多個(gè)與靶基因RNA區(qū)互補(bǔ)的特異性底物結(jié)合位點(diǎn)，和它在該底物結(jié)合位點(diǎn)內(nèi)或周圍具有賦予所述分子RNA切割活性的核苷酸序列。因此，核酶構(gòu)建體不必限于這里提及的特殊基元。
可以如國際專利申請公開號WO 93/23569和國際專利申請公開號WO 94/02595中所述設(shè)計(jì)核酶(每篇特別引入這里用作參考)，并如所述進(jìn)行合成以在體外和體內(nèi)檢測。這種核酶也可以優(yōu)化用于遞送。盡管提供了具體的例子，本領(lǐng)域技術(shù)人員將認(rèn)識到需要時(shí)可利用其它物種中同等的RNA靶。
核酶活性可以優(yōu)化，通過改變核酶結(jié)合臂的長度，或化學(xué)合成核酶，帶有防止其被血清核糖核酸酶降解的修飾(如見國際專利申請公開號WO 92/07065；國際專利申請公開號WO 93/15187；國際專利申請公開號WO 91/03162；歐洲專利申請公開號92110298.4；美國專利5,334,711；和國際專利申請公開號WO 94/13688，這些文獻(xiàn)描述了可以對酶性RNA分子的糖部分進(jìn)行的各種化學(xué)修飾)，增強(qiáng)它們在細(xì)胞中的功效的修飾，和去除莖區(qū)II堿基以縮短RNA合成時(shí)間和降低化學(xué)要求。
Sullivan等(國際專利申請公開號WO 94/02595)描述了送遞酶性RNA分子的一般方法。核酶可以通過熟悉本領(lǐng)域的技術(shù)人員所知的各種方法給予細(xì)胞，包括但不限于，脂質(zhì)體包裝，離子電滲療法或引入其它載體，如水凝膠、環(huán)糊精、生物可降解的微囊和生物粘合微球體。對于有些適應(yīng)癥，核酶可以用或不用前述載體直接離體送遞給細(xì)胞或組織?？晒┻x擇地，RNA/載體組合可以通過直接吸入，直接注射或使用導(dǎo)管，輸液泵或支架局部送遞。其它送遞途徑包括但不限于血管內(nèi)、肌肉內(nèi)、皮下或關(guān)節(jié)注射、氣霧吸入、口服(片劑或丸劑形式)、局部、全身、眼部、腹膜內(nèi)和/或鞘內(nèi)送遞。核酶送遞和給藥的更詳細(xì)說明在國際專利申請公開號WO 94/02595和國際專利申請公開號WO 93/23569中給出，每篇特別引入這里作為參考。
在細(xì)胞內(nèi)積累高濃度核酶的另一個(gè)方法是將編碼核酶的序列摻入DNA表達(dá)載體中。核酶序列的轉(zhuǎn)錄由真核RNA聚合酶I(pol I)、RNA聚合酶II(pol II)或RNA聚合酶III(pol III)的啟動子驅(qū)動。來自pol II或pol III啟動子的轉(zhuǎn)錄物將在所有細(xì)胞中高水平表達(dá)；給定的pol II啟動子在給定細(xì)胞類型中的水平將依賴于附近存在的基因調(diào)控序列的性質(zhì)(增強(qiáng)子、沉默子等)。也可以使用原核RNA聚合酶啟動子，只要原核RNA聚合酶在合適的細(xì)胞中表達(dá)。已經(jīng)表明由這種啟動子表達(dá)的核酶在哺乳動物細(xì)胞中具有功能。這種轉(zhuǎn)錄單位可以摻入到各種載體中導(dǎo)入哺乳動物細(xì)胞，包括但不限于質(zhì)粒DNA載體，病毒DNA載體(例如腺病毒或腺伴隨病毒載體)，或病毒RNA載體(如逆轉(zhuǎn)錄病毒、賽姆利基森林病毒、新培斯病毒載體)。
在本發(fā)明的另一個(gè)實(shí)施方案中，提供了肽核酸(PNAs)組合物。PNA是核堿基與假肽骨架相連的模擬DNA(Good和Nielsen，Antisense Nucleic Acid Drug Dev.1997 7(4)431-37)。PNA能夠用于傳統(tǒng)使用RNA或DNA的許多方法。通常PNA序列在技術(shù)中比相應(yīng)的RNA或DNA序列表現(xiàn)得更好且具有非RNA或DNA固有的用途。包括PNA的制備方法、特征和使用方法的綜述由Corey(TrendsBiotechnol 1997 Jun；15(6)224-9)提供。由此在某些實(shí)施方案中，可以制備與ACE mRNA序列的一個(gè)或多個(gè)部分互補(bǔ)的PNA序列，且這種PNA組合物可以用于調(diào)節(jié)、改變、減少或降低ACE特異性mRNA的翻譯，并因此改變在已經(jīng)施用這種PNA組合物的宿主細(xì)胞中的ACE活性水平。
PNA具有取代正常DNA磷酸二酯骨架的2-氨乙基甘氨酸鍵合(Nielsen等，Science 1991 Dec 6；254(5037)1497-500；Hanvey等，Science.1992 Nov 27；258(5087)1481-5；Hyrup和Nielsen，Bioorg Med Chem.1996 Jan；4(1)5-23)。這個(gè)化學(xué)結(jié)構(gòu)具有三個(gè)重要的結(jié)果首先，與DNA或硫代磷酸寡核苷酸比較，PNA是中性分子；其次，PNA是非手性的，避免進(jìn)行立體選擇合成的需要；和第三，PNA合成使用固相肽合成的標(biāo)準(zhǔn)Boc或Fmoc方案，盡管也曾使用其它方法包括改良的Merrifield方法。
從PerSeptive Biosystems(Framingham，MA)可商業(yè)購得PNA單體或現(xiàn)成的寡聚體。用Boc或Fmoc方案合成PNA都是使用人工或自動方案直接合成(Norton等，Bioorg Med Chem.1995 Apr；3(4)437-45)。人工方案使其自身產(chǎn)生經(jīng)化學(xué)修飾的PNA或同時(shí)合成密切相關(guān)的PNA家族。
對于肽合成，特定PNA合成的成功依賴于所選序列的性能。例如，盡管理論上PNA可摻入任何核苷酸堿基的組合，但是鄰近嘌呤的存在可導(dǎo)致產(chǎn)物中一個(gè)或多個(gè)殘基缺失。預(yù)測到這個(gè)困難，建議在產(chǎn)生帶有鄰近嘌呤的PNA時(shí)，應(yīng)該重復(fù)偶聯(lián)可能無效加入的殘基。這之后應(yīng)該用反相高壓液相色譜純化PNA，提供類似于肽合成過程中觀察到的產(chǎn)物產(chǎn)量和純度。
將PNA針對給定應(yīng)用進(jìn)行修飾可通過在固相合成期間偶聯(lián)氨基酸或?qū)⒑恤人峄鶊F(tuán)的化合物與暴露的N末端胺連接來完成?？晒┻x擇地，可在合成后通過偶聯(lián)至引入的賴氨酸或半胱氨酸來修飾PNA。PNAs可以很容易被修飾利于將其優(yōu)化成具有更好的溶解度或針對特殊的功能需要。一旦合成后，可以用質(zhì)譜分析法進(jìn)行PNAs和其衍生物的鑒定。幾項(xiàng)研究已制備并利用了PNA的修飾。(例如，Norton等，Bioorg Med Chem.1995 Apr；3(4)437-45；Petersen等，J.Pept Sci.1995 May-Jun；1(3)175-83；Orum等，Biotechniques.1995 Sep；19(3)472-80；Footer等，Biochemistry.1996 Aug 20；35(33)10673-9；Griffith等，Nucleic Acids Res.1995 Aug 11；23(15)3003-8；Pardridge等，Proc Natl Acad Sci USA.1995 Jun 6；92(12)5592-6；Boffa等，Proc Natl Acad Sci U S A.1995 Mar 14；92(6)1901-5；Gambacorti-Passerini等，Blood.1996 Aug15；88(4)1411-7；Armitage等，Proc Natl Acad Sci U SA.1997 NoV 11；94(23)12320-5；Seeger等，Biotechniques.1997 Sep；23(3)512-7)。美國專利5,700,922討論了PNA-DNA-PNA嵌合分子及其在診斷、調(diào)節(jié)生物體中的蛋白和治療對治療敏感的病癥中的用途。
在Rose(Anal Chem.1993 Dec 15；65(24)3545-9)和Jensen等(Biochemistry.1997 Apr 22；36(16)5072-7)中討論了表征PNA的反義結(jié)合性能的方法。Rose使用毛細(xì)管凝膠電泳確定PNA與其互補(bǔ)寡核苷酸的結(jié)合，測定相對結(jié)合動力學(xué)和化學(xué)計(jì)量，Jensen等使用BIAcoreTM技術(shù)進(jìn)行了類似類型的測量。
已經(jīng)描述過的和對本領(lǐng)域技術(shù)人員將很明顯的PNA的其它應(yīng)用包括用于DNA鏈侵入、反義抑制、突變分析、轉(zhuǎn)錄增強(qiáng)子、核酸純化、轉(zhuǎn)錄活性基因的分離、轉(zhuǎn)錄因子結(jié)合的阻斷、基因組切割、生物傳感器，原位雜交等等。多核苷酸鑒定、表征和表達(dá)使用各種確立的技術(shù)(普遍參見Sambrook等，MolecularCloningA Laboratory Manual，Cold Spring HarborLaboratories，Cold Spring Harbor，NY，1989，和其它類似參考文獻(xiàn))中任何一種可以鑒定、制備和/或操作本發(fā)明的多核苷酸組合物。例如，通過篩選cDNA微陣列中的腫瘤相關(guān)表達(dá)(即，使用這里提供的代表性試驗(yàn)測定在腫瘤中比在正常組織中高至少兩倍的表達(dá))可以鑒定多核苷酸，如下更詳細(xì)描述?？梢允褂美鏏ffymetrix，Inc.(Santa Clara，CA)的微陣列技術(shù)，根據(jù)制造商的使用說明(基本如Schena等，Proc.Natl.Acad.Sci.USA 9310614-10619，1996和Heller等，Proc.Natl.Acad.Sci.USA 942150-2155，1997所述)實(shí)施這種篩選?？晒┻x擇地，可以由從表達(dá)這里所述的蛋白的細(xì)胞如腫瘤細(xì)胞中制備的cDNA擴(kuò)增多核苷酸。
許多模板依賴性方法能夠擴(kuò)增樣本中存在的感興趣的靶序列。最為熟知的擴(kuò)增方法之一是聚合酶鏈?zhǔn)椒磻?yīng)(PCRTM)，在美國專利4,683,195，4,683,202和4,800,159中詳細(xì)描述，每篇以其完整形式引入這里作為參考。簡言之，在PCRTM中，制備與靶序列的相反互補(bǔ)鏈上的區(qū)域互補(bǔ)的兩條引物序列。向反應(yīng)混合物中加入過量的脫氧核苷三磷酸，以及DNA聚合酶(如Taq聚合酶)。如果樣本中存在靶序列，引物將與靶結(jié)合，聚合酶通加添加核苷酸使引物延著靶序列延伸。通過提高和降低反應(yīng)混合物的溫度，延伸的引物將與靶解離形成反應(yīng)產(chǎn)物，過量的引物將與靶和反應(yīng)產(chǎn)物結(jié)合，重復(fù)此過程。為了定量擴(kuò)增的mRNA的量，優(yōu)選可以實(shí)施逆轉(zhuǎn)錄和PCRTM擴(kuò)增步驟。聚合酶鏈?zhǔn)椒磻?yīng)方法是本領(lǐng)域熟知的。
大量其它模板依賴性方法中的任何方法，其中許多是PCRTM擴(kuò)增技術(shù)的變型，是本領(lǐng)域容易獲知和利用的。舉例說明，一些這種方法包括連接酶鏈?zhǔn)椒磻?yīng)(稱作LCR)，在例如歐洲專利申請公開號320,308和美國專利4,883,750中描述；Qbeta復(fù)制酶在PCT國際專利申請公開號PCT/US87/00880中描述；鏈置換擴(kuò)增(SDA)和修復(fù)鏈反應(yīng)(RCR)。再有其它擴(kuò)增方法在英國專利申請?zhí)?202328和PCT國際專利申請公開號PCT/US89/01025中描述。其它核酸擴(kuò)增步驟包括基于轉(zhuǎn)錄的擴(kuò)增體系(TAS)(PCT國際專利申請公開號WO 88/10315)，包括基于核酸序列的擴(kuò)增(NASBA)和3SR。歐洲專利申請公開號329,822描述了一種核酸擴(kuò)增方法包括循環(huán)合成單鏈RNA(“ssRNA”)，ssDNA和雙鏈DNA(dsDNA)。PCT國際專利申請公開號WO 89/06700描述了核酸序列擴(kuò)增方案，基于啟動子/引物序列與目標(biāo)單鏈DNA(“ssRNA”)的雜交，然后轉(zhuǎn)錄該序列的許多RNA拷貝。其它擴(kuò)增方法例如“RACE”(Frohman，1990)，和“限性PCR(one-sided PCR)”(Ohara，1989)也是本領(lǐng)域技術(shù)人員熟知的。
使用熟知的技術(shù)，本發(fā)明的多核苷酸的擴(kuò)增部分可以用于從合適的文庫(如腫瘤cDNA文庫)中分離全長基因。在這種技術(shù)中，使用適合擴(kuò)增的一個(gè)或多個(gè)多核苷酸探針或引物篩選文庫(cDNA或基因組)。優(yōu)選，文庫是按大小進(jìn)行選擇的，包括較大分子。也可以優(yōu)選隨機(jī)引物文庫鑒定基因的5’和上游區(qū)。優(yōu)選基因組文庫用于獲得內(nèi)含子和延伸5’序列。
對于雜交技術(shù)，可以使用熟知技術(shù)標(biāo)記部分序列(如，通過缺口平移或用32P末端標(biāo)記)。然后通常用標(biāo)記探針雜交含變性菌落的濾器(或含噬菌斑的菌苔)篩選細(xì)菌或噬菌體文庫(見Sambrook等，Molecular CloningA Laboratory Manual；Cold SpringHarbor Laboratories，Cold Spring Harbor，NY，1989)。選擇和擴(kuò)展雜交的菌落或噬斑，分離DNA作進(jìn)一步分析?？梢苑治鯿DNA克隆確定附加序列的量，例如通過使用來自部分序列的引物和來自載體的引物的PCR?？僧a(chǎn)生限制性圖譜和部分序列來鑒定一個(gè)或多個(gè)重疊克隆。然后用標(biāo)準(zhǔn)技術(shù)確定完整序列，所述技術(shù)可以包括產(chǎn)生一系列缺失克隆。然后可以將所得重疊序列組裝成單一連續(xù)序列。使用熟知技術(shù)連接合適的片段可以產(chǎn)生全長cDNA分子。
可供選擇地，擴(kuò)增技術(shù)，如以上所述的那些，可用以從部分cDNA序列獲得全長編碼序列。一種這樣的擴(kuò)增技術(shù)是反向PCR(見Triglia等，Nucl.Acids Res.168186，1988)，它使用限制性酶產(chǎn)生在基因的已知區(qū)域中的片段。然后通過分子內(nèi)連接將該片段環(huán)化并用作使用來自已知區(qū)的分散引物進(jìn)行PCR的模板。在可供選擇的方法中，用針對接頭序列的引物和對已知區(qū)域特異性的引物進(jìn)行擴(kuò)增可以重新獲得與部分序列鄰近的序列。通常將擴(kuò)增的序列進(jìn)行第二輪擴(kuò)增，使用相同的接頭引物和對已知區(qū)域特異性的第二條引物。WO 96/38591中描述了這個(gè)步驟的變型，它利用從已知序列以相反方向開始延伸的兩條引物。另一個(gè)這種技術(shù)已知是“快速擴(kuò)增cDNA末端”或RACE。這個(gè)技術(shù)包括使用內(nèi)引物和外引物，它與聚腺苷酸區(qū)或載體序列雜交，以鑒定在已知序列的5’和3’的序列。另外的技術(shù)包括捕獲PCR(Lagerstrom等，PCR Methods Applic.l111-19，1991)和步行PCR(Parker等，Nucl.Acids.Res.193055-60，1991)。也可以采用其它利用擴(kuò)增的方法獲得全長cDNA序列。
在某些情況下，通過分析已表達(dá)序列標(biāo)記(EST)數(shù)據(jù)庫中提供的序列，例如可從GenBank得到的序列，可能得到全長cDNA序列。通常可以使用熟知程序(如NCBI BLAST檢索)檢索重疊ESTs，且這種ESTs可以用于產(chǎn)生連續(xù)的全長序列。分析基因組片段也可以得到全長DNA序列。
在本發(fā)明的其它實(shí)施方案中，編碼本發(fā)明多肽或融合蛋白或其功能性等同物的多核苷酸序列或其片段，可以用于重組DNA分子以指導(dǎo)多肽在適當(dāng)?shù)乃拗骷?xì)胞中的表達(dá)。由于遺傳密碼的固有簡并性，可以產(chǎn)生編碼基本相同或功能等同的氨基酸序列的其它DNA序列且這些序列可以用于克隆和表達(dá)給定的多肽。
如本領(lǐng)域技術(shù)人員會理解的，在有些情況下產(chǎn)生具有非天然存在密碼子的編碼多肽的核苷酸序列可能有優(yōu)勢。例如，可以選擇特定原核或真核宿主優(yōu)選的密碼子來增加蛋白表達(dá)率或產(chǎn)生具有期望性能的重組RNA轉(zhuǎn)錄物，例如半衰期比從天然存在序列產(chǎn)生的轉(zhuǎn)錄物長。
此外，為了各種原因而改變編碼多肽的序列，可使用本領(lǐng)域普遍所知的方法改造本發(fā)明的多核苷酸序列，包括但不限于改變基因產(chǎn)物的克隆、加工和/或表達(dá)。例如，通過隨機(jī)斷裂和將基因片段和合成寡核苷酸作PCR重新組裝進(jìn)行DNA改組可以用于改造核苷酸序列。另外，定點(diǎn)誘變可用于插入新的限制性位點(diǎn)，改變糖基化模式，改變密碼子選擇、產(chǎn)生剪接變體或?qū)胪蛔兊鹊取?br> 在本發(fā)明的另一個(gè)實(shí)施方案中，天然的、修飾的或重組的核酸序列可以與異源序列連接以編碼融合蛋白。例如，為篩選肽文庫得到多肽活性的抑制劑，它可用于編碼能為商業(yè)可獲得抗體所識別的嵌合蛋白。也可以改造融合蛋白使其含有位于編碼多肽的序列與異源蛋白序列之間的切割位點(diǎn)，使得多肽可以從異源部分上被切割下來并純化。
使用本領(lǐng)域熟知的化學(xué)方法(見Caruthers，M.H.等(1980)Nucl.Acids Res.Symp.Ser.215-223，Horn，T.等(1980)Nucl.Acids Res.Symp.Ser.225-232)可以全部或部分合成編碼期望多肽的序列?？晒┻x擇地，可以用化學(xué)方法合成多肽的氨基酸序列或其部分來產(chǎn)生蛋白本身。例如，可使用各種固相技術(shù)進(jìn)行肽合成(Roberge，J.Y.等(1995)Science 269202-204)，并且自動合成方法可以使用例如ABI 431A肽合成儀(Perkin Elmer，PaloAlto，CA)完成。
用制備型高效液相層析(如Creighton，T.(1983)Proteins，Structures and Molecular Principles，WH Freeman and Co.，New York，N.Y.)或本領(lǐng)域可利用的其它類似技術(shù)可以基本上純化新合成的肽。合成肽的組成可以通過氨基酸分析或測序(如Edman降解方法)證實(shí)。另外，多肽或其任何部分的氨基酸序列可以在直接合成過程中改變和/或使用化學(xué)方法與來自其它蛋白或其任何部分的序列組合，產(chǎn)生變異多肽。
為了表達(dá)期望的多肽，編碼多肽或其功能性等同物的核苷酸序列可以插入到合適的表達(dá)載體中，即，含有轉(zhuǎn)錄和翻譯插入的編碼序列必需的元件的載體?？梢杂帽绢I(lǐng)域技術(shù)人員熟知的方法構(gòu)建含有編碼感興趣的多肽的序列和適當(dāng)?shù)霓D(zhuǎn)錄和翻譯調(diào)控元件的表達(dá)載體。這些方法包括體外重組DNA技術(shù)、合成技術(shù)和體內(nèi)基因重組。這種技術(shù)在例如Sambrook，J.等(1989)Molecular Cloning，A LaboratoryManual，Cold Spring Harbor Press，Plainview，N.Y.，和Ausubel，F(xiàn).M.等(1989)Current Protocols in MolecularBiology，John Wiley & Sons，New York N.Y.中描述。
可以利用各種表達(dá)載體/宿主體系包含和表達(dá)多核苷酸序列。這些包括但不限于微生物，如用重組噬菌體、質(zhì)?；蛘沉NA表達(dá)載體轉(zhuǎn)化的細(xì)菌；用酵母表達(dá)載體轉(zhuǎn)化的酵母；用病毒表達(dá)載體(如桿狀病毒)感染的昆蟲細(xì)胞體系；用病毒表達(dá)載體(如花椰菜花葉病毒，CaMV；煙草花葉病毒，TMV)或用細(xì)菌表達(dá)載體(如Ti或pBR322質(zhì)粒)轉(zhuǎn)化的植物細(xì)胞體系；或動物細(xì)胞體系。
表達(dá)載體中存在的“調(diào)控元件”或“調(diào)控序列”是載體的非翻譯區(qū)-增強(qiáng)子、啟動子、5’和3’非翻譯區(qū)-它們與宿主細(xì)胞內(nèi)蛋白相互作用進(jìn)行轉(zhuǎn)錄和翻譯。這種元件的強(qiáng)度和特異性可以變化。根據(jù)所利用的載體系統(tǒng)和宿主，可以使用任何數(shù)量的合適轉(zhuǎn)錄和翻譯元件，包括組成型和誘導(dǎo)型啟動子。例如，當(dāng)在細(xì)菌系統(tǒng)中克隆時(shí)，可以使用誘導(dǎo)型啟動子例如PBLUESCRIPT噬菌粒(Stratagene，La Jolla，Calif.)或PSPORT1質(zhì)粒(Gibco BRL，Gaithersburg，MD)的雜合lacZ啟動子等。在哺乳動物細(xì)胞體系中，通常優(yōu)選來自哺乳動物基因或來自哺乳動物病毒的啟動子。如果需要產(chǎn)生含有多拷貝編碼多肽的序列的細(xì)胞系，與適當(dāng)?shù)目蛇x擇標(biāo)記共同使用基于SV40或EBV的載體可能有優(yōu)勢。
在細(xì)菌體系中，可以根據(jù)所表達(dá)多肽傾向的用途來選擇多種表達(dá)載體中任何一種。例如，當(dāng)需要量大時(shí)，例如用于誘導(dǎo)產(chǎn)生抗體，可以使用指導(dǎo)高水平表達(dá)容易純化的融合蛋白的載體。這種載體包括但不限于，多功能大腸桿菌克隆和表達(dá)載體，例如BLUESCRIPT(Stratagene)，其中編碼感興趣多肽的序列可以連入到載體中，符合β-半乳糖苷酶的氨基末端Met和隨后的7個(gè)殘基的序列的讀框，從而產(chǎn)生雜合蛋白；pIN載體(Van Heeke，G.和S.M.Schuster(1989)J.Biol.Chem；2645503-5509)；等等。也可以使用pGEX載體(Promega，Madison，Wis.)作為與谷胱甘肽S-轉(zhuǎn)移酶(GST)一起形成的融合蛋白表達(dá)外來多肽。通常，這種融合蛋白是可溶的，且通過與谷胱甘肽-瓊脂糖珠吸附后在游離谷胱甘肽存在下洗脫很容易從溶解的細(xì)胞中純化?？梢詫⒃谶@種系統(tǒng)中制備的蛋白設(shè)計(jì)成包括肝素、凝血酶或因子XA蛋白酶切割位點(diǎn)，使得感興趣的克隆多肽可隨意與GST部分分離。
在酵母，啤酒酵母中，可以使用含有組成型或誘導(dǎo)型啟動子，如α因子、乙醇氧化酶和PGH的多種載體。綜述見Ausubel等(上文)和Grant等(1987)Methods Enzymol.153516-544。
在使用植物表達(dá)載體的情況下，編碼多肽的序列的表達(dá)可以由多種啟動子中的任何一個(gè)來驅(qū)動。例如，病毒啟動子如CaMV的35S和19S啟動子可以單獨(dú)使用或與來自TMV的omega引導(dǎo)序列組合使用(Takamatsu，N.(1987)EMBO J.6307-311?？晒┻x擇地，可以使用植物啟動子如RUBISCO的小亞基或熱休克啟動子(Coruzzi，G.等(1984)EMBO J.31671-1680；Broglie，R.等(1984)Science 224838-843；和Winter，J.等(1991)ResultsProbl.Cell Differ.1785-105)。這些構(gòu)建體可以通過直接DNA轉(zhuǎn)化或病原體介導(dǎo)的轉(zhuǎn)染導(dǎo)入植物細(xì)胞。這種技術(shù)在多篇通?？色@得的綜述中有述(見，例如，Hobbs，S.或Murry，L.E.in McGrawHill Yearbook of Science and Technology(1992)McGraw Hill，New York，N.Y.；pp.191-196)。
也可以使用昆蟲系統(tǒng)來表達(dá)感興趣的多肽。例如，在一個(gè)這樣的系統(tǒng)中，將苜蓿銀紋夜蛾核型多角體病毒(AcNPV)用作載體在草地夜蛾細(xì)胞或在粉紋夜蛾幼蟲中表達(dá)外來基因。編碼多肽的序列可以克隆到病毒的非必需區(qū)中，例如多角體蛋白基因，并置于多角體蛋白啟動子的控制之下。編碼多肽的序列的成功插入將使多角體蛋白基因失活并產(chǎn)生缺乏外殼蛋白的重組病毒。然后重組病毒可以用于感染例如草地夜蛾細(xì)胞或粉紋夜蛾幼蟲，在其中可以表達(dá)感興趣多肽(Engelhard，E.K.等(1994)Proc.Natl.Acad.Sci.913224-3227)。
在哺乳動物宿主細(xì)胞中，許多基于病毒的表達(dá)體系通常可以得到。例如，在腺病毒用作表達(dá)載體的情況下，編碼感興趣多肽的序列可以連接到由晚期啟動子和三聯(lián)前導(dǎo)序列組成的腺病毒轉(zhuǎn)錄/翻譯復(fù)合體中?？梢圆迦氲讲《净蚪M的非必需E1或E3區(qū)，得到能夠在感染的宿主細(xì)胞中表達(dá)多肽的活病毒(Logan，J.和Shenk，T.(1984)Proc.Natl.Acad.Sci.813655-3659)。此外，可以使用轉(zhuǎn)錄增強(qiáng)子，例如勞斯肉瘤病毒(RSV)增強(qiáng)子以增加在哺乳動物宿主細(xì)胞中的表達(dá)。
特殊起始信號也可以用于使編碼感興趣多肽的序列翻譯更有效，這種信號包括ATG起始密碼子和相鄰序列。在編碼多肽的序列、其起始密碼子和上游序列插入到適當(dāng)?shù)谋磉_(dá)載體中的情況下，可以不需要另外的轉(zhuǎn)錄或翻譯調(diào)控信號。然而，在只有編碼序列或其一部分插入的情況下，應(yīng)當(dāng)提供外源翻譯調(diào)控信號包括ATG起始密碼子。而且，起始密碼子應(yīng)該位于正確的閱讀框架中以確保翻譯完整插入片段。外源翻譯元件和起始密碼子可以是各種來源，包括天然的和合成的。包含適合所使用的特定細(xì)胞系統(tǒng)的增強(qiáng)子，如文獻(xiàn)中所述(Scharf，D.等(19943 Results Probl.Cell Differ.20125-162)可以提高表達(dá)效率。
此外，可以根據(jù)其以期望方式調(diào)節(jié)插入序列的表達(dá)或加工所表達(dá)蛋白的能力來選擇宿主細(xì)胞株。這種多肽的修飾包括但不限于，乙?；Ⅳ然?、糖基化、磷酸化、脂質(zhì)化(lipidation)和?；?。切割“前原(prepro)”形式蛋白的翻譯后加工也可以用來有助于正確插入、折疊和/或發(fā)揮功能。不同的宿主細(xì)胞例如CHO，COS，HeLa，MDCK，HEK293和WI38，具有產(chǎn)生這種翻譯后活性的特殊細(xì)胞裝置和特征性機(jī)制，可被選擇來確保外來蛋白正確修飾和加工。
為了長期高產(chǎn)量生產(chǎn)重組蛋白，通常優(yōu)選穩(wěn)定的表達(dá)。例如，可以使用在同一或單獨(dú)的載體中含有病毒來源的復(fù)制和/或內(nèi)源表達(dá)元件和可選擇標(biāo)記基因的表達(dá)載體轉(zhuǎn)化穩(wěn)定表達(dá)感興趣多核苷酸的細(xì)胞系。載體導(dǎo)入之后，可以使細(xì)胞在轉(zhuǎn)換成選擇性培養(yǎng)基之前在滋養(yǎng)培養(yǎng)基中生長1-2天?？蛇x擇性標(biāo)記的目的是提供選擇抗性，其存在允許成功表達(dá)導(dǎo)入序列的細(xì)胞的生長和回收。可以使用對細(xì)胞類型適合的組織培養(yǎng)技術(shù)增殖穩(wěn)定轉(zhuǎn)化細(xì)胞的抗性克隆。
可以使用任何數(shù)量的選擇體系回收轉(zhuǎn)化的細(xì)胞系。這些包括但不限于可分別用在tk.sup.-或aprt.sup.-細(xì)胞中的單純皰疹病毒胸腺嘧啶核苷激酶(Wigler，M.等(1977)Cell 11223-32)和腺嘌呤磷酸核糖轉(zhuǎn)移酶(Lowy，I.等(1990)Cell 22817-23)基因。抗代謝劑、抗生素或除草劑抗性也可以用作選擇的基礎(chǔ)；例如，dhfr提供了對氨甲蝶呤的抗性(Wigler，M.等(1980)Proc.Natl.Acad.Sci.773567-70)；npt提供了對氨基糖苷類、新霉素和G-418的抗性(Colbere-Garapin，F(xiàn).等(1981)J.Mol.Biol.1501-14)；和als或pat分別提供了對綠黃隆(chlorsulfuron)和膦絲菌素乙酰轉(zhuǎn)移酶的抗性(Murry，上文)。已經(jīng)描述了另外的可選擇基因，例如，trpB，其允許細(xì)胞利用吲哚代替色氨酸，或hisD，其允許細(xì)胞利用組氨醇(histinol)代替組氨酸(Hartman，S.C.和R.C.Mulligan(1988)Proc.Natl.Acad.Sci.858047-31)?？梢姌?biāo)記已經(jīng)普遍使用，如花色素苷、β-葡糖醛酸酶及其底物GUS，和熒光素酶及其底物熒光素，不僅廣泛用于鑒定轉(zhuǎn)化體，還用于定量可歸于特定載體系統(tǒng)的瞬時(shí)或穩(wěn)定蛋白表達(dá)的量(Rhodes，C.A.等(1995)Methods Mol，Biol.55121-131)。
盡管存在/不存在標(biāo)記基因表達(dá)提示感興趣的基因也存在，可能需要證實(shí)其存在和表達(dá)。例如，如果編碼多肽的序列插入標(biāo)記基因序列內(nèi)，標(biāo)記基因功能的缺失可以鑒定含有序列的重組細(xì)胞?？晒┻x擇地，可將標(biāo)記基因串連編碼多肽的序列置于單一啟動子調(diào)控下。作為對誘導(dǎo)或選擇應(yīng)答的標(biāo)記基因表達(dá)通常也指示串連基因的表達(dá)。
可供選擇地，可以用本領(lǐng)域技術(shù)人員所知的各種步驟鑒定含有和表達(dá)期望多核苷酸序列的宿主細(xì)胞。這些步驟包括但不限于，DNA-DNA或DNA-RNA雜交和蛋白生物測定或免疫測定技術(shù)，包括例如用于檢測和/或定量核酸或蛋白的基于膜、溶液或芯片的技術(shù)。
使用對產(chǎn)物特異性的多克隆或單克隆抗體檢測和測定多核苷酸編碼產(chǎn)物的表達(dá)的各種方案是本領(lǐng)域已知的。例子包括酶聯(lián)免疫吸附測定(ELISA)、放射免疫測定法(RIA)和熒光激活細(xì)胞分類術(shù)(FACS)。對于有些應(yīng)用可能優(yōu)選利用與給定多肽上兩個(gè)非干擾表位反應(yīng)的單克隆抗體的雙位點(diǎn)基于單克隆的免疫測定，但是也可以使用競爭性結(jié)合試驗(yàn)。這些和其它測定特別在Hampton，R.等(1990；Serological Methods，a Laboratory Manual，APS Press，StPaul.Minn.)和Maddox，D.E.等(1983，J.Exp.Med.1581211-1216)中描述。
多種標(biāo)記和偶聯(lián)技術(shù)是本領(lǐng)域技術(shù)人員已知的，并可以用于各種核酸和氨基酸測定中。產(chǎn)生標(biāo)記的雜交探針或PCR探針用于檢測與多核苷酸相關(guān)的序列的方法包括寡標(biāo)記(oligo-labeling)、缺口翻譯、末端標(biāo)記或使用標(biāo)記核苷酸進(jìn)行PCR擴(kuò)增。可供選擇地，序列或其任何部分可以克隆進(jìn)入載體產(chǎn)生mRNA探針。這種載體是本領(lǐng)域已知的，可從商業(yè)上得到，并可以通過添加適當(dāng)?shù)腞NA聚合酶如T7，T3或SP6和標(biāo)記的核苷酸用于體外合成RNA探針。這些步驟可以使用各種商業(yè)可得到的試劑盒進(jìn)行?？梢允褂玫暮线m的報(bào)道分子或標(biāo)記包括放射性核素、酶、熒光、化學(xué)發(fā)光或顯色劑以及底物、輔因子、抑制劑、磁性顆粒等等。
用感興趣的核苷酸序列轉(zhuǎn)化的宿主細(xì)胞可以在適合從細(xì)胞培養(yǎng)物中表達(dá)和回收蛋白的條件下培養(yǎng)。取決于使用的序列和/或載體，重組細(xì)胞產(chǎn)生的蛋白可以分泌或含在細(xì)胞內(nèi)。如本領(lǐng)域技術(shù)人員會理解的，含有本發(fā)明多核苷酸的表達(dá)載體可以設(shè)計(jì)成包含指導(dǎo)編碼多肽通過原核或真核細(xì)胞膜分泌的信號序列。可以使用其它重組結(jié)構(gòu)使編碼感興趣多肽的序列與編碼利于可溶蛋白純化的多肽結(jié)構(gòu)域的核苷酸序列連接起來。這種利于純化的結(jié)構(gòu)域包括但不限于金屬螯合肽，例如允許在固定金屬上純化的組氨酸-色氨酸組件，允許在固定免疫球蛋白上純化的蛋白A結(jié)構(gòu)域，和在FLAGS延伸/親和純化體系(ImmunexCorp.，Seattle，Wash.)中利用的結(jié)構(gòu)域?？梢栽诩兓Y(jié)構(gòu)域和編碼多肽之間包含可切割的接頭序列，如對因子XA或腸激酶特異性的序列(Invitrogen.San-Diego，Calif.)以利于純化。一個(gè)這種表達(dá)載體提供了融合蛋白的表達(dá)，所述融合蛋白含有感興趣多肽和編碼硫氧還蛋白之前6個(gè)組氨酸殘基或腸激酶切割位點(diǎn)的核酸。組氨酸殘基利于在IMIAC(固定的金屬離子親和層析)上純化，如Porath，J.等(1992，Prot.Exp.Purif.3263-281)所述，而腸激酶切割位點(diǎn)提供了從融合蛋白中純化期望多肽的方法。Kroll，D.J.等(1993；DNA Cell Biol.12441-453)提出了關(guān)于含有融合蛋白的載體的討論。
除了重組生產(chǎn)方法之外， 可以使用固相技術(shù)(Merrifield J.(1963)J.Am.Chem.Soc.852149-2154)通過直接肽合成來產(chǎn)生本發(fā)明的多肽和其片段?？梢允褂檬止ぜ夹g(shù)或自動化進(jìn)行蛋白合成。自動合成可以使用例如Applied Biosystems 431A肽合成儀(Perkin Elmer)來完成。可供選擇地，可以分別化學(xué)合成各種片段并使用化學(xué)方法結(jié)合以產(chǎn)生全長分子?？贵w組合物、其片段和其它結(jié)合劑根據(jù)另一個(gè)方面，本發(fā)明進(jìn)一步提供了與在此公開的腫瘤多肽或其一部分、變異體或衍生物發(fā)生免疫結(jié)合的結(jié)合劑，例如抗體和其抗原結(jié)合片段。抗體或其抗原結(jié)合片段被述為與本發(fā)明多肽特異性結(jié)合”、“免疫結(jié)合”和/或具有“免疫學(xué)活性”，如果它與多肽以可檢測水平(例如在ELISA測定中)反應(yīng)，且在相似條件下不與無關(guān)多肽發(fā)生可檢測反應(yīng)。
本文中使用的免疫結(jié)合通常是指免疫球蛋白分子與免疫球蛋白對其特異性的抗原之間所發(fā)生類型的非共價(jià)相互作用。免疫結(jié)合相互作用的強(qiáng)度或親和力可以以相互作用的解離常數(shù)(Kd)來表示，其中較小的Kd代表較大的親和力。使用本領(lǐng)域熟知的方法可定量所選多肽的免疫結(jié)合性能。一個(gè)這種方法需要測定抗原結(jié)合位點(diǎn)/抗原復(fù)合體形成和解離的速率，其中那些速率依賴于復(fù)合體配偶體的濃度、相互作用的親和力和在兩個(gè)方向上對速率影響相等的幾何學(xué)參數(shù)。因此，通過計(jì)算濃度和結(jié)合與解離的實(shí)際速率可確定“開啟速率常數(shù)(Kon)”和“關(guān)閉速率常數(shù)(Koff)”。Koff/Kon之比能夠消除所有與親和力無關(guān)的參數(shù)，因此等同于解離常數(shù)Kd。通常見，Davies等(1990)AnnualRev.Biochem.59439-473。
抗體的“抗原結(jié)合位點(diǎn)”或“結(jié)合部分”是指參與抗原結(jié)合的免疫球蛋白分子的一部分?？乖Y(jié)合位點(diǎn)由重鏈(“H”)和輕鏈(“L”)的N末端可變區(qū)(“V”)的氨基酸殘基形成。重鏈和輕鏈的V區(qū)內(nèi)的三個(gè)高度差異片段稱作“高變區(qū)”，其插在更為保守的稱為“構(gòu)架區(qū)”或“FRs”的側(cè)翼片段之間。因此術(shù)語“FR”是指免疫球蛋白中高變區(qū)之間和鄰近高變區(qū)自然發(fā)現(xiàn)的氨基酸序列。在抗體分子中，輕鏈的三個(gè)高變區(qū)和重鏈的三個(gè)高變區(qū)在三維空間上彼此相對排列形成抗原結(jié)合表面?？乖Y(jié)合表面與所結(jié)合抗原的三維表面互補(bǔ)，每條重鏈和輕鏈的三個(gè)高變區(qū)稱作“互補(bǔ)決定區(qū)”或“CDRs”。
使用這里提供的代表性試驗(yàn)，結(jié)合劑可以進(jìn)一步能夠區(qū)分患有和不患癌癥如肺癌的患者。例如，與腫瘤蛋白結(jié)合的抗體或其它結(jié)合劑將優(yōu)選在至少大約20％患有疾病的患者中產(chǎn)生指示癌癥存在的信號，更優(yōu)選至少大約30％的患者?？晒┻x擇地，或此外，抗體將在至少大約90％不患癌癥的個(gè)體中產(chǎn)生指示不存在疾病的陰性信號。為了確定結(jié)合劑是否滿足這個(gè)要求，可以如這里所述測定來自患有和不患癌癥的患者(用標(biāo)準(zhǔn)臨床測試確定的)的生物樣本(如血液、血清、痰、尿和/或腫瘤活檢)中是否存在與結(jié)合劑結(jié)合的多肽。優(yōu)選，將測定統(tǒng)計(jì)學(xué)上具有顯著性的數(shù)量的患有和不患疾病的樣本。每種結(jié)合劑應(yīng)該滿足上述標(biāo)準(zhǔn)；然而，本領(lǐng)域普通技術(shù)人員將認(rèn)識到結(jié)合劑可以組合使用以提高敏感性。
任何滿足上述要求的試劑均可以是結(jié)合劑。例如，結(jié)合劑可以是含或不含肽成分的核糖體，RNA分子或多肽。在優(yōu)選的實(shí)施方案中，結(jié)合劑是抗體或其抗原結(jié)合片段。可以用本領(lǐng)域普通技術(shù)人員所知的各種方法中任何方法制備抗體，如見Harlow和Lane，AntibodiesA Laboratory Manual，Cold Spring HarborLaboratory，1988。通常，細(xì)胞培養(yǎng)技術(shù)可以產(chǎn)生抗體，包括產(chǎn)生這里所述的單克隆抗體，或?yàn)榱嗽试S重組抗體產(chǎn)生，通過將抗體基因轉(zhuǎn)染到合適的細(xì)菌或哺乳動物細(xì)胞宿主中。在一個(gè)技術(shù)中，將包含多肽的免疫原首先注射給多種哺乳動物中任何一種(如小鼠、大鼠、兔、綿羊或山羊)。在這個(gè)步驟中，本發(fā)明的多肽可以作為未作修飾的免疫原?？晒┻x擇地，特別是對于相對較短的多肽，如果多肽與載體蛋白例如牛血清白蛋白或匙孔血藍(lán)蛋白連接的話，可以引發(fā)較強(qiáng)的免疫應(yīng)答。將免疫原注射給動物宿主，優(yōu)選按照預(yù)定方案摻入一次或多次加強(qiáng)免疫，且動物定期放血。然后，可以通過例如使用與合適的固相支持體結(jié)合的多肽進(jìn)行親和層析，從這種抗血清中純化對多肽特異性的多克隆抗體。
對感興趣的抗原多肽特異性的單克隆抗體可以通過例如使用Kohler和Milstein，Eur.J.Immunol.6511-519，1976和其改進(jìn)技術(shù)制備。簡言之，這些方法包括制備能夠產(chǎn)生具有期望特異性(即，與感興趣多肽的反應(yīng)性)的抗體的無限增殖細(xì)胞系。這種細(xì)胞系可以例如從來自如上所述免疫的動物的脾細(xì)胞而產(chǎn)生。然后，通過例如與骨髓瘤細(xì)胞融合配偶體融合而使脾細(xì)胞無限增殖，優(yōu)選所述骨髓瘤細(xì)胞與免疫動物是同基因的?？梢允褂枚喾N融合技術(shù)。例如，脾細(xì)胞和骨髓瘤細(xì)胞可以與非離子去污劑混合幾分鐘，然后以低密度鋪在支持雜交細(xì)胞生長但不支持骨髓瘤細(xì)胞生長的選擇性培養(yǎng)基上。優(yōu)選的選擇技術(shù)使用HAT(次黃嘌呤、氨基蝶呤、胸苷)選擇。經(jīng)過足夠時(shí)間后，通常大約1-2周，觀察雜交集落。選擇單一集落并檢測其培養(yǎng)上清針對多肽的結(jié)合活性。優(yōu)選具有高反應(yīng)性和特異性的雜交瘤。
可以從生長的雜交瘤集落的上清中分離單克隆抗體。此外，可以使用各種技術(shù)增加產(chǎn)量，例如將雜交瘤細(xì)胞系注射到合適的脊椎動物宿主例如小鼠的腹腔中。然后可以從腹水或血液中收獲單克隆抗體。可以用常規(guī)技術(shù)如層析、凝膠過濾、沉淀和提取從抗體中除去污染物。本發(fā)明的多肽可以用于純化過程，例如親和層析步驟中。
本領(lǐng)域已知大量有治療用途的分子，其包含抗體分子的能夠顯示出免疫結(jié)合特性的抗原結(jié)合位點(diǎn)。蛋白水解酶木瓜蛋白酶優(yōu)選切割I(lǐng)gG分子產(chǎn)生幾個(gè)片段，其中兩個(gè)(“F(ab)”片段)各含有包括完整抗原結(jié)合位點(diǎn)的共價(jià)異源二聚體。胃蛋白酶能夠切割I(lǐng)gG分子得到幾個(gè)片段，包括含有兩個(gè)抗原結(jié)合位點(diǎn)的“F(ab’)2”片段。通過優(yōu)選蛋白水解切割I(lǐng)gM，偶爾切割I(lǐng)gG或IgA免疫球蛋白分子，可以產(chǎn)生“Fv”片段。然而，更常見使用本領(lǐng)域已知的重組技術(shù)得到Fv片段。Fv片段包括含抗原結(jié)合位點(diǎn)的非共價(jià)VH∷VL異源二聚體，它保留天然抗體分子的多數(shù)抗原識別和結(jié)合能力。Inbar等(1972)Proc.Nat.Acad.Sci.USA 692659-2662；Hochman等(1976)Biochem 152706-2710；和Ehrlich等(1980)Biochem 194091-4096。
單鏈Fv(“sFv”)多肽是共價(jià)連接的VH∷VL異源二聚體，它從包括由編碼肽的接頭連接的VH-和VL-編碼基因的基因融合表達(dá)。Huston等，(1988)Proc.Nat.Acad.Sci.USA 85(16)5879-5883。已經(jīng)描述了大量方法辨別化學(xué)結(jié)構(gòu)，以將來自抗體V區(qū)的天然聚集—但化學(xué)分離的—輕多肽鏈和重多肽鏈轉(zhuǎn)變成會折疊為與抗原結(jié)合位點(diǎn)結(jié)構(gòu)基本類似的三維結(jié)構(gòu)的sFv分子。如見Huston等的美國專利5,091,513和5,132,405；和Ladner等的美國專利4,946,778。
上述每個(gè)分子包括重鏈和輕鏈CDR組，分別插在為CDRS提供支持和限定CDRs相對彼此的空間關(guān)系的重鏈和輕鏈FR組之間。這里使用的術(shù)語“CDR組”是指重鏈或輕鏈V區(qū)的三個(gè)高變區(qū)。從重鏈或輕鏈N末端開始，這些區(qū)域分別稱作“CDR1”，“CDR2”和“CDR3”。因此，抗原結(jié)合位點(diǎn)包括六個(gè)CDRs，包含來自各重鏈和輕鏈V區(qū)的CDR組。包括單一CDR(如CDR1、CDR2或CDR3)的多肽這里稱為“分子識別單位”。對大量抗原-抗體復(fù)合體的晶體學(xué)分析已經(jīng)證明CDRs的氨基酸殘基與所結(jié)合抗原形成廣泛接觸，其中最廣泛的抗原接觸是與重鏈CDR3。因此，分子識別單位主要負(fù)責(zé)抗原結(jié)合位點(diǎn)的特異性。
這里使用的術(shù)語“FR組”是指構(gòu)成重鏈或輕鏈V區(qū)CDR組的CDRs框架的四條側(cè)翼氨基酸序列。一些FR殘基可能接觸所結(jié)合抗原；然而，F(xiàn)Rs主要負(fù)責(zé)V區(qū)折疊成抗原結(jié)合位點(diǎn)，特別是直接與CDRs相鄰的FR殘基。在FRs中，某些氨基殘基和某些結(jié)構(gòu)特征高度保守。在這方面，所有V區(qū)序列都含有大約90個(gè)氨基酸殘基的內(nèi)部二硫環(huán)。當(dāng)V區(qū)折疊成結(jié)合位點(diǎn)，CDRs呈現(xiàn)為形成抗原結(jié)合表面的突出的環(huán)基元。通常認(rèn)為存在FRs的保守結(jié)構(gòu)區(qū)影響CDR環(huán)折疊成某些“規(guī)范”結(jié)構(gòu)的形狀—不考慮精確的CDR氨基酸序列。而且，已知某些FR殘基參與穩(wěn)定抗體重鏈和輕鏈相互作用的結(jié)構(gòu)域間非共價(jià)接觸。
已經(jīng)描述了包含來自非人免疫球蛋白的抗原結(jié)合位點(diǎn)的許多“人源化”抗體分子，包括具有嚙齒動物V區(qū)和其相關(guān)CDRs與人恒定區(qū)融合的的嵌合抗體(Winter等(1991)Nature 349293-299；Lobuglio等(1989)Proc.Nat.Acad.Sci.USA 864220-4224；Shaw等(1987)J Immunol.1384534-4538；和Brown等(1987).Cancer Res.473577-3583)，在與適當(dāng)?shù)娜丝贵w恒定區(qū)融合前移植入人支持FR的嚙齒動物CDRs(Riechmann等(1988)Nature 332323-327；Verhoeyen等(1988)Science 2391534-1536；和Jones等(1986)Nature 321522-525)，和由重組鑲合的嚙齒動物FRs支持的嚙齒動物CDRs(歐洲專利公開號519,596，1992年12月23日公開)。設(shè)計(jì)這些“人源化”分子將對嚙齒動物抗人抗體分子產(chǎn)生的不期望的免疫應(yīng)答降到最小，這些反應(yīng)限制那些部分在人受體中治療應(yīng)用的持續(xù)時(shí)間和有效性。
這里使用的術(shù)語“鑲合FRs”和“重組鑲合的FRs”是指為了提供包含基本保留全部天然FR多肽折疊結(jié)構(gòu)的抗原結(jié)合位點(diǎn)的異源分子，用人FR殘基選擇性置換來自如嚙齒動物重鏈或輕鏈V區(qū)的FR殘基。鑲合技術(shù)基于理解抗原結(jié)合位點(diǎn)的配體結(jié)合特性主要由抗原結(jié)合表面內(nèi)重鏈和輕鏈CDR組的結(jié)構(gòu)和相對排列來決定。Davies等(1990)Ann.Rev.Biochem.59439-473。因此，僅其中CDR結(jié)構(gòu)、它們彼此的相互作用和它們與V區(qū)結(jié)構(gòu)域的其余部分的相互作用小心保留，抗原結(jié)合特異性才可以保留在人源化抗體中。通過使用鑲合技術(shù)，用人殘基選擇性置換容易遭遇免疫系統(tǒng)的外部(如可接近溶劑的)FR殘基以提供含弱免疫原性，或基本無免疫原性的鑲合表面的雜交分子。
鑲合方法使用Kabat等，Sequences of Proteins ofImmunological Interest，第4版，(U.S.Dept.of Health andHuman Services，U.S.Government Printing Office，1987)匯編的人抗體可變區(qū)的序列數(shù)據(jù)，Kabat更新數(shù)據(jù)庫和其它可進(jìn)入的美國和外國數(shù)據(jù)庫(核酸和蛋白)。V區(qū)氨基酸的溶劑可接近性可從人和小鼠抗體片段的已知三維結(jié)構(gòu)推斷出來。在鑲合小鼠抗原結(jié)合位點(diǎn)中有兩個(gè)通常步驟。首先，將感興趣的抗體分子可變區(qū)的FRs與從上述來源得到的人可變區(qū)的相應(yīng)FR序列進(jìn)行比較。然后將最同源的人V區(qū)與相應(yīng)的小鼠氨基酸逐個(gè)殘基進(jìn)行比較。使用本領(lǐng)域熟知的重組技術(shù)，用人部分中存在的殘基置換小鼠FR中與人相應(yīng)部分不同的殘基。僅僅對至少部分暴露的部分(溶劑可接近)進(jìn)行殘基轉(zhuǎn)換，小心進(jìn)行可能對V區(qū)結(jié)構(gòu)域的三級結(jié)構(gòu)具有顯著影響的氨基酸殘基例如脯氨酸、甘氨酸和帶電荷氨基酸的置換。
以這種方式，所得“鑲合的”小鼠抗原結(jié)合位點(diǎn)由此設(shè)計(jì)成保留小鼠CDR殘基，基本鄰近CDRs的殘基，鑒定為埋藏或大部分埋藏(溶劑不可接近)的殘基，據(jù)信參與重鏈和輕鏈結(jié)構(gòu)域之間非共價(jià)(如靜電和疏水)接觸的殘基，和認(rèn)為影響CDR環(huán)的“規(guī)范”三級結(jié)構(gòu)的來自FRs的保守結(jié)構(gòu)區(qū)的殘基。然后將這些設(shè)計(jì)標(biāo)準(zhǔn)用于制備重組核苷酸序列，它將小鼠重鏈和輕鏈抗原結(jié)合位點(diǎn)的CDRs組合入人樣的FRs，可用于轉(zhuǎn)染哺乳動物細(xì)胞來表達(dá)顯示小鼠抗體分子的抗原特異性的重組人抗體。
在本發(fā)明的另一個(gè)實(shí)施方案中，本發(fā)明的單克隆抗體可以與一種或多種治療劑偶聯(lián)。這方面的合適藥劑包括放射性核素、分化誘導(dǎo)劑、藥物、毒素和其衍生物。優(yōu)選的放射性核素包括90Y，123I，125I，131I，186Re，188Re，211At和212Bi。優(yōu)選藥物包括氨甲蝶呤以及嘧啶和嘌呤類似物。優(yōu)選的分化誘導(dǎo)劑包括佛波醇酯和丁酸。優(yōu)選的毒素包括蓖麻毒蛋白、相思豆毒蛋白、白喉毒素、霍亂毒素、gelonin(植物的核糖體失活蛋白)、假單胞菌屬外毒素、志賀氏菌屬毒素和美洲商陸抗病毒蛋白。
治療劑可以與合適的單克隆抗體直接或間接(如通過接頭基團(tuán))偶聯(lián)(如共價(jià)鍵合)。當(dāng)藥劑和抗體每一種都具有能夠與另一種發(fā)生反應(yīng)的取代基時(shí)，二者之間可能直接發(fā)生反應(yīng)。例如，一個(gè)上面的親核基團(tuán)，如氨基或巰基，可能能與另一個(gè)上面的含羰基基團(tuán)如酸酐或?；u，或含好的離去基團(tuán)的烷基(如鹵化物)發(fā)生反應(yīng)。
可供選擇地，最好治療劑和抗體通過接頭基團(tuán)偶聯(lián)。接頭基團(tuán)可以起間隔作用使抗體與試劑遠(yuǎn)離以避免對結(jié)合能力的干擾。接頭基團(tuán)也可以用來增加試劑或抗體上的取代基的化學(xué)反應(yīng)性，因此增加結(jié)合效率?；瘜W(xué)反應(yīng)性增加也可有助于試劑或試劑上的功能基團(tuán)的利用，否則將不可能。
多種雙功能或多功能試劑，包括同功能和異功能(如在PierceChemical Co.，Rockford，IL目錄中所述的那些)，均可以用作接頭基團(tuán)，這對于本領(lǐng)域技術(shù)人員將很明顯?？梢岳缤ㄟ^氨基、羧基、巰基或氧化碳水化合物殘基來實(shí)現(xiàn)偶聯(lián)。許多參考文獻(xiàn)描述了這種方法，如Rodwell等的美國專利4,671,958。
當(dāng)治療劑從本發(fā)明的免疫綴合物的抗體部分脫離時(shí)更有效時(shí)，最好使用在內(nèi)在化至細(xì)胞中的過程中或當(dāng)時(shí)可裂解的接頭基團(tuán)。已經(jīng)描述了多種不同的可裂解接頭基團(tuán)。試劑在細(xì)胞內(nèi)從這些接頭基團(tuán)中脫離的機(jī)制包括通過二硫鍵還原(如Spitler的美國專利4,489,710)，照射對光不穩(wěn)定的鍵(如Senter等的美國專利4,625,014)，衍生氨基酸側(cè)鏈的水解(如Kohn等的美國專利4,638,045)，血清補(bǔ)體介導(dǎo)的水解(如Rodwell等的美國專利4,671,958)，和酸催化水解(如Blattler等的美國專利4,569,789)而裂解。
最好將多種藥劑與抗體偶聯(lián)。在一個(gè)實(shí)施方案中，將藥劑的多個(gè)分子與一個(gè)抗體分子偶聯(lián)。在另一個(gè)實(shí)施方案中，可以將一種以上類型的藥劑與一個(gè)抗體偶聯(lián)。不考慮具體的實(shí)施方案，可以用多種方法制備含有一種以上藥劑的免疫結(jié)合物。例如，一種以上藥劑可以直接與抗體分子偶聯(lián)，或可以使用提供多個(gè)連接位點(diǎn)的接頭?？晒┻x擇地，可以使用載體。
載體可以以各種方法承載藥劑，包括直接或通過接頭基團(tuán)的共價(jià)鍵合。合適的載體包括蛋白如白蛋白(如Kato等的美國專利4,507,234)，肽和多糖例如氨基葡聚糖(如Shih等的美國專利號4,699,784)。載體也可以通過非共價(jià)鍵合或包封，例如包入脂質(zhì)體囊內(nèi)(如美國專利4,429,008和4,873,088)而承載藥劑。對放射性核素劑異性的載體包括放射性鹵素化的小分子和螯合化合物。例如，美國專利4,735,792公開了代表性放射性鹵素化的小分子及其合成。放射性核素螯合物可以由螯合包括那些含有氮和硫原子作為供體原子以結(jié)合金屬、或金屬氧化物、放射性核素的化合物而形成。例如，Davison等的美國專利4,673,562公開了代表性的螯合化合物及其合成。T細(xì)胞組合物在本發(fā)明另一個(gè)方面，提供了對這里公開的腫瘤多肽或其變異體或衍生物特異性的T細(xì)胞。這種細(xì)胞通?？梢允褂脴?biāo)準(zhǔn)步驟在體外或離體制備。例如，可以從患者的骨髓、外周血或者骨髓或外周血的級分來分離T細(xì)胞，采用商業(yè)可獲得的細(xì)胞分離系統(tǒng)，例如IsolexTM系統(tǒng)，來自Nexell Therapeutics，Inc.(Irvine，CA；也見美國專利5,240,856；美國專利5,215,926；WO 89/06280；WO 91/16116和WO 92/07243)?？晒┻x擇地，T細(xì)胞可以來自相關(guān)或無關(guān)的人、非人哺乳動物，細(xì)胞系或培養(yǎng)物。
可以用多肽、編碼多肽的多核苷酸和/或表達(dá)這種多肽的抗原呈遞細(xì)胞(APC)刺激T細(xì)胞。這種刺激在足以允許產(chǎn)生對感興趣多肽特異性的T細(xì)胞的條件下進(jìn)行足夠的時(shí)間。優(yōu)選，本發(fā)明的腫瘤多肽或多核苷酸存在于送遞載體中，如微球體，以利于特異性T細(xì)胞產(chǎn)生。
如果T細(xì)胞特異性增殖，分泌細(xì)胞因子或殺死被多肽包裹或表達(dá)編碼該多肽的基因的靶細(xì)胞的話，認(rèn)為T細(xì)胞對本發(fā)明多肽是特異性的。可以使用多種標(biāo)準(zhǔn)技術(shù)中任何一種估計(jì)T細(xì)胞的特異性。例如，在鉻釋放測定或增殖測定中，與陰性對照相比，刺激指數(shù)在溶解和/或增殖中增加兩倍以上表明T細(xì)胞特異性。這種測定可以如例如Chen等，Cancer Res.541065-1070，1994所述進(jìn)行。可供選擇地，對T細(xì)胞增殖的檢測可以用各種已知技術(shù)完成。例如，可以通過測定DNA合成速率增加(如通過用含氚胸苷脈沖標(biāo)記T細(xì)胞培養(yǎng)物并測定摻入到DNA中的含氚胸苷量)檢測T細(xì)胞增殖。與腫瘤多肽(100ng/ml-100μg/ml，優(yōu)選200ng/ml-25μg/ml)接觸3-7天通常會使T細(xì)胞增殖增加至少兩倍。如上所述接觸2-3小時(shí)應(yīng)該導(dǎo)致T細(xì)胞活化，如使用標(biāo)準(zhǔn)細(xì)胞因子試驗(yàn)所測定，其中細(xì)胞因子(如TNF或IFN-γ)釋放水平增加兩倍表示T細(xì)胞活化(見Coligan等，Current Protocols in Immunology，vol.1，Wiley Interscience(Greene 1998))。對腫瘤多肽、多核苷酸或表達(dá)多肽的APC產(chǎn)生應(yīng)答而活化的T細(xì)胞可以是CD4+和/或CD8+?？梢允褂脴?biāo)準(zhǔn)技術(shù)擴(kuò)充對腫瘤多肽特異性的T細(xì)胞。在優(yōu)選的實(shí)施方案中，T細(xì)胞來自患者、相關(guān)供體或無關(guān)供體，并在刺激和擴(kuò)充后給予患者。
為了治療目的，可以在體外或體內(nèi)將對腫瘤多肽、多核苷酸或APC應(yīng)答而增殖的CD4+或CD8+T細(xì)胞進(jìn)行數(shù)量擴(kuò)充?？梢杂酶鞣N方法完成這種T細(xì)胞的體外增殖。例如，T細(xì)胞可以重新接觸腫瘤多肽或相應(yīng)于這種多肽免疫原性部分的短肽，添加或不添加T細(xì)胞生長因子，例如白介素-2，和/或合成腫瘤多肽的刺激細(xì)胞?？晒┻x擇地，可以通過克隆擴(kuò)充一種或多種在腫瘤多肽存在下增殖的T細(xì)胞的數(shù)量?？寺〖?xì)胞的方法是本領(lǐng)域熟知的，且包括有限稀釋。藥物組合物在另外的實(shí)施方案中，本發(fā)明涉及這里公開的一種或多種多核苷酸、多肽、T細(xì)胞和/或抗體組合物在藥學(xué)可接受載體中的制劑，單獨(dú)或與一種或多種其它形式治療組合，施用于細(xì)胞或動物。
應(yīng)該理解的是，如果期望，這里公開的組合物也可以與其它藥劑組合進(jìn)行給藥，例如，其它蛋白或多肽或各種藥物活性試劑。事實(shí)上，沒有限制可以包括的其它成分，只要另外的藥劑不對與靶細(xì)胞或宿主組織的接觸產(chǎn)生明顯的不利作用。因此組合物可以與具體情況所需的各種其它藥劑一起送遞。這種組合物可以從宿主細(xì)胞或其它生物來源純化，或可供選擇地可以如這里所述化學(xué)合成。同樣，這種組合物可以進(jìn)一步包含取代或衍生的RNA或DNA組合物。
因此，在本發(fā)明的另一個(gè)方面，提供了藥物組合物，其包含一種或多種這里描述的多核苷酸、多肽、抗體和/或T細(xì)胞組合物與生理可接受載體組合。在某些優(yōu)選實(shí)施方案中，本發(fā)明的藥物組合物包含本發(fā)明的免疫原性多核苷酸和/或多肽組合物用于預(yù)防性和治療性疫苗應(yīng)用。疫苗制劑通常在例如M.F.Powell和M.J.Newman主編，″Vaccine Design(the subunit and adjuvant approach)，″Plenum Press(NY，1995)中描述。通常，這種組合物將包含一種或多種本發(fā)明的多核苷酸和/和多肽組合物與一種或多種免疫刺激劑組合。
很明顯這里描述的任何藥物組合物可包含本發(fā)明多核苷酸和多肽的藥學(xué)可接受鹽。這種鹽可以從例如藥學(xué)可接受無毒堿，包括有機(jī)堿(如一級、二級和三級胺和堿性氨基酸的鹽)和無機(jī)堿(如鈉、鉀、鋰、銨、鈣和鎂鹽)來制備。
在另一個(gè)實(shí)施方案中，本發(fā)明的示例性免疫原性組合物，如疫苗組合物包含編碼一種或多種這里描述的多肽的DNA，使得多肽在原位產(chǎn)生。如上指出，多核苷酸可以在本領(lǐng)域普通技術(shù)人員所知的多種送遞系統(tǒng)的任何一種中給予。實(shí)際上，本領(lǐng)域熟知許多基因送遞技術(shù)，例如Rolland Crit.Rev.Therap.Drug Carrier Systems 15143-198，1998描述的，和那里引用的參考文獻(xiàn)。適當(dāng)?shù)亩嗪塑账岜磉_(dá)體系將當(dāng)然包含在患者中表達(dá)必需的調(diào)控DNA調(diào)控序列(例如適當(dāng)?shù)膯幼雍徒K止信號)?？晒┻x擇地，細(xì)菌送遞系統(tǒng)可以包括施用在其細(xì)胞表面表達(dá)多肽的免疫原性部分或分泌這種表位的細(xì)菌(例如芽孢桿菌-Calmette-Guerrin)。
因此，在某些實(shí)施方案中，使用多種已知的基于病毒的體系中任何一種，將編碼這里描述的免疫原性多肽的多核苷酸導(dǎo)入合適的哺乳動物細(xì)胞中表達(dá)。在一個(gè)示例的實(shí)施方案中，逆轉(zhuǎn)錄病毒為基因送遞系統(tǒng)提供了方便和有效的平臺。使用本領(lǐng)域所知的技術(shù)，可以將所選編碼本發(fā)明多肽的核苷酸序列插入載體并包裝到逆轉(zhuǎn)錄病毒顆粒中。然后可以將重組病毒分離并送遞給受試者。已經(jīng)描述了大量示例的逆轉(zhuǎn)錄病毒系統(tǒng)(如美國專利5,219,740；Miller和Rosman(1989)BioTechniques 7980-990；Miller，A.D.(1990)Human GeneTherapy 15-14；Scarpa等(1991)Virology 180849-852；Burns等(1993)Proc.Natl.Acad.Sci.USA 908033-8037；和Boris-Lawrie和Temin(1993)Cur.Opin.Genet.Develop.3102-109)。
此外，也描述了大量示例的基于腺病毒的系統(tǒng)。與整合到宿主基因組中的逆轉(zhuǎn)錄病毒不同，腺病毒始終存在于染色體外，因此使與插入誘變相關(guān)的風(fēng)險(xiǎn)降至最小(Haj-Ahmad和Graham(1986)J.Virol.57267-274；Bett等(1993)J.Virol.675911-5921；Mittereder等(1994)Human Gene Therapy 5717-729；Seth等(1994)J.Virol.68933-940；Barr等(1994)GeneTherapy 151-58；Berkner，K.L.(1988)BioTechniques 6616-629；和Rich等(1993)Human Gene Therapy 4461-476)。
各種腺伴隨病毒(AAV)載體系統(tǒng)也已經(jīng)發(fā)展用于送遞多核苷酸。用本領(lǐng)域熟知的技術(shù)可以很容易地構(gòu)建AAV載體。如見美國專利5,173,414和5,139,941；國際公開號WO 92/01070和WO93/03769；Lebkowski等(1988)Molec.Cell.Biol.83988-3996；Vincent等(1990)Vaccines 90(Cold Spring HarborLaboratory Press)；Carter，B.J.(1992)Current Opinion inBiotechnology 3533-539；Muzyczka，N.(1992)CurrentTopics in Microbiol.and Immunol.15897-129；Kotin，R.M.(1994)Human Gene Therapy 5793-801；Shelling和Smith(1994)Gene Therapy 1165-169；和Zhou等(1994)J.Exp.Med.1791867-1875。
其它可用于通過基因轉(zhuǎn)移來送遞編碼本發(fā)明多肽的多核苷酸的病毒載體包括那些來自痘病毒家族的病毒，例如牛痘病毒和鳥痘病毒。舉例來說，可以如下構(gòu)建表達(dá)新分子的牛痘病毒重組體。首先將編碼多肽的DNA插入到適當(dāng)?shù)妮d體中，使得它鄰近牛痘啟動子和側(cè)翼牛痘DNA序列，如編碼胸苷激酶(TK)的序列。然后用這個(gè)載體轉(zhuǎn)染同時(shí)用牛痘感染的細(xì)胞。同源重組將牛痘啟動子和編碼感興趣多肽的基因插入到病毒基因組中。通過在5-溴脫氧尿苷存在下培養(yǎng)細(xì)胞并選擇抗其的病毒噬斑，可以選擇所得的TK.sup.(-)重組體。
可以方便地使用基于牛痘的感染/轉(zhuǎn)染系統(tǒng)來提供這里描述的一種或多種多肽在生物體的宿主細(xì)胞中進(jìn)行可誘導(dǎo)的瞬時(shí)表達(dá)或共表達(dá)。在這個(gè)特定系統(tǒng)中，首先在體外用編碼噬菌體T7 RNA聚合酶的牛痘病毒重組體感染細(xì)胞。這個(gè)聚合酶顯示敏銳的敏感性，它只轉(zhuǎn)錄攜帶T7啟動子的模板。感染后，用所述多核苷酸或感興趣的多核苷酸轉(zhuǎn)染細(xì)胞，由T7啟動子驅(qū)動。在細(xì)胞質(zhì)中表達(dá)的來自牛痘病毒重組體的聚合酶將轉(zhuǎn)染的DNA轉(zhuǎn)錄為RNA，然后被宿主翻譯機(jī)構(gòu)翻譯為多肽。該方法提供了大量RNA及其翻譯產(chǎn)物的高水平、瞬時(shí)、在細(xì)胞質(zhì)中的產(chǎn)生。如見，Elroy-Stein和Moss，Proc.Natl.Acad.Sci.USA(1990)876743-6747；Fuerst等Proc.Natl.Acad.Sci.USA(1986)838122-8126。
可供選擇地，禽痘病毒，例如雞痘和黃雀痘病毒，也可以用于送遞感興趣的編碼序列。已知表達(dá)來自哺乳動物病原體的免疫原的重組禽痘病毒，當(dāng)給予非鳥物種時(shí)，可提供保護(hù)性免疫。禽痘載體用于人和其它哺乳動物物種中特別理想，因?yàn)榍荻粚俪蓡T只能在易感鳥種中生產(chǎn)復(fù)制，因此在哺乳動物細(xì)胞中無感染性。產(chǎn)生重組禽痘病毒的方法是本領(lǐng)域已知的并利用基因重組，如上所述有關(guān)牛痘病毒的產(chǎn)生。如見WO 91/12882；WO 89/03429和WO 92/03545。
也可以使用大量甲病毒載體中的任何一個(gè)送遞本發(fā)明的多核苷酸組合物，例如在美國專利5,843,723；6,015,686；6,008,035和6,015,694中描述的那些載體。也可以使用基于委內(nèi)瑞拉型馬腦炎病毒(VEE)的某些載體，其實(shí)例可在美國專利5,505,947和5,643,576中找到。
此外，分子綴合載體，例如Michael等J.Biol.Chem.(1993)2686866-6869和Wagner等Proc.Natl.Acad.Sci.USA(1992)896099-6103中描述的腺病毒嵌合載體，也可以用于本發(fā)明下的基因送遞。
關(guān)于這些和其它已知的基于病毒的送遞系統(tǒng)的另外說明信息可以在下文獻(xiàn)中找到，例如Fisher-Hoch等，Proc.Natl.Acad.Sci.USA 86317-321，1989；Flexner等，Ann.N.Y.Acad.Sci56986-103，1989；Flexner等，Vaccine 817-21，1990；美國專利4,603,112，4,769,330，和5,017,487；WO 89/01973；美國專利4,777,127；GB 2,200,651；EP 0,345,242；WO91/02805；Berkner，Biotechniques 6616-627，1988；Rosenfeld等，Science 252431-434，1991；Kolls等，Proc.Natl.Acad.Sci.USA 91215-219，1994；Kass-Eisler等，Proc.Natl.Acad.Sci.USA 9011498-11502，1993；Guzman等，Circulation 882838-2848，1993；和Guzman等，Cir.Res.731202-1207，1993。
在某些實(shí)施方案中，多核苷酸可以整合到靶細(xì)胞的基因組中。這種整合可以通過同源重組(基因置換)發(fā)生在特定位置和方向，或可以在隨機(jī)、非特異性位置(基因增大)整合。在其它的實(shí)施方案中，多核苷酸可以作為單獨(dú)的游離DNA片段穩(wěn)定保持在細(xì)胞中。這種多核苷酸片段或“游離體”編碼的序列足以允許獨(dú)立于宿主細(xì)胞周期或與宿主細(xì)胞周期同步的維持和復(fù)制。表達(dá)構(gòu)建體送遞至細(xì)胞的模式和多核苷酸保留在細(xì)胞中的位置取決于使用的表達(dá)構(gòu)建體的類型。
在本發(fā)明的另一個(gè)實(shí)施方案中，多核苷酸作為“裸露”DNA進(jìn)行施用/送遞，例如Ulmer等，Science 2591745-1749，1993所述和Cohen，Science 2591691-1692，1993的綜述。將DNA包被到有效轉(zhuǎn)運(yùn)入細(xì)胞的生物可降解珠上可以增加裸露DNA的攝取。
在另一個(gè)實(shí)施方案中，可以通過粒子轟擊方法送遞本發(fā)明的組合物，其中許多已有描述。在一個(gè)說明的例子中，氣驅(qū)動粒子加速可以用如Powderject Pharmaceuticals PLC(Oxford，UK)和Powderject Vacciries Inc.(Madison，WI)制造的那些裝置來完成，其中一些例子在美國專利5,846,796；6,010,478，5,865,796；5,584,807；和歐洲專利0500799中描述。這個(gè)方法提供了無針?biāo)瓦f方法，其中顯微粒子的干粉劑，例如多核苷酸或多肽粒子，在由手動裝置產(chǎn)生的氦氣流中加速到高速，推動粒子進(jìn)入感興趣的靶組織。
在相關(guān)的實(shí)施方案中，可有效進(jìn)行氣驅(qū)動的無針注射本發(fā)明組合物的其它裝置和方法包括Bioject，Inc.(Portland，OR)提供的那些，其中一些例子在美國專利4,790,824；5,064,413；5,312,335；5,383,851；5,399,163；5,520,639和5,993,412中描述。
根據(jù)另一個(gè)實(shí)施方案，這里描述的藥物組合物除了包含本發(fā)明的免疫原性多核苷酸、多肽、抗體、T細(xì)胞和/或APC組合物外，還將包含一種或多種免疫刺激劑。免疫刺激劑是指基本上任何增強(qiáng)或加強(qiáng)對外源抗原的免疫應(yīng)答(抗體和/或細(xì)胞介導(dǎo)的)的物質(zhì)。一種優(yōu)選類型的免疫刺激劑包含佐劑。許多佐劑含有設(shè)計(jì)為保護(hù)抗原不發(fā)生快速分解代謝的物質(zhì)，例如氫氧化鋁或礦物油，和免疫應(yīng)答刺激劑，例如脂質(zhì)A、來自百日咳博德特氏菌或結(jié)核分枝桿菌的蛋白。某些佐劑是商業(yè)可得到的，例如弗氏不完全佐劑和完全佐劑(DifcoLaboratories，Detroit，MI)；Merck佐劑65(Merck和Company，Inc.，Rahway，NJ)；AS-2(SmithKline Beecham，Philadelphia，PA)；鋁鹽例如氫氧化鋁凝膠(明礬)或磷酸鋁；鈣、鐵或鋅鹽；?；野彼岬牟蝗苄詰乙海货；?；陽離子或陰離子衍生多糖；聚磷腈；可生物降解的微球體；單磷酰脂A和quil A。細(xì)胞因子，例如GM-CSF、白介素-2，-7，-12和其它類似的生長因子也可以用作佐劑。
本發(fā)明的某些實(shí)施方案中，優(yōu)選佐劑組合物主要誘導(dǎo)Th1型免疫應(yīng)答。高水平Th1型細(xì)胞因子(如IFN-γ、TNFα、IL-2和IL-12)傾向于誘導(dǎo)針對所施用抗原的細(xì)胞介導(dǎo)的免疫應(yīng)答。與此相比，高水平Th2型細(xì)胞因子(如IL-4、IL-5、IL-6和IL-10)傾向于誘導(dǎo)體液免疫應(yīng)答。應(yīng)用如這里提供的疫苗后，患者將支持包括Th1和Th2型應(yīng)答的免疫應(yīng)答。在優(yōu)選的實(shí)施方案中，其中主要是Th1型的應(yīng)答，Th1型細(xì)胞因子的水平將增加到比Th2型細(xì)胞因子水平更高的程度。使用標(biāo)準(zhǔn)測定很容易估計(jì)這些細(xì)胞因子的水平。細(xì)胞因子家族的綜述見Mosmann和Coffman，Ann.Rev.Immunol.7145-173，1989。
某些優(yōu)選的主要引起Th1型應(yīng)答的佐劑包括例如單磷酰脂A，優(yōu)選3-脫-O-酰單磷酰脂A和鋁鹽的組合。MPL_佐劑從Corixa公司可以得到(Seattle，WA；例如見美國專利4,436,727；4,877,611；4,866,034和4,912,094)。含CpG的寡核苷酸(其中CpG二核苷酸是非甲基化的)也主要誘導(dǎo)Th1應(yīng)答。這種寡核苷酸是熟知的且在例如WO 96/02555，WO 99/33488和美國專利6,008,200和5,856,462中描述。免疫刺激性DNA序列也在例如Sato等，Science273352，1996中描述。另一種優(yōu)選的佐劑包括皂甙，例如QuilA，或其衍生物，包括QS21和QS7(Aquila BiopharmaceuticalsInc.，F(xiàn)ramingham，MA)；七葉皂苷；毛地黃皂甙；或Gypsophila或Chenopodium quinoa皂甙。其它優(yōu)選制劑在本發(fā)明的佐劑組合物中包括一種以上的皂甙，例如至少兩種下列皂甙的組合QS21，QS7，Quil A，β-七葉皂苷或毛地黃皂甙。
可供選擇地，皂甙制劑可以與疫苗載體組合，所述疫苗載體包括脫乙酰殼多糖或其它聚陽離子聚合物、聚交酯和聚交酯-共-乙交酯微粒、基于聚N乙酰葡糖胺的聚合物基質(zhì)，包括多糖或化學(xué)修飾的多糖的微粒，脂質(zhì)體和基于脂質(zhì)的微粒，包括甘油單酯的微粒等。皂甙也可以在膽固醇存在下配制以形成微粒結(jié)構(gòu)如脂質(zhì)體或ISCOMs。此外，皂甙可以與聚氧乙烯醚或酯共同配制，在非微粒溶液或懸液中，或在微粒結(jié)構(gòu)如少層脂質(zhì)體或ISCOM中。皂甙也可以與賦形劑例如CarbopolR共同配制，以增加粘性，或可以與粉狀賦形劑如乳糖共同配制成干粉形式。
在一個(gè)優(yōu)選實(shí)施方案中，佐劑系統(tǒng)包括單磷酰脂A和皂甙衍生物的組合，例如QS21和3D-MPL_佐劑組合，如WO 94/00153所述，或反應(yīng)原性較低的組合物，其中QS21用膽固醇淬滅，如WO 96/33739所述。其它優(yōu)選的制劑包括水包油乳液和生育酚。WO 95/17210中描述了另一個(gè)特別優(yōu)選的使用在水包油乳液中的QS21、3D-MPL_佐劑和生育酚的佐劑制劑。
另一個(gè)增強(qiáng)佐劑系統(tǒng)包括含CpG寡核苷酸和皂甙衍生物的組合，特別是CpG和QS21的組合在WO 00/09159中公開。優(yōu)選制劑另外包括水包油乳液和生育酚。
另外的用在本發(fā)明的藥物組合物中的示例佐劑包括MontanideISA 720(Seppic，法國)，SAF(Chiron，加利福尼亞州，美國)，ISCOMS(CSL)，MF-59(Chiron)，SBAS佐劑系列(如SBAS-2或SBAS-4，可從SmithKline Beecham，Rixensart，Belgium得到)，Detox(Enhanzyn_)(Corixa，Hamilton，MT)，RC-529(Corixa，Hamilton，MT)和其它氨烷基氨基葡糖苷4-磷酸鹽(AGPs)，例如在待審的美國專利申請系列號08/853,826和09/074,720中描述的那些，其公開以其完整形式引入這里作為參考，以及聚氧乙烯醚佐劑如在WO 99/52549A1中描述的那些。
其它優(yōu)選佐劑包括通式(I)HO(CH2CH2O)n-A-R的佐劑分子，其中n是1-50，A是一個(gè)鍵或-C(O)-，R是C1-50烷基或苯基C1-50烷基。
本發(fā)明的一個(gè)實(shí)施方案由包含通式(I)的聚氧乙烯醚的疫苗制劑組成，其中n在1和50之間，優(yōu)選4-24，最優(yōu)選9；R是C1-50，優(yōu)選C4-C20烷基和最優(yōu)選C12烷基，A是一個(gè)鍵。聚氧乙烯醚的濃度應(yīng)該在0.1-20％的范圍內(nèi)，優(yōu)選0.1-10％，最優(yōu)選在0.1-1％的范圍內(nèi)。優(yōu)選的聚氧乙烯醚選自下組聚氧乙烯-9-月桂基醚、聚氧乙烯-9-硬脂基醚、聚氧乙烯-8-硬脂基醚、聚氧乙烯-4-月桂基醚、聚氧乙烯-35-月桂基醚和聚氧乙烯-23-月桂基醚。Merck索引(12th版；登錄項(xiàng)7717)中描述了聚氧乙烯醚例如聚氧乙烯月桂醚。WO 99/52549中描述了這些佐劑分子。
如果期望，根據(jù)上面通式(I)的聚氧乙烯醚可以與另一種佐劑組合。例如，優(yōu)選的佐劑組合優(yōu)選含有如待審的英國專利申請GB9820956.2所述的CpG。
根據(jù)本發(fā)明的另一個(gè)實(shí)施方案，這里描述的免疫原性組合物通過抗原呈遞細(xì)胞(APCs)如樹突細(xì)胞、巨噬細(xì)胞、B細(xì)胞、單核細(xì)胞和其它可以改造成有效APCs的細(xì)胞送遞給宿主。這種細(xì)胞可以但不是必需被遺傳修飾以增加呈遞抗原的能力，以提高活化和/或維持T細(xì)胞應(yīng)答，以本身具有抗腫瘤效果和/或與接受者免疫相容(即相配的HLA單倍型)。APCs通?？梢詮亩喾N生物體液和器官的任何一種中分離，包括腫瘤和腫瘤旁組織，且可以是自體的、同種異體的、同基因的或異基因的細(xì)胞。
本發(fā)明的某些優(yōu)選實(shí)施方案使用樹突細(xì)胞或其祖細(xì)胞作為抗原呈遞細(xì)胞。樹突細(xì)胞是非常有效的APCs(Banchereau和Steinman，Nature 392245-251，1998)且已經(jīng)表明可有效作為生理佐劑引起預(yù)防性或治療性抗腫瘤免疫(見Timmerman和Levy，Ann.Rev.Med 50507-529，1999)。通常，樹突細(xì)胞可以基于其典型的性狀(在原位是星狀，在體外可見到明顯的細(xì)胞質(zhì)突起(樹突))，其高效攝取、加工和呈遞抗原的能力及其活化幼稚T細(xì)胞應(yīng)答的能力而鑒定。當(dāng)然可以改造樹突細(xì)胞以表達(dá)通常在體內(nèi)或離體樹突細(xì)胞中未發(fā)現(xiàn)的特異性細(xì)胞表面受體或配體，并且這種修飾的樹突細(xì)胞包括在本發(fā)明中。作為樹突細(xì)胞的可替換物，在疫苗中可以使用承載分泌囊泡抗原的樹突細(xì)胞(稱作外來體)(見Zitvogel等，Nature Med.4594-600，1998)。
樹突細(xì)胞和祖細(xì)胞可以從外周血、骨髓、腫瘤浸潤細(xì)胞、旁腫瘤組織浸潤細(xì)胞、淋巴結(jié)、脾、皮膚、臍帶血或其它合適的組織或液體得到。例如，通過向從外周血收獲的單核細(xì)胞培養(yǎng)物中加入細(xì)胞因子如GM-CSF、IL-4、IL-13和/或TNFα的組合，樹突細(xì)胞可以離體分化?？晒┻x擇地，通過向培養(yǎng)基中加入GM-CSF、IL-3、TNFα、CD40配體、LPS、flt3配體和/或誘導(dǎo)樹突細(xì)胞分化、成熟和增殖的其它化合物的組合，從外周血、臍帶血或骨髓收獲的CD34陽性細(xì)胞可以分化為樹突細(xì)胞。
樹突細(xì)胞很方便地分為“未成熟”和“成熟”細(xì)胞，它提供了區(qū)分兩種表征清楚的表型的簡單方法。然而，不這個(gè)命名應(yīng)該解釋為排除所有可能的分化中間階段。未成熟樹突細(xì)胞表征為抗原攝取和加工能力高的APC，其與Fcγ受體和甘露糖受體高表達(dá)有關(guān)。成熟表型典型的特征是這些標(biāo)志表達(dá)低，但負(fù)責(zé)T細(xì)胞活化的細(xì)胞表面分子如I類和II類MHC、粘附分子(如CD54和CD11)和共刺激分子(如CD40、CD80、CD86和4-1BB)的表達(dá)高。
通?？梢杂帽景l(fā)明的多核苷酸(或其部分或其它變異體)轉(zhuǎn)染APCs，使得編碼的多肽或其免疫原性部分在細(xì)胞表面表達(dá)。這種轉(zhuǎn)染可以在體外內(nèi)發(fā)生，然后包含這種轉(zhuǎn)染細(xì)胞的藥物組合物可以用于治療目的，如這里所述?？晒┻x擇地，定向于樹突細(xì)胞或其它抗原呈遞細(xì)胞的基因送遞載體可以施用于患者，引起體內(nèi)發(fā)生的轉(zhuǎn)染。通?？梢允褂美缛魏伪绢I(lǐng)域所知的方法進(jìn)行體內(nèi)和離體轉(zhuǎn)染樹突細(xì)胞，例如WO 97/24447中描述的方法，或Mahvi等，Immunology and cellBiology 75456-460，1997描述的基因槍方法。樹突細(xì)胞承載抗原可以通過將樹突細(xì)胞或祖細(xì)胞與腫瘤多肽、DNA(裸露的或在質(zhì)粒載體中)或RNA一起溫育；或與表達(dá)抗原的重組細(xì)菌或病毒(如牛痘、禽痘、腺病毒或慢病毒載體)共同溫育來完成。承載前，多肽可以與提供T輔助細(xì)胞的免疫配偶體(如載體分子)共價(jià)結(jié)合。可供選擇地，可以單獨(dú)或在多肽存在下，用未結(jié)合的免疫配偶體對樹突細(xì)胞進(jìn)行脈沖。
盡管本領(lǐng)域普通技術(shù)人員所知的任何合適載體可以用于本發(fā)明的藥物組合物，載體類型通常會取決于給藥方式而不同。本發(fā)明的組合物可以配制用于任何適當(dāng)?shù)慕o藥方式，包括例如，局部、口服、鼻、粘膜、靜脈內(nèi)、顱內(nèi)、腹膜內(nèi)、皮下和肌肉內(nèi)給藥。
用于這種藥物組合物的載體是生物相容性的，并可以也是生物可降解的。在某些實(shí)施方案中，優(yōu)選制劑提供活性成分釋放水平相對恒定。然而，在其它實(shí)施方案中，可能期望給藥后立即發(fā)生更快速的釋放。這種組合物的配制在本領(lǐng)域普通技術(shù)人員使用已知技術(shù)的水平內(nèi)。這方面有效的示例載體包括聚(丙交酯-共-乙交酯)微粒、聚丙烯酸酯、膠乳、淀粉、纖維素、葡聚糖等等。其它示例的延遲釋放的載體包括超分子生物載體，它包括非液體親水芯(如交聯(lián)多糖或低聚糖)和，任選的包括兩親化合物如磷脂的外層(如見美國專利5,151,254和PCT申請WO 94/20078，WO/94/23701和WO96/06638)。在緩釋制劑中所含活性化合物的量取決于植入的部位、釋放速度和期望的持續(xù)時(shí)間以及待治療或預(yù)防病癥的性質(zhì)。
在另一個(gè)示例的實(shí)施方案中，使用生物可降解微球體(如聚乳酸聚甘醇酸酯)作為本發(fā)明組合物的載體。合適的生物可降解微球體在例如美國專利4,897,268；5,075,109；5,928,647；5,811,128；5,820,883；5,853,763；5,814,344，5,407,609和5,942,252中公開。改進(jìn)的乙型肝炎核心蛋白載體系統(tǒng)，例如WO/99 40934和那里引用的文獻(xiàn)中所述，也將在許多應(yīng)用中有效。另一個(gè)示例載體/送遞體系使用包含顆粒蛋白復(fù)合體的載體，例如美國專利5,928,647中所述的那些，它能夠在宿主中誘導(dǎo)I類限制性細(xì)胞毒性T淋巴細(xì)胞應(yīng)答。
本發(fā)明的藥物組合物通常將進(jìn)一步包含一種或多種緩沖液(如中性緩沖鹽水或磷酸緩沖鹽水)、碳水化合物(如葡萄糖、甘露糖、蔗糖或葡聚糖)、甘露醇、蛋白、多肽或氨基酸如甘氨酸、抗氧化劑、抑菌劑、螯合劑如EDTA或谷胱甘肽、佐劑(如氫氧化鋁)、使制劑與受體血液等滲、低滲或弱高滲的溶質(zhì)、懸浮劑、增稠劑和/或防腐劑?？晒┻x擇地，本發(fā)明的組合物可以配制成冷凍干燥物。
這里描述的藥物組合物可以存在于單位劑量或多劑量容器中，例如密封的安瓿或小瓶。通常這種容器的封裝方式保持制劑的無菌性和穩(wěn)定性直到使用時(shí)。通常，制劑可以以油狀或含水載體中的懸浮劑、溶液或乳劑形式保存?？晒┻x擇地，藥物組合物可以在僅需在使用前立即添加無菌液體載體的冷凍干燥條件下保存。
開發(fā)在各種治療方案中使用這里描述的特定組合物的合適劑量和治療方案，包括如口服、腸胃外、靜脈內(nèi)、鼻內(nèi)和肌肉內(nèi)給藥和制劑，是本領(lǐng)域熟知的，在下面簡要討論其中的一些作一般說明目的。
在某些應(yīng)用中，這里公開的藥物組合物可以通過口服給予動物。為此，這些組合物可以與無活性稀釋劑或與可同化可食用載體共同配制，或它們可以包入硬殼或軟殼明膠膠囊中，或它們可以壓成片劑，或它們可以直接摻入膳食食物中。
活性化合物甚至可以與賦形劑摻合并以可攝入片劑、口含片劑、錠劑、膠囊、酏劑、懸浮劑、糖漿、糯米紙囊劑等等形式使用(見，例如Mathiowitz等，Nature 1997 Mar 27；386(6623)410-4；Hwang等Crit Rev Ther Drug Carrier Syst 1998；15(3)243-84；美國專利5,641,515；美國專利5,580,579和美國專利5,792,451)。片劑、錠劑、丸劑、膠囊等等也可以含有多種另外的成分中任何成分，例如，可以加入粘合劑，如黃蓍膠、阿拉伯膠、玉米淀粉或明膠；賦形劑，如磷酸二鈣；崩解劑，如玉米淀粉、馬鈴薯淀粉、藻酸等等；潤滑劑，如硬脂酸鎂；和甜味劑，如蔗糖、乳糖或糖精，或調(diào)味劑，如薄荷、冬青油或櫻桃調(diào)味劑。當(dāng)劑量單位形式是膠囊時(shí)，除了上述類型的材料外，它還可以含有液體載體?？纱嬖诟鞣N其它材料作為包衣或改進(jìn)劑量單位的物理形式。例如，片劑、丸劑或膠囊可以用紫膠、糖或二者包衣。當(dāng)然，用于制備任何劑量單位形式的任何材料應(yīng)該是藥學(xué)純的且所使用的量基本無毒。此外，活性化合物可以摻入緩釋制劑中。
典型地，這些制劑含有至少大約0.1％活性化合物或更多，盡管活性成分的百分比當(dāng)然可以變化且可以方便地在總制劑重量或體積的大約1或2％至大約60％或70％或更高之間。自然，可以制備每種治療有效組合物中活性化合物的量使在任何給定單位劑量化合物中可以得到合適的劑量。如溶解度、生物可利用率、生物半衰期、給藥途徑、產(chǎn)品保質(zhì)期，以及其它藥學(xué)考慮因素將是制備這種藥物制劑領(lǐng)域的技術(shù)人員可以想到的，由此可取多種劑量和治療方案。
對于口服，本發(fā)明的組合物可以選擇性地與一種或多種賦形劑摻合為漱口劑、牙膏、口含片劑、口腔噴霧或舌下口服制劑的形式。可供選擇地，活性成分可以摻入口服溶液中，如含硼酸鈉、甘油和碳酸氫鉀的溶液，或分散在牙膏中，或以治療有效量加入到組合物中，組合物可以包括水，粘合劑、磨擦劑、調(diào)味劑、發(fā)泡劑和濕潤劑?？晒┻x擇地，組合物可以形成可置于舌下或在口中溶解的片劑或溶液形式。
在某些情況下，會期望腸胃外、靜脈內(nèi)、肌肉內(nèi)或甚至腹膜內(nèi)送遞這里公開的藥物組合物。這種方法是本領(lǐng)域技術(shù)人員熟知的，其中一些進(jìn)一步在例如美國專利5,543,158；美國專利5,641,515和美國專利5,399,363中描述。在某些實(shí)施方案中，可以在水中適當(dāng)混合表面活性劑，如羥丙基纖維素來制備作為游離堿或藥學(xué)可接受鹽的活性化合物的溶液。也可以在甘油、液態(tài)聚乙二醇和其混合物和油中制備分散劑。在普通保存和使用條件下，這些制劑通常將含有防腐劑以防止微生物生長。
適合注射使用的示例藥物形式包括無菌水溶液或分散劑和臨時(shí)制備無菌注射溶液或分散劑的無菌粉劑(例如，見美國專利5,466,468)。在所有情況下，所用形式必須無菌且流動性必須能容易注射。在制造和保存條件下，它必須穩(wěn)定且必須保持抵抗微生物的污染作用，如細(xì)菌和真菌。載體可以是含有例如水、乙醇、多元醇(如甘油、丙二醇和液態(tài)聚乙二醇等等)，其合適的混合物，和/或植物油的溶劑或分散介質(zhì)。可以例如通過使用包衣如卵磷脂，在分散劑的情況下通過維持所需的微粒大小和/或通過使用表面活性劑來維持適當(dāng)?shù)牧鲃有浴８鞣N抗菌劑和抗真菌劑，例如對羥基苯甲酸酯類、氯丁醇、苯酚、山梨酸、硫柳汞等等可利于防止微生物作用。在許多情況下，將優(yōu)選包括等滲劑，例如糖或氯化鈉。組合物中使用延遲吸收劑可使注射組合物的吸收延遲，例如一硬脂酸鋁和明膠。
在一個(gè)實(shí)施方案中，對于以水溶液進(jìn)行胃腸外給藥，如果需要，溶液應(yīng)該適當(dāng)緩沖，并用足夠的鹽水或葡萄糖首先使得液體稀釋劑等滲。這些特定的水溶液特別適合靜脈內(nèi)、肌肉內(nèi)、皮下和腹膜內(nèi)給藥。與此相關(guān)，按照本發(fā)明的公開，本領(lǐng)域技術(shù)人員將知道可使用的無菌含水介質(zhì)。例如，一個(gè)劑量可以溶于1ml等滲NaCl溶液中加入1000ml皮下輸注液或在計(jì)劃輸入部位注射，(見例如，″Remington’s Pharmaceutical Sciences″15版，1035-1038頁和1570-1580頁)。根據(jù)所治療的受試者的情況，將對劑量作必要的改動。此外，對于人體施用，制劑當(dāng)然將優(yōu)選滿足FDA生物標(biāo)準(zhǔn)局要求的無菌性、熱原性和一般安全性和純度標(biāo)準(zhǔn)。
在本發(fā)明的另一個(gè)實(shí)施方案中，這里公開的組合物可以配制成中性或鹽形式。示例的藥學(xué)可接受鹽包括酸加成鹽(與蛋白的游離氨基所形成)，和與無機(jī)酸所形成的鹽，無機(jī)酸如鹽酸或磷酸，或與有機(jī)酸如醋酸、草酸、酒石酸、杏仁酸等等形成的鹽。與游離羧基形成的鹽也可以來自無機(jī)堿，例如，鈉、鉀、銨、鈣或三價(jià)鐵的氫氧化物，和有機(jī)堿如異丙胺、三甲胺、組氨酸、普魯卡因等等。配制后，溶液將以與劑量制劑相容的方式和治療有效量進(jìn)行給藥。
載體可進(jìn)一步包含任何和所有溶劑、分散介質(zhì)、載體、包衣、稀釋劑、抗菌劑和抗真菌劑、等滲劑和吸收延遲劑、緩沖液、載體溶液、懸浮劑、膠體等等。這種用于藥物活性物質(zhì)的介質(zhì)和試劑的使用是本領(lǐng)域熟知的。除了與活性成分不相容的任何常規(guī)介質(zhì)或試劑外，可以預(yù)計(jì)它在治療組合物中的使用。補(bǔ)充活性成分也可以摻入到組合物中。短語“藥學(xué)可接受”是指當(dāng)施用于人體時(shí)，不產(chǎn)生過敏或類似不利反應(yīng)的分子實(shí)體和組合物。
在某些實(shí)施方案中，可以通過鼻內(nèi)噴霧、吸入和/或其它氣霧送遞載體送遞藥物組合物。已經(jīng)描述了通過鼻氣霧噴霧將基因、核酸和肽組合物直接送遞至肺的方法，例如，在美國專利5,756,353和美國專利5,804,212中。類似地，使用鼻內(nèi)微粒樹脂(Takenaga等，JControlled Release 1998 Mar 2；52(1-2)81-7)和溶血磷脂酰甘油化合物(美國專利5,725,871)送遞藥物也是藥物領(lǐng)域熟知的。類似地，美國專利5,780,045描述了示例的以聚四氟乙烯支持基質(zhì)形式跨粘膜送遞藥物。
在某些實(shí)施方案中，使用脂質(zhì)體、微膠囊、微粒、脂質(zhì)微粒、囊泡等等將本發(fā)明的組合物導(dǎo)入合適的宿主細(xì)胞/生物體。特別是，本發(fā)明的組合物可以配制成包入脂質(zhì)微粒、脂質(zhì)體、囊泡、微球體或微顆粒等等進(jìn)行送遞。可供選擇地，本發(fā)明的組合物可以共價(jià)或非共價(jià)結(jié)合至這種載體表面。
脂質(zhì)體和脂質(zhì)體樣制劑作為有效藥物載體的形成和使用是本領(lǐng)域技術(shù)人員通常所知的(見例如，Lasic，Trends Biotechnol 1998Jul；16(7)307-21；Takakura，Nippon Rinsho 1998 Mar；56(3)691-5；Chandran等，Indian J Exp Biol.1997 Aug；35(8)801-9；Margalit，Crit Rev Ther Drug Carrier Syst.1995；12(2-3)233-61；美國專利5,567,434；美國專利5,552,157；美國專利5,565,213；美國專利5,738,868和美國專利5,795,587，每篇以其完整形式特別引入這里作為參考)。
脂質(zhì)體已經(jīng)成功用于通常難于用其它方法轉(zhuǎn)染的許多細(xì)胞類型，包括T細(xì)胞懸液，原代肝細(xì)胞培養(yǎng)物和PC12細(xì)胞(Renneisen等，J.Biol Chem.1990 Sep 25；265(27)16337-42；Muller等，DNA Cell Biol.1990 Apr；9(3)221-9)。此外，脂質(zhì)體不受DNA長度的限制，后者對于基于病毒的送遞系統(tǒng)是典型的特征。脂質(zhì)體已經(jīng)有效用于將基因、各種藥物、放射治療劑、酶、病毒、轉(zhuǎn)錄因子、別構(gòu)劑等導(dǎo)入多種培養(yǎng)細(xì)胞系和動物中。此外，使用脂質(zhì)體在全身送遞后似乎不伴發(fā)自身免疫應(yīng)答或不可接受的毒性。
在某些實(shí)施方案中，脂質(zhì)體由分散于含水介質(zhì)的磷脂形式并自動形成多層同心雙層囊泡(術(shù)語也稱作多層囊泡(MLVs))。
可供選擇地，在其它實(shí)施方案中，本發(fā)明提供了本發(fā)明組合物的藥學(xué)可接受微膠囊制劑。微膠囊通?？梢砸苑€(wěn)定和可重復(fù)的方式包入化合物(見，例如Quintanar-Guerrero等，Drug Dev Ind Pharm.1998 Dec；24(12)1113-28)。為了避免由于細(xì)胞內(nèi)聚合物過載造成的副作用，可以使用能夠在體內(nèi)降解的聚合物設(shè)計(jì)這種超細(xì)微粒(大小約0.1μm)。這種微?？梢匀缋鏑ouvreur等，Crit RevTher Drug Carrier Syst.1988；5(1)1-20；zur Muhlen等，Eur J Pharm Biopharm.1998 Mar；45(2)149-55；Zambaux等J Controlled Release.1998 Jan 2；50(1-3)31-40；和美國專利5,145,684所述制備。癌癥治療方法在本發(fā)明進(jìn)一步的方面，這里描述的藥物組合物可以用于治療癌癥，特別是用于肺癌的免疫治療。在這種方法中，將這里描述的藥物組合物施用于患者，典型的是溫血?jiǎng)游?，?yōu)選是人?；颊呖梢灶净蓟蛭搭净及┌Y。因此，上面的藥物組合物可以用于預(yù)防癌癥發(fā)生或治療罹患癌癥的患者。藥物組合物和疫苗可以在手術(shù)去除原發(fā)腫瘤和/或給予例如放射治療或常規(guī)化療藥物的治療之前或之后給予。如上面討論的，可以用任何合適的方法施用藥物組合物，包括靜脈內(nèi)、腹膜內(nèi)、肌肉內(nèi)、皮下、鼻內(nèi)、真皮內(nèi)、肛門、陰道、局部和口服途徑給藥。
在某些實(shí)施方案中，免疫治療可以是主動免疫治療，其中治療依賴于給予免疫應(yīng)答改進(jìn)劑(例如這里提供的多肽和多核苷酸)后在體內(nèi)刺激內(nèi)源宿主免疫系統(tǒng)發(fā)生對抗腫瘤的反應(yīng)。
在其它實(shí)施方案中，免疫治療可以是被動免疫治療，其中治療包括送遞可直接或間接介導(dǎo)抗腫瘤效應(yīng)且不必依賴完整的宿主免疫系統(tǒng)的具有確定的腫瘤免疫活性的試劑(例如效應(yīng)細(xì)胞或抗體)。效應(yīng)細(xì)胞的例子包括如上討論的T細(xì)胞，T淋巴細(xì)胞(例如CD8+細(xì)胞毒性T淋巴細(xì)胞和CD4+T輔助腫瘤浸潤淋巴細(xì)胞)，殺傷細(xì)胞(如自然殺傷細(xì)胞和淋巴因子激活的殺傷細(xì)胞)，B細(xì)胞和表達(dá)這里提供的多肽的抗原呈遞細(xì)胞(如樹突細(xì)胞和巨噬細(xì)胞)。對這里引用的多肽特異性的T細(xì)胞受體和抗原受體可以被克隆、表達(dá)并轉(zhuǎn)移到其它載體或效應(yīng)細(xì)胞中進(jìn)行過繼免疫治療。這里提供的多肽也可以用于產(chǎn)生抗體或抗獨(dú)特型抗體(如上所述和在美國專利4,918,164中)進(jìn)行被動免疫治療。
如這里所述通過體外生長通?？梢缘玫阶銐驍?shù)量的效應(yīng)細(xì)胞用于過繼免疫治療。將單個(gè)抗原特異性效應(yīng)細(xì)胞數(shù)量擴(kuò)充到幾十億且保留體內(nèi)抗原識別的培養(yǎng)條件是本領(lǐng)域熟知的。這種體外培養(yǎng)條件典型地使用通常在細(xì)胞因子(如IL-2)和未分裂飼養(yǎng)細(xì)胞存在下用抗原間斷刺激。如上指出，為了產(chǎn)生用于免疫治療的足夠數(shù)量的細(xì)胞，可以用這里提供的免疫活性多肽快速擴(kuò)充抗原特異性T細(xì)胞培養(yǎng)物。特別是，可以使用本領(lǐng)域熟知的標(biāo)準(zhǔn)技術(shù)，對抗原呈遞細(xì)胞，例如樹突細(xì)胞、巨噬細(xì)胞、單核細(xì)胞、成纖維細(xì)胞和/或B細(xì)胞用免疫活性多肽進(jìn)行脈沖或用一種或多種多核苷酸進(jìn)行轉(zhuǎn)染。例如，可用具有適合增加在重組病毒或其它表達(dá)系統(tǒng)中表達(dá)的啟動子的多核苷酸轉(zhuǎn)染抗原呈遞細(xì)胞。用于治療的培養(yǎng)的效應(yīng)細(xì)胞必須能夠生長和廣泛分布，和在體內(nèi)長期存活。研究已經(jīng)表明用補(bǔ)充IL-2的抗原重復(fù)刺激可以誘導(dǎo)培養(yǎng)的效應(yīng)細(xì)胞在體內(nèi)生長和以相當(dāng)大的數(shù)量長期存活(見，例如Cheever等，Immunological Reviews 157177，1997)。
可供選擇地，表達(dá)這里引用的多肽的載體可以導(dǎo)入取自患者的抗原呈遞細(xì)胞并離體克隆繁殖以植回給同一患者?？梢允褂帽绢I(lǐng)域所知的任何方法將轉(zhuǎn)染細(xì)胞再次導(dǎo)入患者，優(yōu)選以無菌形式通過靜脈內(nèi)、腔內(nèi)、腹膜內(nèi)或腫瘤內(nèi)施用。
這里描述的治療組合物的給藥途徑和頻率，以及劑量，在個(gè)體與個(gè)體之間將會不同，使用標(biāo)準(zhǔn)技術(shù)可以很容易確定。通常，可以通過注射(如皮內(nèi)、肌肉內(nèi)、靜脈內(nèi)或皮下)、鼻內(nèi)(如通過吸入)或口服給予藥物組合物和疫苗。優(yōu)選，在52周內(nèi)可以給予1至10個(gè)劑量。優(yōu)選以1個(gè)月的間隔給予6個(gè)劑量，其后可以周期性地給予加強(qiáng)免疫。交替的方案可能對個(gè)體患者適合。合適的劑量是當(dāng)如上所述給予后，化合物的量能夠促進(jìn)抗腫瘤免疫應(yīng)答，且至少在基線(即未治療)水平以上10-50％?？梢酝ㄟ^測定患者抗腫瘤抗體或通過能夠在體外殺死患者腫瘤細(xì)胞的細(xì)胞溶解效應(yīng)細(xì)胞的疫苗依賴性產(chǎn)生來監(jiān)測這種反應(yīng)。與未接種患者相比，在接種的患者中這種疫苗應(yīng)該也能夠引起使臨床結(jié)果改善(如更頻繁緩解、完全或部分或更長時(shí)間無病存活)的免疫應(yīng)答。通常，對于含一種或多種多肽的藥物組合物和疫苗，劑量中存在的每種多肽的量范圍從每公斤宿主大約25μg至5mg。合適的劑量大小將隨患者大小變化，但典型的范圍從0.1mL至大約5mL。
通常，適當(dāng)?shù)膭┝亢椭委煼桨柑峁┗钚曰衔锏牧孔銐蛱峁┲委熀?或預(yù)防收益。這種反應(yīng)可以通過治療的患者與未治療的患者相比確定臨床結(jié)果改善(如更頻繁緩解、完全或部分或更長時(shí)間的無病存活)來監(jiān)測。對腫瘤蛋白的先前存在的免疫應(yīng)答的增加通常與臨床結(jié)果改善有關(guān)。通?？梢允褂脴?biāo)準(zhǔn)的增殖、細(xì)胞毒性或細(xì)胞因子測定來估計(jì)這種免疫應(yīng)答，所述測定可以使用得自患者治療前后的樣本來實(shí)施。癌癥檢測和診斷組合物、方法和試劑盒通常，可以基于得自患者的生物樣本(例如，血液、血清、痰、尿和/或腫瘤活檢)中存在一種或多種肺腫瘤蛋白和/或編碼這種蛋白的多核苷酸在患者中檢測癌癥。換言之，這種蛋白可以用作指示癌癥如肺癌存在或不存在的標(biāo)志。此外，這種蛋白可用于檢測其它癌癥。這里提供的結(jié)合劑通常允許檢測生物樣本中與結(jié)合劑結(jié)合的抗原水平。多核苷酸引物和探針可以用于檢測編碼腫瘤蛋白的mRNA水平，它也是癌癥存在或不存在的標(biāo)志。通常，肺腫瘤序列應(yīng)該是在腫瘤組織中以至少高于正常組織三倍的水平存在。
有多種本領(lǐng)域普通技術(shù)人員所知的各種測定格式來使用結(jié)合劑檢測樣本中的多肽標(biāo)志。如見，Harlow和Lane，AntibodiesALaboratory Manual，Cold Spring Harbor Laboratory，1988。通常，可以通過(a)使得自患者的生物樣本接觸結(jié)合劑；(b)檢測樣本中與結(jié)合劑結(jié)合的多肽水平；和(c)將多肽水平與預(yù)先確定的截?cái)嘀颠M(jìn)行比較來確定患者存在或不存在癌癥。
在優(yōu)選實(shí)施方案中，測定包括使用固定在固相支持體上的結(jié)合劑結(jié)合多肽并與樣本其余成分分開。然后可以用含有報(bào)道基因基團(tuán)并與結(jié)合劑/多肽復(fù)合體特異性結(jié)合的檢測試劑檢測結(jié)合多肽。這種檢測試劑可以包括，例如，與多肽特異性結(jié)合的結(jié)合劑或抗體或與結(jié)合劑特異性結(jié)合的其它物質(zhì)，如抗免疫球蛋白、蛋白G、蛋白A或凝集素?？晒┻x擇地，可以采用競爭性測定，其中用報(bào)道基團(tuán)標(biāo)記多肽并在結(jié)合劑與樣本溫育后，使多肽結(jié)合固定的結(jié)合劑。樣本成分抑制標(biāo)記的多肽與結(jié)合劑結(jié)合的程度指示樣本與固定的結(jié)合劑的反應(yīng)性。適合用于這種測定的多肽包括全長肺腫瘤蛋白和它與結(jié)合劑結(jié)合的多肽部分，如上所述。
固相支持體可以是本領(lǐng)域普通技術(shù)人員所知的腫瘤蛋白可以附著的任何材料。例如，固相支持體可以是微量滴定板中的檢測孔或硝酸纖維素膜或其它合適的膜。可供選擇地，該支持體可以是珠或盤，例如玻璃、玻璃纖維、膠乳或塑料材料，例如聚苯乙烯或聚氯乙稀。支持體也可以是磁性顆?；蚶w維光傳感器，例如在美國專利5,359,681中公開的那些。可以使用各種本領(lǐng)域技術(shù)人員已知的技術(shù)將結(jié)合劑固定在固相支持體上，所述方法在專利和科技文獻(xiàn)中充分描述。在本發(fā)明的內(nèi)容中，術(shù)語“固定”是指非共價(jià)結(jié)合如吸附，和共價(jià)附著(可以是試劑和支持體上功能基團(tuán)間的直接連接或可以是通過交聯(lián)試劑的方法連接)。優(yōu)選吸附于微滴定板的孔中或膜上的固定。在這種情況下，在合適的緩沖液中使結(jié)合劑與固相支持體接觸一段合適的時(shí)間可以完成吸附。接觸時(shí)間隨溫度變化，但典型地在大約1小時(shí)至大約1天之間。通常，塑料微滴定板(如聚苯乙烯或聚氯乙稀)的孔與大約10ng至大約10μg范圍內(nèi)，優(yōu)選大約100ng至大約1μg的結(jié)合劑接觸，足以固定足量的結(jié)合劑。
結(jié)合劑與固相支持體的共價(jià)附著通?？梢酝ㄟ^首先使支持體與將與支持體和結(jié)合劑上的功能基團(tuán)如羥基或氨基反應(yīng)的雙功能試劑反應(yīng)來完成。例如，使用苯醌，或使支持體上的醛基與結(jié)合配偶體上的胺和活性氫縮合，結(jié)合劑共價(jià)附著于具有適當(dāng)聚合物包被的支持體(如見Pierce Immunotechnology Catalog and Handbook，1991，A12-A13)。
在某些實(shí)施方案中，測定是雙抗夾心測定。這個(gè)測定的實(shí)施可以首先使已固定在固相支持體通常是微滴定板的孔中的抗體與樣本接觸，使得樣本中的多肽結(jié)合固定的抗體。接著從固定的多肽-抗體復(fù)合體中去除未結(jié)合的樣本，并加入含報(bào)道基團(tuán)的檢測試劑(優(yōu)選能夠結(jié)合到多肽上不同位點(diǎn)的二抗)。然后用適合特定報(bào)道基團(tuán)的方法測定與固相支持體保持結(jié)合的檢測試劑的量。
更具體地，一旦抗體如上所述固定在支持體上后，支持體上剩余的蛋白結(jié)合位點(diǎn)典型地被封閉。本領(lǐng)域普通技術(shù)人員已知任何合適的封閉劑，如牛血清白蛋白或Tween 20TM(Sigma Chemical Co.，St.Louis，MO)。然后，固定的抗體與樣本溫育，使多肽結(jié)合抗體。溫育前，可以用適當(dāng)?shù)南♂寗┫♂寴颖?，如磷酸緩沖鹽水(PBS)。通常，合適的接觸時(shí)間(即溫育時(shí)間)是足夠檢測從肺癌個(gè)體得到的樣本內(nèi)多肽的存在的一段時(shí)間。優(yōu)選，接觸時(shí)間足夠達(dá)到結(jié)合和未結(jié)合多肽間達(dá)到平衡的至少大約95％的結(jié)合水平。本領(lǐng)域普通技術(shù)人員會認(rèn)識到測定進(jìn)行一段時(shí)間后的結(jié)合水平可以很容易確定達(dá)到平衡所需時(shí)間。在室溫下，通常大約30分鐘的溫育時(shí)間就足夠。
接著，用合適的緩沖液洗滌固相支持體可以去除未結(jié)合的樣本，如含0.1％Tween 20TM的PBS。然后可以將含有報(bào)道基團(tuán)的二抗加入固相支持體。優(yōu)選的報(bào)道基團(tuán)包括上面引用的那些基團(tuán)。
然后，將檢測試劑與固定的抗體-多肽復(fù)合體溫育足以檢測結(jié)合多肽的一段時(shí)間。通?？梢詼y定一段時(shí)間后的結(jié)合水平來確定合適的時(shí)間。接著去除未結(jié)合的檢測試劑并用報(bào)道基團(tuán)檢測結(jié)合的檢測試劑。檢測報(bào)道基團(tuán)使用的方法依賴于報(bào)道基團(tuán)的性質(zhì)。對于放射性基團(tuán)，閃爍計(jì)數(shù)或放射自顯影方法通常是合適的。光譜學(xué)方法可以用于檢測染料、發(fā)光基團(tuán)和熒光基團(tuán)?？梢杂每股锼氐鞍着悸?lián)不同的報(bào)道基團(tuán)(通常是放射性或熒光基團(tuán)或酶)檢測生物素。添加底物(通常進(jìn)行特定的一段時(shí)間)，隨后進(jìn)行反應(yīng)產(chǎn)物的光譜學(xué)分析或其它分析，通?？梢詸z測酶報(bào)道基團(tuán)。
為了確定癌癥如肺癌的存在或不存在，通常將從與固相支持體保持結(jié)合的報(bào)道基團(tuán)檢測到的信號與相應(yīng)于預(yù)先確定的截?cái)嘀档男盘栠M(jìn)行比較。在一個(gè)優(yōu)選實(shí)施方案中，檢測癌癥的截?cái)嘀凳钱?dāng)固定抗體與沒有癌癥的患者樣本溫育時(shí)所得信號的平均值。通常，認(rèn)為產(chǎn)生信號超過預(yù)先確定的截?cái)嘀等齻€(gè)標(biāo)準(zhǔn)差的樣本是癌癥陽性。在可供選擇的優(yōu)選實(shí)施方案中，用Receiver Operator Curve確定截?cái)嘀?，根?jù)Sackett等，Clinical EpidemiologyA Basic Science forClinical Medicine，Little Brown and Co.，1985，106-7頁的方法。簡言之，在這個(gè)實(shí)施方案中，可以從相當(dāng)于診斷檢測結(jié)果的每個(gè)可能的截?cái)嘀档某蓪φ骊栃月?即敏感性)和假陽性率(100％-特異性)的圖確定截?cái)嘀?。與左上角最接近的圖上的截?cái)嘀?即包圍最大面積的值)是最準(zhǔn)確的截?cái)嘀担梢哉J(rèn)為產(chǎn)生信號高于用這個(gè)方法確定的截?cái)嘀档臉颖臼顷栃??？晒┻x擇地，截?cái)嘀悼梢匝刂鴪D向左移動，使假陽性率降至最小，或向右移動，使假陰性率降至最小。通常認(rèn)為產(chǎn)生信號高于用這個(gè)方法確定的截?cái)嘀档臉颖臼前┌Y陽性。
在一個(gè)相關(guān)的實(shí)施方案中，以流通或帶狀測試格式進(jìn)行測定，其中結(jié)合劑固定在膜上，如硝酸纖維素。在流通測試中，當(dāng)樣本經(jīng)過膜時(shí)，樣本內(nèi)的多肽與固定的結(jié)合劑結(jié)合。然后，當(dāng)含第二種結(jié)合劑的溶液流經(jīng)膜時(shí)，第二種標(biāo)記的結(jié)合劑與結(jié)合劑-多肽復(fù)合體結(jié)合。然后可以如上所述進(jìn)行結(jié)合的第二種結(jié)合劑的檢測。在帶狀測試格式中，將結(jié)合劑結(jié)合的膜的一端浸在含樣本的溶液中。樣本沿著膜遷移通過含第二種結(jié)合劑的區(qū)域并到達(dá)固定的結(jié)合劑區(qū)。在固定的抗體區(qū)域的第二種結(jié)合劑的濃度指示癌癥的存在。典型地，第二種結(jié)合劑在那個(gè)位置的濃度產(chǎn)生可以肉眼讀取的模式，如線。不存在這種模式表示陰性結(jié)果。通常，選擇固定在膜上的結(jié)合劑的量使得當(dāng)生物樣本含多肽水平足以在如上討論的格式的雙抗夾心測定中產(chǎn)生陽性信號時(shí)，產(chǎn)生如上討論的格式的肉眼可辨的模式。優(yōu)選的用于這種試驗(yàn)的結(jié)合劑是抗體及其抗原結(jié)合片段。優(yōu)選，固定在膜上的抗體的量范圍從大約25ng至大約1μg，更優(yōu)選從大約50ng至大約500ng。通?？捎煤苌倭康纳飿颖具M(jìn)行這種測試。
當(dāng)然，存在適合用本發(fā)明的腫瘤蛋白或結(jié)合劑的許多其它試驗(yàn)方案。上面的說明僅僅旨在示范。例如，對本領(lǐng)域普通技術(shù)人員將很明顯，可以很容易改進(jìn)上述方案，用腫瘤多肽檢測生物樣本中結(jié)合這種多肽的抗體。這種腫瘤蛋白特異性的抗體的檢測可能與癌癥存在有關(guān)。
也可以，或可供選擇地，基于生物樣本中與腫瘤蛋白發(fā)生特異性反應(yīng)的T細(xì)胞的存在檢測癌癥。在某些方法中，將從患者分離的含CD4+和/或CD8+T細(xì)胞的生物樣本與腫瘤多肽、編碼這種多肽的多核苷酸和/或表達(dá)至少這種多肽的免疫原性部分的APC一起溫育，并檢測存在或不存在T細(xì)胞的特異性活化。合適的生物樣本包括但不限于分離的T細(xì)胞。例如，可以用常規(guī)技術(shù)(例如通過Ficoll/Hypaque密度梯度離心外周血淋巴細(xì)胞)從患者分離T細(xì)胞。T細(xì)胞可以與多肽(如5-25μg/ml)在體外37℃培養(yǎng)2-9天(通常4天)?？赡茏詈门囵B(yǎng)另一等份不存在腫瘤多肽的T細(xì)胞樣本作為對照。對于CD4+T細(xì)胞，優(yōu)選通過估計(jì)T細(xì)胞增殖檢測活化。對于CD8+T細(xì)胞，優(yōu)選通過估計(jì)溶解細(xì)胞活性檢測活化。增殖水平比無病患者高至少兩倍和/或溶解細(xì)胞活性水平比無病患者高至少20％表明患者存在癌癥。
如上指出，也可以，或可供選擇地，基于生物樣本中編碼腫瘤蛋白的mRNA水平來檢測癌癥。例如，在基于聚合酶鏈?zhǔn)椒磻?yīng)(PCR)的測定中可以使用至少兩條寡核苷酸引物，擴(kuò)增來自生物樣本的腫瘤cDNA的一部分，其中至少一條寡核苷酸引物對編碼腫瘤蛋白的多核苷酸具有特異性(即與其雜交)。然后，用本領(lǐng)域熟知的技術(shù)分離和檢測擴(kuò)增的cDNA，如凝膠電泳。類似地，與編碼腫瘤蛋白的多核苷酸特異性雜交的寡核苷酸探針可以用于雜交試驗(yàn)以檢測生物樣本中編碼腫瘤蛋白的多核苷酸的存在。
為了允許在測定條件下雜交，寡核苷酸引物和探針應(yīng)該包含與編碼本發(fā)明腫瘤蛋白的多核苷酸一部分(長度至少10個(gè)核苷酸，優(yōu)選至少20個(gè)核苷酸)具有至少大約60％，優(yōu)選至少大約75％和更優(yōu)選至少大約90％同一性的寡核苷酸序列。優(yōu)選寡核苷酸引物和/或探針與編碼這里所述的多肽的多核苷酸在中等嚴(yán)格條件下雜交，如上限定。可以有效用于這里所述的診斷方法的寡核苷酸引物和/或探針優(yōu)選長度至少10-40個(gè)核苷酸。在一個(gè)優(yōu)選的實(shí)施方案中，寡核苷酸引物包含具有這里公開序列的DNA分子的至少10個(gè)連續(xù)核苷酸，更優(yōu)選至少15個(gè)連續(xù)的核苷酸?；赑CR的測定和雜交試驗(yàn)的技術(shù)是本領(lǐng)域熟知的(如見Mullis等，Cold Spring Harbor Symp.Quant.Biol.，51263，1987；Erlich ed.，PCR Technology，Stockton Press，NY，1989)。
一個(gè)優(yōu)選的測定使用RT-PCR，其中PCR與逆轉(zhuǎn)錄聯(lián)合使用。典型地，從生物樣本如活檢組織中提取RNA，并逆轉(zhuǎn)錄產(chǎn)生cDNA分子。使用至少一條特異性引物的PCR擴(kuò)增產(chǎn)生cDNA分子，它可以用例如凝膠電泳分離和觀察。可以對取自測試患者和取自沒有罹患癌癥的個(gè)體的生物樣本進(jìn)行擴(kuò)增?？梢詫缭絻蓚€(gè)數(shù)量級的幾個(gè)稀釋度的cDNA進(jìn)行擴(kuò)增反應(yīng)。與同一稀釋度的無癌癥樣本相比，在幾個(gè)稀釋度的測試患者樣本中表達(dá)增加兩倍或更高，通常認(rèn)為是陽性。
在另一個(gè)實(shí)施方案中，這里所述的組合物可以用作癌癥進(jìn)展的標(biāo)記。在這個(gè)實(shí)施方案中，可以隨著時(shí)間實(shí)施如上所述的診斷癌癥的測定，估計(jì)反應(yīng)性多肽或多核苷酸水平的改變。例如，可以每24-72小時(shí)進(jìn)行測定，持續(xù)6個(gè)月至一年，其后按需實(shí)施。通常，檢測的多肽或多核苷酸水平隨時(shí)間增加的那些患者中癌癥在進(jìn)展。相比之下，當(dāng)反應(yīng)性多肽或多核苷酸水平保持不變或隨時(shí)間而降低時(shí)，癌癥沒有進(jìn)展。
某些體內(nèi)診斷試驗(yàn)可以直接在腫瘤上進(jìn)行。一個(gè)這種試驗(yàn)包括使腫瘤細(xì)胞接觸結(jié)合劑。然后，可以直接或通過報(bào)道基團(tuán)間接檢測結(jié)合的結(jié)合劑。這種結(jié)合劑也可以用于組織學(xué)應(yīng)用。可供選擇地，在這種應(yīng)用中可以使用多核苷酸探針。
如上指出，為了提高敏感性，在給定的樣本中可以測定多個(gè)腫瘤蛋白標(biāo)記。很明顯，在單個(gè)試驗(yàn)中可以組合對這里提供的不同蛋白特異性的結(jié)合劑。此外，可以同時(shí)使用多個(gè)引物或探針。選擇腫瘤蛋白標(biāo)記可以基于常規(guī)試驗(yàn)以確定產(chǎn)生最佳敏感性的組合。而且，或可供選擇地，測定這里提供的腫瘤蛋白可以與其它已知的腫瘤抗原測定組合。
本發(fā)明進(jìn)一步提供了試劑盒用于任何上面的診斷方法。這種試劑盒典型包括兩個(gè)或更多實(shí)施診斷測定所必需的成分。成分可以是化合物、試劑、容器和/或裝置。例如，試劑盒中的一個(gè)容器可以含有與腫瘤蛋白特異性結(jié)合的單克隆抗體或其片段?？梢蕴峁┻@種抗體或片段與支持體材料附著，如上所述。一個(gè)或更多另外的容器可以包含組分，如測定待用的試劑或緩沖液。這種試劑盒也可以，或可供選擇地，含有如上所述的含有適合直接或間接檢測抗體結(jié)合的報(bào)道基團(tuán)的檢測試劑。
可供選擇地，可以設(shè)計(jì)試劑盒以檢測生物樣本中編碼腫瘤蛋白的mRNA水平。這種試劑盒通常包括至少一條與編碼腫瘤蛋白的多核苷酸雜交的寡核苷酸探針或引物，如上所述。這種寡核苷酸可以用在例如PCR或雜交試驗(yàn)中。這種試劑盒中可存在的另外的成分包括第二種寡核苷酸和/或診斷試劑或容器以利于檢測編碼腫瘤蛋白的多核苷酸。
提供下列實(shí)施用來說明，不用來限制。
實(shí)施例1使用差異展示RT-PCR制備肺腫瘤特異性cDNA序列這個(gè)實(shí)施例闡明了采用差異展示篩選制備編碼肺腫瘤特異性多肽的cDNA分子。
在從患者身上取樣后從病理學(xué)證實(shí)有肺癌的患者的肺腫瘤和正常組織制備組織樣本。從樣本中提取正常RNA和腫瘤RNA，分離mRNA并用(dT)12AG(SEQ ID NO47)錨定3’引物轉(zhuǎn)變?yōu)閏DNA。然后用隨機(jī)選擇引物(SEQ ID NO48)執(zhí)行差異展示PCR。擴(kuò)增條件是含1.5mM MgCl2的標(biāo)準(zhǔn)緩沖液，20 pmol引物，500 pmol dNTP和1單位Taq DNA聚合酶(Perkin--Elmer，Branchburg，NJ)。采用94℃變性30秒，42℃退火1分鐘和72℃延伸30秒進(jìn)行四十個(gè)擴(kuò)增循環(huán)。切下銀染凝膠中的重復(fù)觀察到的對腫瘤RNA指紋圖譜模式特異性的條帶，亞克隆到pGEM-T載體(Promega，Madison，WI)中并測序。分離的3’序列在SEQ ID NO1-6中提供。
用BLASTN程序?qū)⑦@些序列與公共數(shù)據(jù)庫中的序列進(jìn)行比較，顯示與SEQ ID NO1-11提供的序列沒有明顯的同源性。就發(fā)明人所知，分離的DNA序列無一曾先前顯示在人肺腫瘤組織中表達(dá)水平高于正常肺組織。
實(shí)施例2使用患者血清鑒定編碼肺腫瘤抗原的DNA序列這個(gè)實(shí)施例闡明了通過用患者自身血清進(jìn)行肺腫瘤樣本的表達(dá)篩選分離編碼肺腫瘤抗原的cDNA序列。
使用Lambda ZAP Express表達(dá)體系(Stratagene，La Jolla，CA)構(gòu)建人肺腫瘤定向cDNA表達(dá)文庫。文庫的總RNA取自晚期SCID小鼠傳代的人鱗狀上皮肺癌，用Message Maker試劑盒(Gibco BRL，Gaithersburg，MD)分離聚腺苷酸+RNA。用大腸桿菌吸收的患者自身血清篩選所得文庫，如Sambrook等所述(Molecular.CloningALaboratory Manual，Cold Spring Harbor Laboratories，ColdSpring Harbor，NY，1989)，山羊抗人IgG-A-M(H+L)二抗與堿性磷酸酶偶聯(lián)，用NBT/BCIP(Gibco BRL)顯影。純化表達(dá)免疫活性抗原的陽性噬斑。收回噬斑中的噬菌粒并確定克隆的核苷酸序列。
分離十五個(gè)克隆，以下稱作LT86-1-LT86-15。SEQ ID NO17-24和26-31分別提供了LT86-1-LT86-8和LT86-10-LT86-15分離的cDNA序列，SEQ ID NO32-39和41-46分別提供了相應(yīng)的預(yù)測氨基酸序列。SEQ ID NO25提供了LT86-9的確定的cDNA序列，SEQ ID NO40和65分別提供了相應(yīng)的從3’和5’末端的預(yù)測氨基酸序列。如上所述將這些序列與基因庫中的那些序列進(jìn)行比較。發(fā)現(xiàn)克隆LT86-3，LT86-6-LT86-9，LT86-11-LT86-13和LT86-15(分別是SEQ ID NO19，22-25，27-29和31)與以前鑒定的已表達(dá)序列標(biāo)志(ESTs)顯示出一些同源性，克隆LT86-6，LT86-8，LT86-11，LT86-12和LT86-15似乎彼此相似或等同。發(fā)現(xiàn)克隆LT86-3與人轉(zhuǎn)錄阻遏物顯示出一些同源性。發(fā)現(xiàn)克隆LT86-6，8，9，11，12和15與酵母RNA Pol II轉(zhuǎn)錄調(diào)控介體顯示出一些同源性。發(fā)現(xiàn)克隆LT86-13與C.Elegans亮氨酸氨肽酶顯示出一些同源性。克隆LT86-9看來含有兩個(gè)插入片段，其5’序列與以前鑒定的干擾素α誘導(dǎo)的P27的反義序列顯示出同源性，3’序列與LT86-6類似。發(fā)現(xiàn)克隆LT86-14(SEQ ID NO30)與trithorax基因顯示出一些同源性且具有“RGD”細(xì)胞粘附序列和在青霉素水解中起作用的β-內(nèi)酰胺酶A位點(diǎn)。發(fā)現(xiàn)克隆LT86-1，LT86-2，LT86-4，LT86-5和LT86-10(分別是SEQ ID NOS17，18，20，21和26)與以前鑒定的基因顯示出同源性。SEQ ID NO66提供了后來確定的LT86-4的延伸cDNA序列，SEQ ID NO67提供了其相應(yīng)的預(yù)測氨基酸序列。
后來的研究通向另外五個(gè)克隆的分離，稱作LT86-20，LT86-21，LT86-22，LT86-26和LT86-27。SEQ ID NO68和70-72分別提供了LT86-20，LT86-22，LT86-26和LT86-27的測定的5’cDNA序列，SEQ ID NO69提供了LT86-21測定的3’cDNA序列。SEQ ID NO73-77分別提供了LT86-20，LT86-21，LT86-22，LT86-26和LT86-27的相應(yīng)的預(yù)測氨基酸序列。發(fā)現(xiàn)LT86-22和LT86-27彼此非常相似。如上所述將這些序列與基因庫中的序列比較，顯示與LT86-22和LT86-27沒有明顯的同源性。發(fā)現(xiàn)LT86-20，LT86-21和LT86-26與以前鑒定的基因顯示出同源性。
進(jìn)一步的研究中，用來自lambda ZAP Express表達(dá)載體(Stratagene)中的肺小細(xì)胞癌細(xì)胞系的mRNA制備cDNA表達(dá)文庫，如上所述進(jìn)行篩選，用兩個(gè)肺小細(xì)胞癌患者的混合血清。用大腸桿菌溶胞產(chǎn)物吸收混合血清并向血清中加入人PBMC溶胞產(chǎn)物封閉抗體與正常組織中發(fā)現(xiàn)的蛋白結(jié)合。分離了七十三個(gè)克隆。SEQ ID NO290-362提供了這些克隆的測定cDNA序列。發(fā)現(xiàn)SEQ ID NO289-292，294，296-297，300，302，303，305，307-315，317-320，322-325，327-332，334，335，338-341，343-352，354-358，360和362的序列與以前分離的基因顯示出一些同源性。發(fā)現(xiàn)SEQ IDNO293，295，298，299，301，304，306，316，321，326，333，336，337，342，353，359和361的序列與以前鑒定的ESTs顯示出一些同源性。
實(shí)施例3使用小鼠抗血清鑒定編碼肺腫瘤抗原的DNA序列這個(gè)實(shí)施例闡述了通過用小鼠抗腫瘤血清篩選肺腫瘤cDNA文庫來分離編碼肺腫瘤抗原的cDNA序列。
如上實(shí)施例2所述制備定向cDNA肺腫瘤表達(dá)文庫。血清得自含晚期傳代的人鱗狀細(xì)胞和腺癌腫瘤的SCID小鼠?；旌线@些血清并注射給正常小鼠以產(chǎn)生抗肺腫瘤血清。用這個(gè)抗血清從未擴(kuò)增文庫中篩選到大約200,000PFUs。使用NBT/BCIP(BRL Labs.)顯影的山羊抗小鼠IgG-A-M(H+L)堿性磷酸酶二抗，鑒定了大約40個(gè)陽性噬斑。純化噬菌體并切除在pBK-CMV載體中有插入片段的9個(gè)克隆的噬菌粒用于在原核或真核細(xì)胞中表達(dá)。
SEQ ID NO49-55提供了7個(gè)分離的克隆(以下稱作L86S-3，L86S-12，L86S-16，L86S-25，L86S-36，L86S-40和L86S-46)的測定的cDNA序列，SEQ ID NO56-62分別提供了相應(yīng)的預(yù)測氨基酸序列。SEQ ID NO63和64提供了剩余2個(gè)克隆(以下稱作L86S-30和L86S-41)的5’cDNA序列。后來確定L86S-36和L86S-46代表相同的基因。如上所述將這些序列與公共數(shù)據(jù)庫中的序列比較，顯示與克隆L86S-30，L86S-36和L86S-46(分別是SEQ ID NO63，53和55)沒有明顯的同源性。發(fā)現(xiàn)L86S-16(SEQ ID NO51)與以前在胎肺和生殖細(xì)胞腫瘤中鑒定的EST顯示出一些同源性。發(fā)現(xiàn)剩余克隆與以前鑒定的人基因顯示出至少一定程度的同源性。SEQ ID NO78-80分別提供了后來確定的L86S-12，L86S-36和L86S-46的延伸cDNA序列，SEQ ID NO81-83提供了相應(yīng)的預(yù)測氨基酸序列。
后來的研究確定了另外的九個(gè)克隆的5’cDNA序列，稱作L86S-6，L86S-11，L86S-14，L86S-29，L86S-34，L86S-39，L86S-47，L86S-49和L86S-51(分別是SEQ ID NO84-92)。SEQ ID NO93-101分別提供了相應(yīng)的預(yù)測氨基酸序列。發(fā)現(xiàn)L86S-30，L86S-39和L86S-47彼此相似。如上所述將這些序列與基因庫中的序列比較，顯示與L86S-14沒有明顯的同源性。發(fā)現(xiàn)L86S-29與以前鑒定的EST顯示出一些同源性。發(fā)現(xiàn)L86S-6，L86S-11，L86S-34，L86S-39，L86S-47，L86S-49和L86S-51與以前鑒定的基因顯示出一些同源性。
在進(jìn)一步的研究中，用帶Lambda Zap Express載體的Stratagene試劑盒構(gòu)建定向cDNA文庫。從兩個(gè)原發(fā)性鱗狀細(xì)胞肺腫瘤分離文庫總RNA，用oligo dT柱分離聚腺苷酸+RNA。用來自移植人鱗狀細(xì)胞肺癌的三只SCID小鼠的混合血清在正常小鼠中產(chǎn)生抗血清。用大腸桿菌吸收的小鼠抗SCID腫瘤血清從未擴(kuò)增文庫中篩選到大約700,000PFUs。如上所述鑒定陽性噬斑。純化噬菌體和切除在pBK-CMV載體中有插入片段的180個(gè)克隆的噬菌粒用于在原核或真核細(xì)胞中表達(dá)。
SEQ ID NO126-148提供了23個(gè)分離克隆的測定的cDNA序列。如上所述將這些序列與公共數(shù)據(jù)庫中的序列比較，顯示與SEQID NO139和143-148的序列沒有明顯的同源性。發(fā)現(xiàn)SEQ IDNO126-138和140-142的序列與以前鑒定的人多核苷酸序列顯示出同源性。
實(shí)施例4使用小鼠抗血清篩選由SCID小鼠制備的肺腫瘤文庫這個(gè)實(shí)施例闡述了通過用小鼠抗腫瘤血清篩選從SCID小鼠制備的肺腫瘤cDNA文庫來分離編碼肺腫瘤抗原的cDNA序列。
用帶Lambda Zap Express載體的Stratagene試劑盒制備定向cDNA肺腫瘤表達(dá)文庫。文庫總RNA取自在SCID小鼠中生長的晚期傳代的肺腺癌。用Message Maker試劑盒(Gibco BRL)分離聚腺苷酸+RNA。血清得自兩只移植肺腺癌的SCID小鼠?；旌线@些血清并注射給正常小鼠以產(chǎn)生抗肺腫瘤血清。用大腸桿菌吸收的小鼠抗SCID腫瘤血清從未擴(kuò)增的文庫中篩選到大約700,000PFUs。用NBT/BCIP(Gibco BRL)顯影的山羊抗小鼠IgG-A-M(H+L)堿性磷酸酶二抗鑒定陽性噬斑。純化噬菌體和切除在pBK-CMV載體中有插入片段的100個(gè)克隆的噬菌粒用于在原核或真核細(xì)胞中表達(dá)。
SEQ ID NO149-181提供了33個(gè)分離的克隆的測定的5’cDNA序列。SEQ ID NO182，183，186，188-193和194-215分別提供了SEQ ID NO149，150，152-154，156-158和160-181相應(yīng)的預(yù)測氨基酸序列。發(fā)現(xiàn)SEQ ID NO151的克隆(稱作SAL-25)含有兩個(gè)可讀框(ORFs)。SEQ ID NO184和185提供了這些ORFs編碼的預(yù)測氨基酸序列。發(fā)現(xiàn)SEQ ID NO153的克隆(稱作SAL-50)含有兩個(gè)編碼SEQ ID NO187和216的預(yù)測氨基酸序列的可讀框。類似地，發(fā)現(xiàn)SEQ ID NO155的克隆(稱作SAL-66)含有兩個(gè)編碼SEQ ID NO189和190的預(yù)測氨基酸序列的可讀框。將分離的序列與公共數(shù)據(jù)庫的序列比較，顯示與SEQ ID NO151，153和154的序列沒有明顯的同源性。發(fā)現(xiàn)SEQ ID NO149，152，156，157和158的序列與以前分離的已表達(dá)序列標(biāo)志(ESTs)顯示出一些同源性。發(fā)現(xiàn)SEQ ID NO150，155和159-181的序列與以前在人中鑒定的序列顯示出同源性。用上述的步驟，由在SCID小鼠中生長的兩個(gè)晚期傳代的肺鱗癌制備兩個(gè)定向cDNA文庫(稱作LT46-90和LT86-21)并用從移植人鱗狀細(xì)胞肺癌的SCID小鼠得到的血清篩選。SEQ ID NO217-237和286-289提供了分離克隆的測定cDNA序列。發(fā)現(xiàn)SEQ ID NO286是LT4690-71(SEQ ID NO237)的更長序列。這些序列與公共數(shù)據(jù)庫中的序列的比較顯示與序列SEQ ID NO219，220，225，226，287和288沒有已知的同源性。發(fā)現(xiàn)SEQ ID NO218，221，222和224的序列與以前鑒定的功能未知的序列顯示出一些同源性。發(fā)現(xiàn)序列SEQ ID NO236與已知的小鼠mRNA序列顯示出同源性。SEQ IDNO217，223，227-237，286和289的序列與已知的人DNA和/或RNA序列顯示出一些同源性。
在進(jìn)一步的研究中，使用上述技術(shù)，用大腸桿菌吸收的小鼠抗SCID腫瘤血清篩選一個(gè)上述的cDNA文庫(LT86-21)。該血清得自用取自移植人鱗狀細(xì)胞肺癌的SCID小鼠的3份血清的混合所免疫的正常小鼠。SEQ ID NO238-285提供了分離克隆的測定cDNA序列。這些序列與公共數(shù)據(jù)庫的序列的比較顯示與SEQ ID NO253，260，277和285的序列沒有明顯的同源性。發(fā)現(xiàn)SEQ ID NO249，250，256，266，276和282的序列與以前分離的已表達(dá)序列標(biāo)志(ESTs)顯示出一些同源性。發(fā)現(xiàn)SEQ ID NO238-248，251，252，254，255，257-259，261-263，265，267-275，278-281，283和284的序列與以前鑒定的DNA或RNA序列顯示出一些同源性。
分離的某些抗原在肺腫瘤組織中的表達(dá)水平與正常組織中的表達(dá)水平的比較用微陣列技術(shù)確定。這些研究的結(jié)果在下表2中顯示，連同對這些序列的數(shù)據(jù)庫分析。表2


LT+F/N＝肺腫瘤加胎兒組織比正常組織SC+M/N＝肺小細(xì)胞癌加轉(zhuǎn)移比正常組織Squa/N＝鱗狀細(xì)胞肺腫瘤比正常組織Aden/N＝腺癌比正常組織對抗原2LT-128(SEQ ID NO282)的全長測序研究得到SEQ IDNO392提供的全長cDNA序列的分離。SEQ ID NO393提供了由該全長cDNA序列編碼的這個(gè)氨基酸序列。這個(gè)抗原在鱗狀細(xì)胞癌中顯示出20倍超量表達(dá)，在肺腺癌中2.5倍超量表達(dá)。這個(gè)基因已經(jīng)被述為潛在的ras癌基因(Fenwick等Science，287869-873，2000)。
獲得克隆2LT-3(SEQ ID NO238)，2LT-26(SEQ-ID NO242)，2LT-57(SEQ ID NO249)，2LT-58(SEQ ID-NO250)，2LT-98(SEQ ID NO268)和2LT-124(SEQ ID NO279)的延伸序列信息。這些克隆的延伸cDNA序列分別在SEQ ID NOs428-433中列舉，分別編碼SEQ ID NOs434-439列舉的多肽序列。
實(shí)施例5肺腫瘤多肽的組織特異性的確定使用基因特異性引物，用RT-PCR檢測各種正常和腫瘤組織中代表性肺腫瘤多肽的mRNA表達(dá)水平。
簡言之，用Trizol試劑從各種正常和腫瘤組織中提取總RNA。用2μg總RNA與SuperScript II逆轉(zhuǎn)錄酶(BRL Life Technologies)在42℃反應(yīng)1個(gè)小時(shí)進(jìn)行第一條鏈的合成。然后用基因特異性引物通過PCR擴(kuò)增cDNA。為了確保RT-PCR的半定量性質(zhì)，將β-肌動蛋白用作各檢測組織的內(nèi)對照。使用1μl的1∶30稀釋的cDNA使得β-肌動蛋白模板能夠線性范圍擴(kuò)增且足夠敏感以反映起始拷貝數(shù)的差異。使用這些條件，對每個(gè)組織的每個(gè)逆轉(zhuǎn)錄反應(yīng)確定β-肌動蛋白水平。用DNA酶處理和當(dāng)使用未加入逆轉(zhuǎn)錄酶制備的第一條鏈cDNA時(shí)確保PCR結(jié)果陰性而將DNA污染降至最小。
檢測五個(gè)不同類型的腫瘤組織(來自3個(gè)患者的肺鱗狀細(xì)胞腫瘤、肺腺癌、前列腺腫瘤、結(jié)腸腫瘤和肺腫瘤)，和不同的正常組織，包括來自四個(gè)患者的肺、前列腺、腦、腎、肝、卵巢、骨骼肌、皮膚、小腸、心肌、視網(wǎng)膜和睪丸中的mRNA表達(dá)水平。發(fā)現(xiàn)L86S-46在肺鱗狀細(xì)胞腫瘤、結(jié)腸腫瘤和前列腺腫瘤中以高水平表達(dá)，而在檢測的其它組織中檢測不到。發(fā)現(xiàn)L86S-5在肺腫瘤樣本和4個(gè)正常肺樣本中的2個(gè)中表達(dá)，但不在檢測的其它正?；蚰[瘤組織中表達(dá)。發(fā)現(xiàn)L86S-16在除正常肝和正常胃之外的所有組織中表達(dá)。使用實(shí)時(shí)PCR，發(fā)現(xiàn)L86S-46在肺鱗狀組織和正常扁桃體中超量表達(dá)，在檢測的所有其它組織中表達(dá)低或檢測不到。
實(shí)施例6分離編碼肺腫瘤抗原的DNA序列編碼潛在參與鱗狀細(xì)胞肺腫瘤形成的抗原的DNA序列分離如下。
使用Lambda ZAP Express表達(dá)體系(Stratagene，La Jolla，CA)構(gòu)建肺腫瘤定向cDNA表達(dá)文庫。文庫總RNA取自兩個(gè)人鱗狀上皮肺癌的混合物，用oligo-dT纖維素(Gibco BRL，Gaithersburg，MD)分離聚腺苷酸+RNA。隨機(jī)收回噬菌粒并測定分離克隆的cDNA序列。
SEQ ID NO102提供了克隆SLT-Tl的測定cDNA序列，SEQ IDNO103-110分別提供了克隆SLT-T2，SLT-T3，SLT-T5，SLT-T7，SLT-T9，S-LT-T10，SLT-T11和SLT-T12的測定的5’cDNA序列。SEQID NO111-115分別提供了SLT-T1，SLT-T2，SLT-T3，SLT-T10和SLT-T12的相應(yīng)預(yù)測的氨基酸序列。如上所述將SLT-T2，SLT-T3，SLT-T5，SLT-T7，SLT-T9和SLT-T11的序列與公共數(shù)據(jù)庫中的那些序列比較，顯示沒有明顯的同源性。發(fā)現(xiàn)SLT-T10和SLT-T12的序列與以前在人中鑒定的序列顯示出一些同源性。
確定SLT-T1的序列與蛋白功能未知的PAC克隆顯示出一些同源性。發(fā)現(xiàn)SLT-T1的cDNA序列(SEQ ID NO102)含有增變(MUTT)結(jié)構(gòu)域。已知這種結(jié)構(gòu)域在從DNA中去除可引起A顛換為為G的損傷的鳥嘌呤中起作用(如見el-Deiry，W.S.，1997 Curr.Opin.Oncol.979-87；Okamoto，K.等1996 Int.J.Cancer 65437-41；Wu，C.等1995 Biochem.Biophys.Res.Commun.2141239-45；Porter，D.W.等1996 Chem.Res.Toxicol.91375-81)。因此SLT-Tl通過基因治療，可以用于治療由DNA修復(fù)中的破壞引起的或與之有關(guān)的肺癌。
在進(jìn)一步的研究中，編碼潛在參與腺癌肺腫瘤形成的抗原的DNA序列分離如下。使用Lambda ZAP Express表達(dá)體系(Stratagene，La Jolla，CA)構(gòu)建人肺腫瘤定向cDNA表達(dá)文庫。文庫總RNA取自晚期SCID小鼠傳代的人腺癌，用Message Maker試劑盒(Gibco BRL，Gaithersburg，MD)分離聚腺苷酸+RNA。隨機(jī)收回噬菌粒并測定分離克隆的cDNA序列。
SEQ ID NO116-120提供了五個(gè)分離克隆(稱作SALT-T3，SALT-T4，SALT-T7，SALT-T8和SALT-T9)的測定5’cDNA序列，SEQID NO121-125提供了相應(yīng)的預(yù)測氨基酸序列。發(fā)現(xiàn)SALT-T3與以前鑒定的人轉(zhuǎn)導(dǎo)素樣增強(qiáng)子蛋白TLE2顯示出98％的同一性。SALT-T4看來是小鼠Hβ58基因的人同源物。發(fā)現(xiàn)SALT-T7與人3-巰基丙酮酸硫轉(zhuǎn)移酶具有97％的同一性，發(fā)現(xiàn)SALT-T8與人干擾素誘導(dǎo)蛋白1-8U顯示出同源性。SALT-T9與人粘蛋白MUC 5B顯示出大約90％的同一性。
編碼潛在參與小細(xì)胞肺癌發(fā)生的抗原的cDNA序列分離如下。使用Lambda ZAP Express表達(dá)體系(Stratagene，La Jolla，CA)，用來自小細(xì)胞肺癌細(xì)胞系NCIH69、NCIH128和DMS79(全部可以從American Type Culture Collection，Manassas，VA得到)的mRNA構(gòu)建cDNA表達(dá)文庫。隨機(jī)收回噬菌粒并確定27個(gè)分離克隆的cDNA序列。測定的cDNA序列的比較顯示與SEQ ID NO372和373的序列沒有明顯的同源性。SEQ ID NO364，369，377，379和386的序列與以前分離的ESTs顯示出一些同源性。剩余20個(gè)克隆的序列與以前鑒定的基因顯示出一些同源性。SEQ ID NO363，365-368，370，371，374-376，378，380-385和387-389提供了這些克隆的cDNA序列，其中SEQ ID NO363，366-368，370，375，376，378，380-382，384和385是全長序列。
比較SEQ ID NO372的cDNA序列表明這個(gè)克隆(稱作128T1)是推定的七跨膜蛋白家族的一個(gè)新成員。特別是，使用計(jì)算機(jī)算法PSORT，預(yù)測該蛋白是IIIA型質(zhì)膜七跨膜蛋白。在Genbank數(shù)據(jù)庫中鑒定了基因組克隆，其含有SEQ ID NO372編碼的氨基酸序列所缺失的預(yù)測的N末端58個(gè)氨基酸。SEQ ID NO390提供了測定的128T1克隆的全長cDNA序列，SEQ ID NO391提供了相應(yīng)的氨基酸序列。
用微陣列技術(shù)測定某些分離抗原在肺腫瘤組織中與在正常組織中相比的表達(dá)水平。這些研究結(jié)果在下表3中顯示，連同對這些序列的數(shù)據(jù)庫分析。表3

LT+F/N＝肺腫瘤加胎兒組織比正常組織SC+M/N＝肺小細(xì)胞癌加轉(zhuǎn)移比正常組織Squa/N＝鱗狀細(xì)胞肺腫瘤比正常組織Aden/N＝腺癌比正常組織實(shí)施例7多肽的合成可以用FMOC化學(xué)方法及HPTU(O-苯并三唑-N，N，N’，N’-tetramethyluronium六氟磷酸)活化在Perkin Elmer/AppliedBiosystems DiVision 430A肽合成儀上合成多肽。Gly-Cys-Gly序列可以與肽的氨基末端相連以提供偶聯(lián)、結(jié)合至固定的表面、或標(biāo)記肽的方法。可以使用下列裂解混合物三氟乙酸∶乙二硫酚∶苯硫基甲烷∶水∶苯酚(40∶1∶2∶2∶3)從固相支持體上將肽切下。切割2小時(shí)后，可以在冷甲基叔丁基醚中沉淀肽。然后可以將肽沉淀溶于含0.1％三氟乙酸(TFA)的水中并在用C18反相HPLC純化前冷凍干燥。可以使用0％-60％乙腈(含0.1％TFA)在水(含0.1％TFA)中的梯度洗脫肽。冷凍干燥純級分后，使用電噴射或其它類型的質(zhì)譜分析法和氨基酸分析來表征肽。
實(shí)施例8通過T細(xì)胞表達(dá)克隆分離和表征編碼肺腫瘤抗原的DNA序列也可以用T細(xì)胞表達(dá)克隆鑒定肺腫瘤抗原。腫瘤特異性T細(xì)胞的一個(gè)來源是來自從人患者手術(shù)切除的腫瘤。
將非小細(xì)胞肺癌切碎并酶促消化幾個(gè)小時(shí)以釋放腫瘤細(xì)胞和浸潤的淋巴細(xì)胞(腫瘤浸潤T細(xì)胞，或TILs)。在HBSS緩沖液中洗滌細(xì)胞并通過Ficoll(100％/75％/HBSS)不連續(xù)梯度以將無活性細(xì)胞與腫瘤細(xì)胞和淋巴細(xì)胞分開。從交界面收獲兩條帶；在75％/HBSS界面的上方條帶主要含有腫瘤細(xì)胞，而在100％/75％/HBSS界面的下方條帶含有大多數(shù)淋巴細(xì)胞。培養(yǎng)擴(kuò)充TILs，在含有添加10ng/ml IL-7和100U/ml IL-2的培養(yǎng)基的24孔板中，或可供選擇地，在已經(jīng)用抗CD3單克隆抗體OKT3預(yù)先包被的24孔板中。用FACS分析所得TIL培養(yǎng)物以證實(shí)占高百分比的是CD8+T細(xì)胞(通過群體的90％以上)，CD4+細(xì)胞只占小的百分比。
此外，使用標(biāo)準(zhǔn)技術(shù)培養(yǎng)擴(kuò)充非小細(xì)胞肺癌細(xì)胞以建立腫瘤細(xì)胞系(稱作LT391-06)，后來經(jīng)免疫組化分析證實(shí)它是肺癌細(xì)胞系。用逆轉(zhuǎn)錄病毒載體轉(zhuǎn)導(dǎo)這個(gè)腫瘤細(xì)胞系來表達(dá)人CD80，并通過FACS分析表征證實(shí)其CD80，I類MHC和II類MHC分子的高表達(dá)水平。
細(xì)胞因子釋放測定(IFN-γ和TNF-α)以及51Cr釋放測定證明TIL系特異性識別自身肺腫瘤的能力。簡言之，來自第21天培養(yǎng)物的TIL細(xì)胞與自身的或同種異體的腫瘤細(xì)胞，EBV-永生化LCL，或?qū)φ占?xì)胞系Daudi和K562共同培養(yǎng)，用ELISA監(jiān)測培養(yǎng)上清細(xì)胞因子的存在。TIL特異性識別自身腫瘤但不識別同種異體的腫瘤。此外，不識別EBV-永生化LCL或?qū)φ占?xì)胞系，表明TIL系是腫瘤特異性的并且潛在識別由自身MHC分子呈遞的腫瘤抗原。
在培養(yǎng)物中使用可溶性抗CD3抗體及經(jīng)照射的EBV轉(zhuǎn)化的LCLs和PBL飼養(yǎng)細(xì)胞在20U/ml IL-2存在下，將經(jīng)表征的腫瘤特異性TIL系擴(kuò)充到適合的數(shù)量以進(jìn)行T細(xì)胞表達(dá)克隆。用標(biāo)準(zhǔn)有限稀釋技術(shù)產(chǎn)生來自經(jīng)擴(kuò)充TIL系的克隆。具體地說，將TIL細(xì)胞以0.5細(xì)胞/孔接種在96孔U底板中并用CD-80轉(zhuǎn)導(dǎo)的自身腫瘤細(xì)胞，EBV轉(zhuǎn)化的LCL和PBL飼養(yǎng)細(xì)胞在50U/ml IL-2存在下刺激。用51Cr微量細(xì)胞毒試驗(yàn)和IFN-γ生物測定證實(shí)這些克隆對自身腫瘤的特異性。
抗體阻斷試驗(yàn)證明這些CTL克隆是HLA-B/C限制性的。在同種異體肺癌板上檢測代表性的CTL克隆，它識別自身腫瘤和肺鱗狀細(xì)胞癌(936T)。由于這些腫瘤共同具有的唯一I類MHC分子是HLA-Cw1203，這表明這是CTL所使用的限制因子。CTL識別用編碼HLA-Cw1203的逆轉(zhuǎn)錄病毒載體轉(zhuǎn)導(dǎo)的多種同種異體肺癌證實(shí)了這個(gè)發(fā)現(xiàn)。
使用Message Maker(Life Technologies；Rockville，MD)從稱作LT391-06的肺腫瘤細(xì)胞系制備聚腺苷酸mRNA。包括cDNA合成的后來步驟根據(jù)Life Technologies克隆指南(cDNA合成和質(zhì)?？寺〉腟uperScript Plasmid System)進(jìn)行。如下進(jìn)行方案改進(jìn)。在添加連接物步驟中，置換EcoRI-XmnI連接體(New England Biolabs；Beverly，MA)。將大小分級的cDNAs連接到表達(dá)載體系統(tǒng)HisMax A，B，C(Invitrogen；Carlsbad，CA)中以優(yōu)化在全部三個(gè)編碼框架中的蛋白表達(dá)。然后，以大約100CFU/孔將文庫質(zhì)粒等分到96孔封閉而過夜液體擴(kuò)增。從這些培養(yǎng)物中，自動機(jī)器人(Qiagen；Valencia，CA)制備甘油原液和混合質(zhì)粒。確定文庫板每個(gè)孔中質(zhì)粒DNA的濃度為大約150ng/ul。隨機(jī)測序24個(gè)原始轉(zhuǎn)化體并將所得序列針對可利用數(shù)據(jù)庫進(jìn)行BLAST檢索，來初步表征cDNA表達(dá)文庫。SEQ ID NO443-480提供了測定的cDNA序列，BLAST檢索結(jié)果在表4中提供。表4


對于T細(xì)胞篩選，根據(jù)制造商的使用說明將脂質(zhì)Fugene與大約80ng文庫質(zhì)粒DNA和80ng HLA-Cw1203質(zhì)粒DNA混合并一式兩份轉(zhuǎn)染到COS-7細(xì)胞。在37℃培養(yǎng)48小時(shí)后，去除轉(zhuǎn)染混合物并向每個(gè)孔中加入在含人血清的新鮮培養(yǎng)基中的10,000個(gè)LT391-06 CTL。
6小時(shí)(TNF-α，WEHI生物測定)后或24小時(shí)(IFN-γ，ELISA)后，通過細(xì)胞因子釋放估計(jì)T細(xì)胞識別文庫中抗原的能力。用這個(gè)系統(tǒng)在COS-7細(xì)胞中篩選大約2.0×105個(gè)克隆(100個(gè)質(zhì)粒庫)。鑒定了LT391-06 CTL識別的三個(gè)質(zhì)粒庫(稱作14F10，19A4和20E10)。這些質(zhì)粒庫轉(zhuǎn)染到COS-7細(xì)胞中使從LT391-06 CTL產(chǎn)生的IFN-γ和TNF-a水平明顯高于背景。14F10，19A4和20E10庫“分解”為幾百個(gè)獨(dú)立質(zhì)粒DNA并重復(fù)測試。SEQ ID NO481-511提供了從14F10庫分離的24個(gè)新克隆的序列。
14F10庫的一個(gè)質(zhì)粒(3D9)，20E10庫的一個(gè)質(zhì)粒和19A4庫的5個(gè)質(zhì)粒(2A6，2E11，2F12，3F4，3H8)能夠重新構(gòu)成T細(xì)胞識別。對這些質(zhì)粒測序從而鑒定了7.8kB cDNA插入片段(稱作克隆14F10)，2.2kB cDNA插入片段(稱作克隆19A4；SEQ ID NO；440)和稱作20E10的克隆。SEQ ID NO441提供了14F10的全長cDNA序列。克隆14F10不含在19A4的5’末端發(fā)現(xiàn)的前兩個(gè)″G″核苷酸，并且19A4的3’近端的24 bp與14F10的相應(yīng)區(qū)域(核苷酸2145-2165)不同。此外，分離了14F10克隆的3837bp的3’額外序列。SEQID NO442提供了克隆20E10的5’末端cDNA序列(337bp)。在5’最末端，20E10含有額外的3個(gè)核苷酸(與19A4相比)。克隆20E10的5’末端的額外序列含有“ATG”，因此看來含有新的可讀框的翻譯起始位點(diǎn)。對GenBank數(shù)據(jù)庫的BLAST檢索分析鑒定這些序列與截短人胱氨酸/谷氨酸報(bào)道基因具有顯著的同源性。然而，不象公開的序列，克隆14F10和19A4含有由181個(gè)核苷酸組成的獨(dú)特5’末端。這個(gè)新的序列取代公開的5’區(qū)，導(dǎo)致去掉了報(bào)道的起始甲硫氨酸(起始密碼子)和報(bào)道的轉(zhuǎn)運(yùn)蛋白的另外兩個(gè)氨基酸。因此，克隆14F10和19A4的翻譯產(chǎn)物與胱氨酸/谷氨酸轉(zhuǎn)運(yùn)蛋白不同。此外，T細(xì)胞識別其它肺腫瘤證明其它腫瘤也表達(dá)這個(gè)抗原。
重新構(gòu)成T細(xì)胞識別抗LT391-06細(xì)胞的克隆19A4和14F10內(nèi)編碼的表位和氨基酸序列作圖如下。用80ng/孔HLA-Cw1203以及編碼克隆19A4的滴定量cDNA，位于19A4的獨(dú)特5’末端的潛在可讀框，或胱氨酸/谷氨酸(Cys-Glu)轉(zhuǎn)運(yùn)蛋白基因的可讀框，克隆到真核表達(dá)載體中轉(zhuǎn)染Cos-7細(xì)胞，并檢測TNF測定中抗LT391-06 T細(xì)胞的刺激。作為陽性對照，用HLA-Cw1203和上述的陽性質(zhì)?？寺?9A4共轉(zhuǎn)染Cos-7細(xì)胞。使用對轉(zhuǎn)運(yùn)蛋白的已知ORF特異性的5’和3’引物，以19A4為模板，采用PCR分離Cys-Glu轉(zhuǎn)運(yùn)蛋白表達(dá)構(gòu)建體。此外，每個(gè)5’引物含有Kozak翻譯起始位點(diǎn)和起始甲硫氨酸以驅(qū)動多肽的翻譯?？筁T391-06的CTL不識別表達(dá)Cys-Glu轉(zhuǎn)運(yùn)蛋白構(gòu)建體的轉(zhuǎn)染子，但確實(shí)識別表達(dá)19A4和19A4的5’ORF的轉(zhuǎn)染子。
在后來實(shí)驗(yàn)中，用80ng/孔HLA-Cw1203分別與轉(zhuǎn)座突變體F10和C12的滴定量DNA共轉(zhuǎn)染Cos-7細(xì)胞，并檢測TNF測定中抗LT391-06T細(xì)胞的刺激。作為陽性對照，用HLA-Cw1203和19A4的5’ORF克隆共轉(zhuǎn)染Cos-7細(xì)胞。通過14F10克隆的轉(zhuǎn)座子介導(dǎo)突變并通過序列分析篩選插入位點(diǎn)得到轉(zhuǎn)座突變體F10和C12。突變體F10的轉(zhuǎn)座子插入到離14F10 cDNA的5’EcoRI克隆位點(diǎn)大約304bp處。這個(gè)突變不打斷T細(xì)胞表位的翻譯。相比之下，發(fā)現(xiàn)突變體C12的轉(zhuǎn)座子插入離14F10 cDNA的5’EcoRI克隆位點(diǎn)大約116bp處，打斷了T細(xì)胞表位的翻譯。因此將14F10中的表位作圖在這兩個(gè)轉(zhuǎn)座子插入位點(diǎn)之間。SEQ ID NO586提供了C12和F10轉(zhuǎn)座子插入位點(diǎn)之間區(qū)域的氨基酸序列。
制備SEQ ID NO586中所示區(qū)域中一系列11個(gè)重疊的16-聚體和15-聚體肽并檢測抗LT391-06細(xì)胞的刺激，由TNF和IFN-γ測定中細(xì)胞因子釋放來確定。只有SEQ ID NO587(相當(dāng)于SEQ ID NO586的殘基5-20)提供的肽刺激細(xì)胞因子釋放。這些研究證明SEQID NO587中含有LT391-06抗原的HLA-Cw1203限制性表位。
實(shí)施例9通過PCR消減(PCR subtraction)分離和表征編碼肺腫瘤抗原的DNA序列這個(gè)實(shí)施例描述了從上述的人肺腫瘤細(xì)胞系LT391-06制備的PCT消減表達(dá)文庫得到的cDNA克隆的分離和表征。
如上所述從細(xì)胞系LT391-06制備測試聚腺苷酸mRNA。從來自非肺細(xì)胞并且不被LT391-06反應(yīng)性T細(xì)胞識別的人急性T細(xì)胞白血病/T淋巴細(xì)胞細(xì)胞系(Jurkat)分離驅(qū)動聚腺苷酸mRNA。根據(jù)Clontech的方法(Palo Alto，CA)進(jìn)行消減，并作如下改變1)使用酶混合物(MscI，PvuII，StuI和DraI)完成cDNA第二次限制性消化反應(yīng)。這是附加并獨(dú)立于Clonetch推薦的用RsaI進(jìn)行的單一限制性酶消化。每個(gè)限制性消化組作為單獨(dú)的文庫進(jìn)行處理以確保最后混合的文庫含有重疊的片段。因此，T細(xì)胞識別的表位應(yīng)該存在于文庫內(nèi)的片段上且不因其中單一限制性位點(diǎn)的存在而破壞。2)在雜交步驟中增加驅(qū)動與測試cDNA的比以增加消減嚴(yán)格性。為了分析消減的效率，從消減以及未消減的PCR樣本的稀釋物中PCR擴(kuò)增肌動蛋白。第二次擴(kuò)增步驟使用由那些正常使用的引物修改而得到的引物。設(shè)計(jì)三個(gè)嵌套式PCR引物使其含有在三個(gè)框架之一內(nèi)的可切割EcoRI位點(diǎn)(在克隆過程中不使用)。因此，用這些引物進(jìn)行的第二次擴(kuò)增產(chǎn)生了可直接連接到真核表達(dá)質(zhì)粒pcDNA4His/Max-Topo(Invitrogen)中的產(chǎn)物。這使PCR消減和擴(kuò)增的片段在文庫內(nèi)某處符合讀框。由于消減的機(jī)制，將僅有50％的片段是正確的方向。從最終混合的PCR消減表達(dá)文庫，稱作LT391-6PCR中隨機(jī)挑選96個(gè)克隆測序來表征文庫復(fù)雜性和豐余性。通過與公眾可利用數(shù)據(jù)庫中的序列作比較分析這些序列(SEQ ID NO512-581)(表5)。表5




實(shí)施例10分離和表征來自對肺腫瘤抗原特異性的T細(xì)胞克隆的T細(xì)胞受體這個(gè)實(shí)施例描述了來自對肺腫瘤細(xì)胞系LT391-06表達(dá)的抗原特異性的CD8 T細(xì)胞克隆的T細(xì)胞受體(TCR)α和β的克隆和測序。T細(xì)胞的壽命有限。TCR鏈的克隆和隨后的轉(zhuǎn)移將基本上使T細(xì)胞特異性能夠無限增殖。腫瘤抗原TCR鏈的克隆允許將特異性轉(zhuǎn)移給從具有TCR MHC限制性等位基因的患者分離的T細(xì)胞。然后這種T細(xì)胞可以擴(kuò)充并用于進(jìn)繼轉(zhuǎn)移技術(shù)以將腫瘤抗原特異性導(dǎo)入攜帶表達(dá)該抗原的腫瘤的患者(如見Clay等J.Immunol.163507(1999))。
產(chǎn)生對肺腫瘤細(xì)胞系LT391-06特異性的細(xì)胞毒性T淋巴細(xì)胞(CTL)克隆。使用Trizol試劑從15個(gè)這種克隆的2×106個(gè)細(xì)胞中分離總mRNA，并用Ready-to-Go試劑盒(Pharmacia)合成cDNA。為了確定這些克隆中的Va和Vb序列，合成一系列Va和Vb亞型特異性引物并用于從每個(gè)克隆產(chǎn)生的cDNA的RT-PCR反應(yīng)。RT-PCR反應(yīng)證明每個(gè)克隆表達(dá)共同的對應(yīng)于Vb13亞族的Vb序列。使用從克隆之一(稱作1105)產(chǎn)生的cDNA，確定所表達(dá)的Va序列是Va22。為了從克隆1105克隆全TCRα和β鏈，設(shè)計(jì)引物跨越編碼起始子和終止子的TCR核苷酸。用從CTL克隆合成的cDNA和引物，和PWO(BMB)作為耐熱聚合酶建立標(biāo)準(zhǔn)的35個(gè)循環(huán)RT-PCR反應(yīng)。將所得的特異性條帶(α鏈大約850bp和β鏈大約950bp)連接到PCR平端載體(Invitrogen)并轉(zhuǎn)化至大腸桿菌。鑒定用含全長α和β鏈的質(zhì)粒轉(zhuǎn)化的大腸桿菌，大規(guī)模制備相應(yīng)的質(zhì)粒。對含全長TCRα和β鏈的質(zhì)粒進(jìn)行測序。SEQ ID NO583和582分別提供了α和β鏈的測定的cDNA序列，SEQ ID NO584和585分別提供了相應(yīng)的氨基酸序列。
從前述將會領(lǐng)會到，盡管為了舉例說明的目的，這里已經(jīng)描述了本發(fā)明的具體實(shí)施方案，可以進(jìn)行各種變型而不偏離本發(fā)明的精神和范圍。因此，除了所附權(quán)利要求，本發(fā)明不受限制。
序列表<110>Corixa CorporationReed，Steven G.
Henderson，Robert A.
Lodes，Michael J.
Fling，Steven P.
Mohamath，RaodohAlgate，Paul A.
Secrist，HeatherIndirias，Carol YosephBenson，Darin R.
Elliot，MarkMannion，JaneKalos，Michael D.
<120>治療和診斷肺癌的組合物和方法<130>210121.47501PC<140>PCT<141>2001-03-38<160>587<170>FastSEQ for Windows Version 3.0<210>1<211>339<212>DNA<213>智人(Homo sapiens)<400>1gtactcagac aggatagtca tcatgtagca caaagcamat cctgtttcta tacttgtagt 60ttgctctcac tcagtggcat ratcattact atacagtgta gaatgttrtt atgtagcata120gatgtggggt ctctagccca cagctctsta cctttgtcta gcactcctgt cctcatacct180ragtggcctg tccatcagca tgtttctcat ctactttgct tgtccagtcc actgtggtcc240tcccttgccc tctcccttat gtggcagagt ggaaccagct gtcctgagac ttgagttcaa300catctggttc gcccatytgc atgtttgtgg tctgagtac 339<210>2<211>698<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(698)<223>n＝A、T、C或G<400>2gtactcagac cacgactgca ttttctccac tgctgacggg tctaatacca gctgcttccc 60tttcttggag gcagagctng tgaccttgag aaagtgacct gtgaccatca tgtgggtagt120gagctgctgc aaggtgtcat gggagctccc acactccatg cactttwaga tctgggactt180gcaggcctca ractgccagg tgtagctcgc tccattttgg tagccatagc gsttgttgga240ggacaactgc aagttggcgt tcttctgaga agaaaaagaa tctgcaaaag atcctgtggt300tgaatcgggg gaacacggcc gattgacatc aaaaacgcgt ttcttagccc gggtgaccat360tttcgaggaa atggttgggg actggctcct tcaaaggcac tttttggtta tgttttgttt420yaatcatgtk gacgctccaa tcttggragg gaatcgaang rantcnccnc caaaacatrc480stttcagraa ccttttgarc atcctctttt ttccgtrtcc cggmaargcc cytttccckg540ggctttgaaa wyagcctsgt tgggttctta aattaccart ccacnwgttg gaattccccg600ggccccctgc ccggktccaa ccaattttgg graaaacccc cncansccgt tkggantgcn660acaacntggn ntttttcntt tcgtgntccc ctngaacc698<210>3<211>697<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(697)<223>n＝A、T、C或G<400>3gtactcagac ccccaacctc gaacagccag aagacaggtt gtctcctggg ccttggacac 60agccngccag gccattgaag ganaagcaaa gacgaagcga accatctctc tccattgtgg120gggccaagta gctgcantan ccttcagtcc cagttgcatt gggttaaaga gctcatacat180actatgtgtn aggggtacag aagcttttcc tcatagggca tgagctctcc nagagttgac240cttttgcctn aacttggggt ttctgtggtt cataaagttn ggatatgtat tttttttcaa300atggaanaaa atccgtattt ggcaaaaaga ctccaggggg atgatactgt ccttgccact360tacagtccaa angatnttcc ccaaagaata gacatttttt cctctcatca cttctggatg420caaaatcttt tatttttttc ctttctcgca ccnccccaga ccccttnnag gttnaaccgc480ttcccatctc ccccattcca cacgatnttg aattngcann ncgttgntgg tcgggtcccn540nccgaaaggg tntttttatt cggggtnctg anttnnnaac cnctnagttg aatccgcggg600gcggccnngn gggttnnacc atgntgggga naactncccn ccgcgnttgg aatgccanag660ccttgaaant tttcttttgg tcgccccccn gagattc 697<210>4<211>712<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(712)<223>n＝A、T、C或G<400>4gtactcagac aaccaatagg tgtgttyctc anatctgaaa cacaaaaaga ttctagctna 60taatgttsaa tggttgaggg tttaagtgat cttggtatgt tngatttagc agcgatnggc120cgggtgcggt ggctcacgca tgtatcccag cactttggga ggccgaggca ggaggatcac180ctgaggtcag gagtttgaga ccagcctggc cgacatggtn aaaccccgtc tctactanga240atacanaaat tagcccgggc atagtggcgc gtgcctrtga cctcsgctac tttggggatt300ctcctgagga agaattgctt gaactcaggg aagtggargt ttgcagtgag cttaaatcaa360gccactggca ctcccagcct gggktaacag agccamgact ctkgccgaaa aaaaaraama420cgacggagaa nmagntctgt tattccatgg gaaattkgaa tttccttcyt tkaaatatct480taaaatnggt cctcctwaaa aaagttcggc tggggcccgk tggctcacat tttkttaycc540cycccccttt tggggarggc caarggccgg kttgawtnnc ccttgagggg ccanaactcc600agnaaccrgn cccgggccar smgwkgkstr armccctttc cyyccmaraa aawwcsmaaa660wwttycccsc cygsykggct ggkasckgtt myyyyygmtm csyagcttgc tt712
<210>5<211>679<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(679)<223>n＝A、T、C或G<400>5gtactcagac cacctcacat gcagggtnag aaacatggag tgtgcggcag catcctcctc 60acatcccttt gtgagcacgg ctgctccgga atactgacca tctgggctag cacgacctaa120cagagggttc tgcaggatgt gctattttaa agcagctggg tgcaacttgt gaaaacggga180atctngaagc agaacatgtn atcagcgatg gctgggattg gtggacagga ttgacaggag240tatttgaggc tctaccaggc ctgtctacag gacagcttca tcgaagggac attttttaac300ctgttatttt anatnccaca tatntttttt aatgctnaag catacaggtt gaatttctgg360atcgtaacta ctagtgactt ctgaggttta cagttngaat atgttctcnn aggtttatca420agttntgtta ttgatgatng gtaatctaca cctctggaag ctgtngaatg tgaaaaagat480ncntncanct gaccagtttg nagggcactc tcttctggna agnaatccgn ccaaaaaaat540tgtttcnagg gggcntgggg ggtttaaaaa aatgtttctn ttnccntaaa aatgtttacc600cnnctattga aaaaatgggg gtcgnggggg gcttnaaatc cccnanttnt gaatnttnta660tccggaanct tggtttccc 679<210>6<211>369<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(369)<223>n＝A、T、C或G<400>6tcagtccagt catgggtcct ataagagaag tcactctgtg agtttccatg gaggaagaaa 60aagcttcatt tctttaccct gcagcaacag cggagggagg gagagcctat cttctttgca120aattcattaa ctttgtggtt gaagggagca gcgtcngaaa ctgctttagc acagtgggag180gaaaacaaac agattcatct ccggaaacca aaggaaaggg tragtgggtt tttattagcc240agctgtatcc tagatggtca atttccagtg gatgaataca ccttacgtac gtttctcttg300cttcctacct nggcctgatc agctnggcac ttraatcatt ccgtnggggt wgctgtnaca360ctggactga369<210>7<211>264<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(264)<223>n＝A、T、C或G<400>7tgctggatra gggatggggc acgggagcac agatmgactt taactgcccc cacgttntcm 60aggaaaggat tacaggcgtg agccactgcg cccggcctct tctccacttt cataggttcc120agtctctggt tcttctttct cagtttgttg tttttgcttc ttaaatmatg gagatnagaa180tgaacactac actcggaatc aggaagccct gcctggcgcc tctgtcacct gtctaggggc240ttcttctcac tgagtcatcc agca264<210>8<211>280<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(280)<223>n＝A、T、C或G<400>8acctcaactg cccanaacan aactgttgta caagatttga ggatttaaca atatttcaca 60tgaaatattt cagacctacg ngagggctta aagacnaatt aaatgagcac cngtgtgccc120accgccccna ttaagaatta gagcaagcag tgaggtgaag ccttgtcctt gcttttaaca180tagaaagtga tccaaattca ccaaacttga cttnnggttt tgcagtgtgg cctcctgatt240ctagacnctg gcgaaacatt tgatgggcaa aaaaaaaaaa 280<210>9<211>449<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(449)<223>n＝A、T、C或G<400>9tcgtcaactc caggatggct ttgaaaatna atggacacag atctctcctg ttttgatrat 60ntgcagtgct natgactggc tttgcagttn attttgattc aggcaacaga tgttcctttt120ggttccctgt ctcccatggg cgtcatttca tgttgtcctc tgccttcccc cagatattct180aagttcagga cacaagcttc tggcccatgc agagcagagg ccatgagggg tcacagcatg240ggtacgggag gaaacactgg gctnacccag atnctggact tgagtcttgc ctctgctgct300tgctgcacag cttctgtcat ggtgctaaac ctgtgacctg cctcacaggc ttagagcatg360cccgtagaag tactctnaac taaratgctt tccacaaatg agatggtttc atgaaaactt420caaatagagg gcctgggcaa aaaaaaaaa 449<210>10<211>538<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(538)<223>n＝A、T、C或G<400>10tttttttttt ttcccaaagg cctcaraaca ctagtcttct aattccaagc agaaagttac 60atccgccggg atacatgcca cttggtttga taaatcaaaa tacagcatcc ttcagatccc120tttgctgagc aatacaatta tttgtatatg ttactttttt ttctgtttgg ctnaaagatt180tgatatgagc tgaggaaaat gaagccntta ctgctatnag atctnatccc tttccaccac240ctttcaggga tnttggcact gcayatattc agaattcccc nnagtcgctn gtgataaaaa300tgtcttcaga gatggcagaa tatgtttcct ttggtacatg ttcattaaaa atatacacgt360gctcactact gtggatatgt atgtnttgac cgatnacaca ggctgattta gggaagagat420aaaagcacac ttngaattta ttagcctttc accnagacta anattctgaa attaagaatg480tattccttgg tcaacaattt tcctcttctc ttagccctct tacattgtan tggactga 538<210>11<211>543<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(543)<223>n＝A、T、C或G<400>11tttttttttt ttgcccacag ctgccatctt tgtgtgataa ggccaacctt ctatgggaat 60caaccctcgc catcccagca aatcccctct ctcccttctc atgggagtgc cttgtattca120tcaggcatct gggacttgat gtgggtntgg gatttgaaat cagagcacct nggtctctst180caccattctn tcacttatta gctctnacct tgggtnaata cctgccttag tgtcntaggt240acaatatgaa tattgtctat ttctcaggga ttgcaatgac nagtnnatna gtgcatgaga300gggtaaaacc acagggtact ccgctcctcc naagaatgga gaattttttc tagaagccca360natntgcttg gaaggttggc caccnagagc cnnaatcttc ttttatttnc cactgaangc420ctaagaggna attctgaact catccccnna tgacctctcc cgaatmagaa tatctctggc480acttaccata ttttcttgcc ctcttccact tacnaaactc ctttattcct taacnggacg540aaa 543<210>12<211>329<212>DNA<213>智人(Homo sapiens)<400>12cgatgacttg ggcagtgagt gggcctcctg ccaggtggca gggcacagct tagaccaaac 60ccttggcctc ccccctctgc agstacctct gaccaagaag gaaactagca agcctatgct120ggcaagacca taggtggggt gctgggaatc ctcggggccg gctggcaccc actcctggtg180ctcaagggag agacccactt gttcagatgc atrggcctca ggcggttcaa ggcrgtctta240gagccacaga gtcaaataaa aatcaatttt gagagaccac agcacctgct gctttgatcg300tgatgttcaa ggcaagttgc aagtcatcg 329<210>13<211>314<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(314)<223>n＝A、T、C或G<400>13cgatgacttg cacccgggag ctgtgacagt ggcctggaag cagatggcag ccccgtcaag 60gcgggagtgg agaccaccaa accctccaaa cagagcaaca actagtacgc ggccagcagc120tacctgagcc tgacgcccga gcagtggaag tcccacagaa gctacagctg ccaggtcacg180catgaaggga gcaccgtgga gaagacagtg gcccctacag aatgttcata ggttcccnac240tctnacccca cccacgggag cctgganctg cangatcccg ggggaagggt ctctctcccc300atcccaagtc atcg 314<210>14<211>691<212>DNA
<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(691)<223>n＝A、T、C或G<400>14cgattacttg cacaatgcan attagaaccc aaatgaaggg tacaacccag atcttctggc 60ttccagttca gtgctgctgg gtttttctta ctaaaccaaa acaatkaaga gcatagaagg120gaagagaaga ataaagtcta ttttggtctt tggtagcchg ggtaangaga atgctstcac180tctacnagaa aacccnaagt gaacccggct aatcaggacc gtgcttggga agggagcagg240ggcattacct ttcaacacca gaggttcttt gccttctctc tgcagggact cgargactat300gtgaagtggc tgggarggca tcactcggct tggttcattg gtrttctcat cataaactat360natttctttg gaaaaagatc ctcttgaaag artccttgcc ttccctacag gaaatcaagt420ctaggacagt gatcttgccc ctgcttgcas tctccgccgg ctgatcttat csgscccagt480tkatgtgsam cgctccttgg atrtkactct tgttttwctc cvaggaaggg gcytgcmagt540ccnwtnaatg amssgggccc ttaactccgg scrggtnamy ncttgsctsc rattttgggt600ycytcttcyt ttgsccmggt tcktcnaaac cacttngttr aattccccgg sccgcctkgc660nggtycaacc wttttgggaa mamcyccccc c 691<210>15<211>355<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(355)<223>n＝A、T、C或G<400>15acctgaactg tgtgttgaag agtgatgtcc tgctgcctgg agctcaagtc actactgatg 60accgtgccta tgtccgacag ctagttncct ccatggatgt gactgagacc aatgtcttct120tcyaccctcg gctcttacct ttgacnaagt ctcccgttga gagtactacc gaaccaccag180cagttcgagc ctctnaagag cgtctaagcg atggggatat atatttactg gagaatgggc240tcaacctctt cctctgggtg ggagcaagcg tccagcaggg tgttgtccag agccttttca300gcgtctcctc cttcagtcag atcaccagtg gtntgagtgt tctgccagtt caggt 355<210>16<211>522<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(522)<223>n＝A、T、C或G<400>16tcagtccagt gaggtggaag acttcgaggc tcgtgggagc cgcttctcca agtctgctga 60tgagagacag cgcatgctgg tgcagcgtan ggacgaactc ctccagcaag ctcgcagacg120tttcttgaac aaaagttctg aagatgatgc ggcctcagag agcttcctcc cctcggaagg180tgcgtcctct gaccccgtga ccctncgtcg aangatgctg gctgccgccg cggaacggan240gcttcagaag cagcagacct cctngcgctc ccttgccttc ctcagctgcc tcctgcgccc300tgtgcccggc tgactggagg aggcctgtcc aattctgccc gccccatgga aaagcgggct360tgactgcatt gccgctgtat naaagcatgt ggtcttacag tgttnggacn gctnatnaat420ttnatcctnc tntgtaatac ttcctatgtg acatttctct tccccttgga aacactgcan480attttaactg tgagtttgat ctcttctngt gttactggac tg522<210>17<211>317<212>DNA<213>智人(Homo sapiens)<400>17gtgtcgcgaa ttcgcggtgg tgctaagaaa aggaagaaga agtcttacac cactcccaag 60aaggataagc accagagaaa gaaggttcag ccggccgtcc tgaaatatta taaggtggat120gagaatggca aaattagttg ccttcgtcga gagtgcccct ctgatgaatg tggtgctggg180gtgtttatgg caagtcactt tgacagacat tattgtggca aatgttgtct gacccactgt240ttcaactaac cagaagacaa gtaactgtat gagttaatta aagacatgaa ctaaaaaaaa300aaaaaaaaaa actcgag 317<210>18<211>392<212>DNA<213>智人(Homo sapiens)<400>18tggagatttc taatgaggtg aggaagttcc gtacattgac agaattgatc ctcgatgctc 60aggaacatgt taaaaatcct tacaaaggca aaaaactcaa gaaacaccca gacttcccca120agaagcccct gaccccttat ttccgcttct tcatggagaa gcgggccaag tatgcgaaac180tccaccctca gatgagcaac ctggacctga ccaagattct gtccaagaaa tacaaggagc240ttccggagaa gaagaagatg aaatatgttc cggacttcca gagaagagaa acaggagttc300gagcgaaacc tggcccgatt cagggaggat cacccccacc ttatccagaa tgccaagaat360cggacatccc agagaagccc caagaccccc cg 392<210>19<211>2624<212>DNA<213>智人(Homo sapiens)<400>19gaaacagtga gaaggagatt cctgtgctca atgagctgcc agtccccatg gtggcccgct 60acattcgcat aaaccctcag tcctggtttg ataacgggag catctgcatg aggatggaga 120tcttgggctg cccactgccg gatcctaata actattatca ccgacgtaat gagatgacca 180ccacggatga cctggatttt aagcaccaca actattagga aatgcgccag ttgatgaagg 240ttgtcaatga aatgtgcccc aatattacca ggatttacaa cattggcaaa agccaccagg 300gcctgaaatt gtatgcggta gagatctctg accatcctgg ggaacatgaa gttggtgagc 360ccgagttcca ctacatcgca ggggcccacg gcaatgaggt tctgggacga gaactgctgc 420tgctgctgct gcacttcctc tgccaggaat actcggcgca gaacgcacgc atcgtccgct 480tggtggagga gactcgaatc cacattctac cctccctcaa tcctgatggc tatgagaagg 540cctatgaagg aggttccgag ttgggaggct ggtccctggg acgttggacc catgatggca 600tcgatatcaa caacaacttt ccggatttaa actcgctgct ctgggaggca gaggaccagc 660agaatgcccc aaggaaggtc cccaaccact acattgccat ccctgagtgg tttctgtctg 720agaatgccac agtggccaca gagaccagag ccgtcatcgc ctggatggag aagatcccgt 780ttgtgctggg aggcaaccta caggggggtg agctggtcgt ggcatacccc tatgacatgg 840tgcggtccct gtggaagacc caggagcaca ccccaacacc tgatgatcat gtgttccgct 900ggctggcgta ttcctacgcc tccactcacc gcctcatgac agatgccagg aggcgagtgt 960gccacacgga agattttcag aaggaggagg gcaccgtcaa tggggcttcc tggcacacag1020tggctggaag tctaaacgat ttcagctacc tccatacaaa ctgctttgag ctgtccatct1080acgtgggctg tgataaatac ccacacgaga gcgagctgcc ggaggaatgg gagaataacc1140gggagtctct gattgtgttc atggagcagg ttcatcgagg catcaaaggc atagtgagag1200atttacaagg gaaagggatt tcaaatgctg tcatctctgt ggaaggtgtt aaccatgaca1260tccggacagc cagcgatggg gattactggc gtctactgaa ccctggcgaa tatgtggtca1320cagccaaggc ggaaggcttt atcacttcca ccaagaactg catggttggc tatgatatgg1380gagctactcg gtgtgacttc accctcacaa agaccaacct ggctaggata agagaaatta1440tggagacatt tgggaagcag cctgtcagcc taccctccag gcgcctgaag ctgcggggac1500ggaaaaggcg gcagcgtggg tgaccctgtc ggacacttga gacatacccc agaccgtgca1560aataaaaatc cactccagta gtaactctgt agcaggcttt ccctgttgtt ttgactgtaa1620ttcaagagac actcaggagc atacctgcat ggcttggctg accccaaagg ggagggctgg1680tggctcaggg tgttttgttt tttgtttttt gttttttcct ttgttctcat ttatccaaat1740accttgaaca gagcagcaga gaaaggccgg tggcagtgag ggaattaatt cagtgagtca1800gtctgagatt ctaaaaaggg tgcttgacca ctggccagga agggaaatca ggccttcccc1860catttgcgtg acattcaagc ttcccagtgc atttgcaagt ggcacagttg acattgcagc1920acccagggaa tcctttgccc cagatgttat catttgagat gctcttatgc agcctaagaa1980aatccatcct ctctggcccc aggggacaag ccaagctgct atgtacacac tcggtgttct2040attgacaata gaggcattta ttaccaagtg tgcatcgctg agtcctaaat cagctctgtt2100cctttttcca acaaagcttg tcttcctaag agcagacaga agtggagagc acccaagaat2160gagtgctggg cagcagaccc tgggggaggg ggcttgctat cccagaaagc ccctaaaccc2220tttgctgctc cattagccct ggggtgagga gagccagaca tgttaggagg ccagagcagt2280cagtcagggc atcttggaaa agaccttgaa ggaagcaaac cctgggttcc ttttgctcca2340gaatgtgaga gctccaagtt ggccccaatc aggaggggag taatgatgaa catacagacg2400gccacatctt gccaatcaag catcatctga tgaaaaagaa agcaatctta ggattacctg2460ggacacgtca gtctgggaga ggtggttgaa tcattgtgta agggaatagt gtatctaatc2520tgtgttgatc ctgctgcctt gttgacctgg agagaatgaa acaaacaaac acataaacaa2580ataaagcaaa tggtaagatt aaaaaaaaaa aaaaaaaact cgag 2624<210>20<211>488<212>DNA<213>智人(Homo sapiens)<400>20ctttcaaccc gcgctcgccg gctccagccc cgcgcgcccc caccccttgc cctcccggcg 60gctccgcagg gtgaggtggc tttgaccccg ggttgcccgg ccagcacgac cgaggaggtg120gctggacagc tggaggatga acggagaagc cgactgcccc acagacctgg aaatggccgc180ccccagaggc caagaccgtt ggtcccagga agacatgctg actttgctgg aatgcatgaa240gaacaacctt ccatccaatg acagctccca gttcaaaacc acccaaacac acatggaccg300ggaaaaagtt gcattgaaag acttttctgg agacatgtgc aagctcaaat gggtcgagat360ctctaatgag gtgaggaagt tccgtacatt gacagaattg atcctcgata ctcaggaaca420tgtttaaaat ccttacaaag gcaaaaaatc aagaaacacc ccgacttccc cgagaaagcc480cctaaccc 488<210>21<211>391<212>DNA<213>智人(Homo sapiens)<400>21atggaattgt ggttttctct ttgggatcaa tggtctcaga aattccagag aagaaagctg 60tggcgattgc tgatgctttg ggcaaaatcc ctcagacagt cctgtggcgg tacactggaa120cccgaccatc gaatcttgcg aacaacacga tacttgttca gtggctaccc caaaacgatc180tgcttggtca cccaatgacc cgtgccttta tcacccatgc tagttcccat ggtgttaatg240aaagcatatg caatggcgtt cccatggtga tgataccctt atttggtgat cagatggaca300atgcaaagcg cagggagact aagggagctg gagtgaccct gaatgttctg gagatgactt360ctgaagatct agaagatgct ctgaagagca g 391<210>22<211>1320<212>DNA<213>智人(Homo sapiens)<400>22aatctgctgg gaatttcttg ggttgacagc tcttggatcc ctattttgaa cagtggtagt 60gtcctggatt acttttcaga aagaagtaat cctttttatg acagaacatg taataatgaa 120gtggtcaaaa tgcagaggct aacattagaa cacttgaatc agatggttgg aatcgagtac 180atccttttgc atgctcaaga gcccattctt ttcatcattc ggaagcaaca gcggcagtcc 240cctgcccaag ttatcccact agctgattac tatatcattg ctggagtgat ctatcaggca 300ccagacttgg gatcagttat aaactctaga gtgcttactg cagtgcatgg tattcagtca 360gcttttgatg aagctatgtc atactgtcga tatcatcctt ccaaagggta ttggtggcac 420ttcaaagatc atgaagagca agataaagtc agacctaaag ccaaaaggaa agaagaacca 480agctctattt ttcagagaca acgtgtggat gctttacttt tagacctcag acaaaaattt 540ccacccaaat ttgtgcagct aaagcctgga gaaaagcctg ttccagtgga tcaaacaaag 600aaagaggcag aacctatacc agaaactgta aaacctgagg agaaggagac cacaaagaat 660gtacaacaga cagtgagtgc taaaggcccc cctgaaaaac ggatgagact tcagtgagta 720ctggacaaaa gagaagcctg gaagactcct catgctagtt atcatacctc agtactgtgg 780ctcttgagct ttgaagtact ttattgtaac cttcttattt gtatggaatg cgcttatttt 840ttgaaaggat attaggccgg atgtggtggc tcacgcctgt aatcccagca ctttgggagg 900ccatggcggg tggatcactt gaggtcagaa gttcaagacc agcctgacca atatggtgaa 960accccgtctc tactaaaaat acaaaaatta gccgggcgtg gtggcgggcg cccatagtcc1020cagctactcg ggaggctgag acaggagact tgcttgaacc cgggaggtgg aggttgccct1080gagctgatca tcctgctgtt gcactccagc ttgggcgaaa gagcgagact ttgtctctat1140aaagaaggaa agatattatt cccatcatga tttcttgtga atatttgtaa tatgtttttt1200gtaacctttc ctttcccgga cttgagcaac ctacacactc acatgtttaa tggtagatat1260gttttaaagc aagataaagg tattggtttt aaaaaaaaaa aaaaaaaaaa aaaactcgag1320<210>23<211>633<212>DNA<213>智人(Homo sapiens)<400>23ctaagggcag tgaaggtgaa aaccctctca cggtcccagg gagggagaag gaaggcatgc 60tgatgggggt taagccgggg gaggacgcat cggggcctgc tgaagacctt gtgagaagat120ctgagaaaga tactgcagct gttgtctcca gacagggcag ctccctgaac ctctttgaag180atgtgcagat cacagaacca gaagctgagc cagagtccaa gtctgaaccg agacctccaa240tttcctctcc gagggctccc cagaccagag ctgtcaagcc ccgacttcat cctgtgaagc300caatgaatgc cacggccacc aaggttgcta actgcagctt gggaactgcc accatcatcg360gtgagaactt gaacaatgag gtcatgatga agaaatacag cccctcggac cctgcatttg420catatgcgca gctgacccac gatgagctga ttcagctggt cctcaaacag aaggaaacga480taagcaagaa ggagttccag gtccgcgagc tggaagacta cattgacaac ctgctcgtca540gggtcatgga agaaaccccc aatatcctcc gcatcccgac tcaggttggc aaaaaagcag600gaaagatgta aattagcaga aaaaaaactc gag 633<210>24<211>1328<212>DNA<213>智人(Homo sapiens)<400>24gtaaacgctc tcggaattat ggcggcggtg gatatccgag acaatctgct gggaatttct 60tgggttgaca gctcttggat ccctattttg aacagtggta gtgtcctgga ttacttttca 120gaaagaagta atccttttta tgacagaaca tgtaataatg aagtggtcaa aatgcagagg 180ctaacattag aacacttgaa tcagatggtt ggaatcgagt acatcctttt gcatgctcaa 240gagcccattc ttttcatcat tcggaagcaa cagcggcagt cccctgccca agttatccca 300ctagctgatt actatatcat tgctggagtg atctatcagg caccagactt gggatcagtt 360ataaactcta gagtgcttac tgcagtgcat ggtattcagt cagcttttga tgaagctatg 420tcatactgtc gatatcatcc ttccaaaggg tattggtggc acttcaaaga tcatgaagag 480caagataaag tcagacctaa agccaaaagg aaagaagaac caagctctat ttttcagaga 540caacgtgtgg atgctttact tttagacctc agacaaaaaa tttccaccca aatttgtgca 600gtggatcaaa caaagaaaga ggcagaacct ataccagaaa ctgtaaaacc tgaggagaag 660gagaccacaa agaatgtaca acagacagtg agtgctaaag gcccccctga aaaacggatg 720agacttcagt gagtactgga caaaagagaa gcctggaaga ctcctcatgc tagttatcat 780acctcagtac tgtggctctt gagctttgaa gtactttatt gtaaccttct tatttgtatg 840gaatgcgctt atttttttga aaggatatta ggccggatgt ggtggctcac gcctgtaatc 900ccagcacttt gggaggccat ggcgggtgga tcacttgagg tcagaagttc aagaccagcc 960tgaccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattagccg ggcgtggtgg1020cgggcgccca tagtcccagc tactcgggag gctgagacag gagacttgct tgaacccggg1080aggtggaggt tgccctgagc tgattatcat gctgttgcac tccagcttgg gcgacagagc1140gagactttgt ctcaaaaaag aagaaaagat attattccca tcatgatttc ttgtgaatat1200ttgtgatatg tcttctgtaa cctttcctct cccggacttg agcaacctac acactcacat1260gtttactggt agatatgttt aaaagcaaaa taaaggtatt tgtataaaaa aaaaaaaaaa1320aaactcga 1328<210>25<211>1758<212>DNA<213>智人(Homo sapiens)<400>25gttttttttt tttttttttt aaagagttgc aacaattcat ctttatttct tattttcctc 60tggagatgca gaatttggta tatttcaccc caagtatatt tgggatagtt ggctcctcgc 120tgggtcagga tggctgggtg ccttctcccc tggcatggtt ctcttctctg cagggcgagg 180ggcagggagc tagtaaaacc tcgcaatgac agccgcaatg gcagacccaa tggagcccag 240gatgaacttg gtcaatccgg agagtccagt tgctcccagt gactgcagag tagccacaag 300gctgcccgag gcaactccac ccccattggc aatggccgcc gcggacatca tcttggctgc 360tatggaggac gaggcgattc ccgccgcagt gaagcccatg gcactgagtg gcggcggtgg 420atatccgaga caatctgctg ggaatttctt gggttgacag ctcttggatc cctattttga 480acagtggtag tgtcctggat tacttttcag aaagaagtaa tcctttttat gacagaacat 540gtaataatga agtggtcaaa atgcagaggc taacattaga acacttgaat cagatggttg 600gaatcgagta catccttttg catgctcaag agcccattct tttcatcatt cggaagcaac 660agcggcagtc ccctgcccaa gttatcccac tagctgatta ctatatcatt gctggagtga 720tctatcaggc accagacttg ggatcagtta taaactctag agtgcttact gcagtgcatg 780gtattcagtc agcttttgat gaagctatgt catactgtcg atatcatcct tccaaagggt 840attggtggca cttcaaagat catgaagagc aagataaagt cagacctaaa gccaaaagga 900aagaagaacc aagctctatt tttcagagac aacgtgtgga tgctttactt ttagacctca 960gacaaaaatt tccacccaaa tttgtgcagc taaagcctgg agaaaagcct gttccagtgg1020atcaaacaaa gaaagaggca gaacctatac cagaaactgt aaaacctgag gagaaggaga1080ccacaaagaa tgtacaacag acagtgagtg ctaaaggccc ccctgaaaaa cggatgagac1140ttcagtgagt actggacaaa agagaagcct ggaagactcc tcatgctagt tatcatacct1200cagtactgtg gctcttgagc tttgaagtac tttattgtaa ccttcttatt tgtatggaat1260gcgcttattt tttgaaagga tattaggccg gatgtggtgg ctcacgcctg taatcccagc1320actttgggag gccatggcgg gtggatcact tgaggtcaga agttcaagac cagcctgacc1380aatatggtga aaccccgtct ctactaaaaa tacaaaaatt agccgggcgt ggtggcgggc1440gcccatagtc ccagctactc gggaggctga gacaggagac ttgcttgaac ccgggaggtg1500gaggttgccc tgagctgatt atcatgctgt tgcactccag cttgggcgac agagcgagac1560tttgtctcaa aaaagaagaa aagatattat tcccatcatg atttcttgtg aatatttgtt1620atatgtcttc tgttaccttt cctctcccgg aattgagcaa cctacacact cacatgttta1680ctggtagata tgtttaaaag caaataaagg tattggtata tattgcttca aaaaaaaaaa1740aaaaaaaaaa aactcgag 1758<210>26<211>493<212>DNA<213>智人(Homo sapiens)<400>26gaggcgagcg gcagggcctg gtggcgagag cgcggctgtc actgcgcccg agcatcccag 60agctttccga gcggacgagc cggccgtgcc gggcatcccc agcctcgcta ccctcgcagc120acacgtcgag ccccgcacag gcaagggtcc ggaacttagc ccaaagcacg tttcccctgg180cagcgcagga gacgcccggc cgcgcgccgg cgcacgcccc cctctcctcc tttgttccgg240gggtcggcgg ccgctctcct gccagcgtcg ggatctcggc cccgggaggc gggccgtcgg300gcgcagccgc gaagattccg ttggaactga cgcagagccg agtgcagaag atctgggtgc360ccgtggacca caggccctcg ttgcccagat cctgtgggcc aaagctgacc aactcccccg420ccgtcttcgt catggtgggc ctcccccgcc cggggcaaga cctacttctc cacgaaagct480tactcgctgc ctc 493<210>27<211>1331<212>DNA<213>智人(Homo sapiens)<400>27ggtggatatc cgagacaatc tgctgggaat ttcttgggtt gacagctctt ggatccctat 60tttgaacagt ggtagtgtcc tggattactt ttcagaaaga agtaatcctt tttatgacag 120aacatgtaat aatgaagtgg tcaaaatgca gaggctaaca ttagaacact tgaatcagat 180ggttggaatc gagtacatcc ttttgcatgc tcaagagccc attcttttca tcattcggaa 240gcaacagcgg cagtcccctg cccaagttat cccactagct gattactata tcattgctgg 300agtgatctat caggcaccag acttgggatc agttataaac tctagagtgc ttactgcagt 360gcatggtatt cagtcagctt ttgatgaagc tatgtcatac tgtcgatatc atccttccaa 420agggtattgg tggcacttca aagatcatga agagcaagat aaagtcagac ctaaagccaa 480aaggaaagaa gaaccaagct ctatttttca gagacaacgt gtggatgctt tacttttaga 540cctcagacaa aaatttccac ccaaatttgt gcagctaaag cctggagaaa agcctgttcc 600agtggatcaa acaaagaaag aggcagaacc tataccagaa actgtaaaac ctgaggagaa 660ggagaccaca aagaatgtac aacagacagt gagtgctaaa ggcccccctg aaaaacggat 720gagacttcag tgagtactgg acaaaagaga agcctggaag actcctcatg ctagttatca 780tacctcagta ctgtggctct tgagctttga agtactttat tgtaaccttc ttatttgtat 840ggaatgcgct tattttttga aaggatatta ggccggatgt ggtggctcac gcctgtaatc 900ccagcacttt gggaggccat ggcgggtgga tcacttgagg tcagaagttc aagaccagcc 960tgaccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattagccg ggcgtggtgg1020cgggcgccca tagtcccagc tactcgggag gctgagacag gagacttgct tgaacccggg1080aggtggaggt tgccctgagc tgattatcat gctgttgcac tccagcttgg gcgacagagc1140gagactttgt ctcaaaaaaa gaagaaaaga tattattccc atcatgattt cttgtgaata1200tttgttatat gtcttctgta acctttcctc tcccggactt gagcaaccta cacactcaca1260tgtttactgg tagatatgtt taaaagcaaa ataaaggtat tggtataaaa aaaaaaaaaa1320aaaaactcga g 1331<210>28<211>1333<212>DNA<213>智人(Homo sapiens)<400>28cggcggtgga tatccgagac aatctgctgg gaatttcttg ggttgacagc tcttggatcc 60ctattttgaa cagtggtagt gtcctggatt acttttcaga aagaagtaat cctttttatg 120acagaacatg taataatgaa gtggtcaaaa tgcagaggct aacattagaa cacttgaatc 180agatggttgg aatcgagtac atccttttgc atgctcaaga gcccattctt ttcatcattc 240ggaagcaaca gcggcagtcc cctgcccaag ttatcccact agctgattac tatatcattg 300ctggagtgat ctatcaggca ccagacttgg gatcagttat aaactctaga gtgcttactg 360cagtgcatgg tattcagtca gcttttgatg aagctatgtc atactgtcga tatcatcctt 420ccaaagggta ttggtggcac ttcaaagatc atgaagagca agataaagtc agacctaaag 480ccaaaaggaa agaagaacca agctctattt ttcagagaca acgtgtggat gctttacttt 540tagacctcag acaaaaattt ccacccaaat ttgtgcagct aaagcctgga gaaaagcctg 600ttccagtgga tcaaacaaag aaagaggcag aacctatacc agaaactgta aaacctgagg 660agaaggagac cacaaagaat gtacaacaga cagtgagtgc taaaggcccc cctgaaaaac 720ggatgagact tcagtgagta ctggacaaaa gagaagcctg gaagactcct catgctagtt 780atcatacctc agtactgtgg ctcttgagct ttgaagtact ttattgtaac cttcttattt 840gtatggaatg cgcttatttt ttgaaaggat attaggccgg atgtggtggc tcacgcctgt 900aatcccagca ctttgggagg ccatggcggg tggatcactt gaggtcagaa gttcaagacc 960agcctgacca atatggtgaa accccgtctc tactaaaaat acaaaaatta gccgggcgtg1020gtggcgggcg cccatagtcc cagctactcg ggaggctgag acaggagact tgcttgaacc1080cgggaggtgg aggttgccct gagctgatta tcatgctgtt gcactccagc ttgggcgaca1140gagcgagact ttgtctcaaa aaagaagaaa agatattatt cccatcatga tttcttgtga1200atatttgtga tatgtcttct gtaacctttc ctctcccgga cttgagcaac ctacacactc1260acatgtttac tggtagatat gtttaaaagc aaaataaagg tatttgtata aaaaaaaaaa1320aaaaaaactc gag 1333<210>29<211>813<212>DNA<213>智人(Homo sapiens)<400>29ctgagctgca cttcagcgaa ttcacctcgg ctgtggctga catgaagaac tccgtggcgg 60accgagacaa cagccccagc tcctgtgctg gcctcttcat tgcttcacac atcgggtttg120actggcccgg ggtctgggtc cacctggaca tcgctgctcc agtgcatgct ggcgagcgag180ccacaggctt tggggtggct ctcctactgg ctctttttgg ccgtgcctcc gaggacccgc240tgctgaacct ggtatccccg ctggactgtg aggtggatgc ccaggaaggc gacaacatgg300ggcgtgactc caagagacgg aggctcgtgt gagggctact tcccagctgg tgacacaggg360ttccttacct cattttgcac tgactgattt taagcaattg aaagattaac taactcttaa420gatgagtttg gcttctcctt ctgtgcccag tggtgacagg agtgagccat tcttctctta480gaagcagctt aggggcttgg tggggtctgg agaaaattgt cacagacccc ataggtctcc540atctgtaagc tctgtccctt gtcctccacc ctggtcttta gagccacctc aggtcaccct600ctgtagtgag tgtacttcct gacccaggcc cttgctcaag ctggggctcc ctggggtgtc660taaccagccc tgggtagatg tgactggctg ttagggaccc cattctgtga agcaggagac720cctcacagct cccaccaacc cccagttcac ttgaagttga attaaatatg gccacaacat780aaaaaaaaaa aaaaaaaaaa aaaaaaactc gag 813<210>30<211>1316<212>DNA<213>智人(Homo sapiens)<400>30caggcgccca gtcatggccc aagagacagc accaccgtgt ggcccagtct caaggggtga 60cagtccaatc atagaaaaga tggaaaaaag gacatgtgcc ctgtgccctg aaggccacga 120gtggagtcaa atatactttt caccatcagg aaatatagtt gctcatgaaa actgtttgct 180gtattcatca ggactggtgg agtgtgagac tcttgatcta cgtaatacaa ttagaaactt 240tgatgtcaaa tctgtaaaga aagagatctg gagaggaaga agattgaaat gctcattctg 300taacaaagga ggcgccaccg tggggtgtga tttatggttc tgtaagaaga gttaccacta 360tgtctgtgcc aaaaaggacc aagcaattct tcaagttgat ggaaaccatg gaacttacaa 420attattttgc ccagaacatt ctccagaaca agaagaggcc actgaaagtg ctgatgaccc 480aagcatgaag aagaagagag gaaaaaacaa acgcctctca tcaggccctc ctgcacagcc 540aaaaacgatg aaatgtagta acgccaaaag acatatgaca gaagagcctc atggtcacac 600agatgcagct gtcaaatctc cttttcttaa gaaatgccag gaagcaggac ttcttactga 660actatttgaa cacatactag aaaatatgga ttcagttcat ggaagacttg tggatgagac 720tgcctcagag tcggactatg aagggatcga gaccttactg tttgactgtg gattatttaa 780agacacacta agaaaattcc aagaagtaat caagagtaaa gcttgtgaat gggaagaaag 840gcaaaggcag atgaagcagc agcttgaggc acttgcagac ttacaacaaa gcttgtgctc 900atttcaagaa aatggggacc tggactgctc aagttctaca tcaggatcct tgctacctcc 960tgaggaccac cagtaaaagc tgttcctcag gaaaactgga tggggcctcc atgttctcca1020aggatcgagg aagtcttcct gcctaccctg cccaccccag tcaagggcag caacaccaga1080gctttgctca gccttaaatg gaatcttaga gctttctctt gcttctgcta ctcctacaga1140tggcctcatc atggtctcca ctcagtatta ataactccat cagcatagag caaactcaac1200actgtgcatt gcacactgtt accatgggtt tatgctcact atcatatcac attgccaata1260tttagcacac ttaataaatg cttgtcaaaa cccaaaaaaa aaaaaaaaaa ctcgag1316<210>31<211>1355<212>DNA<213>智人(Homo sapiens)<400>31cggcggtgga tatccgagac aatctgctgg gaatttcttg ggttgacagc tcttggatcc 60ctattttgaa cagtggtagt gtcctggatt acttttcaga aagaagtaat cctttttatg 120acagaacatg taataatgaa gtggtcaaaa tgcagaggct aacattagaa cacttgaatc 180agatggttgg aatcgagtac atccttttgc atgctcaaga gcccattctt ttcatcattc 240ggaagcaaca gcggcagtcc cctgcccaag ttatcccact agctgattac tatatcattg 300ctggagtgat ctatcaggca ccagacttgg gatcagttat aaactctaga gtgcttactg 360cagtgcatgg tattcagtca gcttttgatg aagctatgtc atactgtcga tatcatcctt 420ccaaagggta ttggtggcac ttcaaagatc atgaagagca agataaagtc agacctaaag 480ccaaaaggaa agaagaacca agctctattt ttcagagaca acgtgtggat gctttacttt 540tagacctcag acaaaaattt ccacccaaat ttgtgcagct aaagcctgga gaaaagcctg 600ttccagtgga tcaaacaaag aaagaggcag aacctatacc agaaactgta aaacctgagg 660agaaggagac cacaaagaat gtacaacaga cagtgagtgc taaaggcccc cctgaaaaac 720ggatgagact tcagtgagta ctggacaaaa gagaagcctg gaagactcct catgctagtt 780atcatacctc agtactgtgg ctcttgagct ttgaagtact ttattgtaac cttcttattt 840gtatggaatg cgcttatttt ttgaaaggat attaggccgg atgtggtggc tcacgcctgt 900aatcccagca ctttgggagg ccatggcggg tggatcactt gaggtcagaa gttcaagacc 960agcctgacca atatggtgaa accccgtctc tactaaaaat acaaaaatta gccgggcgtg1020gtggcgggcg cccatagtcc cagctactcg ggaggctgag acaggagact tgcttgaacc1080cgggaggtgg aggttgccct gagctgatta tcatgctgtt gcactccagc ttgggcgaca1140gaacgagact ttgtctcaaa aaaagaagaa aagatattat tcccatcatg atttcttgtg1200aatatttgtt atatgtcttc tggtaacctt tcctctcccg gacttgaagc aacctcacac1260actcacatgt ttactggtag atatgtttta aaagcaaaat aaaggtattt gtttttccaa1320aaaaaaaaaa aaaaaaaaaa aaaaaaaaac tcgag 1355<210>32<211>80<212>PRT<213>智人(Homo sapiens)<400>32Val Ser Arg Ile Arg Gly Gly Ala Lys Lys Arg Lys Lys Lys Ser Tyr1 5 10 15Thr Thr Pro Lys Lys Asp Lys His Gln Arg Lys Lys Val Gln Pro Ala20 25 30Val Leu Lys Tyr Tyr Lys Val Asp Glu Asn Gly Lys Ile Ser Cys Leu35 40 45Arg Arg Glu Cys Pro Ser Asp Glu Cys Gly Ala Gly Val Phe Met Ala50 55 60Ser His Phe Asp Arg His Tyr Cys Gly Lys Cys Cys Leu Thr His Cys65 70 75 80<210>33<211>130<212>PRT<213>智人(Homo sapiens)<400>33Glu Ile Ser Asn Glu Val Arg Lys Phe Arg Thr Leu Thr Glu Leu Ile1 5 10 15Leu Asp Ala Gln Glu His Val Lys Asn Pro Tyr Lys Gly Lys Lys Leu
20 25 30Lys Lys His Pro Asp Phe Pro Lys Lys Pro Leu Thr Pro Tyr Phe Arg35 40 45Phe Phe Met Glu Lys Arg Ala Lys Tyr Ala Lys Leu His Pro Gln Met50 55 60Ser Asn Leu Asp Leu Thr Lys Ile Leu Ser Lys Lys Tyr Lys Glu Leu65 70 75 80Pro Glu Lys Lys Lys Met Lys Tyr Val Pro Asp Phe Gln Arg Arg Glu85 90 95Thr Gly Val Arg Ala Lys Pro Gly Pro Ile Gln Gly Gly Ser Pro Pro100 105 110Pro Tyr Pro Glu Cys Gln Glu Ser Asp Ile Pro Glu Lys Pro Gln Asp115 120 125Pro Pro130<210>34<211>506<212>PRT<213>智人(Homo sapiens)<400>34Asn Ser Glu Lys Glu Ile Pro Val Leu Asn Glu Leu Pro Val Pro Met1 5 10 15Val Ala Arg Tyr Ile Arg Ile Asn Pro Gln Ser Trp Phe Asp Asn Gly20 25 30Ser Ile Cys Met Arg Met Glu Ile Leu Gly Cys Pro Leu Pro Asp Pro35 40 45Asn Asn Tyr Tyr His Arg Arg Asn Glu Met Thr Thr Thr Asp Asp Leu50 55 60Asp Phe Lys His His Asn Tyr Lys Glu Met Arg Gln Leu Met Lys Val65 70 75 80Val Asn Glu Met Cys Pro Asn Ile Thr Arg Ile Tyr Asn Ile Gly Lys85 90 95Ser His Gln Gly Leu Lys Leu Tyr Ala Val Glu Ile Ser Asp His Pro100 105 110Gly Glu His Glu Val Gly Glu Pro Glu Phe His Tyr Ile Ala Gly Ala115 120 125His Gly Asn Glu Val Leu Gly Arg Glu Leu Leu Leu Leu Leu Leu His130 135 140Phe Leu Cys Gln Glu Tyr Ser Ala Gln Asn Ala Arg Ile Val Arg Leu145 150 155 160Val Glu Glu Thr Arg Ile His Ile Leu Pro Ser Leu Asn Pro Asp Gly165 170 175Tyr Glu Lys Ala Tyr Glu Gly Gly Ser Glu Leu Gly Gly Trp Ser Leu180 185 190Gly Arg Trp Thr His Asp Gly Ile Asp Ile Asn Asn Asn Phe Pro Asp195 200 205Leu Asn Ser Leu Leu Trp Glu Ala Glu Asp Gln Gln Asn Ala Pro Arg210 215 220Lys Val Pro Asn His Tyr Ile Ala Ile Pro Glu Trp Phe Leu Ser Glu225 230 235 240Asn Ala Thr Val Ala Thr Glu Thr Arg Ala Val Ile Ala Trp Met Glu245 250 255Lys Ile Pro Phe Val Leu Gly Gly Asn Leu Gln Gly Gly Glu Leu Val260 265 270Val Ala Tyr Pro Tyr Asp Met Val Arg Ser Leu Trp Lys Thr Gln Glu275 280 285His Thr Pro Thr Pro Asp Asp His Val Phe Arg Trp Leu Ala Tyr Ser290 295 300Tyr Ala Ser Thr His Arg Leu Met Thr Asp Ala Arg Arg Arg Val Cys305 310 315 320His Thr Glu Asp Phe Gln Lys Glu Glu Gly Thr Val Asn Gly Ala Ser325 330 335Trp His Thr Val Ala Gly Ser Leu Asn Asp Phe Ser Tyr Leu His Thr340 345 350Asn Cys Phe Glu Leu Ser Ile Tyr Val Gly Cys Asp Lys Tyr Pro His355 360 365Glu Ser Glu Leu Pro Glu Glu Trp Glu Asn Asn Arg Glu Ser Leu Ile370 375 380Val Phe Met Glu Gln Val His Arg Gly Ile Lys Gly Ile Val Arg Asp385 390 395 400Leu Gln Gly Lys Gly Ile Ser Asn Ala Val Ile Ser Val Glu Gly Val405 410 415Asn His Asp Ile Arg Thr Ala Ser Asp Gly Asp Tyr Trp Arg Leu Leu420 425 430Asn Pro Gly Glu Tyr Val Val Thr Ala Lys Ala Glu Gly Phe Ile Thr435 440 445Ser Thr Lys Asn Cys Met Val Gly Tyr Asp Met Gly Ala Thr Arg Cys450 455 460Asp Phe Thr Leu Thr Lys Thr Asn Leu Ala Arg Ile Arg Glu Ile Met465 470 475 480Glu Thr Phe Gly Lys Gln Pro Val Ser Leu Pro Ser Arg Arg Leu Lys485 490 495Leu Arg Gly Arg Lys Arg Arg Gln Arg Gly500 505<210>35<211>96<212>PRT<213>智人(Homo sapiens)<400>35Met Asn Gly Glu Ala Asp Cys Pro Thr Asp Leu Glu Met Ala Ala Pro1 5 10 15Arg Gly Gln Asp Arg Trp Ser Gln Glu Asp Met Leu Thr Leu Leu Glu20 25 30Cys Met Lys Asn Asn Leu Pro Ser Asn Asp Ser Ser Gln Phe Lys Thr35 40 45Thr Gln Thr His Met Asp Arg Glu Lys Val Ala Leu Lys Asp Phe Ser50 55 60Gly Asp Met Cys Lys Leu Lys Trp Val Glu Ile Ser Asn Glu Val Arg65 70 75 80Lys Phe Arg Thr Leu Thr Glu Leu Ile Leu Asp Thr Gln Glu His Val85 90 95<210>36<211>129<212>PRT<213>智人(Homo sapiens)<400>36Gly Ile Val Val Phe Ser Leu Gly Ser Met Val Ser Glu Ile Pro Glu1 5 10 15Lys Lys Ala Val Ala Ile Ala Asp Ala Leu Gly Lys Ile Pro Gln Thr20 25 30Val Leu Trp Arg Tyr Thr Gly Thr Arg Pro Ser Asn Leu Ala Asn Asn35 40 45Thr Ile Leu Val Gln Trp Leu Pro Gln Asn Asp Leu Leu Gly His Pro50 55 60Met Thr Arg Ala Phe Ile Thr His Ala Ser Ser His Gly Val Asn Glu65 70 75 80Ser Ile Cys Asn Gly Val Pro Met Val Met Ile Pro Leu Phe Gly Asp85 90 95Gln Met Asp Asn Ala Lys Arg Arg Glu Thr Lys Gly Ala Gly Val Thr100 105 110Leu Asn Val Leu Glu Met Thr Ser Glu Asp Leu Glu Asp Ala Leu Lys115 120 125Ser<210>37<211>238<212>PRT<213>智人(Homo sapiens)<400>37Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu1 5 10 15Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe20 25 30Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr35 40 45Leu Glu His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His50 55 60Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser65 70 75 80Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val85 90 95Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu100 105 110Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr115 120 125Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His130 135 140Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro145 150 155 160Ser Ser Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu165 170 175Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu Lys Pro Gly Glu Lys180 185 190Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu195 200 205Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr210 215 220Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln225 230 235<210>38<211>202<212>PRT<213>智人(Homo sapiens)<400>38Lys Gly Ser Glu Gly Glu Asn Pro Leu Thr Val Pro Gly Arg Glu Lys1 5 10 15Glu Gly Met Leu Met Gly Val Lys Pro Gly Glu Asp Ala Ser Gly Pro20 25 30Ala Glu Asp Leu Val Arg Arg Ser Glu Lys Asp Thr Ala Ala Val Val35 40 45Ser Arg Gln Gly Ser Ser Leu Asn Leu Phe Glu Asp Val Gln Ile Thr50 55 60Glu Pro Glu Ala Glu Pro Glu Ser Lys Ser Glu Pro Arg Pro Pro Ile65 70 75 80Ser Ser Pro Arg Ala Pro Gln Thr Arg Ala Val Lys Pro Arg Leu His85 90 95Pro Val Lys Pro Met Asn Ala Thr Ala Thr Lys Val Ala Asn Cys Ser100 105 110Leu Gly Thr Ala Thr Ile Ile Gly Glu Asn Leu Asn Asn Glu Val Met115 120 125Met Lys Lys Tyr Ser Pro Ser Asp Pro Ala Phe Ala Tyr Ala Gln Leu130 135 140Thr His Asp Glu Leu Ile Gln Leu Val Leu Lys Gln Lys Glu Thr Ile145 150 155 160Ser Lys Lys Glu Phe Gln Val Arg Glu Leu Glu Asp Tyr Ile Asp Asn165 170 175Leu Leu Val Arg Val Met Glu Glu Thr Pro Asn Ile Leu Arg Ile Pro180 185 190Thr Gln Val Gly Lys Lys Ala Gly Lys Met195 200<210>39<211>243<212>PRT<213>智人(Homo sapiens)<400>39Val Asn Ala Leu Gly Ile Met Ala Ala Val Asp Ile Arg Asp Asn Leu1 5 10 15Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser20 25 30Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe Tyr Asp35 40 45Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu50 55 60His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His Ala Gln65 70 75 80Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser Pro Ala85 90 95Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr100 105 110Gln Ala pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu Thr Ala115 120 125Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg130 135 140Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu145 150 155 160Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Ser Ser165 170 175Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln180 185 190Lys Ile Ser Thr Gln Ile Cys Ala Val Asp Gln Thr Lys Lys Glu Ala
195 200 205Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys210 215 220Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met225 230 235 240Arg Leu Gln<210>40<211>245<212>PRT<213>智人(Homo sapiens)<400>40Ala Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp1 5 10 15Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe20 25 30Ser Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val35 40 45Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly50 55 60Ile Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile65 70 75 80Arg Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp85 90 95Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser100 105 110Val Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala115 120 125Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr130 135 140Trp Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys145 150 155 160Ala Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val165 170 175Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val180 185 190Gln Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys195 200 205Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr210 215 220Thr Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys225 230 235 240Arg Met Arg Leu Gln245<210>41<211>163<212>PRT<213>智人(Homo sapiens)<400>41Gly Glu Arg Gln Gly Leu Val Ala Arg Ala Arg Leu Ser Leu Arg Pro1 5 10 15Ser Ile Pro Glu Leu Ser Glu Arg Thr Ser Arg Pro Cys Arg Ala Ser20 25 30Pro Ala Ser Leu Pro Ser Gln His Thr Ser Ser Pro Ala Gln Ala Arg
35 40 45Val Arg Asn Leu Ala Gln Ser Thr Phe Pro Leu Ala Ala Gln Glu Thr50 55 60Pro Gly Arg Ala Pro Ala His Ala Pro Leu Ser Ser Phe Val Pro Gly65 70 75 80Val Gly Gly Arg Ser Pro Ala Ser Val Gly Ile Ser Ala Pro Gly Gly85 90 95Gly Pro Ser Gly Ala Ala Ala Lys Ile Pro Leu Glu Leu Thr Gln Ser100 105 110Arg Val Gln Lys Ile Trp Val Pro Val Asp His Arg Pro Ser Leu Pro115 120 125Arg Ser Cys Gly Pro Lys Leu Thr Asn Ser Pro Ala Val Phe Val Met130 135 140Val Gly Leu Pro Arg Pro Gly Gln Asp Leu Leu Leu His Glu Ser Leu145 150 155 160Leu Ala Ala<210>42<211>243<212>PRT<213>智人(Homo sapiens)<400>42Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser1 5 10 15Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu20 25 30Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys35 40 45Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile Glu50 55 60Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys65 70 75 80Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr85 90 95Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile100 105 110Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp115 120 125Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp130 135 140His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys145 150 155 160Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp Ala165 170 175Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu180 185 190Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala195 200 205Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys210 215 220Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met225 230 235 240Arg Leu Gln<210>43
<2ll>244<212>PRT<213>智人(Homo sapiens)<400>43Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser1 5 10 15Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser20 25 30Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val35 40 45Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile50 55 60Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg65 70 75 80Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr85 90 95Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val100 105 110Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe115 120 125Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp130 135 140Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala145 150 155 160Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp165 170 175Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln180 185 190Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu195 200 205Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr210 215 220Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg225 230 235 240Met Arg Leu Gln<210>44<211>109<212>PRT<213>智人(Homo sapiens)<400>44Glu Leu His Phe Ser Glu Phe Thr Ser Ala Val Ala Asp Met Lys Asn1 5 10 15Ser Val Ala Asp Arg Asp Asn Ser Pro Ser Ser Cys Ala Gly Leu Phe20 25 30Ile Ala Ser His Ile Gly Phe Asp Trp Pro Gly Val Trp Val His Leu35 40 45Asp Ile Ala Ala Pro Val His Ala Gly Glu Arg Ala Thr Gly Phe Gly50 55 60Val Ala Leu Leu Leu Ala Leu Phe Gly Arg Ala Ser Glu Asp Pro Leu65 70 75 80Leu Asn Leu Val Ser Pro Leu Asp Cys Glu Val Asp Ala Gln Glu Gly85 90 95Asp Asn Met Gly Arg Asp Ser Lys Arg Arg Arg Leu Val100 105
<210>45<211>324<212>PRT<213>智人(Homo sapiens)<400>45Arg Arg Pro Val Met Ala Gln Glu Thr Ala Pro Pro Cys Gly Pro Vall 5 10 15Ser Arg Gly Asp Ser Pro Ile Ile Glu Lys Met Glu Lys Arg Thr Cys20 25 30Ala Leu Cys Pro Glu Gly His Glu Trp Ser Gln Ile Tyr Phe Ser Pro35 40 45Ser Gly Asn Ile Val Ala His Glu Asn Cys Leu Leu Tyr Ser Ser Gly50 55 60Leu Val Glu Cys Glu Thr Leu Asp Leu Arg Asn Thr Ile Arg Asn Phe65 70 75 80Asp Val Lys Ser Val Lys Lys Glu Ile Trp Arg Gly Arg Arg Leu Lys85 90 95Cys Ser Phe Cys Asn Lys Gly Gly Ala Thr Val Gly Cys Asp Leu Trp100 105 110Phe Cys Lys Lys Ser Tyr His Tyr Val Cys Ala Lys Lys Asp Gln Ala115 120 125Ile Leu Gln Val Asp Gly Asn His Gly Thr Tyr Lys Leu Phe Cys Pro130 135 140Glu His Ser Pro Glu Gln Glu Glu Ala Thr Glu Ser Ala Asp Asp Pro145 150 155 160Ser Met Lys Lys Lys Arg Gly Lys Asn Lys Arg Leu Ser Ser Gly Pro165 170 175Pro Ala Gln Pro Lys Thr Met Lys Cys Ser Asn Ala Lys Arg His Met180 185 190Thr Glu Glu Pro His Gly His Thr Asp Ala Ala Val Lys Ser Pro Phe195 200 205Leu Lys Lys Cys Gln Glu Ala Gly Leu Leu Thr Glu Leu Phe Glu His210 215 220Ile Leu Glu Asn Met Asp Ser Val His Gly Arg Leu Val Asp Glu Thr225 230 235 240Ala Ser Glu Ser Asp Tyr Glu Gly Ile Glu Thr Leu Leu Phe Asp Cys245 250 255Gly Leu Phe Lys Asp Thr Leu Arg Lys Phe Gln Glu Val Ile Lys Ser260 265 270Lys Ala Cys Glu Trp Glu Glu Arg Gln Arg Gln Met Lys Gln Gln Leu275 280 285Glu Ala Leu Ala Asp Leu Gln Gln Ser Leu Cys Ser Phe Gln Glu Asn290 295 300Gly Asp Leu Asp Cys Ser Ser Ser Thr Ser Gly Ser Leu Leu Pro Pro305 310 315 320Glu Asp His Gln<210>46<211>244<212>PRT<213>智人(Homo sapiens)<400>46Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser1 5 10 15Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser20 25 30Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val35 40 45Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile50 55 60Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg65 70 75 80Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr85 90 95Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val100 105 110Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe115 120 125Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp130 135 140Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala145 150 155 160Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp165 170 175Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln180 185 190Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu195 200 205Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr210 215 220Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg225 230 235 240Met Arg Leu Gln<210>47<211>14<212>DNA<213>智人(Homo sapiens)<400>47tttttttttt ttag 14<210>48<211>10<212>DNA<213>智人(Homo sapiens)<400>48cttcaacctc 10<210>49<211>496<212>DNA<213>智人(Homo sapiens)<400>49gcaccatgta ccgagcactt cggctcctcg cgcgctcgcg tcccctcgtg cgggctccag 60ccgcagcctt agcttcggct cccggcttgg gtggcgcggc cgtgccctcg ttttggcctc120cgaacgcggc tcgaatggca agccaaaatt ccttccggat agaatatgat acctttggtg180aactaaaggt gccaaatgat aagtattatg gcgcccagac cgtgagatct acgatgaact240ttaagattgg aggtgtgaca gaacgcatgc caaccccagt tattaaagct tttggcatct300tgaagcgagc ggccgctgaa gtaaaccagg attatggtct tgatccaaag attgctaatg360caataatgaa ggcagcagat gaggtagctg aaggtaaatt aaatgatcat tttcctctcg420tggtatggca gactggatca ggaactcaga caaatatgaa tgtaaatgaa gtcattagcc480aatagagcaa ttgaaa496<210>50<211>499<212>DNA<213>智人(Homo sapiens)<400>50agaaaaagtc tatgtttgca gaaatacaga tccaagacaa agacaggatg ggcactgctg 60gaaaagttat taaatgcaaa gcagctgtgc tttgggagca gaagcaaccc ttctccattg120aggaaataga agttgcccca ccaaagacta aagaagttcg cattaagatt ttggccacag180gaatctgtcg cacagatgac catgtgataa aaggaacaat ggtgtccaag tttccagtga240ttgtgggaca tgaggcaact gggattgtag agagcattgg agaaggagtg actacagtga300aaccaggtga caaagtcatc cctctctttc tgccacaatg tagagaatgc aatgcttgtc360gcaacccaga tggcaacctt tgcattagga gcgatattac tggtcgtgga gtactggctg420atggcaccac cagatttaca tgcaagggcg aaccagtcca ccacttcatg aacaccagta480catttaccga gtacacagt 499<210>51<211>887<212>DNA<213>智人(Homo sapiens)<400>51gagtctgagc agaaaggaaa agcagccttg gcagccacgt tagaggaata caaagccaca 60gtggccagtg accagataga gatgaatcgc ctgaaggctc agctggagaa tgaaaagcag120aaagtggcag agctgtattc tatccataac tctggagaca aatctgatat tcaggacctc180ctggagagtg tcaggctgga caaagaaaaa gcagagactt tggctagtag cttgcaggaa240gatctggctc atacccgaaa tgatgccaat cgattacagg atgccattgc taaggtagag300gatgaatacc gagccttcca agaagaagct aagaaacaaa ttgaagattt gaatatgacg360ttagaaaaat taagatcaga cctggatgaa aaagaaacag aaaggagtga catgaaagaa420accatctttg aacttgaaga tgaagtagaa caacatcgtg ctgtgaaact tcatgacaac480ctcattattt ctgatctaga gaatacagtt aaaaaactcc aggaccaaaa gcacgacatg540gaaagagaaa taaagacact ccacagaaga cttcgggaag aatctgcgga atggcggcag600tttcaggctg atctccagac tgcagtagtc attgcaaatg acattaaatc tgaagcccaa660gaggagattg gtgatctaaa gcgccggtta catgaggctc aagaaaaaaa tgagaaactc720acaaaagaat tggaggaaat aaagtcacgc aagcaagagg aggagcgagg cgggtataca780attacatgaa tgccgttgag agagatttgg cagccttaag gcagggaatg ggactgagta840gaaggtcctc gacttcctca gagccaactc ctacagtaaa aaccctc 887<210>52<211>491<212>DNA<213>智人(Homo sapiens)<400>52ggcacgagct tttccaaaaa tcatgctgct cctttctcta aagttcttac attttataga 60aaggaacctt tcactcttga ggcctactac agctctcctc aggatttgcc ctatccagat120cctgctatag ctcagttttc agttcagaaa gtcactcctc agtctgatgg ctccagttca180aaagtgaaag tcaaagttcg agtaaatgtc catggcattt tcagtgtgtc cagtgcatct240ttagtggagg ttcacaagtc tgaggaaaat gaggagccaa tggaaacaga tcagaatgca300aaggaggaag agaagatgca agtggaccag gaggaaccac atgttgaaga gcaacagcag360cagacaccag gcagaaaata aggcagagtc tgaagaaatg gagacctctc aagctggatc420caaggataaa aagatggacc aaccacccca agccaagaag gcaaaagtga agaccagtac480tgtggacctg g 491
<210>53<211>787<212>DNA<213>智人(Homo sapiens)<400>53aagcagttga gtaggcagaa aaaagaacct cttcattaag gattaaaatg tataggccag 60cacgtgtaac ttcgacttca agatttctga atccatatgt agtatgtttc attgtcgtcg120caggggtagt gatcctggca gtcaccatag ctctacttgt ttacttttta gcttttgatc180aaaaatctta cttttatagg agcagttttc aactcctaaa tgttgaatat aatagtcagt240taaattcacc agctacacag gaatacagga ctttgagtgg aagaattgaa tctctgatta300ctaaaacatt caaagaatca aatttaagaa atcagttcat cagagctcat gttgccaaac360tgaggcaaga tggtagtggt gtgagagcgg atgttgtcat gaaatttcaa ttcactagaa420ataacaatgg agcatcaatg aaaagcagaa ttgagtctgt tttacgacaa atgctgaata480actctggaaa cctggaaata aacccttcaa ctgagataac atcacttact gaccaggctg540cagcaaattg gcttattaat gaatgtgggg ccggtccaga cctaataaca ttgtctgagc600agagaatcct tggaggcact gaggctgagg agggaagctg gccgtggcaa gtcagtctgc660ggctcaataa tgcccaccac tgtggaggca gcctgatcaa taacatgtgg atcctgacag720cagctcactg cttcagaagc aactctaatc ctcgtgactg gattgccacg tctggtattt780ccacaac 787<210>54<211>386<212>DNA<213>智人(Homo sapiens)<400>54ggcattttca gtgtgtccag tgcatcttta gtggaggttc acaagtctga ggaaaatgag 60gagccaatgg aaacagatca gaatgcaaag gaggaagaga agatgcaagt ggaccaggag120gaaccacatg ttgaagagca acagcagcag acaccagcag aaaataaggc agagtctgaa180gaaatggaga cctctcaagc tggatccaag gataaaaaga tggaccaacc accccaagcc240aagaaggcaa aagtgaagac cagtactgtg gacctgccaa tcgagaatca gctattatgg300cagatagaca gagagatgct caacttgtac attgaaaatg agggtaagat gatcatgcag360gataaactgg agaaggagcg gaatga 386<210>55<211>1462<212>DNA<213>智人(Homo sapiens)<400>55aagcagttga gtaggcagaa aaaagaacct cttcattaag gattaaaatg tataggccag 60cacgtgtaac ttcgacttca agatttctga atccatatgt agtatgtttc attgtcgtcg 120caggggtagt gatcctggca gtcaccatag ctctacttgt ttacttttta gcttttgatc 180aaaaatctta cttttatagg agcagttttc aactcctaaa tgttgaatat aatagtcagt 240taaattcacc agctacacag gaatacagga ctttgagtgg aagaattgaa tctctgatta 300ctaaaacatt caaagaatca aatttaagaa atcagttcat cagagctcat gttgccaaac 360tgagggaaga tggtagtggt gtgagagcgg atgttgtcat gaaatttcaa ttcactagaa 420ataacaatgg agcatcaatg aaaagcagaa ttgagtctgt tttacgacaa atgctgaata 480actctggaaa cctggaaata aacccttcaa ctgagataac atcacttact gaccaggctg 540cagcaaattg gcttattaat gaatgtgggg ccggtccaga cctaataaca ttgtctgagc 600agagaatcct tggaggcact gaggctgagg agggaagctg gccgtggcaa gtcagtctgc 660ggctcaataa tgcccaccac tgtggaggca gcctgatcaa taacatgtgg atcctgacag 720cagctcactg cttcagaagc aactctaatc ctcgtgactg gattgccacg tctggtattt 780ccacaacatt tcctaaacta agaatgagag taagaaatat tttaattcat aacaattata 840aatctgcaac tcatgaaaat gacattgcac ttgtgagact tgagaacagt gtcaccttta 900ccaaagatat ccatagtgtg tgtctcccag ctgctaccca gaatattcca cctggctcta 960ctgcttatgt aacaggatgg ggcgctcaag aatatgctgg ccacacagtt ccagagctaa1020ggcaaggaca ggtcagaata ataagtaatg atgtatgtaa tgcaccacat agttataatg1080gagccatctt gtctggaatg ctgtgtgctg gagtacctca aggtggagtg gacgcatgtc1140agggtgactc tggtggccca ctagtacaag aagactcacg gcggctttgg tttattgtgg1200ggatagtaag ctggggagat cagtgtggcc tgccggataa gccaggagtg tatactcgag1260tgacagcata cattgactgg attaggcaac aaactgggat ctagtgcaac aagtgcatcc1320ctgttgcaaa gtctgtatgc aggtgtgcct gtcttaaatt ccaaagcttt acatttcaac1380tgaaaaagaa actagaaatg tcctaattta acatcttgtt acataaatat ggtttaacaa1440aaaaaaaaaa aaaaaactcg ag 1462<210>56<211>159<212>PRT<213>智人(Homo sapiens)<400>56Thr Met Tyr Arg Ala Leu Arg Leu Leu Ala Arg Ser Arg Pro Leu Val1 5 10 15Arg Ala Pro Ala Ala Ala Leu Ala Ser Ala Pro Gly Leu Gly Gly Ala20 25 30Ala Val Pro Ser Phe Trp Pro Pro Asn Ala Ala Arg Met Ala Ser Gln35 40 45Asn Ser Phe Arg Ile Glu Tyr Asp Thr Phe Gly Glu Leu Lys Val Pro50 55 60Asn Asp Lys Tyr Tyr Gly Ala Gln Thr Val Arg Ser Thr Met Asn Phe65 70 75 80Lys Ile Gly Gly Val Thr Glu Arg Met Pro Thr Pro Val Ile Lys Ala85 90 95Phe Gly Ile Leu Lys Arg Ala Ala Ala Glu Val Asn Gln Asp Tyr Gly100 105 110Leu Asp Pro Lys Ile Ala Asn Ala Ile Met Lys Ala Ala Asp Glu Val115 120 125Ala Glu Gly Lys Leu Asn Asp His Phe Pro Leu Val Val Trp Gln Thr130 135 140Gly Ser Gly Thr Gln Thr Asn Met Asn Val Asn Glu Val Ile Ser145 150 155<210>57<211>165<212>PRT<213>智人(Homo sapiens)<400>57Lys Lys Ser Met Phe Ala Glu Ile Gln Ile Gln Asp Lys Asp Arg Met1 5 10 15Gly Thr Ala Gly Lys Val Ile Lys Cys Lys Ala Ala Val Leu Trp Glu20 25 30Gln Lys Gln Pro Phe Ser Ile Glu Glu Ile Glu Val Ala Pro Pro Lys35 40 45Thr Lys Glu Val Arg Ile Lys Ile Leu Ala Thr Gly Ile Cys Arg Thr50 55 60Asp Asp His Val Ile Lys Gly Thr Met Val Ser Lys Phe Pro Val Ile65 70 75 80Val Gly His Glu Ala Thr Gly Ile Val Glu Ser Ile Gly Glu Gly Val85 90 95Thr Thr Val Lys Pro G1y Asp Lys Val Ile Pro Leu Phe Leu Pro Gln100 105 110Cys Arg Glu Cys Asn Ala Cys Arg Asn Pro Asp Gly Asn Leu Cys Ile
115 120 125Arg Ser Asp Ile Thr Gly Arg Gly Val Leu Ala Asp Gly Thr Thr Arg130 135 140Phe Thr Cys Lys Gly Glu Pro Val His His Phe Met Asn Thr Ser Thr145 150 155 160Phe Thr Glu Tyr Thr165<210>58<211>259<212>PRT<213>智人(Homo sapiens)<400>58Glu Ser Glu Gln Lys Gly Lys Ala Ala Leu Ala Ala Thr Leu Glu Glu1 5 10 15Tyr Lys Ala Thr Val Ala Ser Asp Gln Ile Glu Met Asn Arg Leu Lys20 25 30Ala Gln Leu Glu Asn Glu Lys Gln Lys Val Ala Glu Leu Tyr Ser Ile35 40 45His Asn Ser Gly Asp Lys Ser Asp Ile Gln Asp Leu Leu Glu Ser Val50 55 60Arg Leu Asp Lys Glu Lys Ala Glu Thr Leu Ala Ser Ser Leu Gln Glu65 70 75 80Asp Leu Ala His Thr Arg Asn Asp Ala Asn Arg Leu Gln Asp Ala Ile85 90 95Ala Lys Val Glu Asp Glu Tyr Arg Ala Phe Gln Glu Glu Ala Lys Lys100 105 110Gln Ile Glu Asp Leu Asn Met Thr Leu Glu Lys Leu Arg Ser Asp Leu115 120 125Asp Glu Lys Glu Thr Glu Arg Ser Asp Met Lys Glu Thr Ile Phe Glu130 135 140Leu Glu Asp Glu Val Glu Gln His Arg Ala Val Lys Leu His Asp Asn145 150 155 160Leu Ile Ile Ser Asp Leu Glu Asn Thr Val Lys Lys Leu Gln Asp Gln165 170 175Lys His Asp Met Glu Arg Glu Ile Lys Thr Leu His Arg Arg Leu Arg180 185 190Glu Glu Ser Ala Glu Trp Arg Gln Phe Gln Ala Asp Leu Gln Thr Ala195 200 205Val Val Ile Ala Asn Asp Ile Lys Ser Glu Ala Gln Glu Glu Ile Gly210 215 220Asp Leu Lys Arg Arg Leu His Glu Ala Gln Glu Lys Asn Glu Lys Leu225 230 235 240Thr Lys Glu Leu Glu Glu Ile Lys Ser Arg Lys Gln Glu Glu Glu Arg245 250 255Gly Gly Tyr<210>59<211>125<212>PRT<213>智人(Homo sapiens)<400>59Gly Thr Ser Phe Ser Lys Asn His Ala Ala Pro Phe Ser Lys Val Leu1 5 10 15Thr Phe Tyr Arg Lys Glu Pro Phe Thr Leu Glu Ala Tyr Tyr Ser Ser
20 25 30Pro Gln Asp Leu Pro Tyr Pro Asp Pro Ala Ile Ala Gln Phe Ser Val35 40 45Gln Lys Val Thr Pro Gln Ser Asp Gly Ser Ser Ser Lys Val Lys Val50 55 60Lys Val Arg Val Asn Val His Gly Ile Phe Ser Val Ser Ser Ala Ser65 70 75 80Leu Val Glu Val His Lys Ser Glu Glu Asn Glu Glu Pro Met Glu Thr85 90 95Asp Gln Asn Ala Lys Glu Glu Glu Lys Met Gln Val Asp Gln Glu Glu100 105 110Pro His Val Glu Glu Gln Gln Gln Gln Thr Pro Gly Arg115 120 125<210>60<211>246<212>PRT<213>智人(Homo sapiens)<400>60Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro1 5 10 15Tyr Val Val Cys Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val20 25 30Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr35 40 45Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln50 55 60Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile65 70 75 80Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln85 90 95Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val100 105 110Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly115 120 125Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn130 135 140Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu145 150 155 160Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cys Gly Ala Gly165 170 175Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu180 185 190Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn195 200 205Ala His His Cys Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr210 215 220Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala225 230 235 240Thr Ser Gly Ile Ser Thr245<210>61<211>128<212>PRT<213>智人(Homo sapiens)
<400>6lGly Ile Phe Ser Val Ser Ser Ala Ser Leu Val Glu Val His Lys Ser1 5 10 15Glu Glu Asn Glu Glu Pro Met Glu Thr Asp Gln Asn Ala Lys Glu Glu20 25 30Glu Lys Met Gln Val Asp Gln Glu Glu Pro His Val Glu Glu Gln Gln35 40 45Gln Gln Thr Pro Ala Glu Asn LVs Ala Glu Ser Glu Glu Met Glu Thr50 55 60Ser Gln Ala Gly Ser Lys Asp Lys Lys Met Asp Gln Pro Pro Gln Ala65 70 75 80Lys Lys Ala Lys Val Lys Thr Ser Thr Val Asp Leu Pro Ile Glu Asn85 90 95Gln Leu Leu Trp Gln Ile Asp Arg Glu Met Leu Asn Leu Tyr Ile Glu100 105 110Asn Glu Gly Lys Met Ile Met Gln Asp Lys Leu Glu Lys Glu Arg Asn115 120 125<210>62<211>418<212>PRT<213>智人(Homo sapiens)<400>62Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro1 5 10 15Tyr Val Val Cys Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val20 25 30Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr35 40 45Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln50 55 60Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile65 70 75 80Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln85 90 95Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val100 105 110Arg Ala Asp Val Val Met Lys Phe Gln phe Thr Arg Asn Asn Asn Gly115 120 125Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn130 135 140Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu145 150 155 160Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cys Gly Ala Gly165 170 175Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu180 185 190Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn195 200 205Ala His His Cys Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr210 215 220Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala225 230 235 240Thr Ser Gly Ile Ser Thr Thr Phe Pro Lys Leu Arg Met Arg Val Arg245 250 255Asn Ile Leu Ile His Asn Asn Tyr Lys Ser Ala Thr His Glu Asn Asp260 265 270Ile Ala Leu Val Arg Leu Glu Asn Ser Val Thr Phe Thr Lys Asp Ile275 280 285His Ser Val Cys Leu Pro Ala Ala Thr Gln Asn Ile Pro Pro Gly Ser290 295 300Thr Ala Tyr Val Thr Gly Trp Gly Ala Gln Glu Tyr Ala Gly His Thr305 310 315 320Val Pro Glu Leu Arg Gln Gly Gln Val Arg Ile Ile Ser Asn Asp Val325 330 335Cys Asn Ala Pro His Ser Tyr Asn Gly Ala Ile Leu Ser Gly Met Leu340 345 350Cys Ala Gly Val Pro Gln Gly Gly Val Asp Ala Cys Gln Gly Asp Ser355 360 365Gly Gly Pro Leu Val Gln Glu Asp Ser Arg Arg Leu Trp Phe Ile Val370 375 380Gly Ile Val Ser Trp Gly Asp Gln Cys Gly Leu Pro Asp Lys Pro Gly385 390 395 400Val Tyr Thr Arg Val Thr Ala Tyr Ile Asp Trp Ile Arg Gln Gln Thr405 410 415Gly Ile<210>63<211>776<212>DNA<213>智人(Homo sapiens)<400>63cacagatggt gatagaggaa tccatcttgc agtcagataa agccctcact gatagagaga 60aggcagtagc agtggatcgg gccaagaagg aggcagctga gaaggaacag gaacttttaa120aacagaaatt acaggagcag ccagcaacag atggaggctc aagataagag tcgcaaggaa180aactagccaa ctgaaggaga agctgcagat ggagagagaa cacctactga gagagcagat240tatgatgttg gagcacacgc agaaggtcca aaatgattgg cttcatgaag gatttaagaa300gaagtatgag gagatgaatg cagagataag tcaatttaaa cgtatgattg atactacaaa360aaatgatgat actccctgga ttgcacgaac cttggacaac cttgccgatg agctaactgc420aatattgtct gctcctgcta aattaattgg tcatggtgtc aaaggtgtga gctcactctt480taaaaagcat aagctcccct tttaaggata ttatagattg tacatatatg ctttggacta540tttttgatct gtatgttttt cattttcatt cagcaagttt tttttttttt tcagagtctt600actctgttgc ccaggctgga gtacagtggt gcaatctcag ctcactgcaa cctctgcctc660ctgggttcaa gagattcacc tgcctcagcc ccctagtagc tgggattata ggtgtacacc720accacaccca gctaattttt gtatttttag tagagatggg gtttcactat gttggc776<210>64<211>160<212>DNA<213>智人(Homo sapiens)<400>64gcagcgctct cggttgcagt acccactgga aggacttagg cgctcgcgtg gacaccgcaa 60gcccctcagt agcctcggcc caagaggcct gctttccact cgctagcccc gccgggggtc120cgtgtcctgt ctcggtggcc ggacccgggc ccgagcccga 160<210>65<211>72<212>PRT<213>智人(Homo sapiens)<400>65Leu Ser Ala Met Gly Phe Thr Ala Ala Gly Ile Ala Ser Ser Ser Ilel 5 10 15Ala Ala Lys Met Met Ser Ala Ala Ala Ile Ala Asn Gly Gly Gly Val20 25 30Ala Ser Gly Ser Leu Val Ala Thr Leu Gln Ser Leu Gly Ala Thr Gly35 40 45Leu Ser Gly Leu Thr Lys Phe Ile Leu Gly Ser Ile Gly Ser Ala Ile50 55 60Ala Ala Val Ile Ala Arg Phe Tyr65 70<210>66<211>2581<212>DNA<213>智人(Homo sapiens)<400>66ctttcaaccc gcgctcgccg gctccagccc cgcgcgcccc caccccttgc cctcccggcg 60gctccgcagg gtgaggtggc tttgaccccg ggttgcccgg ccagcacgac cgaggaggtg 120gctggacagc tggaggatga acggagaagc cgactgcccc acagacctgg aaatggccgc 180ccccaaaggc caagaccgtt ggtcccagga agacatgctg actttgctgg aatgcatgaa 240gaacaacctt ccatccaatg acagctccaa gttcaaaacc accgaatcac acatggactg 300ggaaaaagta gcatttaaag acttttctgg agacatgtgc aagctcaaat gggtggagat 360ttctaatgag gtgaggaagt tccgtacatt gacagaattg atcctcgatg ctcaggaaca 420tgttaaaaat ccttacaaag gcaaaaaact caagaaacac ccagacttcc caaagaagcc 480cctgacccct tatttccgct tcttcatgga gaagcgggcc aagtatgcga aactccaccc 540tgagatgagc aacctggacc taaccaagat tctgtccaag aaatacaagg agcttccgga 600gaagaagaag atgaaatata ttcaggactt ccagagagag aaacaggagt tcgagcgaaa 660cctggcccga ttcagggagg atcaccccga cctaatccag aatgccaaga aatcggacat 720cccagagaag cccaaaaccc cccagcagct gtggtacacc cacgagaaga aggtgtatct 780caaagtgcgg ccagatgcca ctacgaagga ggtgaaggac tccctgggga agcagtggtc 840tcagctctcg gacaaaaaga ggctgaaatg gattcataag gccctggagc agcggaagga 900gtacgaggag atcatgagag actatatcca gaagcaccca gagctgaaca tcagtgagga 960gggtatcacc aagtccaccc tcaccaaggc cgaacgccag ctcaaggaca agtttgacgg1020gcgacccacc aagccacctc cgaacagcta ctcgctgtac tgcgcagagc tcatggccaa1080catgaaggac gtgcccagca cagagcgcat ggtgctgtgc agccagcagt ggaagctgct1140gtcccagaag gagaaggacg cctatcacaa gaagtgtgat cagaaaaaga aagattacga1200ggtggagctg ctccgtttcc tcgagagcct gcctgaggag gagcagcagc gggtcttggg1260ggaagagaag atgctgaaca tcaacaagaa gcaggccacc agccccgcct ccaagaagcc1320agcccaggaa gggggcaagg gcggctccga gaagcccaag cggcccgtgt cggccatgtt1380catcttctcg gaggagaaac ggcggcagct gcaggaggag cggcctgagc tctccgagag1440cgagctgacc cgcctgctgg cccgaatgtg gaacgacctg tctgagaaga agaaggccaa1500gtacaaggcc cgagaggcgg cgctcaaggc tcagtcggag aggaagcccg gcggggagcg1560cgaggaacgg ggcaagctgc ccgagtcccc caaaagagct gaggagatct ggcaacagag1620cgttatcggc gactacctgg cccgcttcaa gaatgaccgg gtgaaggcct tgaaagccat1680ggaaatgacc tggaataaca tggaaaagaa ggagaaactg atgtggatta agaaggcagc1740cgaagaccaa aagcgatatg agagagagct gagtgagatg cgggcacctc cagctgctac1800aaattcttcc aagaagatga aattccaggg agaacccaag aagcctccca tgaacggtta1860ccagaagttc tcccaggagc tgctgtccaa tggggagctg aaccacctgc cgctgaagga1920gcgcatggtg gagatcggca gtcgctggca gcgcatctcc cagagccaga aggagcacta1980caaaaagctg gccgaggagc agcaaaagca gtacaaggtg cacctggacc tctgggttaa2040gagcctgtct ccccaggacc gtgcagcata taaagagtac atctccaata aacgtaagag2100catgaccaag ctgcgaggcc caaaccccaa atccagccgg actactctgc agtccaagtc2160ggagtccgag gaggatgatg aagaggatga ggatgacgag gacgaggatg aagaagagga2220agatgatgag aatggggact cctctgaaga tggcggcgac tcctctgagt ccagcagcga2280ggacgagagc gaggatgggg atgagaatga agaggatgac gaggacgaag acgacgacga2340ggatgacgat gaggatgaag ataatgagtc cgagggcagc agctccagct cctcctcctt2400aggggactcc tcagactttg actccaactg aggcttagcc ccaccccagg ggagccaggg2460agagcccagg agctcccctc cccaactgac cacctttgtt tcttccccat gttctgtccc2520ttgcccccct ggcctccccc actttctttc tttctttaaa aaaaaaaaaa aaaaactcga2580g2581<210>67<211>764<212>PRT<213>智人(Homo sapiens)<400>67Met Asn Gly Glu Ala Asp Cys Pro Thr Asp Leu Glu Met Ala Ala Pro1 5 10 15Lys Gly Gln Asp Arg Trp Ser Gln Glu Asp Met Leu Thr Leu Leu Glu20 25 30Cys Met Lys Asn Asn Leu Pro Ser Asn Asp Ser Ser Lys Phe Lys Thr35 40 45Thr Glu Ser His Met Asp Trp Glu Lys Val Ala Phe Lys Asp Phe Ser50 55 60Gly Asp Met Cys Lys Leu Lys Trp Val Glu Ile Ser Asn Glu Val Arg65 70 75 80Lys Phe Arg Thr Leu Thr Glu Leu Ile Leu Asp Ala Gln Glu His Val85 90 95Lys Asn Pro Tyr Lys Gly Lys Lys Leu Lys Lys His Pro Asp Phe Pro100 105 110Lys Lys Pro Leu Thr Pro Tyr Phe Arg Phe Phe Met Glu Lys Arg Ala115 120 125Lys Tyr Ala Lys Leu His Pro Glu Met Ser Asn Leu Asp Leu Thr Lys130 135 140Ile Leu Ser Lys Lys Tyr Lys Glu Leu Pro Glu Lys Lys Lys Met Lys145 150 155 160Tyr Ile Gln Asp Phe Gln Arg Glu Lys Gln Glu Phe Glu Arg Asn Leu165 170 175Ala Arg Phe Arg Glu Asp His Pro Asp Leu Ile Gln Asn Ala Lys Lys180 185 190Ser Asp Ile Pro Glu Lys Pro Lys Thr Pro Gln Gln Leu Trp Tyr Thr195 200 205His Glu Lys Lys Val Tyr Leu Lys Val Arg Pro Asp Ala Thr Thr Lys210 215 220Glu Val Lys Asp Ser Leu Gly Lys Gln Trp Ser Gln Leu Ser Asp Lys225 230 235 240Lys Arg Leu Lys Trp Ile His Lys Ala Leu Glu Gln Arg Lys Glu Tyr245 250 255Glu Glu Ile Met Arg Asp Tyr Ile Gln Lys His Pro Glu Leu Asn Ile260 265 270Ser Glu Glu Gly Ile Thr Lys Ser Thr Leu Thr Lys Ala Glu Arg Gln275 280 285Leu Lys Asp Lys Phe Asp Gly Arg Pro Thr Lys Pro Pro Pro Asn Ser290 295 300Tyr Ser Leu Tyr Cys Ala Glu Leu Met Ala Asn Met Lys Asp Val Pro305 310 315 320Ser Thr Glu Arg Met Val Leu Cys Ser Gln Gln Trp Lys Leu Leu Ser325 330 335Gln Lys Glu Lys Asp Ala Tyr His Lys Lys Cys Asp Gln Lys Lys Lys340 345 350Asp Tyr Glu Val Glu Leu Leu Arg Phe Leu Glu Ser Leu Pro Glu Glu355 360 365Glu Gln Gln Arg Val Leu Gly Glu Glu Lys Met Leu Asn Ile Asn Lys370 375 380Lys Gln Ala Thr Ser Pro Ala Ser Lys Lys Pro Ala Gln Glu Gly Gly385 390 395 400Lys Gly Gly Ser Glu Lys Pro Lys Arg Pro Val Ser Ala Met Phe Ile405 410 415Phe Ser Glu Glu Lys Arg Arg Gln Leu Gln Glu Glu Arg Pro Glu Leu420 425 430Ser Glu Ser Glu Leu Thr Arg Leu Leu Ala Arg Met Trp Asn Asp Leu435 440 445Ser Glu Lys Lys Lys Ala Lys Tyr Lys Ala Arg Glu Ala Ala Leu Lys450 455 460Ala Gln Ser Glu Arg Lys Pro Gly Gly Glu Arg Glu Glu Arg Gly Lys465 470 475 480Leu Pro Glu Ser Pro Lys Arg Ala Glu Glu Ile Trp Gln Gln Ser Val485 490 495Ile Gly Asp Tyr Leu Ala Arg Phe Lys Asn Asp Arg Val Lys Ala Leu500 505 510Lys Ala Met Glu Met Thr Trp Asn Asn Met Glu Lys Lys Glu Lys Leu515 520 525Met Trp Ile Lys Lys Ala Ala Glu Asp Gln Lys Arg Tyr Glu Arg Glu530 535 540Leu Ser Glu Met Arg Ala Pro Pro Ala Ala Thr Asn Ser Ser Lys Lys545 550 555 560Met Lys Phe Gln Gly Glu Pro Lys Lys Pro Pro Met Asn Gly Tyr Gln565 570 575Lys Phe Ser Gln Glu Leu Leu Ser Asn Gly Glu Leu Asn His Leu Pro580 585 590Leu Lys Glu Arg Met Val Glu Ile Gly Ser Arg Trp Gln Arg Ile Ser595 600 605Gln Ser Gln Lys Glu His Tyr Lys Lys Leu Ala Glu Glu Gln Gln Lys610 615 620Gln Tyr Lys Val His Leu Asp Leu Trp Val Lys Ser Leu Ser Pro Gln625 630 635 640Asp Arg Ala Ala Tyr Lys Glu Tyr Ile Ser Asn Lys Arg Lys Ser Met645 650 655Thr Lys Leu Arg Gly Pro Asn Pro Lys Ser Ser Arg Thr Thr Leu Gln660 665 670Ser Lys Ser Glu Ser Glu Glu Asp Asp Glu Glu Asp Glu Asp Asp Glu675 680 685Asp Glu Asp Glu Glu Glu Glu Asp Asp Glu Asn Gly Asp Ser Ser Glu690 695 700Asp Gly Gly Asp Ser Ser Glu Ser Ser Ser Glu Asp Glu Ser Glu Asp705 710 715 720Gly Asp Glu Asn Glu Glu Asp Asp Glu Asp Glu Asp Asp Asp Glu Asp725 730 735Asp Asp Glu Asp Glu Asp Asn Glu Ser Glu Gly Ser Ser Ser Ser Ser740 745 750Ser Ser Leu Gly Asp Ser Ser Asp Phe Asp Ser Asn755 760<210>68<211>434<212>DNA<213>智人(Homo sapiens)<400>68ctaagatgct ggatgctgaa gacatcgtcg gaactgcccg gccagatgag aaagccatta 60tgacttatgt gtctagcttc tatcatgcct tctctggagc ccagaaggca gaaacagcag120ccaatcgcat ctgcaaagtg ttggcggtca atcaagagaa cgagcagctt atggaagact180atgagaagct ggccagtgat ctgttggagt ggatccgccg caccatccca tggctggaga240atcgggtgcc tgagaacacc atgcatgcca tgcagcagaa gctggaggac ttccgagact300atagacgcct gcacaagccg cccaaggtgc aggagaagtg ccagctggag atcaacttta360acacgctgca gaccaaactg cggctcagca accggcctgc cttcatgccc tccgagggca420ggatggtctc ggat 434<210>69<211>244<212>DNA<213>智人(Homo sapiens)<400>69aggcagcatg ctcgttgaga gtcatcacca ctccctaatc tcaagtacgc agggacacaa 60acactgcgga aggccgcagg gtcctctgcc taggaaaacc agagaccttt gttcacttgt120ttatgtgctg accttccctc cactattgtc ctgtgaccct gccaaatccc cctttgtgag180aaacacccaa gaatgatcaa taaaaaataa attaatttag gaaaaaaaaa aaaaaaaact240cgag 244<210>70<211>437<212>DNA<213>智人(Homo sapiens)<400>70ctgggacggg agcgtccagc gggactcgaa ccccagatgt gaaggcgttt ctggaaagtc 60cttggtccct ggatccagcg tcggccagcc cagagcccgt gccgcacatc cttgcgtcct120ccaggcagtg ggaccccgcg agctgcacgt ccctgggcac ggacaagtgt gaggcactgt180tggggctgtg ccaggtgcgg ggtgggctgc cccctttctc agaaccttcc agcctggtgc240cgtggccccc aggccggagt cttcctaagg ctgtgaggcc acccctgtcc tggcctccgt300tctcgcagca gcagaccttg cccgtgatga gcggggaggc ccttggctgg ctgggccagg360ctggttccct ggccatgggg gctgcacctc tgggggagcc agccaaggag gaccccatgc420tggcgcagga agccggg 437<210>71<211>271<212>DNA<213>智人(Homo sapiens)<400>71gcgcagagtt ctgtcgtcca ccatcgagtg aggaagagag cattggttcc cctgagatag 60aagagatggc tctcttcagt gcccagtctc catacattaa cccgatcatc ccctttactg120gaccaatcca aggagggctg caggagggac ttcaggtgac cctccagggg actaccgaga180gttttgcaca aaagtttgtg gtgaactttt cagaacagct tcaatggaga tgacttggcc240ttccacttca accccggtta tgaggaagga g 271<210>72<211>290<212>DNA<213>智人(Homo sapiens)<400>72ccgagcccta cccggaggtc tccagaatcc ccaccgtcag gggatgcaac ggctccctgt 60ctggtgccct ctcctgctgc gaggactcgg cccagggctc gggcccgccc aaggccccta120cggtggccga gggtcccagc tcctgccttc ggcggaacgt gatcagcgag agggagcgca180ggaagcggat gtcgttgagc tgtgagcgtc tgcgggccct gctgccccag ttcgatggcc240ggcgggagga catggcctcg gtcctggaga tgtctgttgc aattcctgcg 290<210>73<211>144
<212>PRT<213>智人(Homo sapiens)<400>73Lys Met Leu Asp Ala Glu Asp Ile Val Gly Thr Ala Arg Pro Asp Glu1 5 10 15Lys Ala Ile Met Thr Tyr Val Ser Ser Phe Tyr His Ala Phe Ser Gly20 25 30Ala Gln Lys Ala Glu Thr Ala Ala Asn Arg Ile Cys Lys Val Leu Ala35 40 45Val Asn Gln Glu Asn Glu Gln Leu Met Glu Asp Tyr Glu Lys Leu Ala50 55 60Ser Asp Leu Leu Glu Trp Ile Arg Arg Thr Ile Pro Trp Leu Glu Asn65 70 75 80Arg Val Pro Glu Asn Thr Met His Ala Met Gln Gln Lys Leu Glu Asp85 90 95Phe Arg Asp Tyr Arg Arg Leu His Lys Pro Pro Lys Val Gln Glu Lys100 105 110Cys Gln Leu Glu Ile Asn Phe Asn Thr Leu Gln Thr Lys Leu Arg Leu115 120 125Ser Asn Arg Pro Ala Phe Met Pro Ser Glu Gly Arg Met Val Ser Asp130 135 140<210>74<211>64<212>PRT<213>智人(Homo sapiens)<400>74Gly Ser Met Leu Val Glu Ser His His His Ser Leu Ile Ser Ser Thr1 5 10 15Gln Gly His Lys His Cys Gly Arg Pro Gln Gly Pro Leu Pro Arg Lys20 25 30Thr Arg Asp Leu Cys Ser Leu Val Tyr Val Leu Thr Phe Pro Pro Leu35 40 45Leu Ser Cys Asp Pro Ala Lys Ser Pro Phe Val Arg Asn Thr Gln Glu50 55 60<210>75<211>145<212>PRT<213>智人(Homo sapiens)<400>75Gly Thr Gly Ala Ser Ser Gly Thr Arg Thr Pro Asp Val Lys Ala Phe1 5 10 15Leu Glu Ser Pro Trp Ser Leu Asp Pro Ala Ser Ala Ser Pro Glu Pro20 25 30Val Pro His Ile Leu Ala Ser Ser Arg Gln Trp Asp Pro Ala Ser Cys35 40 45Thr Ser Leu Gly Thr Asp Lys Cys Glu Ala Leu Leu Gly Leu Cys Gln50 55 60Val Arg Gly Gly Leu Pro Pro Phe Ser Glu Pro Ser Ser Leu Val Pro65 70 75 80Trp Pro Pro Gly Arg Ser Leu Pro Lys Ala Val Arg Pro Pro Leu Ser85 90 95Trp Pro Pro Phe Ser Gln Gln Gln Thr Leu Pro Val Met Ser Gly Glu100 105 110Ala Leu Gly Trp Leu Gly Gln Ala Gly Ser Leu Ala Met Gly Ala Ala115 120 125Pro Leu Gly Glu Pro Ala Lys Glu Asp Pro Met Leu Ala Gln Glu Ala130 135 140Gly145<210>76<211>69<212>PRT<213>智人(Homo sapiens)<400>76Ala Glu Phe Cys Arg Pro Pro Ser Ser Glu Glu Glu Ser Ile Gly Ser1 5 10 15Pro Glu Ile Glu Glu Met Ala Leu Phe Ser Ala Gln Ser Pro Tyr Ile20 25 30Asn Pro Ile Ile Pro Phe Thr Gly Pro Ile Gln Gly Gly Leu Gln Glu35 40 45Gly Leu Gln Val Thr Leu Gln Gly Thr Thr Glu Ser Phe Ala Gln Lys50 55 60Phe Val Val Asn Phe65<210>77<211>96<212>PRT<213>智人(Homo sapiens)<400>77Glu Pro Tyr Pro Glu Val Ser Arg Ile Pro Thr Val Arg Gly Cys Asn1 5 10 15Gly Ser Leu Ser Gly Ala Leu Ser Cys Cys Glu Asp Ser Ala Gln Gly20 25 30Ser Gly Pro Pro Lys Ala Pro Thr Val Ala Glu Gly Pro Ser Ser Cys35 40 45Leu Arg Arg Asn Val Ile Ser Glu Arg Glu Arg Arg Lys Arg Met Ser50 55 60Leu Ser Cys Glu Arg Leu Arg Ala Leu Leu Pro Gln Phe Asp Gly Arg65 70 75 80Arg Glu Asp Met Ala Ser Val Leu Glu Met Ser Val Ala Ile Pro Ala85 90 95<210>78<211>2076<212>DNA<213>智人(Homo sapiens)<400>78agaaaaagtc tatgtttgca gaaatacaga tccaagacaa agacaggatg ggcactgctg 60gaaaagttat taaatgcaaa gcagctgtgc tttgggagca gaagcaaccc ttctccattg 120aggaaataga agttgcccca ccaaagacta aagaagttcg cattaagatt ttggccacag 180gaatctgtcg cacagatgac catgtgataa aaggaacaat ggtgtccaag tttccagtga 240ttgtgggaca tgaggcaact gggattgtag agagcattgg agaaggagtg actacagtga 300aaccaggtga caaagtcatc cctctctttc tgccacaatg tagagaatgc aatgcttgtc 360gcaacccaga tggcaacctt tgcattagga gcgatattac tggtcgtgga gtactggctg 420atggcaccac cagatttaca tgcaagggca aaccagtcca ccacttcatg aacaccagta 480catttaccga gtacacagtg gtggatgaat cttctgttgc taagattgat gatgcagctc 540ctcctgagaa agtctgttta attggctgtg ggttttccac tggatatggc gctgctgtta 600aaactggcaa ggtcaaacct ggttccactt gcgtcgtctt tggcctgaga ggagttggcc 660tgtcagtcat catgggctgt aagtcagctg gtgcatctag gatcattggg attgacctca 720acaaagacaa atttgagaag gccatggctg taggtgccac tgagtgtatc agtcccaagg 780actctaccaa acccatcagt gaggtgctgt cagaaatgac aggcaacaac gtgggataca 840cctttgaagt tattgggcat cttgaaacca tgattgatgc cctggcatcc tgccacatga 900actatgggac cagcgtggtt gtaggagttc ctccatcagc caagatgctc acctatgacc 960cgatgttgct cttcactgga cgcacatgga agggatgtgt ctttggaggt ttgaaaagca1020gagatgatgt cccaaaacta gtgactgagt tcctggcaaa gaaatttgac ctggaccagt1080tgataactca tgtcttacca tttaaaaaaa tcagtgaagg atttgagctg ctcaattcag1140gacaaagcat tcgaacggtc ctgacgtttt gagatccaaa gtggcaggag gtctgtgttg1200tcatggtgaa ctggagtttc tcttgtgaga gttccctcat ctgaaatcat gtatctgtct1260cacaaataca agcataagta gaagatttgt tgaagacata gaacccttat aaagaattat1320taacctttat aaacatttaa agtcttgtga gcacctggga attagtataa taacaatgtt1380aatatttttg atttacattt tgtaaggcta taattgtatc ttttaagaaa acatacactt1440ggatttctat gttgaaatgg agatttttaa gagttttaac cagctgctgc agatatatat1500ctcaaaacag atatagcgta taaagatata gtaaatgcat ctcctagagt aatattcact1560taacacattg aaactattat tttttagatt tgaatataaa tgtatttttt aaacacttgt1620tatgagttaa cttggattac attttgaaat cagttcattc catgatgcat attactggat1680tagattaaga aagacagaaa agattaaggg acgggcacat ttttcaacga ttaagaatca1740tcattacata acttggtgaa actgaaaaag tatatcatat gggtacacaa ggctatttgc1800cagcatatat taatatttta gaaaatattc cttttgtaat actgaatata aacatagagc1860tagaatcata ttatcatact tatcataatg ttcaatttga tacagtagaa ttgcaagtcc1920ttaagtccct attcactgtg cttagtagtg actccattta ataaaaagtg tttttagttt1980ttaacaacta cactgatgta tttatatata tttataacat gttaaaaatt tttaaggaaa2040ttaaaaatta tataaaaaaa aaaaaaaaaa ctcgag 2076<210>79<211>2790<212>DNA<213>智人(Homo sapiens)<400>79aagcagttga gtaggcagaa aaaagaacct cttcattaag gattaaaatg tataggccag 60cacgtgtaac ttcgacttca agatttctga atccatatgt agtatgtttc attgtcgtcg 120caggggtagt gatcctggca gtcaccatag ctctacttgt ttacttttta gcttttgatc 180aaaaatctta cttttatagg agcagttttc aactcctaaa tgttgaatat aatagtcagt 240taaattcacc agctacacag gaatacagga ctttgagtgg aagaattgaa tctctgatta 300ctaaaacatt caaagaatca aatttaagaa atcagttcat cagagctcat gttgccaaac 360tgaggcaaga tggtagtggt gtgagagcgg atgttgtcat gaaatttcaa ttcactagaa 420ataacaatgg agcatcaatg aaaagcagaa ttgagtctgt tttacgacaa atgctgaata 480actctggaaa cctggaaata aacccttcaa ctgagataac atcacttact gaccaggctg 540cagcaaattg gcttattaat gaatgtgggg ccggtccaga cctaataaca ttgtctgagc 600agagaatcct tggaggcact gaggctgagg agggaagctg gccgtggcaa gtcagtctgc 660ggctcaataa tgcccaccac tgtggaggca gcctgatcaa taacatgtgg atcctgacag 720cagctcactg cttcagaagc aactctaatc ctcgtgactg gattgccacg tctggtattt 780ccacaacatt tcctaaacta agaatgagag taagaaatat tttaattcat aacaattata 840aatctgcaac tcatgaaaat gacattgcac ttgtgagact tgagaacagt gtcaccttta 900ccaaagatat ccatagtgtg tgtctcccag ctgctaccca gaatattcca cctggctcta 960ctgcttatgt aacaggatgg ggcgctcaag aatatgctgg ccacacagtt ccagagctaa1020ggcaaggaca ggtcagaata ataagtaatg atgtatgtaa tgcaccacat agttataatg1080gagccatctt gtctggaatg ctgtgtgctg gagtacctca aggtggagtg gacgcatgtc1140agggtgactc tggtggccca ctagtacaag aagactcacg gcggctttgg tttattgtgg1200ggatagtaag ctggggagat cagtgtggcc tgccggataa gccaggagtg tatactcgag1260tgacagccta ccttgactgg attaggcaac aaactgggat ctagtgcaac aagtgcatcc1320ctgttgcaaa gtctgtatgc aggtgtgcct gtcttaaatt ccaaagcttt acatttcaac1380tgaaaaagaa actagaaatg tcctaattta acatcttgtt acataaatat ggtttaacaa1440acactgttta acctttcttt attattaaag gttttctatt ttctccagag aactatatga1500atgttgcata gtactgtggc tgtgtaacag aagaaacaca ctaaactaat tacaaagtta1560acaatttcat tacagttgtg ctaaatgccc gtagtgagaa gaacaggaac cttgagcatg1620tatagtagag gaacctgcac aggtctgatg ggtcagaggg gtcttctctg ggtttcactg1680aggatgagaa gtaagcaaac tgtggaaaca tgcaaaggaa aaagtgatag aataatattc1740aagacaaaaa gaacagtatg aggcaagaga aatagtatgt atttaaaatt tttggttact1800caatatctta tacttagtat gagtcctaaa attaaaaatg tgaaactgtt gtactatacg1860tataacctaa ccttaattat tctgtaagaa catgcttcca taggaaatag tggataattt1920tcagctattt aaggcaaaag ctaaaatagt tcactcctca actgagaccc aaagaattat1980agatattttt catgatgacc catgaaaaat atcactcatc tacataaagg agagactata2040tctattttat agagaagcta agaaatatac ctacacaaac ttgtcaggtg ctttacaact2100acatagtact ttttaacaac aaaataataa ttttaagaat gaaaaattta atcatcggga2160agaacgtccc actacagact tcctatcact ggcagttata tttttgagcg taaaagggtc2220gtcaaacgct aaatctaagt aatgaattga aagtttaaag agggggaaga gttggtttgc2280aaaggaaaag tttaaatagc ttaatatcaa tagaatgatc ctgaagacag aaaaaacttt2340gtcactcttc ctctctcatt ttctttctct ctctctcccc ttctcataca catgcctccc2400cgaccaaaga atataatgta aattaaatcc actaaaatgt aatggcatga aaatctctgt2460agtctgaatc actaatattc ctgagttttt atgagctcct agtacagcta aagtttgcct2520atgcatgatc atctatgcgt cagagcttcc tccttctaca agctaactcc ctgcatctgg2580gcatcaggac tgctccatac atttgctgaa aacttcttgt atttcctgat gtaaaattgt2640gcaaacacct acaataaagc catctacttt tagggaaagg gagttgaaaa tgcaaccaac2700tcttggcgaa ctgtacaaac aaatctttgc tatactttat ttcaaataaa ttctttttga2760aatgaaaaaa aaaaaaaaaa aaaactcgag 2790<210>80<211>1460<212>DNA<213>智人(Homo sapiens)<400>80ctcaaagcag ttgagtaggc agaaaaaaga acctcttcat taaggattaa aatgtatagg 60ccagcacgtg taacttcgac ttcaagattt ctgaatccat atgtagtatg tttcattgtc 120gtcgcagggg tagtgatcct ggcagtcacc atagctctac ttgtttactt tttagctttt 180gatcaaaaat cttactttta taggagcagt tttcaactcc taaatgttga atataatagt 240cagttaaatt caccagctac acaggaatac aggactttga gtggaagaat tgaatctctg 300attactaaaa cattcaaaga atcaaattta agaaatcagt tcatcagagc tcatgttgcc 360aaactgaggc aagatggtag tggtgtgaga gcggatgttg tcatgaaatt tcaattcact 420agaaataaca atggagcatc aatgaaaagc agaattgagt ctgttttacg acaaatgctg 480aataactctg gaaacctgga aataaaccct tcaactgaga taacatcact tactgaccag 540gctgcagcaa attggcttat taatgaatgt ggggccggtc cagacctaat aacattgtct 600gagcagagaa tccttggagg cactgaggct gaggagggaa gctggccgtg gcaagtcagt 660ctgcggctca ataatgccca ccactgtgga ggcagcctga tcaataacat gtggatcctg 720acagcagctc actgcttcag aagcaactct aatcctcgtg actggattgc cacgtctggt 780atttccacaa catttcctaa actaagaatg agagtaagaa atattttaat tcataacaat 840tataaatctg caactcatga aaatgacatt gcacttgtga gacttgagaa cagtgtcacc 900tttaccaaag atatccatag tgtgtgtctc ccagctgcta cccagaatat tccacctggc 960tctactgctt atgtaacagg atggggcgct caagaatatg ctggccacac agttccagag1020ctaaggcaag gacaggtcag aataataagt aatgatgtat gtaatgcacc acatagttat1080aatggagcca tcttgtctgg aatgctgtgt gctggagtac ctcaaggtgg agtggacgca1140tgtcagggtg actctggtgg cccactagta caagaagact cacggcggct ttggtttatt1200gtggggatag taagctgggg agatcagtgt ggcctgccgg ataagccagg agtgtatact1260cgagtgacag cctaccttga ctggattagg caacaaactg ggatctagtg caacaagtgc1320atccctgttg caaagtctgt atgcaggtgt gcctgtctta aattccaaag ctttacattt1380caactgaaaa agaaactaga aatgtcctaa tttaacatct tgttacataa atatggttta1440acaaaaaaaa aaaaaaaaaa1460<210>81<211>386<212>PRT
<213>智人(Homo sapiens)<400>81Met Phe Ala Glu Ile Gln Ile Gln Asp Lys Asp Arg Met Gly Thr Ala1 5 10 15Gly Lys Val Ile Lys Cys Lys Ala Ala Val Leu Trp Glu Gln Lys Gln20 25 30Pro Phe Ser Ile Glu Glu Ile Glu Val Ala Pro Pro Lys Thr Lys Glu35 40 45Val Arg Ile Lys Ile Leu Ala Thr Gly Ile Cys Arg Thr Asp Asp His50 55 60Val Ile Lys Gly Thr Met Val Ser Lys Phe Pro Val Ile Val Gly His65 70 75 80Glu Ala Thr Gly Ile Val Glu Ser Ile Gly Glu Gly Val Thr Thr Val85 90 95Lys Pro Gly Asp Lys Val Ile Pro Leu Phe Leu Pro Gln Cys Arg Glu100 105 110Cys Asn Ala Cys Arg Asn Pro Asp Gly Asn Leu Cys Ile Arg Ser Asp115 120 125Ile Thr Gly Arg Gly Val Leu Ala Asp Gly Thr Thr Arg Phe Thr Cys130 135 140Lys Gly Lys Pro Val His His Phe Met Asn Thr Ser Thr Phe Thr Glu145 150 155 160Tyr Thr Val Val Asp Glu Ser Ser Val Ala Lys Ile Asp Asp Ala Ala165 170 175Pro Pro G1u Lys Val Cys Leu Ile Gly Cys Gly Phe Ser Thr Gly Tyr180 185 190Gly Ala Ala Val Lys Thr Gly Lys Val Lys Pro Gly Ser Thr Cys Val195 200 205Val Phe Gly Leu Arg Gly Val Gly Leu Ser Val Ile Met Gly Cys Lys210 215 220Ser Ala Gly Ala Ser Arg Ile Ile Gly Ile Asp Leu Asn Lys Asp Lys225 230 235 240Phe Glu Lys Ala Met Ala Val Gly Ala Thr Glu Cys Ile Ser Pro Lys245 250 255Asp Ser Thr Lys Pro Ile Ser Glu Val Leu Ser Glu Met Thr Gly Asn260 265 270Asn Val Gly Tyr Thr Phe Glu Val Ile Gly His Leu Glu Thr Met Ile275 280 285Asp Ala Leu Ala Ser Cys His Met Asn Tyr Gly Thr Ser Val Val Val290 295 300Gly Val Pro Pro Ser Ala Lys Met Leu Thr Tyr Asp Pro Met Leu Leu305 310 315 320Phe Thr Gly Arg Thr Trp Lys Gly Cys Val Phe Gly Gly Leu Lys Ser325 330 335Arg Asp Asp Val Pro Lys Leu Val Thr Glu Phe Leu Ala Lys Lys Phe340 345 350Asp Leu Asp Gln Leu Ile Thr His Val Leu Pro Phe Lys Lys Ile Ser355 360 365Glu Gly Phe Glu Leu Leu Asn Ser Gly Gln Ser Ile Arg Thr Val Leu370 375 380Thr Phe385<210>82<211>418<212>PRT<213>智人(Homo sapiens)
<400> 82Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro1 5 10 15Tyr Val Val Cys Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val20 25 30Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr35 40 45Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln50 55 60Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile65 70 75 80Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln85 90 95Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val100 105 110Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly115 120 125Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn130 135 140Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu145 150 155 160Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cys Gly Ala Gly165 170 175Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu180 185 190Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn195 200 205Ala His His Cys Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr210 215 220Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala225 230 235 240Thr Ser Gly Ile Ser Thr Thr Phe Pro Lys Leu Arg Met Arg Val Arg245 250 255Asn Ile Leu Ile His Asn Asn Tyr Lys Ser Ala Thr His Glu Asn Asp260 265 270Ile Ala Leu Val Arg Leu Glu Asn Ser Val Thr Phe Thr Lys Asp Ile275 280 285His Ser Val Cys Leu Pro Ala Ala Thr Gln Asn Ile Pro Pro Gly Ser290 295 300Thr Ala Tyr Val Thr Gly Trp Gly Ala Gln Glu Tyr Ala Gly His Thr305 310 315 320Val Pro Glu Leu Arg Gln Gly Gln Val Arg Ile Ile Ser Asn Asp Val325 330 335Cys Asn Ala Pro His Ser Tyr Asn Gly Ala Ile Leu Ser Gly Met Leu340 345 350Cys Ala Gly Val Pro Gln Gly Gly Val Asp Ala Cys Gln Gly Asp Ser355 360 365Gly Gly Pro Leu Val Gln Glu Asp Ser Arg Arg Leu Trp Phe Ile Val370 375 380Gly Ile Val Ser Trp Gly Asp Gln Cys Gly Leu Pro Asp Lys Pro Gly385 390 395 400Val Tyr Thr Arg Val Thr Ala Tyr Leu Asp Trp Ile Arg Gln Gln Thr405 410 415Gly Ile<210>83
<211>418<212>PRT<213>智人(Homo sapiens)<400>83Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro1 5 10 15Tyr Val Val Cys Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val20 25 30Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr35 40 45Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln50 55 60Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile65 70 75 80Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln85 90 95Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val100 105 110Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly115 120 125Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn130 135 140Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu145 150 155 160Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cys Gly Ala Gly165 170 175Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu180 185 190Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn195 200 205Ala His His Cys Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr210 215 220Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala225 230 235 240Thr Ser Gly Ile Ser Thr Thr Phe Pro Lys Leu Arg Met Arg Val Arg245 250 255Asn Ile Leu Ile His Asn Asn Tyr Lys Ser Ala Thr His Glu Asn Asp260 265 270Ile Ala Leu Val Arg Leu Glu Asn Ser Val Thr Phe Thr Lys Asp Ile275 280 285His Ser Val Cys Leu Pro Ala Ala Thr Gln Asn Ile Pro Pro Gly Ser290 295 300Thr Ala Tyr Val Thr Gly Trp Gly Ala Gln Glu Tyr Ala Gly His Thr305 310 315 320Val Pro Glu Leu Arg Gln Gly Gln Val Arg Ile Ile Ser Asn Asp Val325 330 335Cys Asn Ala Pro His Ser Tyr Asn Gly Ala Ile Leu Ser Gly Met Leu340 345 350Cys Ala Gly Val Pro Gln Gly Gly Val Asp Ala Cys Gln Gly Asp Ser355 360 365Gly Gly Pro Leu Val Gln Glu Asp Ser Arg Arg Leu Trp Phe Ile Val370 375 380Gly Ile Val Ser Trp Gly Asp Gln Cys Gly Leu Pro Asp Lys Pro Gly385 390 395 400Val Tyr Thr Arg Val Thr Ala Tyr Leu Asp Trp Ile Arg Gln Gln Thr405 410 415Gly Ile
<210>84<211>489<212>DNA<213>智人(Homo sapiens)<400>84aaaagggtaa gcttgatgat taccaggaac gaatgaacaa aggggaaagg cttaatcaag 60atcagctgga tgccgtttct aagtaccagg aagtcacaaa taatttggag tttgcaaaag120aattacagag gagtttcatg gcactaagtc aagatattca gaaaacaata aagaagacag180cacgtcggga gcagcttatg agagaagaag ctgaacagaa acgtttaaaa actgtacttg240agctacagta tgttttggac aaattgggag atgatgaagt gcggactgac ctgaaacaag300gtttgaatgg agtgccaata ttgtccgaag aggagttgtc attgttggat gaattctata360agctagtaga ccctgaacgg gacatgagct tgaggttgaa tgaacagtat gaacatgcct420ccattcacct gtgggacctg ctggaaggga aggaaaaacc tgtatgtgga accacctata480aagttctaa489<210>85<211>304<212>DNA<213>智人(Homo sapiens)<400>85gggacctgga ggaggccacg ctgcagcatg aagccacagc agccaccctg aggaagaagc 60acgcggacag cgtggccgag ctcggggagc agatcgacaa cctgcagcgg gtgaagcaga120agctggagaa ggagaagagc gagatgaaga tggagatcga tgacctcgct tgtaacatgg180aggtcatctc caaatctaag ggaaaccttg agaagatgtg ccgcacactg gaggaccaag240tgagtgagct gaagacccag gaggaggaac agcagcggct gatcaatgaa ctgactgcgc300agag 304<210>86<211>296<212>DNA<213>智人(Homo sapiens)<400>86gaaaatcctt cctttgaatg ggaatctcca agcagttgaa ttgggcgaaa aaagaacctc 60ttccttaagg attaaaatgt ttagggcaac acgtgttact tccacttcca gatttctgaa120tccatatgtt gtatgtttcc ttgtcctccc aggggttgtg atcctggcag tccccatagc180tctacttgtt tactttttag cttttgatca aaaatcttac ttttattgga gcaattttcc240actcccaaat gttgaatata atagtccgtt taattccccc gcttcaccgg gaattc296<210>87<211>904<212>DNA<213>智人(Homo sapiens)<400>87gtgtccagga aacgattcat gaacataaca agcttgctgc aaattcagat catctcatgc 60agattcaaaa atgtgagttg gtcttgatcc acacctaccc agttggtgaa gacagccttg120tatctgatcg ttctaaaaaa gagttgtccc cggttttaac cagtgaagtt catagtgttc180gtgcaggacg gcatcttgct accaaattga atattttagt acagcaacat tttgacttgg240cttcaactac tattacaaat attccaatga aggaagaaca gcatgctaac acatctgcca300attatgatgt ggagctactt catcacaaag atgcacatgt agatttcctg aaaagtggtg360attcgcatct aggtggcggc agtcgagaag gctcgtttaa agaaacaata acattaaagt420ggtgtacacc aaggacaaat aacattgaat tacactattg tactggagct tatcggattt480cacctgtaga tgtaaatagt agaccttcct cctgccttac taattttctt ctaaatggtc540gttctgtttt attggaacaa ccacgaaagt caggttctaa agtcattagt catatgctta600gtagccatgg aggagagatt tttttgcacg tccttagcag ttctcgatcc attctagaag660atccaccttc aattagtgaa ggatgtggag gaagagttac agactaccgg attacagatt720ttggtgaatt tatgagggga aaacagatta actccttttc tacaccccag atataaaatc780gatggaagtc ttgaggtccc tttggaaccg agccaaaaga tcagttaaaa aaacataccc840gttactggcc tatgatttca aaaacccacc atttttaaca tgcaagcggt agttccgtta900acca 904<210>88<211>387<212>DNA<213>智人(Homo sapiens)<400>88cgtctctccc ccagtttgcc gttcacccgg agcgctcggg acttgccgat agtggtgacg 60gcggcaacat gtctgtggct ttcgcggccc cgaggcagcg aggcaagggg gagatcactc120ccgctgcgat tcagaagatg ttggatgaca ataaccatct tattcagtgt ataatggact180ctcagaataa aggaaagacc tcagagtgtt ctcagtatca gcagatgttg cacacaaact240tggtatacct tgctacaata gcagattcta atcaaaatat gcagtctctt ttaccagcac300cacccacaca gaatatgcct atgggtcctg gagggatgaa tcagagcggg cctcccccac360ctccacgctc tcacaacatg ccttcaa387<210>89<211>481<212>DNA<213>智人(Homo sapiens)<400>89tgttcttgga cctgcggtgc tatagagcag gctcttctag gttggcagtt gccatggaat 60ctggacccaa aatgttggcc cccgtttgcc tggtggaaaa taacaatgag cagctattgg120tgaaccagca agctatacag attcttgaaa agatttctca gccagtggtg gtggtggcca180ttgtaggact gtaccgtaca gggaaatcct acttgatgaa ccatctggca ggacagaatc240atggcttccc tctgggctcc acggtgcagt ctgaaaccaa gggcatctgg atgtggtgcg300tgccccaccc atccaagcca aaccacaccc tggtccttct ggacaccgaa ggtctgggcg360atgtggaaaa gggtgaccct aagaatgact cctggatctt tgccctggct gtgctcctgt420gcagcacctt tgtctacaac agcatgagca ccatcaacca ccaggccctg gagcagctgc480a481<210>90<211>491<212>DNA<213>智人(Homo sapiens)<400>90tgaaaactgt tcttggacct gcggtgctat agagcaggtt ggcagttgcc atggaatctg 60gacccaaaat gttggccccc gtttgcctgg tggaaaataa caatgagcag ctattggtga120accagcaagc tatacagatt cttgaaaaga tttctcagcc agtggtggtg gtggccattg180taggactgta ccgtacaggg aaatcctact tgatgaacca tctggcagga cagaatcatg240gcttccctct gggctccacg gtgcagtctg aaaccaaggg catctggatg tggtgcgtgc300cccacccatc caagccaaac cacaccctgg tccttctgga caccgaaggt ctgggcgatg360tggaaaaggg tgaccctaag aatgactcct ggatctttgc cctggctgtg ctcctgtgca420gcacctttgt ctacaacagc atgagcacca tcaaccacca agccctggag cagctgcatt480atgtgacgga c 491<210>91<211>488<212>DNA<213>智人(Homo sapiens)
<400>91ttcgacagtc agccgcatct tcttttgcgt cgccagccga gccacatcgc tcagacacca 60tggggaaggt gaaggtcgga gtcaacggat ttggtcgtat tgggcgcctg gtcaccaggg120ctgcttttaa ctctggtaaa gtggatattg ttgccatcaa tgaccccttc attgacctca180actacatggt ttacatgttc caatatgatt ccacccatgg caaattccat ggcaccgtcg240aggctgagaa cgggaagctt gtcatcaatg gaaatcccat caccatcttc caggagcgag300atccctccaa aatcaagtgg ggcgatgctg gcgctgagta cgtcgtggag tccactggcg360tcttcaccac catggagaag gctggggctc atttgcaggg gggagccaaa agggtcatca420tctctgcccc tctgctgatg ccccatgttc gtcatgggtg tgaaccatga gaagtatgac480acagcctc 488<210>92<211>384<212>DNA<213>智人(Homo sapiens)<400>92gacagtcagc cgcatcttct tttgcgtcgc cagccgagcc acatcgctca gacaccatgg 60ggaaggtgaa ggtcggagtc aacggatttg gtcgtattgg gcgcctggtc accagggctg120cttttaactc tggtaaagtg gatattgttg ccatcaatga ccccttcatt gacctcaact180acatggttta catgttccaa tatgattcca cccatggcaa attccatggc accgtcgagg240ctgagaacgg gaagcttgtc atcaatggaa atcccatcac catcttccag gagcgagatc300cctccaaaat caagtggggc gatactggcg ctgagtacgt cgtggagtcc actggcgtct360tcaccaccat ggagaaggct gggg 384<210>93<211>162<212>PRT<213>智人(Homo sapiens)<400>93Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg1 5 10 15Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr20 25 30Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu35 40 45Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln50 55 60Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu65 70 75 80Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp85 90 95Leu Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu100 105 110Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp Pro Glu Arg Asp Met115 120 125Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp130 135 140Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys145 150 155 160Val Leu<210>94<211>100<212>PRT
<213>智人(Homo sapiens)<400>94Asp Leu Glu Glu Ala Thr Leu Gln His Glu Ala Thr Ala Ala Thr Leul 5 10 15Arg Lys Lys His Ala Asp Ser Val Ala Glu Leu Gly Glu Gln Ile Asp20 25 30Asn Leu Gln Arg Val Lys Gln Lys Leu Glu Lys Glu Lys Ser Glu Met35 40 45Lys Met Glu Ile Asp Asp Leu Ala Cys Asn Met Glu Val Ile Ser Lys50 55 60Ser Lys Gly Asn Leu Glu Lys Met Cys Arg Thr Leu Glu Asp Gln Val65 70 75 80Ser Glu Leu Lys Thr Gln Glu Glu Glu Gln Gln Arg Leu Ile Asn Glu85 90 95Leu Thr Ala Gln100<210>95<211>99<212>PRT<213>智人(Homo sapiens)<400>95Lys Ile Leu Pro Leu Asn Gly Asn Leu Gln Ala Val Glu Leu Gly Glu1 5 10 15Lys Arg Thr Ser Ser Leu Arg Ile Lys Met Phe Arg Ala Thr Arg Val20 25 30Thr Ser Thr Ser Arg Phe Leu Asn Pro Tyr Val Val Cys Phe Leu Val35 40 45Leu Pro Gly Val Val Ile Leu Ala Val Pro Ile Ala Leu Leu Val Tyr50 55 60Phe Leu Ala Phe Asp Gln Lys Ser Tyr Phe Tyr Trp Ser Asn Phe Pro65 70 75 80Leu Pro Asn Val Glu Tyr Asn Ser Pro Phe Asn Ser Pro Ala Ser Pro85 90 95Gly Ile Pro<210>96<211>257<212>PRT<213>智人(Homo sapiens)<400>96Val Gln Glu Thr Ile His Glu His Asn Lys Leu Ala Ala Asn Ser Asp1 5 10 15His Leu Met Gln Ile Gln Lys Cys Glu Leu Val Leu Ile His Thr Tyr20 25 30Pro Val Gly Glu Asp Ser Leu Val Ser Asp Arg Ser Lys Lys Glu Leu35 40 45Ser Pro Val Leu Thr Ser Glu Val His Ser Val Arg Ala Gly Arg His50 55 60Leu Ala Thr Lys Leu Asn Ile Leu Val Gln Gln His Phe Asp Leu Ala65 70 75 80Ser Thr Thr Ile Thr Asn Ile Pro Met Lys Glu Glu Gln His Ala Asn85 90 95Thr Ser Ala Asn Tyr Asp Val Glu Leu Leu His His Lys Asp Ala His
100 105 ll0Val Asp Phe Leu Lys Ser Gly Asp Ser His Leu Gly Gly Gly Ser Arg115 120 125Glu Gly Ser Phe Lys Glu Thr Ile Thr Leu Lys Trp Cys Thr Pro Arg130 135 140Thr Asn Asn Ile Glu Leu His Tyr Cys Thr Gly Ala Tyr Arg Ile Ser145 150 155 160Pro Val Asp Val Asn Ser Arg Pro Ser Ser Cys Leu Thr Asn Phe Leu165 170 175Leu Asn Gly Arg Ser Val Leu Leu Glu Gln Pro Arg Lys Ser Gly Ser180 185 190Lys Val Ile Ser His Met Leu Ser Ser His Gly Gly Glu Ile Phe Leu195 200 205His Val Leu Ser Ser Ser Arg Ser Ile Leu Glu Asp Pro Pro Ser Ile210 215 220Ser Glu Gly Cys Gly Gly Arg Val Thr Asp Tyr Arg Ile Thr Asp Phe225 230 235 240Gly Glu Phe Met Arg Gly Lys Gln Ile Asn Ser Phe Ser Thr Pro Gln245 250 255Ile<210>97<211>128<212>PRT<213>智人(Homo sapiens)<400>97Ser Leu Pro Gln Phe Ala Val His Pro Glu Arg Ser Gly Leu Ala Asp1 5 10 15Ser Gly Asp Gly Gly Asn Met Ser Val Ala Phe Ala Ala Pro Arg Gln20 25 30Arg Gly Lys Gly Glu Ile Thr Pro Ala Ala Ile Gln Lys Met Leu Asp35 40 45Asp Asn Asn His Leu Ile Gln Cys Ile Met Asp Ser Gln Asn Lys Gly50 55 60Lys Thr Ser Glu Cys Ser Gln Tyr Gln Gln Met Leu His Thr Asn Leu65 70 75 80Val Tyr Leu Ala Thr Ile Ala Asp Ser Asn Gln Asn Met Gln Ser Leu85 90 95Leu Pro Ala Pro Pro Thr Gln Asn Met Pro Met Gly Pro Gly Gly Met100 105 1l0Asn Gln Ser Gly Pro Pro Pro Pro Pro Arg Ser His Asn Met Pro Ser115 120 125<210>98<211>159<212>PRT<213>智人(Homo sapiens)<400>98Phe Leu Asp Leu Arg Cys Tyr Arg Ala Gly Ser Ser Arg Leu Ala Val1 5 10 15Ala Met Glu Ser Gly Pro Lys Met Leu Ala Pro Val Cys Leu Val Glu20 25 30Asn Asn Asn Glu Gln Leu Leu Val Asn Gln Gln Ala Ile Gln Ile Leu35 40 45Glu Lys Ile Ser Gln Pro Val Val Val Val Ala Ile Val Gly Leu Tyr
50 55 60Arg Thr Gly Lys Ser Tyr Leu Met Asn His Leu Ala Gly Gln Asn His65 70 75 80Gly Phe Pro Leu Gly Ser Thr Val Gln Ser Glu Thr Lys Gly Ile Trp85 90 95Met Trp Cys Val Pro His Pro Ser Lys Pro Asn His Thr Leu Val Leu100 105 110Leu Asp Thr Glu Gly Leu Gly Asp Val Glu Lys Gly Asp Pro Lys Asn115 120 125Asp Ser Trp Ile Phe Ala Leu Ala Val Leu Leu Cys Ser Thr Phe Val130 135 140Tyr Asn Ser Met Ser Thr Ile Asn His Gln Ala Leu Glu Gln Leu145 150 155<210>99<21l>147<212>PRT<213>智人(Homo sapiens)<400>99Met Glu Ser Gly Pro Lys Met Leu Ala Pro Val Cys Leu Val Glu Asnl 5 10 15Asn Asn Glu Gln Leu Leu Val Asn Gln Gln Ala Ile Gln Ile Leu Glu20 25 30Lys Ile Ser Gln Pro Val Val Val Val Ala Ile Val Gly Leu Tyr Arg35 40 45Thr Gly Lys Ser Tyr Leu Met Asn His Leu Ala Gly Gln Asn His Gly50 55 60Phe Pro Leu Gly Ser Thr Val Gln Ser Glu Thr Lys Gly Ile Trp Met65 70 75 80Trp Cys Val Pro His Pro Ser Lys Pro Asn His Thr Leu Val Leu Leu85 90 95Asp Thr Glu Gly Leu Gly Asp Val Glu Lys Gly Asp Pro Lys Asn Asp100 105 110Ser Trp Ile Phe Ala Leu Ala Val Leu Leu Cys Ser Thr Phe Val Tyr115 120 125Asn Ser Met Ser Thr Ile Asn His Gln Ala Leu Glu Gln Leu His Tyr130 135 140Val Thr Asp145<210>100<211>124<212>PRT<213>智人(Homo sapiens)<400>100Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile Gly Arg1 5 10 15Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile Val Ala20 25 30Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met Phe Gln35 40 45Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Glu Ala Glu Asn50 55 60Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg65 70 75 80Asp Pro Ser Lys Ile Lys Trp Gly Asp Ala Gly Ala Glu Tyr Val Val
85 90 95Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly Ala His Leu100 105 110Gln Gly Gly Ala Lys Arg Val Ile Ile Ser Ala Pro115 120<210>101<211>127<212>PRT<213>智人(Homo sapiens)<400>101Gln Ser Ala Ala Ser Ser Phe Ala Ser Pro Ala Glu Pro His Arg Ser1 5 10 15Asp Thr Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile20 25 30Gly Arg Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile35 40 45Val Ala Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met50 55 60Phe Gln Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Glu Ala65 70 75 80Glu Asn Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln85 90 95Glu Arg Asp Pro Ser Lys Ile Lys Trp Gly Asp Thr Gly Ala Glu Tyr100 105 110Val Val Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly115 120 125<210>102<211>1225<212>DNA<213>智人(Homo sapiens)<400>102atggcggcgc ggtcgtcgtc gggggtggcg gcggcagagg gggcggcggc cctggcggca 60gcggagacgg cagccgtgac ggtggcagcg gcggcgcggg acctgggcct gggggaatga 120ggcggccgcg gcgggccagc ggcggagccg tgtagcggag aagctccccc tccctgcttc 180ccttggccga gccgggggcg cgcgcgcacg cggccgtcca gagcgggctc cccacccctc 240gactcctgcg acccgcaccg cacccccacc cgggcccgga ggatgatgaa gctcaagtcg 300aaccagaccc gcacctacga cggcgacggc tacaagaagc gggccgcatg cctgtgtttc 360cgcagcgaga gcgaggagga ggtgctactc gtgagcagta gtcgccatcc agacagatgg 420attgtccctg gaggaggcat ggagcccgag gaggagccaa gtgtggcagc agttcgtgaa 480gtctgtgagg aggctggagt aaaagggaca ttgggaagat tagttggaat ttttgagaac 540caggagagga agcacaggac gtatgtctat gtgctcattg tcactgaagt gctggaagac 600tgggaagatt cagttaacat tggaaggaag agggaatggt ttaaaataga agacgccata 660aaagtgctgc agtatcacaa acccgtgcag gcatcatatt ttgaaacatt gaggcaaggc 720tactcagcca acaatggcac cccagtcgtg gccaccacat actcggtttc tgctcagagc 780tcgatgtcag gcatcagatg actgaagact tcctgtaaga gaaatggaaa ttggaaacta 840gactgaagtg caaatcttcc ctctcaccct ggctctttcc acttctcaca ggcctcctct 900ttcaaataag gcatggtggg cagcaaagaa agggtgtatt gataatgttg ctgtttggtg 960ttaagtgatg gggctttttc ttctgttttt attgagggtg ggggttgggt gtgtaatttg1020taagtacttt tgtgcatgat ctgtccctcc ctcttcccac ccctgcagtc ctctgaagag1080aggccaacag ccttcccctg ccttggattc tgaagtgttc ctgtttgtct tatcctggcc1140ctggccagac gttttctttg atttttaatt tttttttttt attaaaagat accagtatga1200gaaaaaaaaa aaaaaaaaac tcgag 1225<210>103
<211>741<212>DNA<213>智人(Homo sapiens)<400>103agaaacctca atcggattca gcaaaggaat ggtgttatta tcactacata ccaaatgtta 60atcaataact ggcagcaact ttcaagcttt aggggccaag agtttgtgtg ggactatgtc120atcctcgatg aagcacataa aataaaaacc tcatctacta agtcagcaat atgtgctcgt180gctattcctg caagtaatcg cctcctcctc acaggaaccc caatccagaa taatttacaa240gaactatggt ccctatttga ttttgcttgt caagggtccc tgctgggaac attaaaaact300tttaagatgg agtatgaaaa tcctattact agagcaagag agaaggatgc taccccagga360gaaaaagcct tgggatttaa aatatctgaa aacttaatgg caatcataaa accctatttt420ctcaggagga ctaaagaaga cgtacagaag aaaaagtcaa gcaacccaga ggccagactt480aatgaaaaga atccagatgt tgatgccatt tgtgaaatgc cttccctttc caggagaaat540gatttaatta tttggatacg acttgtgcct ttacaagaag aaatatacag gaaatttgtg600tctttagatc atatcaagga gttgctaatg gagacgcgct cacctttggc tgagctaggt660gtcttaaaga agctgtgtga tcatcctagg ctgctgtctg cacgggcttg ttgtttgcta720aatcttggga cattctctgc t 741<210>104<211>321<212>DNA<213>智人(Homo sapiens)<400>104ttgctctgcg tcatcaaaga caccaaactg ctgtgctata aaagttccaa ggaccagcag 60cctcagatgg aactgccact ccaaggctgt aacattacgt acatcccgaa agacagcaaa120aagaagaagc acgagctgaa gattactcag cagggcacgg acccgcttgt tctcgccgtc180cagagcaagg aacaggccga gcagtggctg aaggtgatca aagaagccta cagtggttgt240agtggccccg tggattcaga gtgtcctcct ccaccaagct ccccggtgca caaggcagaa300ctggagaaga aactgtcttc a 321<210>105<211>389<212>DNA<213>智人(Homo sapiens)<400>105cagcactggc cacactataa aattcaggtt cagaaaaaca gggtaagtca cagacagcaa 60cgcttccagc atttattttc tttgcaccca tgggcaattt gagaaaattt acctttagaa120cgaactctgt taaaggtaca gacagtacaa tactttttat tcagaaggtt tctgcataaa180ggtgatagtc ttttgactta atatattatt gtctcctgcc ttgtgtttct ggaatgaatg240aaggtcatta tttagaagat aatctgggtt gtatttgtgt cgtcagattg aattttcatt300gcacatgcta cttaatgtct ttaccaaata ataacaaagg gaaagaaaac caaatataga360tgtataataa ggaaaagctg gcctataga 389<210>106<211>446<212>DNA<213>智人(Homo sapiens)<400>106gccacatttg ccctggtcat agtttaaaca ccaggtcctg tgtcacatct ttttggtgcc 60acaagtatca ctccattgtt cagagagtaa tgtattagtt ctgcccaatt cattcttcac120ttttatttct tccatttcat tagcatttat atcagctcaa gaagttaagg ttagaaaatt180ttccacttca aattttcagt acagaaatgt gctgtgatgt ttgacaagac tatttcatag240taagtgagtt aatgtttatt ggcctctgct ctcctctgtg tcagacctag gaagcctgag300gattacttag ttgttctgtc tctgggtcca caggcagaat ttggcccatc caaagactgg360ccaagtgcca aaaaaaggcc tgattaggcc ctgaaattca gtgaaattct gcctgaagaa420acctcttatt gaatttgaaa accata 446<210>107<211>467<212>DNA<213>智人(Homo sapiens)<400>107ccgccgctgc cgtcgccttc ctgggattgg agtctcgagc tttcttcgtt cgttcgccgg 60cgggttcgcg cccttctcgc gcctcggggc tgcgaggctg gggaaggggt tggagggggc120tgttgatcgc cgcgtttaag ttgcgctcgg ggcggccatg tcggccggcg aggtcgagcg180cctagtgtcg gagctgagcg gcgggaccgg aggggatgag gaggaagagt ggctctatgg240cgatgaagat gaagttgaaa ggccagaaga agaaaatgcc agtgctaatc ctccatctgg300aattgaagat gaaactgctg aaaatggtgt accaaaaccg aaagtgactg agaccgaaga360tgatagtgat agtgacagcg atgatgatga agatgatgtg catgtcacta taggagacat420taaaacggga gcaccacagt atgggagtta tggtacagca cctgtaa 467<210>108<211>491<212>DNA<213>智人(Homo sapiens)<400>108gaaagataca acttccccaa cccaaacccg tttgtggagg acgacatgga taagaatgaa 60atcgcctctg ttgcgtaccg ttaccgcagg tggaagcttg gagatgatat tgaccttatt120gtccgttgtg agcacgatgg cgtcatgact ggagccaacg gggaagtgtc cttcatcaac180atcaagacac tcaatgagtg ggattccagg cactgtaatg gcgttgactg gcgtcagaag240ctggactctc agcgaggggc tgtcattgcc acggagctga agaacaacag ctacaagttg300gcccggtgga cctgctgtgc tttgctggct ggatctgagt acctcaagct tggttatgtg360tctcggtacc acgtgaaaga ctcctcacgc cacgtcatcc taggcaccca gcagttcaag420cctaatgagt ttgccagcca gatcaacctg agcgtggaga atgcctgagg cattttacgc480tgcgtcattg a 491<210>109<211>489<212>DNA<213>智人(Homo sapiens)<400>109ctcagatagt actgaaccct ttatcaacta tgttttttca gtctgacaac caaggcggct 60actaagtgac taaggggcag gtagtataca gtgtggataa gcaggacaaa ggggtgattc120acatcccagg caggacagag caggagatca tgagatttca tcactcagga tggcttgtga180tttattttat tttattcttt tttttttttg agatggagtc tcactcttgc ccaggctgga240gtgcagtggt gcgatcttgg ctcactgcaa cctctgcctc ctgggttcaa gcagttctcc300tgcctcagcc tcccaagtag ctgggattac aggcgtccgc caccatgccc agccaatttt360tgtactttta gtagagatgg ggtttcacca tgttggccag gctggtctcg aactcctgac420ctcaggtgat ccactcgcct cggcctccca aagtgctggg attataggca tgcgccacca480tgcccgggc489<210>110<211>391<212>DNA<213>智人(Homo sapiens)<400>110gcggagtccg ctggctgacc cgagcgctgg tctccgccgg gaaccctggg gcatggagag 60gtctgagtac ctcggccgcg gcgcacgctg catcgcggag ccaggctgcc gctgtcccag120tggagttcca ggagcaccac ctgagtgagg tgcagaatat ggcatctgag gagaagctgg180agcaggtgct gagttccatg aaggagaaca aagtggccat cattggaaag attcataccc240cgatggagta taagggggag ctagcctcct atgatatgcg gctgaggcgt aagttggact300tatttgccaa cgtaatccat gtgaagtcac ttcctgggta tatgactcgg cacaacaatc360tagacctggt gatcattcga gagcagacag a 391<210>111<211>172<212>PRT<213>智人(Homo sapiens)<400>111Met Met Lys Leu Lys Ser Asn Gln Thr Arg Thr Tyr Asp Gly Asp Gly1 5 10 15Tyr Lys Lys Arg Ala Ala Cys Leu Cys Phe Arg Ser Glu Ser Glu Glu20 25 30Glu Val Leu Leu Val Ser Ser Ser Arg His Pro Asp Arg Trp Ile Val35 40 45Pro Gly Gly Gly Met Glu Pro Glu Glu Glu Pro Ser Val Ala Ala Val50 55 60Arg Glu Val Cys Glu Glu Ala Gly Val Lys Gly Thr Leu Gly Arg Leu65 70 75 80Val Gly Ile Phe Glu Asn Gln Glu Arg Lys His Arg Thr Tyr Val Tyr85 90 95Val Leu Ile Val Thr Glu Val Leu Glu Asp Trp Glu Asp Ser Val Asn100 105 110Ile Gly Arg Lys Arg Glu Trp Phe Lys Ile Glu Asp Ala Ile Lys Val115 120 125Leu Gln Tyr His Lys Pro Val Gln Ala Ser Tyr Phe Glu Thr Leu Arg130 135 140Gln Gly Tyr Ser Ala Asn Asn Gly Thr Pro Val Val Ala Thr Thr Tyr145 150 155 160Ser Val Ser Ala Gln Ser Ser Met Ser Gly Ile Arg165 170<210>112<211>247<212>PRT<213>智人(Homo sapiens)<400>112Arg Asn Leu Asn Arg Ile Gln Gln Arg Asn Gly Val Ile Ile Thr Thr1 5 10 15Tyr Gln Met Leu Ile Asn Asn Trp Gln Gln Leu Ser Ser Phe Arg Gly20 25 30Gln Glu Phe Val Trp Asp Tyr Val Ile Leu Asp Glu Ala His Lys Ile35 40 45Lys Thr Ser Ser Thr Lys Ser Ala Ile Cys Ala Arg Ala Ile Pro Ala50 55 60Ser Asn Arg Leu Leu Leu Thr Gly Thr Pro Ile Gln Asn Asn Leu Gln65 70 75 80Glu Leu Trp Ser Leu Phe Asp Phe Ala Cys Gln Gly Ser Leu Leu Gly85 90 95Thr Leu Lys Thr Phe Lys Met Glu Tyr Glu Asn Pro Ile Thr Arg Ala100 105 110Arg Glu Lys Asp Ala Thr Pro Gly Glu Lys Ala Leu Gly Phe Lys Ile115 120 125Ser Glu Asn Leu Met Ala Ile Ile Lys Pro Tyr Phe Leu Arg Arg Thr
130 135 140Lys Glu Asp Val Gln Lys Lys Lys Ser Ser Asn Pro Glu Ala Arg Leu145 150 155 160Asn Glu Lys Asn Pro Asp Val Asp Ala Ile Cys Glu Met Pro Ser Leu165 170 175Ser Arg Arg Asn Asp Leu Ile Ile Trp Ile Arg Leu Val Pro Leu Gln180 185 190Glu Glu Ile Tyr Arg Lys Phe Val Ser Leu Asp His Ile Lys Glu Leu195 200 205Leu Met Glu Thr Arg Ser Pro Leu Ala Glu Leu Gly Val Leu Lys Lys210 215 220Leu Cys Asp His Pro Arg Leu Leu Ser Ala Arg Ala Cys Cys Leu Leu225 230 235 240Asn Leu Gly Thr Phe Ser Ala245<210>113<211>107<212>PRT<213>智人(Homo sapiens)<400>113Leu Leu Cys Val Ile Lys Asp Thr Lys Leu Leu Cys Tyr Lys Ser Ser1 5 10 15Lys Asp Gln Gln Pro Gln Met Glu Leu Pro Leu Gln Gly Cys Asn Ile20 25 30Thr Tyr Ile Pro Lys Asp Ser Lys Lys Lys Lys His Glu Leu Lys Ile35 40 45Thr Gln Gln Gly Thr Asp Pro Leu Val Leu Ala Val Gln Ser Lys Glu50 55 60Gln Ala Glu Gln Trp Leu Lys Val Ile Lys Glu Ala Tyr Ser Gly Cys65 70 75 80Ser Gly Pro Val Asp Ser Glu Cys Pro Pro Pro Pro Ser Ser Pro Val85 90 95His Lys Ala Glu Leu Glu Lys Lys Leu Ser Ser100 105<210>114<211>155<212>PRT<213>智人(Homo sapiens)<400>114Glu Arg Tyr Asn Phe Pro Asn Pro Asn Pro Phe Val Glu Asp Asp Met1 5 10 15Asp Lys Asn Glu Ile Ala Ser Val Ala Tyr Arg Tyr Arg Arg Trp Lys20 25 30Leu Gly Asp Asp Ile Asp Leu Ile Val Arg Cys Glu His Asp Gly Val35 40 45Met Thr Gly Ala Asn Gly Glu Val Ser Phe Ile Asn Ile Lys Thr Leu50 55 60Asn Glu Trp Asp Ser Arg His Cys Asn Gly Val Asp Trp Arg Gln Lys65 70 75 80Leu Asp Ser Gln Arg Gly Ala Val Ile Ala Thr Glu Leu Lys Asn Asn85 90 95Ser Tyr Lys Leu Ala Arg Trp Thr Cys Cys Ala Leu Leu Ala Gly Ser100 105 110Glu Tyr Leu Lys Leu Gly Tyr Val Ser Arg Tyr His Val Lys Asp Ser
115 120 125Ser Arg His Val Ile Leu Gly Thr Gln Gln Phe Lys Pro Asn Glu Phe130 135 140Ala Ser Gln Ile Asn Leu Ser Val Glu Asn Ala145 150 155<210>115<211>129<212>PRT<213>智人(Homo sapiens)<400>115Gly Val Arg Trp Leu Thr Arg Ala Leu Val Ser Ala Gly Asn Pro Gly1 5 10 15Ala Trp Arg Gly Leu Ser Thr Ser Ala Ala Ala His Ala Ala Ser Arg20 25 30Ser Gln Ala Ala Ala Val Pro Val Glu Phe Gln Glu His His Leu Ser35 40 45Glu Val Gln Asn Met Ala Ser Glu Glu Lys Leu Glu Gln Val Leu Ser50 55 60Ser Met Lys Glu Asn Lys Val Ala Ile Ile Gly Lys Ile His Thr Pro65 70 75 80Met Glu Tyr Lys Gly Glu Leu Ala Ser Tyr Asp Met Arg Leu Arg Arg85 90 95Lys Leu Asp Leu Phe Ala Asn Val Ile His Val Lys Ser Leu Pro Gly100 105 110Tyr Met Thr Arg His Asn Asn Leu Asp Leu Val Ile Ile Arg Glu Gln115 120 125Thr<210>116<211>550<212>DNA<213>智人(Homo sapiens)<400>116gaattcggca ccagcctcag agccccccag cccggctacc accccctgcg gaaaggtacc 60catctgcatt cctgcccgtc gggacctggt ggacagtcca gcctccttgg cctctagcct120tggctcaccg ctgcctagag ccaaggagct catcctgaat gaccttcccg ccagcactcc180tgcctccaaa tcctgtgact cctccccgcc ccaggacgct tccaccccca ggcccagctc240ggccagtcac ctctgccagc ttgctgccaa gccagcacct tccacggaca gcgtcgccct300gaggagcccc ctgactctgt ccagtccctt caccacgtcc ttcagcctgg gctcccacag360cactctcaac ggagacctct ccgtgcccag ctcctacgtc agcctccacc tgtcccccca420ggtcagcagc tctgtggtgt acggacgctc ccccgtgatg gcatttgagt ctcatcccca480tctccgaggg tcatccgtct cttcctccct acccagcatc cctgggggaa agccggccta540ctccttccac 550<210>117<211>154<212>DNA<213>智人(Homo sapiens)<400>117ttctgaggga aagccgagtg gagtgggcga cccggcggcg gtgacaatga gttttcttgg 60aggctttttt ggtcccattt gtgagattga tgttgccctt aatgatgggg aaaccaggaa120aatggcagaa atgaaaactg aggatggcaa agta154
<210>118<211>449<212>DNA<213>智人(Homo sapiens)<400>118gaattcggca ccagggcccg cagcccgagt gtcgccgcca tggcttcgcc gcagctctgc 60cgcgcgctgg tgtcggcgca atgggtggcg gaggcgctgc gggccccgcg cgctgggcag120cctctgcagc tgctggscgc ctcctggtsc ctgccgaagc tggggcgcga cgcgcgscgc180gagttcgagg agcgccacat cccgggcgcc gctttcttcg scatcgacca gtgcagcgac240cgcacctcgc cctacgacca catgctgccc ggggccgagc atttcgcgga gtacgcaggc300cgcctgggcg tgggcgcggc cacccacgtc gtgatctacg scgccagcga ccagggcctc360tactccgccc cgcgcgtctg gtggatgttc cgcgccttcg gccaccacgc cgtgtcactg420cttgatggcg gcctccgcca ctggctgcg 449<210>119<211>642<212>DNA<213>智人(Homo sapiens)<400>119gaattcggca cgagcagtaa cccgaccgcc gctggtcttc gctggacacc atgaatcaca 60ctgtccaaac cttcttctct cctgtcaaca gtggccagcc ccccaactat gagatgctca120aggaggagca cgaggtggct gtgctggggg cgccccacaa ccctgctccc ccgacgtcca180ccgtgatcca catccgcagc gagacctccg tgcccgacca tgtcgtctgg tccctgttca240acaccctctt catgaacccc tgctgcctgg gcttcatagc attcgcctac tccgtgaagt300ctagggacag gaagatggtt ggcgacgtga ccggggccca ggcctatgcc tccaccgcca360agtgcctgaa catctgggcc ctgattctgg gcatcctcat gaccattctg ctcatcgtca420tcccagtgct gatcttccag gcctatggat agatcaggag gcatcactga ggccaggagc480tctgcccatg acctgtatcc cacgtactcc aacttccatt cctcgccctg cccccggagc540cgagtcctgt atcagccctt tatcctcaca cgcttttcta caatggcatt caataaagtg600cacgtgtttc tggtgaaaaa aaaaaaaaaa aaaaaactcg ag 642<210>120<211>603<212>DNA<213>智人(Homo sapiens)<400>120gaattcggca cgagccacaa cagccactac gactgcatcc actggatcca cggccacccc 60gtcctccacc ccgggaacag ctccccctcc caaagtgctg accagcccgg ccaccacacc120catgtccacc atgtccacaa tccacacctc ctctactcca gagaccaccc acacctccac180agtgctgacc accacagcca ccatgacaag ggccaccaat tccacggcca caccctcctc240cactctgggg acgacccgga tcctcactga gctgaccaca acagccacta caactgcagc300cactggatcc acggccaccc tgtcctccac cccagggacc acctggatcc tcacagagcc360gagcactata gccaccgtga tggtgcccac cggttccacg gccaccgcct cctccactct420gggaacagct cacaccccca aagtggtgac caccatggcc actatgccca cagccactgc480ctccacggtt cccagctcgt ccaccgtggg gaccacccgc acccctgcag tgctccccag540cagcctgcca accttcagcg tgtccactgt gtcctcctca gtcctcacca ccctgagacc600cac 603<210>121<211>178<212>PRT<213>智人(Homo sapiens)<400>121Ser Glu Pro Pro Ser Pro Ala Thr Thr Pro Cys Gly Lys Val Pro Ilel 5 l0 15Cys Ile Pro Ala Arg Arg Asp Leu Val Asp Ser Pro Ala Ser Leu Ala20 25 30Ser Ser Leu Gly Ser Pro Leu Pro Arg Ala Lys Glu Leu Ile Leu Asn35 40 45Asp Leu Pro Ala Ser Thr Pro Ala Ser Lys Ser Cys Asp Ser Ser Pro50 55 60Pro Gln Asp Ala Ser Thr Pro Arg Pro Ser Ser Ala Ser His Leu Cys65 70 75 80Gln Leu Ala Ala Lys Pro Ala Pro Ser Thr Asp Ser Val Ala Leu Arg85 90 95Ser Pro Leu Thr Leu Ser Ser Pro Phe Thr Thr Ser Phe Ser Leu Gly100 105 110Ser His Ser Thr Leu Asn Gly Asp Leu Ser Val Pro Ser Ser Tyr Val115 120 125Ser Leu His Leu Ser Pro Gln Val Ser Ser Ser Val Val Tyr Gly Arg130 135 140Ser Pro Val Met Ala Phe Glu Ser His Pro His Leu Arg Gly Ser Ser145 150 155 160Val Ser Ser Ser Leu Pro Ser Ile Pro Gly Gly Lys Pro Ala Tyr Ser165 170 175Phe His<210>122<211>36<212>PRT<213>智人(Homo sapiens)<400>122Met Ser Phe Leu Gly Gly Phe Phe Gly Pro Ile Cys Glu Ile Asp Val1 5 10 15Ala Leu Asn Asp Gly Glu Thr Arg Lys Met Ala Glu Met Lys Thr Glu20 25 30Asp Gly Lys Val35<210>123<211>136<212>PRT<213>智人(Homo sapiens)<400>123Met Ala Ser Pro Gln Leu Cys Arg Ala Leu Val Ser Ala Gln Trp Val1 5 10 15Ala Glu Ala Leu Arg Ala Pro Arg Ala Gly Gln Pro Leu Gln Leu Leu20 25 30Asp Ala Ser Trp Tyr Leu Pro Lys Leu Gly Arg Asp Ala Arg Arg Glu35 40 45Phe Glu Glu Arg His Ile Pro Gly Ala Ala Phe Phe Asp Ile Asp Gln50 55 60Cys Ser Asp Arg Thr Ser Pro Tyr Asp His Met Leu Pro Gly Ala Glu65 70 75 80His Phe Ala Glu Tyr Ala Gly Arg Leu Gly Val Gly Ala Ala Thr His85 90 95Val Val Ile Tyr Asp Ala Ser Asp Gln Gly Leu Tyr Ser Ala Pro Arg100 105 110Val Trp Trp Met Phe Arg Ala Phe Gly His His Ala Val Ser Leu Leu
115 120 125Asp Gly Gly Leu Arg His Trp Leu130 135<210>124<211>133<212>PRT<213>智人(Homo sapiens)<400>124Met Asn His Thr Val Gln Thr Phe Phe Ser Pro Val Asn Ser Gly Gln1 5 10 15Pro Pro Asn Tyr Glu Met Leu Lys Glu Glu His Glu Val Ala Val Leu20 25 30Gly Ala Pro His Asn Pro Ala Pro Pro Thr Ser Thr Val Ile His Ile35 40 45Arg Ser Glu Thr Ser Val Pro Asp His Val Val Trp Ser Leu Phe Asn50 55 60Thr Leu Phe Met Asn Pro Cys Cys Leu Gly Phe Ile Ala Phe Ala Tyr65 70 75 80Ser Val Lys Ser Arg Asp Arg Lys Met Val Gly Asp Val Thr Gly Ala85 90 95Gln Ala Tyr Ala Ser Thr Ala Lys Cys Leu Asn Ile Trp Ala Leu Ile100 105 110Leu Gly Ile Leu Met Thr Ile Leu Leu Ile Val Ile Pro Val Leu Ile115 120 125Phe Gln Ala Tyr Gly130<210>125<211>195<212>PRT<213>智人(Homo sapiens)<400>125Thr Thr Ala Thr Thr Thr Ala Ser Thr Gly Ser Thr Ala Thr Pro Ser1 5 10 15Ser Thr Pro Gly Thr Ala Pro Pro Pro Lys Val Leu Thr Ser Pro Ala20 25 30Thr Thr Pro Met Ser Thr Met Ser Thr Ile His Thr Ser Ser Thr Pro35 40 45Glu Thr Thr His Thr Ser Thr Val Leu Thr Thr Thr Ala Thr Met Thr50 55 60Arg Ala Thr Asn Ser Thr Ala Thr Pro Ser Ser Thr Leu Gly Thr Thr65 70 75 80Arg Ile Leu Thr Glu Leu Thr Thr Thr Ala Thr Thr Thr Ala Ala Thr85 90 95Gly Ser Thr Ala Thr Leu Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu100 105 110Thr Glu Pro Ser Thr Ile Ala Thr Val Met Val Pro Thr Gly Ser Thr115 120 125Ala Thr Ala Ser Ser Thr Leu Gly Thr Ala His Thr Pro Lys Val Val130 135 140Thr Thr Met Ala Thr Met Pro Thr Ala Thr Ala Ser Thr Val Pro Ser145 150 155 160Ser Ser Thr Val Gly Thr Thr Arg Thr Pro Ala Val Leu Pro Ser Ser165 170 175Leu Pro Thr Phe Ser Val Ser Thr Val Ser Ser Ser Val Leu Thr Thr
180 185 190Leu Arg Pro195<210>126<211>509<212>DNA<213>智人(Homo sapiens)<400>126gaattcggca cgagccaagt accccctgag gaatctgcag cctgcatctg agtacaccgt 60atccctcgtg gccataaagg gcaaccaaga gagccccaaa gccactggag tctttaccac120actgcagcct gggagctcta ttccacctta caacaccgag gtgactgaga ccaccattgt180gatcacatgg acgcctgctc caagaattgg ttttaagctg ggtgtacgac caagccaggg240aggagaggca ccacgagaag tgacttcaga ctcaggaagc atcgttgtgt ccggcttgac300tccaggagta gaatacgtct acaccatcca agtcctgaga gatggacagg aaagagatgc360gccaattgta aacaaagtgg tgacaccatt gtctccacca acaaacttgc atctggaggc420aaaccctgac actggagtgc tcacagtctc ctggagagga gcaccacccc agacattact480gggtatagaa ttaccacaac ccctacaaa 509<210>127<211>500<212>DNA<213>智人(Homo sapiens)<400>127gaattcggca cgagccactg atgtccgggg agtcagccag gagcttgggg aagggaagcg 60cgcccccggg gccggtcccg gagggctcga tccgcatcta cagcatgagg ttctgcccgt120ttgctgagag gacgcgtcta gtcctgaagg ccaagggaat caggcatgaa gtcatcaata180tcaacctgaa aaataagcct gagtggttct ttaagaaaaa tccctttggt ctggtgccag240ttctggaaaa cagtcagggt cagctgatct acgagtctgc catcacctgt gagtacctgg300atgaagcata cccagggaag aagctgttgc cggatgaccc ctatgagaaa gcttgccaga360agatgatctt agagttgttt tctaaggtgc catccttggt aggaagcttt attagaagcc420aaaataaaga agactatgct ggcctaaaag aagaatttcg taaagaattt accaagctag480aggaggttct gactaataag500<210>128<211>500<212>DNA<213>智人(Homo sapiens)<400>128agctttcctc tgctgccgct cggtcacgct tgtgcccgaa ggaggaaaca gtgacagacc 60tggagactgc agttctctat ccttcacaca gctctttcac catgcctgga tcacttcctt120tgaatgcaga agcttgctgg ccaaaagatg tgggaattgt tgcccttgag atctattttc180cttctcaata tgttgatcaa gcagagttgg aaaaatatga tggtgtagat gctggaaagt240ataccattgg cttgggccag gccaagatgg gcttctgcac agatagagaa gatattaact300ctctttgcat gactgtggtt cagaatctta tggagagaaa taacctttcc tatgattgca360ttgggcggct ggaagttgga acagagacaa tcatcgacaa atcaaagtct gtgaagacta420atttgatgca gctgtttgaa gagtctggga atacagatat agaaggaatc gacacaacta480atgcatgcta tggaggcaca500<210>129<211>497<212>DNA<213>智人(Homo sapiens)<400>129gaattcggca cgagcagagg tctccagagc cttctctctc ctgtgcaaaa tggcaactct 60taaggaaaaa ctcattgcac cagttgcgga agaagaggca acagttccaa acaataagat120cactgtagtg ggtgttggac aagttggtat ggcgtgtgct atcagcattc tgggaaagtc180tctggctgat gaacttgctc ttgtggatgt tttggaagat aagcttaaag gagaaatgat240ggatctgcag catgggagct tatttcttca gacacctaaa attgtggcag ataaagatta300ttctgtgacc gccaattcta agattgtagt ggtaactgca ggagtccgtc agcaagaagg360ggagagtcgg ctcaatctgg tgcagagaaa tgttaatgtc ttcaaattca ttattcctca420gatcgtcaag tacagtcctg attgcatcat aattgtggtt tccaacccag tggacattct480tacgtatgtt acctgga 497<210>130<211>383<212>DNA<213>智人(Homo sapiens)<400>130gaattcggca cgagggccgc ggctgccgac tgggtcccct gccgctgtcg ccaccatggc 60tccgcaccgc cccgcgcccg cgctgctttg cgcgctgtcc ctggcgctgt gcgcgctgtc120gctgcccgtc cgcgcggcca ctgcgtcgcg gggggcgtcc caggcggggg cgccccaggg180gcgggtgccc gaggcgcggc ccaacagcat ggtggtggaa caccccgagt tcctcaaggc240agggaaggag cctggcctgc agatctggcg tgtggagaaa gttcgatctg gtggcccgtg300cccaccaacc tttatggaga cttcttcacg ggcgacgcct acgtcatcct gaagacagtg360cagcttaaga acggaaaatc ttg383<210>131<211>509<212>DNA<213>智人(Homo sapiens)<400>131gaattcggca cgagagtcag ccgcatcttc ttttgcgtcg ccagccgagc cacatcgctc 60agacaccatg gggaaggtga aggtcggagt caacggattt ggtcgtattg ggcgcctggt120caccagggct gcttttaact ctggtaaagt ggatattgtt gccatcaatg accccttcat180tgacctcaac tacatggttt acatgttcca atatgattcc acccatggca aattccatgg240caccgtcaag gctgagaacg ggaagcttgt catcaatgga aatcccatca ccatcttcca300ggagcgagat ccctccaaaa tcaagtgggg cgatgctggc gctgagtacg tcgtggagtc360cactggccgt cttcaccacc atggagaagg ctggggctca tttgcagggg ggagccaaaa420gggtcatcat ctctgccccc tctgctgacg cccccatgtt cgtcatgggt gtgaaccatg480agaagtatga caacagcctc aagatcatc 509<210>132<211>357<212>DNA<213>智人(Homo sapiens)<400>132gaattcggca cgagtaagaa gaagccccta gaccacagct ccacaccatg gactggacct 60ggaggatcct cttcttggtg gcagcagcaa caggtgccca ctcccaggtg caactggtgc120aatctgggtc tgagttgaag aagcctgggg cctcagtgaa ggtttcctgc aaggcttctg180gacacatctt cagtatctat ggtttgaatt gggtgcgaca ggcccctggt caaggccttg240agtggatggg atggatcaaa gtcgacactg cgaacccaac gtatgcccag ggcttcacag300gacgatttgt cttctccctg gacacctctg tcagcacggc atatctgcag atcagca 357<210>133<211>468<212>DNA<213>智人(Homo sapiens)
<400>133gaattcggca cgaggcgccc cgaaccgtcc tcctgctgct ctcggcggcc ctggccctga 60ccgagacctg ggccggctcc cactccatga ggtatttcga caccgccatg tcccggcccg120gccgcgggga gccccgcttc atctcagtgg gctacgtgga cgacacgcag ttcgtgaggt180tcgacagcga cgccgcgagt ccgagagagg agccgcgggc gccgtggata gagcaggagg240ggccggagta ttgggaccgg aacacacaga tcttcaagac caacacacag actgaccgag300agagcctgcg gaacctgcgc ggctactaca accagagcga ggccgggtct cacaccctcc360agagcatgta cggctgcgac gtggggccgg acgggcgcct cctccgcggg cataaccagt420acgcctacga cggcaaggat tacatcgccc tgaacgagga cctgcgct 468<210>134<211>214<212>DNA<213>智人(Homo sapiens)<400>134gaattcggca cgagctgcgt cctgctgagc tctgttctct ccagcacctc ccaacccact 60agtgcctggt tctcttgctc caccaggaac aagccaccat gtctcgccag tcaagtgtgt120ccttccggag cgggggcagt cgtagcttca gcaccgcctc tgccatcacc ccgtctgtct180cccgcaccag cttcacctcc gtgtcccggt ccgg214<210>135<211>355<212>DNA<213>智人(Homo sapiens)<400>135gaattcggca cgaggtgaac aggacccgtc gccatgggcc gtgtgatccg tggacagagg 60aagggcgccg ggtctgtgtt ccgcgcgcac gtgaagcacc gtaaaggcgc tgcgcgcctg120cgcgccgtgg atttcgctga gcggcacggc tacatcaagg gcatcgtcaa ggacatcatc180cacgacccgg gccgcggcgc gcccctcgcc aaggtggtct tccgggatcc gtatcggttt240aagaagcgga cggagctgtt cattgccgcc gagggcattc acacgggcca gtttgtgtat300tgcggcaaga aggcccagct caacattggc aatgtgctcc ctgtgggcac catgc 355<210>136<211>242<212>DNA<213>智人(Homo sapiens)<400>136gaattcggca cgagccagct cctaaccgcg agtgatccgc cagcctccgc ctcccgaggt 60gcccggattg cagacggagt ctccttcact cagtgctcaa tggtgcccag gctggagtgc120agtggtgtga tctcggctcg ctacaacatc cacctcccag cagcctgcct tggcctccca180aagtgccgag attgcagctc tctgcccggc cgccacccct gtctgggaag tgaggatgct240gt 242<210>137<211>424<212>DNA<213>智人(Homo sapiens)<400>137gaattcggca cgagcccaga tcccgaggtc cgacagcgcc cggcccagat ccccacgcct 60gccaggagca agccgagagc cagccggccg gcgcactccg actccgagca gtctctgtcc120ttcgacccga gccccgcgcc ctttccggga cccctgcccc gcgggcagcg ctgccaacct180gccggccatg gagaccccgt cccagcggcg cgccacccgc agcggggcgc aggccagctc240cactccgctg tcgcccaccc gcatcacccg gctgcaggag aaggaggacc tgcaggagct300caatgatcgc ttggcggtct acatcgaccg tgtgcgctcg ctggaaacgg agaacgcagg360gctgcgcctt cgcatcaccg agtctgaaga ggtggtcagc cgcgaggtgt ccggcatcaa420ggcc 424<210>138<211>448<212>DNA<213>智人(Homo sapiens)<400>138gaattcggca cgagcctgtg ttccaggagc cgaatcagaa atgtcatcct caggcacgcc 60agacttacct gtcctactca ccgatttgaa gattcaatat actaagatct tcataaacaa120tgaatggcat gattcagtga gtggcaagaa atttcctgtc tttaatcctg caactgagga180ggagctctgc caggtagaag aaggagataa ggaggatgtt gacaaggcag tgaaggccgc240aagacaggct tttcagattg gatccccgtg gcgtactatg gatgcttccg agagggggcg300actattatac aagttggctg atttaatcga aagagatcgt ctgctgctgg ccgacaatgg360agtcaatgaa tggtggaaaa ctctattcca atgcatatct gaatgattta gcaggctgca420tcaaaacatt gcgctactgt gcaggttg 448<210>139<211>510<212>DNA<213>智人(Homo sapiens)<400>139gaattcggca cgaggttccg tgcagctcac ggagaagcga atggacaaag tcggcaagta 60ccccaaggag ctgcgcaagt gctgcgagga cggcatgcgg gagaacccca tgaggttctc120gtgccagcgc cggacccgtt tcatctccct ggcgaggcgt gcaagaaggt cttcctggac180tgctgcaact acatcacaga gctgcggcgg cagcacgcgc gggccagcca cctggcctgc240caggagtaac ctggatgagg acatcattgc agaagagaac atcgtttccc gaagtgagtt300cccagagagc tggctgtgga acgttgagga cttgaaagag ccaccgaaaa atggaatctc360tacgaagctc atgaatatat ttttgaaaga ctccatcacc acgtgggaga ttctggctgt420gagcatgtcg gacaagaaag ggatctgtgt ggcagacccc ttcgaggtca cagtaatgca480ggacttcttc atcgacctgc ggctacccta 510<210>140<211>360<212>DNA<213>智人(Homo sapiens)<400>140gaattcggca cgagcggtaa ctaccccggc tgcgcacagc tcggcgctcc ttcccgctcc 60ctcacacacc ggcctcagcc cgcaccggca gtagaagatg gtgaaagaaa caacttacta120cgatgttttg ggggtcaaac ccaatgctac tcaggaagaa ttgaaaaagg cttataggaa180actggctttg aagtaccatc ctgataagaa cccaaatgaa ggagagaagt ttaaacagat240ttctcaagct tacgaagttc tctctgatgc aaagaaaagg gaattatatg acaaaggagg300agaacaggca attaaagagg gtggagcagg tggcggtttt ggctccccca tggacatctt360<210>141<211>483<212>DNA<213>智人(Homo sapiens)<400>141gaattcggca cgagagcaga ggctgatctt tgctggaaaa cagctggaag atgggctgca 60ccctgtctga ctacaacatc cagaaagagt ccaccctgca cctggtgctc cgtctcagag120gtgggatgca aatcttcgtg aagacactca ctggcaagac catcaccctt gaggtggagc180ccagtgacac catcgagaac gtcaaagcaa agatccagga caaggaaggc attcctcctg240accagcagag gttgatcttt gccggaaagc agctggaaga tgggcgcacc ctgtctgact300acaacatcca gaaagagtct accctgcacc tggtgctccg tctcagaggt gggatgcaga360tcttcgtgaa gaccctgact ggtaagacca tcaccctcga ggtggagccc agtgacacca420tcgagaatgt caaggcaaag atccaagata aggaaggcat tcctcctgat cagcagaggt480tga 483<210>142<211>500<212>DNA<213>智人(Homo sapiens)<400>142gaattcggca cgaggcggcg acgaccgccg ggagcgtgtg cagcggcggc ggcggaagtg 60gccggcgagc ccggtccccg ccggcaccat gcttcccttg tcactgctga agacggctca120gaatcacccc atgttggtgg agctgaaaaa tggggagacg tacaatggac acctggtgag180ctgcgacaac tggatgaaca ttaacctgcg agaagtcatc tgcacgtcca gggacgggga240caagttctgg cggatgcccg agtgctacat ccgcggcagc accatcaagt acctgcgcat300ccccgacgag atcatcgaca tggtcaagga ggaggtggtg gccaagggcc gcggccgcgg360aggcctgcag cagcagaagc agcagaaagg ccgcggcatg ggcggcgctg gccgaggtgt420gtttggtggc cggggccgag gtgggatccc gggcacaggc agaagccagc cagagaagaa480gcctggcaga caggcgggca500<210>143<211>400<212>DNA<213>智人(Homo sapiens)<400>143gaattcggca cgagctcgga tgtcagcagg cgtcccaacc cagcaggaac tggctcaatt 60ctcagaagaa agcgatcggc cccgaggcag gaaggccggc tccggtgcag ggcgcgccgc120ctgcgggctg cttcgggcca gggtcgaccc gagggccagc gcaagcagcg gcaacaggag180cgccaggagg acatgaggct ctgcctgcag tcagcaactt ggaatattca gacttcagac240cagcatcaca gattataacc ctccgtaaat catctgcatc ccagctccca tcaaaagcca300gcctgaagga cccatggaca cgtgactcca gtgttctcaa caacatctta gatcaagttg360gtttgcacaa catttgcatc tacttgggac aaagcaagaa 400<210>144<211>243<212>DNA<213>智人(Homo sapiens)<400>144gaattcggca cgagccagct cctaaccgcg agtgatccgc cagcctccgc ctcccgaggt 60gcccggattg cagacggagt ctccttcact cagtgctcaa tggtgcccag gctggagtgc120agtggtgtga tctcggctcg ctacaacatc cacctcccag cagcctgcct tggcctccca180aagtgccgag attgcagcct ctgcccggcc gtcaccccgt ctgggaagtg aggagcgttt240ctg 243<210>145<211>450<212>DNA<213>智人(Homo sapiens)<400>145gaattcggca cgaggacagc aggaccgtgg aggccgcggc aggggtggca gtggtggcgg 60cggcggcggc ggcggtggtg gttacaaccg cagcagtggt ggctatgaac ccagaggtcg120tggaggtggc cgtggaggca gaggtggcat gggcggaagt gaccgtggtg gcttcaataa180atttggtggc cctcgggacc aaggatcacg tcatgactcc gaacaggata attcagacaa240caacaccatc tttgtgcaag gcctgggtga gaatgttaca attgagtctg tggctgatta300cttcaagcag attggtatta ttaagacaaa caagaaaacg ggacagccca tgattaattt360gtacacagac agggaaactg gcaagctgaa gggagaggca acggtctctt ttgatgaccc420accttcagct aaagcagcct attgactggt 450<210>146<211>451<212>DNA<213>智人(Homo sapiens)<400>146gaattcggca cgagccatcg agtccctgcc tttcgacttg cagagaaatg tctcgctgat 60gcgggagatc gacgcgaaat accaagagat cctgaaggag ctagacgagt gctacgagcg120cttcagtcgc gagacagacg gggcgcagaa gcggcggatg ctgcactgtg tgcagcgcgc180gctgatccgc accaggagct gggcgacgag aagatccaga tcgtgagcca gatggtggag240ctggtggaga accgcacgcg gcaggtggac agccacgtgg agctgttcga ggcgcagcag300gagctgggcg acacagcggg caacagcggc aaggctggcg cggacaggcc caaaggcgag360gcggcagcgc aggctgacaa gcccaacagc aagcgctcac ggcggcagcg caacaacgag420aaccgtgaga acgcgtccag caaccacgac c 451<210>147<211>400<212>DNA<213>智人(Homo sapiens)<400>147gaattcggca cgagctcgga tgtcagcagg cgtcccaacc cagcaggaac tggctcaatt 60ctcagaagaa agcgatcggc cccgaggcag gaaggccggc tccggtgcag ggcgcgccgc120ctgcgggctg cttcgggcca gggtcgaccc gagggccagc gcaagcagcg gcaacaggag180cgccaggagg acatgaggct ctgcctgcag tcagcaactt ggaatattca gacttcagac240cagcatcaca gattataacc ctccgtaaat catctgcatc ccagctccca tcaaaagcca300gcctgaagga cccatggaca cgtgactcca gtgttctcaa caacatctta gatcaagttg360gtttgcacaa catttgcatc tacttgggac aaagcaagaa 400<210>148<211>503<212>DNA<213>智人(Homo sapiens)<400>148aaaagaattc ggcacgagcg gcgccgctca tccccctctc ccagcagatt cccactggaa 60attcgttgta tgaatcttat tacaagcagg tcgatccggc atacacaggg agggtggggg120cgagtgaagc tgcgcttttt ctaaagaagt ctggcctctc ggacattatc cttgggaaga180tatgggactt ggccgatcca gaaggtaaag ggttcttgga caaacagggt ttctatgttg240cactgagact ggtggcctgt gcacagagtg gccatgaagt taccttgagc aatctgaatt300tgagcatgcc accgcctaaa tttcacgaca ccagcagccc tctgatggtc acaccgccct360ctgcagaggc ccactgggct gtgagggtgg aagaaaaggc caaatttgat gggatttttg420aaagcctctt gcccatcaat ggtttgctct ctggagacaa agtcaagcca gtcctcatga480actcaaagct gcctcttgat gtc503<210>149<211>1061<212>DNA<213>智人(Homo sapiens)<400>149gaattcggca cgaggccttt tccagcaacc ccaaggtcca ggtggaggcc atcgaagggg 60gagccctgca gaagctgctg gtcatcctgg ccacggagca gccgctcact gcaaagaaga 120aggtcctgtt tgcactgtgc tccctgctgc gccacttccc ctatgcccag cggcagttcc 180tgaagctcgg ggggctgcag gtcctgagga ccctggtgca ggagaagggc acggaggtgc 240tcgccgtgcg cgtggtcaca ctgctctacg acctggtcac ggagaagatg ttcgccgagg 300aggaggctga gctgacccag gagatgtccc cagagaagct gcagcagtat cgccaggtac 360acctcctgcc aggcctgtgg gaacagggct ggtgcgagat cacggcccac ctcctggcgc 420tgcccgagca tgatgcccgt gagaaggtgc tgcagacact gggcgtcctc ctgaccacct 480gccgggaccg ctaccgtcag gacccccagc tcggcaggac actggccagc ctgcaggctg 540agtaccaggt gctggccagc ctggagctgc aggatggtga ggacgagggc tacttccagg 600agctgctggg ctctgtcaac agcttgctga aggagctgag atgaggcccc acaccagtac 660tggactggga tgccgctagt gaggctgagg ggtgccagcg tgggtgggct tctcaggcag 720gaggacatct tggcagtgct ggcttggcca ttaaatggaa acctgaaggc catcctcttt 780ctgctgtgtg tctgtgtaga ctgggcacag ccctgtggcc ggggggtcag gtgagtggtt 840gggtgatggg ctctgctgac gtgcagggct cagcccaggg catccaggaa caggctccag 900ggcaggaacc tgggcccagg agttgcaagt ctctgcttct taccaagcag cagctctgta 960ccttgggaag tcgcttaatt gctctgagct tgtttcctca tctgtcagga gtgccattaa1020aggagaaaaa tcacgtaaaa aaaaaaaaaa aaaaactcga g1061<210>150<211>781<212>DNA<213>智人(Homo sapiens)<400>150gaattcggca cgagaaatgg cggcaggggt cgaagcggca gccgaagtgg cggcgacaga 60acccaaaatg gaggaagaga gcggcgcgcc ctgcgtgccg agcggcaacg gagctccggg120cccgaagggt gaagaacgac ctactcagaa tgagaagagg aaggagaaaa acataaaaag180aggaggcaat cgctttgagc catattccaa cccaactaaa agatacagag ccttcattac240aaatatacct tttgatgtga aatggcagtc acttaaagac ctggttaaag aaaaagttgg300tgaggtaaca tacgtggagc tcttaatgga cgctgaagga aagtcaaggg gatgtgctgt360tgttgaattc aagatggagg agagcatgaa aaaagctgct gaagttctaa acaagcatag420tctgagtgga aggccactga aagtcaagga agatcctgat ggtgaacatg caaggagagc480aatgcaaaag gctggaagac ttggaagcac agtatttgta gcaaatctgg attataaagt540tggctggaag aaactgaagg aagtatttag tatggctggt gtggtggtcc gagcagacat600tctggaagat aaagatggga aaagtcgtgg aataggcatt gtgacttttg aacagtccat660tgaagctgtg caagcaatat ctatgtttaa tggccagttg ctgtttgata gaccgatgca720cgtcaagatg gatgagaggg ctttaccaaa gggagacttt tttcctcctg aacgccacag780c781<210>151<211>3275<212>DNA<213>智人(Homo sapiens)<400>151cttaagtgga tcctgcatca ggagggagca gacaccggag aaagaaaaac aagttgtgct 60gtttgaggaa gcaagttgga cctgcactcc agcctgtgga gatgaaccta ggactgtgat 120tctgctatcc agtatgttgg ctgaccacag gctcaaactg gaggattata aggatcgcct 180gaaaagtgga gagcatctta atccagacca gttggaagct gtagagaaat atgaagaagt 240gctacataat ttggaatttg ccaaggagct tcaaaaaacc ttttctgggt tgagcctaga 300tctactaaaa gcgcaaaaga aggcccagag aagggagcac atgctaaaac ttgaggctga 360gaagaaaaag cttcgaacta tacttcaagt tcagtatgta ttgcagaact tgacacagga 420gcacgtacaa aaagacttca aagggggttt gaatggtgca gtgtatttgc cttcaaaaga 480acttgactac ctcattaagt tttcaaaact gacctgccct gaaagaaatg aaagtctgag 540acaaacactt gaaggatcta ctgtctaaat tgctgaactc aggctatttt gaaagtatcc 600cagttcccaa aaatgccaag gaaaaggaag taccactgga ggaagaaatg ctaatacaat 660cagagaaaaa aacacaatta tcgaagactg aatctgtcaa agagtcagag tctctaatgg 720aatttgccca gccagagata caaccacaag agtttcttaa cagacgctat atgacagaag 780tagattattc aaacaaacaa ggcgaagagc aaccttggga agcagattat gctagaaaac 840caaatctccc aaaacgttgg gatatgctta ctgaaccaga tggtcaagag aagaaacagg 900agtcctttaa gtcctgggag gcttctggta agcaccagga ggtatccaag cctgcagttt 960ccttagaaca gaggaaacaa gacacctcaa aactcaggtc tactctgccg gaagagcaga1020agaagcagga gatctccaaa tccaagccat ctcctagcca gtggaagcaa gatacaccta1080aatccaaagc agggtatgtt caagaggaac aaaagaaaca ggagacacca aagctgtggc1140cagttcagct gcagaaagaa caagatccaa agaagcaaac tccaaagtct tggacacctt1200ccatgcagag cgaacagaac accaccaagt catggaccac tcccatgtgt gaagaacagg1260attcaaaaca gccagagact ccaaaatcct gggaaaacaa tgttgagagt caaaaacact1320ctttaacatc acagtcacag atttctccaa agtcctgggg agtagctaca gcaagcctca1380taccaaatga ccagctgctg cccaggaagt tgaacacaga acccaaagat gtgcctaagc1440ctgtgcatca gcctgtaggt tcttcctcta cccttccgaa ggatccagta ttgaggaaag1500aaaaactgca ggatctgatg actcagattc aaggaacttg taactttatg caagagtctg1560ttcttgactt tgacaaacct tcaagtgcaa ttccaacgtc acaaccgcct tcagctactc1620caggtagccc cgtagcatct aaagaacaaa atctgtccag tcaaagtgat tttcttcaag1680agccgttaca ggtatttaac gttaatgcac ctctgcctcc acgaaaagaa caagaaataa1740aagaatcccc ttattcacct ggctacaatc aaagttttac cacagcaagt acacaaacac1800caccccagtg ccaactgcca tctatacatg tagaacaaac tgtccattct caagagactg1860cagcaaatta tcatcctgat ggaactattc aagtaagcaa tggtagcctt gccttttacc1920cagcacagac gaatgtgttt cccagaccta ctcagccatt tgtcaatagc cggggatctg1980ttagaggatg tactcgtggt gggagattaa taaccaattc ctatcggtcc cctggtggtt2040ataaaggttt tgatacttat agaggactcc cttcaatttc caatggaaat tatagccagc2100tgcagttcca agctagagag tattctggag caccttattc ccaaagggat aatttccagc2160agtgttataa gcgaggaggg acatctggtg gtccacgagc aaattcgaga gcagggtgga2220gtgattcttc tcaggtgagc agcccagaaa gagacaacga aacctttaac agtggtgact2280ctggacaagg agactcccgt agcatgaccc ctgtggatgt gccagtgaca aatccagcag2340ccaccatact gccagtacac gtctaccctc tgcctcagca gatgcgagtt gccttctcag2400cagccagaac ctctaatctg gcccctggaa ctttagacca acctattgtg tttgatcttc2460ttctgaacaa cttaggagaa acttttgatc ttcagcttgg tagatttaat tgcccagtga2520atggcactta cgttttcatt tttcacatgc taaagctggc agtgaatgtg ccactgtatg2580tcaacctcat gaagaatgaa gaggtcttgg tatcagccta tgccaatgat ggtgctccag2640accatgaaac tgctagcaat catgcaattc ttcagctctt ccagggagac cagatatggt2700tacgtctgca caggggagca atttatggaa gtagctggaa atattctacg ttttcaggct2760atcttcttta tcaagattga aagtcagtac agtattgaca ataaaaggat ggtgttctaa2820ttagtgggat tgaaggaaaa gtagtctttg ccctcatgac tgattggttt aggaaaatgt2880ttttgttcct agagggagga ggtccttact tttttgtttt ccttcctgag gtgaaaaatc2940aagctgaatg acaattagca ctaatctggc actttataaa ttgtgatgta gcctcgctag3000tcaagctgtg aatgtatatt gtttgcactt aatccttaac tgtattaacg ttcagcttac3060taaactgact gcctcaagtc caggcaagtt acaatgcctt gttgtgcctc aataaaaaag3120ttacatgcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa3180aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa3240aaaaaaaaaa aaaaaaaaaa aaaaaaaaac tcgag 3275<210>152<211>2179<212>DNA<213>智人(Homo sapiens)<400>152gaattcggca ccaggcacta ttaaatgtga ggcagcctcc atctactaca acatttgtgc 60tgaatcaaat aaatcatctt ccacccttgg gatctacaat tgtaatgact aaaacaccac 120ctgtaacaac caacaggcaa accatcactt taactaagtt tatccagact actgcaagca 180cacgcccgtc agtctcagca ccaacagtac gaaatgccat gacctctgca ccttcaaaag 240accaagttca gcttaaagat ctactgaaaa ataatagtct taatgaactg atgaaactaa 300agccacctgc taatattgct cagccagtag caacagcagc tactgatgta agcaatggta 360cagtaaagaa agagtcttct aataaagaag gagctagaat gtggataaac gacatgaaga 420tgaggagttt ttccccaacc atgaaggttc ctgttgtaaa agaagatgat gaaccagagg 480aagaagatga agaagaaatg ggtcatgcag aaacctatgc agaatacatg ccaataaaat 540taaaaattgg cctacgtcat ccagatgctg tagtggaaac cagctcttta tccagtgtta 600ctcctcctga tgtttggtac aaaacatcca tttctgagga aaccattgat aatggctggt 660tatcagcatt gcagcttgag gcaattacat atgcagccca gcaacatgaa actttcctac 720ctaatggaga tcgtgctggc ttcttaatag gtgatggtgc cggtgtagga aaaggaagga 780cgatagcagg aatcatctat gaaaattatt tgttgagtag aaaacgagca ttgtggttta 840gtgtttcaaa tgacttaaag tatgatgctg aaagagattt aagggatatt ggagcaaaaa 900acattttggt tcattcgtta aataagttta aatacggaaa aatttcttcc aaacataatg 960ggagtgtgaa aaagggtgtt atttttgcta cttactcttc acttattggt gaaagccagt1020ctggcggcaa gtataaaact aggttaaaac aacttctgca ttggtgcggt gatgacttcg1080atggagtgat agtgtttgat gagtgtcata aagccaaaaa cttatgtcct gttggttctt1140caaagccaac caagacaggc ttagcagttt tagagcttca gaacaaattg ccaaaagcca1200gagttgttta tgctagtgca actggtgctt ctgaaccacg caacatggcc tatatgaacc1260gtcttggcat atggggtgag ggtactccat ttagagaatt cagtgatttt attcaagcag1320tagaacggag aggagttggt gccatggaaa tagttgctat ggatatgaag cttagaggaa1380tgtacattgc tcgacaactg agctttactg gagtgacctt caaaattgag gaagttcttc1440tttctcagag ctacgttaaa atgtataaca aagctgtcaa gctgtgggtc attgccagag1500agcggtttca gcaagctgca gatctgattg atgctgagca acgaatgaag aagtccatgt1560ggggtcagtt ctggtctgct caccagaggt tcttcaaata cttatgcata gcatccaaag1620ttaaaagggt tgtgcaacta gctcgagagg aaatcaagaa tggaaaatgt gttgtaattg1680gtctgcagtc tacaggagaa gctagaacat tagaagcttt ggaagagggc gggggagaat1740tgaatgattt tgtttcaact gccaaaggtg tgttgcagtc actcattgaa aaacattttc1800ctgctccaga caggaaaaaa ctttatagtt tactaggaat cgatttgaca gctccaagta1860acaacagttc gccaagagat agtccttgta aagaaaataa aataaagaag cggaaaggtg1920aagaaataac tcgagaagcc aaaaaagcac gaaaagtagg tggccttact ggtagcagtt1980ctgacgacag tggaagtgaa tctgatgcct ctgataatga agaaagtgac tatgagagct2040ctaaaaacat gagttctgga gatgatgacg atttcaaccc atttttagat gagtctaatg2100aggatgatga aaatgatccc tggttaatta aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa2160aaaaaaaaaa aaactcgag 2179<210>153<211>2109<212>DNA<213>智人(Homo sapiens)<400>153cagagagccc caggcatcga ggagaaggcg gcggagaatg gggccctggg gtcccccgag 60agagaagaga aagtgctgga gaatggggag ctgacacccc caaggaggga ggagaaagcg 120ctggagaatg gggagctgag gtccccagag gccggggaga aggtgctggt gaatgggggc 180ctgacacccc caaagagcga ggacaaggtg tcagagaatg ggggcctgag attccccagg 240aacacggaga ggccaccaga gactgggcct tggagagccc cagggccctg ggagaagacg 300cccgagagtt ggggtccagc ccccacgatc ggggagccag ccccagagac ctctctggag 360agagcccctg cacccagcgc agtggtctcc tcccggaacg gcggggagac agcccctggc 420ccccttggcc cagcccccaa gaacgggacg ctggaacccg ggaccgagag gagagccccc 480gagactgggg gggcgccgag agccccaggg gctgggaggc tggacctcgg gagtgggggc 540cgagccccag tgggcacggg gacggccccc ggcggcggcc ccggaagcgg cgtggacgca 600aaggccggat gggtagacaa cacgaggccg cagccaccgc cgccaccgct gccaccgcca 660ccggaggcac agccgaggag gctggagcca gcgcccccga gagccaggcc ggaggtggcc 720cccgagggag agcccggggc cccagacagc agggccggcg gagacacggc actcagcgga 780gacggggacc cccccaagcc cgagaggaag ggccccgaga tgccacgact attcttggac 840ttgggacccc ctcaggggaa cagcgagcag atcaaagcca ggctctcccg gctctcgctg 900gcgctgccgc cgctcacgct cacgccattc ccggggccgg gcccgcggcg gcccccgtgg 960gagggcgcgg acgccggggc ggctggcggg gaggccggcg gggcgggagc gccggggccg1020gcggaggagg acggggagga cgaggacgag gacgaggagg aggacgagga ggcggcggcg1080ccgggcgcgg cggcggggcc gcggggcccc gggagggcgc gagcagcccc ggtgcccgtc1140gtggtgagca gcgccgacgc ggacgcggcc cgcccgctgc gggggctgct caagtctccg1200cgcggggccg acgagccaga ggacagcgag ctggagagga agcgcaagat ggtctccttc1260cacggggacg tgaccgtcta cctcttcgac caggagacgc caaccaacga gctgagcgtc1320caggcccccc ccgaggggga cacggacccg tcaacgcctc cagcgccccc gacacctccc1380caccccgcca cccccggaga tgggtttccc agcaacgaca gcggctttgg aggcagtttc1440gagtgggcgg aggatttccc cctcctcccc cctccaggcc ccccgctgtg cttctcccgc1500ttctccgtct cgcctgcgct ggagaccccg gggccacccg cccgggcccc cgacgcccgg1560cccgcaggcc ccgtggagaa ttgattcccc gaagacccga ccccgctgca ccctcagaag1620aggggttgag aatggaatcc tctgtggatg acggcgccac tgccaccacc gcagacgccg1680cctctgggga ggcccccgag gctgggccct ccccctccca ctcccctacc atgtgccaaa1740cgggaggccc cgggcccccg cccccccagc cccccagatg gctcccctga cccccctgac1800cccctcggag ccaaatgagg caggaatccc cccgcccctc catagagagc cgcctttctc1860ggaactgaac tgaactcttt tgggcctgga gcccctcgac acagcggagg tccctcctca1920cccactcctg gcccaagaca ggggccgcag gcttcgggga cccggacccc ccatttcgcg1980tctccccttt ccctccccag cccggcccct ggaggggcct ctggttcaaa ccttcgcgtg2040gcattttcac attatttaaa aaagacaaaa acaacttttt ggaggaaaaa aaaaaaaaaa2100aaactcgag2109<210>154<211>1411<212>DNA<213>智人(Homo sapiens)<400>154gaattcggca ccaggggaga tgaggaagtt cgatgttcct agcatggagt ctacccttaa 60ccagccagcc atgctagaga cgttatactc agatccacat taccgagccc atttccccaa 120cccaagacct gatacaaata aggatgtata caaagtattg ccagaatcca agaaggcacc 180gggcagtggt gcagtatttg agaggaacgg accacatgct agcagtagtg gggtgctccc 240tttgggactc cagcctgcgc ctggactttc caagtcacta tcctctcagg tgtggcaacc 300aagtcctgac ccttggcatc ctggagaaca atcctgtgaa ctcagtactt gtcgacagca 360gttggaattg atccgtttac agatggagca aatgcagctt cagaacggag ccatgtgtca 420ccatcctgct gctttcgctc cattactgcc caccctagag ccagcacagt ggctcagcat 480cctgaacagt aacgagcatc tcctgaagga gaaggagctc ctcattgaca agcaaaggaa 540gcatatctct cagctggagc agaaagtgcg agagagtgaa ctgcaagtcc acagtgccct 600tttgggccgc cctgccccct ttggggatgt ctgcttattg aggctacagg agttgcagcg 660agagaacact ttcttacggg cacagtttgc acagaagaca gaagccctga gcaaggagaa 720gatggagctt gaaaagaaac tctctgcatc tgaagttgaa attcagctca ttagggagtc 780tctaaaagtg acactacaga agcattcgga ggaggggaag aaacaggagg aaagggtcaa 840aggtcgtgat aaacatatca ataatttgaa aaagaaatgt cagaaggaat cagagcagaa 900ccgggagaag cagcagcgta ttgaaacctt ggagcgctat ctagctgacc tgcccaccct 960agaagaccat cagaaacaga cggagcagct taaggacgct gaattaaaga acacagaact1020gcaagagaga gtggctgagc tggagacttt gctggaggac acccaggcaa cctgcagaga1080gaaggaggtt cagctggaaa gtctgagaca aagagaagca gacctctcct ctgctagaca1140taggtaatgc cctgtgtact tgggggaagg agggagttcg gttctggtgc tctgttaact1200cttgtgtgtt caacagtgtt catttcaagt tcctttcttc taagagcttt gtgttctttg1260aattgaaagt cacttatggc cgggtgtggt ggcgcacacc tttaatccca gcacttggga1320gtcagaggca ggctaatttc tgagtttcag gacagccagg gctatacaga gaaaccctgt1380ctcaaacaaa aaaaaaaaaa aaaaactcga g 1411<210>155<211>678<212>DNA<213>智人(Homo sapiens)<400>155ctggagtgaa gggagctagt ggtaaaggga gctggtggag gggtggcggc aggggtaagg 60ggcaggggac accctctaga cggagagcgg gctccgaggt cctggctggc cctcggtgcg120cccgcccctg tgttggtccc acaatccctg gcaatgagag gccagggttt attggacaga180gtcagttgtg gggttcagag ggtcagcaat caatcaatcc tccgaatcca gagatttaga240cccagtcgtc cgtattagga ctggaggggg gtcaataggt tcagtgtttg agatgccaag300ggaacctgtc ttttgatttg gggttcaaca tacagagttc aggtacctgc aggaatttgc360ccccctaggc acagggggtg gtctttacca ttttcgagac cagatcctgg ctgggagccc420cgaggcattc ttcgtgctca atgctgatgt ctgctccgac ttccccttga gtgctatgtt480ggaagcccac cgacgccagc gtcacccttt cttactcctt ggcactacgg ctaacaggac540gcaatccctc aactacggct gcatcgttga gaatccacag acacacgagg tattgcacta600tgtggagaaa cccagcacat ttatcagtga catcatcaac tgcggcacct acctcttttc660tcctgaagcc ttgaagcc 678<210>156<211>2668<212>DNA<213>智人(Homo sapiens)<400>156gggaaggcgg ctgcgctgct gggcgggggc gggagctgga gccggagctg gagccggggc 60cggggcccgg gtcagcgctt gagccgggag aagagtttga gatcgtggac cgaagccagc 120tgcccggccc aggcgacctg cggagcgcaa cgaggccgcg ggcggccgag ggctggtcgg 180cgcccatcct gaccctggca cgcagggcca ccgggaacct gtcggcgagc tgcgggagcg 240cgctgcgcgc ggccgcgggg ctgggcggcg gggacagcgg ggacggcacg gcgcgcgcag 300cttctaagtg ccagatgatg gaggagcgtg ccaacctgat gcacatgatg aaactcagca 360tcaaggtgtt gctccagtcg gctctgagcc tgggccgcag cctggatgcg gaccatgccc 420ccttgcagca gttctttgta gtgatggagc actgcctcaa acatgggctg aaagttaaga 480agagttttat tggccaaaat aaatcattct ttggtccttt ggagctggtg gagaaacttt 540gtccagaagc atcagatata gcgactagtg tcagaaatct tccagaatta aagacagctg 600tgggaagagg ccgagcgtgg ctttatcttg cactcatgca aaagaaactg gcagattatc 660tgaaagtgct tatagacaat aaacatctct taagcgagtt ctatgagcct gaggctttaa 720tgatggagga agaagggatg gtgattgttg gtctgctggt gggactcaat gttctcgatg 780ccaatctctg cttgaaagga gaagacttgg attctcaggt tggagtaata gatttttccc 840tctaccttaa ggatgtgcag gatcttgatg gtggcaagga gcatgaaaga attactgatg 900tccttgatca aaaaaattat gtggaagaac ttaaccggca cttgagctgc acagttgggg 960atcttcaaac caagatagat ggcttggaaa agactaactc aaagcttcaa gaagagcttt1020cagctgcaac agaccgaatt tgctcacttc aagaagaaca gcagcagtta agagaacaaa1080atgaattaat tcgagaaaga agtgaaaaga gtgtagagat aacaaaacag gataccaaag1140ttgagctgga gacttacaag caaactcggc aaggtctgga tgaaatgtac agtgatgtgt1200ggaagcagct aaaagaggag aagaaagtcc ggttggaact ggaaaaagaa ctggagttac1260aaattggaat gaaaaccgaa atggaaattg caatgaagtt actggaaaag gacacccacg1320agaagcagga cacactagtt gccctccgcc agcagctgga agaagtcaaa gcgattaatt1380tacagatgtt tcacaaagct cagaatgcag agagcagttt gcagcagaag aatgaagcca1440tcacatcctt tgaaggaaaa accaaccaag ttatgtccag catgaaacaa atggaagaaa1500ggttgcagca ctcggagcgg gcgaggcagg gggctgagga gcggagccac aagctgcagc1560aggagctggg cgggaggatc ggcgccctgc agctgcagct ctcccagctg cacgagcaat1620gctcaagcct ggagaaagaa ttgaaatcag aaaaagagca aagacaggct cttcagcgcg1680aattacagca cgagaaagac acttcctctc tactcaggat ggagctgcaa caagtggaag1740gactgaaaaa ggagttgcgg gagcttcagg acgagaaggc agagctgcag aagatctgcg1800aggagcagga acaagccctc caggaaatgg gcctgcacct cagccagtcc aagctgaaga1860tggaagatat aaaagaagtg aaccaggcac tgaagggcca cgcctggctg aaagatgacg1920aagcgacaca ctgtaggcag tgtgagaagg agttctccat ttcccggaga aagcaccact1980gccggaactg tggccacatc ttctgcaaca cctgctccag caacgagctg gccctgccct2040cctaccccaa gccggtgcga gtgtgcgaca gctgccacac cctgctcctg cagcgctgct2100cctccacggc ctcctgaacg tccgtcctca ggagcacagc ctcacggaca gtgccaaacc2160ctgtgggtct ccaggggctt gggaaatgtg ttctttccca agagtatcaa aggaaagaat2220caaatttctt gcccggtcac tggcactcca gaagacagcg tgccggaacc ggcagctctc2280acctttctgt gacttgttcg gaattaactc ctctggatgg aaacttccat cttacttggt2340tacatcacgg ctctggttca gatacaactt catgattttg ctactatcat ttttcacttt2400tcaaagaatt taacctattt tacagcagtt cagttctgct agtgagtagt tttcctctcc2460taccttcctt ctaaaaacct gattcatgca cagcgtttga cacacatgga gtctgccagt2520gtgccttctc tgcttcagac aagagatctg ccatttcatg cccttgtgac tacctatcat2580tggccctgca ataaaatcat ttatttttca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa2640aaaaaaaaaa aaaaaaaaaa aactcgag 2668<210>157<211>2313
<212>DNA<213>智人(Homo sapiens)<400>157gaattcggca ccaggccggg cgggcgcctc agccatggcc ctgcgcaagg aactgctcaa 60gtccatctgg tacgccttta ccgcgctgga cgtggagaag agtggcaaag tctccaagtc 120ccagctcaag gtgctgtccc acaacctgta cacggtcctg cacatccccc atgaccccgt 180ggccctggag gaacacttcc gagatgatga tgacggccct gtgtccagcc agggatacat 240gccctacctc aacaagtaca tcctggacaa ggtggaggag ggggcttttg ttaaagagca 300ctttgatgag ctgtgctgga cgctgacggc caagaagaac tatcgggcag atagcaacgg 360gaacagtatg ctctccaatc aggatgcctt ccgcctctgg tgcctcttca acttcctgtc 420tgaggacaag taccctctga tcatggttcc tgatgaggtg gaatacctgc tgaaaaaggt 480actcagcagc atgagcttgg aggtgagctt gggtgagctg gaggagcttc tggcccagga 540ggcccaggtg gcccagacca ccggggggct cagcgtctgg cagttcctgg agctcttcaa 600ttcgggccgc tgcctgcggg gcgtgggccg ggacaccctc agcatggcca tccacgaggt 660ctaccaggag ctcatccaag atgtcctgaa gcagggctac ctgtggaagc gagggcacct 720gagaaggaac tgggccgaac gctggttcca gctgcagccc agctgcctct gctactttgg 780gagtgaagag tgcaaagaga aaaggggcat tatcccgctg gatgcacact gctgcgtgga 840ggtgctgcca gaccgcgacg gaaagcgctg catgttctgt gtgaagacag ccacccgcac 900gtatgagatg agcgcctcag acacgcgcca gcgccaggag tggacagctg ccatccagat 960ggcgatccgg ctgcaggccg aggggaagac gtccctacac aaggacctga agcagaaacg1020gcgcgagcag cgggagcagc gggagcggcg ccgggcggcc aaggaagagg agctgctgcg1080gctgcagcag ctgcaggagg agaaggagcg gaagctgcag gagctggagc tgctgcagga1140ggcgcagcgg caggccgagc ggctgctgca ggaggaggag gaacggcgcc gcagccagca1200ccgcgagctg cagcaggcgc tcgagggcca actgcgcgag gcggagcagg cccgggcctc1260catgcaggct gagatggagc tgaaggagga ggaggctgcc cggcagcggc agcgcatcaa1320ggagctggag gagatgcagc agcggttgca ggaggccctg caactagagg tgaaagctcg1380gcgagatgaa gaatctgtgc gaatcgctca gaccagactg ctggaagagg aggaagagaa1440gctgaagcag ttgatgcagc tgaaggagga gcaggagcgc tacatcgaac gggcgcagca1500ggagaaggaa gagctgcagc aggagatggc acagcagagc cgctccctgc agcaggccca1560gcagcagctg gaggaggtgc ggcagaaccg gcagagggct gacgaggatg tggaggctgc1620ccagagaaaa ctgcgccagg ccagcaccaa cgtgaaacac tggaatgtcc agatgaaccg1680gctgatgcat ccaattgagc ctggagataa gcgtccggtc acaagcagct ccttctcagg1740cttccagccc cctctgcttg cccaccgtga ctcctcccta aagcgcctga cccgctgggg1800atcccagggc aacaggaccc cctcgcccaa cagcaatgag cagcagaagt ccctcaatgg1860tggggatgag gctcctgccc cggcttccac ccctcaggaa gataaactgg atccagcacc1920agaaaattag cctctcttag ccccttgttc ttcccaatgt catatccacc aggacctggc1980cacagctggc ctgtgggtga tcccagctct tactaggaga gggagctgag gtcctggtgc2040caggggccca ggccctccaa ccataaacag tccaggatgg aacctggttc acccttcata2100ccagctccaa gccccagacc atgggagctg tctgggatgt tgatccttga gaacttggcc2160ctgtgcttta gacccaagga cccgattcct gggctaggaa agagagaaca agcaagccgg2220ggctacctgc ccccaggtgg ccaccaagtt gtggaagcac atttctaaat aaaaactgct2280cttagaatga aaaaaaaaaa aaaaaaactc gag 2313<210>158<211>2114<212>DNA<213>智人(Homo sapiens)<400>158gaattcggca cgaggaagaa ctcgcctctg ttgagtgtaa gtagccaaac aataaccaag 60gagaataaca gaaatgtcca tttggagcac tcagagcaga atcctggttc atcagcaggt 120gacacctcag cagcgcacca ggtggtttta ggagaaaact tgatagccac agccctttgt 180ctttctggca gtgggtctca gtctgatttg aaggatgtgg ccagcacagc aggagaggag 240ggggacacaa gccttcggga gagcctccat ccagtcactc ggtctcttaa ggcagggtgc 300catactaagc agcttgcctc caggaattgc tctgaagaga aatccccaca aacctccatc 360ctaaaggaag gtaacaggga cacaagcttg gatttccgac ctgtagtgtc tccagcaaat 420ggggttgaag gagtccgagt ggatcaggat gatgatcaag atagctcttc cctgaagctt 480tctcagaaca ttgctgtaca gactgacttt aagacagctg attcagaggt aaacacagat 540caagatattg aaaagaattt ggataaaatg atgacagaga gaaccctgtt gaaagagcgt 600taccaggagg tcctggacaa acagaggcaa gtggagaatc agctccaagt gcaattaaag 660cagcttcagc aaaggagaga agaggaaatg aagaatcacc aggagatatt aaaggctatt 720caggatgtga caataaagcg ggaagaaaca aagaagaaga tagagaaaga gaagaaggag 780tttttgcaga aggagcagga tctgaaagct gaaattgaga agctttgtga gaagggcaga 840agagaggtgt gggaaatgga actggataga ctcaagaatc aggatggcga aataaatagg 900aacattatgg aagagactga acgggcctgg aaggcagaga tcttatcact agagagccgg 960aaagagttac tggtactgaa actagaagaa gcagaaaaag aggcagaatt gcaccttact1020tacctcaagt caactccccc aacactggag acagttcgtt ccaaacagga gtgggagacg1080agactgaatg gagttcggat aatgaaaaag aatgttcgtg accaatttaa tagtcatatc1140cagttagtga ggaacggagc caagctgagc agccttcctc aaatccctac tcccacttta1200cctccacccc catcagagac agacttcatg cttcaggtgt ttcaacccag tccctctctg1260gctcctcgga tgcccttctc cattgggcag gtcacaatgc ccatggttat gcccagtgca1320gatccccgct ccttgtcttt cccaatcctg aaccctgccc tttcccagcc cagccagcct1380tcctcacccc ttcctggctc ccatggcaga aatagccctg gcttgggttc ccttgtcagc1440cctggtgccg aattcggcac gaggtaccac tggtctgtgt gctagaggag ggtgttgcca1500tagaaccagt ggccacagtt gtggtggtgg tggtcagcac tgtgggggtg tgggtggtcc1560ccgggacgga ggagggggtc accgtgaagc cactggttgt gggtgtggtg gttgtgctga1620tccacactgg aggcgtgcgt gccgtccctg ggctgaagga gggggtgact gtgaagcccg1680tggttgtggt agtcggcact ttggtagtgt gagctgttcc tggggtggaa gagggggtgg1740ccacagagcc ggtggccctg gttgtggtgg ccgtggtggt aagcactgtg gaggtgtggg1800cagtctctgg agtggaggag ggtgtggctg tggacatggt ggccgtgggt gtggtggtct1860gtgataggcg ggtccaggtg gtgcccaggg aggaggaggg gatggctgta aagctggtag1920ctgtgggtgt ggtggctgtg cttctcagtg ctggaagggc ggttgcagtc cctggactgg1980agaagggagt ggctttggag ctggtgactg tgggtgtcgt ggccgtggtg ctcacatgtg2040gggtgccagc agttgcctgg gtggaggagg cggtggccgt ggatccggtg ggcaccgtca2100cgggagtact tcta 2114<210>159<211>278<212>DNA<213>智人(Homo sapiens)<400>159gaattcggca caggtaactt tgcctggggt atttaaaaaa aaaaaaaaaa aaaaaaaaag 60tcaaatatct gagtactaat ttcctgaaaa gtatgttccg atagatgaac agatcattaa120tgcagaatga gaatcactcc taaaataggt aatggtaaaa attaaattga caattacctc180tctctatgca gaaggaaata tcacctatat gacatcatca tcatctattg atacttgctg240gcagtgctaa taatggtttt aatgccaatt tgtaagaa278<210>160<211>848<212>DNA<213>智人(Homo sapiens)<400>160gaattcggca cgagccccag aggagctcgg cctgcgctgc gccacgatgt ccggggagtc 60agccaggagc ttggggaagg gaagcgcgcc cccggggccg gtcccggagg gctcgatccg120catctacagc atgaggttct gcccgtttgc tgagaggacg cgtctagtcc tgaaggccaa180gggaatcagg catgaagtca tcaatatcaa cctgaaaaat aagcctgagt ggttctttaa240gaaaaatccc tttggtctgg tgccagttct ggaaaacagt cagggtcagc tgatctacga300gtctgccatc acctgtgagt acctggatga agcataccca gggaagaagc tgttgccgga360tgacccctat gagaaagctt gccagaagat gatcttagag ttgttttcta aggtgccatc420cttggtagga agctttatta gaagccaaaa taaagaagac tatgctggcc taaaagaaga480atttcgtaaa gaatttacca agctagagga ggttctgact aataagaaga cgaccttctt540tggtggcaat tctatctcta tgattgatta cctcatctgg ccctggtttg aacggctgga600agcaatgaag ttaaatgagt gtgtagacca cactccaaaa ctgaaactgt ggatggcagc660catgaaggaa gatcccacag tctcagccct gcttactagt gagaaagact ggcaaggttt720cctagagctc tacttacaga acagccctga ggcctgtgac tatgggctct gaagggggca780ggagtcagca ataaagctat gtctgatatt ttccttcact aaaaaaaaaa aaaaaaaaaa840aactcgag 848<210>161<211>432<212>DNA<213>智人(Homo sapiens)<400>161gaattcggca cgagggcaga ccaagatcct ggaggaggac ctggaacaga tcaagctgtc 60cttgagagag cgaggccggg agctgaccac tcagaggcag ctgatgcagg aacgggcaga120ggaagggaag ggcccaagta aagcacagcg cgggagccta gagcacatga agctgatcct180gcgtgataag gagaaggagg tggaatgtca gcaggagcat atccatgaac tccaggagct240caaagaccag ctggagcagc agctccaggg cctgcacagg aaggtaggtg agaccagcct300cctcctgtcc cagcgagagc aggaaatagt ggtcctgcag cagcaactgc aggaagccag360ggaacaaggg gagctgaagg agcagtcact tcagagtcaa ctggatgagg cccagagagc420cctagcccag ag432<210>162<211>433<212>DNA<213>智人(Homo sapiens)<400>162gattcggcac gagccggagc tgggttgctc ctgctcccgt ctccaagtcc tggtacctcc 60ttcaagctgg gagagggctc tagtccctgg ttctgaacac tctggggttc tcgggtgcag120gccgccatga gcaaacggaa ggcgccgcag gagactctca acgggggaat caccgacatg180ctcacagaac tcgcaaactt tgagaagaac gtgagccaag ctatccacaa gtacaatgct240tacagaaaag cagcatctgt tatagcaaaa tacccacaca aaataaagag tggagctgaa300gctaagaaat tgcctggagt aggaacaaaa attgctgaaa agattgatga gtttttagca360actggaaaat tacgtaaact ggaaaagatt cggcaggatg atacgagttc atccatcaat420ttcctgactc gag 433<210>163<211>432<212>DNA<213>智人(Homo sapiens)<400>163gaattcggca ccagatgagg ccaacgaggt gacggacagc gcgtacatgg gctccgagag 60cacctacagt gagtgtgaga ccttcacgga cgaggacacc agcaccctgg tgcaccctga120gctgcaacct gaaggggacg cagacagtgc cggcggctcg gccgtgccct ctgagtgcct180ggacgccatg gaggagcccg accatggtgc cctgctgctg ctcccaggca ggcctcaccc240ccatggccag tctgtcatca cggtgatcgg gggcgaggag cactttgagg actacggtga300aggcagtgag gcggagctgt ccccagagac cctatgcaac gggcagctgg gctgcagtga360ccccgctttc ctcacgccca gtccgacaaa gcggctctcc agcaagaagg tggcaaggta420cctgcaccag tc432<210>164<211>395<212>DNA<213>智人(Homo sapiens)<400>164gacacttgaa tcatgggtga cgttaaaaat tttctgtatg cctggtgtgg caaaaggaag 60atgaccccat cctatgaaat tagagcagtg gggaacaaaa acaggcagaa attcatgtgt120gaggttcagg tggaaggtta taattacact ggcatgggaa attccaccaa taaaaaagat180gcacaaagca atgctgccag agactttgtt aactatttgg ttcgaataaa tgaaataaag240agtgaagaag ttccagcttt tggggtagca tctccgcccc cacttactga tactcctgac300actacagcaa atgctgaagg catcttgttg acatcgaata tgactttgat aataaatacc360ggttcctgaa aaaaaaaaaa aaaaaaaaac tcgag 395<210>165<211>503<212>DNA<213>智人(Homo sapiens)<400>165gaattcggca ccaggaacgc tcggtgagag gcggaggagc ggtaactacc ccggttgcgc 60acagctcggc gctccttccc gctccctcac acaccggcct cagcccgcac cggcagtaga120agatggtgaa agaaacaact tactacgatg ttttgggggt caaacccaat gctactcagg180aagaattgaa aaaggcttat aggaaactgg ccttgaagta ccatcctgat aagaacccaa240atgaaggaga gaagtttaaa cagatttctc aagcttacga agttctctct gatgcaaaga300aaagggaatt atatgacaaa ggaggagaac aggcaattaa agagggtgga gcaggtggcg360gttttggctc ccccatggac atctttgata tgttttttgg aggaggagga aggatgcaga420gagaaaggag aggtaaaaat gttgtacatc agctctcagt aaccctagaa gacttatata480atggtgcaac aagaaaactg gct503<210>166<211>893<212>DNA<213>智人(Homo sapiens)<400>166gaattcggca cgagaggaac ttctcttgac gagaagagag accaaggagg ccaagcaggg 60gctgggccag aggtgccaac atggggaaac tgaggctcgg ctcggaaggg tgagagtgag120actacatctc aaaaaaaaaa aaaaaaaaaa aaaagaaaga aaagaaaaga aaaaagaaag180aacggaagta gttgtaggta gtggtatggt ggtatgagtc tgttttctgt tacttataac240aacaacaaca acaaaaaacg ctgaaactgg gtaatttata aagaaaagga aaaaaagcag300aaaaaaatca ggaagaagag aaaggaaaag aagacaaata aatgaaattt atgtattaca360gttctgaagg ctgagacatc ccaggtcaag ggtccacact tggcgagggc tttcttgctg420gtggagactc tttgtggagt cctgggacag tgcagaagga tcacgcctcc ctaccgctcc480aagcccagcc ctcagccatg gcatgccccc tggatcaggc cattggcctc ctcgtggcca540tcttccacaa gtactccggc agggagggtg acaagcacac cctgagcaag aaggagctga600aggagctgat ccagaaggag ctcaccattg gctcgaagct gcaggatgct gaaattgcaa660ggctgatgga agacttggac cggaacaagg accaggaggt gaacttccag gagtatgtca720ccttcctggg ggccttggct ttgatctaca atgaagccct caagggctga aaataaatag780ggaagatgga gacaccctct gggggtcctc tctgagtcaa atccagtggt gggtaattgt840acaataaatt ttttttggtc aaatttaaaa aaaaaaaaaa aaaaaaactc gag 893<210>167<211>549<212>DNA<213>智人(Homo sapiens)<400>167gaattcggca cgagcccaga tcccgaggtc cgacagcgcc cggcccagat ccccacgcct 60gccaggagca agccgagagc cagccggccg gcgcactccg actccgagca gtctctgtcc120ttcgacccga gccccgcgcc ctttccggga cccctgcccc gcgggcagcg ctgccaacct180gccggccatg gagaccccgt cccagcggcg cgccacccgc agcggggcgc aggccagctc240cactccgctg tcgcccaccc gcatcacccg gctgcaggag aaggaggacc tgcaggagct300caatgatcgc ttggcggtct acatcgaccg tgtgcgctcg ctggaaacgg agaacgcagg360gctgcgcctt cgcatcaccg agtctgaaga ggtggtcagc cgcgaggtgt ccggcatcaa420ggccgcctac gaggccgagc tcggggatgc ccgcaagacc cttgactcag tagccaagga480gcgcgcccgc ctgcagctgg agctgagcaa agtgcgtgaa gagtttaagg agctgaaagc540gcgcaatac549<210>168<211>547<212>DNA<213>智人(Homo sapiens)<400>168gaattcggca cgagatggcg gcaggggtcg aagcggcggc ggaggtggcg gcgacggaga 60tcaaaatgga ggaagagagc ggcgcgcccg gcgtgccgag cggcaacggg gctccgggcc120ctaagggtga aggagaacga cctgctcaga atgagaagag gaaggagaaa aacataaaaa180gaggaggcaa tcgctttgag ccatatgcca atccaactaa aagatacaga gccttcatta240caaacatacc ttttgatgtg aaatggcagt cacttaaaga cctggttaaa gaaaaagttg300gtgaggtaac atacgtggag ctcttaatgg acgctgaagg aaagtcaagg ggatgtgctg360ttgttgaatt caagatggaa gagagcatga aaaaagctgc ggaagtccta aacaagcata420gtctgagcgg aagaccactg aaagtcaaag aagatcctga tggtgaacat gccaggagag480caatgcaaaa ggctggaaga cttggaagca cagtatttgt agcaaatctg gattataaag540ttggctg 547<210>169<211>547<212>DNA<213>智人(Homo sapiens)<400>169gaattcggca ccaggagtcc gactgtgctc gctgctcagc gccgcacccg gaagatgagg 60ctcgccgtgg gagccctgct ggtctgcgcc gtcctggggc tgtgtctggc tgtccctgat120aaaactgtga gatggtgtgc agtgtcggag catgaggcca ctaagtgcca gagtttccgc180gaccatatga aaagcgtcat tccatccgat ggtcccagtg ttgcttgtgt gaagaaagcc240tcctaccttg attgcatcag ggccattgcg gcaaacgaag cggatgctgt gacactggat300gcaggtttgg tgtatgatgc ttacctggct cccaataacc tgaagcctgt ggtggcagag360ttctatgggt caaaagagga tccacagact ttctattatg ctgttgctgt ggtgaagaag420gatagtggct tccagatgaa ccagcttcga ggcaagaagt cctgccacac gggtctaggc480aggtccgctg ggtggaacat ccccataggc ttactttact gtgacttacc tgagccacgt540aaacctc 547<210>170<211>838<212>DNA<213>智人(Homo sapiens)<400>170gaattcggca ccagaggagc tcggcctgcg ctgcgccacg atgtccgggg agtcagccag 60gagcttgggg aagggaagcg cgcccccggg gccggtcccg gagggctcga tccgcatcta120cagcatgagg ttctgcccgt ttgctgagag gacgcgtcta gtcctgaagg ccaagggaat180caggcatgaa gtcatcaata tcaacctgaa aaataagcct gagtggttct ttaagaaaaa240tccctttggt ctggtgccag ttctggaaaa cagtcagggt cagctgatct acgagtctgc300catcacctgt gagtacctgg atgaagcata cccagggaag aagctgttgc cggatgaccc360ctatgagaaa gcttgccaga agatgatctt agagttgttt tctaaggtgc catccttggt420aggaagcttt attagaagcc aaaataaaga agactatgat ggcctaaaag aagaatttcg480taaagaattt accaagctag aggaggttct gactaataag aagacgacct tctttggtgg540caattctatc tctatgattg attacctcat ctggccctgg tttgaacggc tggaagcaat600gaagttaaat gagtgtgtag accacactcc aaaactgaaa ctgtggatgg cagccatgaa660ggaagatccc acagtctcag ccctgcttac tagtgagaaa gactggcaag gtttcctaga720gctctactta cagaacagcc ctgaggcctg tgactatggg ctctgaaggg ggcaggagtc780agcaataaag ctatgtctga tattttcctt cactaaaaaa aaaaaaaaaa aactcgag 838
<210>171<211>547<212>DNA<213>智人(Homo sapiens)<400>171gaattcggca ccagcgggat ttgggtcgca gttcttgttt gtggattgct gtgatcgtca 60cttgacaatg cagatcttcg tgaagactct gactggtaag accatcaccc tcgaggttga120gcccagtgac accatcgaga atgtcaaggc aaagatccaa gataaggaag gcatccctcc180tgaccagcag aggctgatct ttgctggaaa acagctggaa gatgggcgca ccctgtctga240ctacaacatc cagaaagagt ccaccctgca cctggtgctc cgtctcagag gtgggatgca300aatcttcgtg aagacactca ctggcaagac catcaccctt gaggtcgagc ccagtgacac360catcgagaac gtcaaagcaa agatccagga caaggaaggc attcctcctg accagcagag420gttgatcttt gccggaaagc agctggaaga tgggcgcacc ctgtctgact acaacatcca480gaaagagtct accctgcacc tggtgctccg tctcagaggt gggatgcaga tcttcgtgaa540gaccctg 547<210>172<211>608<212>DNA<213>智人(Homo sapiens)<400>172gaattcggca ccagagactt ctccctctga ggcctgcgca cccctcctca tcagcctgtc 60caccctcatc tacaatggtg ccctgccatg tcagtgcaac cctcaaggtt cactgagttc120tgagtgcaac cctcatggtg gtcagtgcct gtgcaagcct ggagtggttg ggcgccgctg180tgacctctgt gcccctggct actatggctt tggccccaca ggctgtcaag gcgcttgcct240gggctgccgt gatcacacag ggggtgagca ctgtgaaagg tgcattgctg gtttccacgg300ggacccacgg ctgccatatg ggggccagtg ccggccctgt ccctgtcctg aaggccctgg360gagccaacgg cactttgcta cttcttgcca ccaggatgaa tattcccagc agattgtgtg420ccactgccgg gcaggctata cggggctgcg atgtgaagct tgtgcccctg ggcactttgg480ggacccatca aggccaggtg gccggtgcca actgtgtgag tgcagtggga acattgaccc540aatggatcct gatgcctgtg acccccacac ggggcaatgc ctgcgctgtt tacaccacac600agagggtc 608<210>173<211>543<212>DNA<213>智人(Homo sapiens)<400>173gaattcggca ccagagatca tccgccagca gggtctggcc tcctacgact acgtgcgccg 60ccgcctcacg gctgaggacc tgttcgaggc tcggatcatc tctctcgaga cctacaacct120gctccgggag ggcaccagga gcctccgtga ggctctcgag gcggagtccg cctggtgcta180cctctatggc acgggctccg tggctggtgt ctacctgccc ggttccaggc agacactgag240catctaccag gctctcaaga aagggctgct gagtgccgag gtggcccgcc tgctgctgga300ggcacaggca gccacaggct tcctgctgga cccggtgaag ggggaacggc tgactgtgga360tgaagctgtg cggaagggcc tcgtggggcc cgaactgcac gaccgcctgc tctcggctga420gcgggcggtc accggctacc gtgaccccta caccgagcag accatctcgc tcttccaggc480catgaagaag gaactgatcc ctactgagga ggccctgcgg ctgtggatgc ccagctggcc540acc 543<210>174<211>548<212>DNA<213>智人(Homo sapiens)<400>174gaattcggca cgagaaatgg cggcaggggt cgaagcggcg gcggaggtgg cggcgacgga 60gatcaaaatg gaggaagaga gcggcgcgcc cggcgtgccg agcggcaacg gggctccggg120ccctaagggt gaaggagaac gacctgctca gaatgagaag aggaaggaga aaaacataaa180aagaggaggc aatcgctttg agccatatgc caatccaact aaaagataca gagccttcat240tacaaacata ccttttgatg tgaaatggca gtcacttaaa gacctggtta aagaaaaagt300tggtgaggta acatacgtgg agctcttaat ggacgctgaa ggaaagtcaa ggggatgtgc360tgttgttgaa ttcaagatgg aagagagcat gaaaaaagct gcggaagtcc taaacaagca420tagtctgagc ggaagaccac tgaaagtcaa agaagatcct gatggtgaac atgccaggag480agcaatgcaa aaggtgatgg ctacgactgg tgggatgggt atgggaccag gtggcccagg540aatgatta 548<210>175<211>604<212>DNA<213>智人(Homo sapiens)<400>175gaattcggca ccagaggacc tccaggacat gttcatcgtc cataccatcg aggagattga 60gggcctgatc tcagcccatg accagttcaa gtccaccctg ccggacgccg atagggagcg120cgaggccatc ctggccatcc acaaggaggc ccagaggatc gctgagagca accacatcaa180gctgtcgggc agcaacccct acaccaccgt caccccgcaa atcatcaact ccaagtggga240gaaggtgcag cagctggtgc caaaacggga ccatgccctc ctggaggagc agagcaagca300gcagtccaac gagcacctgc gccgccagtt cgccagccag gccaatgttg tggggccctg360gatccagacc aagatggagg agatcgggcg catctccatt gagatgaacg ggaccctgga420ggaccagctg agccacctga agcagtatga acgcagcatc gtggactaca agcccaacct480ggacctgctg gagcagcagc accagcttat ccaggaggcc ctcatcttcg acaacaagca540caccaactat accatggagc acatccgcgt gggctgggag cagctgctca ccaccattgc600ccgg 604<210>176<211>486<212>DNA<213>智人(Homo sapiens)<400>176gaattcggca ccagccaagc tcactattga atccacgccg ttcaatgtcg cagaggggaa 60ggaggttctt ctactcgccc acaacctgcc ccagaatcgt attggttaca gctggtacaa120aggcgaaaga gtggatggca acagtctaat tgtaggatat gtaataggaa ctcaacaagc180taccccaggg cccgcataca gtggtcgaga gacaatatac cccaatgcat ccctgctgat240ccagaacgtc acccagaatg acacaggatt ctatacccta caagtcataa agtcagatct300tgtgaatgaa gaagcaaccg gacagttcca tgtatacccg gagctgccca agccctccat360ctccagcaac aactccaacc ccgtggagga caaggatgct gtggccttca cctgtgaacc420tgaggttcag aacacaacct acctgtggtg ggtaaatggt cagagcctcc cggtcagtcc480caaggc 486<210>177<211>387<212>DNA<213>智人(Homo sapiens)<400>177gaattcggca ccagggacag cagaccagac agtcacagca gccttgacaa aacgttcctg 60gaactcaagc tcttctccac agaggaggac agagcagaca gcagagacca tggagtctcc120ctcggcccct ccccacagat ggtgcatccc ctggcagagg ctcctgctca cagcctcact180tctaaccttc tggaacccgc ccaccactgc caagctcact attgaatcca cgccgttcaa240tgtcgcagag gggaaggagg tgcttctact tgtccacaat ctgccccagc atctttttgg300ctacagctgg tacaaaggtg aaagagtgga tggcaaccgt caaattatag gatatgtaat360aggaactcaa caagctaccc cagggcc387
<210>178<211>440<212>DNA<213>智人(Homo sapiens)<400>178gaattcggca cgaggagaag cagaaaaaca aggaatttag ccagacttta gaaaatgaga 60aaaatacctt actgagtcag atatcaacaa aggatggtga actaaaaatg cttcaggagg120aagtaaccaa aatgaacctg ttaaatcagc aaatccaaga agaactctct agagttacca180aactaaagga gacagcagaa gaagagaaag atgatttgga agagaggctt atgaatcaat240tagcagaact taatggaagc attgggaatt actgtcagga tgttacagat gcccaaataa300aaaatgagct attggaatct gaaatgaaga accttaaaaa gtgtgtgagt gaattggaag360aagaaaagca gcagttagtc aaggaaaaaa ctaaggtgga atcagaaata cgaaaggaat420atttggagaa aatacaaggt 440<210>179<211>443<212>DNA<213>智人(Homo sapiens)<400>179gaattcggca ccagcggggg gctacggcgg cggctacggc ggcgtcctga ccgcgtccga 60cgggctgctg gcgggcaacg agaagctaac catgcagaac ctcaacgacc gcctggcctc120ctacctggac aaggtgcgcg ccctggaggc ggccaacggc gagctagagg tgaagatccg180cgactggtac cagaagcagg ggcctgggcc ctcccgcgac tacagccact actacacgac240catccaggac ctgcgggaca agattcttgg tgccaccatt gagaactcca ggattgtcct300gcagatcgac aacgcccgtc tggctgcaga tgacttccga accaagtttg agacggaaca360ggctctgcgc atgagcgtgg aggccgacat caacggcctg cgcagggtgc tggatgagct420gaccctggcc aggaccgacc tgg443<210>180<211>403<212>DNA<213>智人(Homo sapiens)<400>180gaattcggca cgaggttatg agagtcgact tcaatgttcc tatgaagaac aaccagataa 60caaacaacca gaggattaag gctgctgtcc caagcatcaa attctgcttg gacaatggag120ccaagtcggt agtccttatg agccacctag gccggcctga tggtgtgccc atgcctgaca180agtactcctt agagccagtt gctgtagaac tcagatctct gctgggcaag gatgttctgt240tcttgaagga ctgtgtaggc ccagaagtgg agaaagcctg tgccaaccca gctgctgggt300ctgtcatcct gctggagaac ctccgctttc atgtggagga agaagggaag ggaaaagatg360cttctgggaa caaggttaaa gccgagccag ccaaaataga agc 403<210>181<211>493<212>DNA<213>智人(Homo sapiens)<400>181gaattcggca ccagcagagg tctccagagc cttctctctc ctgtgcaaaa tggcaactct 60taaggaaaaa ctcattgcac cagttgcgga agaagaggca acagttccaa acaataagat120cactgtagtg ggtgttggac aagttggtat ggcgtgtgct atcagcattc tgggaaagtc180tctggctgat gaacttgctc ttgtggatgt tttggaagat aagcttaaag gagaaatgat240ggatctgcag catgggagct tatttcttca gacacctaaa attgtggcag ataaagatta300ttctgtgacc gccaattcta agattgtagt ggtaactgca ggagtccgtc agcaagaagg360ggagagtcgg ctcaatctgg tgcagagaaa tgttaatgtc ttcaaattca ttattcctca420gatcgtcaag tacagtcctg attgcatcat aattgtggtt tccaacccag tggacattct480tacgtatgtt acc 493<210>182<211>209<212>PRT<213>智人(Homo sapiens)<400>182Ala Phe Ser Ser Asn Pro Lys Val Gln Val Glu Ala Ile Glu Gly Gly1 5 10 15Ala Leu Gln Lys Leu Leu Val Ile Leu Ala Thr Glu Gln Pro Leu Thr20 25 30Ala Lys Lys Lys Val Leu Phe Ala Leu Cys Ser Leu Leu Arg His Phe35 40 45Pro Tyr Ala Gln Arg Gln Phe Leu Lys Leu Gly Gly Leu Gln Val Leu50 55 60Arg Thr Leu Val Gln Glu Lys Gly Thr Glu Val Leu Ala Val Arg Val65 70 75 80Val Thr Leu Leu Tyr Asp Leu Val Thr Glu Lys Met Phe Ala Glu Glu85 90 95Glu Ala Glu Leu Thr Gln Glu Met Ser Pro Glu Lys Leu Gln Gln Tyr100 105 110Arg Gln Val His Leu Leu Pro Gly Leu Trp Glu Gln Gly Trp Cys Glu115 120 125Ile Thr Ala His Leu Leu Ala Leu Pro Glu His Asp Ala Arg Glu Lys130 135 140Val Leu Gln Thr Leu Gly Val Leu Leu Thr Thr Cys Arg Asp Arg Tyr145 150 155 160Arg Gln Asp Pro Gln Leu Gly Arg Thr Leu Ala Ser Leu Gln Ala Glu165 170 175Tyr Gln Val Leu Ala Ser Leu Glu Leu Gln Asp Gly Glu Asp Glu Gly180 185 190Tyr Phe Gln Glu Leu Leu Gly Ser Val Asn Ser Leu Leu Lys Glu Leu195 200 205Arg<210>183<211>255<212>PRT<213>智人(Homo sapiens)<400>183Met Ala Ala Gly Val Glu Ala Ala Ala Glu Val Ala Ala Thr Glu Pro1 5 10 15Lys Met Glu Glu Glu Ser Gly Ala Pro Cys Val Pro Ser Gly Asn Gly20 25 30Ala Pro Gly Pro Lys Gly Glu Glu Arg Pro Thr Gln Asn Glu Lys Arg35 40 45Lys Glu Lys Asn Ile Lys Arg Gly Gly Asn Arg Phe Glu Pro Tyr Ser50 55 60Asn Pro Thr Lys Arg Tyr Arg Ala Phe Ile Thr Asn Ile Pro Phe Asp65 70 75 80Val Lys Trp Gln Ser Leu Lys Asp Leu Val Lys Glu Lys Val Gly Glu85 90 95Val Thr Tyr Val Glu Leu Leu Met Asp Ala Glu Gly Lys Ser Arg Gly100 105 110Cys Ala Val Val Glu Phe Lys Met Glu Glu Ser Met Lys Lys Ala Ala115 120 125Glu Val Leu Asn Lys His Ser Leu Ser Gly Arg Pro Leu Lys Val Lys130 135 140Glu Asp Pro Asp Gly Glu His Ala Arg Arg Ala Met Gln Lys Ala Gly145 150 155 160Arg Leu Gly Ser Thr Val Phe Val Ala Asn Leu Asp Tyr Lys Val Gly165 170 175Trp Lys Lys Leu Lys Glu Val Phe Ser Met Ala Gly Val Val Val Arg180 185 190Ala Asp Ile Leu Glu Asp Lys Asp Gly Lys Ser Arg Gly Ile Gly Ile195 200 205Val Thr Phe Glu Gln Ser Ile Glu Ala Val Gln Ala Ile Ser Met Phe210 215 220Asn Gly Gln Leu Leu Phe Asp Arg Pro Met His Val Lys Met Asp Glu225 230 235 240Arg Ala Leu Pro Lys Gly Asp Phe Phe Pro Pro Glu Arg His Ser245 250 255<210>184<211>188<212>PRT<213>智人(Homo sapiens)<400>184Leu Ser Gly Ser Cys Ile Arg Arg Glu Gln Thr Pro Glu Lys Glu Lys1 5 10 15Gln Val Val Leu Phe Glu Glu Ala Ser Trp Thr Cys Thr Pro Ala Cys20 25 30Gly Asp Glu Pro Arg Thr Val Ile Leu Leu Ser Ser Met Leu Ala Asp35 40 45His Arg Leu Lys Leu Glu Asp Tyr Lys Asp Arg Leu Lys Ser Gly Glu50 55 60His Leu Asn Pro Asp Gln Leu Glu Ala Val Glu Lys Tyr Glu Glu Val65 70 75 80Leu His Asn Leu Glu Phe Ala Lys Glu Leu Gln Lys Thr Phe Ser Gly85 90 95Leu Ser Leu Asp Leu Leu Lys Ala Gln Lys Lys Ala Gln Arg Arg Glu100 105 110His Met Leu Lys Leu Glu Ala G1u Lys Lys Lys Leu Arg Thr Ile Leu115 120 125Gln Val Gln Tyr Val Leu Gln Asn Leu Thr Gln Glu His Val Gln Lys130 135 140Asp Phe Lys Gly Gly Leu Asn Gly Ala Val Tyr Leu Pro Ser Lys Glu145 150 155 160Leu Asp Tyr Leu Ile Lys Phe Ser Lys Leu Thr Cys Pro Glu Arg Asn165 170 175Glu Ser Leu Arg Gln Thr Leu Glu Gly Ser Thr Val180 185<210>185<211>746<212>PRT<213>智人(Homo sapiens)<400>185Asp Lys His Leu Lys Asp Leu Leu Ser Lys Leu Leu Asn Ser Gly Tyr1 5 10 15Phe Glu Ser Ile Pro Val Pro Lys Asn Ala Lys Glu Lys Glu Val Pro20 25 30Leu Glu Glu Glu Met Leu Ile Gln Ser Glu Lys Lys Thr Gln Leu Ser35 40 45Lys Thr Glu Ser Val Lys Glu Ser Glu Ser Leu Met Glu Phe Ala Gln50 55 60Pro Glu Ile Gln Pro Gln Glu Phe Leu Asn Arg Arg Tyr Met Thr Glu65 70 75 80Val Asp Tyr Ser Asn Lys Gln Gly Glu Glu Gln Pro Trp Glu Ala Asp85 90 95Tyr Ala Arg Lys Pro Asn Leu Pro Lys Arg Trp Asp Met Leu Thr Glu100 105 110Pro Asp Gly Gln Glu Lys Lys Gln Glu Ser Phe Lys Ser Trp Glu Ala115 120 125Ser Gly Lys His Gln Glu Val Ser Lys Pro Ala Val Ser Leu Glu Gln130 135 140Arg Lys Gln Asp Thr Ser Lys Leu Arg Ser Thr Leu Pro Glu Glu Gln145 150 155 160Lys Lys Gln Glu Ile Ser Lys Ser Lys Pro Ser Pro Ser Gln Trp Lys165 170 175Gln Asp Thr Pro Lys Ser Lys Ala Gly Tyr Val Gln Glu Glu Gln Lys180 185 190Lys Gln Glu Thr Pro Lys Leu Trp Pro Val Gln Leu Gln Lys Glu Gln195 200 205Asp Pro Lys Lys Gln Thr Pro Lys Ser Trp Thr Pro Ser Met Gln Ser210 215 220Glu Gln Asn Thr Thr Lys Ser Trp Thr Thr Pro Met Cys Glu Glu Gln225 230 235 240Asp Ser Lys Gln Pro Glu Thr Pro Lys Ser Trp Glu Asn Asn Val Glu245 250 255Ser Gln Lys His Ser Leu Thr Ser Gln Ser Gln Ile Ser Pro Lys Ser260 265 270Trp Gly Val Ala Thr Ala Ser Leu Ile Pro Asn Asp Gln Leu Leu Pro275 280 285Arg Lys Leu Asn Thr Glu Pro Lys Asp Val Pro Lys Pro Val His Gln290 295 300Pro Val Gly Ser Ser Ser Thr Leu Pro Lys Asp Pro Val Leu Arg Lys305 310 315 320Glu Lys Leu Gln Asp Leu Met Thr Gln Ile Gln Gly Thr Cys Asn Phe325 330 335Met Gln Glu Ser Val Leu Asp Phe Asp Lys Pro Ser Ser Ala Ile Pro340 345 350Thr Ser Gln Pro Pro Ser Ala Thr Pro Gly Ser Pro Val Ala Ser Lys355 360 365Glu Gln Asn Leu Ser Ser Gln Ser Asp Phe Leu Gln Glu Pro Leu Gln370 375 380Val Phe Asn Val Asn Ala Pro Leu Pro Pro Arg Lys Glu Gln Glu Ile385 390 395 400Lys Glu Ser Pro Tyr Ser Pro Gly Tyr Asn Gln Ser Phe Thr Thr Ala405 410 415Ser Thr Gln Thr Pro Pro Gln Cys Gln Leu Pro Ser Ile His Val Glu420 425 430Gln Thr Val His Ser Gln Glu Thr Ala Ala Asn Tyr His Pro Asp Gly435 440 445Thr Ile Gln Val Ser Asn Gly Ser Leu Ala Phe Tyr Pro Ala Gln Thr450 455 460Asn Val Phe Pro Arg Pro Thr Gln Pro Phe Val Asn Ser Arg Gly Ser465 470 475 480Val Arg Gly Cys Thr Arg Gly Gly Arg Leu Ile Thr Asn Ser Tyr Arg485 490 495Ser Pro Gly Gly Tyr Lys Gly phe Asp Thr Tyr Arg Gly Leu Pro Ser500 505 510Ile Ser Asn Gly Asn Tyr Ser Gln Leu Gln Phe Gln Ala Arg Glu Tyr515 520 525Ser Gly Ala Pro Tyr Ser Gln Arg Asp Asn Phe Gln Gln Cys Tyr Lys530 535 540Arg Gly Gly Thr Ser Gly Gly Pro Arg Ala Asn Ser Arg Ala Gly Trp545 550 555 560Ser Asp Ser Ser Gln Val Ser Ser Pro Glu Arg Asp Asn Glu Thr Phe565 570 575Asn Ser Gly Asp Ser Gly Gln Gly Asp Ser Arg Ser Met Thr Pro Val580 585 590Asp Val Pro Val Thr Asn Pro Ala Ala Thr Ile Leu Pro Val His Val595 600 605Tyr Pro Leu Pro Gln Gln Met Arg Val Ala Phe Ser Ala Ala Arg Thr610 615 620Ser Asn Leu Ala Pro GlV Thr Leu Asp Gln Pro Ile Val Phe Asp Leu625 630 635 640Leu Leu Asn Asn Leu Gly Glu Thr Phe Asp Leu Gln Leu Gly Arg Phe645 650 655Asn Cys Pro Val Asn Gly Thr Tyr Val Phe Ile Phe His Met Leu Lys660 665 670Leu Ala Val Asn Val Pro Leu Tyr Val Asn Leu Met Lys Asn Glu Glu675 680 685Val Leu Val Ser Ala Tyr Ala Asn Asp Gly Ala Pro Asp His Glu Thr690 695 700Ala Ser Asn His Ala Ile Leu Gln Leu Phe Gln Gly Asp Gln Ile Trp705 710 715 720Leu Arg Leu His Arg Gly Ala Ile Tyr Gly Ser Ser Trp Lys Tyr Ser725 730 735Thr Phe Ser Gly Tyr Leu Leu Tyr Gln Asp740 745<210>186<211>705<212>PRT<213>智人(Homo sapiens)<400>186Ala Leu Leu Asn Val Arg Gln Pro Pro Ser Thr Thr Thr Phe Val Leu1 5 10 15Asn Gln Ile Asn His Leu Pro Pro Leu Gly Ser Thr Ile Val Met Thr20 25 30Lys Thr Pro Pro Val Thr Thr Asn Arg Gln Thr Ile Thr Leu Thr Lys35 40 45Phe Ile Gln Thr Thr Ala Ser Thr Arg Pro Ser Val Ser Ala Pro Thr50 55 60Val Arg Asn Ala Met Thr Ser Ala Pro Ser Lys Asp Gln Val Gln Leu65 70 75 80Lys Asp Leu Leu Lys Asn Asn Ser Leu Asn Glu Leu Met Lys Leu Lys85 90 95Pro Pro Ala Asn Ile Ala Gln Pro Val Ala Thr Ala Ala Thr Asp Val100 105 110Ser Asn Gly Thr Val Lys Lys Glu Ser Ser Asn Lys Glu Gly Ala Arg115 120 125Met Trp Ile Asn Asp Met Lys Met Arg Ser Phe Ser Pro Thr Met Lys
130 135 140Val Pro Val Val Lys Glu Asp Asp Glu Pro Glu Glu Glu Asp Glu Glu145 150 155 160Glu Met Gly His Ala Glu Thr Tyr Ala Glu Tyr Met Pro Ile Lys Leu165 170 175Lys Ile Gly Leu Arg His Pro Asp Ala Val Val Glu Thr Ser Ser Leu180 185 190Ser Ser Val Thr Pro Pro Asp Val Trp Tyr Lys Thr Ser Ile Ser Glu195 200 205Glu Thr Ile Asp Ash Gly Trp Leu Ser Ala Leu Gln Leu Glu Ala Ile210 215 220Thr Tyr Ala Ala Gln Gln His Glu Thr Phe Leu Pro Asn Gly Asp Arg225 230 235 240Ala Gly Phe Leu Ile Gly Asp Gly Ala Gly Val Gly Lys Gly Arg Thr245 250 255Ile Ala Gly Ile Ile Tyr Glu Asn Tyr Leu Leu Ser Arg Lys Arg Ala260 265 270Leu Trp Phe Ser Val Ser Asn Asp Leu Lys Tyr Asp Ala Glu Arg Asp275 280 285Leu Arg Asp Ile Gly Ala Lys Asn Ile Leu Val His Ser Leu Asn Lys290 295 300Phe Lys Tyr Gly Lys Ile Ser Ser Lys His Asn Gly Ser Val Lys Lys305 310 315 320Gly Val Ile Phe Ala Thr Tyr Ser Ser Leu Ile Gly Glu Ser Gln Ser325 330 335Gly Gly Lys Tyr Lys Thr Arg Leu Lys Gln Leu Leu His Trp Cys Gly340 345 350Asp Asp Phe Asp Gly Val Ile Val Phe Asp Glu Cys His Lys Ala Lys355 360 365Asn Leu Cys Pro Val Gly Ser Ser Lys Pro Thr Lys Thr Gly Leu Ala370 375 380Val Leu Glu Leu Gln Asn Lys Leu Pro Lys Ala Arg Val Val Tyr Ala385 390 395 400Ser Ala Thr Gly Ala Ser Glu Pro Arg Asn Met Ala Tyr Met Asn Arg405 410 415Leu Gly Ile Trp Gly Glu Gly Thr Pro Phe Arg Glu Phe Ser Asp Phe420 425 430Ile Gln Ala Val Glu Arg Arg Gly Val Gly Ala Met Glu Ile Val Ala435 440 445Met Asp Met Lys Leu Arg Gly Met Tyr Ile Ala Arg Gln Leu Ser Phe450 455 460Thr Gly Val Thr Phe Lys Ile Glu Glu Val Leu Leu Ser Gln Ser Tyr465 470 475 480Val Lys Met Tyr Asn Lys Ala Val Lys Leu Trp Val Ile Ala Arg Glu485 490 495Arg Phe Gln Gln Ala Ala Asp Leu Ile Asp Ala Glu Gln Arg Met Lys500 505 510Lys Ser Met Trp Gly Gln Phe Trp Ser Ala His Gln Arg Phe Phe Lys515 520 525Tyr Leu Cys Ile Ala Ser Lys Val Lys Arg Val Val Gln Leu Ala Arg530 535 540Glu Glu Ile Lys Asn Gly Lys Cys Val Val Ile Gly Leu Gln Ser Thr545 550 555 560Gly Glu Ala Arg Thr Leu Glu Ala Leu Glu Glu Gly Gly Gly Glu Leu565 570 575Asn Asp Phe Val Ser Thr Ala Lys Gly Val Leu Gln Ser Leu Ile Glu580 585 590Lys His Phe Pro Ala Pro Asp Arg Lys Lys Leu Tyr Ser Leu Leu Gly
595 600 605Ile Asp Leu Thr Ala Pro Ser Asn Asn Ser Ser Pro Arg Asp Ser Pro610 615 620Cys Lys Glu Asn Lys Ile Lys Lys Arg Lys Gly Glu Glu Ile Thr Arg625 630 635 640Glu Ala Lys Lys Ala Arg Lys Val Gly Gly Leu Thr Gly Ser Ser Ser645 650 655Asp Asp Ser Gly Ser Glu Ser Asp Ala Ser Asp Asn Glu Glu Ser Asp660 665 670Tyr Glu Ser Ser Lys Asn Met Ser Ser Gly Asp Asp Asp Asp Phe Asn675 680 685Pro Phe Leu Asp Glu Ser Asn Glu Asp Asp Glu Asn Asp Pro Trp Leu690 695 700Ile705<210>187<211>595<212>PRT<213>智人(Homo sapiens)<400>187Glu Ser Pro Arg His Arg Gly Glu Gly Gly Gly Glu Trp Gly Pro Gly1 5 10 15Val Pro Arg Glu Arg Arg Glu Ser Ala Gly Glu Trp Gly Ala Asp Thr20 25 30Pro Lys Glu Gly Gly Glu Ser Ala Gly Glu Trp Gly Ala Glu Val Pro35 40 45Arg Gly Arg Gly Glu Gly Ala Gly Glu Trp Gly Pro Asp Thr Pro Lys50 55 60Glu Arg Gly Gln Gly Val Arg Glu Trp Gly Pro Glu Ile Pro Gln Glu65 70 75 80His Gly Glu Ala Thr Arg Asp Trp Ala Leu Glu Ser Pro Arg Ala Leu85 90 95Gly Glu Asp Ala Arg Glu Leu Gly Ser Ser Pro His Asp Arg Gly Ala100 105 110Ser Pro Arg Asp Leu Ser Gly Glu Ser Pro Cys Thr Gln Arc Ser Gly115 120 125Leu Leu Pro Glu Arg Arg Gly Asp Ser Pro Trp Pro Pro Trp Pro Ser130 135 140Pro Gln Glu Arg Asp Ala Gly Thr Arg Asp Arg Glu Glu Ser Pro Arg145 150 155 160Asp Trp Gly Gly Ala Glu Ser Pro Arg Gly Trp Glu Ala Gly Pro Arg165 170 175Glu Trp Gly Pro Ser Pro Ser Gly His Gly Asp Gly Pro Arg Arg Arg180 185 190Pro Arg Lys Arg Arg Gly Arg Lys Gly Arg Met Gly Arg Gln His Glu195 200 205Ala Ala Ala Thr Ala Ala Thr Ala Ala Thr Ala Thr Gly Gly Thr Ala210 215 220Glu Glu Ala Gly Ala Ser Ala Pro Glu Ser Gln Ala Gly Gly Gly Pro225 230 235 240Arg Gly Arg Ala Arg Gly Pro Arg Gln Gln Gly Arg Arg Arg His Gly245 250 255Thr Gln Arg Arg Arg Gly Pro Pro Gln Ala Arg Glu Glu Gly Pro Arg260 265 270Asp Ala Thr Thr Ile Leu Gly Leu Gly Thr Pro Ser Gly Glu Gln Arg275 280 285Ala Asp Gln Ser Gln Ala Leu Pro Ala Leu Ala Gly Ala Ala Ala Ala290 295 300His Ala His Ala Ile Pro Gly Ala Gly Pro Ala Ala Ala Pro Val Gly305 310 315 320Gly Arg Gly Arg Arg Gly Gly Trp Arg Gly Gly Arg Arg Gly Gly Ser325 330 335Ala Gly Ala Gly Gly Gly Gly Arg Gly Gly Arg Gly Arg Gly Arg Gly340 345 350Gly Gly Arg Gly Gly Gly Gly Ala Gly Arg Gly Gly Gly Ala Ala Gly355 360 365Pro Arg Glu Gly Ala Ser Ser Pro Gly Ala Arg Arg Gly Glu Gln Arg370 375 380Arg Arg Gly Arg Gly Pro Pro Ala Ala Gly Ala Ala Gln Val Ser Ala385 390 395 400Arg Gly Arg Arg Ala Arg Gly Gln Arg Ala Gly Glu Glu Ala Gln Asp405 410 415Gly Leu Leu Pro Arg Gly Arg Asp Arg Leu Pro Leu Arg Pro Gly Asp420 425 430Ala Asn Gln Arg Ala Glu Arg Pro Gly Pro Pro Arg Gly Gly His Gly435 440 445Pro Val Asn Ala Ser Ser Ala Pro Asp Thr Ser Pro Pro Arg His Pro450 455 460Arg Arg Trp Val Ser Gln Gln Arg Gln Arg Leu Trp Arg Gln Phe Arg465 470 475 480Val Gly Gly Gly Phe Pro Pro Pro Pro Pro Ser Arg Pro Pro Ala Val485 490 495Leu Leu Pro Leu Leu Arg Leu Ala Cys Ala Gly Asp Pro Gly Ala Thr500 505 510Arg Pro Gly Pro Arg Arg Pro Ala Arg Arg Pro Arg Gly Glu Leu Ile515 520 525Pro Arg Arg Pro Asp Pro Ala Ala Pro Ser Glu Glu Gly Leu Arg Met530 535 540Glu Ser Ser Val Asp Asp Gly Ala Thr Ala Thr Thr Ala Asp Ala Ala545 550 555 560Ser Gly Glu Ala Pro Glu Ala Gly Pro Ser Pro Ser His Ser Pro Thr565 570 575Met Cys Gln Thr Gly Gly Pro Gly Pro Pro Pro Pro Gln Pro Pro Arg580 585 590Trp Leu Pro595<210>188<211>376<212>PRT<213>智人(Homo sapiens)<400>188Glu Met Arg Lys Phe Asp Val Pro Ser Met Glu Ser Thr Leu Asn Gln1 5 10 15Pro Ala Met Leu Glu Thr Leu Tyr Ser Asp Pro His Tyr Arg Ala His20 25 30Phe Pro Asn Pro Arg Pro Asp Thr Asn Lys Asp Val Tyr Lys Val Leu35 40 45Pro Glu Ser Lys Lys Ala Pro Gly Ser Gly Ala Val Phe Glu Arg Asn50 55 60Gly Pro His Ala Ser Ser Ser Gly Val Leu Pro Leu Gly Leu Gln Pro65 70 75 80Ala Pro Gly Leu Ser Lys Ser Leu Ser Ser Gln Val Trp Gln Pro Ser
85 90 95Pro Asp Pro Trp His Pro Gly Glu Gln Ser Cys Glu Leu Ser Thr Cys100 105 110Arg Gln Gln Leu Glu Leu Ile Arg Leu Gln Met Glu Gln Met Gln Leu115 120 125Gln Asn Gly Ala Met Cys His His Pro Ala Ala Phe Ala Pro Leu Leu130 135 140Pro Thr Leu Glu Pro Ala Gln Trp Leu Ser Ile Leu Asn Ser Asn Glu145 150 155 160His Leu Leu Lys Glu Lys Glu Leu Leu Ile Asp Lys Gln Arg Lys His165 170 175Ile Ser Gln Leu Glu Gln Lys Val Arg Glu Ser Glu Leu Gln Val His180 185 190Ser Ala Leu Leu Gly Arg Pro Ala Pro Phe Gly Asp Val Cys Leu Leu195 200 205Arg Leu Gln Glu Leu Gln Arg Glu Asn Thr Phe Leu Arg Ala Gln Phe210 215 220Ala Gln Lys Thr Glu Ala Leu Ser Lys Glu Lys Met Glu Leu Glu Lys225 230 235 240Lys Leu Ser Ala Ser Glu Val Glu Ile Gln Leu Ile Arg Glu Ser Leu245 250 255Lys Val Thr Leu Gln Lys His Ser Glu Glu Gly Lys Lys Gln Glu Glu260 265 270Arg Val Lys Gly Arg Asp Lys His Ile Asn Asn Leu Lys Lys Lys Cys275 280 285Gln Lys Glu Ser Glu Gln Asn Arg Glu Lys Gln Gln Arg Ile Glu Thr290 295 300Leu Glu Arg Tyr Leu Ala Asp Leu Pro Thr Leu Glu Asp His Gln Lys305 310 315 320Gln Thr Glu Gln Leu Lys Asp Ala Glu Leu Lys Asn Thr Glu Leu Gln325 330 335Glu Arg Val Ala Glu Leu Glu Thr Leu Leu Glu Asp Thr Gln Ala Thr340 345 350Cys Arg Glu Lys Glu Val Gln Leu Glu Ser Leu Arg Gln Arg Glu Ala355 360 365Asp Leu Ser Ser Ala Arg His Arg370 375<210>189<211>160<212>PRT<213>智人(Homo sapiens)<400>189Met Leu Glu Ala His Arg Arg Gln Arg His Pro Phe Leu Leu Leu Gly1 5 10 15Thr Thr Ala Asn Arg Thr Gln Ser Leu Asn Tyr Gly Cys Ile Val Glu20 25 30Asn Pro Gln Thr His Glu Val Leu His Tyr Val Glu Lys Pro Ser Thr35 40 45Phe Ile Ser Asp Ile Ile Asn Cys Gly Ile Tyr Leu Phe Ser Pro Glu50 55 60Ala Leu Lys Pro Leu Arg Asp Val Phe Gln Arg Asn Gln Gln Asp Gly65 70 75 80Gln Leu Glu Asp Ser Pro Gly Leu Trp Pro Gly Ala Gly Thr Ile Arg85 90 95Leu Glu Gln Asp Val Phe Ser Ala Leu Ala Gly Gln Gly Gln Ile Tyr100 105 110Val His Leu Thr Asp Gly Ile Trp Ser Gln Ile Lys Ser Ala Gly Ser115 120 125Ala Leu Tyr Ala Ser Arg Leu Tyr Leu Ser Arg Tyr Gln Asp Thr His130 135 140Pro Glu Arg Leu Ala Lys His Thr Pro Gly Gly Pro Trp Ile Arg Gly145 150 155 160<210>190<211>146<212>PRT<213>智人(Homo sapiens)<400>190Met Asp Pro Arg Ala Ser Leu Leu Leu Leu Gly Asn Val Tyr Ile His1 5 10 15Pro Thr Ala Lys Val Ala Pro Ser Ala Val Leu Gly Pro Asn Val Ser20 25 30Ile Gly Lys Gly Val Thr Val Gly Glu Gly Val Arg Leu Arg Glu Ser35 40 45Ile Val Leu His Gly Ala Thr Leu Gln Glu His Thr Cys Val Leu His50 55 60Ser Ile Val Gly Trp Gly Ser Thr Val Gly Arg Trp Ala Arg Val Glu65 70 75 80Gly Thr Pro Ser Asp Pro Asn Pro Asn Asp Pro Arg Ala Arg Met Asp85 90 95Ser Glu Ser Leu Phe Lys Asp Gly Lys Leu Leu Pro Ala Ile Thr Ile100 105 1l0Leu Gly Cys Arg Val Arg Ile Pro Ala Glu Val Leu Ile Leu Asn Ser115 120 125Ile Val Leu Pro His Lys Glu Leu Ser Arg Ser Phe Thr Asn Gln Ile130 135 140Ile Leu145<210>191<211>704<212>PRT<213>智人(Homo sapiens)<400>191Glu Gly Gly Cys Ala Ala Gly Arg Gly Arg Glu Leu Glu Pro Glu Leu1 5 10 15Glu Pro Gly Pro Gly Pro Gly Ser Ala Leu Glu Pro Gly Glu Glu Phe20 25 30Glu Ile Val Asp Arg Ser Gln Leu Pro Gly Pro Gly Asp Leu Arg Ser35 40 45Ala Thr Arg Pro Arg Ala Ala Glu Gly Trp Ser Ala Pro Ile Leu Thr50 55 60Leu Ala Arg Arg Ala Thr Gly Asn Leu Ser Ala Ser Cys Gly Ser Ala65 70 75 80Leu Arg Ala Ala Ala Gly Leu Gly Gly Gly Asp Ser Gly Asp Gly Thr85 90 95Ala Arg Ala Ala Ser Lys Cys Gln Met Met Glu Glu Arg Ala Asn Leu100 105 110Met His Met Met Lys Leu Ser Ile Lys Val Leu Leu Gln Ser Ala Leu115 120 125Ser Leu Gly Arg Ser Leu Asp Ala Asp His Ala Pro Leu Gln Gln Phe130 135 140Phe Val Val Met Glu His Cys Leu Lys His Gly Leu Lys Val Lys Lys145 150 155 160Ser Phe Ile Gly Gln Asn Lys Ser Phe Phe Gly Pro Leu Glu Leu Val165 170 175Glu Lys Leu Cys Pro Glu Ala Ser Asp Ile Ala Thr Ser Val Arg Asn180 185 190Leu Pro Glu Leu Lys Thr Ala Val Gly Arg Gly Arg Ala Trp Leu Tyr195 200 205Leu Ala Leu Met Gln Lys Lys Leu Ala Asp Tyr Leu Lys Val Leu Ile210 215 220Asp Asn Lys His Leu Leu Ser Glu Phe Tyr Glu Pro Glu Ala Leu Met225 230 235 240Met Glu Glu Glu Gly Met Val Ile Val Gly Leu Leu Val Gly Leu Asn245 250 255Val Leu Asp Ala Asn Leu Cys Leu Lys Gly Glu Asp Leu Asp Ser Gln260 265 270Val Gly Val Ile Asp Phe Ser Leu Tyr Leu Lys Asp Val Gln Asp Leu275 280 285Asp Gly Gly Lys Glu His Glu Arg Ile Thr Asp Val Leu Asp Gln Lys290 295 300Asn Tyr Val Glu Glu Leu Asn Arg His Leu Ser Cys Thr Val Gly Asp305 310 315 320Leu Gln Thr Lys Ile Asp Gly Leu Glu Lys Thr Asn Ser Lys Leu Gln325 330 335Glu Glu Leu Ser Ala Ala Thr Asp Arg Ile Cys Ser Leu Gln Glu Glu340 345 350Gln Gln Gln Leu Arg Glu Gln Asn Glu Leu Ile Arg Glu Arg Ser Glu355 360 365Lys Ser Val Glu Ile Thr Lys Gln Asp Thr Lys Val Glu Leu Glu Thr370 375 380Tyr Lys Gln Thr Arg Gln Gly Leu Asp Glu Met Tyr Ser Asp Val Trp385 390 395 400Lys Gln Leu Lys Glu Glu Lys Lys Val Arg Leu Glu Leu Glu Lys Glu405 410 415Leu Glu Leu Gln Ile Gly Met Lys Thr Glu Met Glu Ile Ala Met Lys420 425 430Leu Leu Glu Lys Asp Thr His Glu Lys Gln Asp Thr Leu Val Ala Leu435 440 445Arg Gln Gln Leu Glu Glu Val Lys Ala Ile Asn Leu Gln Met Phe His450 455 460Lys Ala Gln Asn Ala Glu Ser Ser Leu Gln Gln Lys Asn Glu Ala Ile465 470 475 480Thr Ser Phe Glu Gly Lys Thr Asn Gln Val Met Ser Ser Met Lys Gln485 490 495Met Glu Glu Arg Leu Gln His Ser Glu Arg Ala Arg Gln Gly Ala Glu500 505 510Glu Arg Ser His Lys Leu Gln Gln Glu Leu Gly Gly Arg Ile Gly Ala515 520 525Leu Gln Leu Gln Leu Ser Gln Leu His Glu Gln Cys Ser Ser Leu Glu530 535 540Lys Glu Leu Lys Ser Glu Lys Glu Gln Arg Gln Ala Leu Gln Arg Glu545 550 555 560Leu Gln His Glu Lys Asp Thr Ser Ser Leu Leu Arg Met Glu Leu Gln565 570 575Gln Val Glu Gly Leu Lys Lys Glu Leu Arg Glu Leu Gln Asp Glu Lys580 585 590Ala Glu Leu Gln Lys Ile Cys Glu Glu Gln Glu Gln Ala Leu Gln Glu595 600 605Met Gly Leu His Leu Ser Gln Ser Lys Leu Lys Met Glu Asp Ile Lys6l0 615 620Glu Val Asn Gln Ala Leu Lys Gly His Ala Trp Leu Lys Asp Asp Glu625 630 635 640Ala Thr His Cys Arg Gln Cys Glu Lys Glu Phe Ser Ile Ser Arg Arg645 650 655Lys His His Cys Arg Asn Cys Gly His Ile Phe Cys Asn Thr Cys Ser660 665 670Ser Asn Glu Leu Ala Leu Pro Ser Tyr Pro Lys Pro Val Arg Val Cys675 680 685Asp Ser Cys His Thr Leu Leu Leu Gln Arg Cys Ser Ser Thr Ala Ser690 695 700<210>192<211>331<212>PRT<213>智人(Homo sapiens)<400>192Arg Ala Gly Ala Ser Ala Met Ala Leu Arg Lys Glu Leu Leu Lys Ser1 5 10 15Ile Trp Tyr Ala Phe Thr Ala Leu Asp Val Glu Lys Ser Gly Lys Val20 25 30Ser Lys Ser Gln Leu Lys Val Leu Ser His Asn Leu Tyr Thr Val Leu35 40 45His Ile Pro His Asp Pro Val Ala Leu Glu Glu His Phe Arg Asp Asp50 55 60Asp Asp Gly Pro Val Ser Ser Gln Gly Tyr Met Pro Tyr Leu Asn Lys65 70 75 80Tyr Ile Leu Asp Lys Val Glu Glu Gly Ala Phe Val Lys Glu His Phe85 90 95Asp Glu Leu Cys Trp Thr Leu Thr Ala Lys Lys Asn Tyr Arg Ala Asp100 105 110Ser Asn Gly Asn Ser Met Leu Ser Asn Gln Asp Ala Phe Arg Leu Trp115 120 125Cys Leu Phe Asn Phe Leu Ser Glu Asp Lys Tyr Pro Leu Ile Met Val130 135 140Pro Asp Glu Val Glu Tyr Leu Leu Lys Lys Val Leu Ser Ser Met Ser145 150 155 160Leu Glu Val Ser Leu Gly Glu Leu Glu Glu Leu Leu Ala Gln Glu Ala165 170 175Gln Val Ala Gln Thr Thr Gly Gly Leu Ser Val Trp Gln Phe Leu Glu180 185 190Leu Phe Asn Ser Gly Arg Cys Leu Arg Gly Val Gly Arg Asp Thr Leu195 200 205Ser Met Ala Ile His Glu Val Tyr Gln Glu Leu Ile Gln Asp Val Leu210 215 220Lys Gln Gly Tyr Leu Trp Lys Arg Gly His Leu Arg Arg Asn Trp Ala225 230 235 240Glu Arg Trp Phe Gln Leu Gln Pro Ser Cys Leu Cys Tyr Phe Gly Ser245 250 255Glu Glu Cys Lys Glu Lys Arg Gly Ile Ile Pro Leu Asp Ala His Cys260 265 270Cys Val Glu Val Leu Pro Asp Arg Asp Gly Lys Arg Cys Met Phe Cys275 280 285Val Lys Thr Ala Thr Arg Thr Tyr Glu Met Ser Ala Ser Asp Thr Arg290 295 300Gln Arg Gln Glu Trp Thr Ala Ala Ile Gln Met Ala Ile Arg Leu Gln305 310 315 320Ala Glu Gly Lys Thr Ser Leu His Lys Asp Leu325 330<210>193<211>475<212>PRT<213>智人(Homo sapiens)<400>193Lys Asn Ser Pro Leu Leu Ser Val Ser Ser Gln Thr Ile Thr Lys Glu1 5 l0 15Asn Asn Arg Asn Val His Leu Glu His Ser Glu Gln Asn Pro Gly Ser20 25 30Ser Ala Gly Asp Thr Ser Ala Ala His Gln Val Val Leu Gly Glu Asn35 40 45Leu Ile Ala Thr Ala Leu Cys Leu Ser Gly Ser Gly Ser Gln Ser Asp50 55 60Leu Lys Asp Val Ala Ser Thr Ala Gly Glu Glu Gly Asp Thr Ser Leu65 70 75 80Arg Glu Ser Leu His Pro Val Thr Arg Ser Leu Lys Ala Gly Cys His85 90 95Thr Lys Gln Leu Ala Ser Arg Asn Cys Ser Glu Glu Lys Ser Pro Gln100 105 110Thr Ser Ile Leu Lys Glu Gly Asn Arg Asp Thr Ser Leu Asp Phe Arg115 120 125Pro Val Val Ser Pro Ala Asn Gly Val Glu Gly Val Arg Val Asp Gln130 135 140Asp Asp Asp Gln Asp Ser Ser Ser Leu Lys Leu Ser Gln Asn Ile Ala145 150 155 160Val Gln Thr Asp Phe Lys Thr Ala Asp Ser Glu Val Asn Thr Asp Gln165 170 175Asp Ile Glu Lys Asn Leu Asp Lys Met Met Thr Glu Arg Thr Leu Leu180 185 190Lys Glu Arg Tyr Gln Glu Val Leu Asp Lys Gln Arg Gln Val Glu Asn195 200 205Gln Leu Gln Val Gln Leu Lys Gln Leu Gln Gln Arg Arg Glu Glu Glu210 215 220Met Lys Asn His Gln Glu Ile Leu Lys Ala Ile Gln Asp Val Thr Ile225 230 235 240Lys Arg Glu Glu Thr Lys Lys Lys Ile Glu Lys Glu Lys Lys Glu Phe245 250 255Leu Gln Lys Glu Gln Asp Leu Lys Ala Glu Ile Glu Lys Leu Cys Glu260 265 270Lys Gly Arg Arg Glu Val Trp Glu Met Glu Leu Asp Arg Leu Lys Asn275 280 285Gln Asp Gly Glu Ile Asn Arg Asn Ile Met Glu Glu Thr Glu Arg Ala290 295 300Trp Lys Ala Glu Ile Leu Ser Leu Glu Ser Arg Lys Glu Leu Leu Val305 310 315 320Leu Lys Leu Glu Glu Ala Glu Lys Glu Ala Glu Leu His Leu Thr Tyr325 330 335Leu Lys Ser Thr Pro Pro Thr Leu Glu Thr Val Arg Ser Lys Gln Glu340 345 350Trp Glu Thr Arg Leu Asn Gly Val Arg Ile Met Lys Lys Asn Val Arg35S 360 365Asp Gln Phe Asn Ser His Ile Gln Leu Val Arg Asn Gly Ala Lys Leu370 375 380Ser Ser Leu Pro Gln Ile Pro Thr Pro Thr Leu Pro Pro Pro Pro Ser385 390 395 400Glu Thr Asp Phe Met Leu Gln Val Phe Gln Pro Ser Pro Ser Leu Ala405 410 415Pro Arg Met Pro Phe Ser Ile Gly Gln Val Thr Met Pro Met Val Met420 425 430Pro Ser Ala Asp Pro Arg Ser Leu Ser Phe Pro Ile Leu Asn Pro Ala435 440 445Leu Ser Gln Pro Ser Gln Pro Ser Ser Pro Leu Pro Gly Ser His Gly450 455 460Arg Asn Ser Pro Gly Leu Gly Ser Leu Val Ser465 470 475<210>194<211>241<212>PRT<213>智人(Homo sapiens)<400>194Met Ser Gly Glu Ser Ala Arg Ser Leu Gly Lys Gly Ser Ala Pro Pro1 5 10 15Gly Pro Val Pro Glu Gly Ser Ile Arg Ile Tyr Ser Met Arg Phe Cys20 25 30Pro Phe Ala Glu Arg Thr Arg Leu Val Leu Lys Ala Lys Gly Ile Arg35 40 45His Glu Val Ile Asn Ile Asn Leu Lys Asn Lys Pro Glu Trp Phe Phe50 55 60Lys Lys Asn Pro Phe Gly Leu Val Pro Val Leu Glu Asn Ser Gln Gly65 70 75 80Gln Leu Ile Tyr Glu Ser Ala Ile Thr Cys Glu Tyr Leu Asp Glu Ala85 90 95Tyr Pro Gly Lys Lys Leu Leu Pro Asp Asp Pro Tyr Glu Lys Ala Cys100 105 110Gln Lys Met Ile Leu Glu Leu Phe Ser Lys Val Pro Ser Leu Val Gly115 120 125Ser Phe Ile Arg Ser Gln Asn Lys Glu Asp Tyr Ala Gly Leu Lys Glu130 135 140Glu Phe Arg Lys Glu Phe Thr Lys Leu Glu Glu Val Leu Thr Asn Lys145 150 155 160Lys Thr Thr Phe Phe Gly Gly Asn Ser Ile Ser Met Ile Asp Tyr Leu165 170 175Ile Trp Pro Trp Phe Glu Arg Leu Glu Ala Met Lys Leu Asn Glu Cys180 185 190Val Asp His Thr Pro Lys Leu Lys Leu Trp Met Ala Ala Met Lys Glu195 200 205Asp Pro Thr Val Ser Ala Leu Leu Thr Ser Glu Lys Asp Trp Gln Gly210 215 220Phe Leu Glu Leu Tyr Leu Gln Asn Ser Pro Glu Ala Cys Asp Tyr Gly225 230 235 240Leu<210>195<211>138<212>PRT<213>智人(Homo sapiens)<400>195Gln Thr Lys Ile Leu Glu Glu Asp Leu Glu Gln Ile Lys Leu Ser Leu1 5 10 15Arg Glu Arg Gly Arg Glu Leu Thr Thr Gln Arg Gln Leu Met Gln Glu20 25 30Arg Ala Glu Glu Gly Lys Gly Pro Ser Lys Ala Gln Arg Gly Ser Leu35 40 45Glu His Met Lys Leu Ile Leu Arg Asp Lys Glu Lys Glu Val Glu Cys50 55 60Gln Gln Glu His Ile His Glu Leu Gln Glu Leu Lys Asp Gln Leu Glu65 70 75 80Gln Gln Leu Gln Gly Leu His Arg Lys Val Gly Glu Thr Ser Leu Leu85 90 95Leu Ser Gln Arg Glu Gln Glu Ile Val Val Leu Gln Gln Gln Leu Gln100 105 110Glu Ala Arg Glu Gln Gly Glu Leu Lys Glu Gln Ser Leu Gln Ser Gln115 120 125Leu Asp Glu Ala Gln Arg Ala Leu Ala Gln130 135<210>196<211>102<212>PRT<213>智人(Homo sapiens)<400>196Met Ser Lys Arg Lys Ala Pro Gln Glu Thr Leu Asn Gly Gly Ile Thr1 5 10 15Asp Met Leu Thr Glu Leu Ala Asn Phe Glu Lys Asn Val Ser Gln Ala20 25 30Ile His Lys Tyr Asn Ala Tyr Arg Lys Ala Ala Ser Val Ile Ala Lys35 40 45Tyr Pro His Lys Ile Lys Ser Gly Ala Glu Ala Lys Lys Leu Pro Gly50 55 60Val Gly Thr Lys Ile Ala Glu Lys Ile Asp Glu Phe Leu Ala Thr Gly65 70 75 80Lys Leu Arg Lys Leu Glu Lys Ile Arg Gln Asp Asp Thr Ser Ser Ser85 90 95Ile Asn Phe Leu Thr Arg100<210>197<211>138<212>PRT<213>智人(Homo sapiens)<400>197Glu Ala Asn Glu Val Thr Asp Ser Ala Tyr Met Gly Ser Glu Ser Thr1 5 10 15Tyr Ser Glu Cys Glu Thr Phe Thr Asp Glu Asp Thr Ser Thr Leu Val20 25 30His Pro Glu Leu Gln Pro Glu Gly Asp Ala Asp Ser Ala Gly Gly Ser35 40 45Ala Val Pro Ser Glu Cys Leu Asp Ala Met Glu Glu Pro Asp His Gly50 55 60Ala Leu Leu Leu Leu Pro Gly Arg Pro His Pro His Gly Gln Ser Val65 70 75 80Ile Thr Val Ile Gly Gly Glu Glu His Phe Glu Asp Tyr Gly Glu Gly85 90 95Ser Glu Ala Glu Leu Ser Pro Glu Thr Leu Cys Asn Gly Gln Leu Gly100 105 110Cys Ser Asp Pro Ala Phe Leu Thr Pro Ser Pro Thr Lys Arg Leu Ser115 120 125Ser Lys Lys Val Ala Arg Tyr Leu His Gln130 135<210>198<211>100<212>PRT<213>智人(Homo sapiens)<400>198Met Gly Asp Val Lys Asn Phe Leu Tyr Ala Trp Cys Gly Lys Arg Lys1 5 10 15Met Thr Pro Ser Tyr Glu Ile Arg Ala Val Gly Asn Lys Asn Arg Gln20 25 30Lys Phe Met Cys Glu Val Gln Val Glu Gly Tyr Asn Tyr Thr Gly Met35 40 45Gly Asn Ser Thr Asn Lys Lys Asp Ala Gln Ser Asn Ala Ala Arg Asp50 55 60Phe Val Asn Tyr Leu Val Arg Ile Asn Glu Ile Lys Ser Glu Glu Val65 70 75 80Pro Ala Phe Gly Val Ala Ser Pro Pro Pro Leu Thr Asp Thr Pro Asp85 90 95Thr Thr Ala Asn100<210>199<211>127<212>PRT<213>智人(Homo sapiens)<400>199Met Val Lys Glu Thr Thr Tyr Tyr Asp Val Leu Gly Val Lys Pro Asn1 5 10 15Ala Thr Gln Glu Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys20 25 30Tyr His Pro Asp Lys Asn Pro Asn Glu Gly Glu Lys Phe Lys Gln Ile35 40 45Ser Gln Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Glu Leu Tyr50 55 60Asp Lys Gly Gly Glu Gln Ala Ile Lys Glu Gly Gly Ala Gly Gly Gly65 70 75 80Phe Gly Ser Pro Met Asp Ile Phe Asp Met Phe Phe Gly Gly Gly Gly85 90 95Arg Met Gln Arg Glu Arg Arg Gly Lys Asn Val Val His Gln Leu Ser100 105 110Val Thr Leu Glu Asp Leu Tyr Asn Gly Ala Thr Arg Lys Leu Ala115 120 125<210>200<211>90<212>PRT<213>智人(Homo sapiens)<400>200Met Ala Cys Pro Leu Asp Gln Ala Ile Gly Leu Leu Val Ala Ile Phel 5 l0 15His Lys Tyr Ser Gly Arg Glu Gly Asp Lys His Thr Leu Ser Lys Lys20 25 30Glu Leu Lys Glu Leu Ile Gln Lys Glu Leu Thr Ile Gly Ser Lys Leu35 40 45Gln Asp Ala Glu Ile Ala Arg Leu Met Glu Asp Leu Asp Arg Asn Lys50 55 60Asp Gln Glu Val Asn Phe Gln Glu Tyr Val Thr Phe Leu Gly Ala Leu65 70 75 80Ala Leu Ile Tyr Asn Glu Ala Leu Lys Gly85 90<210>201<211>120<212>PRT<213>智人(Homo sapiens)<400>201Met Glu Thr Pro Ser Gln Arg Arg Ala Thr Arg Ser Gly Ala Gln Ala1 5 10 15Ser Ser Thr Pro Leu Ser Pro Thr Arg Ile Thr Arg Leu Gln Glu Lys20 25 30Glu Asp Leu Gln Glu Leu Asn Asp Arg Leu Ala Val Tyr Ile Asp Arg35 40 45Val Arg Ser Leu Glu Thr Glu Asn Ala Gly Leu Arg Leu Arg Ile Thr50 55 60Glu Ser Glu Glu Val Val Ser Arg Glu Val Ser Gly Ile Lys Ala Ala65 70 75 80Tyr Glu Ala Glu Leu Gly Asp Ala Arg Lys Thr Leu Asp Ser Val Ala85 90 95Lys Glu Arg Ala Arg Leu Gln Leu Glu Leu Ser Lys Val Arg Glu Glu100 105 110Phe Lys Glu Leu Lys Ala Arg Asn115 120<210>202<211>177<212>PRT<213>智人(Homo sapiens)<400>202Met Ala Ala Gly Val Glu Ala Ala Ala Glu Val Ala Ala Thr Glu Ile1 5 l0 15Lys Met Glu Glu Glu Ser Gly Ala Pro Gly Val Pro Ser Gly Asn Gly20 25 30Ala Pro Gly Pro Lys Gly Glu Gly Glu Arg Pro Ala Gln Asn Glu Lys35 40 45Arg Lys Glu Lys Asn Ile Lys Arg Gly Gly Asn Arg Phe Glu Pro Tyr50 55 60Ala Asn Pro Thr Lys Arg Tyr Arg Ala Phe Ile Thr Asn Ile Pro Phe65 70 75 80Asp Val Lys Trp Gln Ser Leu Lys Asp Leu Val Lys Glu Lys Val Gly85 90 95Glu Val Thr Tyr Val Glu Leu Leu Met Asp Ala Glu Gly Lys Ser Arg100 105 110Gly Cys Ala Val Val Glu Phe Lys Met Glu Glu Ser Met Lys Lys Ala115 120 125Ala Glu Val Leu Asn Lys His Ser Leu Ser Gly Arg Pro Leu Lys Val
130 135 140Lys Glu Asp Pro Asp Gly Glu His Ala Arg Arg Ala Met Gln Lys Ala145 150 155 160Gly Arg Leu Gly Ser Thr Val Phe Val Ala Asn Leu Asp Tyr Lys Val165 170 175Gly<210>203<211>164<212>PRT<213>智人(Homo sapiens)<400>203Met Arg Leu Ala Val Gly Ala Leu Leu Val Cys Ala Val Leu Gly Leu1 5 10 15Cys Leu Ala Val Pro Asp Lys Thr Val Arg Trp Cys Ala Val Ser Glu20 25 30His Glu Ala Thr Lys Cys Gln Ser Phe Arg Asp His Met Lys Ser Val35 40 45Ile Pro Ser Asp Gly Pro Ser Val Ala Cys Val Lys Lys Ala Ser Tyr50 55 60Leu Asp Cys Ile Arg Ala Ile Ala Ala Asn Glu Ala Asp Ala Val Thr65 70 75 80Leu Asp Ala Gly Leu Val Tyr Asp Ala Tyr Leu Ala Pro Asn Asn Leu85 90 95Lys Pro Val Val Ala Glu Phe Tyr Gly Ser Lys Glu Asp Pro Gln Thr100 105 110Phe Tyr Tyr Ala Val Ala Val Val Lys Lys Asp Ser Gly Phe Gln Met115 120 125Asn Gln Leu Arg Gly Lys Lys Ser Cys His Thr Gly Leu Gly Arg Ser130 135 140Ala Gly Trp Asn Ile Pro Ile Gly Leu Leu Tyr Cys Asp Leu Pro Glu145 150 155 160Pro Arg Lys Pro<210>204<211>241<212>PRT<213>智人(Homo sapiens)<400>204Met Ser Gly Glu Ser Ala Arg Ser Leu Gly Lys Gly Ser Ala Pro Pro1 5 10 15Gly Pro Val Pro Glu Gly Ser Ile Arg Ile Tyr Ser Met Arg Phe Cys20 25 30Pro Phe Ala Glu Arg Thr Arg Leu Val Leu Lys Ala Lys Gly Ile Arg35 40 45His Glu Val Ile Asn Ile Asn Leu Lys Asn Lys Pro Glu Trp Phe Phe50 55 60Lys Lys Asn Pro Phe Gly Leu Val Pro Val Leu Glu Asn Ser Gln Gly65 70 75 80Gln Leu Ile Tyr Glu Ser Ala Ile Thr Cys Glu Tyr Leu Asp Glu Ala85 90 95Tyr Pro Gly Lys Lys Leu Leu Pro Asp Asp Pro Tyr Glu Lys Ala Cys100 105 110Gln Lys Met Ile Leu Glu Leu Phe Ser Lys Val Pro Ser Leu Val Gly
115 120 125Ser Phe Ile Arg Ser Gln Asn Lys Glu Asp Tyr Asp Gly Leu Lys Glu130 135 140Glu Phe Arg Lys Glu Phe Thr Lys Leu Glu Glu Val Leu Thr Asn Lys145 150 155 160Lys Thr Thr Phe Phe Gly Gly Asn Ser Ile Ser Met Ile Asp Tyr Leu165 170 175Ile Trp Pro Trp Phe Glu Arg Leu Glu Ala Met Lys Leu Asn Glu Cys180 185 190Val Asp His Thr Pro Lys Leu Lys Leu Trp Met Ala Ala Met Lys Glu195 200 205Asp Pro Thr Val Ser Ala Leu Leu Thr Ser Glu Lys Asp Trp Gln Gly210 215 220Phe Leu Glu Leu Tyr Leu Gln Asn Ser Pro Glu Ala Cys Asp Tyr Gly225 230 235 240Leu<210>205<211>160<212>PRT<213>智人(Homo sapiens)<400>205Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu1 5 10 15Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp20 25 30Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys35 40 45Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu50 55 60Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe65 70 75 80Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser85 90 95Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile100 105 110Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp115 120 125Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His130 135 140Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu145 150 155 160<210>206<211>197<212>PRT<213>智人(Homo sapiens)<400>206Thr Ser Pro Ser Glu Ala Cys Ala Pro Leu Leu Ile Ser Leu Ser Thr1 5 10 15Leu Ile Tyr Asn Gly Ala Leu Pro Cys Gln Cys Asn Pro Gln Gly Ser20 25 30Leu Ser Ser Glu Cys Asn Pro His Gly Gly Gln Cys Leu Cys Lys Pro35 40 45Gly Val Val Gly Arg Arg Cys Asp Leu Cys Ala Pro Gly Tyr Tyr Gly
50 55 60Phe Gly Pro Thr Gly Cys Gln Gly Ala Cys Leu Gly Cys Arg Asp His65 70 75 80Thr Gly Gly Glu His Cys Glu Arg Cys Ile Ala Gly Phe His Gly Asp85 90 95Pro Arg Leu Pro Tyr Gly Gly Gln Cys Arg Pro Cys Pro Cys Pro Glu100 105 110Gly Pro Gly Ser Gln Arg His Phe Ala Thr Ser Cys His Gln Asp Glu115 120 125Tyr Ser Gln Gln Ile Val Cys His Cys Arg Ala Gly Tyr Thr Gly Leu130 135 140Arg Cys Glu Ala Cys Ala Pro Gly His Phe Gly Asp Pro Ser Arg Pro145 150 155 160Gly Gly Arg Cys Gln Leu Cys Glu Cys Ser Gly Asn Ile Asp Pro Met165 170 175Asp Pro Asp Ala Cys Asp Pro His Thr Gly Gln Cys Leu Arg Cys Leu180 185 190His His Thr Glu Gly195<210>207<211>175<212>PRT<213>智人(Homo sapiens)<400>207Ile Ile Arg Gln Gln Gly Leu Ala Ser Tyr Asp Tyr Val Arg Arg Arg1 5 10 15Leu Thr Ala Glu Asp Leu Phe Glu Ala Arg Ile Ile Ser Leu Glu Thr20 25 30Tyr Asn Leu Leu Arg Glu Gly Thr Arg Ser Leu Arg Glu Ala Leu Glu35 40 45Ala Glu Ser Ala Trp Cys Tyr Leu Tyr Gly Thr Gly Ser Val Ala Gly50 55 60Val Tyr Leu Pro Gly Ser Arg Gln Thr Leu Ser Ile Tyr Gln Ala Leu65 70 75 80Lys Lys Gly Leu Leu Ser Ala Glu Val Ala Arg Leu Leu Leu Glu Ala85 90 95Gln Ala Ala Thr Gly Phe Leu Leu Asp Pro Val Lys Gly Glu Arg Leu100 105 110Thr Val Asp Glu Ala Val Arg Lys Gly Leu Val Gly Pro Glu Leu His115 120 125Asp Arg Leu Leu Ser Ala Glu Arg Ala Val Thr Gly Tyr Arg Asp Pro130 135 140Tyr Thr Glu Gln Thr Ile Ser Leu Phe Gln Ala Met Lys Lys Glu Leu145 150 155 160Ile Pro Thr Glu Glu Ala Leu Arg Leu Trp Met Pro Ser Trp Pro165 170 175<210>208<211>177<212>PRT<213>智人(Homo sapiens)<400>208Met Ala Ala Gly Val Glu Ala Ala Ala Glu Val Ala Ala Thr Glu Ile1 5 10 15Lys Met Glu Glu Glu Ser Gly Ala Pro Gly Val Pro Ser Gly Asn Gly
20 25 30Ala Pro Gly Pro Lys Gly Glu Gly Glu Arg Pro Ala Gln Asn Glu Lys35 40 45Arg Lys Glu Lys Asn Ile Lys Arg Gly Gly Asn Arg Phe Glu Pro Tyr50 55 60Ala Asn Pro Thr Lys Arg Tyr Arg Ala Phe Ile Thr Asn Ile Pro Phe65 70 75 80Asp Val Lys Trp Gln Ser Leu Lys Asp Leu Val Lys Glu Lys Val Gly85 90 95Glu Val Thr Tyr Val Glu Leu Leu Met Asp Ala Glu Gly Lys Ser Arg100 105 110Gly Cys Ala Val Val Glu Phe Lys Met Glu Glu Ser Met Lys Lys Ala115 120 125Ala Glu Val Leu Asn Lys His Ser Leu Ser Gly Arg Pro Leu Lys Val130 135 140Lys Glu Asp Pro Asp Gly Glu His Ala Arg Arg Ala Met Gln Lys Val145 150 155 160Met Ala Thr Thr Gly Gly Met Gly Met Gly Pro Gly Gly Pro Gly Met165 170 175Ile<210>209<211>196<212>PRT<213>智人(Homo sapiens)<400>209Asp Leu Gln Asp Met Phe Ile Val His Thr Ile Glu Glu Ile Glu Gly1 5 10 15Leu Ile Ser Ala His Asp Gln Phe Lys Ser Thr Leu Pro Asp Ala Asp20 25 30Arg Glu Arg Glu Ala Ile Leu Ala Ile His Lys Glu Ala Gln Arg Ile35 40 45Ala Glu Ser Asn His Ile Lys Leu Ser Gly Ser Asn Pro Tyr Thr Thr50 55 60Val Thr Pro Gln Ile Ile Asn Ser Lys Trp Glu Lys Val Gln Gln Leu65 70 75 80Val Pro Lys Arg Asp His Ala Leu Leu Glu Glu Gln Ser Lys Gln Gln85 90 95Ser Asn Glu His Leu Arg Arg Gln Phe Ala Ser Gln Ala Asn Val Val100 105 110Gly Pro Trp Ile Gln Thr Lys Met Glu Glu Ile Gly Arg Ile Ser Ile115 120 125Glu Met Asn Gly Thr Leu Glu Asp Gln Leu Ser His Leu Lys Gln Tyr130 135 140Glu Arg Ser Ile Val Asp Tyr Lys Pro Asn Leu Asp Leu Leu Glu Gln145 150 155 160Gln His Gln Leu Ile Gln Glu Ala Leu Ile Phe Asp Asn Lys His Thr165 170 175Asn Tyr Thr Met Glu His Ile Arg Val Gly Trp Glu Gln Leu Leu Thr180 185 190Thr Ile Ala Arg195<210>210<211>156<212>PRT
<213>智人(Homo sapiens)<400>210Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly Lys Glu1 5 10 15Val Leu Leu Leu Ala His Asn Leu Pro Gln Asn Arg Ile Gly Tyr Ser20 25 30Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Ser Leu Ile Val Gly Tyr35 40 45Val Ile Gly Thr Gln Gln Ala Thr Pro Gly Pro Ala Tyr Ser Gly Arg50 55 60Glu Thr Ile Tyr Pro Asn Ala Ser Leu Leu Ile Gln Asn Val Thr Gln65 70 75 80Asn Asp Thr Gly Phe Tyr Thr Leu Gln Val Ile Lys Ser Asp Leu Val85 90 95Asn Glu Glu Ala Thr Gly Gln Phe His Val Tyr Pro Glu Leu Pro Lys100 105 110Pro Ser Ile Ser Ser Asn Asn Ser Asn Pro Val Glu Asp Lys Asp Ala115 120 125Val Ala Phe Thr Cys Glu Pro Glu Val Gln Asn Thr Thr Tyr Leu Trp130 135 140Trp Val Asn Gly Gln Ser Leu Pro Val Ser Pro Lys145 150 155<210>211<211>92<212>PRT<213>智人(Homo sapiens)<400>211Met Glu Ser Pro Ser Ala Pro Pro His Arg Trp Cys Ile Pro Trp Gln1 5 10 15Arg Leu Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Pro Pro Thr20 25 30Thr Ala Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly35 40 45Lys Glu Val Leu Leu Leu Val His Asn Leu Pro Gln His Leu Phe Gly50 55 60Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Arg Gln Ile Ile65 70 75 80Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly85 90<210>212<211>142<212>PRT<213>智人(Homo sapiens)<400>212Glu Lys Gln Lys Asn Lys Glu Phe Ser Gln Thr Leu Glu Asn Glu Lys1 5 10 15Asn Thr Leu Leu Ser Gln Ile Ser Thr Lys Asp Gly Glu Leu Lys Met20 25 30Leu Gln Glu Glu Val Thr Lys Met Asn Leu Leu Asn Gln Gln Ile Gln35 40 45Glu Glu Leu Ser Arg Val Thr Lys Leu Lys Glu Thr Ala Glu Glu Glu50 55 60Lys Asp Asp Leu Glu Glu Arg Leu Met Asn Gln Leu Ala Glu Leu Asn65 70 75 80Gly Ser Ile Gly Asn Tyr Cys Gln Asp Val Thr Asp Ala Gln Ile Lys85 90 95Asn Glu Leu Leu Glu Ser Glu Met Lys Asn Leu Lys Lys Cys Val Ser100 105 110Glu Leu Glu Glu Glu Lys Gln Gln Leu Val Lys Glu Lys Thr Lys Val115 120 125Glu Ser Glu Ile Arg Lys Glu Tyr Leu Glu Lys Ile Gln Gly130 135 140<210>213<211>142<212>PRT<213>智人(Homo sapiens)<400>213Gly Gly Tyr Gly Gly Gly Tyr Gly Gly Val Leu Thr Ala Ser Asp Gly1 5 10 15Leu Leu Ala Gly Asn Glu Lys Leu Thr Met Gln Asn Leu Asn Asp Arg20 25 30Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Ala Ala Asn Gly35 40 45Glu Leu Glu Val Lys Ile Arg Asp Trp Tyr Gln Lys Gln Gly Pro Gly50 55 60Pro Ser Arg Asp Tyr Ser His Tyr Tyr Thr Thr Ile Gln Asp Leu Arg65 70 75 80Asp Lys Ile Leu Gly Ala Thr Ile Glu Asn Ser Arg Ile Val Leu Gln85 90 95Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg Thr Lys Phe Glu100 105 110Thr Glu Gln Ala Leu Arg Met Ser Val Glu Ala Asp Ile Asn Gly Leu115 120 125Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr Asp Leu130 135 140<210>214<211>129<212>PRT<213>智人(Homo sapiens)<400>214Val Met Arg Val Asp Phe Asn Val Pro Met Lys Asn Asn Gln Ile Thr1 5 10 15Asn Asn Gln Arg Ile Lys Ala Ala Val Pro Ser Ile Lys Phe Cys Leu20 25 30Asp Asn Gly Ala Lys Ser Val Val Leu Met Ser His Leu Gly Arg Pro35 40 45Asp Gly Val Pro Met Pro Asp Lys Tyr Ser Leu Glu Pro Val Ala Val50 55 60Glu Leu Arg Ser Leu Leu Gly Lys Asp Val Leu Phe Leu Lys Asp Cys65 70 75 80Val Gly Pro Glu Val Glu Lys Ala Cys Ala Asn Pro Ala Ala Gly Ser85 90 95Val Ile Leu Leu Glu Asn Leu Arg Phe His Val Glu Glu Glu Gly Lys100 105 110Gly Lys Asp Ala Ser Gly Asn Lys Val Lys Ala Glu Pro Ala Lys Ile115 120 125Glu
<210>215<211>148<212>PRT<213>智人(Homo sapiens)<400>215Met Ala Thr Leu Lys Glu Lys Leu Ile Ala Pro Val Ala Glu Glu Glu1 5 10 15Ala Thr Val Pro Asn Asn Lys Ile Thr Val Val Gly Val Gly Gln Val20 25 30Gly Met Ala Cys Ala Ile Ser Ile Leu Gly Lys Ser Leu Ala Asp Glu35 40 45Leu Ala Leu Val Asp Val Leu Glu Asp Lys Leu Lys Gly Glu Met Met50 55 60Asp Leu Gln His Gly Ser Leu Phe Leu Gln Thr Pro Lys Ile Val Ala65 70 75 80Asp Lys Asp Tyr Ser Val Thr Ala Asn Ser Lys Ile Val Val Val Thr85 90 95Ala Gly Val Arg Gln Gln Glu Gly Glu Ser Arg Leu Asn Leu Val Gln100 105 110Arg Asn Val Asn Val Phe Lys Phe Ile Ile Pro Gln Ile Val Lys Tyr115 120 125Ser Pro Asp Cys Ile Ile Ile Val Val Ser Asn Pro Val Asp Ile Leu130 135 140Thr Tyr Val Thr145<210>216<211>527<212>PRT<213>智人(Homo sapiens)<400>216Gln Arg Ala Pro Gly Ile Glu Glu Lys Ala Ala Glu Asn Gly Ala Leu1 5 10 15Gly Ser Pro Glu Arg Glu Glu Lys Val Leu Glu Asn Gly Glu Leu Thr20 25 30Pro Pro Arg Arg Glu Glu Lys Ala Leu Glu Asn Gly Glu Leu Arg Ser35 40 45Pro Glu Ala Gly Glu Lys Val Leu Val Asn Gly Gly Leu Thr Pro Pro50 55 60Lys Ser Glu Asp Lys Val Ser Glu Asn Gly Gly Leu Arg Phe Pro Arg65 70 75 80Asn Thr Glu Arg Pro Pro Glu Thr Gly Pro Trp Arg Ala Pro Gly Pro85 90 95Trp Glu Lys Thr Pro Glu Ser Trp Gly Pro Ala Pro Thr Ile Gly Glu100 105 110Pro Ala Pro Glu Thr Ser Leu Glu Arg Ala Pro Ala Pro Ser Ala Val115 120 125Val Ser Ser Arg Asn Gly Gly Glu Thr Ala Pro Gly Pro Leu Gly Pro130 135 140Ala Pro Lys Asn Gly Thr Leu Glu Pro Gly Thr Glu Arg Arg Ala Pro145 150 155 160Glu Thr Gly Gly Ala Pro Arg Ala Pro Gly Ala Gly Arg Leu Asp Leu165 170 175Gly Ser Gly Gly Arg Ala Pro Val Gly Thr Gly Thr Ala Pro Gly Gly
180 185 190Gly Pro Gly Ser Gly Val Asp Ala Lys Ala Gly Trp Val Asp Asn Thr195 200 205Arg Pro Gln Pro Pro Pro Pro Pro Leu Pro Pro Pro Pro Glu Ala Gln210 215 220Pro Arg Arg Leu Glu Pro Ala Pro Pro Arg Ala Arg Pro Glu Val Ala225 230 235 240Pro Glu Gly Glu Pro Gly Ala Pro Asp Ser Arg Ala Gly Gly Asp Thr245 250 255Ala Leu Ser Gly Asp Gly Asp Pro Pro Lys Pro Glu Arg Lys Gly Pro260 265 270Glu Met Pro Arg Leu Phe Leu Asp Leu Gly Pro Pro Gln Gly Asn Ser275 280 285Glu Gln Ile Lys Ala Arg Leu Ser Arg Leu Ser Leu Ala Leu Pro Pro290 295 300Leu Thr Leu Thr Pro Phe Pro Gly Pro Gly Pro Arg Arg Pro Pro Trp305 310 315 320Glu Gly Ala Asp Ala Gly Ala Ala Gly Gly Glu Ala Gly Gly Ala Gly325 330 335Ala Pro Gly Pro Ala Glu Glu Asp Gly Glu Asp Glu Asp Glu Asp Glu340 345 350Glu Glu Asp Glu Glu Ala Ala Ala Pro Gly Ala Ala Ala Gly Pro Arg355 360 365Gly Pro Gly Arg Ala Arg Ala Ala Pro Val Pro Val Val Val Ser Ser370 375 380Ala Asp Ala Asp Ala Ala Arg Pro Leu Arg Gly Leu Leu Lys Ser Pro385 390 395 400Arg Gly Ala Asp Glu Pro Glu Asp Ser Glu Leu Glu Arg Lys Arg Lys405 410 415Met Val Ser Phe His Gly Asp Val Thr Val Tyr Leu Phe Asp Gln Glu420 425 430Thr Pro Thr Asn Glu Leu Ser Val Gln Ala Pro Pro Glu Gly Asp Thr435 440 445Asp Pro Ser Thr Pro Pro Ala Pro Pro Thr Pro Pro His Pro Ala Thr450 455 460Pro Gly Asp Gly Phe Pro Ser Asn Asp Ser Gly Phe Gly Gly Ser Phe465 470 475 480Glu Trp Ala Glu Asp Phe Pro Leu Leu Pro Pro Pro Gly Pro Pro Leu485 490 495Cys Phe Ser Arg Phe Ser Val Ser Pro Ala Leu Glu Thr Pro Gly Pro500 505 510Pro Ala Arg Ala Pro Asp Ala Arg Pro Ala Gly Pro Val Glu Asn515 520 525<210>217<211>466<212>DNA<213>智人(Homo sapiens)<400>217gaatggtgcc tgtcctgctg tctctgctgc tgcttctggg tcctgctgtc ccccaggaga 60accaagatgg tcgttactct ctgacctata tctacactgg gctgtccaag catgttgaag120acgtccccgc gtttcaggcc cttggctcac tcaatgacct ccagttcttt agatacaaca180gtaaagacag gaagtctcag cccatgggac tctggagaca ggtggaagga atggaggatt240ggaagcagga cagccaactt cagaaggcca gggaggacat ctttatggag accctgaaag300acatcgtgga gtattacaac gacagtaacg ggtctcacgt attgcaggga aggtttggtt360gtgagatcga gaataacaga agcagcggag cattctggaa atattactat gatggaaagg420actacattga attcaacaaa gaaatcccag cctgggtccc cttcga 466
<210>218<211>381<212>DNA<213>智人(Homo sapiens)<400>218gagtttcctt cgcaagttca tgtggggtac cttcccaggc tgcctggctg accagctggt 60tttaaagcgc cggggtaacc agttggagat ctgtgccgtg gtcctgaggc agttgtctcc120acacaagtac tacttcctcg tgggctacag tgaaactttg ctgtcctact tttacaaatg180tcctgtgcga ctccacctcc aaactgtgcc ctcaaaggtt gtgtataagt acctctagaa240caatcccctt ttttccatca agctgtagcc tgcagagaat ggaaacgtgg gaaaggaatg300gtatgtgggg gaaatgcatc ccctcagagg actgaggcat agtctctcat ctgctattga360ataaagacct tctatcttgt a 381<210>219<211>1293<212>DNA<213>智人(Homo sapiens)<400>219gaggggaggc gcatggcggg gatggcgctg gcgcgggcct ggaagcagat gtcctggttc 60tactaccagt acctgctggt cacggcgctc tacatgctgg agccctggga gcggacggtg 120ttcaattcca tgctggtttc cattgtgggg atggcactat acacaggata cgtcttcatg 180ccccagcaca tcatggcgat attgcactac tttgaaatcg tacaatgacc aagatgcgac 240caggatcaga ggttccttgg ggaagaccca ccctacgaag ttggaatgag accatcagat 300gtgataagaa actcttctag atgtcaacat aaccaacctt ataaagacta aaattcatga 360gtagaacagg aaaatcatcc tgactcatgt gttgtgttct ttatttttaa ttttcaaaga 420ggctcttgta tagcagtttt tgtctatttt aacattgtag tcatttgtac tttgatatca 480gtattttctt aacctttgtg actgtttcaa tattaccccc gtgaaagctt ttcttaatgt 540aactttgagt acattttaat tgccttctat ttttaaaact caaaatcatt agttgggctt 600tactgttctt gctattgtat ggcatataca tctgcctgga tatatttcta ctcttgacca 660aagttttgta aagaacaata taagatttcg ggtaggggta tggggaggga agatatttta 720ttgagaacta cttaacaaaa gatttatctg taagcttgaa ctcaggagta cagttttagc 780tatctagact ctaacagctt ttgctttaaa attattaaag tgtttcttaa tgaaaaagaa 840aagatcttgc taaagttaaa ataaggaaca tttcaccttt taaatattta attcttatgt 900ggacttattt ccagaaaact ttggtgataa ttcttgagac aaaaggtggt taagtagcat 960tattatgtaa tgcttatata ccatagagtt tttaatagaa gagaaatcca tttcctccga1020gggtcactat taacaatgta cttccttaaa tttagtttaa tgattgtaat gggtgctgca1080tttgcacatt gcattaagtt atgatgagac gaattgttgt taaaaattat agcaaaaaga1140aatgtaaact tggttaaaat cctttcactc tttgtattgt tttttttaag gtttttattc1200cttaaatgta aaatgactac ctaatttttt gatgtaaata cattaaattc aaagagaaaa1260aaaatcaaaa aaaaaaaaaa aaaaaaactc gag 1293<210>220<211>983<212>DNA<213>智人(Homo sapiens)<400>220caggttattc tgatcctgcc gcctgtcttc cctgtaagag tggagcctcg aggtgtacct 60taaagtgacc ggaatgttag agatgcaatt tgcagagctg gggcaaggaa gggctccttg120tcactgtagt tactttcctt gcagtggcca aatgcccaat aagaaggaat acatgaccac180tgctgtgggg agtcagcagg tgcgtgatgc agctggccac actccatcca cggccatgac240ataaaacaga caagaagtaa ggctggactg taacacctca aggcctgctc cagtgaccca300ctttcttcag agaggctcta ccacacacac aaccaccttc caaatttaca ctcagatcac360tacaccatgt ctcccaagtt aaaacatgta tccacctaga ctttaaatgt gctttgtaac420tgttgatggc actgtacaga gggccaaagt atttcccatc agatagcatt tttctgaacc480catgcctctt gggacgagat cacaggactt gacccatcat caaataggac caggtgacct540acagagacat cacaatgatg gcttcctaca gtcaagtcca tttccaataa tgctctcatc600taagagaacc catgaacctt atttgaatcc tggttcaaac aaaaacctta aattatttat660gagacaatta taaacttgat agattttgat gtgtgaaggt atttatgaat atttttagtc720agtgatggta tactgttaag gaaaaggttc atattttagg gacaaaggct gaaacattta780tggacagagt gatatgatat ctgggatttg ttttaggatg aagtgggagg gaggaaatga840atggaaatag tgttgaaaca gtattggcca cgagtcagct attgtgtgct aagacgctcc900tcacaccagt ctactctgta tgtgtttgaa tatctctgta ataaacttaa caaggaaaaa960aaaaaaaaaa aaaaaaactc gag983<210>221<211>373<212>DNA<213>智人(Homo sapiens)<400>221cattttatgg gttaattttt tattaaatag caataagata cttttataac tcaataaaat 60tattcaatga tacattcgga aaataaatgt ataaaatatg aaaaagtact aaaaagcatt120tttcagtact tttaggtaag attaatccaa ctaaacacta gcatatgtta tacagtaata180ataaggggaa aatacaataa tgttgagaaa gcaaactcaa agcatagatc aatgaaaaaa240ttgagaaatg gacataaatg atttagtatt tttaaagaga gtgaaaaatc attattttat300gcttttgtgt agcgttagat gaattaaata acatatgcac atatagcttt gcgatacaaa360tttccagacc ata 373<210>222<211>544<212>DNA<213>智人(Homo sapiens)<400>222cagagatgct gctgctacaa aggatcggtg taagcagtta acccaggaaa tgatgacaga 60gaaagaaaga agcaatgtgg ttataacaag gatgaaagat cgaattggaa cattagaaaa120ggaacataat gtatttcaaa acaaaataca tgtcagttat caagagactc aacagatgca180gatgaagttt cagcaagttc gtgagcagat ggaggcagag atagctcact tgaagcagga240aaatggtata ctgagagatg cagtcagcaa cactacaaat caactggaaa gcaagcagtc300tgcagaacta aataaactac gccaggatta tgctaggttg gtgaatgagc tgactgagaa360aacaggaaag ctacagcaag aggaagtcca aaagaagaat gctgagcaag cagctactca420gttgaaggtt caactacaag aagctgagag aaggtgggaa gaagttcaga gctacatcag480gaagagaaca gcggaacatg aggcagcaca gctagattta cagagtaaat ttgtggccaa540agaa 544<210>223<211>316<212>DNA<213>智人(Homo sapiens)<400>223gaggcaaggg atatgcttta gtgcctatta tagttaattc ttcaactcca aagtctaaaa 60cagttgaatc tgctgaagga aaatctgaag aagtaaatga aacattagtt atacccactg120aggaagcaga aatggaagaa agtggacgaa gtgcaactcc tgttaactgt gaacagcctg180atatcttggt ttcttctaca ccaataaatg aaggacagac tgtgttagac aaggtggctg240agcagtgtga acctgctgaa agtcagccag aagcacttct gagaggaaga tgtttgcaag300gtaactctaa cagttg316<210>224<211>1583<212>DNA<213>智人(Homo sapiens)
<400>224cagaccacgt ctgccctcgc cgctctagcc ctgcgcccca gcccggccgc ggcacctccg 60cctcgccgcc gctaggtcgg ccggctccgc ccggctgccg cctaggatga atatcatgga 120cttcaacgtg aagaagctgg cggccgacgc aggcaccttc ctcagtcgcg ccgtgcagtt 180cacagaagaa aagcttggcc aggctgagaa gacagaattg gatgctcact tagagaacct 240ccttagcaaa gctgaatgta ccaaaatatg gacagaaaaa ataatgaaac aaactgaagt 300gttattgcag ccaaatccaa atgccaggat agaagaattt gtttatgaga aactggatag 360aaaagctcca agtcgtataa acaacccaga acttttggga caatatatga ttgatgcagg 420gactgagttt ggcccaggaa cagcttatgg taatgccctt attaaatgtg gagaaaccca 480aaaaagaatt ggaacagcag acagagaact gattcaaacg tcagccttaa attttcttac 540tcctttaaga aactttatag aaggagatta caaaacaatt gctaaagaaa ggaaactatt 600gcaaaataag agactggatt tggatgctgc aaaaacgaga ctaaaaaagg caaaagctgc 660agaaactaga aattcatctg aacaggaatt aagaataact caaagtgaat ttgatcgtca 720agcagagatt accagacttc tgctagaggg aatcagcagt acacatgccc atcaccttcg 780ctgtctgaat gactttgtag aagcccagat gacttactat gcacagtgtt accagtatat 840gttggacctc cagaaacaac tgggaagttt tccatccaat tatcttagta acaacaatca 900gacttctgtg acacctgtac catcagtttt accaaatgcg attggttctt ctgccatggc 960ttcaacaagt ggcctagtaa tcacctctcc ttccaacctc agtgacctta aggagtgtag1020tggcagcaga aaggccaggg ttctctatga ttatgatgca gcaaacagta ctgaattatc1080acttctggca gatgaggtga tcactgtgtt cagtgttgtt ggaatggatt cagactggct1140aatgggggaa aggggaaacc agaagggcaa ggtgccaatt acctacttag aactgctcaa1200ttaagtaggt ggactatgga aaggttgccc atcatgactt tgtatttata tacaattaac1260tctaaataaa gcaggttaag tatcttccat gttaatgtgt taagagactg aaaataccag1320ccatcagaaa ctggcctttt tgccaataaa gttgcatggt aaatatttca ttacagaatt1380tatgttagag ctttcatgcc aagaatgttt tcttacaaaa ttctcttttt attgaggttt1440cactaataag cagcttctac ttttgagcct caacttaaag cagaactgtt ttttactgga1500tttttcatta acagcaagct ttttttttta tgtaaaataa atctattgtg aattgaaaaa1560aaaaaaaaaa aaaaaaactc gag1583<210>225<211>491<212>DNA<213>智人(Homo sapiens)<400>225gaacaacatc atcttgaatc actagataga ctcttgacgg aaagcaaagg ggaaatgaaa 60aaggaaaata tgaagaaaga tgaagcttta aaagcattac agaaccaagt atctgaagaa120acaatcaagg ttaggcaact agattcagca ttggaaattt gtaaggaaga acttgtcttg180catttgaatc aattggaagg aaataaggaa aagtttgaaa aacagttaaa gaagaaatct240gaagaggtat attgtttaca gaaagagcta aagataaaaa atcacagtct tcaagagact300tctgagcaaa acgttattct acagcatact cttcagcaac agcagcaaat gttacaacaa360gagacaatta gaaatggaga gctagaagat actcaaacta aacttgaaaa acaggtgtca420aaactggaac aagaacttca aaaacaaagg gaaagttcag ctgaaaagtt gagaaaaatg480gaggagaaat g 491<210>226<211>483<212>DNA<213>智人(Homo sapiens)<400>226cagccgcacg ccgcggagca ggggctcgga ggtcccggga ttacggtgct cgagcacgct 60ggtgggaaag gacccgggac ttgaacagtg ttgtgcggcg ccatgcaggt ctccagcctc120aatgaggtga agatttacag cctcagctgc ggcaagtccc ttcctgagtg gctttctgat180aggaagaaga gagcgctaca gaagaaagat gtagatgtcc gtaggagaat tgaacttatt240caggactttg aaatgcctac tgtgtgtacc actattaagg tgtcaaaaga tggacagtac300attttagcaa ctggaacata taaacctcgg gttcgatgtt atgacaccta tcaattatcc360ttgaagtttg aaaggtgttt agattcagaa gttgtcacct ttgaaatttt gtctgatgac420tactcaaaga ttgtcttctt acataatgat agatacattg aatttcattc gcaatcaggt480ttt 483<210>227<211>486<212>DNA<213>智人(Homo sapiens)<400>227gagcctcgct aagctccgac tctgggcggc accgggcgtc ccacgatgcc gaagaacaag 60aagcggaaca ctccccaccg cggtagcagt gctggcggcg gcgggtcagg agcagccgca120gcgacggcgg cgacagcagg tggccagcat cgaaatgttc agccttttag tgatgaagat180gcatcaattg aaacagtgag ccattgcagt ggttatagcg atccttccag ttttgctgaa240gatggaccag aagtccttga tgaggaagga actcaagaag acctagagta caagttgaag300ggattaattg acctaaccct ggataagagt gcgaagacaa ggcaagcagc tcttgaaggt360attaaaaatg cactggcttc aaaaatgctg tatgaattta ttctggaaag gagaatgact420ttaactgata gcattgaacg ctgcctgaaa aaaggtaaga gtgatgagca acgtgcagct480gcagcg 486<210>228<211>494<212>DNA<213>智人(Homo sapiens)<400>228gaggccagga ctccgggaat gcgagcaggc cccttattct cccagtggcc tcggtctgtc 60cccacagcgg cccggtcagg gttgcccgag ccccaaggcg gggggcggca ccggggtgct120gaaagggaca gaatgctttg acctccaagc tgttttaaat ctagtagata agccagatcc180tgtgttgcca taagcccttg gcccacattt aagtgggaat gcagctagct tggatgtctg240aaactttgta agcgccttct gtctgaatcc tgaacacagg caccaagact actgaagaag300ctcgtcattc ttgtgcaggg atagccacac aagcaaacat gtttgcaaaa cttgaaagaa360agaaaattgc agaaagaaga cttgctgttc ttaagaggcc caggaaggtg ctacttagga420atcccaccgg cttgtgaagc aagggaatca agtttgcctt caatggggaa cttgacttca480ggaaaatgaa cttt 494<210>229<211>465<212>DNA<213>智人(Homo sapiens)<400>229gtcagagagc tggtataacc tcctgttgga catgcagaac cgactcaata aggtcatcaa 60aagcgtgggc aagattgagc actccttctg gagatccttt cacactgagc gaaagacaga120accagccaca ggcttcatcg atggtgatct gattgaaagt ttcctagata tcagccgccc180taagatgcag gaggttgtgg caaacttgca gtatgatgat ggcagtggta tgaagcggga240ggcaactgca gatgacctca tcaaagtcgt ggaggaacta actcggatcc attagccaag300gacaggatct cttttcctga ccctcctaaa ggcgttgccc tcctatcctc ccttccttgc360ccacccttgg tttctttggc atgggaaggt tttccttaac cacttgccct agagccacca420gtgaccttgt gtggaaacag ggtttttttt acttaaaaca gttca465<210>230<211>495<212>DNA<213>智人(Homo sapiens)<400>230caggggaaag ggtgtttggc cttgaccagc cactgctgac ctcaatctca gacctacaga 60tggtgaatat ctccctgcga gtgttgtctc gacccaatgc tcaggagctt cctagcatgt120accagcgcct agggctggac tacgaggaac gagtgttgcc gtccattgtc aacgaggtgc180tcaagagtgt ggtggccaag ttcaatgcct cacagctgat cacccagcgg gcccaggtat240ccctgttgat ccgccgggag ctgacagaaa gggccaaagg acttcagcct catcctggat300gatgtggcca tcacagactt gagctttagc cgagaagtac acaagctgcc tgtaagaaac360ccaaccaagt ggggtgaatt ccaaaaaccc gtgggggtga agggcttctt aagaatgcaa420ggaaggagga aaagaattcc atgggggggg ggttccttaa cccaggaaca ggggtttccc480ttgaattttt ttcca 495<210>231<211>498<212>DNA<213>智人(Homo sapiens)<400>231ggcagcttct gagaccaggg ttgctccgtc cgtgctccgc ctcgccatga cttcctacag 60ctatcgccag tcgtcggcca cgtcgtcctt cggaggcctg ggcggcggct ccgtgcgttt120tgggccgggg gtcgcttttc gcgcgcccag cattcacggg ggctccggcg gccgcggcgt180atccgtgtcc tccgcccgct ttgtgtcctc gtcctcctcg gggggctacg gcggcggcta240cggcggcgtc ctgaccgcgt ccgacgggct gctggcgggc aacgagaagc taaccatgca300gaacctcaac gaccgcctgc ctcctacctg gacaaagtgc gcgccctgga agcgggcaac360ggcgaactta gaggtgaaag aatcccgcga actggtacca aaaacaaggg gcctggggcc420ttccgcgact tacagccaac ttactacacc gaacattcaa gaacttgcgg gaacaaaaat480ttttggtgcc acccattt 498<210>232<211>465<212>DNA<213>智人(Homo sapiens)<400>232caggccggcc gagtaggaaa gctggaggcg cgggtgggga acatgtctga gtcggagctc 60ggcaggaagt gggaccggtg tctggcggat gcggtcgtga agataggtac tggttttgga120ttaggaattg ttttctcact taccttcttt aaaagaagaa tgtggccatt agccttcggt180tctggcatgg gattaggaat ggcttattcc aactgtcagc atgatttcca ggctccatat240cttctacatg gaaaatatgt caaagagcag gagcagtgac ttcacctgag aacatcccag300cgggaggaca agagaaaatc atgtttattc ctcaggaata cttgaagtgc cctggagtaa360actgccattc ttctgtaaca atggtatcag taatgcttta aactccagca cctggttatg420catttgaaac ccaagtctgg ttcttggttt ggattttctc tctgg465<210>233<211>366<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(366)<223>n＝A、T、C或G<400>233cagtaaaaaa ggttatgttt tattaattgc tggacaaccg tgggaaaaca aataagcaat 60tgacaccacc aaattcttat tacattcaan ataaaanatt tattcacacc acaaaaagat120aatcacaaca aaatatacac taacttaaaa aacaaaagat tatagtgaca taaaatgtta180tattctcttt ttaagtgggt aaaagtattt tgtttgcttc tacataaatt tctattcatg240ananaataac aaatattaaa atacagtgat agtttgcatt tcttctatag aatgaacata300gacataaccc tgaagctttt agtttacagg gagtttccat gaagccacaa actaaactaa360ttatca 366
<210>234<211>379<212>DNA<213>智人(Homo sapiens)<400>234gagggcagcc ctcctacctg cgcacgtggt gccgccgctg ctgcctcccg ctcgccctga 60acccagtgcc tgcagccatg gctcccggcc agctcgcctt atttagtgtc tctgacaaaa120ccggccttgt ggaatttgca agaaacctga ccgctcttgg tttgaatctg gtcgcttccg180gagggactgc aaaagctctc agggatgctg gtctggcagt cacagatgtc tctgagttga240cgggatttct gaaatgttgg ggggacgtgt gaaaactttg catcctgcac gatcccatgc300tggaatccta gctcctaata ttcagaagat aatgcttgac atgcgccaca cttgattcaa360tcttataaca attgttgcc 379<210>235<211>406<212>DNA<213>智人(Homo sapiens)<400>235caggctgcac catgtacccc accttcagtt taaaagaaaa aaaaaatccc cttcactcct 60actgggaggt gggacccctt tcattttcag ttttgctcat ctagggaaaa taaggctttg120gtttccagtt taattgtttt tgaccttcta aaatgttttt atgttagcac tgatagttgg180cattactgtt gttaagcact gtgttccaga ccgtgtctga cttagtgtaa cctaggagat240tttatagttt tattttaatg aaaccctgat tgacgcacag cagtggggag aacagcgtct300tttacctgtc accgaagcca ggaagccccg tttgtaagcg tgtgttgtgg tgctttattg360tacatcctcc agtggcgttc tttttactct aatgttcttt tggttt 406<210>236<211>278<212>DNA<213>智人(Homo sapiens)<400>236gagattagca cctgtgaaca atgcgttctc tgatgacact ctgagcatgg accaacgcct 60tcttaagcta attctgcaaa atcacatatt gaaagtaaaa gttggcctta gcgacctcta120caatggacag atactggaaa ccattggagg caaacaactc cgagtctttg tgtatcggac180ggctatctgc atagaaaact catgcatggt gagaggaagc aagcagggaa ggaacggtgc240cattcacata ttccgagaga tcatccaacc agcagaat278<210>237<211>322<212>DNA<213>智人(Homo sapiens)<400>237cagggccgtg gcggaggagg agcgctgcac ggtggagcgt cgggccgacc tcacctacgc 60ggagttcgtg cagcagtacg tgcgcccctg atcgcggagg tcgcgtcctg ttcaccggcc120cgtctgcccc gaccgcccaa ggccgccttc ccctgacctc gcgcgcacgc gtggggctgg180ggcggcgagg ctggcggtcc ggcctggccg cgactctgcc cttctttcca gaggttccgg240gccctgtgct cccgcgacag gttgctggct tcgtttgggg acagagtggt ccggtgagca300ccgccaacac ctactcctac ct 322<210>238<211>613<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(399)<223>n＝A、T、C或G<400>238gaattcggca ccagccttct tggatcagga ccagtctcca ccccgtttct acagtggaga 60tcagcctcct tcttatcttg gtgcaagtgt ggataaactc catcaccctt tagaatttgc 120agacaaatct cccacacctc ctaatttacc tagcgataaa atctaccctc cttctgggtc 180ccccgaagag aataccagca cagccaccat gacttacatg acaactactc cagcaacagc 240ccaaatgagc accaaggaag ccagctggga tgtggctgaa caacccacca ctgctgattt 300tgctgctgcc acacttcagc gcacgcacag aactaatcgt ccccttcccc ctccgccttc 360ccagagatct gcagagcagc caccagttgt ggggcaggna caagcagcaa ccaatatagg 420attaaataat tcccacaagg ttcaaggagt agttccagtt ccagagaggc cacctgaacc 480tcgagccatg gatgaccctg cgtctgcctt catcagtgac agtggtgctg ctgctgctca 540gtgtcccatg gctacagctg tccagccagg cctgcctgag aaagtgcggg acggtgcccg 600ggtcccgctg ctg 613<210>239<211>613<212>DNA<213>智人(Homo sapiens)<400>239gaattcggca ccaggggaca ctggtgctga gctggatgat gatcagcact ggtctgacag 60cccgtcggat gctgacagag agctgcgttt gccgtgccca gctgaggggg aagcagagct 120ggagctgagg gtgtcggaag atgaggagaa gctgcccgcc tcaccgaagc accaagagag 180aggtccctcc caagccacca gccccatccg gtctccccag gaatcagctc ttctgttcat 240tccagtccac agcccctcaa cagaggggcc ccaactccca cctgtccctg ccgccaccca 300ggagaaatca cctgaggagc gccttttccc tgagcctttg ctccccaaag agaagcccaa 360agctgatgcc ccctcggatc tgaaagctgt gcactctccc atccgatcac agccagtgac 420cctgccagaa gctaggactc ctgtctcacc agggagcccg cagccccagc cacccgtggc 480ggcctccacg cccccaccca gcgaggtctc cagagccttc tctctcctgt gcaaaatggc 540aactcttaag gaaaaactca ttgcaccagt tgcggaagaa gaggcaacag ttccaaacaa 600taagatcact gta 613<210>240<211>585<212>DNA<213>智人(Homo sapiens)<400>240gaattcggca cgaggtgaga tctacgatga actttaagat tggaggtgtg acagaacgca 60tgccaacccc agttattaaa gcttttggca tcttgaagcg agcggccgct gaagtaaacc 120aggattatgg tcttgatcca aagattgcta atgcaataat gaaggcagca gatgaggtag 180ctgaaggtaa attaaatgat cattttcctc tcgtggtatg gcagactgga tcaggaactc 240agacaaatat gaatgtaaat gaagtcatta gcaatagagc aattgaaatg ttaggaggtg 300aacttggcag caagatacct gtgcatccca acgatcatgt taataaaagc cagagctcaa 360atgatacttt tcccacagca atgcacattg ctgctgcaat agaagttcat gaagtactgt 420taccaggact acagaagtta catgatgctc ttgatgcaaa atccaaagag tttgcacaga 480tcatcaagat tggacgtact catactcagg atgctgttcc acttactctt gggcaggaat 540ttagtggtta tgttcaacaa gtaaaatatg caatgacaag aataa 585<210>241<211>566<212>DNA<213>智人(Homo sapiens)<400>241gaattcggca ccaggcgagc tgcacctcga ggtgaaggcc tcactgatga acgatgactt 60cgagaagatc aagaactggc agaaggaagc ctttcacaag cagatgatgg gcggcttcaa 120ggagaccaag gaagctgagg acggctttcg gaaggcacag aagccctggg ccaagaagct 180gaaagaggta gaagcagcaa agaaagccca ccatgcagcg tgcaaagagg agaagctggc 240tatctcacga gaagccaaca gcaaggcaga cccatccctc aaccctgaac agctcaagaa 300attgcaagac aaaatagaaa agtgcaagca agatgttctt aagaccaaag agaagtatga 360gaagtccctg aaggaactcg accagggcac accccagtac atggagaaca tggagcaggt 420gtttgagcag tgccagcagt tcgaggagaa acgccttcgc ttcttccggg aggttctgct 480ggaggttcag aagcacctag acctgtccaa tgtggctggc tacaaagcca tttaccatga 540cctggagcag agcatcagag cagctg 566<210>242<211>556<212>DNA<213>智人(Homo sapiens)<400>242gaattcggca cgagcaaagg tgaagcagga catgcctccg cccgggggct atgggcccat 60cgactacaaa cggaacttgc cgcgtcgagg actgtcgggc tacagcatgc tggccatagg 120gattggaacc ctgatctacg ggcactggag cataatgaag tggaaccgtg agcgcaggcg 180cctacaaatc gaggacttcg aggctcgcat cgcgctgttg ccactgttac aggcagaaac 240cgaccggagg accttgcaga tgcttcggga gaacctggag gaggaggcca tcatcatgaa 300ggacgtgccc gactggaagg tgggggagtc tgtgttccac acaacccgct gggtgccccc 360cttgatcggg gagctgtacg ggctgcgcac cacagaggag gctctccatg ccagccacgg 420cttcatgtgg tacacgtagg ccctgtgccc tccggccacc tggatccctg cccctcccca 480ctgggacgga ataaatgctc tgcagacctg gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 540aaaaaaaaaa ctcgag 556<210>243<211>591<212>DNA<213>智人(Homo sapiens)<400>243gtctatgttt gcagaaatac agatccaaga caaagacagg atgggcactg ctggaaaagt 60tattaaatgc aaagcagctg tgctttggga gcagaagcaa cccttctcca ttgaggaaat 120agaagttgcc ccaccaaaga ctaaagaagt tcgcattaag attttggcca caggaatctg 180tcgcacagat gaccatgtga taaaaggaac aatggtgtcc aagtttccag tgattgtggg 240acatgaggca actgggattg tagagagcat tggagaagga gtgactacag tgaaaccagg 300tgacaaagtc atccctctct ttctgccaca atgtagagaa tgcaatgctt gtcgcaaccc 360agatggcaac ctttgcatta ggagcgatat tactggtcgt ggagtactgg ctgatggcac 420caccagattt acatgcaagg gcaaaccagt ccaccacttc atgaacacca gtacatttac 480cgagtacaca gtggtggatg aatcttctgt tgctaagatt gatgatgcag ctcctcctga 540gaaagtctgt ttaattggct gtgggttttc cactggatat ggcgctgctg t 591<210>244<211>594<212>DNA<213>智人(Homo sapiens)<400>244gaattcggca cgagaacaga gtgaactgag catcagtcag aaaaagtcta tgtttgcaga 60aatacagatc caagacaaag acaggatggg cactgctgga aaagttatta aatgcaaagc 120agctgtgctt tgggagcaga agcaaccctt ctccattgag gaaatagaag ttgccccacc 180aaagactaaa gaagttcgca ttaagatttt ggccacagga atctgtcgca cagatgacca 240tgtgataaaa ggaacaatgg tgtccaagtt tccagtgatt gtgggacatg aggcaactgg 300gattgtagag agcattggag aaggagtgac tacagtgaaa ccaggtgaca aagtcatccc 360tctctttctg ccacaatgta gagaatgcaa tgcttgtcgc aacccagatg gcaacctttg 420cattaggagc gatattactg gtcgtggagt actggctgat ggcaccacca gatttacatg 480caagggcaaa ccagtccacc acttcatgaa caccagtaca tttaccgagt acacagtggt 540ggatgaatct tctgttgcta agattgatga tgcagctcct cctgagaaag tctg594<210>245<211>615<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(105)<223>n＝A、T、C或G<400>245gtccctttcc tctgctgccg ctcggtcacg cttgtgcccg aaggaggaaa cagtgacaga 60cctggagact gcagttctct atccttccac agctctttca ccatnctgga tcacttcctt 120tgaatgcaga agcttgctgg ccaaaagatg tgggaattgt tgcccttgag atctattttc 180cttctcaata tgttgatcaa gcagagttgg aaaaatatga tggtgtagat gctggaaagt 240ataccattgg cttgggccag gccaagatgg gcttctgcac agatagagaa gatattaact 300ctctttgcat gactgtggtt cagaatctta tggagagaaa taacctttcc tatgattgca 360ttgggcggct ggaagttgga acagagacaa tcatcgacaa atcaaagtct gtgaagacta 420atttgatgca gctgtttgaa gagtctggga atacagatat agaaggaatc gacacaacta 480atgcatgcta tggaggcaca gctgctgtct tcaatgcttg ttaactggat tgagtccagc 540tcttgggatg gacggtatgc cctggtaagt tgcaggagat attgctgtat atgccacagg 600aaatgctaga cctac 615<210>246<211>546<212>DNA<213>智人(Homo sapiens)<400>246gaattcggca ccaggctgcc tcccgctcgc cctgaaccca gtgcctgcag ccatggctcc 60cggccagctc gccttattta gtgtctctgc aaaaccggcc ttgtgaattt gcaagaaacc 120tgaccgctct tggtttgaat ctggtcgctt ccggagggac tgcaaaagct ctcagggatg 180ctggtctggc agtcagagat gtctctgagt tgacgggatt tcctgaaatg ttggggggac 240gtgtgaaaac tttgcatcct gcagtccatg ctggaatcct agctcgtaat attccagaag 300ataatgctga catggccaga cttgatttca atcttataag agttgttgcc tgcaatctct 360atccctttgt aaagacagtg gcttctccag gtgtaactgt tgaggaggct gtggagcaaa 420ttgacattgg tggagtaacc ttactgagag ctgcagccaa aaaccacgct cgagtgacag 480tggtgtgtga accagaggac tatgtgggtg ggtgtccacg gagatgcaga gctccgagag 540taagga 546<210>247<211>564<212>DNA<213>智人(Homo sapiens)<400>247gaattcggca ccagagatca cgtgcagtga gatgcagcaa aaagttgaac ttctgagata 60tgaatctgaa aagcttcaac aggaaaattc tattttgaga aatgaaatta ctactttaaa 120tgaagaagat agcatttcta acctgaaatt agggacatta aatggatctc aggaagaaat 180gtggcaaaaa acggaaactg taaaacaaga aaatgctgca gttcagaaga tggttgaaaa 240tttaaagaaa cagatttcag aattaaaaat caaaaaccaa caattggatt tggaaaatac 300agaacttagc caaaagaact ctcaaaacca ggaaaaactg caagaactta atcaacgtct 360aacagaaatg ctatgccaga aggaaaaaga gccaggaaac agtgcattgg aggaacggga 420acaagagaag tttaatctga aagaagaact ggaacgttgt aaagtgcagt cctccacttt 480agtgtcttct ctggaggcgg agctctctga agttaaaata cagacccata ttgtgcaaca 540ggaaaaccac cttctcaaag atga 564<210>248<211>434<212>DNA<213>智人(Homo sapiens)<400>248gttcttgttt gtggatcgct gtgatcgtca cttgacaatg cagatcttcg tgaagactct 60gactggtaag accatcaccc tcgaggttga gcccagtgac accatcgaga atgtcaaggc 120aaagatccaa gataaggaag gcatccctcc tgaccagcag aggctgatct ttgctggaaa 180acagctggaa gatgggcgca ccctgtctga ctacaacatc cagaaagagt ccaccctgca 240cctggtgctc cgtctcagag gtgggatgca aatcttcgtg aagacactca ctggcaagac 300catcaccctt gaggtggagc ccagtgacac catcgagaac gtcaaagcaa agatccagga 360caaggaaggc attcctcctg accagcagag gttgatcttt gccggaaagc cagcctggga 420agatggggcc gcca434<210>249<211>416<212>DNA<213>智人(Homo sapiens)<400>249gcgggcccag gaggcggcgg cggcggcggc ggacgggccc cccgcggcag acggcgagga 60cggacaggac ccgcacagca agcacctgta cacggccgac atgttcacgc acgggatcca 120gagcgccgcg cacttcgtca tgttcttcgc gccctggtgt ggacactgcc agcggctgca 180gccgacttgg aatgacctgg gagacaaata caacagcatg gaagatgcca aagtctatgt 240ggctaaagtg gactgcacgg cccactccga cgtgtgctcc gcccaggggg tgcgaggata 300ccccacctta aagcttttca agccaggcca agaagctgtg aagtaccagg gtcctcggga 360cttccagaca ctggaaaact ggatgctgca gacactgaac gaggagccag tgacac 416<210>250<211>504<212>DNA<213>智人(Homo sapiens)<400>250gaattcggca cgaggcgggt aacgttatag tatttgtcag aagttggggt ctccgtgggc 60attgtgatcc gtcccaggca gtggattagg aggccagaag gagatccctt ccacggtgct 120aggctgagat ggatcctctc agggcccaac agctggctgc ggagctggag gtggagatga 180tggccgatat gtacaacaga atgaccagtg cctgccaccg gaagtgtgtg cctcctcact 240acaaggaagc agagctctcc aagggcgagt ctgtgtgcct ggaccgatgt gtctctaagt 300acctggacat ccatgagcgg atgggcaaaa agttgacaga gttgtctatg caggatgaag 360agctgatgaa gagggtgcag cagagctctg ggcctgcatg aggtccctgt cagtatacac 420cctggggtgt accccacccc ttcccacttt aataaacgtg ctccctgttg ggtgtcatct 480gtgaagactg ccaggcctag ctct 504<210>251<211>607<212>DNA<213>智人(Homo sapiens)<400>251gatgaaaata cacaatttta ctagcaaatg cctctactgt aatcgctatt tacccacaga 60tactctgctc aaccatatgt taattcatgg tctgtcttgt ccatattgcc gttcaacttt 120caatgatgtg gaaaagatgg ccgcacacat gcggatggtt cacattgatg aagagatggg 180acctaaaaca gattctactt tgagttttga tttgacattg cagcagggta gtcacactaa 240catccatctc ctggtaacta catacaatct gagggatgcc ccagctgaat ctgttgctta 300ccatgcccaa aataatcctc cagttcctcc aaagccacag ccaaaggttc aggaaaaggc 360agatatccct gtaaaaagtt cacctcaagc tgcagtgccc tataaaaaag atgttgggaa 420aaccctttgt cctctttgct tttcaatcct aaaaggaccc atatctgatg cacttgcaca 480tcacttacga gagaggcacc aagttattca gacggttcat ccagttgaga aaaagctcac 540ctacaaatgt atccattgcc ttggtgtgta taccagcaac atgaccgcct caactatcac 600tctgcat607<210>252<211>618<212>DNA<213>智人(Homo sapiens)<400>252gaattcgcac caggggtcct gctggtcttc gcctttcttc tccgcttcta ccccgtcggc 60cgctgccact ggggtccctg gccccaccga catggcggcg gtgttgagca agtcctggag 120cgcacggagc tgaacaagct gcccaagtct gtccagaaca aacttgaaaa gttccttgct 180gatcagcaat ccgagatcga tggcctgaag gggcggcatg agaaatttaa ggtggagagc 240gaacaacagt attttgaaat agaaaagagg ttgtcccaca gtcaggagag acttgtgaat 300gaaacccgag agtgtcaaag cttgcggctt gagctagaga aactcaacaa tcaactgaag 360gcactaactg agaaaaacaa agaacttgaa attgctcagg atcgcaatat tgccattcag 420agccaattta caagaacaaa ggaagaatta gaagctgaga aaagagactt aattagaacc 480aatgagagac tatctcaaga acttgaatac ttaacagagg atgttaaacg tctgaatgaa 540aaacttaaag aaagcaatac aacaaagggt gaacttcagt taaaattgga tgaacttcaa 600gcttctgatg tttctgtt618<210>253<211>1201<212>DNA<213>智人(Homo sapiens)<400>253gaattcggca ccagggtggc gagcgcggct gctgtgctgg ggcgagcagc ggggaccgtg 60tgtgagtttg gcatgatttg gtcccctggg attctgcctt agcaagaaag aagttggaaa 120tacttcctgg aagaaaacta aaacaataca aaagccacag cttattgatt gcatgtcagc 180ccccttacaa atatggacac atttcctagc ctatttccac ctggaggaga tagtaggctg 240aatcctgagc ctgagttcca aaatatgtta attgatgaaa gggtacgctg tgaacatcat 300aaacataatt atcaggctct gaaaattgaa cacaaaaggt tgcaggaaga atatgtaaaa 360tcacaaaatg aacttaaacg tgtattaatt gaaaagcaag caagccagga aaaattccaa 420ctgctccttg aagacttaag gggagaatta gtagagaaag ctagagacat agaaaaaatg 480aaactgcagg tactaacacc acaaaaattg gaattggtaa aagcccaact acaacaagaa 540ttagaagctc caatgcgaga acgttttcgg actcttgatg aagaagtgga aaggtacaga 600gctgagtata acaagctgcg ctacgagtat acatttctca agtcagagtt tgaacaccag 660aaagaagagt ttactcgggt ttcagaagaa gagaaaatga aatacaagtc agaggttgca 720cgactggaga aggacaaaga ggagctacat aaccagctgc ttagtgttga tcccacgaga 780gacagcaaac gaatggagca acttgttcga gaaaaaaccc atttgcttca gaaattgaaa 840agtttagagg ctgaagtagc agaattaagg gctgagaaag aaaattctgg tgctcaggta 900gaaaatgtcc aaagaataca ggtgaggcag ttggctgaga tgcaggctac actcagatcc 960ttggaggctg aaaagcagtc agctaaacta caagctgagc gtttagaaaa agaactacaa 1020tcaagcaatg aacagaatac ctgcttaatc agcaaactgc atagagctga ccgagaaatc 1080agcacactgg ccagtgaagt gaaagagctt aaacatgcaa acaaactaga aataactgac 1140atcaaactgg aggcagcaag agctaagagt gagctcgaaa gagaaaggaa taagatccaa 1200a 1201<210>254<211>560<212>DNA<213>智人(Homo sapiens)<400>254gaattcggca ccagtttggg gggtgaggtt taattggaaa tggtctctgg ggactgaaaa 60ctgatgtttt tgcagattac ctcagggaaa cggaggtttg ttgagttaca gacacattaa 120accaaaggcc gtgggaaaac ccctctccag ctccagggga ttggtcagga ccacccacta 180accagtgcct tccttcttaa cattcacttt tagcagcttg tgtttatttt acatgggcag 240ttttgatggg aaattgccat gaccacaggg gtttggagtt ctgctttttt tttttcttct 300tctttttcgg gggactgggg gactcctccc aagatcacat tttagcatct ttctctccta 360ctccatttag aaaaataagt aacaggtgaa atgtggtctc agtgttaacg ggataattct 420gctaccggct cctccctgat gattctgaaa tacactactg aacgagctct ggctggtcct 480ttctatcctg gatgtggttc ttctgtgtag caattccttg atgtccagtt tggaaagatg 540tactcttctc aacaagaaaa 560<210>255<211>612<212>DNA<213>智人(Homo sapiens)<400>255gaattcggca ccaggcgggg cagcagggcc gcggccatgg ggagcttgaa ggaggagctg 60ctcaaagcca tctggcacgc cttcaccgac tcgaccagga ccacagggca aggtctccaa 120gtcccagctc aaggtccttt cccataacct gtgcacggtg ctgaaggttc ctcatgaccc 180agttgccctt gaagagcact tcagggatga tgatgagggt ccagtgtcca accagggcta 240catgccttat ttaaacaggt tcattttgga aaaggtccaa gacaactttg acaagattga 300attcaatagg atgtgttgga ccctctgtgt caaaaaaaaa cctcacaaag aatcccctgc 360tcattacaga agaagatgca tttaaaatat gggttatttt caacttttta tctgaggaca 420agtatccatt aattattgtg tcagaagaga ttgaatacct gcttaagaag cttacagaag 480ctatgggagg aggttggcag caagaacaat ttgaacatta taaaatcaac tttgatgaca 540gtaaaaatgg cctttctgca tgggaactta ttgagcttat tggaaatgga cagtttagca 600aaggcatgga cc 612<210>256<211>1132<212>DNA<213>智人(Homo sapiens)<400>256gaattcggca cgaggtctgg gagaggcctc tggagcagga ggcccagtgg ctcttctgac 60ccaaggcccc gccgtccagc ttctaagtgc cagatgatgg aggagcgtgc caacctgatg 120cacatgatga aactcagcat caaggtgttg ctccagtcgg ctctgagcct gggccgcagc 180ctggatgcgg accatgcccc cttgcagcag ttctttgtag tgatggagca ctgcctcaaa 240catgggctga aagttaagaa gagttttatt ggccaaaata aatcattctt tggtcctttg 300gagctggtgg agaaactttg tccagaagca tcagatatag cgactagtgt cagaaatctt 360ccagaattaa agacagctgt gggaagaggc cgagcgtggc tttatcttgc actcatgcaa 420aagaaactgg cagattatct gaaagtgctt atagacaata aacatctctt aagcgagttc 480tatgagcctg aggctttaat gatggaggaa gaagggatgg tgattgttgg tctgctggtg 540ggactcaatg ttctcgatgc caatctctgc ttgaaaggag aagacttgga ttctcaggtt 600ggagtaatag atttttccct ctaccttaag gatgtgcagg atcttgatgg tggcaaggag 660catgaaagaa ttactgatgt ccttgatcaa aaaaattatg tggaagaact taaccggcac 720ttgagctgca cagttgggga tcttcaaacc aagatagatg gcttggaaaa gactaactca 780aagcttcaag aagagctttc agctgcaaca gaccgaattt gctcacttca agaagaacag 840cagcagttaa gagaacaaaa tgaattaatt cgagaaagaa gtgaaaagag tgtagagata 900acaaaacagg ataccaaagt tgagctggag acttacaagc aaactcggca aggtctggat 960gaaatgtaca gtgatgtgtg gaagcagcta aaagaggaga agaaagtccg gttggaactg 1020gaaaaagaac tggagttaca aattggaatg aaaaccgaaa tggaaattgc aatgaagtta 1080ctggaaaagg acacccacga gaagcaggac acactagttg ccctccgcca gc 1132<210>257<211>519<212>DNA<213>智人(Homo sapiens)<400>257gaattcgtga cacgaggtgc tcgagatgaa ccccagcgcc cccagctacc ccatggcctc 60tctgtacgtg ggggacctgc accccgacgt gaccgaggcg atgctctacg agaagttcag 120cccggccggg cccatcctct ccatccgggt ctgcagggac atgatcaccc gccgctcctt 180gggctacgcg tacgtgaact tccagcagcc ggcggacgcg gaacgtgctt tggacaccat 240gaattttgat gttataaagg gcaagccagt acgcatcatg tggtctcagc gtgatccatc 300acttcgcaaa agtggagtag gcaacatatt cattaaaaat ttggacaaat ccatcgacaa 360taaagcacta tatgatacgt tttctgcgtt tggtaacatc ctttcatgta aggtggtttg 420tgatgaaaat ggctccaagg gctatggatt tgtacacttt gaaacacagg aagcagctga 480aagagctatt gaaaaaatga atgggatgct tctaaatga 519<210>258<211>596<212>DNA<213>智人(Homo sapiens)<400>258gctttgccaa agacttagaa gctaagcaga aaatgagctt aacatcctgg tttttggtga 60gcagtggagg cactcgccac aggctgccac gagaaatgat ttttgttgga agagatgact 120gtgagctcat gttgcagtct cgtagtgtgg ataagcaaca cgctgtcatc aactatgatg 180cgtctacgga tgagcattta gtgaaggatt tgggcagcct caatgggact tttgtgaatg 240atgtaaggat tccggaacag acttatatca ccttgaaact tgaagataag ctgagatttg 300gatatgatac aaatcttttc actgtagtac aaggagaaat gagggtccct gaagaagctc 360ttaagcatga gaagtttacc attcagcttc agttgtccca aaaatcttca gaatcagaat 420tatccaaatc tgcaagtgcc aaaagcatag attcaaaggt agcagacgct gctactgaag 480tgcagcacaa aactactgaa gcactgaaat ccgaggaaaa agccatggat atttctgcta 540tgccccgtgg tactccatta tatgggcagc cgtcatggtg gggggatgat gaggtg 596<210>259<211>595<212>DNA<213>智人(Homo sapiens)<400>259gaattcggca ccagagaaaa agcttcaagg tatattgagt cagagtcaag ataaatcact 60tcggagaatt tcagaattaa gagaggagct gcaaatggac cagcaagcaa agaaacatct 120tcaggacgag tttgatgcat gtttggagga gaaagatcag tatatcagtg ttctccagac 180tcaggtttct cttctaaagc agcgattaca gaatggccca atgaatgttg atgctcccaa 240acccctccct cccggggagc tccaggcaga agtgcacggt gacacggaga agatggaggg 300cgtcggggaa ccagtgggag gtgggacttc cgctaaaacc ctggaaatgc tccagcaaag 360agtgaaacgt caggagaatc tgcttcagcg ctgtaaggag acaattgggt cccacaagga 420gcagtgcgca ctgctgctga gtgagaagga ggcactgcag gagcagttgg atgaaaggct 480gcaggagctg gaaaagatga aggggatggt aataaccgag acgaagcggc aaatgcttga 540gaccctggaa ctgaaagaag atgaaattgc tcagcttcgt agtcatatca aacag 595<210>260<211>994<212>DNA<213>智人(Homo sapiens)<400>260gaattcggca cgaggcgttg cctgccttct tgctgtctat cagcctttct tgcctcttcc 60ttttcgcctt ccctgttctt ccctttctca aacaaacaag acatggcaaa ccgcagtcta 120acccagccct ttgaaattat ccatagtttt acagacagct ccaggccatg agccacaatg 180tccaaaatta ttcttgagca ctgatataaa ttacttagac cttctttgag ggcagaactc 240agctgttgct ctcatgatgg gcagtgctgg aaagggttct ggtatgtctt caaaatgagt 300ccacgagttt actgagtgct tacaggtaaa ggaatgaata taagatgtct ttctgatcag 360aacaggtgtc ccttcacatg agctttacta gactctggga gggaaaagta gccaagtact 420tctgaaccat tttttaatac ttgttttgtc atggtgaaat tatagcagtt atcccaaaat 480gttttaatta tcaaaatact gtcttttaaa aaaaaaaaaa agtaacacct tttaaagcat 540tagatttcac ttgggtttct tttccaaaaa atgctaggta gacaaggcat tgtaaacatg 600agtttccttt aagaaccatc agaatataaa tttaacatga agaaaactgc tatatctagt 660agaaataata tctaaagttt aacaactaaa gtaccctcac agaatagcaa atacccttct 720gttctggaca tgggttcaaa tttgaatatg gaaataattt ccttggaagt ccctagaggc 780aggtcagagg aagtatgcat taagagggaa aggagagaat ggaaataaaa gtcactataa 840tgcagattta tgccttattt tttagcattt tttaaatgtt gggtctttca aggtgttttt 900tgctttttat tagatctata taaataagtt aactagcaat ttagttttgt atttaagcta 960cacttaatct ttttctttgg tgatatttat ttct 994<210>261<211>594<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(538)<223>n＝A、T、C或G<400>261gaattcggca ccagtggaga tccagctgaa ccatgccaac cgccaggctg cggaggcaat 60caggaacctt cggaacaccc agggaatgct gaaggacaca cagctgcacc tggacgatgc 120tctcagaggc caggacgacc tgaaagagca gctggccatg gttgagcgca gagccaacct 180gatgcaggct gagatcgagg agctcagggc atccctggaa cagacagaga ggagcaggag 240agtggccgag caagagctac tggatgccag tgagcgcgtg cagctcctcc acacccagaa 300caccagcctc atcaacacca agaagaagct ggagacagac atttcccaaa tccagggaga 360gatggaagac atcgtccagg aagcccgcaa cgcagaagag aaggccaaga aagccatcac 420tgatgccgcc atgatggcgg aggagctgaa gaaggagcag gacaccagcg cccacctgga 480gcggatgaag aagaacatgg agcagaccgt gaaggacctg cagcaccgtc tggacgangc 540tgagcagctt ggcgctgaag ggcgggcaag aagcagatcc agaaactgga ggct594<210>262<211>594<212>DNA<213>智人(Homo sapiens)<400>262gaaaaggtgg ctggagccaa aggcatagtc agggttaatg ctcctttttc tttatcccaa 60atcagatagt gtttaggctt tttcatcaaa tataaaaacc cagcccagtt catggctcat 120tcggcagcaa ccctgagacg ctttacagct ctagacccta aaaggtcaaa aggccgtctt 180atgctcaata tacattttat tacccaatct gccccggaca ttaaataaaa ctccaaaaat 240taaatccggc cctcaaaccc cacaacagga cttaattgac ctcaccttca aggtgtagaa 300taataaaaaa aaaaagttgc aattccttgc ctccgctgtg agacaaaccc cagccacatc 360tccagcacac aagaacttcc aaacgcctga accacagcag ccaggcgttc ctccagaacc 420tcctccccca ggagcttgct acatgtgccg gaaatctggc cactaggcca aggaatgcct 480gcagccccgg attcctccta agccgtgtcc catctgtgcg ggaccccact gaaaatcgga 540ctgttcaact cacctggcag ccactctcag agaccctgga actctggccc aagg594<210>263<211>506<212>DNA<213>智人(Homo sapiens)<400>263gaattcggca cgagcggaaa cttaggggcc acgtgagcca cggccacggc cgcataggca 60agcaccggaa gcaccccggc ggccgcggta atgctggtgg tctgcatcac caccggatca 120acttcgacaa ataccaccca ggctactttg ggaaagttgg tatgaagcat taccacttaa 180agaggaacca gagcttctgc ccaactgtca accttgacaa attgtggact ttggtcagtg 240aacagacacg ggtgaatgct gctaaaaaca agactggggc tgctcccatc attgatgtgg 300tgcgatcggg ctactataaa gttctgggaa agggaaagct cccaaagcag cctgtcatcg 360tgaaggccaa attcttcagc agaagagctg aggagaagat taagagtgtt gggggggcct 420gtgtcctggt ggcttgaagc cacatggagg gagtttcatt aaatgctaac tactttttaa 480aaaaaaaaaa aaaaaaaaaa ctcgag 506<210>264<211>600<212>DNA<213>智人(Homo sapiens)<220><221>misc_featute<222>(32)<223>n＝A、T、C或G<400>264ggctcgtgaa cacacactga cagctatagg gnaggcggcg gcaccgtccc cgcttcccct 60cggcggcggg gtgtcccgtc ggcggccctg aagtgaccca taaacatgtc ttgtgagagg 120aaaggcctct cggagctgcg atcggagctc tacttcctca tcgcccggtt cctggaagat 180ggaccctgtc agcaggcggc tcaggtgctg atccgcgagg tggccgagaa ggagctgctg 240ccccggcgca ccgactggac cgggaaggag catcccagga cctaccagaa tctggtgaag 300tattacagac acttagcacc tgatcacttg ctgcaaatat gtcatcgact aggacctctt 360cttgaacaag aaattcctca aagtgttcct ggagtacaaa ctttattagg agctggaaga 420cagtctttac tacgcacaaa taaaagctgc aagcatgttg tgtggaaagg atctgctctg 480gctgcgttgc actgtggaag accacctgag tcaccagtta actatggtag cccacccagc 540attgcggata ctctgttttc aaggaagctg aatgggaaat acagacttga gcgacttgtt 600<210>265<211>534<212>DNA<213>智人(Homo sapiens)<400>265gaattcggca cgagtgagga gcccatcatg gcgacgcccc ctaagcggcg ggcggtggag 60gccacggggg agaaagtgct gcgctacgag accttcatca gtgacgtgct gcagcgggac 120ttgcgaaagg tgctggacca tcgagacaag gtatatgagc agctggccaa ataccttcaa 180ctgagaaatg tcattgagcg actccaggaa gctaagcact cggagttata tatgcaggtg 240gatttgggct gtaacttctt cgttgacaca gtggtcccag atacttcacg catctatgtg 300gccctgggat atggtttttt cctggagttg acactggcag aagctctcaa gttcattgat 360cgtaagagct ctctcctcac agagctcagc aacagcctca ccaaggactc catgaatatc 420aaagcccata tccacatgtt gctagagggg cttagagaac tacaaggcct gcagaatttc 480ccagagaagc ctcaccattg acttcttccc cccatcctca gacattaaag agcc534<210>266<211>552<212>DNA<213>智人(Homo sapiens)<400>266gaattcggca ccagggcacc tccgcctcgc cgccgctagg tcggccggct ccgcccggct 60gccgcctagg atgaatatca tggacttcaa cgtgaagaag ctggcggccg acgcaggcac 120cttcctcagt cgcgccgtgc agttcacaga agaaaagctt ggccaggctg agaagacaga 180attggatgct cacttagaga acctccttag caaagctgaa tgtaccaaaa tatggacaga 240aaaaataatg aaacaaactg aagtgttatt gcagccaaat ccaaatgcca ggatagaaga 300atttgtttat gagaaactgg atagaaaagc tccaagtcgt ataaacaacc cagaactttt 360gggacaatat atgattgatg cagggactga gtttggccca ggaacagctt atggtaatgc 420ccttattaaa tgtggagaaa cccaaaaaag aattggaaca gcagacagag aactgattca 480aacgtcagcc ttaaattttc ttactccttt aagaaacttt atagaaggag attacaaaac 540aattgctaaa ga 552<210>267<211>551<212>DNA<213>智人(Homo sapiens)<400>267gaagcctacc agccaggtgc cggccccccc acccccggcc cagccccctc ctgcagcggt 60ggaagcggct cggcagatcg agcgtgaggc ccagcagcag cagcacctgt accgggtgaa 120catcaacaac agcatgcccc caggacgcac gggcatgggg accccgggga gccagatggc 180ccccgtgagc ctgaatgtgc cccgacccaa ccaggtgagc gggcccgtca tgcccagcat 240gcctcccggg cagtggcagc aggcgcccct tccccagcag cagcccatgc caggcttgcc 300caggcctgtg atatccatgc aggcccaggc ggccgtggct gggccccgga tgcccagcgt 360gcagccaccc aggagcatct cacccagcgc tctgcaagac ctgctgcgga ccctgaagtc 420gcccagctcc cctcagcagc aacagcaggt gctgaacatt ctcaaatcaa acccgcagct 480aatggcagct ttcatcaaac agcgcacagc caagtacgtg gccaatcagc ccggcatgca 540gccccagcct g 551<210>268<211>573<212>DNA<213>智人(Homo sapiens)<400>268gaattcggca ccagggttcc ttgtgggcta gaagaatcct gcaaaaatgt ctctctatcc 60atctctcgaa gacttgaagg tagacaaagt aattcaggct caaactgctt tttctgcaaa 120ccctgccaat ccagcaattt tgtcagaagc ttctgctcct atccctcacg atggaaatct 180ctatcccaga ctgtatccag agctctctca atacatgggg ctgagtttaa atgaagaaga 240aatacgtgca aatgtggccg tggtttctgg tgcaccactt caggggcagt tggtagcaag 300accttccagt ataaactata tggtggctcc tgtaactggt aatgatgttg gaattcgtag 360agcagaaatt aagcaaggga ttcgtgaagt cattttgtgt aaggatcaag atggaaaaat 420tggactcagg cttaaatcaa tagataatgg tatatttgtt cagctagtcc aggctaattc 480tccagcctca ttggttggtc tgagatttgg ggaccaagta cttcagatca atggtgaaaa 540ctgtgcagga tggagctctg ataaagcgca caa 573<210>269<211>500<212>DNA<213>智人(Homo sapiens)<400>269gaatcggcac caggaaacct ttattagcag agatagctgg cttggatcag attacgggga 60atgtggggga gccatgaaga aactaactaa aggggagcct ttggggacca gggggagaca 120agtcactatt ttgagggaga aagctctgga ttgattctga caggacactt gagtgtgaac 180tgtccaagct aagcctctgg gtgtgtagag agagccctta cagatagata gcacctttgc 240tttcagagtg gaaggactag ccactaagga ccagaccaag atgcatgtag gtcactgaca 300agcacctgat gaagaggagg ggtctcctcc aagtttgtgt ttggaactcc tcctgtgttc 360aatttcctaa aagccataat ccagcaagct gaactcatga gaaggtctgc ttcatgttga 420gcatggaaga cagaacacag acggaaactg cagtgatggt gtgaagacac cacggatagg 480ttaggggcag tgaggaggaa 500<210>270<211>224<212>DNA<213>智人(Homo sapiens)<400>270gaattcggca cgagaagact acaatctcca gggaaacctg gggcgtctcg cgcaaacgtc 60cataactgaa agtagctaag gcaccccagc cggaggaagt gagctctcct ggggcgtggt 120tgttcgtgat ccttgcatct gttacttagg gtcaaggctt gggtcttgcc ccgcagaccc 180ttgggacgac ccggccccag cgcagctatg aacctggagc gagt 224<210>271<211>447<212>DNA<213>智人(Homo sapiens)<400>271gaattcggca cgaggctggg ccgggcccga gcggatcgcg ggctcgggct gcggggctcc 60ggctgcgggc gctgggccgc gaggcgcgga gcttgggagc ggagcccagg ccgtgccgcg 120cggcgccatg aagggcaagg aggagaagga gggcggcgca cggctgggcg ctggcggcgg 180aagccccgag aagagcccga gcgcgcagga gctcaaggag cagggcaatc gtctgttcgt 240gggccgaaag tacccggagg cggcggcctg ctacggccgc gcgatcaccc ggaacccgct 300ggtggccgtg tattacacca accgggcctt gtgctacctg aagatgcagc agcacgagca 360ggccctggcc gactgccggc gcgccctgga gctggacggg cagtctgtga aggcgcactt 420cttcctgggg cagtgccagc tggagat 447<210>272<211>606<212>DNA<213>智人(Homo sapiens)<400>272gcaactactt atattccttt gatggataat gctgactcaa gtcctgtggt agataagaga 60gaggttattg atttgcttaa acctgaccaa gtagaaggga tccagaaatc tgggactaaa 120aaactgaaga ccgaaactga caaagaaaat gctgaagtga agtttaaaga ttttcttctg 180tccttgaaga ctatgatgtt ttctgaagat gaggctcttt gtgttgtaga cttgctaaag 240gagaagtctg gtgtaataca agatgcttta aagaagtcaa gtaagggaga attgactacg 300cttatacatc agcttcaaga aaaggacaag ttactcgctg ctgtgaagga agatgctgct 360gctacaaagg atcggtgtaa gcagttaacc caggaaatga tgacagagaa agaaagaagc 420aatgtggtta taacaaggat gaaagatcga attggaacat tagaaaagga acataatgta 480tttcaaaaca aaatacatgt cagttatcaa gagactcaac agatgcagat gaagtttcag 540caagttcgtg agcagatgga ggcagagata gctcacttga agcaggaaaa tgggtatact 600ggagaa 606<210>273<211>598<212>DNA<213>智人(Homo sapiens)<400>273gaattcggca ccaggcccgg tcccgcggtc gcagctccag ccgcctcctc cgcgcagccg 60ccgcctcagc tgctcgctct gtgggtcggt cctctccggc acttgggctc cagtcgcgcc 120ctccaagccc ttcaggccgc cccagtgtcc tcctccttct ccggccagac ccagccccgc 180gaagatggtg gaccgcgagc aactggtgca gaaagcccgg ctggccgagc aggcggagcg 240ctacgacgac atggccgcgg ccatgaagaa cgtgacagag ctgaatgagc cactgtcgaa 300tgaggaacga aaccttctgt ctgtggccta caagaacgtt gtgggggcac gccgctcttc 360ctggagggtc atcagtagca ttgagcagaa gacatctgca gacggcaatg agaagaagat 420tgagatggtc cgtgcgtacc gggagaagat agagaaggag ttggaggctg tgtgccagga 480tgtgctgagc ctgctggata actacctgat caagaattgc agcgagaccc agtacgagag 540caaagtgttc tacctgaaga tgaaagggga ctactaccgc tacctggctg aagtggcc598<210>274<211>536<212>DNA<213>智人(Homo sapiens)<400>274gcaccaagag actaaacaag aaagtggatc agggaagaag aaagcttcat caaagaaaca 60aaagacagaa aatgtcttcg tagatgaacc ccttattcat gcaactactt atattccttt 120gatggataat gctgactcaa gtcctgtggt agataagaga gaggttattg atttgcttaa 180acctgaccaa gtagaaggga tccagaaatc tgggactaaa aaactgaaga ccgaaactga 240caaagaaaat gctgaagtga agtttaaaga ttttcttctg tccttgaaga ctatgatgtt 300ttctgaagat gaggctcttt gtgttgtaga cttgctaaag gagaagtctg gtgtaataca 360agatgcttta aagaagtcaa gtaagggaga attgactacg cttatacatc agcttcaaga 420aaaggacaag ttactcgctg ctgtgaagga agatgctgct gctacaaagg atcggtgtaa 480gcagttaacc caggaaatga tgacagagaa agaaagaagc aatgtggtta taacaa 536<210>275<211>494<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(379)<223>n＝A、T、C或G<400>275gaattcggca ccagggtcgc ggttcttgtt tgtggatcgc tgtgatcgtc acttgacaat 60gcagatcttc gtgaagactc tgactggtaa gaccatcacc ctcgaggttg agcccagtga 120caccatcgag aatgtcaagg caaagatcca agataaggaa ggcatccctc ctgaccagca 180gaggctgatc tttgctggaa aacagctgga agatgggcgc accctgtctg actacaacat 240ccagaaagag tccaccctgc acctggtgct ccgtctcaga ggtgggatgc aaatcttcgt 300gaagacactc actggcaaga ccatcaccct tgaggtggag cccagtgaca ccatcgagaa 360cgtcaaagca aagatccang acaaggaagg cattcctcct gaccagcaga ggttgatctt 420tgccggaaag cagctggaag atgggcgcac cctgtctgac tacaacatcc agaaagagtc 480taccctgcac ctgg494<210>276<211>484<212>DNA<213>智人(Homo sapiens)<400>276ggcttttaac cagaagtcaa acctgttcag acagaaggca gtcacagcag aaaaatcttc 60agacaaaagg cagtcacagg tgtgcaggga gtgtgggcga ggctttagca ggaagtcaca 120gctcatcata caccagagga cacacacagg agaaaagcct tatgtctgcg gagagtgtgg 180gcgaggcttt atagttgagt cagtcctccg caaccacctg agtacacact ccggggagaa 240accttatgtg tgcagccatt gtgggcgagg ctttagctgc aagccatacc tcatcagaca 300tcagaggaca cacacaaggg agaaatcgtt tatgtgcaca gtgtgtgggc gaggctttcg 360tgaaaagtca gagctcatta agcaccagag aattcacacg ggggataagc cttatgtgtg 420cagagattga ggccgaggct ttgtaaagga gatcatgtct caacacacac cagaggatta 480catt 484<210>277<211>513<212>DNA<213>智人(Homo sapiens)<400>277gcttgaggct gccaatcaga gcttggcaga gctgagagat cagcggcagg gggagcgcct 60ggaacatgca gcagctttgc gggccctaca agatcaggta tccatccaga gtgcagatgc 120acaggaacaa gtggaagggc ttttggctga gaacaatgcc ttgaggacta gcctggctgc 180cctggagcag atccaaacag caaagaccca agaactgaat atgctccggg aacagaccac 240tgggctggca gctgagttgc agcagcagca ggctgagtac gaggacctta tgggacagaa 300agatgacctc aactcccagc tccaggagtc attacgggcc aatagtcgac tgctggaaca 360acttcaagaa atagggcagg agaaggagca gttgacccag gaattacagg aggctcggaa 420gagtgcggag aagcggaagg ccatgcttgg atgagctagc aatggaaacg ctgcaagaga 480agtcccacac aaggaagagc ttgggagcag ttc 513<210>278<211>471<212>DNA<213>智人(Homo sapiens)<400>278gaattcggca ccagccaagg ccctgtccct ggctcgggcc cttgaagagg ccttggaagc 60caaagaggaa ctcgagcgga ccaacaaaat gctcaaagcc gaaatggaag acctggtcag 120ctccaaggat gacgtgggca agaacgtcca tgagctggag aagtccaagc gggccctgga 180gacccagatg gaggagatga agacgcagct ggaagagctg gaggacgagc tgcaagccac 240ggaggacgcc aaactgcggc tggaagtcaa catgcaggcg ctcaagggcc agttcgaaag 300ggatctccaa gcccgggacg agcagaatga ggagaagagg aggcaactgc agagacagct 360tcacgagtat gagacggaac tggaagacga gcgaaagcaa cgtgccctgg cagctgcagc 420aaagaagaag ctggaagggg acctgaaaga cctggagctt caggccgact t 471<210>279<211>497<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(457)<223>n＝A，T，C或G<221>misc_feature<222>(471)<223>n＝A，T，C或G<400>279gaattcggca cgaggccaca gaggcggcgg agagatggcc ttcagcggtt cccaggctcc 60ctacctgagt ccagctgtcc ccttttctgg gactattcaa ggaggtctcc aggacggact 120tcagatcact gtcaatggga ccgttctcag ctccagtgga accaggtttg ctgtgaactt 180tcagactggc ttcagtggaa atgacattgc cttccacttc aaccctcggt ttgaagatgg 240agggtacgtg gtgtgcaaca cgaggcagaa cggaagctgg gggcccgagg agaggaagac 300acacatgcct ttccagaagg ggatgccctt tgacctctgc ttcctggtgc agagctcaga 360tttcaaggtg atggtgaacg ggatcctctt cgtgcagtac ttccaccgcg tgcccttcca 420ccgtgtggac accatctccg tcaatggctc tgtgcanctg tcctacatca ncttccagac 480ccagacagtc atccaca 497<210>280<211>544<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(451)<223>n＝A、T、C或G<400>280gaattcggca ccagaatagg aacagctccg gtctacagct cccagcgtga gcgacgcaga 60agacgggtga tttctgcatt tccatctgag gtaccgggtt catctcacta gggagtgcca 120gacagtgggc gcaggccagt gtgtgtgcgc accgtgcgcg agccgaagca gggcgaggca 180ttgcctcacc tgggaagcac aaggggtcag ggagttccct ttccgagtca aagaaagggg 240tgacggacgc acctggaaaa tcgggtcact cccacccgaa tattgtgctt ttcagaccgg 300cttaagaaac ggcgcaccac gagactatat cccacacctg gctcagaggg tcctacgccc 360acggaatctc gctgattgct agcacagcag tcttagatca aactgcaagg ggggcaacga 420ggctggggga ggggcgcccg ccattgccca ngcttgctta ggtaaacaaa gcagccggga 480agcttgaact gggtggagcc caccacagct caaggaggcc tgcctgcctc tgtagctcca 540cctc 544<210>281<211>527<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(456)<223>n＝A、T、C或G<400>281gaattcggca cgaggcctcg ctcagctcca acatggcaaa aatctccagc cctacagaga 60ctgagcggtg catcgagtcc ctgattgctg tcttccagaa gtatgctgga aaggatggtt 120ataactacac tctctccaag acagagttcc taagcttcat gaatacagaa ctagctgcct 180tcacaaagaa ccagaaggac cctggtgtcc ttgaccgcat gatgaagaaa ctggacacca 240acagtgatgg tcagctagat ttctcagaat ttcttaatct gattggtggc ctagctatgg 300cttgccatga ctccttcctc aaggctgtcc cttcccagaa gcggacctga ggaccccttg 360gccctggcct tcaaacccac cccctttcct tccagccttt ctgtcatcat ctccacagcc 420cacccatccc ctgagcacac taaccacctc atgcanggcc cccctgccaa tagtaataaa 480gcaatgtcct tttttaaaac atgaaaaaaa aaaaaaaaaa actcgag527<210>282<211>514<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(494)<223>n＝A、T、C或G<400>282ggaagactgg agcctttgcg gcggcgctgc ccctcccctg gtccccgcga gctcggaggg 60cccggctggt gctgcggggg ccccgggagg ttgaaaacta agcatgggga agagctgcaa 120ggtggtcgtg tgtggccagg cgtctgtggg caaaacttca atcctggagc agcttctgta 180tgggaaccat gtagtgggtt cggagatgat cgagacgcag gaggacatct acgtgggctc 240cattgagaca gaccgggggg tgcgagagca ggtgcgtttc tatgacaccc gggggctccg 300agatggggcc gaactgcccc gacactgctt ctcttgcact gatggctacg tcctggtcta 360tagcacagat agcagagagt cttttcagcg tgtggagctg ctcaagaagg agattgacaa 420atccaaggac aagaaggagg tcaccatcgt ggtccttggc aacaagtgtg acttacagga 480gcagcggcgt gtanacccaa atgtggctca acac 514<210>283<211>484<212>DNA<213>智人(Homo sapiens)<400>283gggcgggcgg tggacagtca tggcggcccg gcgcggggct ctcatagtgc tggagggcgt 60ggaccgcgcc gggaagagca cgcagagccg caagctggtg gaagcgctgt gcgccgcggg 120ccaccgcgcc gaactgctcc ggttcccgga aagatcaact gaaatcggca aacttctgag 180ttcctacttg caaaagaaaa gtgacgtgga ggatcactcg gtgcacctgc ttttttctgc 240aaatcgctgg gaacaagtgc cgttaattaa ggaaaagttg agccagggcg tgaccctcgt 300cgtggacaga tacgcatttt ctggtgtggc cttcaccggt gccaaggaga atttttccct 360agactggtgt aaacagccag acgtgggcct tcccaaaccc gacctggtcc tgttcctcca 420gttacagctg gcggatgctg ccaagcgggg agcgtttggc catgagcgct atgagaacgg 480ggct 484<210>284<211>514<212>DNA<213>智人(Homo sapiens)<400>284gaattcggca cgaggcggag gccgcggagg ctcctcggtc cttcagcacc cctcggcccg 60acgcacccac gcccctcacc ccccgagagc cgaaaatgga cccaagtggg gtcaaagtgc 120tggaaacagc agaggacatc caggagaggc ggcagcaggt cctagaccga taccaccgct 180tcaaggaact ctcaaccctt aggcgtcaga agctggaaga ttcctatcga ttccagttct 240ttcaaagaga tgctgaagag ctggagaaat ggatacagga aaaacttcag attgcatctg 300atgagaatta taaagaccca accaacttgc agggaaagct tcagaagcat caagcatttg 360aagctgaagt gcaggccaac tcaggagcca ttgttaagct ggatgaaact ggaaacctga 420tgatctcaga agggcatttt gcatctgaaa ccatacggac ccgtttgatg gagctgcacc 480gccagtggga attacttttg gagaagatgc gaga 514<210>285<211>383<212>DNA<213>智人(Homo sapiens)<400>285gaattcggca cgaggccggg ctccaccgcg catcctgctc cactctggcg accgcccccg 60gggcccccgc cgcgggcgcg gcgcccgcca tgggcgagga ggactactat ctggagctgt 120gcgagcggcc ggtgcagttc gagaaggcga accctgtcaa ctgcgtcttc ttcgatgagg 180ccaacaagca ggtttttgct gttcgatctg gtggagctac tggcgtggta gttaaaggcc 240cagatgatag gaatcccatc tcatttagaa tggatgacaa aggagaagtg aagtgcatta 300agttttcctt agaaaataag atattggctg ttcagaggac ctcaaagact gtggattttt 360gtaattttat ccctgataat tcc 383<210>286<211>943<212>DNA<213>智人(Homo sapiens)<400>286gaattcggca ccagggccgt ggcggaggag gagcgctgca cggtggagcg tcgggccgac 60ctcacctacg cggagttcgt gcagcagtac gtgcgcccct gatcgcggag gtcgcgtcct 120gttcaccggc ccgtctgccc cgaccgccca aggccgcctt cccctgacct cgcgcgcacg 180cgtggggctg gggcggcgag gctggcggtc cggcctggcc gcgactctgc ccttctttcc 240agaggttccg ggccctgtgc tcccgcgaca ggttgctggc ttcgtttggg gacagagtgg 300tccggctgag caccgccaac acctactcct accacaaagt ggacttgccc ttccaggagt 360atgtggagca gctgctgcac ccccaggacc ccacctccct gggcaatggt gaggcagccc 420taggcggcgg tagggggtgg ggacgcttgg agtctccagg tgccaggatc cctgtccccg 480ccgtctctgt tggcagacac cctgtacttc ttcggggaca acaacttcac cgagtgggcc 540tctctctttc ggcactactc cccaccccca tttggcctgc tgggaaccgc tccagcttac 600agctttggaa tcgcaggagc tggctcgggg gtgcccttcc actggcatgg acccgggtac 660tcagaagtga tctacggtcg taagcgctgg ttcctttacc cacctgagaa gacgccagag 720ttccacccca acaagaccac actggcctgg ctccgggaca catacccagc cctgccaccg 780tctgcacggc ccctggagtg taccatccgg gctggtgagg tgctgtactt ccccgaccgc 840tggtggcatg ctacgctcaa ccttgacacc agcgtcttca tctccacctt cctcggctag 900ccaaaacagc tggcaggact gccggtcaca caccagcacg tcc943<210>287<211>1143<212>DNA<213>智人(Homo sapiens)<400>287gaattcggca cgagggaaga acagctgttg gaacaacaag aatatttaga aaaagaaatg 60gaggaagcaa agaaaatgat atcaggacta caggccttac tgctcaatgg atccttacct 120gaagatgaac aggagaggcc cttggccctc tgtgaaccag gtgtcaatcc cgaggaacaa 180ctgattataa tccaaagtcg tctggatcag agtatggagg agaatcagga cttaaagaag 240gaactgctga aatgtaaaca agaagccaga aacttacagg ggataaagga tgccttgcag 300cagagattga ctcagcagga cacatctgtt cttcagctca aacaagagct actgagggca 360aatatggaca aagatgagct gcacaaccag aatgtggatc tgcagaggaa gctagatgag 420aggaaccggc tcttgggaga atataaaaaa gagctggggc agaaggatcg ccttcttcag 480cagcaccagg ccaagttaga agaagcactc cggaaactct ctgatgtcag ttaccaccag 540gtggatctag agcgagagct agaacacaaa gatgtcctct tggctcactg tatgaaaaga 600gaggcagatg aggcgaccaa ctacaacagt cacaactctc aaagcaatgg ttttctcctt 660ccaacggcag gaaaaggagc tacttcagtc agcaacagag ggaccagcga cctgcagctt 720gttcgagatg ctctccgcag cctgcgcaac agcttcagtg gccacgatcc tcagcaccac 780actattgaca gcttggagca gggcatttct agcctcatgg agcgcctgca tgttatggag 840acgcagaaga aacaagaaag aaaggttcgg gtcaagtcac ccagaactca agtaggtagt 900gaataccggg agtcctggcc ccctaactca aagttgcctc actcacagag ctctccaact 960gtcagcagca cctgtactaa agtgctctat ttcactgacc ggtcacttac gcccttcatg 1020gtcaatatac caaagaggtt ggaggaggtg acgttaaagg attttaaagc agctattgat 1080cgggaaggaa atcaccggta tcacttcaaa gcactggatc ctgagtttgg cactgtcaaa 1140gag1143<210>288<211>881<212>DNA<213>智人(Homo sapiens)<400>288gtgagagcgg gccgaggaga ttggcgacgg tgtcgcccgt gttttcgttg gcgggtgcct 60gggctggtgg gaacagccgc ccgaaggaag caccatgatt tcggccgcgc agttgttgga 120tgagttaatg ggccgggacc gaaacctagc cccggacgag aagcgcagca acgtgcggtg 180ggaccacgag agcgtttgta aatattatct ctgtggtttt tgtcctgcgg aattgttcac 240aaatacacgt tctgatcttg gtccgtgtga aaaaattcat gatgaaaatc tacgaaaaca 300gtatgagaag agctctcgtt tcatgaaagt tggctatgag agagattttt tgcgatactt 360acagagctta cttgcagaag tagaacgtag gatcagacga ggccatgctc gtttggcatt 420atctcaaaac cagcagtctt ctggggccgc tggcccaaca ggcaaaaatg aagaaaaaat 480tcaggttcta acagacaaaa ttgatgtact tctgcaacag attgaagaat tagggtctga 540aggaaaagta gaagaagccc aggggatgat gaaattagtt gagcaattaa aagaagagag 600agaactgcta aggtccacaa cgtcgacaat tgaaagcttt gctgcacaag aaaaacaaat 660ggaagtttgt gaagtatgtg gagccttttt aatagtagga gatgcccagt cccgggtaga 720tgaccatttg atgggaaaac aacacatggg ctatgccaaa attaaagcta ctgtagaaga 780attaaaagaa aagttaagga aaagaaccga agaacctgat cgtgatgagc gtctaaaaaa 840ggagaagcaa gaaagagaaa aaaaaaaaaa aaaaactcga g 881<210>289<211>987<212>DNA<213>智人(Homo sapiens)<400>289gaattcggca cgagggactg tggtttccag gaatggtggc gtctcacgct tcttgtgctt 60tttcctttgg ggcctccgag cggctggggt tgggggactg ggcaggaggc tccctgtaaa 120catttggact tgggctgggg caggggctgg tgttgggcaa agctgggggt ccaggctgga 180gaagcagggg cccctccaga cgcagccttg ggagactcag catgtgcccc cctcccctca 240tcacagaaca agacaatggt taaaaaccag aacagatgcc cagaaggggg taccatggcc 300attaccagca tctcagacaa gggcaggctt caaacaggga ggcctgtggc aacccctccc 360ctacgtctgg agctgagggg acagggggag ctgagaacaa agagaggaaa gaggagaaaa 420gcggcggggg aacaggcggg gagcgtgatc ttcttgcccc catcttcctc aggggttggg 480gggtacaaag tcggcggtgg cccatcccgc caggccccgc tgcccctcag aagaggccgc 540agtccttcag gttgttcttg atgatgacat cggtgacggc gtcaaacacg aactgcacgt 600tcttggtgtc ggtggcgcac gtgaagtgcg tgtagatctc cttggtgtct ttgcgcttat 660tcaggtcctc aaacttactc tggatgtagc tggctgcctc atcatatttg ttggcccctg 720tatactcagg gaagcagatg gtcaggggac tgtgtgtgat cttctcctca aacaggtcct 780tcttgttgag gaagaggatg atggacgtgt ctgtgaacca cttgttgttg cagatgctat 840cgaatagctt catgctctca tgcatgcggt tcatctcctc gtcctcagct agcaccaagt 900cataggcgct caaggctacg cagaagatga tggctgtgac gccctcaaag cagtggatcc 960acttcttccg ctcagaccgc tgaccac 987<210>290<211>300<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(300)<223>n＝A、T、C或G<400>290gattcaagat gtaccccatt gactttgaga aggatgatga cagcaacttt catatggatt 60tcatcgtggc tgcatccaac ctccgggcag aaaactatga cattccttct gcagaccggc120acaagagcaa gctgattgca gggaagatca tcccagccat tgccacgacc acagcagccg180tggttggcct tgtgtgtctg gagctgtaca aggttgtgca ggggcaccga cancttgact240cctacangaa tgggtgcctc aacttgagcc ctgcctttct ttggtttctc tgaacccctt300<210>291<211>352<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(352)<223>n＝A、T、C或G
<400>291aaccaagctg ccaccggggg tggatcggat gcggcttgag aggcatctgt ctgccgagga 60cttctcaagg gtatttgcca tgtcccctga agagtttggc aagctggctc tgtggaagcg120gaatgagctc aagaagaagg cctctctctt ctgatggccc ccacctgctc cgggacggcc180cccttacccc tgctgcttca gggtttttcc ccggcgggtt gggaggggca ggaggtgggg240tggaaatngg gtgggcncct ttcctcaggt agagnggggg gccaaaacct ctgcngtccc300cggagngagc tatggacttt cttccccctc acaaggntgg gggcctcctg ct352<210>292<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>292cgcggtggct gcgcactcng cctgagaaac tcggcaagcg cgcagtgtcg actccccggt 60ctatgccagg cgcatctcag ctaatccaaa agtaaatgag aaacttagaa aaagattgcc120aattccaaat caacatattt agagaaaatt ggaaaaggag aagcttacta cagctttatt180tgaggacttt ttaaagaacg ctgggttcta tctgtgagct gcaaatcttg gagcaaaaac240cagagacatt gccagagcaa acaagaacag aaatacaaat ggagaactgg tcaaaagaca300taacccacag ttatcttgaa caagaaacta cggggataaa taaaagtacg canccagatg360agcaactgac tatgaattct gagaaaagta tgcatcggaa atccactgaa ttagntaatg420aaataacatg ngagaacaca gaatggccag gggcagagat caacgaattt tcanatcatc480agttcttatc cagatgatga gtctgtttac t 511<210>293<211>526<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(526)<223>n＝A、T、C或G<400>293gataaaaaga actttaatgg aaggcactgt tgtccaaaat cacataaagg gtaagagccc 60acacggtacc accctgctct cctacttctc aaacccacat ccaccaccca gacaggaggg120tgcanacccc acaggaaatt acctcccgga gcactgactg atatttttcc ttaaaacaaa180aaaatggctg tctcagacta ataacagaac atcttaagag ctataccagc tattacagcc240tggtaatana agcagctttc taanaattcc caagtttata anaggcccaa naaatgcatt300tattctgttg tctattaagc ctccatgaca aggagaaagt tatgagtaaa tccttggttc360atcaggagtt aagagctgtg ngcctcatga ggagttaana gctgtgtgca taagcaggtt420caagaaacaa actcctgttt gtttgcctct ttgatggttc aaaaacattc agctgctttc480acctctanga caaaatgctt aaagaattta ctctcatcac cttggg 526<210>294<211>601<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature
<222>(1)...(601)<223>n＝A、T、C或G<400>294actttaaaag ccaaatatat ttttaaaaga tcatgcttat aataagtaaa ttacncatta 60aggaaacatc aaaataaagt agatgaataa aaaggcacac tcgaaaaatt tgagcgcaga120aaggacagtt ctttttgttt tgtttctaat gtcggaagaa aaagaaagag atatattaaa180atcattgttt tcaagtgaag gtttctgtca gttgaagtag ttagcaatgg cttcttttct240cccgtgtcca aagcaggctc ttcctgcgct gacttctgag gaggngttca gtcctctgcc300atgtataggc gatacatcaa ggcgacggcc actgcagaga tggcagggat cacccagttg360gtccaccaac tggaactaga atcaatagta gtgataagag tttccggagg cttgtttaac420tttggtctgt catctggatg gagctcccca atgatgaatg ttttggacat ttccctggca480tctgtagant gcccgacatc ctcaaagttc tcagtagcng tcacctccac ttgttccctt540aaaacttctt ccccaccagg atgctcttcc agaaatttgg gncaaatcgn acaccttgtg600g601<210>295<211>262<212>DNA<213>智人(Homo sapiens)<400>295cccttagccc caagggccct gggggcagcc accctcccgc ctgtcggccc gtagatttat 60caagggtgtt atgggcccag ctttgggggg ccagtcccga tgcactttga ggggtgttgg120agaggggact cccccactcg cacttaactc aacggctctc gggccctggg gctgttttta180ccatgtttgt ttttgaagct caggtgtctc acgtctgggc tgcaccaggc gaagagagaa240attaaagatt tgaggttttt cc 262<210>296<211>598<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(598)<223>n＝A、T、C或G<400>296gttagaacaa ctcagcaaaa taaaattcct gtttattgtt ggacaacatt gtttcacaca 60tacatcaaac aggccaaaaa aaataaacag caacttcata gacaaaaaag gaaaaaaaaa120gaaacctttt atctttggcc tttttaacca tctcatacaa accaactact tatagtacag180ctaagtacat acacaaaaaa gttactggaa tgctcggaat aagattgttt ttctgttgtc240atttttgctt tttttacaag gntttttttc tcctttgaga ttataatgaa catggncaca300ccacaagtaa agtcagaagt aggacagana acgctccgaa ggctggtttg gtcatccgan360atcattaaaa atggctgacc ctaacaatat gtacaaaaat ataaaatgta aataaaaaat420acaaacaaat ttccttttta aagtactttt aagaaaaaaa gcagggcctt ggaagttttg480gttctttttt cctcccctgt tgcaaattct catggtttgg gttgggtggn gganancccg540tgtcatctgc gggtggcact gccccggngg gcgggcgggc ctctctctcg aangngac 598<210>297<211>509<212>DNA<213>智人(Homo sapiens)<400>297agaacacagg tgtcgtgaaa actaccccta aaagccaaaa tgggaaagga aaagactcat 60atcaacattg tcgtcattgg acacgtagat tcgggcaagt ccaccactac tggccatctg120atctataaat gcggtggcat cgacaaaaga accattgaaa aatttgagaa ggaggctgct180gagatgggaa agggctcctt caagtatgcc tgggtcttgg ataaactgaa agctgagcgt240gaacgtggta tcaccattga tatctccttg tggaaatttg agaccagcaa gtactatgtg300actatcattg atgccccagg acacagagac tttatcaaaa acatgattac agggacatct360caggctgact gtgctgtcct gattgttgct gctggtgttg gtgaatttga agctggtatc420tccaagaatg ggcaggaccc gagagcatgc ccttctggct tacacactgg gtgtgaaaca480actaattgtc ggtgttaaca aaatggatt 509<210>298<211>267<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(267)<223>n＝A、T、C或G<400>298gggacggggg aaaggagacg cttcttcctc ttgctgctct tctcgttccc gagatcagcg 60gcggcggtga ccgcgagtgg gtcggcaccg tctccggctc cgggngcnaa caatgctgac120tgatagcgga ggcggnggca cctccttnna ggaggacctg gactctgtgg ctccgcgatc180cgccccagct ggggcctcgg agccgcctcc gccgggaggg gtcggtctgg ggatccncac240cgngaggctn tttggggagg gcgggcc267<210>299<211>121<212>DNA<213>智人(Homo sapiens)<400>299ggcacgaggg ccctcggagc tcgtttccag atcgaggtaa gagggacttt cttaaaggcc 60tagtctatgg gatggggcgg cggagggaat tttttgagaa ataaaatgaa gctgcagtgt120a121<210>300<211>533<212>DNA<213>智人(Homo sapiens)<400>300aaggtgcaca gtatttgatg caggctgctg gtcttggtcg tatgaagcca aacacacttg 60tccttggatt taagaaagat tggttgcaag cagatatgag ggatgtggat atgtatataa120acttatttca tgatgctttt gacatacaat atggagtagt ggttattcgc ctaaaagaag180gtctggatat atctcatctt caaggacaag aagaattatt gtcatcacaa gagaaatctc240ctggcaccaa ggatgtggta gtaagtgtgg aatatagtaa aaagtccgat ttagatactt300ccaaaccact cagtgaaaaa ccaattacac acaaagttga ggaagaggat ggcaagactg360caactcaacc actgttgaaa aaagaatcca aaggccctat tgtgccttta aatgtagctg420accaaaagct tcttgaagct agtacacagt ttcagaaaaa acaaggaaag aatactattg480atgtctggtg gctttttgat gatggaggtt tgaccttatt gataccttac ctt 533<210>301<211>560<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature
<222>(1)...(560)<223>n＝A、T、C或G<400>301ataaatgatc ccttttattg taagtaatgc gcaacactgg cctggctttg cactgcaagc 60cctcggtcaa gatatagtca aataactatg gctgcaggtt ccacagttcc acaataacca120tggctgcacg atccacaatt cagacacaga catagagctg gggtgggtgg aaggggcagg180agggtggcag agtgcggact gtccccagcc ctggcctctc catgcanagt tggcccaggc240agacacaccc catggaatga tgagaaagtg acggcacggc cccttcccac agcaagcctg300gggctgccag gaactgccct tcanaacctt tgggcccagg tcnccctgaa nccccacaac360tttttatctg gaataagtat taaaaaacaa taaattaagc aaacaacntg gnccttgaag420gatgttgacc nacatggtcc acagtttttg gcncaaaaaa ataagggctg gtttgctttt480tttggaaggc agggtttgtg gnttggcttt caaatnattt tcaaaccatt ccccagggag540gganaacccc cgggggggaa560<210>302<211>599<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(599)<223>n＝A、T、C或G<400>302gcaaagttac aaatttattg gtctggaaat aaatacaaat atctcattaa naaactcctc 60tggaaagact tgtgcacaat agtttcccat ccgtactcag cctctcttgc cccgatcccc120gacttttcta ctcaaggcca gggaaggcct ccaaggngat gggcggcagg taacgagtca180ttgcctctca cgccacctgg aaggctggac tacttcctcc tcccaactgc ggggtcccan240aaatcctcgg gtcccagngg ctgacttaca atattcaatt cactctgacc aaacttccta300tganaaaatc cacggngagc caaaatgaaa agtacaaggc agtagtacag gaacctggca360gccgcactgg ccgcccanaa acgtcagtgg ngctgcccca ttcggcgaaa ggttagggag420caggaaaaga ggaagcagga gagggaagga aagtcccatg gaatatgtat tccanaatcc480ttacattttc tcagccaccg ctccccacgt gagttcccac ccccaccccg acaagaagca540aagagttctg aggatccaag aacgtgaccg ggtcanacan gttcagctac tgagttcac 599<210>303<211>591<212>DNA<213>智人(Homo sapiens)<400>303cggagttgta acgctccact gactgataga gcgaccggcc gaccatggcg cccggagtgg 60cccgcgggcc gacgccgtac tggaggttgc gcctcggtgg cgccgcgctg ctcctgctgc120tcatcccggt ggccgccgcg caggagcctc ccggagctgc ttgttctcag aacacaaaca180aaacctgtga agagtgcctg aagaacgtct cctgtctttg gtgcaacact aacaaggctt240gtctggacta cccagttaca agcgtcttgc caccggcttc cctttgtaaa ttgagctctg300cacgctgggg agtttgttgg gtgaactttg aggcgctgat catcaccatg tcggtagtcg360ggggaaccct cctcctgggc attgccatct gctgctgctg ctgctgcagg aggaagagga420gccggaagcc ggacaggagt gaggagaagg ccatgcgtga gcgggaggag aggcggatac480ggcaggagga acggagagca gagatgaaga caagacatga tgaaatcaga aaaaaatatg540gcctgtttaa agaagaaaac ccgtatgcta gatttgaaaa caactaaagc g 591<210>304<211>441<212>DNA<213>智人(Homo sapiens)
<220>
<221>misc_feature<222>(1)...(441)<223>n＝A、T、C或G<400>304gctggacgga gacctgctgg aggaggagga gctggaggaa gcagaggagg aggaccggtc 60gtcgctgctg ctgctgtcgc cgcccgcggc caccgcctct cagacccagc agatcccagg120cgggtccctg gggtctgtgc tgctgccagc cgccaggttc gatgcccggg aggcggcggc180ggcggcgggg gtgctgtacg gaggggacga tgcccagggc atgatggcgg cgatgctgtc240ccacgcctac ggccccggcg gttgtggggc ggcggcggcc gccctgaacg gggagcaggc300ggccctgctc cggagaaaga gcgtcaacac caccgagtgc gtcccggtgc ccagctccga360gcacgtcgcc gagatcgtcg gccgccaggg ttgtaaaatt aaagcactga nagccaagac420aaacacgtat atcaagactc c 441<210>305<211>491<212>DNA<213>智人(Homo sapiens)<400>305tcgccatgcc cccttcttag cactgcaccg ccaggtccat gctgctgcca ccccagacct 60gggctttgcc tgccacctct gtgggcagag cttccgaggc tgggtggccc tggttctgca120tctgcgggcc cattcagctg caaagcggcc catcgcttgt cccaaatgcg agagacgctt180ctggcgacga aagcagcttc gagctcatct gcggcggtgc caccctcccg ccccggaggc240ccggcccttc atatgcggca actgtggccg gagctttgcc cagtgggacc agctagttgc300ccacaagcgg gtgcacgtag ctgaggccct ggaggaggcc gcagccaagg ctctggggcc360ccggcccagg ggccgccccg cggtgaccgc cccccggccc ggtggagatg ccgtcgaccg420ccccttccag tgtgcctgtt gtggcaagcg cttccggcac aagcccaact tgatcgctca480cccgcgcgtg c 491<210>306<211>547<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(547)<223>n＝A、T、C或G<400>306tctctttctt ttaagacagg aatgtaagcc acaacattta caaatacaat gttttaactc 60tctacatgta ggaagccaac ctgctccttt ttgatcttct tctttggcac aacctcagtg120gatttctctg attcagaacg agttctaatt gatcttctct gttgcttctt ttctactgag180cctgtagaac cagatgttgc ttcaggagat gatacactct gcgttggctt ttcatttctc240tggtttggtg tagaaattat aagcctgtct tgccccctga cacttatttc tgttttgtta300ccaattccct ttgttgaata aacaaattga tcgataaatt tcccatcccc tgtagcattc360tgaagagcaa acacttgttc aattttcaca actggagaca tgttacactt ctgcaaatcc420aggctccctt tgtgcatccg taatggaagc tggtaaggat ttccttgctg ccgcagtttt480ccaggctatt ttaacaggcg gnggctcttc ctctttccgc acttgtgtgc cgcctctggc540tatgtct 547<210>307<211>571<212>DNA<213>智人(Homo sapiens)
<220>
<221>misc_feature<222>(1)...(571)<223>n＝A、T、C或G<400>307cgctgcatgt gataatgtca tcatttattt ttaaatggtt ctaaattgca natttaagtt 60gatttcaaat caaccctatt tttaaattac ttttaatagg aanaaatgaa gcaaggacat120acataatcta ctatatttga aggactcaaa caaatacatg tttggctgtg aattctgtac180tctcaccaaa acagagataa aaatccacct aaaatacact ttccttcatt tagtgcttgt240ggganaaggt caagtattgc actttaaaat tactttcatc taacatttgc cccaactttc300cccctgaatt cactatatgt tttcagcaaa catgatttta taaattttaa gtataaaagc360aactaggttt tctaattcaa ctttggaagg tttactttac tctacanagc tatttttgta420aaacggcata tttacttaca aaattganag ataggggcat ccagctgagg tacatttcct480cccttggcgt tgagtttctg gacttgggtc gggggcacag gcttgtgtga ctgccccgtg540gcccgataca tggcctggac cccaggatgc g 571<210>308<211>591<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(591)<223>n＝A、T、C或G<400>308ctccttatgt gtctgcctac ttcattcttc ggcatttcct gcttatccaa gttcaccatt 60tcaggtcacc actggatatc agttgcctgt atataattat caggcatttc ctgcttatcc120aagttcacca tttcaggtca ccactggata tcagttgcct gtatataatt atcaggcatt180tcctgcttat ccaagttcac catttcaggt caccactgga tatcagttgc ctgtatataa240ttatcaggca tttcctgctt atccaagttc accatttcag gtcaccactg gatatcagtt300gcctgtatat aattatcagg catttcctgc ttatccaagt tcaccatttc aggtcaccac360tggatatcag ttgcctgtat ataattatca ggcatttcct gcttatccaa gttcaccatt420tcaggtcacc actggatatc agttgcctgt atataattat caggcatttc ctgcttatcc480aaattcagca gttcaggtca ccactggata tcagttccat gtatacaatt accagatgcc540accgcagtgc cctgttgggg gagcaaagga gaaatntgtg gaccgaagca t 591<210>309<211>591<212>DNA<213>智人(Homo sapiens)<400>309agggggtgca cgtactccca actgtggtcg cgctctcacc ccttctgctg ctctcgtggc 60cccctcgcga tggcgggcat cctgtttgag gatattttcg atgtgaagga tattgacccg120gagggcaaga agtttgaccg aggtaagtaa gtgtctcgac tgcattgtga gagtgaatct180ttcaagatgg atctaatctt agatgtaaac attcaaattt accctgtaga cttgggtgac240aagtttcggt tggtcatagc tagtaccttg tatgaagatg gtaccctgga tgatggtgaa300tacaacccca ctgatgatag gccttccagg gctgaccagt ttgagtatgt aatgtatgga360aaagtgtaca ggattgaggg agatgaaact tctactgaag cagcaacacg cctgctgaga420ttgagagctg ctgagtggca gtgctccaga atcacgggat ggggccttct gtttcagctc480tgcgtacgtg tcctatgggg gcctgctcat gaggctgcag ggggatgcca acaacctgca540tggattcgag gtggactcca gagtttatct cctgatgaag aagctagcct t 591<210>310
<211>488<212>DNA<213>智人(Homo sapiens)<400>310tggtctcaag cctgaagagg ctccgcccac aagctggccc atgaagttag caatgcctgt 60ggcttcagtc aattgtcttg agactgtgaa gaggctgaaa gacaccttcc cgggtggaag120aaggagttca ctgaaaactt atcttaaact gacccttccc tttgagtgag tcttcattcc180tctcccatgt gggaacccag cctccgatgc cccggggact aggggaaaca gttggaggtc240cgtgccgtcc ccagcctgcc acgggtgcga ggacagccaa gtcctgagtg actcaagatg300cttcacttac atggaagaaa cttctaaaac tctaccgagt ggtttttgta tatactaaag360ttctatttag agcttttctg ttttgggcaa gttcgctgct ccttctattt gggcactttg420gtttttgtac tgtcttttgt gacggcattg attgaacatt ttttactagt agtcttatga480cttttgta 488<210>311<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>311cccgtttntg nagcaaaana gggggaagat ttataggtag aggcgacaaa cctaccgagc 60ctggtgatag ctggttgtcc aagatagaat cttagttcaa ctttaaattt gcccacagaa120ccctctaaat ccccttgtaa atttaactgt tagtccaaag aggaacagct ctttggacac180taggaaaaaa ccttgtagag agagtaaaaa atttaacacc catagtaggc ctaaaagcag240ccaccaatta agaaagcgtt caagctcaac acccactacc taaaaaatcc caaacatata300actgaactcc tcacacccaa ttggaccaat ctatcaccct atagaagaac taatgttagt360ataagtaaca tgaaaacatt ctcctccgca taagcctgcg tcagattaaa acactgaact420gacaattaac agcccaatat ctacaatcaa ccaacaagtc attattaccc tcactgtcaa480cccaacacag gcatgctcat aaggaaaggt t 511<210>312<211>591<212>DNA<213>智人(Homo sapiens)<400>312gaacttgcgt tgaaggaagc agaaactgat gaaataaaaa ttttgctgga agaaagcaga 60gcccagcaga aggagacctt gaaatctctt cttgaacaag agacagaaaa tttgagaaca120gaaattagta aactcaacca aaagattcag gataataatg aaaattatca ggtgggctta180gcagagctaa gaactttaat gacaattgaa aaagatcagt gtatttccga gttaattagt240agacatgaag aagaatctaa tatacttaaa gctgaattaa acaaagtaac atctttgcat300aaccaagcat ttgaaataga aaaaaaccta aaagaacaaa taattgaact gcagagtaaa360ttggattcag aattgagtgc tcttgaaaga caaaaagatg aaaaaattac ccaacaagaa420gagaaatacg aagctattat ccagaacctt gagaaagaca gacaaaaatt ggtcagcagc480caggagcaag acagagaaca gttaattcag aagcttaatt gtgaaaaaga tgaagctatt540cagactgccc taaaagaatt taaattggag agagaagttg ttgagaaaga g 591<210>313<211>373<212>DNA<213>智人(Homo sapiens)
<220>
<221>misc_feature<222>(1)...(373)<223>n＝A、T、C或G<400>313ttgattttta ttctgnattt tattactgaa atangttgtc ctantnatcc caccccacaa 60taaaaatntn acccangccc cccntttctt tncctnatnc cctnttccac cacaccatcc120cggaacaagt gctccaggat tccctgccca ctggccattt tggagtgtgn ccattgggta180gcaatgtgga aaccaccaag gcctttgtgg anaaaatgga gggggttgag ggagncccan240gaggggctna tttgagggcc tttgccactt gctcataggc gagctcnatc tcctcntnat300ctgnacangt ggaagcaaat tcttcccggg cgtnggnant gctnaagnac cgatgcactc360cccggaaggn ctn 373<210>314<211>591<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(591)<223>n＝A、T、C或G<400>314cccgtgccgc cgccgcctcc tgggaagaga ggaagcggga gaggagccca cgtcgcctgt 60cacccaatat ctccagccgc gcagtcccga agagtgtaag atgttcgcct gcgccaagct120cgcctgcacc ccctctctga tccgagctgg atccagagtt gcatacagac caatttctgc180atcagtgtta tctcgaccag aggctagtag gactggagag ggctctacgg tatttaatgg240ggcccagaat ggtgtgtctc agctaatcca aagggagttt cagaccagtg caatcagcag300agacattgat actgctgcca aatttattgg tgcaggtgct gcaacagtag gagtggctgg360ttctggtgct ggtattggaa cagtctttgg cagccttatc attggttatg ccagaaaccc420ttcgctgaag cagcagctgt tctcatatgc tatcctggga tttgccttgt ctgaagctat480gggtctcttt tgtttgatgg ttgctttctt gattttgttt gccatgtaac aaattactgc540ttgacatgtt ggcattcata ttaattacng atgtaattct gtgtatctta c 591<210>315<211>591<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(591)<223>n＝A、T、C或G<400>315aagcccttca ccaacaaaga tgcctatact tgtgcaaatt gcagtgcttt tgtccacaaa 60ggctgccgag aaagtctagc ctcctgtgca aaggtcaaaa tgaagcagcc caaagggagc120cttcaggcac atgacacatc atcactgccc acggtcatta tgagaaacaa gccctcacag180cccaaggagc gtcctcggtc cgcagtcctc ctggtggatg aaaccgctac caccccaata240tttgccaata gacgatccca gcagagtgtc tcgctctcca aaagtgtctc catacagaac300attactggag ttggcaatga tgagaacatg tcaaacacct ggaaattcct gtctcattca360acagactcac taaataaaat cagcaaggtc aatgagtcaa cagaatcact tactgatgag420ggtacagaca tgaatgaagg acaactactg ggagactttg agattgagtc caaacagctg480gaagcagagt cttggagtcg gataatagac agcaagtttc taaaacagcc aaaagaaaga540tgtgggtcaa acngcgagaa gtaatatatg agttggatgc agacagagtt t 591
<210>316<211>591<212>DNA<213>智人(Homo sapiens)<400>316gtttttataa gaataaaatt ccattcaagc cagatggtgt ttacattgaa gaagttctaa 60gtaaatggaa aggagattat gaaaaactgg agcacaacca cacttacatt caatggcttt120tccccctgag agaacaaggc ttgaacttct atgccaaaga actaactaca tatgaaattg180aggaattcaa aaaaacaaaa gaagcaatta gaagattcct cctggcttat aaaatgatgc240tagaattttt tggaataaaa ctgactgata aaactggaaa tgttgctcgg gctgttaact300ggcaggaaag atttcagcat ctgaatgagt cccagcacaa ctatttaaga atcactcgta360ttcttaaaag ccttggtgag cttggatatg aaagttttaa atctcctctt gtaaaattta420ttcttcatga agctcttgtg gagaatacta ttcccaatat taagcagagt gctctagagt480attttgttta tacaattaga gacagaagag aaaggagaaa gctcctgcgg ttcgcccaga540aacactacac gccttcagag aactttatct ggggacccgc ctcgaaaaga a 591<210>317<211>323<212>DNA<213>智人(Homo sapiens)<400>317ccaagctacg gaagcaagtg gaagagattt ttaatttgaa atttgctcaa gctcttggac 60tcaccgaggc agtaaaagta ccatatcctg tgtttgaatc aaacccggag ttcttctatg120tggaaggctt gccagagggg attcccttcc gaagccctac ctggtttgga attccacgac180ttgaaaggat cgtccacggg agtaataaaa tcaagttcgt tgttaaaaaa cctgaactag240ttatttccta cttgcctcct gggatggcta gtaaaataaa cactaaagct ttgcagtccc300ccaaaagacc acgaagtcct ggg323<210>318<211>591<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(591)<223>n＝A、T、C或G<400>318gatggcgtac ttggcttgga gactggcgcg gcgttcgtgt ccgagttctc tgcaggtcac 60tagtttcccg gtagttcagc tgcacatgaa tagaacagca atgagagcca gtcagaagga120ctttgaaaat tcaatgaatc aagtgaaact cttgaaaaag gatccaggaa acgaagtgaa180gctaaaactc tacgcgctat ataagcaggc cactgaagga ccttgtaaca tgcccaaacc240aggtgtattt gacttgatca acaaggccaa atgggacgca tggaatgccc ttggcagcct300gcccaaggaa gctgccaggc agaactatgt ggatttggtg tccagtttga gtccttcatt360ggaatcctct agtcaggtgg agcctggaac agacaggaaa tcaactgggt ttgaaactct420ggtggtgacc tccgaagatg gcatcacaaa gatcatgttc aaccggccca aaaagaaaaa480tgccataaac actgagatgt atcatgaaat tatgcgtgca cttaaagctg ccagcaanga540tgactcaatc atcacttgtt ttaacaggaa atggtgacta ttacagtagn g 591<210>319<211>591<212>DNA<213>智人(Homo sapiens)<400>319gaattcggca cgaggttgct gctaagcgaa cgccctttgg agcttacgga ggccttctga 60aagacttcac tgctactgac ttgtctgaat ttgctgccaa ggctgccttg tctgctggca120aagtctcacc tgaaacagtt gacagtgtga ttatgggcaa tgtcctgcag agttcttcag180atgctatata tttggcaagg catgttggtt tgcgtgtggg aatcccaaag gagaccccag240ctctcacgat taataggctc tgtggttctg gttttcagtc cattgtgaat ggatgtcagg300aaatttgtgt taaagaagct gaagttgttt tatgtggagg aaccgaaagc atgagccaag360ctccctactg tgtcagaaat gtgcgttttg gaaccaagct tggatcagat atcaagctgg420aagattcttt atgggtatca ttaacagatc agcatgtcca gctccccatg gcaatgactg480cagagaatct tgctgtaaaa cacaaaataa gcagagaaga atgtgacaaa tatgccctgc540agtcacagca gagatggaaa gctgctaatg atgctggcta ctttaatgat g 591<210>320<211>591<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(591)<223>n＝A、T、C或G<400>320ggctccggcg tctgcagggg tcgccgagct aacccgtggc taggcgagtg gggcggggcg 60gccggcacca tgtcgaggca ggcgaaccgt ggcaccgaga gcaagaaaat gagctctgag120ctcttcaccc tgacctatgg tgccctggtc acccagctat gtaaggacta tgaaaatgat180gaagatgtga ataaacagct ggacaaaatg ggctttaaca ttggagtccg gctgattgaa240gatttcttgg ctcggtcaaa tgttgggagg tgccatgact ttcgggaaac tgcggatgtc300attgccaagg tggcgttcaa gatgtacttg ggcatcactc caagcattac taattggagc360ccagctggtg atgaattctc cctcattttg gaaaataacc ccttggtgga ctttgtggaa420cttcctgata accactcatc ccttatttat tccaatctct tgtgtggggt gttgcgggga480gctttggaga tggtccagat ggctngngga ggcccaagtt tgtccaggac accctnaaag540gagacgggng tgacagaaat ccggatgaga ttcatcaggc ggattganga c 591<210>321<211>260<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(260)<223>n＝A、T、C或G<400>321ctgcttggct ccacacgtgg gccgccgtag gtattccgac cggtaattcc tcctattggt 60gtgcagcagc cacattgaag gatagagtgg cagcagaggc caaggatcgt gagttgatgg120agtttgctgc tgaaaatgaa gggaagtctg ggggaggtct ccacagcgta gctgaggggg180tgcggctaag tccagagcct ggcagggagg gagtaaggga cttagcaggg gcggaggagt240tctgcggngg anaggagggg260<210>322<211>559<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(559)
<223>n＝A、T、C或G<400>322ttccacatga catggagtgt gaagctggat gagcacatca ttccactggg aagcatggca 60nttaacagca tctcaaaact gactnanctc acccagtctt ccatgtattc acttcctaat120gcacccactc tggcanacct gnaggacnat acacatgaag ncantgatga tcagccagan180aancctcact ttgactctcg canngtgata tttgagctgg attcatgcaa tggnagtggg240aaagtttgcc ttgtctacaa aagtgggaaa ccagnattag cagaanacac tgagatctgg300ttcctgnaca nancgttata ctggcatttt ctcacanaca cctttactgc ctattaccgc360ctgctcatca cccacctggg cctgccccag tggcaatatg ccttcccagc tatggcatta420gcccacaggc caagcaatgg ttcagcatgt ataaacctat cacctacaac acaaacctgc480tcacagaaga naccgactcc tttgtgaata agctagatcc canctnagtg tttaagagca540agaacaagat cgttatccc 559<210>323<211>492<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(492)<223>n＝A、T、C或G<400>323cctgtctccc agccgtacca gcgagggctc ggccggcagc gccgggctgg ggggcggcgg 60cgccggcgcc ggagccgggg tgggtgcagg cggcggcggg ggcagcggcg cgagcagcgg120cggcggggcc ggggggctgc aacccagcag ccgcgctggc ggcggccggc cctccagccc180cagcccgtcg gtggtgagcg agaaggagaa ggaagagttg gagcggctgc agaaagagga240ggaggagagg aagaagaggc tgcagctgta tgtgttcgtg atgcgctgca tcgcctaccc300ctttaatgcc aagcagccca ccgacatggc tcgccggcag cagaagatca gcaaacagca360gctgcagaca gtcaaggacc ggtttcaggc tttcctcaat ggggaaaccc anatcatggc420tgacgaagcc ttcatgaacc gctgtngcag agttactatg aggtgttcct gaagaccacc480cgtgtggccg ca492<210>324<211>474<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(474)<223>n＝A、T、C或G<400>324aatttcagca acatacttct caatttcttc aggatttaaa atcttgaggg attgatctcg 60cctcatgaca gcaagttcaa tgtttttgcc acctgactga accacttcca ggagtgcctt120gatcaccagc ttaatggtca natcatctgt ttcaatggct tcgtcagtat agttcttctc180cagnaactca cgcactgact tggcaccccg gcctatggca ttggccttcc aggcatggta240tgtgcccgag gggtcagtct gatagagcct aggagtgcca tcaaagtcga aacccacgat300gagggcagag atgccaaacg gcctgcgccc attgctctgc gtataacgct gcttcanact360ggcgatgtag cgggtgatgt actccacagt gaccgggtcc tccacagtca gccggtggct420ctggcactcc acccgggccc tgttgatgac tatccttgca tcggcggtga ggcc 474<210>325<211>532<212>DNA
<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(532)<223>n＝A、T、C或G<400>325gaggagacag gacagagcgt ctggagaggc aggaggacac cgagttcccc gtgttggcct 60ccaggtcctg tgcttgcgga gccgtccggc ggctgggatc gagccccgac aatgggcaac120gcgcaggagc ggccgtcaga gactatcgac cgcgagcgga aacgcctggt cgagacgctg180caggcggact cgggactgct gttggacgcg ctgctggcgc ggggcgtgct caccgggcca240gagtacgagg cattggatgc actgcctgat gccgagcgca gggtgcgccg cctactgctg300ctggtgcagg gcaagggcga ggccgcctgc caggagctgc tacgctgtgc ccagcgtacc360gcgggcgcgc cggaccccgc ttgggactgg cagcacgtgg gtccgggcta ccgggaccgc420agctatgacc ctccatgccc aggccactgg acgccggagg cacccggctc ggggaccaca480tgccccgggt tgcccagact tcagaccctg acgaggncgg gggccctgag gg532<210>326<211>322<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(322)<223>n＝A、T、C或G<400>326caaaattaac atttttatta aatcaagtta aaaaaaatgt tcagtgtana aaagtcaaca 60agggttttaa caaaaccaaa atataccttt ttatacaata tatgtatata ttagcagcaa120actacttctg anattctctt tcttttatgt tcttctagtt attttaaaga aagcataaac180aatgtatatt agtatggaat gtcagcaaat ccactcttag tcctttattc tgtgatttgg240gccttctaca aaatactttg tgattctcac taatgaatat taagaacata cccaatttta300actaaaaagt agtgaaacag tg 322<210>327<211>387<212>DNA<213>智人(Homo sapiens)<400>327aaaaccgtgt actattagcc atggtcaacc ccaccgtgtt cttcgacatt gccgtcgacg 60gcgagccctt gggccgcgtc tcctttgagc tgtttgcaga caaggtccca aagacagcag120aaaattttcg tgctctgagc actggagaga aaggatttgg ttataagggt tcctgctttc180acagaattat tccagggttt atgtgtcagg gtggtgactt cacacgccat aatggcactg240gtggcaagtc catctatggg gagaaatttg aagatgagaa cttcatccta aagcatacgg300gtcctggcat cttgtccatg gcaaatgctg gacccaacac aaatggttcc cagtttttca360tctgcactgc caagactgag tggttgg387<210>328<211>502<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(502)
<223>n＝A、T、C或G<400>328agcagcccgg cgcggccgcc gcgccggcgg gcggcaaggc tccgggccag catgggggct 60tcgtggtgac tgtcaagcaa gagcgcggcg agggtccacg cgcgggcgag aaggggtccc120acgaggagga gccggtgaag aaacgcggct ggcccaaggg caagaagcgg aagaagattc180tgccgaatgg gcccaaggca ccggtcacgg gctacgtgcg cttcctgaac gagcggcgcg240agcagatccg cacgcgccac ccggatctgc cctttcccga gatcaccaag atgctgggcg300ccgagtggag caagctgcag ccaacggaaa agcagcggta cctggatgag gccnagagag360agaagcagca gtacatgaag gagctgcggg cgtaccagca gtctgaagcc tataagatgt420gcacggagaa gatccaggag aagaagatca agaaagaaga ctcgagctct gggctcatga480acactcttct gaatggacac aa 502<210>329<211>463<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(463)<223>n＝A、T、C或G<400>329caagttgcac attttaattt acaattttta ccaataaaaa ggattagttt acaaaaaggg 60aagtccttta tacaaaataa ggacaatttg taaaganaat ccactgtcat gttttgcctt120gtcaagtcaa aactcaaata gcttgttttg gtaaaattat tccagaaaca taatccagac180aaaatcaata acgtcatcag cttcctaacc atgtttaana ggaataactt catgaacatt240ttgccctgaa ctgaanagtt ctaaatactt gtaaaccttt aggaaaaaat gactgctcgc300aggcagcttg actggtaaga gggtacacca nagactccgg gtcactcact gtcagaatat360tcttatacat acaatgagtc tccacgcctg tacaatgagt gtcgtgcaac ataattggag420taatggcctc taaaatttta caagtaaact ttattgnggc ccc 463<210>330<211>500<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(500)<223>n＝A、T、C或G<400>330taattataga tctacaaaat atgaaatgta ttccaagaat gcagaaaaac catctagaag 60caaaaggact ataaaacaaa aacagagaag aaaattcatg gctaaaccag ctgaagaaca120gcttgatgtg ggacagtcta aagatgaaaa catacataca tcacatatta cccaagacga180atttcaaaga aattcagaca gaaatatgga agagcatgaa gagatgggaa atgattgtgt240ttccaaaaaa acagatgcca cctgtgggaa gcaagaaaag tagcactaga aaagataagg300aagaatctaa aaagaagcgc ttttccagtg agtccaagaa caaacttgtn cctgaagaag360tgacttcaac tgtcacgaaa agtcgaanaa tttccangcg tccatctgat tggtgggtgg420taaaancaga ggagagtcct gtttatagca attcttcagt aagaaatgaa ttaccaantg480catcacaatn ntgcccggaa500<210>331<211>494<212>DNA<213>智人(Homo sapiens)
<220>
<221>misc_feature<222>(1)...(494)<223>n＝A、T、C或G<400>331tctctctctc tctcaaaatt acagtgttca ttgtcattga cctcagcagc aaatttgact 60tgaattcact taggatcgca ggaatcaggg gaaagtgatt ttaaaggtgg tttctccagc120acattttaag aaaagggacc aaaagttatt ttagcttcct caatagattg catgttgctt180attaggataa taaattaata ttaaatgcaa tatatgtctt gnctttatta tggcatctat240ttaggagttg ttcaaatcac tgcagtaggg ctctgcaaat aaaataatgn aacctattat300catggatcta atgnactgna actttatcag tgaaaggnaa aatctcaaat aacaagtaca360aacattggac aattacctat aaagatttgt aaaaggaaaa tttttccata gatttcattc420ttggcatttt gtaaagacga ccctgcagnc ccctgtttgn aactttttta ataaaataga480catctgttta cttg 494<210>332<211>538<212>DNA<213>智人(Homo sapiens)<400>332aaagaacaaa tggaacgcga tggttgttct gaacaagagt ctcaaccgtg tgcatttatt 60gggataggaa atagtgacca agaaatgcag cagctaaact tggaaggaaa gaactattgc120acagccaaaa cattgtatat atctgactca gacaagcgaa agcacttcat gttgtctgta180aagatgttct atggcaacag tgatgacatt ggtgtgttcc tcagcaagcg gataaaagtc240atctccaaac cttccaaaaa gaagcagtca ttgaaaaatg ctgacttatg cattgcctca300ggaacaaagg tggctctgtt taatcgacta cgatcccaga cagttagtac cagatacttg360catgtagaag gaggtaattt tcatgccagt tcacagcagt ggggagcctt ttttattcat420ctcttggatg atgatgaatc agaaggagaa gaattcacag tccgagatgg ctacatccat480tatggacaaa cagtcaaact tgtgtgctca gttactggca tggcactccc aagattga 538<210>333<211>499<212>DNA<213>智人(Homo sapiens)<400>333ctcagcctgc gggactgctc ggctcggctt ctaggcggtt ttgatgaaca cctggcttta 60ttcttgcaat gaagaaaggt tctcaacaaa aaatattctc caaagcaaag ataccatcat120catctcactc tcctatccca tcatctatgt ccaatatgag atctaggtca ctttcacctt180tgattggatc agagactcta ccttttcatt ctggaggaca gtggtgtgag caagttgaga240ttgcagatga aaacaatatg cttttggact atcaagacca taaaggagct gattcacatg300caggagttag atatattaca gaggccctca ttaaaaaact tactaaacag gataatttgg360ctttgataaa atctctgaac ctttcacttt ctaaagacgg tggcaagaaa tttaagtata420ttgagaattt ggaaaaatgt gttaaacttg aagtactgaa tctcagctat aatctaatag480ggaagattga aaagtcgga 499<210>334<211>561<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(561)<223>n＝A、T、C或G
<400>334ttcccggtag ttcagctgca catgaataga acagcaatga gagccagtca gaaggacttt 60gaaaattcaa tgaatcaagt gaaactcttg aaaaaggatc caggaaacga agtgaagcta120aaactctacg cgctatataa gcaggccact gaaggacctt gtaacatgcc caaaccaggt180gtatttgact tgatcaacaa ggccaaatgg gacgcatgga atgcccttgg cagcctgccc240aaggaagctg ccaggcagaa ctatgtggat ttggtgtcca gtttgagtcc ttcattggaa300tcctctagtc aggtggagcc tggaacagac aggaaatcaa ctgggtttga aactctggtg360gtgacctccg aagatggcat cacaaagatc atgttcaacc cggcccaaaa agaaaaatgc420cataaacact gagatgtatc atgaaattat gcgtgcactt aaagctgcca gcaaggatga480ctcaatcatc actgttttaa cangaaatgg tgactattac agtagtggga atgatctgac540taacttcnct gatattcccc c 561<210>335<211>551<212>DNA<213>智人(Homo sapiens)<400>335aagctggtca tggctgggga gaccaccaac tcccgcggcc agcggctgcc ccagaaggga 60gacgtggaga tgctgtgcgg cgggccgccc tgccagggct tcagcggcat gaaccgcttc120aattcgcgca cctactccaa gttcaaaaac tctctggtgg tttccttcct cagctactgc180gactactacc ggccccggtt cttcctcctg gagaatgtca ggaactttgt ctccttcaag240cgctccatgg tcctgaagct caccctccgc tgcctggtcc gcatgggcta tcagtgcacc300ttcggcgtgc tgcaggccgg tcagtacggc gtggcccaga ctaggaggcg ggccatcatc360ctggccgcgg cccctggaga gaagctccct ctgttcccgg agccactgca cgtgtttgct420ccccgggcct gccagctgag cgtggtgggt ggatgacaag aagtttgtga gcaacataac480caggttgagc tcgggtcctt tccggaccat acggtgcgag aaacgatgtc cgacctgccg540gaagtgcgga a 551<210>336<211>540<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(540)<223>n＝A、T、C或G<400>336aggtctatgt ctactgaagg caataaacga ggaatgatcc agcttattgt tgcaaggaga 60ataagcaagt gcaatgagct gaagtcacct gggagccccc ctggacctga gctgcccatt120gaaacagcgt tggatgatag agaacgaaga atttcccatt ccctctacag tgggattgag180gggcttgatg aatcgcccag cagaaatgct gccctcagta ggataatggg taaataccag240ctgtccccta cagtgaatat gccccaagat gacactgtca ttatagaaga tgacaggttg300ccagtgcttc ctccacatct ctctgaccag tcctcttcca gctcccatga tgatgtgggg360tttgtgacgg cagatgctgg tacttgggcc aaggctgcaa tcagtgattc agccgactgc420tctttgagtc cagatgttga tccagttctt gcttttcaac gaaaaaggat ttggacgtca480gaagtatgtc agaaaaacgc accaaagcaa ttttcanatg ccagtcaatt ggatttcgtt540<210>337<211>422<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature
<222>(1)...(422)<223>n＝A、T、C或G<400>337gcagcaggaa cagttacagc agcagcagca acagcagctg ttgcaacagc agcaggaaca 60atgtcagcag caacaactgc agcctcctcc cctggagccc gaggaggagg aagaggtgga120gctggagctc atgccggtgg acctggggtc agagcaggag ctggagcagc agcggcagga180gttggagcgg cagcaggagc tggaacggca gcaggagcag cggcagctgc agctcaaact240gcaggaggag ctgcagcagc tggagcaaca gctggagcag cagcagcagc agctggagca300gcaggaggtg cagctggagc tgaccccggt ggagctaggc gcccagcagc aggaggtgca360gctggagctg acccccgtgc agccggagct gcagctggaa ctggtgccan cccagggggc420gg 422<210>338<211>601<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(601)<223>n＝A、T、C或G<400>338catcttacga acgctctatg atgtcttatg agcggtctat gatgtcccct atggctgaac 60gctctatgat gtcagcctac gagcgctcta tgatgtcagc ctacgagcgc tctatgatgt120cccctatggc tgagcgctct atgatgtcag cttatgaacg ctccatgatg tcagcttatg180aacgctccat gatgtcccca atggctgatc gatctatgat gtccatgggt gctgaccggt240ctatgatgtc gtcatactct gctgctgacc ggtctatgat gtcatcgtac tctgcagctg300accgatctat gatgtcatct tatactgctg atcgttcaat gatgtctatg gctgctgatt360cttacaccga ttcttacact gacacatata cagaggcata tatggtgcca cctttgcctc420ctgaagagcc cccaacaatg ccaccgttgc cacctgagga gccaccaatg acaccaccat480tgcctnctga ggaaccaccc agagggtcca gcattgccca cttgagcagt cagcattaac540cagcttgaaa atacttggcc ctacanangg tgccatcatt accatctgaa gagctgtatc600g601<210>339<211>440<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(440)<223>n＝A、T、C或G<400>339agagggagga ggcccaactg gtgatgctgc tgctgctgct gctgccgccg ccgccgcctc 60tattgctgat actctagtgg ggctggaagg gtggttccta ttcgcaccat cgccaaccag120agacagaggg aaaaaaaaaa ccggcagcca ctgctgatgt tgggttcgga ggctgcatcc180gactcggtca caaggaaaat ggattcagtt tgcatctctc cctcctttaa acagcttctc240cgggtctcag catggtatca aagcttgaaa gagagaagac tcaagaagcg aagaggattc300gtgagctgga gcagcgcaag cacacggtgc tggtgacaga actcaaagcc aagctccatg360aggagaagat gaaggagctg caggctgtga gggagaacct tatcaagcag cacgacagga420aatgtcaang acggtgaagg440<210>340<211>450
<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(450)<223>n＝A、T、C或G<400>340gatttccagg ggcggatatt gagtgtcgac ccagaggaag aaagggagga gggcccgcct 60aggattcctc aggccgacca gtggaagtct tcaaacaaga gcctggtgga ggctctgggg120ctggaagccg agggtgcagt tcctgagaca cagactttga ccggatggag taaggggttc180attggcatgc acagggaaat gcaagtcaac cccatttcaa agcggatggg gcccatgact240gtggtcagga tggacgcttc agtccagcca ggcccttttc ggaccctgct ccagtttctt300tatacgggac aactggatga aaaggaaaag gatttggtgg gcctggctca gatcgcagag360gtcctcgaga tgttcgattt gaggatgatg gtggaaaaca tcatgaacaa ggaagccttc420atgaaccagg agattacgaa nncctttcac 450<210>341<211>451<212>DNA<213>智人(Homo sapiens)<400>341aacagctatt aaaacagaaa atggatgaac ttcataagaa gttgcatcag gtggtggaga 60catcccatga ggatctgccc gcttcccagg aaaggtccga ggttaatcca gcacgtatgg120ggccaagtgt aggctcccag caggaactga gagcgccatg tcttccagta acctatcagc180agacaccagt gaacatggaa aagaacccaa gagaggcacc tcctgttgtt cctcctttgg240caaatgctat ttctgcagct ttggtgtccc cagccaccag ccagagcatt gctcctcctg300ttcctttgaa agcccagaca gtaacagact ccatgtttgc agtggccagc aaagatgctg360gatgtgtgaa taagagtact catgaattca agccacagag tggagcagag atcaaagaag420ggtgtgaaac acataaggtt gccaacacaa g 451<210>342<211>498<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(498)<223>n＝A、T、C或G<400>342ctcaagcagg ctattgaaga ggaaggaggc gatccagata atattgaatt aactgtttca 60actgatactc caaacaagaa accaactaaa ggcaaaggta aaaaacatga agcagatgag120ttgagtggag atgcttctgt gggaagatga tgcttttatc aaggactgtg aattggagaa180tcaagaggca catgagcaag atggaaatga tgaactaaag gactctgaag aatttggtga240aaatgaagaa gaaaatgtgc attccaagga gttactctct gcagaagaaa acaagagagc300tcatgaatta atagaggcag aaggaataga agatatagaa aaagaggaca tcgaaagtca360ggaaattgaa gctcaagaag gtgaagatga tacctttcta acagcccaag atggtgagga420agaagaaaat gagaaagata tagcagggtt ctggtgatgg cncacaagaa gtatntaaac480ctcttccttc aaaaaggg 498<210>343<211>491<212>DNA<213>智人(Homo sapiens)
<400>343ccgaccccta ctcggcggcg caactccaca accagtacgg ccccatgaat atgaacatgg 60gtatgaacat ggcagcagcc gcggcccacc accaccacca ccaccaccac caccccggtg120cctttttccg ctatatgcgg cagcagtgca tcaagcagga gctaatctgc aagtggatcg180accccgagca actgagcaat cccaagaaga gctgcaacaa aactttcagc accatgcacg240agctggtgac acacgtctcg gtggagcacg tcggcggccc ggagcagagc aaccacgtct300gcttctggga ggagtgtccg cgcgagggca agcccttcaa ggccaaatac aaactggtca360accacatccg cgtgcacaca ggcgagaaac ccttccctgc ccttccgggt gtggcaaagt420cttcgcgcgc tccgagaacc tcaagatcca caaaaggacc acacagggga gaagccgtcc480agtggagttg a 491<210>344<211>412<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(412)<223>n＝A、T、C或G<400>344gtgcgctgtc ttcccgcttg cgtcagggac ctgcccgact cagtggccgc catggcatca 60gatgaaggca aactttttgt tggagggctg agttttgaca ccaatgagca gtcgctggag120caggtcttct caaagtacgg acagatctct gaagtggtgg ttgtgaaaga cagggagacc180cagagatctc ggggatttgg gtttgtcacc tttgagaaca ttgacgacgc taaggatgcc240atgatggcca tgaatgggaa gtctgtagat ggacggcaga tccgagtaga ccaggcaggc300aagtcgtcan acaaccgatc ccgtgggtac cgtggtggct ctgccggggg ccggggcttc360ttccgtgggg gcccgangac ggggcccgtg ggttctctaa aagaagaggg ga412<210>345<211>498<212>DNA<213>智人(Homo sapiens)<400>345aactagtctc gggccatcct ttctgcgcac ccggtgtcgc tgggctgcac cccgggcggg 60gacgtccgcc gggcacggga gggggccaag atgccgatca ataaatcaga gaagccagaa120agctgcgata atgtgaaggt tgttgttagg tgccggcccc tcaatgagag agagaaatca180atgtgctaca aacaggctgt cagtgtggat gagatgaggg gaactatcac tgtacataag240actgattctt ccaatgaacc tccaaagaca tttacttttg atactgtttt tggaccagag300agtaaacaac ttgatgttta taacttaact gcaagaccta ttattgattc tgtacttgaa360ggctacaatg ggactatttt tgcatatgga caaaccggaa caggcaaaac ttttaccatg420gaaaggtgtc gagctattcc tgaacttaga ggaataattc cccaatttct ttgctcacaa480tatttgggcc atatttgc 498<210>346<211>427<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(427)<223>n＝A、T、C或G<400>346agatggcggt cgccgtgaga actttgcagg aacagctgga aaaggccaaa gagagtctta 60agaacgtgga tgagaacatt cgcaagctca ccgggcggga tccgaatgac gtgaggccca120tccaagccag attgctggcc ctttctggtc ctggtggagg tagaggacgt ggtagtttat180tactgaggcg tggattctca gatagtggag gaggaccccc agccaaacag agagaccttg240aaggggcagt cagtaggctg ggcggggagc gtcggaccag aagagaatca cgccaggaaa300gcgacccgga ggatgatgat gttaaaaagc cagcattgca gtcttcannt gtagctacct360cccaaagagc gccccacgta gagaccttat ccagggatca aaattttgga tgaaaaaggg420gaaagcc 427<210>347<211>280<212>DNA<213>智人(Homo sapiens)<400>347cacagaaagt tctccgctcc cagacatggg tccctcggct tcctgcctcg gaagcgcagc 60agcaggcatc gtgggaaggt gaagagcttc cctaaggatg acccgtccaa gccggtccac120ctcacagcct tcctgggata caaggctggc atgactcaca tcgtgcggga agtcgacagg180ccgggatcca aggtgaacaa gaaggaggtg gtggaggctg tgaccattgt agagacacca240cccatggtgg ttgtgggcat tgtgggctac gtggaaaccc 280<210>348<211>411<212>DNA<213>智人(Homo sapiens)<400>348caactatgat gtgcctgaaa aatgggcacg attctatact gcagaagtag ttcttgcatt 60ggatgcaatc cattccatgg gttttattca cagagatgtg aagcctgata acatgctgct120ggataaatct ggacatttga agttagcaga ttttggtact tgtatgaaga tgaataagga180aggcatggta cgatgtgata cagcggttgg aacacctgat tatatttccc ctgaagtatt240aaaatcccaa ggtggtgatg gttattatgg aagagaatgt gactggtggt cggttggggt300atttttatac gaaatgcttg taggtgatac acctttttat gcagattctt tggttggaac360ttacagtaaa attatgaacc attaaaaatt cacttacctt tcctgatgat a 411<210>349<211>408<212>DNA<213>智人(Homo sapiens)<400>349gatgggcatc tctcgggaca actggcacaa gcgccgcaaa accgggggca agagaaagcc 60ctaccacaag aagcggaagt atgagttggg gcgcccagct gccaacacca agattggccc120ccgccgcatc cacacagtcc gtgtgcgggg aggtaacaag aaataccgtg ccctgaggtt180ggacgtgggg aatttctcct ggggctcaga gtgttgtact cgtaaaacaa ggatcatcga240tgttgtctac aatgcatcta ataacgagct ggttcgtacc aagaccctgg tgaagaattg300catcgtgctc atcgacagca caccgtaccg acagtggtac gagtcccact atgcgctgcc360cctgggccgc aagaagggag ccaaactgac ttctgaggaa gaagaaaa 408<210>350<211>409<212>DNA<213>智人(Homo sapiens)<400>350ggttccccca gctctgggta cccggctctg catcgcgtcg ccatgatggg ccatcgtcca 60gtgctcgtgc tcagccagaa cacaaagcgt gaatccggaa gaaaagttca atctggaaac120atcaatgctg ccaagactat tgcagatatc atccgaacat gtttgggacc caagtccatg180atgaagatgc ttttggaccc aatgggaggc attgtgatga ccaatgatgg caatgccatt240cttcgagaga ttcaagtcca gcatccagcg gccaagtcca tgatcgaaat tagccggacc300caggatgaag aggttggaga tgggaccaca tcagtaatta ttcttgcagg ggaaatgctg360tctgtagctg agcacttcct ggagcagcag atgcacccaa caggtgggg409<210>351<211>226<212>DNA<213>智人(Homo sapiens)<400>351aatcccaaac atataactga actcctcaca cccaattgga ccaatctatc accctataga 60agaactaatg ttagtataag taacatgaaa acattctcct ccgcataagc ctgcgtcaga120ttaaaacact gaactgacaa ttaacagccc aatatctaca atcaaccaac aagtcattat180taccctcact gtcaacccaa cacaggcatg ctcataagga aaggtt 226<210>352<211>410<212>DNA<213>智人(Homo sapiens)<400>352gcggaggggc tggctgggca ggaggggttg gcggggcagc agggccgcgg ccatggggag 60cttgaaggag gagctgctca aagccatctg gcacgccttc accgcactcg accaggacca120cagcggcaag gtctccaagt cccagctcaa ggtcctttcc cataacctgt gcacggtgct180gaaggttcct catgacccag ttgcccttga agagcacttc agggatgatg atgagggtcc240agtgtccaac cagggctaca tgccttattt aaacaggttc attttggaaa aggtccaaga300caactttgac aagattgaat tcaataggat gtgttggacc ctctgtgtca aaaaaaacct360cacaaagaat cccctgctca ttacagaaga agatgcattt aaaatatggg 410<210>353<211>380<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(380)<223>n＝A、T、C或G<400>353gagtttattt agaaagtatc atagtgtaaa caaacaaatt gtaccacttt gattttcttg 60gaatacaaga ctcgtgatgc aaagctgaag ttgtgtgtac aagactcttg acagttgtgc120ttctctagga ggntgggttt ttttaaaaaa agaattatct gngaaccata cgtgattaat180aaagatttcc tttaaggcan aggctggtcn agatgctgct gttatcttct gcctcagaca240gacagtataa gnggtcttgt ttctaagatt cctaccacca gttactttgg gccaagtatc300cacatcccct tgcgtatggg aggngggtga anagtgttgg atgcaaagng gttattatgg360gaagnagctc natggtaaaa380<210>354<211>379<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(379)<223>n＝A、T、C或G
<400>354caacacatct ttattaaaca cctgaagtta ctgggaggag gccatgatgc tggacacact 60gtcaaagtca atcttctcca caatgttctt gggtttaatg ctctcttctt ggctacagan120gaanatctgc cccgactngt cggcactcca gccgtatttg ctcatccaca cctttagctg180gctgtccgac aganccccga gcatntcggc cagcagccan cggncaatgt gctggtaagt240gatacccaca acatggcaga taaactttcg gacanagtct tcaaagccag ttataccttc300caagaggtcc atgttttcat ccagggcttg ccanaagcct ggaaatggca ggtctccaac360aggtccccca ggtacaaaa 379<210>355<211>499<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(499)<223>n＝A、T、C或G<400>355gtccagagct gctggtgctc ccgttcccca gaccctaccc ctatccccag tggagccgga 60gtgcgggcgc gccccaccac cgccctcacc atggtgctgt tggcagcagc ggtctgcaca120aaagcaggaa aggctattgt ttctcgacag tttgtggaaa tgacccgaac tcggattgag180ggcttattag cagcttttcc aaagctcatg aacactggaa aacaacatac gtttgttgaa240acagagagtg taagatatgt ctaccagcct atggagaaac tgtatatggt actgatcact300accaaaaaca gcaacatttt agaagatttg gagaccctaa ggctcttctc aagagtgatc360cctgaatatt gcgagcctta gaagagaatg aaatatctga gcactgnttt gatttgattt420ttgcttttga tgaaaatgtc gcactgggat acccgggang aatgttaact tggcacagat480canaaccttt cacagaaaa 499<210>356<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>356gggcttctgc tgagggggca ggcggagctt gaggaaaccg cagataagtt tttttctctt 60tgaaagatag agattaatac aactacttaa aaaatatagt caataggtta ctaagatatt120gcttagcgtt aagtttttaa cgtaatttta atagcttaag attttaagag aaaatatgaa180gacttagaag agtagcatga ggaaggaaaa gataaaaggt ttctaaaaca tgacggaggt240tgagatgaag cttcttcatg gagtaaaaaa tgtatttaaa agaaaattga gagaaaggac300tacagagccc cgaattaata ccaatagaag ggcaatgctt ttagattaaa atgaaggtga360cttaaacagc ttaaagttta ntttaaaagt tgtaggtgat taaaataatt tgaaggcgat420cttttaaaaa gagattaaac ccgaaggtga ttaaaagacc ttgaaatcca tgacgccagg480gagaattgcc gtcatttaaa gcctagttaa c 511<210>357<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>357gatacttcac atttccctag ggacgggagc ccgaggggtc cgttcggccc tcttcctctc 60gctgggccga caccccgctg taggaccgta acccttagtc ccaatgcctc cgtaagcgga120gttgagtggg tgcctgtggt tggagctgtg gaggtgtccc cggtggcgag cgcggccaga180actgcggtca cttaagtttt ccgtgtgcgg gttgcaagga gcgtgcgtgc gtctggtata240atttggcttc ctgagattct gcttacaaga aaggagtggg aaataccctt ggaaagaaaa300ctaaaacagt aagaaaacca aaacttattt ttacatggnt gtcagcacat ttaccgatat360ggacactttt cccaataatt tcctcctggt ggagacagtg gattgacagg ttctcagtcg420gaattccaga aaaatgttaa ttgatgaaaa gggtacnatg tgagcatcat aaagntaatt480attaanacac tgaaggctga acacacaagg g 511<210>358<211>401<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(401)<223>n＝A、T、C或G<400>358acggatgaag atgatgacct tcaagaaaat gaagacaata aacaacataa agaaagcttg 60aaaagagtga cctttgcttt accagatgat gcggaaactg aagatacagg tgttttaaat120gtaaagaaaa attctgatga agttaaatcc tcctttgaaa aaagacagga aaagatgaat180gaaaaaattg catctttaga aaaagagttg ttagaaaaaa agcccgtggc agcttcaggg240ggaagtgaca gcacagaaga ggccagagaa cacctcctgg aggagaccct acctttgcca300tctgcccgat ggccctgtga ttacagagga acccccttca ctggagattt ctttaacnga360ngatagagat cngnttggga tatgtntcct taagaaaacc t401<210>359<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>359gcgatgcccg cgcgcccagg acgcctcctc ccgctgctgg cccggccggc ggccctgact 60gcgctgctgc tgctgctgct gggccatggc ggcggcgggc gctggggcgc ccgggcccag120gaggcggcgg cggcggcggc ggacgggccc cccgcggcag acggcgagga cggacaggac180ccgcacagca agcacctgta cacggccgac atgttcacgc acgggatcca gagcgcccgc240gcacttcgtc atgttcttcg cgccctggtg tggacacttg ccagcggctt gcagccgant300ttggaatgac cttggganga acaaatacaa cagcatggaa agaatgccaa aagtctatgt360ggnttaaagt ggacttgcac nggccacttc gactngtgct cccccaaggg gngggaagat420acccacctta aaacttttca accaagccaa aaactttgaa aaccaggtct cggattcaaa480atggaaaact gatgttcaac ctgaacaaga a 511<210>360<211>511<212>DNA
<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>360tactgggaga ctttgagatt gagtccaaac agctggaagc agagtcttgg agtcggataa 60tagacagcaa gtttctaaaa cagcaaaaga aagatgtggt caaacggcaa gaagtaatat120atgagttgat gcagacagag tttcatcatg tcccgactct caagatcatg agtggtgtgt180cnagccnggg gatgatggcg gatctgnttt ttgagcanca gatggtagaa aaagctggtt240ccctgtttgg atgagcttga tcagtatccc atacccattc tttccagagg attcttggag300ccggaaagaa nggagtcttc ttggtgggat aaaaagtgaa aaagaacttt ctcttcaana360aggatagggg gatgtgcttt gtaaaatcan tttttcaggg ngganaatgc cnnaaccgtt420ttaaagaaaa acatnttggg naagtttttg tgggccaaca ttacccggtc ttgtaaacct480accttcaaag aacctttttg cccagggtta a 511<210>361<211>411<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(411)<223>n＝A、T、C或G<400>361gctcagcggc ccgatcccac ggaagcgcgc tcggaggggt gggacccggc cggaccggag 60atggcgccgc cagcgggcgg ggcggcggcg gcggcctcgg acttgggctc cgccgcagtg120ctcttggctg tgcacgccgc ggtgaggccg ctgggcgccg ggccagacgc cgaagcacaa180cttgcggagg ctgcagctta acgcggaccc tgagaagcct ggcgcttncn gctggaactt240cttggcgcgg gacctggggc ggtaatttga gtggccctga gtcatttcta caccatccag300gcccaccaca cgactaagct cacaagaagg ctgaactnnc tgattctnaa cctagaanta360cgtgcatcta tcagtgccng aagaaatgac aacataccac tggcaactct g 411<210>362<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(511)<223>n＝A、T、C或G<400>362cgggggaccg ggctgccttg gcccctcagc gctcgcgtct tttccggcag ttggaacgct 60tcctgttgtc ctcacccgta accgcctgtt gccccctgtc tcagagtccc tcacgcgtcc120cctcccgtct ttggctcgtt ggctgccgcc gccggggctt cgccagcctt caagtcgaga180ctactggccg aaggggcgtc tgcggctctc cgccgtcccc agccctgcct ctccctgggc240tctgccatgg caatgacagg ctcaacacct tgctcatcca tgagtaacca cacaaaggaa300agggtgacaa tgaccaaaag tgacactgga gaatttttat agcaacctta tcgctcacat360gaagaacgag aaatgagaca aaagaagtta gaaaaagggg atggaagaag aaggcctaaa420aaaatgaagg agaaaaccaa cttccgaaga tcaaccacat tgcttcggaa anggaaacaa480aantttcttt cgtttgaaan aaaaacaaan a 511
<210>363<211>401<212>DNA<213>智人(Homo sapiens)<400>363caggatctgg ggagaaagag ccccatccct tctctctctg ccaccatttc ggacaccccg 60cagggactcg ttttgggatt cgcactgact tcaaggaagg acgcgaaccc ttctctgacc120ccagctcggg cggccacctg tctttgccgc ggtgaccctt ctctcatgac cctgcggtgc180cttgagccct ccgggaatgg cggggaaggg acgcggagcc agtgggggac cgcggggtcg240gcggaggagc catccccgca ggcggcgcgt ctggcgaagg ccctgcggga gctcggtcag300acaggatggt actggggaag tatgactgtt aatgaagcca aagagaaatt aaaagaggca360ccagaaggaa ctttcttgat tagagatagc tcgcattcag a401<210>364<211>401<212>DNA<213>智人(Homo sapiens)<400>364agtcaaaggt ttcttttccc tttttaccat ggtttctaca aaaataacct tcaggaaaaa 60gaaaatcagg aaaaaaattt tttttcaata atcttattcc ctatattaaa ttagatttga120agaggattaa cgttgtttta gtttgggtcc agatcagcct tatacaacat ttctaaactc180atttgtactt ttaaaaaatt taaacacaga cttctaaaat tacttgatgt aagtaattta240aatcacttat gaccaagtta ttaaccttat gaatcagaag tctgaccctt gtaggaaatt300atattcacat ataaagtaca tcagatcttt gccatatatt gatggttatt atgcataaac360acattgagtt gtgttggaag cagatttata aacctgcatg t401<210>365<211>361<212>DNA<213>智人(Homo sapiens)<400>365atctggagtt gcacaaatag ttctttagaa cataaaacta aatggattta tacataacag 60ttacattcag catttaagag aggcagtaca aaaatgtgtt ctgcttttat ctgatataaa120ttgcatgtaa taccatgatt taaacaatat cagttatatt aactaatgcc atgagatata180tcttactcag aacgtctgat gtttcccata atagacagaa aaaatgcagt tgtatgagca240actgagtttc ttttcatctt caaattcatt tgtgatggtg ggaagatcta aggacaatcc300ttccattgaa gaagtaggaa aaacagttca gcactgttct gaactcatca aaaatgaaat360t361<210>366<211>401<212>DNA<213>智人(Homo sapiens)<400>366cgggagcagc agaggtctag cagccgggcg ccgcgggccg ggggcctgag gaggccacag 60gacgggcgtc ttcccggcta gtggagcccg gcgcggggcc cgctgcggcc gcaccgtgag120gggaggaggc cgaggaggac gcagcgccgg ctgccggcgg gaggaagcgc tccaccaggg180cccccgacgg cactcgttta accacatccg cgcctctgct ggaaacgctt gctggcgcct240gtcaccggtt ccctccattt tgaaagggaa aaaggctctc cccacccatt cccctgcccc300taggagctgg agccggagga gccgcgctca tggcgttcag cccgtggcag atcctgtccc360ccgtgcagtg ggcgaaatgg acgtggtctg cggtacgcgg c401<210>367
<211>401<212>DNA<213>智人(Homo sapiens)<400>367catggagtcg ggcaagatgg cgcctcccaa gaacgctccg agagatgcct tggtgatggc 60acagatcctg aaggatatgg gaatcacaga gtatgaacca agggttataa atcaaatgtt120ggaatttgct ttccgttatg tgactacaat tctggatgat gcaaaaattt attcgagcca180tgctaagaaa cctaatgttg atgcagatga tgtgagactg gcaatccagt gtcgtgctga240ccaatctttt acctctcctc ccccaagaga ttttttactg gatatcgcaa ggcagaaaaa300tcaaacccct ttgccactga ttaagccata tgcaggacct agactgccac ctgatagata360ctgcttaaca gctccaaact ataggctgaa gtccttaatt a401<210>368<211>401<212>DNA<213>智人(Homo sapiens)<400>368cggagcggta ggagcagcaa tttatccgtg tgcagcccca aactggaaag aagatgctaa 60ttaaagtgaa gacgctgacc ggaaaggaga ttgagattga cattgaacct acagacaagg120tggagcgaat caaggagcgt gtggaggaga aagagggaat ccccccacaa cagcagaggc180tcatctacag tggcaagcag atgaatgatg agaagacagc agctgattac aagattttag240gtggttcagt ccttcacctg gtgttggctc tgagaggagg aggtggtctt aggcagtgat300ggaccctcca ttttacctct ttaccctgtc gctcataatg aggcatcata tatcctctca360ctctctggga caccatagcc ctgccccctc ccctggatgc c401<210>369<211>174<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(174)<223>n＝A、T、C或G<400>369gcgagnnggg cgccaagcgc ggggccggag cggccttccc ggagtccttt gcgcggcacc 60tggcgacaaa atggctgccc gagggagacg ggcggagcct cagggccggg aggctccggg120ccccgcgggc ggtggcggtg gcgggagccg ttgggctgag tcgggatcgg ggac 174<210>370<211>375<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(375)<223>n＝A、T、C或G<400>370tgcttttcca actttattta gaaaaacaaa tccaggtccc agtgccccct gtaccctccc 60cgaccccagc cataatttaa ataacttana gacagagttg gagggagggg acagganagg120ttggggtcac ggtggaagga ggaaganagc ccactacagc cgccgcagcg cccgcttctt180gtccgtcttt ttcttggccg ccagcttctt atcgcgctcg ccagcatgct tnttggccat240gggaccctca gcccctcccg ggccccctgg ggccccaggg tcggtggagg aagcttcagt300gccactggcc agggcccgac cggcttcggc cctgccgctg ggcccgccgg cgcccccgtg360gatctctgtg agcag 375<210>371<211>375<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(375)<223>n＝A、T、C或G<400>371taaattctaa aaaatatttt aatacttgaa aacttctaaa acaaaaggta aggtaacatg 60ttctttcaaa agtgaatttc acatgcaaac cattaattat atttatttta ctgngagata120aaagcaaaac ataacattcg gagaaagaga ccagtaactg acctatttat tttatattat180attaatgnga atcctcatta gaaatgtgat aacgttattg cacaaacaaa accgtgggca240gaaacatccc agcaatgcag gggcgcccat accgggttac aagggatgtc cagcatgtgt300ttccctggaa cactcanagt ctgcactttt cctgcaaatg ggaccatgtc tgattattta360ttatgaaaga acact 375<210>372<211>164<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(164)<223>n＝A、T、C或G<400>372cgctctgtnt cctcaacctc tacctggcgg aggttatatg taaagtcaga tgtgccactg 60aacttgacag acacaaaatt ctactgcatt tgggctttat aatggcaagc ctgctctttt120tagtggtgaa cttgacttgc gcaatgctag ttcatggaga tgtc 164<210>373<211>401<212>DNA<213>智人(Homo sapiens)<400>373gcgctgttcg cctttgccta cctgcagctg tggcggctgc tcctgtaccg cgagcggcgg 60ctgagttacc agagcctctg cctcttcctc tgtctcctgt gggcagcgct caggaccacc120ctcttctccg ccgccttctc gctcagcggc tccctgccct tgctccggcc gcccgctcac180ctgcacttct tcccccactg gctgctctac tgcttcccct cctgtctcca gttctccacg240ctctgtctcc tcaacctcta cctggcggag gttatatgta aagtcagatg tgccactgaa300cttgacagac acaaaattct actgcatttg ggctttataa tggcaagcct gctcttttta360gtggtgaact tgacttgcgc aatgctagtt catggagatg t401<210>374<211>401<212>DNA<213>智人(Homo sapiens)<400>374ggaatgatac cattcagatt gatttggaga ctggcaagat tactgatttc atcaagttcg 60acactggtaa cctgtgtatg gtgactggag gtgctaacct aggaagaatt ggtgtgatca120ccaacagaga gaggcaccct ggatcttttg acgtggttca cgtgaaagat gccaatggca180acagctttgc cactcgactt tccaacattt ttgttattgg caagggcaac aaaccatgga240tttctcttcc ccgaggaaag ggtatccgcc tcaccattgc tgaagagaga gacaaaagac300tggcggccaa acagagcagt gggtgaaatg ggtccctggg tgacatgtca gatctttgta360cgtaattaaa aatattgtgg caggattaat agcaaaaaaa a401<210>375<211>401<212>DNA<213>智人(Homo sapiens)<400>375gagcggagtc cgctggctga cccgagcgct ggtctccgcc gggaaccctg gggcatggag 60aggtctgagt acctcggccg cggcgcacgc tgcatcgcgg agccaggccg aggacgtgag120ggtggagggc tcctttcccg tgaccatgct tccgggagac ggtgtggggc ctgagctgat180gcacgccgtc aaggaggtgt tcaaggctgc cgctgtccca gtggagttcc aggagcacca240cctgagtgag gtgcagaata tggcatctga ggagaagctg gagcaggtgc tgagttccat300gaaggagaac aaagtggcca tcattggaaa gattcatacc ccgatggagt ataaggggga360gctagcctcc tatgatatgc ggctgaggcg taagttggac t401<210>376<211>284<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(284)<223>n＝A、T、C或G<400>376ggaacaaggt cgtgaaaaaa aaggtcttgg tgaggtgccg ccatttcatc tgtcctcatt 60ctctgcgcct ttcgcagagc ttccancagc tggtatgttg ggccagagca tccggaggtt120cacaacctct gtggtccgta ggagccacta tgaggagggc cctgggaaga atttgccatt180ttcagtggaa aacaagtggt cgttactagc taagatgtgt ttgtactttg gatctgcatt240tgctacaccc ttccttgtan taagacacca actgcttaaa acat 284<210>377<211>401<212>DNA<213>智人(Homo sapiens)<400>377atttatgtta ttgcactctc ggtgtgattt atcgtatgta tctgataggt tttatgaatt 60gttttgagtt gtaaactcct atacccttta ttaaaatgga cctaattaag tgatttatgc120tttgtgcaat ttcttaaatc agatctctct aggattgaag ggatccatag gtatctttca180cttagtgtga agcctagtag tatactttta tattcctgaa gagagaccag cattaacata240aagagagaag tcttaggaaa aaatatacct aagaattatt tttaaaattc atactgtgaa300ggagaatctg cctgcctatt tcctctccaa atttcagaaa ataacacaga gtgctatttg360cctgaacttt aatgagcttg actttgttat gattcaggga g401<210>378<211>401<212>DNA<213>智人(Homo sapiens)<400>378ccagaacaca ggtgtcgtga aaactacccc taaaagccaa aatgggaaag gaaaagactc 60atatcaacat tgtcgtcatt ggacacgtag attcgggcaa gtccaccact actggccatc120tgatctataa atgcggtggc atcgacaaaa gaaccattga aaaatttgag aaggaggctg180ctgagatggg aaagggctcc ttcaagtatg cctgggtctt ggataaactg aaagctgagc240gtgaacgtgg tatcaccatt gatatctcct tgtggaaatt tgagaccagc aagtactatg300tgactatcat tgatgcccca ggacacagag actttatcaa aaacatgatt acagggacat360ctcaggctga ctgtgctgtc ctgattgttg ctgctggtgt t401<210>379<211>401<212>DNA<213>智人(Homo sapiens)<400>379tcagatatca ggtggcttct tcaaatgatt tttaagtatc tcgatgatga tgaagaacaa 60agacatcaat caggattcag gaagacagct tttgcggaaa atgcttaaag ggaagcatca120aggattggtg ttgatatttg aaagtttaag agtggtatac ttttattcag tcaacacatg180acaaatgtaa aaggcactca tttgttgttc ctggaagaag cctggcagca ttccattcag240acatctgccc tttcatcgtc ccacttttta cttattgcag tcctttcagt ctgaatattt300cctcctgacg catcttctgc cgtccgaaat gactccctgc tcccagatcc tgtagccctt360attattgaca cctttcattt agaaatttag cacatgtcac a401<210>380<211>401<212>DNA<213>智人(Homo sapiens)<400>380cctgactctc tgaggctcat tttgcagttg ttgaaattgt ccccgcagtt ttcaatcatg 60tctgaaccaa tcagagtcct tgtgactgga gcagctggtc aaattgcata ttcactgctg120tacagtattg gaaatggatc tgtctttggt aaagatcagc ctataattct tgtgctgttg180gatatcaccc ccatgatggg tgtcctggac ggtgtcctaa tggaactgca agactgtgcc240cttcccctcc tgaaagatgt catcgcaaca gataaagaag acgttgcctt caaagacctg300gatgtggcca ttcttgtggg ctccatgcca agaagggaag gcatggagag aaaagattta360ctgaaagcaa atgtgaaaat cttcaaatcc cagggtgcag c401<210>381<211>401<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(1)...(401)<223>n＝A、T、C或G<400>381ggggcttcgc tggcagtctg aacggcaagc ttgagcaacg cggtaaaaat attgcttcgg 60tgggtgacgc ggtacagctg tccaagggcn ttngtaacgg gaatgccgaa gcgtgggaaa120aagggagcgg tggcggaaga cggggatgag ctcaggacag agccagaggc caagaagagt180aagacggccg caaagaaaaa tgacaaagag gcagcaggag agggcccagc cctgtatgag240gaccccccag atcagaaaac ctcacccagt ggcaaacctg ccacactcaa gatctgctct300tggaatgtgg atgggcttcg agcctggatt aagaagaaag gattagattg ggtaaaggaa360gaagccccag atatactgtg ccttcaagag accaaatgtt c401<210>382<211>491<212>DNA
<213>智人(Homo sapiens)<400>382gagcagcccc cggcggctga aagccggggc agaagtgctg gtctcggtcg ggattccggg 60cttggtccca ccgaggcggc gactgcggta ggagggaaga ggttttggac gcgctggcct120cccgccgctg tgcattgcag cattatttca gttcaaaatg aactatatgc ctggcaccgc180cagcctcatc gaggacattg acaaaaagca cttggttctg cttcgagatg gaaggacact240tataggcttt ttaagaagca ttgatcaatt tgcaaactta gtgctacatc agactgtgga300gcgtattcat gtgggcaaaa aatacggtga tattcctcga gggatttttg tggtcagagg360agaaaatgtg gtcctactag gagaaataga cttggaaaag gagagtgaca cacccctcca420gcaagtatcc attgaagaaa ttctagaaga acaaagggtg gaacagcaga ccaagctgga480agcagagaag t 491<210>383<211>491<212>DNA<213>智人(Homo sapiens)<400>383gagtccatct cagcgcctgg aaaatgcagt gaaaaaacct gaagataaaa aggaagtttt 60cagacccctc aagcctgctg gcgaagtgga tctgaccgca ctggccaaag agcttcgagc120agtggaagat gtacggccac ctcacaaagt aacggactac tcctcatcca gtgaggagtc180ggggacgacg gatgaggagg acgacgatgt ggagcaggaa ggggctgacg agtccacctc240aggaccagag gacaccagag cagcgtcatc tctgaatttg agcaatggtg aaacggaatc300tgtgaaaacc atgattgtcc atgatgatgt agaaagtgag ccggccatga ccccatccaa360ggagggcact ctaatcgtcc gccagagtac agttgaccaa aagcgtgcca gccatcatga420gagcaatggc tttgccggtc gcattcacct cttgccagat ctcttacagc aaagccattc480ctcctccact t 491<210>384<211>491<212>DNA<213>智人(Homo sapiens)<400>384gagcctaatc tcaggtggtc cacccgagac cccttgagca ccaaccctag tcccccgcgc 60ggccccttat tcgctccgac aaggtacaaa aaggctctgg acggcggcgt ggtaggagga120cgggagcggg ggcgggaagt tccctgaagg agcgagacag ggagggacag ggcagaggag180gagaggaagg cgatgcgacg gacaggcgca cccgctcagg ctgactctcg ggggcgaggt240cgagccaggg gcggctgccc tgggggcgag gcgacgctgt ctcaacctcc acctcgcggc300ggaacccgag gacaggagcc tcagatgaaa gaaacaatca tgaaccagga aaaactcgcc360aaactgcagg cacaagtgcg cattggtggg aaaggaactg ctcgcagaaa gaagaaggtg420gttcatagaa cagccacagc agatgacaaa aaacttcagt tctccttaaa gaagttaggg480gtaaacaata t 491<210>385<211>483<212>DNA<213>智人(Homo sapiens)<400>385agccgctgcg aagggagccg ccgccatgtc tgcgcatctg caatggatgg tcgtgcggaa 60ctgctccagt ttcctgatca agaggaataa gcagacctac agcactgagc ccaataactt120gaaggcccgc aattccttcc gctacaacgg actgattcac cgcaagactg tgggcgtgga180gccggcagcc gacggcaaag gtgtcgtggt ggtcattaag cggagatccg gccagcggaa240gcctgccacc tcctatgtgc ggaccaccat caacaagaat gctcgcgcca cgctcagcag300catcagacac atgatccgca agaacaagta ccgccccgac ctgcgcatgg cagccatccg360cagggccagc gccatcctgc gcagccagaa gcctgtgatg gtgaagagga agcggacccg420ccccaccaag agctcctgag ccccctgccc ccagagcaat aaagtcagct ggctttctca480cct 483<210>386<211>491<212>DNA<213>智人(Homo sapiens)<400>386aggtggaagg aaaaaacata aatgaagtta atgcacttct tttcctagcc caaaagtcac 60tgtgattata tttttttaat gaagtttaga aaaaaagctg ttgtcttctc aattgtaaaa120ttagtttcaa aatgctgctt ctcttatcat tagtctagta attgttgaac ttttctgcaa180actgcatttt acaaaattga aacttggaag ctgtattaac ttttatagtt aaacattgta240ttaaataaac tatactataa taaacagttt ggttttgtat tttttaaatt gtattatcca300gccttttaaa aattaaaagc taaataatga aaataaacca attaaaacat acttttactc360tcagatatac aggtatttac attatgaaaa aactgaacaa agttttaaca atactgagct420ttaagaattt agccagcagg gaaaatttcc aggtttgaga atgttctaat gtaaatattt480aatcataata c 491<210>387<211>491<212>DNA<213>智人(Homo sapiens)<400>387ccacaccacc gtgtcccaag tccagccccc tccctccaag gcatcagcac ctgaaccccc 60tgcagaagaa gaagtggcaa ctggtacaac ctcagcctct gatgacctgg aagccctggg120tacactgagc ctggggacca cagaggagaa ggcagcagct gaggcggctg tgcccaggac180cattggggcc gagctgatgg agctggtgcg gagaaacact ggcctgagcc acgaattatg240ccgggtggcc atcggcatca tagtgggtca catccaggcc tcggtgccgg ccagctcacc300agtcatggag caggtcctcc tctcactcgt agagggcaag gacctcagca tggccctgcc360ctcagggcag gtctgccacg accagcagag gctggaggtg atctttgcag acctggctcg420ccggaaggac gacgcccagc agcgcagttg ggcactatat gaggatgagg gtgtcatccg480ctgctaccta g 491<210>388<211>491<212>DNA<213>智人(Homo sapiens)<400>388gagactatca aactcctgag ccaacaactt aatatgacta gcttacacaa tagcttttat 60agtaaagata cctctttacg gactccactt atgactccct aaagcccatg tcgaagcccc120catcgctggg tcaatagtac ttgccgcagt actcttgaaa ctaggcggct atggtataat180acgcctcaca ctcattctca accccctgac aaaacacata gcctacccct tccttgtact240atccctatga ggcataatta taacaagctc catctgccta cgacaaacag acctaaaatc300gctcattgca tactcttcaa tcagccacat agccctcgta gtaacagcca ttctcatcca360aaccccctga agcttcaccg gcgcagtcat tctcataatc gcccacggac ttacatcctc420attactattc tgcctagcaa actcaaacta cgaacgcact cacagtcgca tcataatcct480ctctcaagga c 491<210>389<211>511<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature
<222>(1)...(511)<223>n＝A、T、C或G<400>389tactgatatc tctttaatac tttcatcatt caagtttgtt canaacatta caagaggcat 60gaaagaaaaa ataattccat ttttaaaact ctgtctgtcc aaagtataac atatgaaacc120atgccattat ctnttaggaa acaaaagcat tcaaaattaa tttggtatta aagttcaaga180ttcanactaa cctcaaagta cggcatgtgc agtgtttaag tgcaanaagt attttcattc240caattatttt acananatgc tggagtgacg tgtgcaattt gaaatattca aatcctttaa300ggnttctgaa ctaagtgttt aaatgaaaac tgaaatgctg catagtttca gtggctttca360atttcctgtt tgatctcaga aatatatgga tgatctttgc cgtgagctac ttccatgatt420gcaatggcct tcttcagggc tttctcccct gcggctttgt gttccaggcc catgtagagt480ctccctagct tcaaccacat ggaggccacg t 511<210>390<211>1984<212>DNA<213>智人(Homo sapiens)<400>390cctggggtta gaggctgggg tgggtggggg gtaagggggc agtccttctc cccttcgacg 60gcggctccga gtccagcccc ttccttcccg cgctcgctcg cccggccccc agccccctca 120tgagggtgtc cgtgccgggt ccggcggccg ctgccgcccc cgcagccggc cgcgagccct 180ccacgcccgg cgggggcagc ggaggcggag gcgccgtcgc tgcagcctca ggcgccgcgg 240tgccgggctc cgtgcagttg gcgctgagcg tcctgcacgc cctgctctac gccgcgctgt 300tcgcctttgc ctacctgcag ctgtggcggc tgctcctgta ccgcgagcgg cggctgagtt 360accagagcct ctgcctcttc ctctgtctcc tgtgggcagc gctcaggacc accctcttct 420ccgccgcctt ctcgctcagc ggctccctgc ccttgctccg gccgcccgct cacctgcact 480tcttccccca ctggctgctc tactgcttcc cctcctgtct ccagttctcc acgctctgtc 540tcctcaacct ctacctggcg gaggttatat gtaaagtcag atgtgccact gaacttgaca 600gacacaaaat tctactgcat ttgggcttta taatggcaag cctgctcttt ttagtggtga 660acttgacttg cgcaatgcta gttcatggag atgtcccaga aaatcagttg aagtggactg 720tgtttgttcg agcattaatt aatgatagcc tgtttattct ttgtgccatc tctttagtgt 780gttacatatg caaaattaca aaaatgtcat cagctaatgt ctacctcgaa tcaaagggta 840tgtctctgtg ccagactgtc atcgtgggct ctgtagtcat tcttctgtac tcttccagag 900cttgttataa tttggtggtg gtcaccatat ctcaggatac attagaaagt ccatttaatt 960atggctggga taatctttca gataaggctc atgtagaaga cataagtgga gaagagtata 1020tagtatttgg aatggtcctc tttctgtggg aacatgtgcc agcatggtcg gtggtactgt 1080ttttccgggc acagagatta aaccagaatt tggcacctgc tggcatgata aatagtcaca 1140gttatagttc cagagcttac tttttcgaca atccaagacg atatgatagt gatgatgacc 1200tgccaagact gggaagttca agagaaggaa gtttaccaaa ttcgcaaagt ttgggctggt 1260atggcaccat gactgggtgt ggcagcagca gttacacagt cactccccac ctgaatggac 1320ctatgacaga tactgctcct ttgctcttta cttgtagtaa tttagatttg aacaatcatc 1380atagcttata tgtgacacca caaaactgac agcatcacca agtcatgatt cttgagttgt 1440ttttcataaa tgtgtatatt caatgtgttt aaattccatc tacataaaca ttccattatc 1500tgttgcaact gaaaacaaaa tctggaagtg tggctgtgtt tggtaaataa cacagctatt 1560atttttgacc tcttcatagt aaaatgaagt aaaatggaaa gtttggagta ggagaaaaga 1620gagattagat cttaaggcac ttgatggcct ccaaaaatcc tgactttgga acatcaaatg 1680catatgtgca cttttatctt tgttctgagt cactgcagtc cccaaagtca tatgccaatg 1740ttcacactga aatactgtat tgtacaccaa actggaaggc aattttccta tgaaaatcaa 1800agccggtata ttcattggta tgctctatac agatatctta ataaaaattt tatagtgtga 1860acagtgcaca gagttaaggc ataaaaatgt atcattcttt ataaaaatct actgaaaatg 1920tgtaatcatt gaagacagtt cttttaagca tgattttaaa atagcaactg aaattcaatc 1980attt 1984<210>391<211>429<212>PRT<213>智人(Homo sapiens)<400>391Met Arg Val Ser Val Pro Gly Pro Ala Ala Ala Ala Ala Pro Ala Ala5 10 15Gly Arg Glu Pro Ser Thr Pro Gly Gly Gly Ser Gly Gly Gly Gly Ala20 25 30Val Ala Ala Ala Ser Gly Ala Ala Val Pro Gly Ser Val Gln Leu Ala35 40 45Leu Ser Val Leu His Ala Leu Leu Tyr Ala Ala Leu Phe Ala Phe Ala50 55 60Tyr Leu Gln Leu Trp Arg Leu Leu Leu Tyr Arg Glu Arg Arg Leu Ser65 70 75 80Tyr Gln Ser Leu Cys Leu Phe Leu Cys Leu Leu Trp Ala Ala Leu Arg85 90 95Thr Thr Leu Phe Ser Ala Ala Phe Ser Leu Ser Gly Ser Leu Pro Leu100 105 110Leu Arg Pro Pro Ala His Leu His Phe Phe Pro His Trp Leu Leu Tyr115 120 125Cys Phe Pro Ser Cys Leu Gln Phe Ser Thr Leu Cys Leu Leu Asn Leu130 135 140Tyr Leu Ala Glu Val Ile Cys Lys Val Arg Cys Ala Thr Glu Leu Asp145 150 155 160Arg His Lys Ile Leu Leu His Leu Gly Phe Ile Met Ala Ser Leu Leu165 170 175Phe Leu Val Val Asn Leu Thr Cys Ala Met Leu Val His Gly Asp Val180 185 190Pro Glu Asn Gln Leu Lys Trp Thr Val Phe Val Arg Ala Leu Ile Asn195 200 205Asp Ser Leu Phe Ile Leu Cys Ala Ile Ser Leu Val Cys Tyr Ile Cys210 215 220Lys Ile Thr Lys Met Ser Ser Ala Asn Val Tyr Leu Glu Ser Lys Gly225 230 235 240Met Ser Leu Cys Gln Thr Val Ile Val Gly Ser Val Val Ile Leu Leu245 250 255Tyr Ser Ser Arg Ala Cys Tyr Asn Leu Val Val Val Thr Ile Ser Gln260 265 270Asp Thr Leu Glu Ser Pro Phe Asn Tyr Gly Trp Asp Asn Leu Ser Asp275 280 285Lys Ala His Val Glu Asp Ile Ser Gly Glu Glu Tyr Ile Val Phe Gly290 295 300Met Val Leu Phe Leu Trp Glu His Val Pro Ala Trp Ser Val Val Leu305 310 315 320Phe Phe Arg Ala Gln Arg Leu Asn Gln Asn Leu Ala Pro Ala Gly Met325 330 335Ile Asn Ser His Ser Tyr Ser Ser Arg Ala Tyr Phe Phe Asp Asn Pro340 345 350Arg Arg Tyr Asp Ser Asp Asp Asp Leu Pro Arg Leu Gly Ser Ser Arg355 360 365Glu Gly Ser Leu Pro Asn Ser Gln Ser Leu Gly Trp Tyr Gly Thr Met370 375 380Thr Gly Cys Gly Ser Ser Ser Tyr Thr Val Thr Pro His Leu Asn Gly385 390 395 400Pro Met Thr Asp Thr Ala Pro Leu Leu Phe Thr Cys Ser Asn Leu Asp405 410 415Leu Asn Asn His His Ser Leu Tyr Val Thr Pro Gln Asn420 425<210>392<211>1584<212>DNA<213>智人(Homo sapiens)<400>392ggaagactgg agcctttgcg gcggcgctgc ccctcccctg gtccccgcga gctcggaggg 60cccggctggt gctgcggggg ccccgggagg ttgaaaacta agcatgggga agagctgcaa 120ggtggtcgtg tgtggccagg cgtctgtggg caaaacttca atcctggagc agcttctgta 180tgggaaccat gtagtgggtt cggagatgat cgagacgcag gaggacatct acgtgggctc 240cattgagaca gaccgggggg tgcgagagca ggtgcgtttc tatgacaccc gggggctccg 300agatggggcc gaactgcccc gacactgctt ctcttgcact gatggctacg tcctggtcta 360tagcacagat agcagagagt cttttcagcg tgtggagctg ctcaagaagg agattgacaa 420atccaaggac aagaaggagg tcaccatcgt ggtccttggc aacaagtgtg acttacagga 480gcagcggcgt gtagacccag atgtggctca gcactgggcc aagtcagaga aggtgaagct 540gtgggaggtg tcagtggcgg accggcgctc cctcctggag ccctttgtct acttggccag 600caagatgacg caaccccaga gcaagtctgc cttccccctc agccggaaga acaagggcag 660cggctccttg gatggctgaa gagctgccgt tcctctttca cgatcccagc cccatttcag 720tgtctggggc tctggtagat gtgttgaggg caaagtagag gacaagctgt ctttcccagt 780cagccaggga gctccccgcc aggccacgcc ccagccactt tgctccctct cacctctggg 840aagtgcaaat actcttggtt gacatcccct tcctcagccc tcccagccta ctccccatcc 900cagcttttag aggatctgct ccactgtctc ctggggcagt tgtgggtcac tgtcccttcc 960agctgcccca gacaggaagc agagtcacca cgcagcagtg tcccttcttg ggtctgagtt 1020cctattatag gtaggggccc caccctctgg gcttcccatc agcgacacac acacacttat 1080ggcaccagcc tggactccag aaaaagggtg tccaggtatt gtgtgtatgc atttagttgt 1140gcacacacaa atatgctcct atactggcat taggcgtctc ctcatccctc accctgacct 1200ttctcctgtc cttttcttgg ctggaagaag ttggcctcct gggagtgtag ttttctgttt 1260taaatccccc acccctggct gggctcagtg gctcacccct gtaatcccag cactttggga 1320ggccaaggcg ggtcgattac ttgaggtcag gagttcacga ccagcctggc caacattgtg 1380aaaccccatc tctgccaaaa atacaaaagt tagccgggcg tagtggcaca tgcctgtaat 1440cccagctacc cggggaggct gaggcaggag aattgcttga actcagaagg cggaggctgc 1500agtgagccga gatcgtgcca ctgcactcca gcctggtcaa cagagcaaga ctccatctcg 1560aaaaaaaaaa aaaaaaaact cgag 1584<210>393<211>191<212>PRT<213>智人(Homo sapiens)<400>393Met Gly Lys Ser Cys Lys Val Val Val Cys Gly Gln Ala Ser Val Gly5 10 15Lys Thr Ser Ile Leu Glu Gln Leu Leu Tyr Gly Asn His Val Val Gly20 25 30Ser Glu Met Ile Glu Thr Gln Glu Asp Ile Tyr Val Gly Ser Ile Glu35 40 45Thr Asp Arg Gly Val Arg Glu Gln Val Arg Phe Tyr Asp Thr Arg Gly50 55 60Leu Arg Asp Gly Ala Glu Leu Pro Arg His Cys Phe Ser Cys Thr Asp65 70 75 80Gly Tyr Val Leu Val Tyr Ser Thr Asp Ser Arg Glu Ser Phe Gln Arg85 90 95Val Glu Leu Leu Lys Lys Glu Ile Asp Lys Ser Lys Asp Lys Lys Glu100 105 110Val Thr Ile Val Val Leu Gly Asn Lys Cys Asp Leu Gln Glu Gln Arg115 120 125Arg Val Asp Pro Asp Val Ala Gln His Trp Ala Lys Ser Glu Lys Val130 135 140Lys Leu Trp Glu Val Ser Val Ala Asp Arg Arg Ser Leu Leu Glu Pro145 150 155 160Phe Val Tyr Leu Ala Ser Lys Met Thr Gln Pro Gln Ser Lys Ser Ala165 170 175Phe Pro Leu Ser Arg Lys Asn Lys Gly Ser Gly Ser Leu Asp Gly180 185 190<210>394<211>1937<212>DNA<213>智人(Homo sapiens)<400>394ccggttcccc cagctctggg tacccggctc tgcatcgcgt cgccatgatg ggccatcgtc 60cagtgctcgt gctcagccag aacacaaagc gtgaatccgg aagaaaagtt caatctggaa 120acatcaatgc tgccaagact attgcagata tcatccgaac atgtttggga cccaagtcca 180tgatgaagat gcttttggac ccaatgggag gcattgtgat gaccaatgat ggcaatgcca 240ttcttcgaga gattcaagtc cagcatccag cggccaagtc catgatcgaa attagccgga 300cccaggatga agaggttgga gatgggacca catcagtaat tattcttgca ggggaaatgc 360tgtctgtagc tgagcacttc ctggagcagc agatgcaccc aacagtggtg atcagtgctt 420accgcaaggc attggatgat atgatcagca ccctaaagaa aataagtatc ccagtcgaca 480tcagtgacag tgatatgatg ctgaacatca tcaacagctc tattactacc aaagccatca 540gtcggtggtc atctttggct tgcaacattg ccctggatgc tgtcaagatg gtacagtttg 600aggagaatgg tcggaaagag attgacataa aaaaatatgc aagagtggaa aagatacctg 660gaggcatcat tgaagactcc tgtgtcttgc gtggagtcat gattaacaag gatgtgaccc 720atccacgtat gcggcgctat atcaagaacc ctcgcattgt gctgctggat tcttctctgg 780aatacaagaa aggagaaagc cagactgaca ttgagattac acgagaggag gacttcaccc 840gaattctcca gatggaggaa gagtacatcc agcagctctg tgaggacatt atccaactga 900agcccgatgt ggtcatcact gaaaagggca tctcagattt agctcagcac taccttatgc 960gggccaatat cacagccatc cgcagagtcc ggaagacaga caataatcgc attgctagag 1020cctgtggggc ccggatagtc agccgaccag aggaactgag agaagatgat gttggaacag 1080gagcaggcct gttggaaatc aagaaaattg gagatgaata ctttactttc atcactgact 1140gcaaagaccc caaggcctgc accattctcc tccggggggc tagcaaagag attctctcgg 1200aagtagaacg caacctccag gatgccatgc aagtgtgtcg caatgttctc ctggaccctc 1260agctggtgcc agggggtggg gcctccgaga tggctgtggc ccatgccttg acagaaaaat 1320ccaaggccat gactggtgtg gaacaatggc catacagggc tgttgcccag gccctagagg 1380tcattcctcg taccctgatc cagaactgtg gggccagcac catccgtcta cttacctccc 1440ttcgggccaa gcacacccag gagaactgtg agacctgggg tgtaaatggt gagacgggta 1500ctttggtgga catgaaggaa ctgggcatat gggagccatt ggctgtgaag ctgcagactt 1560ataagacagc agtggagacg gcagttctgc tactgcgaat tgatgacatc gtttcaggcc 1620acaaaaagaa aggcgatgac cagagccggc aaggcggggc tcctgatgct ggccaggagt 1680gagtgctagg caaggctact tcaatgcaca gaaccagcag agtctcccct tttcctgagc 1740cagagtgcca ggaacactgt ggacgtcttt gttcagaagg gatcaggttg gggggcagcc 1800cccagtccct ttctgtccca gctcagtttt ccaaaagaca ctgacatgta attcttctct 1860attgtaaggt ttccatttag tttgcttccg atgattaaat ctaagtcatt tgaaaaaaaa 1920aaaaaaaaaa actcgag 1937<210>395<211>1675<212>DNA<213>智人(Homo sapiens)<400>395gcgcgaatcg cggtcgcgag ccatggagga ggaggcatcg tccccggggc tgggctgcag 60caagccgcac ctggagaagc tgaccctggg catcacgcgc atcctagaat cttccccagg 120tgtgactgag gtgaccatca tagaaaagcc tcctgctgaa cgtcatatga tttcttcctg 180ggaacaaaag aataactgtg tgatgcctga agatgtgaag aacttttacc tgatgaccaa 240tggcttccac atgacatgga gtgtgaagct ggatgagcac atcattccac tgggaagcat 300ggcaattaac agcatctcaa aactgactca gctcacccag tcttccatgt attcacttcc 360taatgcaccc actctggcag acctggagga cgatacacat gaagccagtg atgatcagcc 420agagaagcct cactttgact ctcgcagtgt gatatttgag ctggattcat gcaatggcag 480ttggaaagtt tgccttgtct acaaaagtgg gaaaccagca ttagcagaag acactgagat 540ctggttcctg gacagagcgt tatactggca ttttctcaca gacaccttta ctgcctatta 600ccgcctgctc atcacccacc tgggcctgcc ccagtggcaa tatgccttca ccagctatgg 660cattagccca caggccaagc aatggttcag catgtataaa cctatcacct acaacacaaa 720cctgctcaca gaagagaccg actcctttgt gaataagcta gatcccagca aagtgtttaa 780gagcaagaac aagatcgtaa tcccaaaaaa gaaagggcct gtgcagcctg caggtggcca 840gaaagggccc tcaggaccct ccggtccctc cacttcctcc acttctaaat cctcctctgg 900ctctggaaac cccacccgga agtgagcacc cctccctcca actccctacc agctccagag 960tggtggtttc catgcacaga tggccctagg ggtgacctcc agttttgcgt gtggaccgta 1020ggcctctttc tagttgaatg accaaaattg taaggctttt agtcccaccg acattagcca 1080ggctcgtagt gaggcctcca gagcaggttg tgctgtcccc tgcctctgga agcaatgggg 1140aatttggaat cttgtgtaag tgcccaaata agtctgagtg ctttcctctt cttcaacact 1200caaccctcaa tcccttagca ctgattgatt agagaggtcc cccaaagaaa ccactggttt 1260tgacccatga agcattagaa ctgcattgtt cattcaggag ccactagtca catatgacta 1320tttaaattta aagtaaattg tatgaaaaat tcatttcttc aattgcatta gccacatttt 1380gagtattcat gtggctggta gattctgtat tagcacaaag atatggaaca tttccatcac 1440cacagaaagt tctgttggac agcactgcat tagaatattt tcatactgct cttcctcaat 1500taatttttgt tgttaatgtt gatgtcttca ttggatgggt cataatgttc catgaaacct 1560ctcaagtaca caattgtatg ttctttgtat cccttaccac aaatatctcg ctctgctcat 1620ttcttttgca gcttcctata aagtttgtct tcctcatcaa aaaaaaaaaa aaaaa 1675<210>396<211>559<212>PRT<213>智人(Homo sapiens)<400>396Gly Ser Pro Ser Ser Gly Tyr Pro Ala Leu His Arg Val Ala Met Met5 10 15Gly His Arg Pro Val Leu Val Leu Ser Gln Asn Thr Lys Arg Glu Ser20 25 30Gly Arg Lys Val Gln Ser Gly Asn Ile Asn Ala Ala Lys Thr Ile Ala35 40 45Asp Ile Ile Arg Thr Cys Leu Gly Pro Lys Ser Met Met Lys Met Leu50 55 60Leu Asp Pro Met Gly Gly Ile Val Met Thr Asn Asp Gly Asn Ala Ile65 70 75 80Leu Arg Glu Ile Gln Val Gln His Pro Ala Ala Lys Ser Met Ile Glu85 90 95Ile Ser Arg Thr Gln Asp Glu Glu Val Gly Asp Gly Thr Thr Ser Val100 105 110Ile Ile Leu Ala Gly Glu Met Leu Ser Val Ala Glu His Phe Leu Glu115 120 125Gln Gln Met His Pro Thr Val Val Ile Ser Ala Tyr Arg Lys Ala Leu130 135 140Asp Asp Met Ile Ser Thr Leu Lys Lys Ile Ser Ile Pro Val Asp Ile145 150 155 160Ser Asp Ser Asp Met Met Leu Asn Ile Ile Asn Ser Ser Ile Thr Thr165 170 175Lys Ala Ile Ser Arg Trp Ser Ser Leu Ala Cys Asn Ile Ala Leu Asp180 185 190Ala Val Lys Met Val Gln Phe Glu Glu Asn Gly Arg Lys Glu Ile Asp195 200 205Ile Lys Lys Tyr Ala Arg Val Glu Lys Ile Pro Gly Gly Ile Ile Glu210 215 220Asp Ser Cys Val Leu Arg Gly Val Met Ile Asn Lys Asp Val Thr His225 230 235 240Pro Arg Met Arg Arg Tyr Ile Lys Asn Pro Arg Ile Val Leu Leu Asp245 250 255Ser Ser Leu Glu Tyr Lys Lys Gly Glu Ser Gln Thr Asp Ile Glu Ile260 265 270Thr Arg Glu Glu Asp Phe Thr Arg Ile Leu Gln Met Glu Glu Glu Tyr275 280 285Ile Gln Gln Leu Cys Glu Asp Ile Ile Gln Leu Lys Pro Asp Val Val290 295 300Ile Thr Glu Lys Gly Ile Ser Asp Leu Ala Gln His Tyr Leu Met Arg305 310 315 320Ala Asn Ile Thr Ala Ile Arg Arg Val Arg Lys Thr Asp Asn Asn Arg325 330 335Ile Ala Arg Ala Cys Gly Ala Arg Ile Val Ser Arg Pro Glu Glu Leu340 345 350Arg Glu Asp Asp Val Gly Thr Gly Ala Gly Leu Leu Glu Ile Lys Lys355 360 365Ile Gly Asp Glu Tyr Phe Thr Phe Ile Thr Asp Cys Lys Asp Pro Lys370 375 380Ala Cys Thr Ile Leu Leu Arg Gly Ala Ser Lys Glu Ile Leu Ser Glu385 390 395 400Val Glu Arg Asn Leu Gln Asp Ala Met Gln Val Cys Arg Asn ValLeu405 410 415Leu Asp Pro Gln Leu Val Pro Gly Gly Gly Ala Ser Glu Met Ala Val420 425 430Ala His Ala Leu Thr Glu Lys Ser Lys Ala Met Thr Gly Val Glu Gln435 440 445Trp Pro Tyr Arg Ala Val Ala Gln Ala Leu Glu Val Ile Pro Arg Thr450 455 460Leu Ile Gln Asn Cys Gly Ala Ser Thr Ile Arg Leu Leu Thr Ser Leu465 470 475 480Arg Ala Lys His Thr Gln Glu Asn Cys Glu Thr Trp Gly Val Asn Gly485 490 495Glu Thr Gly Thr Leu Val Asp Met Lys Glu Leu Gly Ile Trp Glu Pro500 505 510Leu Ala Val Lys Leu Gln Thr Tyr Lys Thr Ala Val Glu Thr Ala Val515 520 525Leu Leu Leu Arg Ile Asp Asp Ile Val Ser Gly His Lys Lys Lys Gly530 535 540Asp Asp Gln Ser Arg Gln Gly Gly Ala Pro Asp Ala Gly Gln Glu545 550 555<210>397<211>307<212>PRT<213>智人(Homo sapiens)<400>397Arg Glu Ser Arg Ser Arg Ala Met Glu Glu Glu Ala Ser Ser Pro Gly5 10 15Leu Gly Cys Ser Lys Pro His Leu Glu Lys Leu Thr Leu Gly Ile Thr20 25 30Arg Ile Leu Glu Ser Ser Pro Gly Val Thr Glu Val Thr Ile Ile Glu35 40 45Lys Pro Pro Ala Glu Arg His Met Ile Ser Ser Trp Glu Gln Lys Asn50 55 60Asn cys Val Met Pro Glu Asp Val Lys Asn Phe Tyr Leu Met Thr Asn65 70 75 80Gly Phe His Met Thr Trp Ser Val Lys Leu Asp Glu His Ile Ile Pro85 90 95Leu Gly Ser Met Ala Ile Asn Ser Ile Ser Lys Leu Thr Gln Leu Thr100 105 110Gln Ser Ser Met Tyr Ser Leu Pro Asn Ala Pro Thr Leu Ala Asp Leu115 120 125Glu Asp Asp Thr His Glu Ala Ser Asp Asp Gln Pro Glu Lys Pro His130 135 140Phe Asp Ser Arg Ser Val Ile Phe Glu Leu Asp Ser Cys Asn Gly Ser140 150 155 160Gly Lys Val Cys Leu Val Tyr Lys Ser Gly Lys Pro Ala Leu Ala Glu165 170 175Asp Thr Glu Ile Trp Phe Leu Asp Arg Ala Leu Tyr Trp His Phe Leu180 185 190Thr Asp Thr Phe Thr Ala Tyr Tyr Arg Leu Leu Ile Thr His Leu Gly195 200 205Leu Pro Gln Trp Gln Tyr Ala Phe Thr ser Tyr Gly Ile Ser Pro Gln210 215 220Ala Lys Gln Trp Phe Ser Met Tyr Lys Pro Ile Thr TVr Asn Thr Asn225 230 235 240Leu Leu Thr Glu Glu Thr Asp Ser Phe Val Asn Lys Leu Asp Pro Ser245 250 255Lys Val Phe Lys Ser Lys Asn Lys Ile Val Ile Pro Lys Lys Lys Gly260 265 270Pro Val Gln Pro Ala Gly Gly Gln Lys Gly Pro Ser Gly Pro Ser Gly275 280 285Pro Ser Thr Ser Ser Thr Ser Lys Ser Ser Ser Gly Ser Gly Asn Pro290 295 300Thr Arg Lys305<210>398<211>416<212>DNA<213>智人(Homo sapiens)<400>398agaattcggc acgaggattg cctatctcca gtgcaacaac catcaagtgt gctgaaagtc 60ttcagccggt tgctgcagca gtggaagaaa gggctacagg tccagtcttg ataagcaccg 120ccgactttga ggggcctatg cccagtgcgc ccccagaagc tgaaagtcct cttgcctcaa 180ccagcaagga ggagaaggat gaatgtgctc tcatttccac tagcatagca gaagaatgtg 240aggcttctgt ttccggtgta gttgttgaaa gtgaaaatga gcgagctggc acagtcatgg 300aagaaaaaga cgggagtggc atcatctcta cgagctcggt ggaagactgt gagggcccag 360tgtccagtgc tgtccctcaa gaggaaggcg acccctcagt cacaccagcg gaagag 416<210>399<211>259<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(259)<223>n＝A、T、C或G<400>399caaagaattc ggcacgaggg ggcgacctgc attcggacgt caccgaggcc atgctgtacg 60aaaagttcag ccccgcgggg cctgtgctgt ncatccgggt ctgccgngat atgatcaccc 120gccgctccct gggctatgcc tacgncaact tccancaacc ggccgacgct gatcgggctt 180tggacaccat gaactttgat gtgattnagg gaaanccaat ccttatcntg tnnnaatcat 240aggnatcctt ctttgacaa 259<210>400<211>410<212>DNA<213>智人(Homo sapiens)<400>400ggcacgaggg gagagcggac cccagagagc cctgagcagc cccaccgccg ccgccggcct 60agttaccatc acaccccggg aggagccgca gctgccgcag ccggccccag tcaccatcac 120cgcaaccatg agcagcgagg ccgagaccca gcagccgccc gccgcccccc cccgccgccc 180ccgccctcag cgccgccgac accaagcccg gcactacggg cagcggcgca gggagcggtg 240gcccgggcgg cctcacatcg gcggcgcctg ccggcgggga caagaaggtc atcgcaacga 300aggttttggg aacagtaaaa tggttcaatg taaggaacgg atatggtttc atcaacagga 360atgacaccaa ggaagatgta tttgtacacc agactgccat aaagaagaat 410<210>401<211>433<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(433)<223>n＝A、T、C或G<400>401ggnacgagga atcatggcgg ctgcgctgtt cgtgctgctg ggattcgcgc tgctgggcac 60ccacggagcc tccggggctg ccggcacagt cttcactacc gtagaagacc ttggctccaa 120gatactcctc acctgctcct tgaatgacag cgccacagag gtcacagggc accgctggct 180gaaggggggc gtggtgctga aggaggacgc gctgcccggc cagaaaacgg agttcaaggt 240ggactccgac gaccagtggg gagagtactc ctgcgtcttc ctccccgagc ccatgggcac 300ggccaacatc cagctccacg ggcctcccag agtgaaggcc gtgaagtcgt cagaacacat 360caacgagggg gagacggcca tgctggtctg caagtcagag tccgtgccac ctgtcactga 420ctgggcctgg tac 433<210>402<211>434<212>DNA<213>智人(Homo sapiens)<400>402ggcacgaggc tcggactgag caggactttc cttatcccag ttgattgtgc agaatacact 60gcctgtcgct tgtcttctat tcaccatggc ttcttctgat atccaggtga aagaactgga 120gaagcgtgcc tcaggccagg cttttgagct gattctcagc cctcggtcaa aaggatctgt 180tccagaattc cccctttccc ctccaaagaa gaaggatctt tccctggagg aaattcagaa 240gaaattagaa gctgcagaag aaagacgcaa gtcccatgaa gctgaggtct tgaagcagct 300ggctgagaaa cgagagcacg agaaagaagt gcttcagaag gcaatagaag agaacaacaa 360cttcagtaaa atggcagaag agaaactgac ccacaaaatg gaagctaata aagagaaccg 420agaggcacaa atgg434<210>403<211>435<212>DNA<213>智人(Homo sapiens)<400>403ggcacgagga actgctgttg ccattcaaac cattgaggag catcctgcat cttttgactg 60gagctctttt aagccaatgg gatttgaagt atcatttctg aagtttcttg aggagtctgc 120agtgaagcag aagaaaaata ctgacaaaga ccatccgaat actggaaaca aaaaaggatc 180ccattcaaat tcaagaaaaa atattgataa gactgctgtg actagtggaa atcatgtatg 240tccttgtaaa gaaagcgaaa cgtttgtaca gtttgccaat ccatcacagc ttcagtgcag 300tgataatgta aaaattgttt tagacaagaa tcttaaagat tgcactgagc ttgtcttaaa 360gcaacttcag gaaatgaaac ctaccgtcag tctgaaaaaa cttgaagtac attcaaatga 420tccagatatg tctgt 435<210>404<211>416<212>DNA<213>智人(Homo sapiens)<400>404aaagaattcg gcacgaggcg ccgctccgcc acgaccaccg ccgcctcctg ccctgcagcc 60accgccaccg cctgtgtcgc cgccgcctcg ggaccggctg tatgattagg ccacaatctt 120caatgagtaa acatattcct caattctgtg gtgttcttgg tcacacattt atggagtttc 180tgaagggcag tggagattac tgccaggcac agcacgacct ctatgcagac aagtgaactg 240tagaaactga ttactgctcc accaagaagc ccccataaga gtggttatcc tggacacaga 300agtgttgaat tgaaatccac agagcatttt acaagagttc tgacctggat ggggtaaacc 360tcagtgcact tcttttctgt tggcctcagt attactggat tgaagaattg ctgctt 416<210>405<211>435<212>DNA<213>智人(Homo sapiens)<400>405ggcacgaggg ctgccggagg gtcgttttaa agggcccgcg cgttgccgcc ccctcggccc 60gccatgctgc tatccgtgcc gctgctgctc ggcctcctcg gcctggccgt cgccgagcct 120gccgtctact tcaaggagca gtttctggac ggagacgggt ggacttcccg ctggatcgaa 180tccaaacaca agtcagattt tggcaaattc gttctcagtt ccggcaagtt ctacggtgac 240gaggagaaag ataaaggttt gcagacaagc caggatgcac gcttttatgc tctgtcggcc 300agtttcgagc ctttcagcaa caaaggccag acgctggtgg tgcagttcac ggtgaaacat 360gagcagaaca tcgactgtgg gggcggctat gtgaagctgt ttcctaatag tttggaccag 420acagacatgc acgga 435<210>406<211>424<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(424)<223>n＝A、T、C或G<400>406gcccaaaccc actccacctt actaccagac aaccttagcc aaaccattta cccaaataaa 60gtataggcga tagaaattga aacctggcgc aatagatata gtaccgcaag ggaaagatga 120aaaattataa ccaagcataa tatagcaagg actaacccct ataccttctg cataatgaat 180taactagaaa taactttgca aggagagcca aagctaagac ccccgaaacc agacgagcta 240cctaagaaca gctaaaagag cacacccgtc tatgtagcaa aatagtggga agatttatag 300gtagaggcga caaacctacc gagcctggtg atagctggtt gtccaagata gaatcttagt 360tcaactttaa atttgcccac agaaccctct aaatcccctt gnaaatttaa ctgntagtcc 420aaag 424<210>407<211>423<212>DNA<213>智人(Homo sapiens)<400>407gctcctaccg gcgcacgtgg tgccgccgct gctgcctccc gctcgccctg aacccagtgc 60ctgcagccat ggctcccggc cagctcgcct tatttagtgt ctctgacaaa accggccttg 120tggaatttgc aagaaacctg accgctcttg gtttgaatct ggtcgcttcc ggagggactg 180caaaagctct cagggatgct ggtctggcag tcagagatgt ctctgagttg acgggatttc 240ctgaaatgtt ggggggacgt gtgaaaactt tgcatcctgc agtccatgct ggaatcctag 300ctcgtaatat tccagaagat aatgctgaca tggccagact tgatttcaat cttataagag 360ttgttgcctg caatctctat ccctttgtaa agacagtggc ttctccaggt gtaagtgttg 420agg423<210>408<211>424<212>DNA<213>智人(Homo sapiens)<400>408gaaaaaaaat agcttactga attctataag atgtgtggga atctcaccta tcaaaaatag 60gtaaaaagag cctccaaacc tgctttgatt ttattcacct attcttttag gccaggaact 120aatttacctc tcactatcct gttccctctt gctatcttgt ggagtctcta aagacaaagg 180tataaagagc ttttggtagg tgaattaata atcaactaga tggcatttcc aaatgggatt 240gcacatactg tggggcaagt cccaagtgaa cttcaaagtg agacgtttat ttgagtaatc 300cttccagatt aacaataatc ataatagcag ttaccacttc ctgagtactt tctatatgcc 360atgtattgag cttgctcact tctttatgtg gattcttatt taatcttaat accaagatga 420ggtg 424<210>409<211>398<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(398)<223>n＝A、T、C或G<400>409gctcgactct tagcttgtcg gggacggtaa ccgggacccg gtgtctgctc ctgtcgcctt 60cgcctcctaa tccctagcca ctatgcgtga gtgcatctcc atccacgttg gccaggctgg 120tgtccagatt ggcaatgcct gctgggagct ctactgcctg gaacacggca tccagcccga 180tggccagatg ccaagtgaca agaccattgg gggaggagat gactccttca acaccttctt 240cagtgagacg ggcgctggca agcacgtgcc ccgggctgng tttgtagact tggaacccac 300agtnattgat gaagntcgna ctggcaccta cccgcaggtc ttncaccctg ancanntcat 360nacaggcaag gaagatgctg ncaaataact atgcccga 398<210>410<211>423<212>DNA<213>智人(Homo sapiens)<400>410gccccacccc acctgcccgc tgcggctctc cgcgggagat ctcaccgttc tggagacagg 60gctcgctcgc tctcacgctg cccggccagc ccgcttctct gcccggagcc atgaatctca 120gtagcgccag tagcacggag gaaaaggcag tgacgaccgt gctctggggc tgcgagctca 180gtcaggagag gcggacttgg accttcagac cccagctgga ggggaagcag agctgcaggc 240tgttgcttca tacgatttgc ttgggggaga aagccaaaga ggagatgcat cgcgtggaga 300tcctgccccc agcaaaccag gaggacaaga agatgcagcc ggtcaccatt gcctcactcc 360aggcctcagt cctccccatg gtctccatgg taggagtgca gctttctccc ccagttactt 420tcc423<210>411<211>424<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(424)<223>n＝A、T、C或G<400>411gcggaggcga ctagcggcgg cgggagcggc gccgagaggc cgtgcgggac gcgggcgcca 60ggaccggccg aacgcagagg ttgattcttc accacactga aaccattagg aaaaatcctt 120gtggttaaca gcagaggctt cagagtgtaa cctgtactcg ggcctagaaa ttatttaaaa 180tggcgactga tacgtctcaa ggtgaactcg tccatcctaa ggcactccca cttatagtag 240gagctcagct gatccacgcg gacaagttag gtgagaaggt agaagatagc accatgccga 300ttcgtcgaac tgtgaattct acccgggaaa ctcctcccaa aagcaagctt gctgaagggg 360aggaagaaan gccagaacca gacataagtt cagaggaatc tgtctccact gtagaagaac 420aaga 424<210>412<211>430<212>DNA<213>智人(Homo sapiens)<400>412ggcacgaggg gaagccggcg ccagttcgcg gggctccggg ccgccactca gagctatgag 60ctacggccgc ccccctcccg atgtggaggg tatgacctcc ctcaaggtgg acaacctgac 120ctaccgcacc tcgcccgaca cgctgaggcg cgtcttcgag aagtacgggc gcgtcggcga 180cgtgtacatc ccgcgggatc gctacaccaa ggagtcccgc ggcttcgcct tcgttcgctt 240tcacgacaag cgcgacgctg aggacgctat ggatgccatg gacggggccg tgctggacgg 300ccgcgagctg cgggtgcaaa tggcgcgcta cggccgcccc ccggactcac accacagccg 360ccggggaccg ccaccccgca ggtacggggg cggtggctac ggacgccgga gccgcagccc 420taggcggcgt 430<210>413<211>429<212>DNA<213>智人(Homo sapiens)<400>413ggcacgaggt cggcccggcc atcttgtggg aagagctgaa gcaggcgctc ttggctcggc 60gcggcccgct gcaatccgtg gaggaacgcg ccgccgagcc accatcatgc ctgggcactt 120acaggaaggc ttcggctgcg tggtcaccaa ccgattcgac cagttatttg acgacgaatc 180ggaccccttc gaggtgctga aggcagcaga gaacaagaaa aaagaagccg gcgggggcgg 240cgttgggggc cctggggcca agagcgcagc tcaggccgcg gcccagacca actccaacgc 300ggcaggcaaa cagctgcgca aggagtccca gaaagaccgc aagaacccgc tgccccccag 360cgttggcgtg gttgacaaga aagaggagac gcagccgccc gtggcgctta agaaagaagg 420aataagacg 429<210>414<211>429<212>DNA<213>智人(Homo sapiens)<400>414ggcacgagga cgggcccggc tgccggcccc cgctctgccc tgcataataa aatggctaat 60caggtgaatg gtaatgcggt acagttaaaa gaagaggaag aaccaatgga tacttccagt 120gtaactcaca cagaacacta caagacactg atagaggcag gcctcccaca gaaggtggca 180gaaagacttg atgaaatatt tcagacagga ttggtagctt atgtcgatct tgatgaaaga 240gcaattgatg ctctcaggga atttaatgaa gaaggagctc tgtctgtact acagcagttc 300aaggaaagtg acttatcaca tgttcagaac aaaagtgcat ttttatgtgg agttatgaag 360acctacaggc agagagagaa acaggggagc aaggtgcaag agtccacaaa gggacctgat 420gaagcgaag 429<210>415<211>398<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(398)<223>n＝A、T、C或G<400>415gcggtcgtaa gggctgagga tttttggtcc gcacgctcct gctcctgact caccgctgtt 60cgctctcgcc gaggaacaag tcggtcagga agcccgcgcg caacagccat ggcttttaag 120gataccggaa aaacacccgt ggagccggag gtggcaattc accgaattcg aatcacccta 180acaagccgca acgtaaaatc cttggaaaag gtgtgtgctg acttgataag aggcgcaaaa 240gaaaagaatc tcaaagtact ttgagaatca ctacaagaaa aactccttgt ggtgaaggtt 300ctaagacgtg ggatcgtttc cagatgagaa ttcacaagcg actcattgac ttgcacagtc 360cttctgagat tgttaagcan attacttcca tcantatt 398<210>416<211>269<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(269)<223>n＝A、T、C或G<400>416gccgaggcag gaagctgtga gtgcgcggtt gcggggtcgc attgtggcta cggctttgcg 60tccccggcgg gcagccccag gctggtcccc gcctccgctc tccccaccgg cggggaaagc 120agctggtgtg ggaggaaagg ctccatcccc cgccccctct ctcccgctgt tggctggcan 180gatcttttgg cagtcctgtg cnctcnctcc ccgnccggat cctnctgacc ctganattcn 240nggtntnacn nnccgtncac gccttgntt269<210>417<211>408<212>DNA<213>智人(Homo sapiens)<400>417ggccgggaga accgttcgcg gaggaaaggc gaactagtgt tgggatggcc accaactggg 60ggagcctctt gcaggataaa cagcagctag aggagctggc acggcaggcc gtggaccggg 120ccctggctga gggagtattg ctgaggacct cacaggagcc cacttcctcg gaggtggtga 180gctatgcccc attcacgctc ttcccctcac tggtccccag tgccctgctg gagcaagcct 240atgctgtgca gatggacttc aacctgctag tggatgctgt cagccagaac gctgccttcc 300tggagcaaac tctttccagc accatcaaac aggatgactt taccgctcgt ctctttgaca 360tccacaagca agtcctaaaa gagggcattg cccagactgt gttcctgg 408<210>418<211>402<212>DNA<213>智人(Homo sapiens)<400>418gagccgggca gccgcttccc gcccccgagc aggagccggt gcgagcggag cagagccgag 60gtcgggccgc gagcggagcc ggctgagcgg gcgccgagct cccgccatgg cccggaacac 120gctgtcctcg cgcttccgcc gggtggacat cgacgaattt gacgagaaca aatttgtgga 180cgagcaggag gaggcggcgg cggcggcggc ggagccaggc ccggacccga gcgaggtgga 240cgggctcctg cggcaagggg acatgcttcg ggcattccat gcagccttgc ggaactctcc 300cgtcaacacc aagaatcaag ctgtgaagga gcgagcccag ggcgtggtgc tgaaagtgct 360cacaaacttc aagagcagtg agattgagca ggctgtgcag tc 402<210>419<211>406<212>DNA<213>智人(Homo sapiens)<400>419gcccgggcta gcggcctggg ttgggctttg tagctgctcc gcaggcccag cccgggccgc 60gctcgcagag tcctaggcgg tgcgcggcct cctgcctcct ccctcctcgg cggtcgcggc 120ccgccggcct ccgcggtgcc tgccttcgct ctcaggttga ggagctcaag cttgggaaaa 180tggtgtgcat tccttgtatc gtcattccag ttctgctctg gatctacaaa aaattcctgg 240agccatatat ataccctctg gtttccccct tcgttaagtc gtatatggcc taaaaaaaga 300attcaaagaa atccaatgat ccaaacaaaa gggcaaaagt aaaaactttt aaaggggtgc 360aagaacattg aaatgggaat tacccaacca aaaaagggaa cccaac 406<210>420<211>371<212>DNA<213>智人(Homo sapiens)<400>420cagccatcgt ggtgtgttct tgactccgct gctcgccatg tcttctcaca agactttcag 60gattaagcga ttcctggcca agaaacaaaa gcaaaatcgt cccattcccc agtggattcg 120gatgaaaact ggaaataaaa tcaggtacaa ctccaaaagg agacattgga gaagaaccaa 180gctgggtcta taaggaattg cacatgagat ggcacacata tttatgctgt ctgaaggtca 240cgatcatgtt accatatcaa gctgaaaatg tcaccactat ctggagattt cgacgtgttt 300tcctctctga atctgttatg aacacgttgg ttggctggat tcagtaataa atatgtaagg 360cctttctttt t 371<210>421<211>51<212>PRT<213>智人(Homo sapiens)<400>421Met Ser Ser His Lys Thr Phe Arg Ile Lys Arg Phe Leu Ala Lys Lys5 10 15Gln Lys Gln Asn Arg Pro Ile Pro Gln Trp Ile Arg Met Lys Thr Gly20 25 30Asn Lys Ile Arg Tyr Asn Ser Lys Arg Arg His Trp Arg Arg Thr Lys35 40 45Leu Gly Leu50<210>422<211>12308<212>DNA<213>智人(Homo sapiens)<400>422ttgttttcta gcagtgacaa gttcactttg aatcaggata tgtgtgtagt ttgtggcagt 60tttggccaag gagcagaagg aagattactt gcctgttctc agtgtggtca gtgttaccat 120ccatactgtg tcagtattaa gatcactaaa gtggttctta gcaaaggttg gaggtgtctt 180gagtgcactg tgtgtgaggc ctgtgggaag gcaactgacc caggaagact cctgctgtgt 240gatgactgtg acataagtta tcacacctac tgcctagacc ctccattgca gacagttccc 300aaaggaggct ggaagtgcaa atggtgtgtt tggtgcagac actgtggagc aacatctgca 360ggtctaagat gtgaatggca gaacaattac acacagtgcg ctccttgtgc aagcttatct 420tcctgtccag tctgctatcg aaactataga gaagaagatc ttattctgca atgtagacaa 480tgtgatagat ggatgcatgc agtttgtcag aacttaaata ctgaggaaga agtggaaaat 540gtagcagaca ttggttttga ttgtagcatg tgcagaccct atatgcctgc gtctaatgtg 600ccttcctcag actgctgtga atcttcactt gtagcacaaa ttgtcacaaa agtaaaagag 660ctagacccac ccaagactta tacccaggat ggtgtgtgtt tgactgaatc agggatgact 720cagttacaga gcctcacagt tacagttcca agaagaaaac ggtcaaaacc aaaattgaaa 780ttgaagatta taaatcagaa tagcgtggcc gtccttcaga cccctccaga catccaatca 840gagcattcaa gggatggtga aatggatgat agtcgagaag gagaacttat ggattgtgat 900ggaaaatcag aatctagtcc tgagcgggaa gctgtggatg atgaaactaa gggagtggaa 960ggaacagatg gtgtcaaaaa gagaaaaagg aaaccataca gaccaggtat tggtggattt 1020atggtgcggc aaagaagtcg aactgggcaa gggaaaacca aaagatctgt gatcagaaaa 1080gattcctcag gctctatttc cgagcagtta ccttgcagag atgatggctg gagtgagcag 1140ttaccagata ctttagttga tgaatctgtt tctgttactg aaagcactga aaaaataaag 1200aagagatacc gaaaaaggaa aaataagctt gaagaaactt tccctgccta tttacaagaa 1260gctttctttg gaaaagatct tctagataca agtagacaaa gcaagataag tttagataat 1320ctgtcagaag atggagctca gcttttatat aaaacaaaca tgaacacagg tttcttggat 1380ccttccttag atccactact tagttcatcc tcggctccaa caaaatctgg aactcacggt 1440cctgctgatg acccattagc tgatatttct gaagttttaa acacagatga tgacattctt 1500ggaataattt cagatgatct agcaaaatca gttgatcatt cagatattgg tcctgtcact 1560gatgatcctt cctctttgcc tcagccaaat gtcaatcaga gttcacgacc attaagtgaa 1620gaacagctag atgggatcct cagtcctgaa ctagacaaaa tggtcacaga tggagcaatt 1680cttggaaaat tatataaaat tccagagctt ggcggaaaag atgttgaaga cttatttaca 1740gctgtactta gtcctgcgaa cactcagcca actccattgc cacagcctcc cccaccaaca 1800cagctgttgc caatacacaa tcaggatgct ttttcacgga tgcctctcat gaatggcctt 1860attggatcca gtcctcatct cccacataat tctttgccac ctggaagcgg actgggaact 1920ttctctgcaa ttgcacaatc ctcttatcct gatgccaggg ataaaaattc agcctttaat 1980ccaatggcaa gtgatcctaa caactcttgg acatcatcag ctcccactgt ggaaggagaa 2040aatgacacaa tgtcgaatgc ccagagaagc acgcttaagt gggagaaaga ggaggctctg 2100ggtgaaatgg caactgttgc cccagttctc tacaccaata ttaatttccc caacttaaag 2160gaagaattcc ctgattggac tactagagtg aagcaaattg ccaaattgtg gagaaaagca 2220agctcacaag aaagagcacc atatgtgcaa aaagccagag ataacagagc tgctttacgc 2280attaataaag tacagatgtc aaatgattcc atgaaaaggc agcaacagca agatagcatt 2340gatcccagct ctcgtattga ttcggagctt tttaaagatc ctttaaagca aagagaatca 2400gaacatgaac aggaatggaa atttagacag caaatgcgtc agaaaagtaa gcagcaagct 2460aaaattgaag ccacacagaa acttgaacag gtgaaaaatg agcagcagca gcagcaacaa 2520cagcaatttg gttctcagca tcttctggtg cagtctggtt cagatacacc aagtagtggg 2580atacagagtc ccttgacacc tcagcctggc aatggaaata tgtctcctgc acagtcattc 2640cataaagaac tgtttacaaa acagccaccc agtaccccta cgtctacatc ttcagatgat 2700gtgtttgtaa agccacaagc tccacctcct cctccagccc catcccggat tcccatccag 2760gatagtcttt ctcaggctca gacttctcag ccaccctcac cgcaagtgtt ttcacctggg 2820tcctctaact cacgaccacc atctccaatg gatccatatg caaaaatggt tggtacccct 2880cgaccacctc ctgtgggcca tagtttttcc agaagaaatt ctgctgcacc agtggaaaac 2940tgtacacctt tatcatcggt atctaggccc cttcaaatga atgagacaac agcaaatagg 3000ccatcccctg tcagagattt atgttcttct tccacgacaa ataatgaccc ctatgcaaaa 3060cctccagaca cacctaggcc tgtgatgaca gatcaatttc ccaaatcctt gggcctatcc 3120cggtctcctg tagtttcaga acaaactgca aaaggcccta tagcagctgg aaccagtgat 3180cactttacta aaccatctcc tagggcagat gtgtttcaaa gacaaaggat acctgactca 3240tatgcacgac ccttgttgac acctgcacct cttgatagtg gtcctggacc ttttaagact 3300ccaatgcaac ctcctccatc ctctcaggat ccttatggat cagtgtcaca ggcatcaagg 3360cgattgtctg ttgaccctta tgaaaggcct gctttgacac caagacctat agataatttt 3420tctcataatc agtcaaatga tccatatagt cagcctcccc ttaccccaca tccagcagtg 3480aatgaatctt ttgcccatcc ttcaagggct ttttcccagc ctggaaccat atcaaggcca 3540acatctcagg acccatactc ccaaccccca ggaactccac gacctgttgt agattcttat 3600tcccaatctt caggaacagc taggtccaat acagaccctt actctcaacc tcctggaact 3660ccccggccta ctactgttga cccatatagt cagcagcccc aaaccccaag accatctaca 3720caaactgact tgtttgttac acctgtaaca aatcagaggc attctgatcc atatgctcat 3780cctcctggaa caccaagacc tggaatttct gtcccttact ctcagccacc agcaacacca 3840aggccaagga tttcagaggg ttttactagg tcctcaatga caagaccagt cctcatgcca 3900aatcaggatc ctttcctgca agcagcacaa aaccgaggac cagctttacc tggcccgttg 3960gtaaggccac ctgatacatg ttcccagaca cctaggcccc ctggacctgg tctttcagac 4020acatttagcc gtgtttcccc atctgctgcc cgtgatccct atgatcagtc tccaatgact 4080ccaagatctc agtctgactc ttttggaaca agtcaaactg cccatgatgt tgctgatcag 4140ccaaggcctg gatcagaggg gagcttctgt gcatcttcaa actctccaat gcactcccaa 4200ggccagcagt tctctggtgt ctcccaactt cctggacctg tgccaacttc aggagtaact 4260gatacacaga atactgtaaa tatggcccaa gcagatacag agaaattgag acagcggcag 4320aagttacgtg aaatcattct ccagcagcaa cagcagaaga agattgcagg tcgacaggag 4380aaggggtcac aggactcacc cgcagtgcct catccagggc ctcttcaaca ctggcaacca 4440gagaatgtta accaggcttt caccagaccc ccacctccct atcctgggaa cattaggtct 4500cctgttgccc ctcctttagg acctagatat gctgttttcc caaaagatca gcgtggaccc 4560tatcctcctg atgttgctag tatggggatg agacctcatg gatttagatt tggatttcca 4620ggaggtagtc atggtaccat gccgagtcaa gagcgcttcc ttgtgcctcc tcagcaaata 4680cagggatctg gagtttctcc acagctaaga agatcagtat ctgtagatat gcctaggcct 4740ttaaataact cacaaatgaa taatccagtt ggacttcctc agcatttttc accacagagc 4800ttgccagttc agcagcacaa catactgggc caagcatata ttgaactgag acatagggct 4860cctgacggaa ggcaacggct gcctttcagt gctccacctg gcagcgttgt agaggcatct 4920tctaatctga gacatggaaa cttcattccc cggccagact ttccgggccc tagacacaca 4980gaccccatgc gacgacctcc ccagggtcta cctaatcagc tacctgtgca cccagatttg 5040gaacaagtgc caccatctca acaagagcaa ggtcattctg tccattcatc ttctatggtc 5100atgaggactc tgaaccatcc actaggtggt gaattttcag aagctccttt gtcaacatct 5160gtaccgtctg aaacaacgtc tgataattta cagataacca cccagccttc tgatggtcta 5220gaggaaaaac ttgattctga tgacccttct gtgaaggaac tggatgttaa agaccttgag 5280ggggttgaag tcaaagactt agatgatgaa gatcttgaaa acttaaattt agatacagag 5340gatggcaagg tagttgaatt ggatacttta gataatttgg aaactaatga tcccaacctg 5400gatgacctct taaggtcagg agagtttgat atcattgcat atacagatcc agaacttgac 5460atgggagata agaaaagcat gtttaatgag gaactagacc ttccaattga tgataagtta 5520gataatcagt gtgtatctgt tgaaccaaaa aaaaaggaac aagaaaacaa aactctggtt 5580ctctctgata aacattcacc acagaaaaaa tccactgtta ccaatgaggt aaaaacggaa 5640gtactgtctc caaattctaa ggtggaatcc aaatgtgaaa ctgaaaaaaa tgatgagaat 5700aaagataatg ttgacactcc ttgctcacag gcttctgctc actcagacct aaatgatgga 5760gaaaagactt ctttgcatcc ttgtgatcca gatctatttg agaaaagaac caatcgagaa 5820actgctggcc ccagtgcaaa tgtcattcag gcatccactc aactacctgc tcaagatgta 5880ataaactctt gtggcataac tggatcaact ccagttctct caagtttact tgctaatgag 5940aaatctgata attcagacat taggccatcg gggtctccac caccaccaac tctgccggcc 6000tccccatcca atcatgtgtc aagtttgcct cctttcatag caccgcctgg ccgtgttttg 6060gataatgcca tgaattctaa tgtgacagta gtctctaggg taaaccatgt tttttctcag 6120ggtgtgcagg taaacccagg gctcattcca ggtcaatcaa cagttaacca cagtctgggg 6180acaggaaaac ctgcaactca aactgggcct caaacaagtc agtctggtac cagtagcatg 6240tctggacccc aacagctaat gattcctcaa acattagcac agcagaatag agagaggccc 6300cttcttctag aagaacagcc tctacttcta caggatcttt tggatcaaga aaggcaagaa 6360cagcagcagc aaagacagat gcaagccatg attcgtcagc gatcagaacc gttcttccct 6420aatattgatt ttgatgcaat tacagatcct ataatgaaag ccaaaatggt ggcccttaaa 6480ggtataaata aagtgatggc acaaaacaat ctgggcatgc caccaatggt gatgagcagg 6540ttccctttta tgggccaggt ggtaactgga acacagaaca gtgaaggaca gaaccttgga 6600ccacaggcca ttcctcagga tggcagtata acacatcaga tttctaggcc taatcctcca 6660aattttggtc caggctttgt caatgattca cagcgtaagc agtatgaaga gtggctccag 6720gagacccaac agctgcttca aatgcagcag aagtatcttg aagaacaaat tggtgctcac 6780agaaaatcta agaaggccct ttcagctaaa caacgtactg ccaagaaagc tgggcgtgaa 6840tttccagagg aagatgcaga acaactcaag catgttactg aacagcaaag catggttcag 6900aaacagctag aacagattcg taaacaacag aaagaacatg ctgaattgat tgaagattat 6960cggatcaaac agcagcagca atgtgcaatg gccccaccta ccatgatgcc cagtgtccag 7020ccccagccac ccctaattcc aggtgccact ccacccacca tgagccaacc cacctttccc 7080atggtgccac agcagcttca gcaccagcag cacacaacag ttatttctgg ccatactagc 7140cctgttagaa tgcccagttt acctggatgg caacccaaca gtgctcctgc ccacctgccc 7200ctcaatcctc ctagaattca gcccccaatt gcccagttac caataaaaac ttgtacacca 7260gccccaggga cagtctcaaa tgcaaatcca cagagtggac caccacctcg ggtagaattt 7320gatgacaaca atccctttag tgaaagtttt caagaacggg aacgtaagga acgtttacga 7380gaacagcaag agagacaacg gatccaactc atgcaggagg tagatagaca aagagctttg 7440cagcagagga tggaaatgga gcagcatggt atggtgggct ctgagataag tagtagtagg 7500acatctgtgt cccagattcc cttctacagt tccgacttac cttgtgattt tatgcaacct 7560ctaggacccc ttcagcagtc tccacaacac caacagcaaa tggggcaggt tttacagcag 7620cagaatatac aacaaggatc aattaattca ccctccaccc aaactttcat gcagactaat 7680gagcgaaggc aggtaggccc tccttcattt gttcctgatt caccatcaat ccctgttgga 7740agcccaaatt tttcttctgt gaagcaggga catggaaatc tttctgggac cagcttccag 7800cagtccccag tgaggccttc ttttacacct gctttaccag cagcacctcc agtagctaat 7860agcagtctcc catgtggcca agattctact ataacccatg gacacagtta tccgggatca 7920acccaatcgc tcattcagtt gtattctgat ataatcccag aggaaaaagg gaaaaagaaa 7980agaacaagaa agaagaaaag agatgatgat gcagaatcca ccaaggctcc atcaactccc 8040cattcagata taactgcccc accgactcca ggcatctcag aaactacctc tactcctgca 8100gtgagcacac ccagtgagct tcctcaacaa gccgaccaag agtcggtgga accagtcggc 8160ccatccactc ccaatatggc agcaggccag ctatgtacag aattagagaa caaactgccc 8220aatagtgatt tctcacaagc aactccaaat caacagacgt atgcaaattc agaagtagac 8280aagctctcca tggaaacccc tgccaaaaca gaagagataa aactggaaaa ggctgagaca 8340gagtcctgcc caggccaaga ggagcctaaa ttggaggaac agaatggtag taaggtagaa 8400ggaaacgctg tagcctgtcc tgtctcctca gcacagagtc ctccccattc tgctggggcc 8460cctgctgcca aaggagactc agggaatgaa cttctgaaac acttgttgaa aaataaaaag 8520tcatcttctc ttttgaatca aaaacctgag ggcagtattt gttcagaaga tgactgtaca 8580aaggataata aactagttga gaagcagaac ccagctgaag gactgcaaac tttgggggct 8640caaatgcaag gtggttttgg atgtggcaac cagttgccaa aaacagatgg aggaagtgaa 8700accaagaaac agcgaagcaa acggactcag aggacgggtg agaaagcagc acctcgctca 8760aagaaaagga aaaaggacga agaggagaaa caagctatgt actctagcac tgacacgttt 8820acccacttga aacaggtgag gcagctctct ctgctccctc taatggaacc aatcattgga 8880gtgaactttg cgcactttct tccttatggc agtggccaat ttaatagtgg gaatcgactt 8940ctaggaactt ttggcagtgc taccctggaa ggggtttcgg actactattc tcagttgatc 9000tacaagcaga ataatttaag taatcctcca acaccccctg cctctcttcc tcctacacca 9060cctcctatgg cttgtcagaa gatggccaat ggttttgcaa caactgaaga acttgctgga 9120aaagccggag tgttagtgag ccatgaagtt accaaaactc taggacctaa accatttcag 9180ctgcccttca gaccccagga cgacttgttg gcccgagctc ttgctcaggg ccccaagaca 9240gttgatgtgc cagcctccct cccaacacca cctcataaca atcaggaaga attaaggata 9300caggatcact gtggtgatcg agatactcct gacagttttg ttccctcatc ctctcctgag 9360agtgtggttg gggtagaagt gagcaggtat ccagatctgt cattggtcaa ggaggagcct 9420ccagaaccgg tgccgtcccc catcattcca attcttccta gcactgctgg gaaaagttca 9480gaatcaagaa ggaatgacat caaaactgag ccaggcactt tatattttgc gtcacctttt 9540ggtccttccc caaatggtcc cagatcaggt cttatatctg tagcaattac tctgcatcct 9600acagctgctg agaacattag cagtgttgtg gctgcatttt ccgaccttct tcacgtccga 9660atccctaaca gctatgaggt tagcagtgct ccagatgtcc catccatggg tttggtcagt 9720agccacagaa tcaacccggg tttggagtat cgacagcatt tacttctccg tgggcctccg 9780ccaggatctg caaaccctcc cagattagtg agctcttacc ggctgaagca gcctaatgta 9840ccatttcctc caacaagcaa tggtctttct ggatataagg attctagtca tggtattgca 9900gaaagcgcag cactcagacc acagtggtgt tgtcattgta aagtggttat tcttggaagt 9960ggtgtgcgga aatctttcaa agatctgacc cttttgaaca aggattcccg agaaagcacc 10020aagagggtag agaaggacat tgtcttctgt agtaataact gctttattct ttattcatca 10080actgcacaag cgaaaaactc agaaaacaag gaatccattc cttcattgcc acaatcacct 10140atgagagaaa cgccttccaa agcatttcat cagtacagca acaacatctc cactttggat 10200gtgcactgtc tcccccagct cccagagaaa gcttctcccc ctgcctcacc acccatcgcc 10260ttccctcctg cttttgaagc agcccaagtc gaggccaagc cagatgagct gaaggtgaca 10320gtcaagctga agcctcggct aagagctgtc catggtgggt ttgaagattg caggccgctc 10380aataaaaaat ggagaggaat gaaatggaag aagtggagca ttcatattgt aatccctaag 10440gggacattta aaccaccttg tgaggatgaa atagatgaat ttctaaagaa attgggcact 10500tcccttaaac ctgatcctgt gcccaaagac tatcggaaat gttgcttttg tcatgaagaa 10560ggtgatggat tgacagatgg accagcaagg ctactcaacc ttgacttgga tctgtgggtc 10620cacttgaact gcgctctgtg gtccacggag gtctatgaga ctcaggctgg tgccttaata 10680aatgtggagc tagctctgag gagaggccta caaatgaaat gtgtcttctg tcacaagacg 10740ggtgccacta gtggatgcca cagatttcga tgcaccaaca tttatcactt cacttgcgcc 10800attaaagcac aatgcatgtt ttttaaggac aaaactatgc tttgccccat gcacaaacca 10860aagggaattc atgagcaaga attaagttac tttgcagtct tcaggagggt ctatgttcag 10920cgtgatgagg tgcgacagat tgctagcatc gtgcaacgag gagaacggga ccataccttt 10980cgcgtgggta gcctcatctt ccacacaatt ggtcagctgc ttccacagca gatgcaagca 11040ttccattctc ctaaagcact cttccctgtg ggctatgaag ccagccggct gtactggagc 11100actcgctatg ccaataggcg ctgccgctac ctgtgctcca ttgaggagaa ggatgggcgc 11160ccagtgtttg tcatcaggat tgtggaacaa ggccatgaag acctggttct aagtgacatc 11220tcacctaaag gtgtctggga taagattttg gagcctgtgg catgtgtgag aaaaaagtct 11280gaaatgctcc agcttttccc agcgtattta aaaggagagg atctgtttgg cctgaccgtc 11340tctgcagtgg cacgcatagc ggaatcactt cctggggttg aggcatgtga aaattatacc 11400ttccgatacg gccgaaatcc tctcatggaa cttcctcttg ccgttaaccc cacaggttgt 11460gcccgttctg aacctaaaat gagtgcccat gtcaagaggc ctcacacctt aaacagcacc 11520agcacctcaa agtcatttca gagcacagtc actggagaac tgaacgcacc ttatagtaaa 11580cagtttgttc actccaagtc atcgcagtac cggaagatga aaactgaatg gaaatccaat 11640gtgtatctgg cacggtctcg gattcagggg ctgggcctgt atgctgctcg agacattgag 11700aaacacacca tggtcattga gtacatcggg actatcattc gaaacgaagt agccaacagg 11760aaagagaagc tttatgagtc tcagaaccgt ggtgtgtaca tgttccgcat ggataacgac 11820catgtgattg acgcgacgct cacaggaggg cccgcaaggt atatcaacca ttcgtgtgca 11880cctaattgtg tggctgaagt ggtgactttt gagagaggac acaaaattat catcagctcc 11940agtcggagaa tccagaaagg agaagagctc tgctatgact ataagtttga ctttgaagat 12000gaccagcaca agattccgtg tcactgtgga gctgtgaact gccggaagtg gatgaactga 12060aatgcattcc ttgctagctc agcgggcggc ttgtccctag gaagaggcga ttcaacacac 12120cattggaatt ttgcagacag aaagagattt ttgttttctg ttttatgact ttttgaaaaa 12180gcttctggga gttctgattt cctcagtcct ttaggttaaa gcagcgccag gaggaagctg 12240acagaagcag cgttcctgaa gtggccgagg ttaaacggaa tcacagaatg gtccagcact 12300tttgcttt 12308<210>423<211>596<212>DNA<213>智人(Homo sapiens)<400>423ggccggtgaa ggaccgcgag gccttccaga ggctcaactt cctgtaccag gtgagtctgc 60gacaagggcc ccacggggac ggtgctcggc gtcccagagt gactgctccc ctcccgcagg 120ccgcccattg tgtccttgcc caggaccccg agaaccaggc gctggcgagg ttttactgct 180acactgagag gaccattgcg aagcggctcg tcttgcggcg ggatccctcg gtgaagagga 240ctctctgtcg aggctgctct tccctcctcg tcccgggcct cacctgcacc caccgccaga 300gacgctgcag gggacagcgc tggaccgtac agacctgcct aacatgccag cgcagccaac 360gcttcctcaa tgatcccggg catttactct ggggagacag gcctgaggcc cagctcggga 420gccaagcaga ttccaaacca ctacaaccct tgccaaacac agcccactcc atttcagacc 480gccttcctga ggagaaaatg cagactcagg gttccagtaa ccagtgatgg attcacccca 540tctcccaaat aaagtttact tgttttacat tcaaaaaaaa aaaaaaaaaa ctcgag 596<210>424<211>1549<212>DNA<213>智人(Homo sapiens)<400>424tgtgagaccg ccaagatggt ggtgggcgcg ttccctatgg cgaagctgct atacttgggc 60atccggcagg tcagcaagcc gcttgccaac cgtattaagg aggccgcccg ccgaagcgag 120ttcttcaaga cctatatctg cctcccgccg gctcaactgt atcactgggt ggagatgcgg 180accaagatgc gcatcatggg cttccggggc acggtcatca agccgctgaa cgaggaggcg 240gcagccgagc tgggcgcaga gctgctgggc gaagccacca tcttcatcgt gggcggcggc 300tgcctagtgc tggagtactg gcgccaccag gcgcagcagc gccacaagga ggaggagcag 360cgtgctgcct ggaacgcgct gcgggacgag gtgggccacc tggcgctggc gctggaagcg 420ctgcaggcgc aggtgcaggc ggcgccgcca cagggcgccc tggaggaact gcgcacagag 480ctgcaagagg tgcgcgccca gctctgcaat cccggccggt ccgcttccca cgcagtgcct 540gcgtccaaga aataggagct tgctggatgg aacctgaatt tggacatggc ctatgtacct 600aacgtggcct tcttcccgca ccacccttgc ctgcgctggc ccagtggaaa ccaccaggat 660cttgatgcaa cttggcattt ggttacccct gctgataaga gcagccatta cctgccactg 720ggaccagcag gtgaagcgtt gcaacatagc cccctccatc atccttcacc tcctatcccc 780cactccaaac caggacgacc tgcaaggtcc cagccagcag gacaccgtgg gcactctggc 840aaatgaaaaa atggaacctg gtcttgagct gaatcaatgt gttattgtta cccccacccc 900cggtttacct gatcagtgtt aacctttact gggacactca tctgttacac tggaacacct 960tcttcttttt gtcaatcggc acagaccact gtaaggaaat gcagtgtgtt gcagtggcct 1020tttctccccc tcaccttcta aggtcagctc tagctgagca tcagtgctct cttaaggagg 1080aaaaaaacgg tgcggctggg agcggtggct cacgcctgta atcctagcac cttgggaggc 1140cgaggcgggc ggatcacttg aggtcaggag ttccagacca gcctggccaa catggtgaaa 1200ctccgtctct actaaaaata caaaaattag ccgggtgtgg tggggtgcgc ttgtaatccc 1260agctactcgg gaggctgagg caggagaatt gcttgaaccc atgaggtgga ggttgcggtg 1320agccaagatg gcaccattgc accctagcct gggcaacaga gcaagacacc gtcttaaaac 1380caaaagttaa ccgggcgtgg tggtgggtgc ctgtaatcct agctacttgg gaggctgagg 1440caggagaatt gcttgaactt gggaggtgga ggccaagatt gtaccactgt attccagccc 1500gggtgacaga gcaagactgt gtctcaaaaa aaaaaaaaaa aaactcgag 1549<210>425<211>4019<212>PRT<213>智人(Homo sapiens)<400>425Leu Phe Ser Ser Ser Asp Lys Phe Thr Leu Asn Gln Asp Met Cys Val5 10 15Val Cys Gly Ser Phe Gly Gln Gly Ala Glu Gly Arg Leu Leu Ala Cys20 25 30Ser Gln Cys Gly Gln Cys Tyr His Pro Tyr Cys Val Ser Ile Lys Ile35 40 45Thr Lys Val Val Leu Ser Lys Gly Trp Arg Cys Leu Glu Cys Thr Val50 55 60Cys Glu Ala Cys Gly Lys Ala Thr Asp Pro Gly Arg Leu Leu Leu Cys65 70 75 80Asp Asp Cys Asp Ile Ser Tyr His Thr Tyr Cys Leu Asp Pro Pro Leu85 90 95Gln Thr Val Pro Lys Gly Gly Trp Lys Cys Lys Trp Cys Val Trp Cys100 105 110Arg His Cys Gly Ala Thr Ser Ala Gly Leu Arg Cys Glu Trp Gln Asn115 120 125Asn Tyr Thr Gln Cys Ala Pro Cys Ala Ser Leu Ser Ser Cys Pro Val130 135 140Cys Tyr Arg Asn Tyr Arg Glu Glu Asp Leu Ile Leu Gln Cys Arg Gln145 150 155 160Cys Asp Arg Trp Met His Ala Val Cys Gln Asn Leu Asn Thr Glu Glu165 170 175Glu Val Glu Asn Val Ala Asp Ile Gly Phe Asp Cys Ser Met Cys Arg180 185 190Pro Tyr Met Pro Ala Ser Asn Val Pro Ser Ser Asp Cys Cys Glu Ser195 200 205Ser Leu Val Ala Gln Ile Val Thr Lys Val Lys Glu Leu Asp Pro Pro210 215 220Lys Thr Tyr Thr Gln Asp Gly Val Cys Leu Thr Glu Ser Gly Met Thr225 230 235 240Gln Leu Gln Ser Leu Thr Val Thr Val Pro Arg Arg Lys Arg Ser Lys245 250 255Pro Lys Leu Lys Leu Lys Ile Ile Asn Gln Asn Ser Val Ala Val Leu260 265 270Gln Thr Pro Pro Asp Ile Gln Ser Glu His Ser Arg Asp Gly Glu Met275 280 285Asp Asp Ser Arg Glu Gly Glu Leu Met Asp Cys Asp Gly Lys Ser Glu290 295 300Ser Ser Pro Glu Arg Glu Ala Val Asp Asp Glu Thr Lys Gly Val Glu305 310 315 320Gly Thr Asp Gly Val Lys Lys Arg Lys Arg Lys Pro Tyr Arg Pro Gly325 330 335Ile Gly Gly Phe Met Val Arg Gln Arg Ser Arg Thr Gly Gln Gly Lys340 345 350Thr Lys Arg Ser Val Ile Arg Lys Asp Ser Ser Gly Ser Ile Ser Glu355 360 365Gln Leu Pro Cys Arg Asp Asp Gly Trp Ser Glu Gln Leu Pro Asp Thr370 375 380Leu Val Asp Glu Ser Val Ser Val Thr Glu Ser Thr Glu Lys Ile Lys385 390 395 400Lys Arg Tyr Arg Lys Arg Lys Asn Lys Leu Glu Glu Thr Phe Pro Ala405 410 415Tyr Leu Gln Glu Ala Phe Phe Gly Lys Asp Leu Leu Asp Thr Ser Arg420 425 430Gln Ser Lys Ile Ser Leu Asp Asn Leu Ser Glu Asp Gly Ala Gln Leu435 440 445Leu Tyr Lys Thr Asn Met Asn Thr Gly Phe Leu Asp Pro Ser Leu Asp450 455 460Pro Leu Leu Ser Ser Ser Ser Ala Pro Thr Lys Ser Gly Thr His Gly465 470 475 480Pro Ala Asp Asp Pro Leu Ala Asp Ile Ser Glu Val Leu Asn Thr Asp485 490 495Asp Asp Ile Leu Gly Ile Ile Ser Asp Asp Leu Ala Lys Ser Val Asp500 505 510His Ser Asp Ile Gly Pro Val Thr Asp Asp Pro Ser Ser Leu Pro Gln515 520 525Pro Asn Val Asn Gln Ser Ser Arg Pro Leu Ser Glu Glu Gln Leu Asp530 535 540Gly Ile Leu Ser Pro Glu Leu Asp Lys Met Val Thr Asp Gly Ala Ile545 550 555 560Leu Gly Lys Leu Tyr Lys Ile Pro Glu Leu Gly Gly Lys Asp Val Glu565 570 575Asp Leu Phe Thr Ala Val Leu Ser Pro Ala Asn Thr Gln Pro Thr Pro580 585 590Leu Pro Gln Pro Pro Pro Pro Thr Gln Leu Leu Pro Ile His Asn Gln595 600 605Asp Ala Phe Ser Arg Met Pro Leu Met Asn Gly Leu Ile Gly Ser Ser610 615 620Pro His Leu Pro His Asn Ser Leu Pro Pro Gly Ser Gly Leu Gly Thr625 630 635 640Phe Ser Ala Ile Ala Gln Ser Ser Tyr Pro Asp Ala Arg Asp Lys Asn645 650 655Ser Ala Phe Asn Pro Met Ala Ser Asp Pro Asn Asn Ser Trp Thr Ser660 665 670Ser Ala Pro Thr Val Glu Gly Glu Asn Asp Thr Met Ser Asn Ala Gln675 680 685Arg Ser Thr Leu Lys Trp Glu Lys Glu Glu Ala Leu Gly Glu Met Ala690 695 700Thr Val Ala Pro Val Leu Tyr Thr Asn Ile Asn Phe Pro Asn Leu Lys705 710 715 720Glu Glu Phe Pro Asp Trp Thr Thr Arg Val Lys Gln Ile Ala Lys Leu725 730 735Trp Arg Lys Ala Ser Ser Gln Glu Arg Ala Pro Tyr Val Gln Lys Ala740 745 750Arg Asp Asn Arg Ala Ala Leu Arg Ile Asn Lys Val Gln Met Ser Asn755 760 765Asp Ser Met Lys Arg Gln Gln Gln Gln Asp Ser Ile Asp Pro Ser Ser770 775 780Arg Ile Asp Ser Glu Leu Phe Lys Asp Pro Leu Lys Gln Arg Glu Ser785 790 795 800Glu His Glu Gln Glu Trp Lys Phe Arg Gln Gln Met Arg Gln Lys Ser805 810 815Lys Gln Gln Ala Lys Ile Glu Ala Thr Gln Lys Leu Glu Gln Val Lys820 825 830Asn Glu Gln Gln Gln Gln Gln Gln Gln Gln Phe Gly Ser Gln His Leu835 840 845Leu Val Gln Ser Gly Ser Asp Thr Pro Ser Ser Gly Ile Gln Ser Pro850 855 860Leu Thr Pro Gln Pro Gly Asn Gly Asn Met Ser Pro Ala Gln Ser Phe865 870 875 880His Lys Glu Leu Phe Thr Lys Gln Pro Pro Ser Thr Pro Thr Ser Thr885 890 895Ser Ser Asp Asp Val Phe Val Lys Pro Gln Ala Pro Pro Pro Pro Pro900 905 910Ala Pro Ser Arg Ile Pro Ile Gln Asp Ser Leu Ser Gln Ala Gln Thr915 920 925Ser Gln Pro Pro Ser Pro Gln Val Phe Ser Pro Gly Ser Ser Asn Ser930 935 940Arg Pro Pro Ser Pro Met Asp Pro Tyr Ala Lys Met Val Gly Thr Pro945 950 955 960Arg Pro Pro Pro Val Gly His Ser Phe Ser Arg Arg Asn Ser Ala Ala965 970 975Pro Val Glu Asn Cys Thr Pro Leu Ser Ser Val Ser Arg Pro Leu Gln980 985 990Met Asn Glu Thr Thr Ala Asn Arg Pro Ser Pro Val Arg Asp Leu Cys995 10001005Ser Ser Ser Thr Thr Asn Asn Asp Pro Tyr Ala Lys Pro Pro Asp Thr101010151020Pro Arg Pro Val Met Thr Asp Gln Phe Pro Lys Ser Leu Gly Leu Ser1025103010351040Arg Ser Pro Val Val Ser Glu Gln Thr Ala Lys Gly Pro Ile Ala Ala104510501055Gly Thr Ser Asp His Phe Thr Lys Pro Ser Pro Arg Ala Asp Val Phe106010651070Gln Arg Gln Arg Ile Pro Asp Ser Tyr Ala Arg Pro Leu Leu Thr Pro107510801085Ala Pro Leu Asp Ser Gly Pro Gly Pro Phe Lys Thr Pro Met Gln Pro109010951100Pro Pro Ser Ser Gln Asp Pro Tyr Gly Ser Val Ser Gln Ala Ser Arg1105111011151120Arg Leu Ser Val Asp Pro Tyr Glu Arg Pro Ala Leu Thr Pro Arg Pro112511301135Ile Asp Asn Phe Ser His Asn Gln Ser Asn Asp Pro Tyr Ser Gln Pro114011451150Pro Leu Thr Pro His Pro Ala Val Asn Glu Ser Phe Ala His Pro Ser115511601165Arg Ala Phe Ser Gln Pro Gly Thr Ile Ser Arg Pro Thr Ser Gln Asp117011751180Pro Tyr Ser Gln Pro Pro Gly Thr Pro Arg Pro Val Val Asp Ser Tyr1185119011951200Ser Gln Ser Ser Gly Thr Ala Arg Ser Asn Thr Asp Pro Tyr Ser Gln120512101215Pro Pro Gly Thr Pro Arg Pro Thr Thr Val Asp Pro Tyr Ser Gln Gln122012251230Pro Gln Thr Pro Arg Pro Ser Thr Gln Thr Asp Leu Phe Val Thr Pro123512401245Val Thr Asn Gln Arg His Ser Asp Pro Tyr Ala His Pro Pro G1y Thr125012551260Pro Arg Pro Gly Ile Ser Val Pro Tyr Ser Gln Pro Pro Ala Thr Pro1265127012751280Arg Pro Arg Ile Ser Glu Gly Phe Thr Arg Ser Ser Met Thr Arg Pro128512901295Val Leu Met Pro Asn Gln Asp Pro Phe Leu Gln Ala Ala Gln Asn Arg130013051310Gly Pro Ala Leu Pro Gly Pro Leu Val Arg Pro Pro Asp Thr Cys Ser131513201325Gln Thr Pro Arg Pro Pro Gly Pro Gly Leu Ser Asp Thr Phe Ser Arg133013351340Val Ser Pro Ser Ala Ala Arg Asp Pro Tyr Asp Gln Ser Pro Met Thr1345135013551360Pro Arg Ser Gln Ser Asp Ser Phe Gly Thr Ser Gln Thr Ala His Asp136513701375Val Ala Asp Gln Pro Arg Pro Gly Ser Glu Gly Ser Phe Cys Ala Ser138013851390Ser Asn Ser Pro Met His Ser Gln Gly Gln Gln Phe Ser Gly Val Ser139514001405Gln Leu Pro Gly Pro Val Pro Thr Ser Gly Val Thr Asp Thr Gln Asn141014151420Thr Val Asn Met Ala Gln Ala Asp Thr Glu Lys Leu Arg Gln Arg Gln1425143014351440Lys Leu Arg Glu Ile Ile Leu Gln Gln Gln Gln Gln Lys Lys Ile Ala144514501455Gly Arg Gln Glu Lys Gly Ser Gln Asp Ser Pro Ala Val Pro His Pro146014651470Gly Pro Leu Gln His Trp Gln Pro Glu Asn Val Asn Gln Ala Phe Thr147514801485Arg Pro Pro Pro Pro Tyr Pro Gly Asn Ile Arg Ser Pro Val Ala Pro149014951500Pro Leu Gly Pro Arg Tyr Ala Val Phe Pro Lys Asp Gln Arg Gly Pro1505151015151520Tyr Pro Pro Asp Val Ala Ser Met Gly Met Arg Pro His Gly Phe Arg152515301535Phe Gly Phe Pro Gly Gly Ser His Gly Thr Met Pro Ser Gln Glu Arg154015451550Phe Leu Val Pro Pro Gln Gln Ile Gln Gly Ser Gly Val Ser Pro Gln155515601565Leu Arg Arg Ser Val Ser Val Asp Met Pro Arg Pro Leu Asn Asn Ser157015751580Gln Met Asn Asn Pro Val Gly Leu Pro Gln His Phe Ser Pro Gln Ser1585159015951600Leu Pro Val Gln Gln His Asn Ile Leu Gly Gln Ala Tyr Ile Glu Leu160516101615Arg His Arg Ala Pro Asp Gly Arg Gln Arg Leu Pro Phe Ser Ala Pro162016251630Pro Gly Ser Val Val Glu Ala Ser Ser Asn Leu Arg His Gly Asn Phe163516401645Ile Pro Arg Pro Asp Phe Pro Gly Pro Arg His Thr Asp Pro Met Arg165016551660Arg Pro Pro Gln Gly Leu Pro Asn Gln Leu Pro Val His Pro Asp Leu1665167016751680Glu Gln Val Pro Pro Ser Gln Gln Glu Gln Gly His Ser Val His Ser168516901695Ser Ser Met Val Met Arg Thr Leu Asn His Pro Leu Gly Gly Glu Phe170017051710Ser Glu Ala Pro Leu Ser Thr Ser Val Pro Ser Glu Thr Thr Ser Asp171517201725Asn Leu Gln Ile Thr Thr Gln Pro Ser Asp Gly Leu Glu Glu Lys Leu173017351740Asp Ser Asp Asp Pro Ser Val Lys Glu Leu Asp Val Lys Asp Leu Glu1745175017551760Gly Val Glu Val Lys Asp Leu Asp Asp Glu Asp Leu Glu Asn Leu Asn176517701775Leu Asp Thr Glu Asp Gly Lys Val Val Glu Leu Asp Thr Leu Asp Asn178017851790Leu Glu Thr Asn Asp Pro Asn Leu Asp Asp Leu Leu Arg Ser Gly Glu179518001805Phe Asp Ile Ile Ala Tyr Thr Asp Pro Glu Leu Asp Met Gly Asp Lys181018151820Lys Ser Met Phe Asn Glu Glu Leu Asp Leu Pro Ile Asp Asp Lys Leu1825183018351840Asp Asn Gln Cys Val Ser Val Glu Pro Lys Lys Lys Glu Gln Glu Asn184518501855Lys Thr Leu Val Leu Ser Asp Lys His Ser Pro Gln Lys Lys Ser Thr186018651870Val Thr Asn Glu Val Lys Thr Glu Val Leu Ser Pro Asn Ser Lys Val187518801885Glu Ser Lys Cys Glu Thr Glu Lys Asn Asp Glu Asn Lys Asp Asn Val189018951900Asp Thr Pro Cys Ser Gln Ala Ser Ala His Ser Asp Leu Asn Asp Gly1905191019151920Glu Lys Thr Ser Leu His Pro Cys Asp Pro Asp Leu Phe Glu Lys Arg192519301935Thr Asn Arg Glu Thr Ala Gly Pro Ser Ala Asn Val Ile Gln Ala Ser194019451950Thr Gln Leu Pro Ala Gln Asp Val Ile Asn Ser Cys Gly Ile Thr Gly195519601965Ser Thr Pro Val Leu Ser Ser Leu Leu Ala Asn Glu Lys Ser Asp Asn197019751980Ser Asp Ile Arg Pro Ser Gly Ser Pro Pro Pro Pro Thr Leu Pro Ala1985199019952000Ser Pro Ser Asn His Val Ser Ser Leu Pro Pro Phe Ile Ala Pro Pro200520102015Gly Arg Val Leu Asp Asn Ala Met Asn Ser Asn Val Thr Val Val Ser202020252030Arg Val Asn His Val Phe Ser Gln Gly Val Gln Val Asn Pro Gly Leu203520402045Ile Pro Gly Gln Ser Thr Val Asn His Ser Leu Gly Thr Gly Lys Pro205020552060Ala Thr Gln Thr Gly Pro Gln Thr Ser Gln Ser Gly Thr Ser Ser Met2065207020752080Ser Gly Pro Gln Gln Leu Met Ile Pro Gln Thr Leu Ala Gln Gln Asn208520902095Arg Glu Arg Pro Leu Leu Leu Glu Glu Gln Pro Leu Leu Leu Gln Asp210021052110Leu Leu Asp Gln Glu Arg Gln Glu Gln Gln Gln Gln Arg Gln Met Gln211521202125Ala Met Ile Arg Gln Arg Ser Glu Pro Phe Phe Pro Asn Ile Asp Phe213021352140Asp Ala Ile Thr Asp Pro Ile Met Lys Ala Lys Met Val Ala Leu Lys2145215021552160Gly Ile Asn Lys Val Met Ala Gln Asn Asn Leu Gly Met Pro Pro Met216521702175Val Met Ser Arg Phe Pro Phe Met Gly Gln Val Val Thr Gly Thr Gln218021852190Asn Ser Glu Gly Gln Asn Leu Gly Pro Gln Ala Ile Pro Gln Asp Gly219522002205Ser Ile Thr His Gln Ile Ser Arg Pro Asn Pro Pro Asn Phe Gly Pro221022152220Gly Phe Val Asn Asp Ser Gln Arg Lys Gln Tyr Glu Glu Trp Leu Gln2225223022352240Glu Thr Gln Gln Leu Leu Gln Met Gln Gln Lys Tyr Leu Glu Glu Gln224522502255Ile Gly Ala His Arg Lys Ser Lys Lys Ala Leu Ser Ala Lys Gln Arg226022652270Thr Ala Lys Lys Ala Gly Arg Glu Phe Pro Glu Glu Asp Ala Glu Gln227522802285Leu Lys His Val Thr Glu Gln Gln Ser Met Val Gln Lys Gln Leu Glu229022952300Gln Ile Arg Lys Gln Gln Lys Glu His Ala Glu Leu Ile Glu Asp Tyr2305231023152320Arg Ile Lys Gln Gln Gln Gln Cys Ala Met Ala Pro Pro Thr Met Met232523302335Pro Ser Val Gln Pro Gln Pro Pro Leu Ile Pro Gly Ala Thr Pro Pro234023452350Thr Met Ser Gln Pro Thr Phe Pro Met Val Pro Gln Gln Leu Gln His235523602365Gln Gln His Thr Thr Val Ile Ser Gly His Thr Ser Pro Val Arg Met237023752380Pro Ser Leu Pro Gly Trp Gln Pro Asn Ser Ala Pro Ala His Leu Pro2385239023952400Leu Asn Pro Pro Arg Ile Gln Pro Pro Ile Ala Gln Leu Pro Ile Lys240524102415Thr Cys Thr Pro Ala Pro Gly Thr Val Ser Asn Ala Asn Pro Gln Ser242024252430Gly Pro Pro Pro Arg Val Glu Phe Asp Asp Asn Asn Pro Phe Ser Glu243524402445Ser Phe Gln Glu Arg Glu Arg Lys Glu Arg Leu Arg Glu Gln Gln Glu245024552460Arg Gln Arg Ile Gln Leu Met Gln Glu Val Asp Arg Gln Arg Ala Leu2465247024752480Gln Gln Arg Met Glu Met Glu Gln His Gly Met Val Gly Ser Glu Ile248524902495Ser Ser Ser Arg Thr Ser Val Ser Gln Ile Pro Phe Tyr Ser Ser Asp250025052510Leu Pro Cys Asp Phe Met Gln Pro Leu Gly Pro Leu Gln Gln Ser Pro251525202525Gln His Gln Gln Gln Met Gly Gln Val Leu Gln Gln Gln Asn Ile Gln253025352540Gln Gly Ser Ile Asn Ser Pro Ser Thr Gln Thr Phe Met Gln Thr Asn2545255025552560Glu Arg Arg Gln Val Gly Pro Pro Ser Phe Val Pro Asp Ser Pro Ser256525702575Ile Pro Val Gly Ser Pro Asn Phe Ser Ser Val Lys Gln Gly His Gly258025852590Asn Leu Ser Gly Thr Ser Phe Gln Gln Ser Pro Val Arg Pro Ser Phe259526002605Thr Pro Ala Leu Pro Ala Ala Pro Pro Val Ala Asn Ser Ser Leu Pro261026152620Cys Gly Gln Asp Ser Thr Ile Thr His Gly His Ser Tyr Pro Gly Ser2625263026352640Thr Gln Ser Leu Ile Gln Leu Tyr Ser Asp Ile Ile Pro Glu Glu Lys264526502655Gly Lys Lys Lys Arg Thr Arg Lys Lys Lys Arg Asp Asp Asp Ala Glu266026652670Ser Thr Lys Ala Pro Ser Thr Pro His Ser Asp Ile Thr Ala Pro Pro267526802685Thr Pro Gly Ile Ser Glu Thr Thr Ser Thr Pro Ala Val Ser Thr Pro269026952700Ser Glu Leu Pro Gln Gln Ala Asp Gln Glu Ser Val Glu Pro Val Gly2705271027152720Pro Ser Thr Pro Asn Met Ala Ala Gly Gln Leu Cys Thr Glu Leu Glu272527302735Asn Lys Leu Pro Asn Ser Asp Phe Ser Gln Ala Thr Pro Asn Gln Gln274027452750Thr Tyr Ala Asn Ser Glu Val Asp Lys Leu Ser Met Glu Thr Pro Ala275527602765Lys Thr Glu Glu Ile Lys Leu Glu Lys Ala Glu Thr Glu Ser Cys Pro277027752780Gly Gln Glu Glu Pro Lys Leu Glu Glu Gln Asn Gly Ser Lys Val Glu2785279027952800Gly Asn Ala Val Ala Cys Pro Val Ser Ser Ala Gln Ser Pro Pro His280528102815Ser Ala Gly Ala Pro Ala Ala Lys Gly Asp Ser Gly Asn Glu Leu Leu282028252830Lys His Leu Leu Lys Asn Lys Lys Ser Ser Ser Leu Leu Asn Gln Lys283528402845Pro Glu Gly Ser Ile Cys Ser Glu Asp Asp Cys Thr Lys Asp Asn Lys285028552860Leu Val Glu Lys Gln Asn Pro Ala Glu Gly Leu Gln Thr Leu Gly Ala2865287028752880Gln Met Gln Gly Gly Phe Gly Cys Gly Asn Gln Leu Pro Lys Thr Asp288528902895Gly Gly Ser Glu Thr Lys Lys Gln Arg Ser Lys Arg Thr Gln Arg Thr290029052910Gly Glu Lys Ala Ala Pro Arg Ser Lys Lys Arg Lys Lys Asp Glu Glu291529202925Glu Lys Gln Ala Met Tyr Ser Ser Thr Asp Thr Phe Thr His Leu Lys293029352940Gln Val Arg Gln Leu Ser Leu Leu Pro Leu Met Glu Pro Ile Ile Gly2945295029552960Val Asn Phe Ala His Phe Leu Pro Tyr Gly Ser Gly Gln Phe Asn Ser296529702975Gly Asn Arg Leu Leu Gly Thr Phe Gly Ser Ala Thr Leu Glu Gly Val298029852990Ser Asp Tyr Tyr Ser Gln Leu Ile Tyr Lys Gln Asn Asn Leu Ser Asn299530003005Pro Pro Thr Pro Pro Ala Ser Leu Pro Pro Thr Pro Pro Pro Met Ala301030153020Cys Gln Lys Met Ala Asn Gly Phe Ala Thr Thr Glu Glu Leu Ala Gly3025303030353040Lys Ala Gly Val Leu Val Ser His Glu Val Thr Lys Thr Leu Gly Pro304530503055Lys Pro Phe Gln Leu Pro Phe Arg Pro Gln Asp Asp Leu Leu Ala Arg306030653070Ala Leu Ala Gln Gly Pro Lys Thr Val Asp Val Pro Ala Ser Leu Pro307530803085Thr Pro Pro His Asn Asn Gln Glu Glu Leu Arg Ile Gln Asp His Cys309030953100Gly Asp Arg Asp Thr Pro Asp Ser Phe Val Pro Ser Ser Ser Pro Glu3105311031153120Ser Val Val Gly Val Glu Val Ser Arg Tyr Pro Asp Leu Ser Leu Val312531303135Lys Glu Glu Pro Pro Glu Pro Val Pro Ser Pro Ile Ile Pro Ile Leu314031453150Pro Ser Thr Ala Gly Lys Ser Ser Glu Ser Arg Arg Asn Asp Ile Lys315531603165Thr Glu Pro Gly Thr Leu Tyr Phe Ala Ser Pro Phe Gly Pro Ser Pro317031753180Asn Gly Pro Arg Ser Gly Leu Ile Ser Val Ala Ile Thr Leu His Pro3185319031953200Thr Ala Ala Glu Asn Ile Ser Ser Val Val Ala Ala Phe Ser Asp Leu320532103215Leu His Val Arg Ile Pro Asn Ser Tyr Glu Val Ser Ser Ala Pro Asp322032253230Val Pro Ser Met Gly Leu Val Ser Ser His Arg Ile Asn Pro Gly Leu323532403245Glu Tyr Arg Gln His Leu Leu Leu Arg Gly Pro Pro Pro Gly Ser Ala325032553260Asn Pro Pro Arg Leu Val Ser Ser Tyr Arg Leu Lys Gln Pro Asn Val3265327032753280Pro Phe Pro Pro Thr Ser Asn Gly Leu Ser Gly Tyr Lys Asp Ser Ser328532903295His Gly Ile Ala Glu Ser Ala Ala Leu Arg Pro Gln Trp Cys Cys His330033053310Cys Lys Val Val Ile Leu Gly Ser Gly Val Arg Lys Ser Phe Lys Asp331533203325Leu Thr Leu Leu Asn Lys Asp Ser Arg Glu Ser Thr Lys Arg Val Glu333033353340Lys Asp Ile Val Phe Cys Ser Asn Asn Cys Phe Ile Leu Tyr Ser Ser3345335033553360Thr Ala Gln Ala Lys Asn Ser Glu Asn Lys Glu Ser Ile Pro Ser Leu336533703375Pro Gln Ser Pro Met Arg Glu Thr Pro Ser Lys Ala Phe His Gln Tyr338033853390Ser Asn Asn Ile Ser Thr Leu Asp Val His Cys Leu Pro Gln Leu Pro339534003405Glu Lys Ala Ser Pro Pro Ala Ser Pro Pro Ile Ala Phe Pro Pro Ala341034153420Phe Glu Ala Ala Gln Val Glu Ala Lys Pro Asp Glu Leu Lys Val Thr3425343034353440Val Lys Leu Lys Pro Arg Leu Arg Ala Val His Gly Gly Phe Glu Asp344534503455Cys Arg Pro Leu Asn Lys Lys Trp Arg Gly Met Lys Trp Lys Lys Trp346034653470Ser Ile His Ile Val Ile Pro Lys Gly Thr Phe Lys Pro Pro Cys Glu347534803485Asp Glu Ile Asp Glu Phe Leu Lys Lys Leu Gly Thr Ser Leu Lys Pro349034953500Asp Pro Val Pro Lys Asp Tyr Arg Lys Cys Cys Phe Cys His Glu Glu3505351035153520Gly Asp Gly Leu Thr Asp Gly Pro Ala Arg Leu Leu Asn Leu Asp Leu352535303535Asp Leu Trp Val His Leu Asn Cys Ala Leu Trp Ser Thr Glu Val Tyr354035453550Glu Thr Gln Ala Gly Ala Leu Ile Asn Val Glu Leu Ala Leu Arg Arg355535603565Gly Leu Gln Met Lys Cys Val Phe Cys His Lys Thr Gly Ala Thr Ser357035753580Gly Cys His Arg Phe Arg Cys Thr Asn Ile Tyr His Phe Thr Cys Ala3585359035953600Ile Lys Ala Gln Cys Met Phe Phe Lys Asp Lys Thr Met Leu Cys Pro360536103615Met His Lys Pro Lys Gly Ile His Glu Gln Glu Leu Ser Tyr Phe Ala362036253630Val Phe Arg Arg Val Tyr Val Gln Arg Asp Glu Val Arg Gln Ile Ala363536403645Ser Ile Val Gln Arg Gly Glu Arg Asp His Thr Phe Arg Val Gly Ser365036553660Leu Ile Phe His Thr Ile Gly Gln Leu Leu Pro Gln Gln Met Gln Ala3665367036753680Phe His Ser Pro Lys Ala Leu Phe Pro Val Gly Tyr Glu Ala Ser Arg368536903695Leu Tyr Trp Ser Thr Arg Tyr Ala Asn Arg Arg Cys Arg Tyr Leu Cys370037053710Ser Ile Glu Glu Lys Asp Gly Arg Pro Val Phe Val Ile Arg Ile Val371537203725Glu Gln Gly His Glu Asp Leu Val Leu Ser Asp Ile Ser Pro Lys Gly373037353740Val Trp Asp Lys Ile Leu Glu Pro Val Ala Cys Val Arg Lys Lys Ser3745375037553760Glu Met Leu Gln Leu Phe Pro Ala Tyr Leu Lys Gly Glu Asp Leu Phe376537703775Gly Leu Thr Val Ser Ala Val Ala Arg Ile Ala Glu Ser Leu Pro Gly378037853790Val Glu Ala Cys Glu Asn Tyr Thr Phe Arg Tyr Gly Arg Asn Pro Leu379538003805Met Glu Leu Pro Leu Ala Val Asn Pro Thr Gly Cys Ala Arg Ser Glu381038153820Pro Lys Met Ser Ala His Val Lys Arg Pro His Thr Leu Asn Ser Thr3825383038353840Ser Thr Ser Lys Ser Phe Gln Ser Thr Val Thr Gly Glu Leu Asn Ala384538503855Pro Tyr Ser Lys Gln Phe Val His Ser Lys Ser Ser Gln Tyr Arg Lys386038653870Met Lys Thr Glu Trp Lys Ser Asn Val Tyr Leu Ala Arg Ser Arg Ile387538803885Gln Gly Leu Gly Leu Tyr Ala Ala Arg Asp Ile Glu Lys His Thr Met389038953900Val Ile Glu Tyr Ile Gly Thr Ile Ile Arg Asn Glu Val Ala Asn Arg3905391039153920Lys Glu Lys Leu Tyr Glu Ser Gln Asn Arg Gly Val Tyr Met Phe Arg392539303935Met Asp Asn Asp His Val Ile Asp Ala Thr Leu Thr Gly Gly Pro Ala394039453950Arg Tyr Ile Asn His Ser Cys Ala Pro Asn Cys Val Ala Glu Val Val395539603965Thr Phe Glu Arg Gly His Lys Ile Ile Ile Ser Ser Ser Arg Arg Ile397039753980Gln Lys Gly Glu Glu Leu Cys Tyr Asp Tyr Lys Phe Asp Phe Glu Asp3985399039954000Asp Gln His Lys Ile Pro Cys His Cys Gly Ala Val Asn Cys Arg Lys400540104015Trp Met Asn<210>426<211>174<212>PRT<213>智人(Homo sapiens)<400>426Pro Val Lys Asp Arg Glu Ala Phe Gln Arg Leu Asn Phe Leu Tyr Gln5 10 15Val Ser Leu Arg Gln Gly Pro His Gly Asp Gly Ala Arg Arg Pro Arg20 25 30Val Thr Ala Pro Leu Pro Gln Ala Ala His Cys Val Leu Ala Gln Asp35 40 45Pro Glu Asn Gln Ala Leu Ala Arg Phe Tyr Cys Tyr Thr Glu Arg Thr50 55 60Ile Ala Lys Arg Leu Val Leu Arg Arg Asp Pro Ser Val Lys Arg Thr65 70 75 80Leu Cys Arg Gly Cys Ser Ser Leu Leu Val Pro Gly Leu Thr Cys Thr85 90 95His Arg Gln Arg Arg Cys Arg Gly Gln Arg Trp Thr Val Gln Thr Cys100 105 110Leu Thr Cys Gln Arg Ser Gln Arg Phe Leu Asn Asp Pro Gly His Leu115 120 125Leu Trp Gly Asp Arg Pro Glu Ala Gln Leu Gly Ser Gln Ala Asp Ser130 135 140Lys Pro Leu Gln Pro Leu Pro Asn Thr Ala His Ser Ile Ser Asp Arg145 150 155 160Leu Pro Glu Glu Lys Met Gln Thr Gln Gly Ser Ser Asn Gln165 170<210>427<211>184<212>PRT<213>智人(Homo sapiens)<400>427Cys Glu Thr Ala Lys Met Val Val Gly Ala Phe Pro Met Ala Lys Leu5 10 15Leu Tyr Leu Gly Ile Arg Gln Val Ser Lys Pro Leu Ala Asn Arg Ile20 25 30Lys Glu Ala Ala Arg Arg Ser Glu Phe Phe Lys Thr Tyr Ile Cys Leu35 40 45Pro Pro Ala Gln Leu Tyr His Trp Val Glu Met Arg Thr Lys Met Arg50 55 60Ile Met Gly Phe Arg Gly Thr Val Ile Lys Pro Leu Asn Glu Glu Ala65 70 75 80Ala Ala Glu Leu Gly Ala Glu Leu Leu Gly Glu Ala Thr Ile Phe Ile85 90 95Val Gly Gly Gly Cys Leu Val Leu Glu Tyr Trp Arg His Gln Ala Gln100 105 110Gln Arg His Lys Glu Glu Glu Gln Arg Ala Ala Trp Asn Ala Leu Arg115 120 125Asp Glu Val Gly His Leu Ala Leu Ala Leu Glu Ala Leu Gln Ala Gln130 135 140Val Gln Ala Ala Pro Pro Gln Gly Ala Leu Glu Glu Leu Arg Thr Glu145 150 155 160Leu Gln Glu Val Arg Ala Gln Leu Cys Asn Pro Gly Arg Ser Ala Ser165 170 175His Ala Val Pro Ala Ser Lys Lys180<210>428<211>6476<212>DNA<213>智人(Homo sapiens)<400>428cactgactgg actgaaaaca gggccaagaa aactgctgct gcagggggtc ctgaaaacag 60ctggaacccg gcagtgatgt gggacctaac ttgaagttaa cctgtggtgg tgaggttgga 120accagttgga ttatgattta ttttctacac tcttgtacgg aatgcagagc tgttgtatcc 180tgatgaatct actgctaaat atagtcattt ggaataattt taagtattga tcttaaaact 240tgtaccacaa caagagtgtc taaaaagcac ggcaagctca ttacgttctt acgaacattc 300atgaagtctc gtccaacaaa acagaagctg aagcagcggg gaatcttgaa agagagggtg 360tttggttgtg acctggggga gcaccttcta aattctggtt ttgaagtgcc gcagttcttc 420aaagctgcac agcattcatt gagagatatg gcatcgtgga tggaatctat cgcctttctg 480gtgttgcctc caatatccag agactacgcc atgaatttga ctctgagcac gtccccgacc 540tgacgaaaga accgtatgtt caggacatcc attctgtggg ttccctatgt aagctgtact 600tccgggaact cccaaaccct ctgcttacct accagctgta tgagaaattt tctgatgcag 660tttcagcagc aacagatgaa gaaaggctga taaaaatcca cgatgtcatc cagcagctcc 720ccccaccaca ctacagaaca ctggagttcc tgatgagaca cttgtctctt ctagctgact 780attgttccat cacaaatatg catgcaaaaa atctagcaat tgtttgggct ccaaacctgt 840taagatcaaa acagatagaa tctgcctgct tcagtggaac agcagctttc atggaagtga 900ggattcagtc tgtggttgtt gagttcatcc tgaatcacgt tgatgtgctg ttcagcggca 960gaatcagcat ggccatgcaa gagggggcag cttctctatc aaggcccaag tccctcctgg 1020tatcctctcc atccaccaaa ctgctgacat tggaagaggc ccaggcacga acacaagctc 1080aggtcaattc tccaattgtg acggaaaata aatatatcga agtaggagaa ggacctgctg 1140cacttcaggg gaaatttcat accataattg agttcccact tgaaagaaag aggcctcaaa 1200ataagatgaa aaagtctcct gtgggtagct ggcgttcctt tttcaacttg gggaaatcat 1260catctgtttc taaacgaaag ctgcagcgga atgagagtga gccttcagag atgaaagcca 1320tggctctgaa aggtggcagg gcagaaggaa ccctccgttc agctaaaagt gaggagtctc 1380ttacatctct ccatgcagtt gatggtgatt ctaagctctt ccgacccaga agacccagat 1440cttccagtga tgcactgtct gcctctttta atggagaaat gctggggaac cgctgtaact 1500cctatgataa tctgcctcat gacaatgaga gtgaggagga aggagggctg cttcatatcc 1560cagcccttat gtctcctcat tcagctgagg atgttgactt gagcccacca gacattggag 1620tagccagcct ggattttgat ccaatgtcat ttcaatgtag tcctcctaag gccgaatcag 1680aatgtctgga gagtggtgct tcctttttag attcaccagg atactccaag gataaaccaa 1740gtgccaataa aaaggatgca gaaacaggta gtagccaatg tcagactcca ggaagcacag 1800caagctctga acctgtctct cctcttcagg agaaactgag tccattcttt accctggact 1860tgagcccaac tgaagataaa tcatctaagc catcctcctt tactgaaaag gtcgtctatg 1920ctttctctcc gaagatagga cggaaattaa gcaaatcacc ttctatgagc atatctgagc 1980caatttcagt gaccctacca ccacgggtgt cagaagtcat tggtacagtc tcaaatacca 2040cagctcagaa tgcatcatct tcaacctggg acaaatgcgt tgaagaaagg gatgccacaa 2100atagatcccc cacccagata gtaaagatga aaacaaatga gacagttgcc caagaagcat 2160atgaatctga agtccagccc ctggaccagg tggctgctga agaagtagaa ttgccaggga 2220aagaggatca gtctgtctca agcagtcaga gtaaggctgt agcttctgga cagactcaga 2280caggagcagt tacccatgac ccccctcagg attccgttcc tgtcagttca gtctctctta 2340tcccaccacc accgcctccg aaaaatgttg cccgaatgtt ggcgctagca ttagctgagt 2400ccgcacagca agcctcaact cagtcattga agagaccagg gacctctcag gctgggtata 2460caaattatgg agacatagcg gtggctacaa ctgaagataa tctgtccagt tcttactctg 2520cagttgctct agataaggcc tatttccaaa ccgatcgacc agcagagcag ttccacctcc 2580agaataatgc accaggaaac tgtgaccatc ctctaccaga gacaacagct actggggatc 2640ctacccattc caacacaact gaatctgggg agcaacatca ccaagtagac ttaacaggga 2700atcagccaca tcaagcatat ttatctgggg acccagaaaa ggccagaatt acttcagttc 2760ccttagactc agagaagtct gatgatcatg taagtttccc tgaagaccag tctgggaaga 2820acagtatgcc aactgtctcc ttcttggatc aggaccagtc tccaccccgt ttctacagtg 2880gagatcagcc tccttcttat cttggtgcaa gtgtggataa actccatcac cctttagaat 2940ttgcagacaa atctcccaca cctcctaatt tacctagcga taaaatctac cctccttctg 3000ggtcccccga agagaatacc agcacagcca ccatgactta catgacaact actccagcaa 3060cagcccaaat gagcaccaag gaagccagct gggatgtggc tgaacaaccc accactgctg 3120attttgctgc tgccacactt cagcgcacgc acagaactaa tcgtcccctt ccccctccgc 3180cttcccagag atctgcagag cagccaccag ttgtggggca ggtacaagca gcaaccaata 3240taggattaaa taattcccac aaggttcaag gagtagttcc agttccagag aggccacctg 3300aacctcgagc catggatgac cctgcgtctg ccttcatcag tgacagtggt gctgctgctg 3360ctcagtgtcc catggctaca gctgtccagc caggcctgcc tgagaaagtg cgggacggtg 3420cccgggtccc gctgctgcac ctgcgcgccg agtctgtccc tgcgcatccc tgtggctttc 3480ctgcaccact gccccccacc aggatgatgg agagtaagat gattgctgcc atacactcca 3540gcagtgcaga tgccaccagc agttcaaatt atcattcctt tgtcactgct tcatccacct 3600ctgtggacga tgcattgcct ttaccacttc ctgtcccaca acctaagcat gcttctcaga 3660aaacagttta ctcctccttt gctaggcccg atgtcaccac tgaacccttt ggtccagata 3720actgtttgca tttcaatatg actccaaact gccagtaccg tccccagagt gtacctcccc 3780atcacaataa attggagcag caccaagtgt atggtgccag gtcagagcca ccagcctcca 3840tgggtcttcg ttataacaca tatgtggccc caggaagaaa cgcatctgga caccactcca 3900agccatgcag ccgggtcgag tatgtgtctt ctttgagctc ctctgtcagg aatacctgtt 3960accccgaaga cattccaccg taccctacca tccggagagt gcagtctctc catgctccgc 4020cgtcttccat gattcgctct gttcccattt cacggacaga agttccccca gatgatgagc 4080cagcctactg cccaagacct ctgtaccaat ataagccata tcagtcctcc caggcccgct 4l40cagattatca tgtcactcag cttcagcctt actttgagaa tggccgggtc cactacaggt 4200atagcccata ttccagttct tctagttcct attacagtcc agatggggcc ctgtgtgatg 4260tggatgccta tggcacagtc cagttgagac cccttcaccg ccttcccaat cgagactttg 4320ctttctacaa tcctaggctg caaggaaaga gcttgtacag ttatgctggt ttggctccac 4380gtccccgggc caacgtgact ggctatttct ctcccaacga ccataatgta gtcagcatgc 4440ctccggctgc tgatgtgaag cacacctaca cctcatggga tcttgaggac atggaaaaat 4500accgcatgca gtccatccgg agagagagcc gtgctcggca gaaggtgaaa gggcctgtca 4560tgtcccaata tgataacatg accccggcgg tgcaggacga cttgggtggg atctatgtca 4620tccatctgcg tagtaaatca gatcctggga aaactggact tctctcagtg gcagaaggaa 4680aggagagccg ccatgcagcc aaggccatca gtcccgaggg agaggaccgc ttctatagga 4740ggcatcccga ggcagagatg gacagagccc accatcacgg aggccatggt agcacgcagc 4800cggagaagcc atccctgcct cagaagcaga gcagcctgag gagcaggaag cttcctgaca 4860tgggctgcag tcttcctgag cacagggcac accaagaagc aagccatagg cagttctgtg 4920agtcaaagaa tgggccccct tatccccagg gagctggcca gttagattat gggtccaaag 4980ggattccaga cacttctgag ccagtcagct accacaactc tggagtaaaa tatgctgcat 5040ccgggcaaga atctttaaga ctgaaccaca aagaggtaag gctctccaaa gagatggagc 5100gaccctgggt taggcagcct tctgccccag agaaacactc cagagactgc tacaaggagg 5160aagaacacct cactcagtca atcgtcccac cccctaaacc agagaggagt catagcctca 5220aactccatca tacccagaac gtggagaggg accccagtgt gctgtaccag taccaaccac 5280acggcaagcg ccagagcagt gtgactgttg tgtcccagta tgataacctg gaagattacc 5340actccctgcc tcagcaccag cgaggagtct ttggaggggg cggcatgggg acgtatgtgc 5400cccctggctt tccccatcca cagagcagga cctatgctac agcgttgggt caaggggcct 5460tcctgcccgc agagttgtcc ttgcagcatc ctgaaacaca gatccatgca gaatgagccc 5520tgcgagcaat agagttgaag cagcctctgc tggacagtgg actgttctat ttttttcaat 5580aaccaaaaag attaaacaaa aaatactata aaacccctga ccacatttaa aaaatgataa 5640taaaagtaaa caaatcagca tctttttccc cttccctgct tcattacccc ctcttccatc 5700tatagacttt gtcatttttg tctttagaaa agatctgaag gatggtaaag ccccgtgctg 5760aaacccagta gagaaacctg tctcaggaca cacttgccat ctagggctag cttgaaagag 5820cctgaggact gcctttaact gaatttgaat tcagcattgt cctttcttct tagtatttgc 5880tgcataattg agagcagttc acatcgattt cctggtaggc gtctgcattc cctgttgtgt 5940tcctgcttct ccttcagtag ctgcacaact tgcgcagatc gacacactgt tgtcacttca 6000ttctccccgt ctgagaagga tcttgtgttc agttagagtc gtggaaaaat ccctgatcct 6060tcaaggtcag tcagacagtt ggcaacatta taattaaaaa taagaaatta agactttaaa 6120ttaaacattt ggtagagtca tcataaaaca ccagaccact tagactcagg ctgaaccata 6180ctctttctat tcttattttt catccttgtt cctcacggtt cagtgaacag gctcatatca 6240tgacagaatg gacttttaaa agttagtact taaggaaact tctttaggtg gaagaaagta 6300aagttcttat tgtcagtgaa ctttattagc accagaaatc tctattgatg cttttaatgc 6360attgcctgcc ttcaggtttt cttcttaccc cacccctcaa taagatttgg tgaattgtaa 6420ttctagtaaa acatgtcata ccattggttt tcctaaatta tcaactttct ttcatt 6476<210>429<211>732<212>DNA<213>智人(Homo sapiens)<400>429tgggatttgg tctctttgac taatcaccaa aaagcaacca actcctccga ctcttccttg 60gcttcaacct tagctggggc tgcagcagca gagcgagcag ctgtggtggc agcagcaacg 120gggcagcagc acaaaggcag atggatcagc caagaaggcc ttgacctttt cagcaagtgg 180gaaggtgtaa tccgtctcca cagacaaggc caggaccggc gtcaaaggtg aagcaggaca 240tgcctccgcc ggggggctat gggcccatcg actacaaacg gaacttgccg cgtcgaggac 300tgtcgggcta cagcatgctg gccataggga ttggaaccct gatctacggg cactggagca 360taatgaagtg gaaccgtgag cgcaggcgcc tacaaatcga ggacttcgag gctcgcatcg 420cgctgttgcc actgttacag gcagaaaccg accggaggac cttgcagatg cttcgggaga 480acctggagga ggaggccatc atcatgaagg acgtgcccga ctggaaggtg ggggagtctg 540tgttccacac aacccgctgg gtgcccccct tgatcgggga gctgtacggg ctgcgcacca 600cagaggaggc tctccatgcc agccacggct tcatgtggta cacgtaggcc ctgtgccctc 660cggccacctg gatccctgcc cctccccact gggacggaat aaatgctctg cagacctgaa 720aaaaaaaaaa aa 732<210>430<211>2843<212>DNA<213>智人(Homo sapiens)<400>430gcgggcccag gaggcggcgg cggcggcggc ggacgggccc cccgcggcag acggcgagga 60cggacaggac ccgcacagca agcacctgta cacggccgac atgttcacgc acgggatcca 120gagcgccgcg cacttcgtca tgttcttcgc gccctggtgt ggacactgcc agcggctgca 180gccgacttgg aatgacctgg gagacaaata caacagcatg gaagatgcca aagtctatgt 240ggctaaagtg gactgcacgg cccactccga cgtgtgctcc gcccaggggg tgcgaggata 300ccccacctta aagcttttca agccaggcca agaagctgtg aagtaccagg gtcctcggga 360cttccagaca ctggaaaact ggatgctgca gacactgaac gaggagccag tgacaccaga 420gccggaagtg gaaccgccca gtgcccccga gctcaagcaa gggctgtatg agctctcagc 480aagcaacttt gagctgcacg ttgcacaagg cgaccacttt atcaagttct tcgctccgtg 540gtgtggtcac tgcaaagccc tggctccaac ctgggagcag ctggctctgg gccttgaaca 600ttccgaaact gtcaagattg gcaaggttga ttgtacacag cactatgaac tctgctccgg 660aaaccaggtt cgtggctatc ccactcttct ctggttccga gatgggaaaa aggtggatca 720gtacaaggga aagcgggatt tggagtcact gagggagtac gtggagtcgc agctgcagcg 780cacagagact ggagcgacgg agaccgtcac gccctcagag gccccggtgc tggcagctga 840gcccgaggct gacaagggca ctgtgttggc actcactgaa aatactttcg atgacaccat 900tgcagaagga ataaccttca tcaagtttta tgctccatgg tgtggtcatt gtaagactct 960ggctcctact tgggaggaac tctctaaaaa ggaattccct ggtctggcgg gggtcaagat 1020cgccgaagta gactgcactg ctgaacggaa tatctgcagc aagtattcgg tacgaggcta 1080ccccacgtta ttgcttttcc gaggagggaa gaaagtcagt gagcacagtg gaggcagaga 1140ccttgactcg ttacaccgct ttgtcctgag ccaagcgaaa gacgaacttt aggaacacag 1200ttggaggtca cctctcctgc ccagctcccg caccctgcgt ttaggagttc agtcccacag 1260aggccactgg gttcccagtg gtggctgttc agaaagcaga acatactaag cgtgaggtat 1320cttctttgtg tgtgtgtttt ccaagccaac acactctaca gattctttat taagttaagt 1380ttctctaagt aaatgtgtaa ctcatggtca ctgtgtaaac attttcagtg gcgatatatc 1440ccctttgacc ttctcttgat gaaatttaca tggtttcctt tgagactaaa atagcgttga 1500gggaaatgaa attgctggac tatttgtggc tcctgagttg agtgattttg gtgaaagaaa 1560gcacatccaa agcatagttt acctgcccac gagttctgga aaggtggcct tgtggcagta 1620ttgacgttcc tctgatctta aggtcacagt tgactcaata ctgtgttggt ccgtagcatg 1680gagcagattg aaatgcaaaa acccacacct ctggaagata ccttcacggc cgctgctgga 1740gcttctgttg ctgtgaatac ttctctcagt gtgagaggtt agccgtgatg aaagcagcgt 1800tacttctgac cgtgcctgag taagagaatg ctgatgccat aactttatgt gtcgatactt 1860gtcaaatcag ttactgttca ggggatcctt ctgtttctca cggggtgaaa catgtcttta 1920gttcctcatg ttaacacgaa gccagagccc acatgaactg ttggatgtct tccttagaaa 1980gggtaggcat ggaaaattcc acgaggctca ttctcagtat ctcattaact cattgaaaga 2040ttccagttgt atttgtcacc tggggtgaca agaccagaca ggctttccca ggcctgggta 2100tccagggagg ctctgcagcc ctgctgaagg gccctaacta gagttctaga gtttctgatt 2160ctgtttctca gtagtccttt tagaggcttg ctatacttgg tctgcttcaa ggaggtcgac 2220cttctaatgt atgaagaatg ggatgcattt gatctcaaga ccaaagacag atgtcagtgg 2280gctgctctgg ccctggtgtg cacggctgtg gcagctgttg atgccagtgt cctctaactc 2340atgctgtcct tgtgattaaa cacctctatc tcccttggga ataagcacat acaggcttaa 2400gctctaagat agataggtgt ttgtcctttt accatcgagc tacttcccat aataaccact 2460ttgcatccaa cactcttcac ccacctccca tacgcaaggg gatgtggata cttggcccaa 2520agtaactggt ggtaggaatc ttagaaacaa gaccacttat actgtctgtc tgaggcagaa 2580gataacagca gcatctcgac cagcctctgc cttaaaggaa atctttatta atcacgtatg 2640gttcacagat aattcttttt ttaaaaaaac ccaacctcct agagaagcac aactgtcaag 2700agtcttgtac acacaacttc agctttgcat cacgagtctt gtattccaag aaaatcaaag 2760tggtacaatt tgtttgttta cactatgata ctttctaaat aaactctttt ttttaaaaaa 2820aaaaaaaaaa aaaaaaactc gag 2843<210>431<211>640<212>DNA<213>智人(Homo sapiens)<400>431ggtaacgtta tagtatttgt cagaagttgg ggtctccgtg ggcattgtga tccgtcccag 60gcagtggatt aggaggccag aaggagatcc cttccacggt gctaggctga gatggatcct 120ctcagggccc aacagctggc tgcggagctg gaggtggaga tgatggccga tatgtacaac 180agaatgacca gtgcctgcca ccggaagtgt gtgcctcctc actacaagga agcagagctc 240tccaagggcg agtctgtgtg cctggaccga tgtgtctcta agtacctgga catccatgag 300cggatgggca aaaagttgac agagttgtct atgcaggatg aagagctgat gaagagggtg 360cagcagagct ctgggcctgc atgaggtccc tgtcagtata caccctgggg tgtaccccac 420cccttcccac tttaataaac gtgctccctg ttgggtgtca tctgtgaaga ctgccaggcc 480taggctctct gtagagagtc ttcaagatcc cggagtggta gcgctgtctc ctggtgaagg 540agtatttgtc acactggaat gtgactgtgt gtgtatgtat gtgtatatat atatatatat 600atatatataa acaagtttgt tgacacctac aaaaaaaaaa640<210>432<21l>2068<212>DNA<213>智人(Homo sapiens)<400>432cctcagaagt ccgtgccagt gaccggaggc ggcggcggcg agcggttcct tgtgggctag 60aagaatcctg caaaaatgtc tctctatcca tctctcgaag acttgaaggt agacaaagta 120attcaggctc aaactgcttt ttctgcaaac cctgccaatc cagcaatttt gtcagaagct 180tctgctccta tccctcacga tggaaatctc tatcccagac tgtatccaga gctctctcaa 240tacatggggc tgagtttaaa tgaagaagaa atacgtgcaa atgtggccgt ggtttctggt 300gcaccacttc aggggcagtt ggtagcaaga ccttccagta taaactatat ggtggctcct 360gtaactggta atgatgttgg aattcgtaga gcagaaatta agcaagggat tcgtgaagtc 420attttgtgta aggatcaaga tggaaaaatt ggactcaggc ttaaatcaat agataatggt 480atatttgttc agctagtcca ggctaattct ccagcctcat tggttggtct gagatttggg 540gaccaagtac ttcagatcaa tggtgaaaac tgtgcaggat ggagctctga taaagcgcac 600aaggtgctca aacaggcttt tggagagaag attaccatga ccattcgtga caggcccttt 660gaacggacga ttaccatgca taaggatagc actggacatg ttggttttat ctttaaaaat 720ggaaaaataa catccatagt gaaagatagc tctgcagcca gaaatggtct tctcacggaa 780cataacatct gtgaaatcaa tggacagaat gtcattggat tgaaggactc tcaaattgca 840gacatactgt caacatctgg gactgtagtt actattacaa tcatgcctgc ttttatcttt 900gaacatatta ttaagcggat ggcaccaagc attatgaaaa gcctaatgga ccacaccatt 960cctgaggttt aaaattcacg gcaccatgga aatgtagctg aacgtctcca gtttccttct 1020ttggcaactt ctgtattatg cacgtgaagc cttcccggag ccagcgagca tatgctgcat 1080gaggaccttt ctatcttaca ttatggctgg gaatcttact ctttcatctg ataccttgtt 1140cagatttcaa aatagttgta gccttatcct ggttttacag atgtgaaact ttcaagagat 1200ttactgactt tcctagaata gtttctctac tggaaacctg atgcttttat aagccattgt 1260gattaggatg actgttacag gcttagcttt gtgtgaaaac cagtcacctt tctcctaggt 1320aatgagtagt gctgttcata ttactttagt tctatagcat actgcatctt taacatgcta 1380tcatagtaca tttagaatga ttgcctttga tttttttttt aaattctgtg tgtgtgtgtg 1440taaaatgcca attaagaaca ctggtttcat tccatgtaag cattaaacag tgtatgtagg 1500tttcaagaga ttgtgatgat tcttaaattt taactacctt cacttaatat gcttgaactg 1560tcgccttaac tatgttaagc atctagacta aaagccaaaa tataattatt gctgcctttc 1620taaaaaccca aaatgtagtt ctctattaac ctgaaatgta cactagccca gaacagttta 1680atggtactta ctgagctata gcatagctgc ttagttgttt ttgagagttt ttagtcaaca 1740cataatggaa acttctttct tctaaaagtt gccagtgcca cttttaagaa gtgaatcact 1800atatgtgatg taaaagttat tacactaaac aggataaact tttgactccc cttttgttca 1860tttgtggatt aagtggtata atacttaatt ttggcatttg actcttaaga ttatgtaacc 1920tagctacttt gggatggtct tagaatattt ttctgataac ttgttccttt tcctgactcc 1980tccttgcaaa caaaatgata gttgacactt tatcctgatt tttttcttct ttttggttta 2040tgtctattct aattaaatat gtataaat 2068<210>433<211>1723<212>DNA<213>智人(Homo sapiens)<400>433tttctttgtt aagtcgttcc ctctacaaag gacttcctag tgggtgtgaa aggcagcggt 60ggccacagag gcggcggaga gatggccttc agcggttccc aggctcccta cctgagtcca 120gctgtcccct tttctgggac tattcaagga ggtctccagg acggacttca gatcactgtc 180aatgggaccg ttctcagctc cagtggaacc aggtttgctg tgaactttca gactggcttc 240agtggaaatg acattgcctt ccacttcaac cctcggtttg aagatggagg gtacgtggtg 300tgcaacacga ggcagaacgg aagctggggg cccgaggaga ggaagacaca catgcctttc 360cagaagggga tgccctttga cctctgcttc ctggtgcaga gctcagattt caaggtgatg 420gtgaacggga tcctcttcgt gcagtacttc caccgcgtgc ccttccaccg tgtggacacc 480atctccgtca atggctctgt gcagctgtcc tacatcagct tccagaaccc ccgcacagtc 540cctgttcagc ctgcctttcc acggtgccgt tctcccagcc tgtctgtttc ccacccaggc 600ccagggggcg cagacaaaaa cctcccggcg tgtggcctgc caacccggct cccattaccc 660agacagtcat ccacacagtg cagagcgccc ctggacagat gttctctact cccgccatcc 720cacctatgat gtacccccac cccgcctatc cgatgccttt catcaccacc attctgggag 780ggctgtaccc atccaagtcc atcctcctgt caggcactgt cctgcccagt gctcagaggt 840tccacatcaa cctgtgctct gggaaccaca tcgccttcca cctgaacccc cgttttgatg 900agaatgctgt ggtccgcaac acccagatcg acaactcctg ggggtctgag gagcgaagtc 960tgccccgaaa aatgcccttc gtccgtggcc agagcttctc agtgtggatc ttgtgtgaag 1020ctcactgcct caaggtggcc gtggatggtc agcacctgtt tgaatactac catcgcctga 1080ggaacctgcc caccatcaac agactggaag tggggggcga catccagctg acccatgtgc 1140agacataggc ggcttcctgg ccctggggcc gggggctggg gtgtggggca gtctgggtcc 1200tctcatcatc cccacttccc aggcccagcc tttccaaccc tgcctgggat ctgggcttta 1260atgcagaggc catgtccttg tctggtcctg cttctggcta cagccaccct ggaacggaga 1320aggcagctga cggggattgc cttcctcagc cgcagcagca cctggggctc cagctgctgg 1380aatcctacca tcccaggagg caggcacagc cagggagagg ggaggagtgg gcagtgaaga 1440tgaagcccca tgctcagtcc cctcccatcc cccacgcagc tccaccccag tcccaagcca 1500ccagctgtct gctcctggtg ggaggtggcc tcctcagccc ctcctctctg acctttaacc 1560tcactctcac cttgcaccgt gcaccaaccc ttcacccctc ctggaaagca ggcctgatgg 1620cttcccactg gcctccacca cctgaccaga gtgttctctt cagaggactg gctcctttcc 1680cagtgtcctt aaaataaaga aatgaaaatg cttgttggca cat1723<210>434<211>1702<212>PRT<213>智人(Homo sapiens)<400>434Ala Ala Val Leu Gln Ser Cys Thr Ala Phe Ile Glu Arg Tyr Gly Ile5 10 15Val Asp Gly Ile Tyr Arg Leu Ser Gly Val Ala Ser Asn Ile Gln Arg20 25 30Leu Arg His Glu Phe Asp Ser Glu His Val Pro Asp Leu Thr Lys Glu35 40 45Pro Tyr Val Gln Asp Ile His Ser Val Gly Ser Leu Cys Lys Leu Tyr50 55 60Phe Arg Glu Leu Pro Asn Pro Leu Leu Thr Tyr Gln Leu Tyr Glu Lys65 70 75 80Phe Ser Asp Ala Val Ser Ala Ala Thr Asp Glu Glu Arg Leu Ile Lys85 90 95Ile His Asp Val Ile Gln Gln Leu Pro Pro Pro His Tyr Arg Thr Leu100 105 110Glu Phe Leu Met Arg His Leu Ser Leu Leu Ala Asp Tyr Cys Ser Ile115 120 125Thr Asn Met His Ala Lys Asn Leu Ala Ile Val Trp Ala Pro Asn Leu130 135 140Leu Arg Ser Lys Gln Ile Glu Ser Ala Cys Phe Ser Gly Thr Ala Ala145 150 155 160Phe Met Glu Val Arg Ile Gln Ser Val Val Val Glu Phe Ile Leu Asn165 170 175His Val Asp Val Leu Phe Ser Gly Arg Ile Ser Met Ala Met Gln Glu
180 185 190Gly Ala Ala Ser Leu Ser Arg Pro Lys Ser Leu Leu Val Ser Ser Pro195 200 205Ser Thr Lys Leu Leu Thr Leu Glu Glu Ala Gln Ala Arg Thr Gln Ala210 215 220Gln Val Asn Ser Pro Ile Val Thr Glu Asn Lys Tyr Ile Glu Val Gly225 230 235 240Glu Gly Pro Ala Ala Leu Gln Gly Lys Phe His Thr Ile Ile Glu Phe245 250 255Pro Leu Glu Arg Lys Arg Pro Gln Asn Lys Met Lys Lys Ser Pro Val260 265 270Gly Ser Trp Arg Ser Phe Phe Asn Leu Gly Lys Ser Ser Ser Val Ser275 280 285Lys Arg Lys Leu Gln Arg Asn Glu Ser Glu Pro Ser Glu Met Lys Ala290 295 300Met Ala Leu Lys Gly Gly Arg Ala Glu Gly Thr Leu Arg Ser Ala Lys305 310 315 320Ser Glu Glu Ser Leu Thr Ser Leu His Ala Val Asp Gly Asp Ser Lys325 330 335Leu Phe Arg Pro Arg Arg Pro Arg Ser Ser Ser Asp Ala Leu Ser Ala340 345 350Ser Phe Asn Gly Glu Met Leu Gly Asn Arg Cys Asn Ser Tyr Asp Asn355 360 365Leu Pro His Asp Asn Glu Ser Glu Glu Glu Gly Gly Leu Leu His Ile370 375 380Pro Ala Leu Met Ser Pro His Ser Ala Glu Asp Val Asp Leu Ser Pro385 390 395 400Pro Asp Ile Gly Val Ala Ser Leu Asp Phe Asp Pro Met Ser Phe Gln405 410 415Cys Ser Pro Pro Lys Ala Glu Ser Glu Cys Leu Glu Ser Gly Ala Ser420 425 430Phe Leu Asp Ser Pro Gly Tyr Ser Lys Asp Lys Pro Ser Ala Asn Lys435 440 445Lys Asp Ala Glu Thr Gly Ser Ser Gln Cys Gln Thr Pro Gly Ser Thr450 455 460Ala Ser Ser Glu Pro Val Ser Pro Leu Gln Glu Lys Leu Ser Pro Phe465 470 475 480Phe Thr Leu Asp Leu Ser Pro Thr Glu Asp Lys Ser Ser Lys Pro Ser485 490 495Ser Phe Thr Glu Lys Val Val Tyr Ala Phe Ser Pro Lys Ile Gly Arg500 505 510Lys Leu Ser Lys Ser Pro Ser Met Ser Ile Ser Glu Pro Ile Ser Val515 520 525Thr Leu Pro Pro Arg Val Ser Glu Val Ile Gly Thr Val Ser Asn Thr530 535 540Thr Ala Gln Asn Ala Ser Ser Ser Thr Trp Asp Lys Cys Val Glu Glu545 550 555 560Arg Asp Ala Thr Asn Arg Ser Pro Thr Gln Ile Val Lys Met Lys Thr565 570 575Asn Glu Thr Val Ala Gln Glu Ala Tyr Glu Ser Glu Val Gln Pro Leu580 585 590Asp Gln Val Ala Ala Glu Glu Val Glu Leu Pro Gly Lys Glu Asp Gln595 600 605Ser Val Ser Ser Ser Gln Ser Lys Ala Val Ala Ser Gly Gln Thr Gln610 615 620Thr Gly Ala Val Thr His Asp Pro Pro Gln Asp Ser Val Pro Val Ser625 630 635 640Ser Val Ser Leu Ile Pro Pro Pro Pro Pro Pro Lys Asn Val Ala Arg
645 650 655Met Leu Ala Leu Ala Leu Ala Glu Ser Ala Gln Gln Ala Ser Thr Gln660 665 670Ser Leu Lys Arg Pro Gly Thr Ser Gln Ala Gly Tyr Thr Asn Tyr Gly675 680 685Asp Ile Ala Val Ala Thr Thr Glu Asp Asn Leu Ser Ser Ser Tyr Ser690 695 700Ala Val Ala Leu Asp Lys Ala Tyr Phe Gln Thr Asp Arg Pro Ala Glu705 710 715 720Gln Phe His Leu Gln Asn Asn Ala Pro Gly Asn Cys Asp His Pro Leu725 730 735Pro Glu Thr Thr Ala Thr Gly Asp Pro Thr His Ser Asn Thr Thr Glu740 745 750Ser Gly Glu Gln His His Gln Val Asp Leu Thr Gly Asn Gln Pro His755 760 765Gln Ala Tyr Leu Ser Gly Asp Pro Glu Lys Ala Arg Ile Thr Ser Val770 775 780Pro Leu Asp Ser Glu Lys Ser Asp Asp His Val Ser Phe Pro Glu Asp785 790 795 800Gln Ser Gly Lys Asn Ser Met Pro Thr Val Ser Phe Leu Asp Gln Asp805 810 815Gln Ser Pro Pro Arg Phe Tyr Ser Gly Asp Gln Pro Pro Ser Tyr Leu820 825 830Gly Ala Ser Val Asp Lys Leu His His Pro Leu Glu Phe Ala Asp Lys835 840 845Ser Pro Thr Pro Pro Asn Leu Pro Ser Asp Lys Ile Tyr Pro Pro Ser850 855 860Gly Ser Pro Glu Glu Asn Thr Ser Thr Ala Thr Met Thr Tyr Met Thr865 870 875 880Thr Thr Pro Ala Thr Ala Gln Met Ser Thr Lys Glu Ala Ser Trp Asp885 890 895Val Ala Glu Gln Pro Thr Thr Ala Asp Phe Ala Ala Ala Thr Leu Gln900 905 910Arg Thr His Arg Thr Asn Arg Pro Leu Pro Pro Pro Pro Ser Gln Arg915 920 925Ser Ala Glu Gln Pro Pro Val Val Gly Gln Val Gln Ala Ala Thr Asn930 935 940Ile Gly Leu Asn Asn Ser His Lys Val Gln Gly Val Val Pro Val Pro945 950 955 960Glu Arg Pro Pro Glu Pro Arg Ala Met Asp Asp Pro Ala Ser Ala Phe965 970 975Ile Ser Asp Ser Gly Ala Ala Ala Ala Gln Cys Pro Met Ala Thr Ala980 985 990Val Gln Pro Gly Leu Pro Glu Lys Val Arg Asp Gly Ala Arg Val Pro995 10001005Leu Leu His Leu Arg Ala Glu Ser Val Pro Ala His Pro Cys Gly Phe101010151020Pro Ala Pro Leu Pro Pro Thr Arg Met Met Glu Ser Lys Met Ile Ala1025103010351040Ala Ile His Ser Ser Ser Ala Asp Ala Thr Ser Ser Ser Asn Tyr His104510501055Ser Phe Val Thr Ala Ser Ser Thr Ser Val Asp Asp Ala Leu Pro Leu106010651070Pro Leu Pro Val Pro Gln Pro Lys His Ala Ser Gln Lys Thr Val Tyr107510801085Ser Ser Phe Ala Arg Pro Asp Val Thr Thr Glu Pro Phe Gly Pro Asp109010951100Asn Cys Leu His Phe Asn Met Thr Pro Asn Cys Gln Tyr Arg Pro Gln1105111011151120Ser Val Pro Pro His His Asn Lys Leu Glu Gln His Gln Val Tyr Gly112511301135Ala Arg Ser Glu Pro Pro Ala Ser Met Gly Leu Arg Tyr Asn Thr Tyr114011451150Val Ala Pro Gly Arg Asn Ala Ser Gly His His Ser Lys Pro Cys Ser115511601165Arg Val Glu Tyr Val Ser Ser Leu Ser Ser Ser Val Arg Asn Thr Cys117011751180Tyr Pro Glu Asp Ile Pro Pro Tyr Pro Thr Ile Arg Arg Val Gln Ser1185119011951200Leu His Ala Pro Pro Ser Ser Met Ile Arg Ser Val Pro Ile Ser Arg120512101215Thr Glu Val Pro Pro Asp Asp Glu Pro Ala Tyr Cys Pro Arg Pro Leu122012251230Tyr Gln Tyr Lys Pro Tyr Gln Ser Ser Gln Ala Arg Ser Asp Tyr His123512401245Val Thr Gln Leu Gln Pro Tyr Phe Glu Asn Gly Arg Val His Tyr Arg125012551260Tyr Ser Pro Tyr Ser Ser Ser Ser Ser Ser Tyr Tyr Ser Pro Asp Gly1265127012751280Ala Leu Cys Asp Val Asp Ala Tyr Gly Thr Val Gln Leu Arg Pro Leu128512901295His Arg Leu Pro Asn Arg Asp Phe Ala Phe Tyr Asn Pro Arg Leu Gln130013051310Gly Lys Ser Leu Tyr Ser Tyr Ala Gly Leu Ala Pro Arg Pro Arg Ala131513201325Asn Val Thr Gly Tyr Phe Ser Pro Asn Asp His Asn Val Val Ser Met133013351340Pro Pro Ala Ala Asp Val Lys His Thr Tyr Thr Ser Trp Asp Leu Glu1345135013551360Asp Met Glu Lys Tyr Arg Met Gln Ser Ile Arg Arg Glu Ser Arg Ala136513701375Arg Gln Lys Val Lys Gly Pro Val Met Ser Gln Tyr Asp Asn Met Thr138013851390Pro Ala Val Gln Asp Asp Leu Gly Gly Ile Tyr Val Ile His Leu Arg139514001405Ser Lys Ser Asp Pro Gly Lys Thr Gly Leu Leu Ser Val Ala Glu Gly141014151420Lys Glu Ser Arg His Ala Ala Lys Ala Ile Ser Pro Glu Gly Glu Asp1425143014351440Arg Phe Tyr Arg Arg His Pro Glu Ala Glu Met Asp Arg Ala His His144514501455His Gly Gly His Gly Ser Thr Gln Pro Glu Lys Pro Ser Leu Pro Gln146014651470Lys Gln Ser Ser Leu Arg Ser Arg Lys Leu Pro Asp Met Gly Cys Ser147514801485Leu Pro Glu His Arg Ala His Gln Glu Ala Ser His Arg Gln Phe Cys149014951500Glu Ser Lys Asn Gly Pro Pro Tyr Pro Gln Gly Ala Gly Gln Leu Asp1505151015151520Tyr Gly Ser Lys Gly Ile Pro Asp Thr Ser Glu Pro Val Ser Tyr His152515301535Asn Ser Gly Val Lys Tyr Ala Ala Ser Gly Gln Glu Ser Leu Arg Leu154015451550Asn His Lys Glu Val Arg Leu Ser Lys Glu Met Glu Arg Pro Trp Val155515601565Arg Gln Pro Ser Ala Pro Glu Lys His Ser Arg Asp Cys Tyr Lys Glu
157015751580Glu Glu His Leu Thr Gln Ser Ile Val Pro Pro Pro Lys Pro Glu Arg1585159015951600Ser His Ser Leu Lys Leu His His Thr Gln Asn Val Glu Arg Asp Pro160516101615Ser Val Leu Tyr Gln Tyr Gln Pro His Gly Lys Arg Gln Ser Ser Val162016251630Thr Val Val Ser Gln Tyr Asp Asn Leu Glu Asp Tyr His Ser Leu Pro163516401645Gln His Gln Arg Gly Val Phe Gly Gly Gly Gly Met Gly Thr Tyr Val165016551660Pro Pro Gly Phe Pro His Pro Gln Ser Arg Thr Tyr Ala Thr Ala Leu1665167016751680Gly Gln Gly Ala Phe Leu Pro Ala Glu Leu Ser Leu Gln His Pro Glu168516901695Thr Gln Ile His Ala Glu1700<210>435<211>160<212>PRT<213>智人(Homo sapiens)<400>435Pro Phe Gln Gln Val Gly Arg Cys Asn Pro Ser Pro Gln Thr Arg Pro5 10 15Gly Pro Ala Ser Lys Val Lys Gln Asp Met Pro Pro Pro Gly Gly Tyr20 25 30Gly Pro Ile Asp Tyr Lys Arg Asn Leu Pro Arg Arg Gly Leu Ser Gly35 40 45Tyr Ser Met Leu Ala Ile Gly Ile Gly Thr Leu Ile Tyr Gly His Trp50 55 60Ser Ile Met Lys Trp Asn Arg Glu Arg Arg Arg Leu Gln Ile Glu Asp65 70 75 80Phe Glu Ala Arg Ile Ala Leu Leu Pro Leu Leu Gln Ala Glu Thr Asp85 90 95Arg Arg Thr Leu Gln Met Leu Arg Glu Asn Leu Glu Glu Glu Ala Ile100 105 110Ile Met Lys Asp Val Pro Asp Trp Lys Val Gly Glu Ser Val Phe His115 120 125Thr Thr Arg Trp Val Pro Pro Leu Ile Gly Glu Leu Tyr Gly Leu Arg130 135 140Thr Thr Glu Glu Ala Leu His Ala Ser His Gly Phe Met Trp Tyr Thr145 150 155 160<210>436<211>396<212>PRT<213>智人(Homo sapiens)<400>436Arg Ala Gln Glu Ala Ala Ala Ala Ala Ala Asp Gly Pro Pro Ala Ala5 10 15Asp Gly Glu Asp Gly Gln Asp Pro His Ser Lys His Leu Tyr Thr Ala20 25 30Asp Met Phe Thr His Gly Ile Gln Ser Ala Ala His Phe Val Met Phe
35 40 45Phe Ala Pro Trp Cys Gly His Cys Gln Arg Leu Gln Pro Thr Trp Asn50 55 60Asp Leu Gly Asp Lys Tyr Asn Ser Met Glu Asp Ala Lys Val Tyr Val65 70 75 80Ala Lys Val Asp Cys Thr Ala His Ser Asp Val Cys Ser Ala Gln Gly85 90 95Val Arg Gly Tyr Pro Thr Leu Lys Leu Phe Lys Pro Gly Gln Glu Ala100 105 110Val Lys Tyr Gln Gly Pro Arg Asp Phe Gln Thr Leu Glu Asn Trp Met115 120 125Leu Gln Thr Leu Asn Glu Glu Pro Val Thr Pro Glu Pro Glu Val Glu130 135 140Pro Pro Ser Ala Pro Glu Leu Lys Gln Gly Leu Tyr Glu Leu Ser Ala145 150 155 160Ser Asn Phe Glu Leu His Val Ala Gln Gly Asp His Phe Ile Lys Phe165 170 175Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Thr Trp Glu180 185 190Gln Leu Ala Leu Gly Leu Glu His Ser Glu Thr Val Lys Ile Gly Lys195 200 205Val Asp Cys Thr Gln His Tyr Glu Leu Cys Ser Gly Asn Gln Val Arg210 215 220Gly Tyr Pro Thr Leu Leu Trp Phe Arg Asp Gly Lys Lys Val Asp Gln225 230 235 240Tyr Lys Gly Lys Arg Asp Leu Glu Ser Leu Arg Glu Tyr Val Glu Ser245 250 255Gln Leu Gln Arg Thr Glu Thr Gly Ala Thr Glu Thr Val Thr Pro Ser260 265 270Glu Ala Pro Val Leu Ala Ala Glu Pro Glu Ala Asp Lys Gly Thr Val275 280 285Leu Ala Leu Thr Glu Asn Thr Phe Asp Asp ThrIle Ala Glu Gly Ile290 295 300Thr Phe Ile Lys Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Thr Leu305 310 315 320Ala Pro Thr Trp Glu Glu Leu Ser Lys Lys Glu Phe Pro Gly Leu Ala325 330 335Gly Val Lys Ile Ala Glu Val Asp Cys Thr Ala Glu Arg Asn Ile Cys340 345 350Ser Lys Tyr Ser Val Arg Gly Tyr Pro Thr Leu Leu Leu Phe Arg Gly355 360 365Gly Lys Lys Val Ser Glu His Ser Gly Gly Arg Asp Leu Asp Ser Leu370 375 380His Arg Phe Val Leu Ser Gln Ala Lys Asp Glu Leu385 390 395<210>437<211>92<212>PRT<213>智人(Homo sapiens)<400>437Ala Glu Met Asp Pro Leu Arg Ala Gln Gln Leu Ala Ala Glu Leu Glu5 10 15Val Glu Met Met Ala Asp Met Tyr Asn Arg Met Thr Ser Ala Cys His20 25 30Arg Lys Cys Val Pro Pro His Tyr Lys Glu Ala Glu Leu Ser Lys Gly
35 40 45Glu Ser Val Cys Leu Asp Arg Cys Val Ser Lys Tyr Leu Asp Ile His50 55 60Glu Arg Met Gly Lys Lys Leu Thr Glu Leu Ser Met Gln Asp Glu Glu65 70 75 80Leu Met Lys Arg Val Gln Gln Ser Ser Gly ProAla85 90<210>438<211>303<212>PRT<213>智人(Homo sapiens)<400>438Lys Asn Pro Ala Lys Met Ser Leu Tyr Pro Ser Leu Glu Asp Leu Lys5 10 15Val Asp Lys Val Ile Gln Ala Gln Thr Ala Phe Ser Ala Asn Pro Ala20 25 30Asn Pro Ala Ile Leu Ser Glu Ala Ser Ala Pro Ile Pro His Asp Gly35 40 45Asn Leu Tyr Pro Arg Leu Tyr Pro Glu Leu Ser Gln Tyr Met Gly Leu50 55 60Ser Leu Asn Glu Glu Glu Ile Arg Ala Asn Val Ala Val Val Ser Gly65 70 75 80Ala Pro Leu Gln Gly Gln Leu Val Ala Arg Pro Ser Ser Ile Asn Tyr85 90 95Met Val Ala Pro Val Thr Gly Asn Asp Val Gly Ile Arg Arg Ala Glu100 105 110Ile Lys Gln Gly Ile Arg Glu Val Ile Leu Cys Lys Asp Gln Asp Gly115 120 125Lys Ile Gly Leu Arg Leu Lys Ser Ile Asp Asn Gly Ile Phe Val Gln130 135 140Leu Val Gln Ala Asn Ser Pro Ala Ser Leu Val Gly Leu Arg Phe Gly145 150 155 160Asp Gln Val Leu Gln Ile Asn Gly Glu Asn Cys Ala Gly Trp Ser Ser165 170 175Asp Lys Ala His Lys Val Leu Lys Gln Ala Phe Gly Glu Lys Ile Thr180 185 190Met Thr Ile Arg Asp Arg Pro Phe Glu Arg Thr Ile Thr Met His Lys195 200 205Asp Ser Thr Gly His Val Gly Phe Ile Phe Lys Asn Gly Lys Ile Thr210 215 220Ser Ile Val Lys Asp Ser Ser Ala Ala Arg Asn Gly Leu Leu Thr Glu225 230 235 240His Asn Ile Cys Glu Ile Asn Gly Gln Asn Val Ile Gly Leu Lys Asp245 250 255Ser Gln Ile Ala Asp Ile Leu Ser Thr Ser Gly Thr Val Val Thr Ile260 265 270Thr Ile Met Pro Ala Phe Ile Phe Glu His Ile Ile Lys Arg Met Ala275 280 285Pro Ser Ile Met Lys Ser Leu Met Asp His Thr Ile Pro Glu Val290 295 300<210>439<211>378<212>PRT<213>智人(Homo sapiens)<400>439Val Val Pro Ser Thr Lys Asp Phe Leu Val Gly Val Lys Gly Ser Gly5 10 15Gly His Arg Gly Gly Gly Glu Met Ala Phe Ser Gly Ser Gln Ala Pro20 25 30Tyr Leu Ser Pro Ala Val Pro Phe Ser Gly Thr Ile Gln Gly Gly Leu35 40 45Gln Asp Gly Leu Gln Ile Thr Val Asn Gly Thr Val Leu Ser Ser Ser50 55 60Gly Thr Arg Phe Ala Val Asn Phe Gln Thr Gly Phe Ser Gly Asn Asp65 70 75 80Ile Ala Phe His Phe Asn Pro Arg Phe Glu Asp Gly Gly Tyr Val Val85 90 95Cys Asn Thr Arg Gln Asn Gly Ser Trp Gly Pro Glu Glu Arg Lys Thr100 105 110His Met Pro Phe Gln Lys Gly Met Pro Phe Asp Leu Cys Phe Leu Val115 120 125Gln Ser Ser Asp Phe Lys Val Met Val Asn Gly Ile Leu Phe Val Gln130 135 140Tyr Phe His Arg Val Pro Phe His Arg Val Asp Thr Ile Ser Val Asn145 150 155 160Gly Ser Val Gln Leu Ser Tyr Ile Ser Phe Gln Asn Pro Arg Thr Val165 170 175Pro Val Gln Pro Ala Phe Ser Thr Val Pro Phe Ser Gln Pro Val Cys180 185 190Phe Pro Pro Arg Pro Arg Gly Arg Arg Gln Lys Pro Pro Gly Val Trp195 200 205Pro Ala Asn Pro Ala Pro Ile Thr Gln Thr Val Ile His Thr Val Gln210 215 220Ser Ala Pro Gly Gln Met Phe Ser Thr Pro Ala Ile Pro Pro Met Met225 230 235 240Tyr Pro His Pro Ala Tyr Pro Met Pro Phe Ile Thr Thr Ile Leu Gly245 250 255Gly Leu Tyr Pro Ser Lys Ser Ile Leu Leu Ser Gly Thr Val Leu Pro260 265 270Ser Ala Gln Arg Phe His Ile Asn Leu Cys Ser Gly Asn His Ile Ala275 280 285Phe His Leu Asn Pro Arg Phe Asp Glu Asn Ala Val Val Arg Asn Thr290 295 300Gln Ile Asp Asn Ser Trp Gly Ser Glu Glu Arg Ser Leu Pro Arg Lys305 310 315 320Met Pro Phe Val Arg Gly Gln Ser Phe Ser Val Trp Ile Leu Cys Glu325 330 335Ala His Cys Leu Lys Val Ala Val Asp Gly Gln His Leu Phe Glu Tyr340 345 350Tyr His Arg Leu Arg Asn Leu Pro Thr Ile Asn Arg Leu Glu Val Gly355 360 365Gly Asp Ile Gln Leu Thr His Val Gln Thr370 375<210>440<211>2239<212>DNA<213>智人(Homo sapiens)<400>440ggaggttgaa gtgagcagag atcatgccag cctgggtgac agtgagactc tgtctcaaac 60agaattaagg aaaaaagaaa gaaagaaaaa gagagagagg aaattccagg ccaattgtgg 120catagatttt atcatattct ggattttttg gattcttttg ttttctcatc actggattca 180ggaaagcctg ttgtgtccac catctccaaa ggaggttacc tgcagggaaa tgttaacggg 240aggctgcctt ccctgggcaa caaggagcca cctgggcagg acgccttttc aggaagagac 300gccttttcag gaagagacgc cttttcagga agagagaaag tgcagctgaa gaggaaagtc 360actttactga ggggagtctc cattatcatt ggcaccatca ttggagcagg aatcttcatc 420tctcctaagg gcgtgctcca gaacacgggc agcgtgggca tgtctctgac catctggacg 480gtgtgtgggg tcctgtcact atttggagct ttgtcttatg ctgaattggg aacaactata 540aagaaatctg gaggtcatta cacatatatt ttggaagtct ttggtccatt accagctttt 600gtacgagtct gggtggaact cctcataata cgccctgcag ctactgctgt gatatccctg 660gcatttggac gctacattct ggaaccattt tttattcaat gtgaaatccc tgaacttgcg 720atcaagctca ttacagctgt gggcataact gtagtgatgg tcctaaatag catgagtgtc 780agctggagcg cccggatcca gattttctta accttttgca agctcacagc aattct gata 840attatagtcc ctggagttat gcagctaatt aaaggtcaaa cgcagaactt taaagacgcc 900ttttcaggaa gagattcaag tattacgcgg ttgccactgg ctttttatta tggaatgtat 960gcatatgctg gctggtttta cctcaacttt gttactgaag aagtagaaaa ccctgaaaaa 1020accattcccc ttgcaatatg tatatccatg gccattgtca ccattggcta tgtgctgaca 1080aatgtggcct actttacgac cattaatgct gaggagctgc tgctttcaaa tgcagtggca 1140gtgacctttt ctgagcggct actgggaaat ttctcattag cagttccgat ctttgttgcc 1200ctctcctgct ttggctccat gaacggtggt gtgtttgctg tctccaggtt attctatgtt 1260gcgtctcgag agggtcacct tccagaaatc ctctccatga ttcatgtccg caagcacact 1320cctctaccag ctgttattgt tttgcaccct ttgacaatga taatgctctt ctctggagac 1380ctcgacagtc ttttgaattt cctcagtttt gccaggtggc tttttattgg gctggcagtt 1440gctgggctga tttatcttcg atacaaatgc ccagatatgc atcgtccttt caaggtgcca 1500ctgttcatcc cagctttgtt ttccttcaca tgcctcttca tggttgccct ttccctctat 1560tcggacccat ttagtacagg gattggcttc gtcatcactc tgactggagt ccctgcgtat 1620tatctcttta ttatatggga caagaaaccc aggtggttta gaataatgtc agagaaaata 1680accagaacat tacaaataat actggaagtt gtaccagaag aagataagtt atgaactaat 1740ggacttgaga tcttggcaat ctgcccaagg ggagacacaa aatagggatt tttacttcat 1800tttctgaaag tctagagaat tacaactttg gtgataaaca aaaggagtca gttattttta 1860ttcatatatt ttagcatatt cgaactaatt tctaagaaat ttagttataa ctctatgtag 1920ttatagaaag tgaatatgca gttattctat gagtcgcaca attcttgagt ctctgatacc 1980tacctattgg ggttaggaga aaagactaga caattactat gtggtcattc tctacaacat 2040atgttagcac ggcaaagaac cttcaaattg aagactgaga tttttctgta tatatgggtt 2100ttgtaaagat ggttttacac actacagatg tctatactgt gaaaagtgtt ttcaattctg 2160aaaaaaagca tacatcatga ttatggcaaa gaggagagaa ggtagagctg ttcttaaatt 2220tattaaaaaa aaaaaaaaa 2239<210>441<211>5981<212>DNA<213>智人(Homo sapiens)<400>441aggttgaagt gagcagagat catgccagcc tgggtgacag tgagactctg tctcaaacag 60aattaaggaa aaaagaaaga aagaaaaaga gagagaggaa attccaggcc aattgtggca 120tagattttat catattctgg attttttgga ttcttttgtt ttctcatcac tggattcagg 180aaagcctgtt gtgtccacca tctccaaagg aggttacctg cagggaaatg ttaacgggag 240gctgccttcc ctgggcaaca aggagccacc tgggcaggag aaagtgcagc tgaagaggaa 300agtcacttta ctgaggggag tctccattat cattggcacc atcattggag caggaatctt 360catctctcct aagggcgtgc tccagaacac gggcagcgtg ggcatgtctc tgaccatctg 420gacggtgtgt ggggtcctgt cactatttgg agctttgtct tatgctgaat tgggaacaac 480tataaagaaa tctggaggtc attacacata tattttggaa gtctttggtc cattaccagc 540ttttgtacga gtctgggtgg aactcctcat aatacgccct gcagctactg ctgtgatatc 600cctggcattt ggacgctaca ttctggaacc attttttatt caatgtgaaa tccctgaact 660tgcgatcaag ctcattacag ctgtgggcat aactgtagtg atggtcctaa atagcatgag 720tgtcagctgg agcgcccgga tccagatttt cttaaccttt tgcaagctca cagcaattct 780gataattata gtccctggag ttatgcagct aattaaaggt caaacgcaga actttaaaga 840cgccttttca ggaagagatt caagtattac gcggttgcca ctggcttttt attatggaat 900gtatgcatat gctggctggt tttacctcaa ctttgttact gaagaagtag aaaaccctga 960aaaaaccatt ccccttgcaa tatgtatatc catggccatt gtcaccattg gctatgtgct 1020gacaaatgtg gcctacttta cgaccattaa tgctgaggag ctgctgcttt caaatgcagt 1080ggcagtgacc ttttctgagc ggctactggg aaatttctca ttagcagttc cgatctttgt 1140tgccctctcc tgctttggct ccatgaacgg tggtgtgttt gctgtctcca ggttattcta 1200tgttgcgtct cgagagggtc accttccaga aatcctctcc atgattcatg tccgcaagca 1260cactcctcta ccagctgtta ttgttttgca ccctttgaca atgataatgc tcttctctgg 1320agacctcgac agtcttttga atttcctcag ttttgccagg tggcttttta ttgggctggc 1380agttgctggg ctgatttatc ttcgatacaa atgcccagat atgcatcgtc ctttcaaggt 1440gccactgttc atcccagctt tgttttcctt cacatgcctc ttcatggttg ccctttccct 1500ctattcggac ccatttagta cagggattgg cttcgtcatc actctgactg gagtccctgc 1560gtattatctc tttattatat gggacaagaa acccaggtgg tttagaataa tgtcagagaa 1620aataaccaga acattacaaa taatactgga agttgtacca gaagaagata agttatgaac 1680taatggactt gagatcttgg caatctgccc aaggggagac acaaaatagg gatttttact 1740tcattttctg aaagtctaga gaattacaac tttggtgata aacaaaagga gtcagttatt 1800tttattcata tattttagca tattcgaact aatttctaag aaatttagtt ataactctat 1860gtagttatag aaagtgaata tgcagttatt ctatgagtcg cacaattctt gagtctctga 1920tacctaccta ttggggttag gagaaaagac tagacaatta ctatgtggtc attctctaca 1980acatatgtta gcacggcaaa gaaccttcaa attgaagact gagatttttc tgtatatatg 2040ggttttgtaa agatggtttt acacactaca gatgtctata ctgtgaaaag tgttttcaat 2100tctgaaaaaa agcatacatc atgattatgg caaagaggag agaaagaaat ttattttaca 2160ttgacattgc attgcttccc cttagatacc aatttagata acaaacactc atgctttaat 2220ggattatacc cagagcactt tgaacaaagg tcagtgggga ttgttgaata cattaaagaa 2280gagtttctag gggctactgt ttatgagaca catccaggag ttatgtttaa gtaaaaatcc 2340ttgagaattt attatgtcag atgttttttc attcattatc aggaagtttt agttatctgt 2400catttttttt tttcacatca gtttgatcag gaaagtgtat aacacatctt agagcaagag 2460ttagtttggt attaaatcct cattagaaca accacctgtt tcactaataa cttacccctg 2520atgagtctat ctaaacatat gcattttaag ccttcaaatt acattatcaa catgagagaa 2580atcaccaaca aagaagatgt tcaaaataat agtcccatat ctgtaatcat atctacatgc 2640aatgttagta attctgaagt tttttaaatt tatggctatt tttacacgat gatgaatttt 2700gacagtttgt gcattttctt tatacatttt atattcttct gttaaaatat ctcttcagat 2760gaaactgtcc agattaatta ggaaaaggca tatattaaca taaaaattgc aaaagaaatg 2820tcgctgtaaa taagatttac aactgatgtt tctagaaaat ttccacttct atatctaggc 2880tttgtcagta atttccacac acacacacac tttttatata tatatatata tatatatata 2940tagtggaact tacaaatgag agtaatataa tgatgaaatt ttgaactgtt atttataaac 3000atctaaggta aaatggttag tcatggccag agtatgtttc atcctttaat ttttgtccat 3060ttgaaaataa ggatttttga aagaattata ccaattaaaa ttattaaagg caaacataga 3120attcataaaa aattgtccaa agtagaaatg atgacctata atttggagca tttccaattc 3180agtaatttca attttgctct tgaaaacatt taatatatat ccaagactga catttcttta 3240gctgaaccta acgtttgggt ctctgagtga atttataata actccttcct tccttagcat 3300agggttttca aaatttgatt tataattcct atttccagta aatattgttc atttgtccac 3360atctctccct atgatatgtt gctggaggta agaatttctt tcatattcct attttttttt 3420tccccataga ctaggctcat agaatttaaa caagcaaatt ttcctgagct ttttcttgcc 3480aaatgaaaga agactggtaa attctcatag agaggtttgt gtagttcttg gctcttcctg 3540gggttaatgt gcttatattc acagtggcaa attggtctca gactttaatt tatttatttt 3600tgatttgaat ttctctttaa aagtatcaat ttaaaaggta actagaatta ttctttctca 3660ttttcaaaag tgatttttgc attattaaat ttccctgcca ttgtaatgcc atttcacgca 3720gaaaaaaagt cagccagtaa ttaagaaaaa aagtgatgga gattaagtag tattttggct 3780tatttttagg actcatcatg agaagacaca gttcctttaa tcaggaaatt aatatccata 3840attttcactc aaaattgcag tatgtaaagc agattctcaa aaactctcct gaacacttat 3900ttatatatat gtttttatat aagtaaaatt tttctcatat ttttatacga tatgcacaca 3960cacacataca tgcacatact acttactaca tgttctgtac ttgtactttg taccatgcat 4020attcaaatgt ttatatacat aagtttatta taacataaac agtaaaagta atgaatactg 4080tttaaaataa ctaatatagt attttttaat ttttgtgggg atggattctc aaatacttgt 4140gattttaaaa gattctaaag ctaaaacaca acttgatttt aaaaagaatg attctcctta 4200cacaattata aatatttgca gtaaatattt tccttataat actgttttga ccccatttaa 4260aaagtattag attatattcc tttgatccaa tgaaaactga accttataaa tggttagctg 4320aaagtagacc ttattcttgt ccttctttag aagagtaaag atttgtccta gggaagatgg 4380ctgacttcgg ttcccaacat gcgtatgcat ttagactgta gctcctcagc cctgtggaca 4440caaaatttgg acagcttatt aggttacgtt agcaatgcat gacggtttct ccaacactaa 4500gatattcacg ttgaaacaga tttcctgttc gtcttatgtg tctggtaaaa ttgtttcccc 4560aattacaatt tgacatatca atagagggtt aacaagagta taattacata acagaattcc 4620tcatgaactg taatcagtct acaggaaaat cattatttta tcttgatttg cagatgaata 4680tactgctaag aaagggagca actctgacct ttgttaaagt tgatcttttg taattgaggt 4740ataaggtatg aaaagataaa aaaccgaagg ccagagaatc aggaaatgaa agatagtatg 4800gactgaaggt aacaatattt taatgttatg caatatagcc agagaaatat taaaaattag 4860ttgtttgctg tgcataggtg gatctcgcag gaagctaatg aaacctaagc ttcagtgcct 4920ctcacttaga catgttccat tcgaggtcct gaacctaact ttgtattagg aattctgtac 4980taattttgtt gaagaagacc agcaaagttg tgtacacttc tacccccaca aaatctgcat 5040tgtccatgtg agtaaagtaa aataattcct gttatttttt tctgttagaa ataagtatgg 5100aggatatgtt tttaaaaatt tatgagttaa ttgaaatatc catatataac aagtgacttt 5160ctcacaatat atatgatgtg atatataggg agatagtttc actttcatca tattttatac 5220gttgattctg aactatagaa aaataataaa tgggatttta attatagctc ttagttggga 5280aagaaatata gagagatgtg ggatttgaat gcccatgaaa gacattttat tttacttgaa 5340tatattcttg cttcacttta ccctccataa tatgttgtac attagtgctg atcaagttta 5400cagagttaca ttttgctttc ctaaccattc agtcaggaat taaaatatgg cattgtataa 5460caactgggaa gaagctcata gtggatataa attagagtag ataatgggtc accttgatag 5520cctctgttta cattacttgt atatgggcaa aataattatt acctatacgt gtatttaagc 5580ttaattttca tataaacagt atttttaatc tatgttaaaa tagataatat ctaaaagtgt 5640gatctctagg tagtccttag tttattagta ctgtacttca aaaagatttt taaataggtc 5700cggcacggtg gctcatgcct gtaatcccag cactttggga ggctgaggcg ggcgaatcac 5760ctgaggtcag gagttcgaga tcagcctggc caacatggtg aaaccctgtc tcaactaaaa 5820atataaaaat tagccgggcg tggtggcagg cgcctgtaat cccagctact cgggaggctg 5880aggcaggaga atcacttgaa cccaaggggc agaagctgca gttagccaag atcgcatcat 5940tgcactccag cctaggggac aagagcgcga gacttcatct c 5981<210>442<211>337<212>DNA<213>智人(Homo sapiens)<400>442gatggaggtt gaagtgagca gagatcatgc cagcctgggt gacagtgaga ctctgtctca 60aacagaatta aggaaaaaag aaagaaagaa aaagagagag aggaaattcc aggccaattg 120tggcatagat tttatcatat tctggatttt ttggattctt ttgttttctc atcactggat 180tcaggaaagc ctgttgtgtc caccatctcc aaaggaggtt acctgcaggg aaatgttaac 240gggaggctgc cttccctggg caacaaggag ccacctgggc aggagaaagt gcagctgaag 300aggaaagtca ctttactgag gggagtctcc attatca 337<210>443<211>739<212>DNA<213>智人(Homo sapiens)<400>443gaattcgaac cccttcggat tctaatcaag aaaatgattt gctatgggaa gagaagtttc 60ctgaaagaac aactgttact gaattacctc agacttcaca tgtatcattc tccgagcctg 120atattccgtc ctcaaaaagt actgagttac ctgtggactg gagtattaaa acgcgactcc 180ttttcacctc ttctcaaccc tttacctggg cagatcattt gaaagcacag gaagaagctc 240aaggtcttgt ccagcattgt agggcaacag aagttacttt gcctaaaagt atacaggatc 300ccaaactctc ctctgagctc cgttgtacct tccagcagag ccttatctat tggctccacc 360ctgctttgtc ttggctacca ctgttccctc gtattggagc tgatagaaaa atggctggaa 420agacaagtcc ttggtcaaat gatgcaaccc tgcagcatgt tttaatgagt gactggtctg 480tgagctttac ttctctatat aatttgctga agacaaaact ttgcccctat ttctacgttt 540gtacctatca gtttactgtc ctgttccgag cagcaggatt agctggaagt gacttaatca 600cagctctcat atctccaaca actcgaggtt taagagaagc tatgagaaat gaaggtattg 660aattttctct gcctttaata aaagaaagtg gccataagaa ggagacagca tctggaacaa 720gcttgggata tggggagga 739<210>444<211>738<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(738)<223>n＝A、T、C或G<400>444tttttttttt ttcgttnaaa agaaatttta tttctanant ggaatgattt ggatgtgacc 60tgataaatac agtttgttat tgnggtctca ttaaattaat cagctttttc acactggggt 120aaagaaacag atgatgatac tagggaatgg aaacaaaatt ggaaacctgg gttatttggg 180gatttatatt gtactctgca cagttgccct tttttttagg cgtgttccct ggaaaagagg 240gacggatgaa cctggaagta agtaaaagac attctaggtg tgtagcatca aggcagttaa 300tatccaagca tcagctttct ctttatacat ctacactgca tggcctgcac caaataagga 360actgaaccag gggtatgttt ttacctccac agctgcctcc ttccatcana gcaccttgat 420gaacttaatg tctagtcaca cgtcattggc atgttttctc cccagcattt aattacaaag 480ctttctttct ttggatagga tcagttctta agagcagccc cggtaactgg aggaatggga 540gccgttttga tganaaaaat gggtttggtg ttcaggatct ccaattataa atgtagtctc 600tcagcaccac attccgtaaa gatgatttcc caagtaacggtatttgacta agttgctcca 660gagtgttagg ggcaaaccac agttagtaag ctccttatga acaaccccca tatcaagtac 720tttgtccatt tgcaggca738<210>445<211>716<212>DNA<213>智人(Homo sapiens)<400>445gcggccgcta gtgctccagc tcgcgctccg ccctcaggca cagcatcccc acgggcctcc 60acgccaacct gtccgagggc cgccccgtgg gtccggcccg ccgtggcgcc tcatcgctgc 120tcggcccgga aggcttcttc cttggcaaga tgggattccg ggaggcggtg gcggccggag 180acgtggattt gcctcaggtg cggagccgca gctacaggag gatgctcgcg aggaccccca 240gagctccgcc cggagggtac tgtgaggccg ttaggagctg gcggtggatg acttccgcat 300tcaaacactg gagccatcac acggaagcac gaggagggta tcctcggcag ctactcccgg 360tcgctcaagg tgtctctcgc tcgccctcta ggtgcgggag gagctcgagg cccaactaag 420ctgcttccgg gagctgctgg gcagggcccc cacgcacgcg gacgggcacc agcacgtgca 480cgtgctccca ggtggacaga cgccttcgtg ggcctgagca cttgcggccg gcacatgtcc 540gctcaccgcg tgtccggggc cctggcgcgg gtcctggaag gtaccctagc gggccacacc 600ctgacagccg agctgatggc gcaccccggc taccccagtg tgcctcccac cggcggctgc 660ggtgaaggcc ccgacgcttt ctctttgctc ttgggaagcg gcttgcattg agcttg 716<210>446<211>641<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(641)<223>n＝A、T、C或G<400>446gctncagctc gcgctccgcc ctcaggcaca gcatccccac gggcctccac gccaacctgt 60ccgaggnccg ccccgtgggt ccggcccgcc gtggcgcctc atcgctgctc ggcccggaag 120gcttnttcct tggcaagatg ggattccggg aggcggnggc ggccggagac gtggatttgc 180ctcaggtgcg gagccgcagc tacaggagga tgctcgcgag gacccccaga gctccgcccg 240gagggtactg tgaggccgtt aggagctggc ggnggatgac ttccgcattc aaacactgga 300gccatcacac ggaagcacga ggagggtatc ctcggcagct actcccggtc gctcaaggtg 360tctntcgctc gccctctagg ngcgggagga gctcgaggcc caactaanct gcttccggga 420gctgctgggc agggccccca cgcacgcgga cgggcaccag cacgtgcacg tgctcccagg 480nggacagacg ccttcgtggg cctgancact tgcggccggn acatgttccc tcacccgcgg 540gtccgggccc ttggcgcggg tcctggaagg taccctacgg gccacaccct gacagccgaa 600ctgatggccc accccggcta ccccangtgt gcctccaccc g 641<210>447<211>652<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(652)<223>n＝A、T、C或G<400>447gaattcgaac cccttcgctt ttagaaaatt gtatatgcag ctggatgaag gcagcctcac 60ctttaatgcc aacccagatg agggagtgaa ctactttatg tccaagggta tcctggatga 120ttcgccaaag gaaatagcaa agtttatctt ctgtacaaga acactaaatt ggaaaaaact 180gagaatctat cttgatgaaa ggagagatgt cttggatgac cttgtaacat tgcataattt 240tagaaatcag ttcttgccaa atgcactgag agaatttttt cgtcatatcc atgcccctga 300agagcgtgga gagtatcttg aaactcttat aacaaagttc tcacatagat tctgtgcttg 360caaccctgat ttaatgcgag aacttggcct tagtcctgat gctgtctatg tactgtgcta 420ctctttgatt ctactttcca ttgacctcac tagccctcat gtgaagaata aaatgtcaaa 480aagggaattt attcgaaata ccccgcgcgc tgctcaaaat attagtgaag aattttgtan 540ggcatcttta tgacaatatc tacccttatt gggccatggn ggctggcata aaaaagcacc 600aattggctaa ggactttcaa gttttttact ttcagaactt aaaagcttac cc 652<210>448<211>677<212>DNA<213>智人(Homo sapiens)<400>448gaattcgaac cccttcggcg cctggcagag gtgaaggact ccctggacat cgaggtcaag 60cagaacttca ttgaccccct ccagaacctg tgcgagaaag acctgaagga gatccagcac 120cacctgaaga aactggaggg ccgccgcctg gactttgact acaagaagaa gcggcagggc 180aagatccccg atgaggagct acgccaggcg ctggagaagt tcgaggagtc caaggaggtg 240gcagaaacca gcatgcacaa cctcctggag actgacatcg agcaggtgag tcagctctcg 300gccctggtgg atgcacagct ggactaccac cggcaggccg tgcagatcct ggacgagctg 360gcggagaagc tcaagcgcag gatgcgggaa gcttcctcac gccctaagcg ggagtataag 420ccgaagcccc gggagccctt tgaccttgga gagcctgagc agtccaacgg gggcttcccc 480tgcaccacag cccccaagat cgcagcttca tcgtctttcc gatcttccga caagcccatc 540cggaccccta gccggagcat gccgcccctg gaccagccga gctgcaaggc gctgtacgac 600ttcgagcccg agaacgacgg ggagctgggc ttcatgaggg cgacgtcatc acgctgacca 660accagatcga tgagaac 677<210>449<211>603<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(603)<223>n＝A、T、C或G<400>449ttttttgtan aaagagacat ttaatacttc tgtttacaaa attcaggcgt acatttcagt 60ttgccctgga ccgtgcccaa agctgtgtgc tcatctctgc gcccctcatg tacttctgac 120gaggggggtg cagggcaggg cagagcagag cctggggtcc ggaggcttca ctggaccaca 180gggggagggg aatgtgaatg tggcctggcc canagaactc cccatttcat cgattttgca 240ttgggcgata gaggaagcag atgtcggggc tgcctgcctt ggtctanagg agatggctgg 300ggccacttcc cacagggtga agtggcagcg gctcagcaag gggagcctgg ccaccagggg 360ctgggacatg cgctcactgg aacctttgtg cttggccctc ggcagcgcgg ctgtggtccc 420gtgtgaggtg tgctggggtg gggtgtgggt ggctggtggt ggcagcttgt gccagagtga 480cacaggcctc cctgggttgg gatgggggca agttaaaaag ctgaaaaggt acttggcttt 540ctgagggcgg gcttgggagc aggccctgca gganaccatg ttctctgtcc tcagcagatc 600cac603<210>450<211>678<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(678)<223>n＝A、T、C或G<400>450gaattcgaac cccttcgcat caatataana tgccacccat ctgcagttaa tttcttttcc 60tcatcatgtg attaaaagtg gtgattcagt gggaactggg aatgttttta gctggtggta 120gaaggctgcc tacactgggc actgttttag attctcatat catttaaaca gcaaggaggt 180tcagggaaga ataaccgtag ccttgggtaa tccactaggg cttttgtgag taggagagct 240gatacctcac attcttagca ggtgaaaact tgccatgatg gaaacagata gtgaagagtt 300actgacgtat cccaaattat atgctgtgac ataaattccc agcatgccca gccctgattt 360ctgagttcat aagtaattct agtgaacctt agtaggaatt ctgggtaaga aaatgaggtt 420gccattggtc ttgtttgcat caccaagacc agacatccag aagagcccct caccttgaaa 480agcagacaga ttttaaatta accccctcct tcccactcac cttcatctcc ctaagagttt 540tggccattta attccacatt ttgaaaggaa tacattggtg aaatttggga agagaatctg 600tgctatgcaa tgtttcatta aaatcttcag tttttcaagt ctctctaaaa ataatttgta 660gatctatctt ggatggat678<210>451<211>651<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(651)<223>n＝A、T、C或G<400>451tttttcatca acaaaaatca agcattttcn tttttttgaa acaagaaaag cgcatcgtan 60aaaccaagat tctgtacaat attctaacat tatatgtaca taaaattata ttactcataa 120ctatattgaa aagtcttatt tgtagaatat ggctggcaac aaagaaagac ccataccatt 180tagcgtttga agcagggcag gtagcaagag aacattagca aagacacctt tgtgcctgga 240tacacaatcc tgctactaag ttatgtgact aaccagcaca ctctaagttc tgtggtttgt 300tcgttgtttc acattctagt agggaattct gcagcaggcg atgcgaaaaa naanacatgg 360tcaaatgaaa tgtgaaatgc tgtttaaaat ctgcatattg gctatgataa tgggtttgng 420aatccaagtt gcattggaag ttcactcatt ctccattcat tatgcatgcc tccagtgatt 480taatgaattt cagcaggngg aaaagacagc tttgaacaga tcagatgggc tgtgagtcan 540attcttgatt ctttttcctc atttggctcc tgaatgttgc anaaaactgg ttttgtacac 600tggggaagga gagagtgaag accctccagt tggttcctca gtcagctccg t 651<210>452<211>679<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(679)<223>n＝A、T、C或G<400>452gaattcgaac cccttcgcat tgctcagccn nctaccactg ctaagagcca tctccaccag 60aagcctggcc agacctggaa gaacaaagag catcatctct ctgacagaga gtttgtgttc 120aaagaacctc agcaggtagt acgtagagct cctgagccac gagtgattga cagagagggt 180gtgtatgaaa tcagcctgtc acccacaggt gtatctaggg tctgtttgta tcctggcttt 240gttgacgtga aagaagctga ctggatattg gaacagcttt gtcaagatgt tccctggaaa 300cagaggaccg gcatcagaga ggatataact tatcagcaac caagacttac agcatggtat 360ggagaacttc cttacactta ttcaagaatc actatggaac caaatcctca ctggcaccct 420gtgctgcgca cactaaagaa ccgcattgaa gagaacactg gccacacctt caactcctta 480ctctgcaatc tttatcgcaa tgagaaggac agcgtggact ggcacagtga tgatgaaccc 540tcactaggga ggtgccccat tattgcttca ctaagttttg gtgccacacg cacatttgag 600atgagaaaga agccaccacc agaagagaat ggagactaca catatgtgga aagagtgaag 660atacccttgg atcatggta 679<210>453<211>630<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(630)<223>n＝A、T、C或G<400>453gaattcgaac cccttcggaa ggccaagggn ntagaaggng gctccggccc cagctgtcgt 60gaagaagcag gaggctaaga aagtggtgaa tcccctgttt gagaaaaggc ctaagaattt 120tggcattgga caggacatcc agcccaaaag agacctcacc cgctttgtga aatggccccg 180ctatatcagg ttgcagcggc agagagccat cctctataag cggctgaaag tgcctcctgc 240gattaaccag ttcacccagg ccctggaccg ccaaacagct actcagctgc ttaagctggc 300ccacaagtac agaccagaga caaagcaaga gaagaagcag agactgttgg cccgggccga 360gaagaaggct gctggcaaag gggacgtccc aacgaagaga ccacctgtcc ttcgagcagg 420agttaacacc cgtcaccacc ttggtggaga acaagaaagc tcagctggtg gtgattgcac 480acgacgtgga tcccatcgag ctggttgtct tcttgcctgc cctgtgtcgt aaaatggggg 540tcccttactg cattatcaag ggaaaggcaa gactgggacg tctagtccac aggaagacct 600gcaccactgt cgccttccac aggtgaactc 630<210>454<211>677<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(677)<223>n＝A、T、C或G<400>454gaattcgaac cccttcgccc gcatgcggna catccccttg gccccagggt cagactggcg 60cgatctgccc aacatcgagg tgcggctctc agacggcacc atggccagga agctgcggta 120tacccaccat gacaggaaga acggccgcag cagctctggg gccctccgtg gggtctgctc 180ctgcgtggaa gccggcaaag cctgcgaccc cgcagccagg cagttcaaca ccctcatccc 240ctggtgcctg ccccacaccg ggaaccggca caaccactgg gctggcctct atggaaggct 300cgagtgggac ggcttcttca gcacaaccgt caccaacccc gagcccatgg gcaagcaggg 360ccgcgtgctc cacccagagc agcaccgtgt ggtgagcgtg cgggagtgtg cccgctccca 420gggcttccct gacacctacc ggctcttcgg caacatcctg gacaagcacc ggcaggtggg 480caatgccgtg ccaccgcccc tggcaaagcc attggcttgg agatcaagct ttgtattgtt 540ggccaaagcc cgagagagtg cctcagctaa aataaaggag gaggaagctg ctaaggacta 600gttctgcctt cccgtcaccc ctgtttctgg caccaggaat cccccacaat gcacttgatg 660gtggggtttt aacatgt 677<210>455<211>598<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(598)<223>n＝A、T、C或G<400>455ttttttggtt tataggagag atttatttga agaaatatta caacatataa aaactacata 60aagtcttaat ttccactcat acagtggtag atttgatata atgcataata aaaaactttt 120aaaatccaga atgcacaaag tactgcacaa tttgatcact aaatcattag ttgataagcg 180aacctcacac aacagcttca tgtcagccaa ggccacaaac accatgtacc acacatgtga 240acggacagat tgacatgtta aaaacacaac atcagtgcat gttggggatt cctggtgcca 300gaaacagggg tgacgggagg gcagaactag tccttagcag cttcctcctc ctttatttta 360gctgaggcac tctctcgggc tttggccaac atacaaagct tgatctccaa gccaatggct 420ttggccaggg gcggtggcac ggcattgccc acctgccggt gcttngtcca ggatgttgcc 480cgaagagccg gtaggtggtc aagggaagcc cctggggaag cgggcacact cccggacgct 540naccacacgg tgctgntttt gggtggagca ccgcggcctt gcttgcccat gggctcgg598<210>456<211>574<212>DNA<213>智人(Homo sapiens)<400>456ggaattcgaa ccccttcggg gcggggagcc ccgtagaacc gagggggtcg gcccgggggt 60cccgggggag gtggagatgg tgaaggggca gccgttcgac gtgggcccgc gctacacgca 120gttgcagtac atcggcgagg gcgcgtacgg catggtcagc tcggcctatg accacgtgcg 180caagactcgc gtggccatca agaagatcag ccccttcgaa catcagacct actgccagcg 240cacgctccgg gagatccaga tcctgctgcg cttccgccat gagaatgtca tcggcatccg 300agacattctg cgggcgtcca ccctggaagc catgagagat gtctacattg tgcaggacct 360gatggagact gacctgtaca agttgctgaa aagccagcag ctgagcaatg accatatctg 420ctacttcctc taccagatcc tgcggggcct caagtacatc cactccgcca acgtgctcca 480ccgagatcta aagccctcca acctgcttca tcaacaccac ctggcgacct ttaaaatttg 540tgaatttccg gcctggcccc cggattgccc gaat 574<210>457<211>546<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(546)<223>n＝A、T、C或G<400>457ttttttgaca catctctata tttatatatt agacgggtca gggaggtggc aggggcgccg 60ggctctccac gccccccagc tccacttctg ctcaccacac acagaagcag cgagggcacg 120cgaagtgaca gctttgacag ggaggggatt cggcccggcc tggctcctca gggatgctag 180cccttgagac taaggaatgt tccttcaggg aaactagggt ggggtttgaa tganatgagg 240ggggcaggca tggccctgag tccctactca gcgcccccca ccctccacct ctgcccttca 300gcaggttggg gcagccagaa cccttccatt ccagaactgc cagagactgg gacgctgggg 360aaggtaaggg cgcagcagca gcagcgggag attgaactgg ggccacctga gctcccgagg 420ccccgtgggg agggcgggtg gggaggaaaa ggccttggcc tgcctgaagc tggaggcctc 480agcaaaggag agaggtggcc aggcccatgc tccaccccgg cctgggctgc caanggtccc 540gggctg 546<210>458<211>674<212>DNA<213>智人(Homo sapiens)<400>458gaattcgaac cccttcggta ttattaagaa ctaagagaat agcttgccag atacaaatgg 60aaacaccttc caaatgagtc ggagaaaatg tcttgcagta ttatgggtaa aatagcaaag 120agcttgggaa tacagtttgc taatatcaag tccttaacaa cgaccattct tcattcaaga 180ttagttgtgt ataaatacat gcttcttcag gagttgactt agaaaacaag caaacaaaca 240aacatcagaa actatttaca actgggagca atccttgaag aacataaaga atataaatat 300caacaaaggc tgaaaactct tttttagatt aaagatcaaa tggacatgtc atcggaatgt 360attgtatggc tcttgattaa atcctggagc aaagtggaga gtgaggaaca actgtaaaga 420atgtgaatac ggactgtgta ttagataaca gtaccataaa tttcctggat gggataatta 480tgttgtgact atgtaagaga atattttgcc cttagaagat atatgatgaa gcatttagaa 540gtaaagtatc atgacatctt gcaaataact ttcaagtgat tcagccagat atataaaaat 600tatatataac acattatata atttatattt atataattat aatacattat ataatttata 660cattataatt atat674<210>459<211>682<212>DNA<213>智人(Homo sapiens)<400>459tttttttaaa tccatggctt gttaattgtc atcccagtta tttacatgtg actatagaga 60ctgcattctc ccagctgcca ggccgccagg gctttgccac tggtataatt tataacacga 120ctaattaaaa tgaatttgct tgcaataagg ttctgtgtgc tatttgtggg agaggagtta 180ttaaaatttt cagtacagta atagtaaact tgaatgcaaa gtaataataa tcatacattt 240ttaattacat gtttaatacc catttggcta atgtagaact attctgaaaa ttacttggga 300tcagcacaat gtctttttgt gcttagtagt atccaaagac atccttctga atgggcttag 360caatatgcac tgtcatcaag atacagctgt ttgatgacag acacacagtg tgttcctatg 420atactttgca caagatcagc tatgacaaat acaagttcat tttgcttatt gcaggcaaat 480aatgtccttt gcaggaactt ggatggagcc agaggccatt attctaagtg aaatacctca 540ggagtggaaa accaaatacc atatgttctc acttacaagt gggaactaag ctatgggtac 600acaaacgcat atagagtaat ggactctggc gactcatact acatattgag tacaatgtac 660actacttggg tgatgggtgc ac 682<210>460<211>663<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(663)<223>n＝A、T、C或G<400>460gaattcgaac cccttcgcgg ggcgcgcgag cggcgccagc tcggggcagc ggaacccaga 60gaagctgagg gggcggtagc ggcggcgacg gcgacgacga cgactcccgc gcgtgtgccc 120agcctcttcc cgccgcagcc gcccttttcc tccctccctt acgtccccga gtgcggcagt 180accgcctcct tcccagccgc gcggcttcct ccagacctct cggcgcgggt gagccctatt 240cccagaggca ggtggtgctg accctgtaac ccaaaggagg aaacagctgg ctaagctcat 300cattgttact ggtgggcacc atgtccttga agcttcaggc aagcaatgta accaacaaga 360atgaccccaa gtccatcaac tctcgagtct tcattggaaa cctcaacaca gctctggtga 420agaaatcaga tgtggagacc atcttctcta agtatggccg tgtggccggc tgttctgtgc 480acaagggcta tgcctttgtt cagtactcca atgagcgcca tgcccgggca gctgtgctgg 540gagagaatgg gcgggtgctg gccgggcaga ccctggacat caacatggct ggagagccta 600agcctgacag acccaagggg ctaaaganaa gcagcatctg gcatatacag gctcttcgac 660tac663<210>461<211>612<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(612)<223>n＝A、T、C或G<400>461ttttttggga tccaatctnt ttattgtcag ggtcccctcc ctgnggcccc ccgccaaacc 60tatagaaaaa acccaagcct gggagtgtcc tggggagggg aggtagtatg gggaaacccc 120tgtgctctac cctntggcct gggcagtgca nacagggagg gctcatgggg aaggagtagg 180ccagtaactc cacctgcana ggacatggca ctggctggga tgcgttgggg gaggaggcgc 240ctgctgccag ctttcctntg gtacccgctg gggggtggca tccagggttg ggtgcccggc 300ttgaggcctg gggcagcgat gcccttcacc tgctggnggc cattgctcct gtcaggctgc 360ttactgcaag gccccatcat ccgcgtctgt gtcctggctg tgttccagct cttcctcgct 420gngtgtcagg agcccttcct catcgccgtc gtctcgggtc cgtgcttccc cctggggcag 480gcctgcctca naagttgtgt tctcttgggg ggctggtggc cggttgttgc caccgcaccg 540caccaccact ggcaccggca ccgntgcacc accaccgccg ccgccgccgn tggngccacc 600ttcatcaccc tt 612<210>462<211>672<212>DNA<213>智人(Homo sapiens)<400>462gaattcgaac cccttcggat ggaaggggcc ggggcagcgt cggggaaagg aagggccgga 60ggcgcggcgg cgggcggccg agaggggcgg cggcggcggc ggcggcgggg ttcccgcgcc 120gcggagcccg gcccgagagc cgcgtccacg ttcctgcctc ctgctcccgc cgccctgggg 180cgccgccatg acgcccgatc tgctcaactt cagccccaga tgtcaccaag ctctcggact 240ctaacaagga gaacgcgctg cacagctaca gcacccagaa gggccccctg aaggcagggg 300agcagcgggc gggctctgag gtcatcagcc ggggtggccc tcggaaggcg gacgggcagc 360gtcaggcctt ggactacgtg gagctctcgc cgctgaccca ggcttccccg cagcgggccc 420gcaccccagc ccgcactcct gaccgccctg gccaagcagg aggagctgga gcgggacctg 480gcccagcgct ccgaggagcg gcgcaagtgg tttgaggcca cagacagcag gaccccagag 540gtgcctgctg gtgaggggcc gcgccggggc ctgggtgccc cctgactgag gaccagcaaa 600accggcttag tgaggagatc gagaagaagt ggcaggagct ggagaagctt gcccttgcgg 660gagaataacc gg 672<210>463<211>562<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(562)<223>n＝A、T、C或G<400>463ttttttaaag tataaagtgt tttggaaaaa aaggaaaaan ntctatataa aaatctcttc 60acatataaaa tcctgaagaa ggtgcaaggt gagacccagt gcgaggggcg tgctcagata 120tgcagtgtgt gtgtgtgtgt gtgtgtgtgt gtatccgtgt gtacatgtgt gcacgtgtgt 180gcgtatgtgt ctgtgtgtct gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt ggtgggtgca 240agtgcacgtg tggcccacag agggtgggga gaaagcttgg ctttttactt ccatccagga 300gggaaggagg gcggctggtc ctccagcctg gagggtctgc agctgggcgg gacctctact 360cagccaggct gttgcgcatc gactccttct cctggagggc ggccatggca agacgcaggt 420gctccttcag ctgctcgatc tcccgctcag accgtgtctt gatgtggctc aactccacat 480agacgtcctg gtactttccc naggtgaagc gcttgtcctt ctgcatcatc tggagctcgt 540cccggaggca ctgcaccttc ct 562<210>464<211>553<212>DNA<213>智人(Homo sapiens)<400>464gaattcgaac cccttcggga ccaggaaccc aggagagcat ggccacgctg cgccggcttc 60gggaggcgcc gcggcactta ctggtttgcg agaaatccaa cttcggcaac cacaagtcgc 120gccaccggca tcttgtgcag acgcactact ataactacag ggtttcattt ctcattcctg 180aatgtgggat actatcggaa gaactgaaaa acctggtcat gaacactgga ccctattact 240ttgtgaagaa tttacctctt catgaattaa ttacacctga attcatcagt acctttataa 300agaaaggttc ttgctatgca ctaacataca atacacatat tgatgaagat aatactgttg 360ccctgctacc aaatgggaaa ttaattttgt cactggataa agacacttat gaagaaactg 420gacttcaggg tcatccatct cagttttctg gcagaaaaat tatgaaattt agttcagaag 480aatcgacaat gatgtcatat ttttccaagt accaaattca ggagcatcag ccaaaagtag 540cactgagccc gtt 553<210>465<211>383<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(383)<223>n＝A、T、C或G<400>465tttttggaag aaaacacgat ttttaatttt tattttttat gggggacagn gatcatttgc 60cccaacagcc atntgaagcc aatagtcctg attattaaaa atcacaaagt tatataaatg 120ntctcctcct tttcgaaaac catgttcatt tttttcccaa naaacagggc tgtctgcaaa 180gccttgaacg gacagngtaa cccatggagc taacttcggt tcatcaaagt agngacagan 240atgttccaat agganacaga tcttntntgg aagtatgaag ccagngattg tacacaaata 300agcttttgcc accactgtgc ttggctcagg acagcaatag gttgatatga aattattagg 360ctcattattt aggncgacat tac 383<210>466<211>673<212>DNA<213>智人(Homo sapiens)<400>466gaattcgaac cccttcgctc cctcctgcac gcaatggtgg cctatgatcc cgatgagaga 60atcgccgccc accaggccct gcagcacccc tacttccaag aacagaggaa aacagagaag 120cgggctctgg gcagccacag aaaagctggc tttccggagc accctgtggc accggaacca 180ctcagtaaca gctgccagat ttccaaggag ggcagaaagc agaaacagtc cctaaagcaa 240gaggaggacc gtcccaagag acgaggaccg gcctatgtca tggaactgcc caaactaaag 300ctttcgggag tggtcagact gtcgtcttac tccagcccca cgctgcagtc cgtgcttgga 360tctggaacaa atggaagagt gccggtgctg agacccttga agtgcatccc tgcgagcaag 420aaggtagcgc ggaaccagct tctctgacgg cgctgctctt cgacccagcc caggccgcca 480ctgaattttg tgtctgtaat ttttctttga cagacagatc cgcagaagga ccttaagcct 540gccccgcagc agtgtcgcct gcccaccata gtgcggaaag gcggaagata actgagcagc 600accgtcgtct cgacttcgga ggcaacacca agcccgaccg ggccaggcct gggtgatctg 660ctgctgagac gcc 673<210>467<211>373<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(373)<223>n＝A、T、C或G<400>467tttttactgg aacgacagct tattntttaa taaaagtcag gggngtcagc agngtcactg 60gtaanacatg atggcgctcc acgactgacc agcagcgctg ggaagggaca cgcanaaccc 120accttccaac cacgcccaac acatnacana aatgcctgct cgtttgtttt gattcatata 180caaagttaca aagtatttcc tgccccaaat tnttaacgaa aatgaaagaa aaccctanaa 240tgcgggggtt ttacaagtat attagcccan aacatcctag gcagctgcnc gggccgcggg 300tgcggcaggg cgcagggcaa cacccaaagc cccggccagc gcgaaacgga cgcaggcgca 360tccccagccc tcc 373<210>468<211>573<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(573)<223>n＝A、T、C或G<400>468gaattcgaac cccttcgctg ctgtcctact tgatgcttgt cactgtcatg atgtggcccc 60tngctgtgta ccaccgactg tgggatcgag catatgtgcg gctgaagcca gctctgcagc 120ggctagactt cagtgtccgt ggctacatga tgtccaagca gagagagaga caattacgcc 180gcagagctct ccacccagaa cgagccatgg acaaccacag tgacagcgaa gaggagcttg 240ctgccttctg tcctcagctg gacgattcta ctgttgccag ggaattggcc atcacagact 300ctgagcactc agacgctgaa gtctcctgta cagacaatgg cacattcaat ctttcaaggg 360gccaaacacc tctaacggaa ggctctgaag acctagatgg tcacagtgat ccagaggaat 420cctttgccag agaccttcca gacttccctt ccattaatat ggatcctgct ggcctggatg 480atgangacga cactagcatt ggcatgccca gcttgatgta ccgttctccg ccagggggct 540gaggagcccc aaggccccac ctgccagccc ggg 573<210>469<211>635<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(635)<223>n＝A、T、C或G<400>469tcncgatcta gaactaggtt ggacaggctt gctcaagttt caccagagtt antactggcc 60tctgttcgca gagtttttag ttnnacactg cagaattggc agactacacg gtttatggaa 120gttgaagtag caataagatt gctgtatatg ttggcagaag ctcttccagt atctcatggt 180gctcacttct caggtgatgt ttcaaaagct agtgctttgc aggatatgat gcgaactgta 240agtatactgg agataatttt gaccataaat ttctgttttc agtataagct aatgggagtt 300ccttaattgt tagagcttag tatatgttaa taccggggca ttttgatgtt gcaataaata 360agaagaggtt tcctaacttt ttcctgatct agctggtaac atcaggagtc agttcctatc 420agcatacatc tgtgacattg gagttcttcg aaactgttgt tagatatgaa aagtttttca 480cagttgaacc tcagcacatt ccatgtgtac taatggcttt cttagatcac agaggtctgc 540ggcattccag ngcaaaagtt cggagcagga cggcttacct gttttctaga tttgtcaaat 600ctctcaataa gcaaatgaat cctttccttg aggat 635<210>470<211>593<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(593)<223>n＝A、T、C或G<400>470gaattcgaac ccttcggtat taacaaatat ntacatttct atttttataa tccataagga 60tatgcctgtt ttaaataaca tacatattaa caatatctat caggaaaacc ctcaagacag 120cttctagtta aaaccttngn tgctgtcctc tcaaactata tttataaaaa tttgctaggg 180ccaaatccat acttgcagaa taattcatca aattttattt ttaagngaaa agtaaccttt 240caggcatttc agcagcatac attgacaatc tagggtatat atgtatgtat gtttcttatt 300gtatgtctat atatgtatgt ggggaggaca ggagtgaatg ttcacacact tttcttgcgt 360actcaactaa attggagaat gtttctgaag aaaattggat gaaattagct gctgagattg 420agtttctgcc ttaaaatctg aaacaaaaaa agggacaaat tgctggtang atctactgac 480tgtngccatc accagaacac ttagtttctt cccagacatg aatttcctga caggctctga 540gccagaaaca cactgtgggc gtgcatntgg gtcaccctgg atatgcctcc act 593<210>471<211>581<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(581)<223>n＝A、T、C或G<400>471tttttttaat cangggacat ttattaacat gcttcaaaag tgaccaaagt gtccagccag 60cacaatagcc gaggcaatca acgttctctt agtgtgtgat ctcgtccaaa acaccaaata 120aataggttta ggaataacct caaataaatt gtaatttaac ttcgcccaaa attatacatc 180ctctactgct cttccctgct cctgtaaaga tactagcggg aggggagaaa gctcaaatga 240ctctgtaatt tagaattaca accagagaag aaatacttca agcacaataa agacgttcca 300ttgaagagcg acattcattc tggaatgttt gttttgaaaa caactcttnt gggggaattc 360aaaaggtact gaacaaagca acataaagta agttttgggt tgttttgcaa aataaaaata 420tacaattgag tggaccagat ggcaaaaaca taccaattac aatctgaatg ctatatttaa 480aacccttaaa ttctgaaggc ctgaatatca acaaacctat ttatgtttat gatcctaaaa 540agacattaaa tattattaaa cccccaactt ccaaaacata g 581<210>472<211>674<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(674)<223>n＝A、T、C或G<400>472gaattcgaac cccttcggat ggcgtgatgt ntcacagaaa gttctccgct cccagacatg 60ggtccctcgg cttcctgcct cggaagcgca gcagcaggca tcgtgggaag gtgaagagct 120tccctaagga tgacccgtcc aagccggtcc acctcacagc cttcctggga tacaaggctg 180gcatgactca catcgtgcgg gaagtcgaca ggccgggatc caaggtgaac aagaaggagg 240tggtggaggc tgtgaccatt gtagagacac cacccatggt ggttgtgggc attgtgggct 300acgtggaaac ccctcgaggc ctccggacct tcaagactgt ctttgctgag cacatcagtg 360atgaatgcaa gaggcgtttc tataagaatt ggcataaatc taagaagaag gcctttacca 420agtactgcaa gaaatggcag gatgaggatg gcaagaagca gctggagaag gacttcagca 480gcatgaagaa gtactgccaa gtcatccgtg tcattgccca cacccagatg cgcctgcttc 540ctctgcgcca gaagaagccc acctgatgga gatccaggtg aacggaggca ctgtggccga 600gaagctggac tgggccccgc gagangcttg agcacaggta cctgtgaacc aagtgtttgg 660gcaggatgaa aatg674<210>473<211>646<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(646)<223>n＝A、T、C或G<400>473ttttttcagn ggaaaataac ttttattgan accccaccaa ctgcaaaatc tgttcctggc 60attaagctcc ttnttccttt gcaattcggt ctttcttcag nggtcccatg aatgctttct 120tctcctccat ggtctggaag cggccatggc caaacttgga ggnggtgtca atgaacttaa 180ggtcaatctt ctccanagcc cgccgnttcg tctgcaccag caaggacttg cggagggtga 240gcacccgctt cttggttccc accacacagc ctttcagcat gacaaagtca ttggtcactt 300caccatagng gacaaagcca cccanagggt tgatgctctt gtcanatagg tcatagtcag 360tggaggcatt gttcttgatc agcttgccgt ccttgataag gtagccctgg ccaatcttat 420aaatcttctt gttgatctca gtgcggtgat ggtagccttt ctgcccagcg cgtgccacag 480agaaggctac acgagcagga tgccatgccc caatacaggc caccttgcgc aggcctcggt 540gggtcttgcg gggcagcttc ttggtgtgcc aacgactggt gacccctttg tagcctttgc 600ccttggtcac cccgatgacg tcgatcatct catcctgccc aaacac 646<210>474<211>544<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(544)<223>n＝A、T、C或G<400>474gaattcgaac cccttcggca gcacactccc antcggccgc agcctgacac gccgcgcggc 60cccccagtct cccgcggctg ctcccccagg catggcacag ggcctcgcct cactatggca 120gcagcacggc acagcacgct cgacttcatg ctcggcgcca aagctgatgg tgagaccatt 180ctaaaaggcc tccagtccat tttccaggag caggggatgg cggagtcggt gcacacctgg 240caggaccatg gctatttagc aacctacaca aacaagaacg gcagctttgc caatttgaga 300atttacccac atggattggt gttgctggac cttcagagtt atgatggtga tgcgcaaggc 360aaagaagaga tcgacagtat tttgaacaaa gtagaggaaa gaatgaaaga attgagtcag 420gacaagtact gggcgggtga aacgattacc acccatagtg cgaggaggag ccatcgacag 480atactggccc accgncgacg ggcgccttgg ttgaatatga catagaatga agtggtatat 540gacg 544<210>475<211>578<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(578)<223>n＝A、T、C或G<400>475gaattcgaac cccttcggga gaaccccatg ngggaacttc gcatccgcaa actctgtctc 60aacatctgtg ttggggagag tggagacaga ctgacgcgag cagccaaggt gttggagcag 120ctcacagggc agacccctgt gttttccaaa gctagataca ctgtcagatc ctttggcatc 180cggagaaatg aaaagattgc tgtccactgc acagttcgag gggccaaggc agaagaaatc 240ttggagaagg gtctaaaggt gcgggagtat gagttaagaa aaaacaactt ctcagatact 300ggaaactttg gttttgggat ccaggaacac atcgatctgg gtatcaaata tgacccaagc 360attggtatct acggcctgga cttctatgtg gtgctgggta ggccaggttt cagcatcgca 420gacaagaagc gcaggacagg ctgcattggg gccaaacaca gaatcagcaa agaggaggcc 480atgcgctggt tccagcagaa gtatgatggg atcatccttc ctggcaaata aattcccgtt 540tctatccaaa agagcaataa aaagttttca gtgaaaaa 578<210>476<211>619<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(619)<223>n＝A、T、C或G<400>476ggaattcgaa ccccttcgct cctgcctgtc cgccatgttt tcaggncggg nctggcttgg 60tcttcccccg taaggaaatg gccggggagc tccaggggac ccaggcgccg tcgcttcggc 120ggagcctggg ctgaccagcc aggacagcgg ggtaaacccg aacaattctg cgcgaggtag 180ggaggccatg gcgtccggca gtaactggct ctccggggtg aatgtcgtgc tggtgatggc 240ctacgggagc ctggtgtttg tactgctatt tatttttgtg aagaggcaaa tcatgcgctt 300tgcaatgaaa tctcgaaggg gacctcatgt ccctgtggga cacaatgccc ccaaggactt 360gaaagaggag attgatattc gactctccag ggttcaggat atcaagtatg agccccagct 420ccttgcagat gatgatgcta gactactaca actggaaacc cagggaaatc aaagttgcta 480caactatctg tataggatga aagctctgga tgccattcgt acctctgaga tcccatttca 540ttctgaaggc cggcatcccc gttccttaat gggcaagaat tttccgcttc taccttgctg 600gatcttgcga aacactagt 619<210>477<211>674<212>DNA<213>智人(Homo sapiens)<400>477gaattcgaac cccttcgggg tgttcgactg ctagagccga gcgaagcgat gcctaaatca 60aaggaacttg tttcttcaag ctcttctggc agtgattctg acagtgaggt tgacaaaaag 120ttaaagagga aaaagcaagt tgctccagaa aaacctgtaa agaaacaaaa gacaggtgag 180acttcgagag ccctgtcatc ttctaaacag agcagcagca gcagagatga taacatgttt 240cagattggga aaatgaggta cgttagtgtt cgcgatttta aaggcaaagt gctaattgat 300attagagaat attggatgga tcctgaaggt gaaatgaaac caggaagaaa aggtatttct 360ttaaatccag aacaatggag ccagctgaag gaacagattt ctgacattga tgatgcagta 420agaaaactgt aaaattcgag ccatataaat aaaacctgta ctgttctagt tgttttaatc 480tgtcttttta cattggcttt tgttttctaa atgttctcca agctattgta tgtttggatt 540gcagaagaat ttgtaagatg aatacttttt tttaatgtgc attattaaaa atattgagtg 600aagctaattg tcaactttat taaggattac tttgtctgcc cacccctagt gtaaaataaa 660atcaagtaat acat674<210>478<211>663<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(663)<223>n＝A、T、C或G<400>478tttttttaag ctttcacaat ttttattaaa tcctagtcta nttgaacaat atctgatgtt 60acagacatca tcccatggtg aacatgttta ataagtgaaa gcaagtcaga catctcatct 120aagtcattat tttctgcaga ctaagcaata actacacaga acactatggg taaacaaaca 180cctgctcagt tttcacacaa gccatgttgt ttatcaaatt agatctgcta atattgaata 240cagtagattc ggtgattgta gttctcatat aagtatctta ttgagataac attttgacag 300tttcactgac tttccaaata agcataccat aatcaaagaa aagaataaag agtgaagtaa 360aaactgaaca tgaagagatt aagttattaa aggaaaatga agtaaataaa aagagtgaaa 420aaccattggg ggtggaagtc aaacaagcct agacatttga ttggaagaga aaagatcaaa 480tatgaagttc acaaaccaaa agtttataaa ctcaatgcaa tacaaatcct ttttattgta 540aaagctgagt tgaaactaaa agatctataa aaactgttac ttttggcctt aaacagtacc 600aactcttatg atcaaaaaag gccacacagt taagattgna ttacttgatt ttattttaca 660cta663<210>479<211>673<212>DNA<213>智人(Homo sapiens)<400>479gaattcgaac cccttcgaat gaagaactct ccagggatct agtgaataaa ctaaaaccct 60acatgagctt cctgactcag tgccgtcccc tgtcagcgag catgcacaac gccatcaagt 120tccttaacaa ggaaatcacc agtgtgggca gttccaagcg ggaagaggag gccaagtcag 180aacttcgagc agccattgat cggtatgtgc aagagaagat tgtgctagca gctcaggcaa 240tttcacgctt tgcttaccag aagatcagta atggagatgt gatcctggta tatggatgct 300catctctggt atcacgaatt cttcaggagg cttggacaga gggccggcggtttcgggtgg 360tagtggtgga cagccggcca tggctggaag gaaggcacac actacgttct ctagtccatg 420ctggtgtccc agcctcctac ctgctgattc ctgcagcctc ctatgtgctc ccagaggttt 480ccaaggtgct attgggagct catgcactct tggccaacgg gtctgtgatg tcacgggtag 540ggacagcaca gttagccctg gtggctcgag cccataatgt accagtgctg gtttgctgtg 600aaacatacaa gttctgtgag cgtgtgcaga ctgatgcctt ttgtctctaa tgagctagat 660gaccctgatg atc 673<210>480<211>203<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(203)<223>n＝A、T、C或G<400>480gaattcgaac cccttcgggg ggaggaagag gaggtggagg aggagggtga tgttgatagt 60gatgaagaag aggangaaga tgangananc tcctcggagg gcttggaggc tgaggactgg 120gcccagggag tagtggaggc cgntggcagc ttcggggctt atggtgccca ggaggaagcc 180cantgcccta ctctgcattt cct 203<210>481<211>482<212>DNA<213>智人(Homo sapiens)<400>481ccagacgctg cccatggagg cgtccagcga gccgccgctg gatgctaagt ccgatgtcac 60caaccagctt gtagattttc agtggaaact gggtatggct gtgagctcag acacttgcag 120atctcttaag tatccttacg ttgcagtgat gctaaaagtg gcagatcatt caggccaagt 180aaagaccaag tgctttgaaa tgacgattcc acagtttcag aatttctaca gacagttcaa 240ggaaattgct gcagttattg aaacggtgtg aagacggatt ctttggttga taaattgcta 300tcattctaaa gtcatggact tcactttcgg caacaaaact aaataaggat ggaacattta 360ttgaatgaaa aatgcacttt tgtttttcca tttttttaaa taataaaaat cagacaaaca 420gaaaaaaaaa aaaaaaaggg cggccgctcg agtctagagg gcccgtttaa acccgctgat 480ca 482<210>482<211>505<212>DNA<213>智人(Homo sapiens)<400>482aaaatcttta gctgccaaga aagaagttaa gactctcagt gctgagagag actgaatcca 60cctaggtgat aaggtgactg gacccagtaa accctttgtg tgctgggggg ttttatgcct 120tgtagaaccc agtgtgagca agatttgggt accctacata cattcagtag ccaggaaagg 180gtgattggat tgccagactc tgcctgctgg caaaaggatg agctgtagaa gctgaagtcc 240taggtagtag atataaagaa gacaaattag gtggcacctt ctagactgtg caatgcatgg 300atttggaatt gaatttttcc tctaattatt ctagggaaac cctgggctaa gaaaccaatg 360taaaacctga tgaggtagtc tgtagtcaca ctgggtagag gtagaggcaa ccacaaaatt 420attcttaaga atgcctccca ggcgcctgga agatgaaact ttctggtgaatatgagctca 480tggtaaaaat ttaggtcgga tgcag505<210>483<211>501<212>DNA<213>智人(Homo sapiens)<400>483tgcaaaaagg taacaaattc ataactggaa agcaaagaga agaacaagta tgatttggat 60gataaagcat tgttttaatg gtgaaaactt cacagatcac taatgtttct agaggttaac 120ttcaagtggg caagctgggg tttttaggta gtcagtggcc tagttcctaa agccacagta 180taggatctgt taaactgaat gtctgttgaa agtttgtttt agctgcttgg aggcttcctt 240ttaagacaaa ctgtatgtga ttaagttgtt ttgagggaac tgaagaacct gatgtagccc 300ctggccagat aactgcctga tttctcagat attatttctc tgggaaacat tctacatagc 360acaggagctt aagagtggca ttatcttctc gccttaattt ccagagatta tttctgtact 420gagaatcctg gaactactat gctaggaaat ttaaagctgc atggtctgtc ttgttttcat 480ttaattattg tgaataccta g501<210>484<211>501<212>DNA<213>智人(Homo sapiens)<400>484gcactaagac caccttctat gaggagcagg gtgactacta cagccagtac atccgggcct 60gcctggacca cctggccccc gactccaaga gttctgggaa ggggaagaag cagccttctc 120ttcattacac tgctgctcag ctcctggaaa agggtgtctt ggtggaaatt gaagatcttc 180ccgcctctca cttcagaaac gtcatctttg acatcacgcc gggagatgag gcaggaaagt 240ttgaagtaaa tgccaagttc ctgggtgtgg acatggagcg atttcagctt cactatcagg 300atctcctgca gctccagtat gagggtgtgg ctgtcatgaa actcttcaac aaggccaaag 360tcaatgtcaa ccttctcatc ttcctcctca acaagaagtt tttgcggaag tgacagaggc 420aaagggtgct acccaagccc ctcttacctc tctggatgct ttctttaaca ctaactcacc 480actgtgcttc cctgcagaca c501<210>485<211>504<212>DNA<213>智人(Homo sapiens)<400>485cgcactcttg gaacattctt tctttcaaca acccaaggca tgcttctatc tccttttgag 60gtttccctct aagtgttacc tctaagatag gcttttcctg gacactctat gatggaacct 120ctaggatttt ctctattgtt ttatgcttat tttgatattt gattcctaga attttaaata 180cattatatat catataaaat aaacctttaa atattgaaat gaaaagataa aaatacatac 240actaagtgaa taggtcaaaa gtgtgagatc atcttgaaca ttatcttgaa gagaagatac 300caatttacct tctgctcaga tcatggtgta cgatatcaca acctgcctag aataactctc 360cttttctgaa ccatttattc actacttttg tcttccaatt aaatattagc ctgacttcaa 420atatcataca ttagtttcct ttgtttatgt aattgaatta tataacatat attcattaga 480gcctattttt tttaaaattt ttgt 504<210>486<211>501<212>DNA<213>智人(Homo sapiens)<400>486gagaggtcac tatggcgcct ttctgcagga cgagtgggac ctgctccaaa gaatgatttt 60gctggcccac gagaaactct ctgttcctgt cacgtgcaaa atccgtgtct tcccggagat 120tgacaagacc gtgaggtacg cccagatgct ggagaaggcc ggctgccagt tgctgacggt 180gcacggacgc accaaggagc agaaggggcc cctgtcgggt gcagcgtcct gggagcatat 240caaggctgtg cggaaggctg tggccatccc tgtgtttgct aacgggaaca tccagtgcct 300gcaggacgtg gagcgctgcc tccgggacac gggtgtgcag ggcgtcatga gcgcagaggg 360caacctgcac aaccccgccc tgttcgaggg ccggagccct gccgtgtggg agctggccga 420ggagtatctg gacatcgtgc gggagcaccc ctgccccctg tcctacgtcc gggcccacct 480cttcaagctg tggcaccaca c501<210>487<211>501<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(501)<223>n＝A、T、C或G<400>487accattattt agcagcaaaa aggaaagttt gaagacatta acaggaactg gttaattgta 60gtccttatct gaaaaggaca gattgaatgc agccaaatta tggcaaagaa atcagtagga 120caacccctat aaagggtagt tcttttaaaa aaaatttctt tattggcaac aacataaaag 180atatgaaaga atcactcata atttatcagc ataacatagc tattctcatt tttgcaattg 240actttttagt tcttgaccaa atgtaatttt tattagttgt gattaactga ttttgtgctt 300tttttaaaaa aaaaaaaaac ctagaataag acatttgttt tgttaattat tataaatgac 360tgtattcatt ctgtttatgt accataattt tggatgttcc tacgatgtta aacttttagg 420ttgtttttaa ttgtttgttc ttatagacaa ctctgtaagg gnttttaact gcttttatca 480ggagaatgtc aaagaagtcc t501<210>488<211>148<212>DNA<213>智人(Homo sapiens)<400>488attctaagga tgaaatggct acagagcaaa ctgcagctga gagaaaactg cttggagttt 60ggacagaggt ggaattgagt gtccacaggc cagctgagga ggtggtaccc agcactctat 120gaacccttcg ctcaagtcag cctggagt 148<210>489<211>501<212>DNA<213>智人(Homo sapiens)<400>489gctgtggatt cccctccaag tggaggagga tgggcaggct ggggatcctg gggcaaatct 60ctgctgtcgt cagcatctgc cacagtaggt catggattga cggcagtcaa ggaaaaagca 120ggagccactc tacggattca tggtgtaaat tctggatctt ctgaaggagc ccaaccaaat 180actgaaaacg gagtccctga aataacagat gcagccacag atcagggccc tgcagaaagc 240ccacccactt ccccttcatc agcctctcgg ggtatgctgt ctgccatcac caatgtggtt 300caaaacacag gtaaaagtgt cttaactgga ggccttgatg cgttggaatt catcggcaag 360aaaaccatga atgtccttgc agaaagtgac ccgggcttta agcggaccaa gacgctcatg 420gagagaactg tttccttgtc tcagatgtta agggaagcta aggagaagga gaagcagaga 480ctggcacagc agctcacgat g 501<210>490<211>482<212>DNA<213>智人(Homo sapiens)<400>490attgcaaact gaaagtggac aaagacttaa ggtaaacctg ctcctcatgg tggaatgctt 60ccaaatgctg gaaggaggac tttagggcag agttcactaa ggaggcttgt gcttatagat 120cagtgggcct gaaagaagtt tctctaggtt ctggttgtgt gctgtacgag gtgtaggtag 180taataatact cttgtcagcc acagtgaagc cccaagctag ccgggatagg ggactgacct 240tgtacaggca gcatggagaa actaagacag agtgtcctgc ccaagtgatg gcactgggga 300gcagtcactc aggtttattt ccaccagggc ccaagaaaaa aagaaatgag gcaacctaaa 360attccatcaa gatagatacc aatatccaag gtgcttggtc ttagcggtgt gggacccacg 420ttaaggctct tggtgggaag gtgggaggtg ttttcagcat gagatagggt tcaggctgtg 480aa 482<210>491<211>483<212>DNA<213>智人(Homo sapiens)<400>491cgcctctccc cgtgatccct ctctcgctaa ccgtaggcgc ttttcgtgaa ggcccgggtt 60tttacagcac ttcgcttttc taaccacgaa cagtgctcgt tcgttcgcag ggccagcaag 120gagagccccg cccccgcccg ccgcccgccg cccgccgccc gccgcctttg gatcccgcgg 180actccgcccg gcccggcctc cccaggcatg gcgccgctgc gcttctccgc caatctgtcc 240tggctattcc ccgagctccc cggcctcccc gcgcgggtgc gggccgcggg cagctcgggc 300ttcgaggccg tcgaggtggc ctggccgtac gcggagacgc ctgaggcgct ggcgcgcgcc 360gcgcgagaag cggggctgcg gcttgtactg atcaacacgc ccccgggaga ccaagagaag 420ggggaaatgg ggctgggggc cgtccccggg agacaggcgg ccttccgaga gggactggag 480cag483<210>492<211>266<212>DNA<213>智人(Homo sapiens)<400>492acctcatctg ctttgctttg gcatgtgagc cttgcctaag ggggcatatc tgggtcccta 60gaaggcccta gatgtggggc ttctagatta ccccctcctc ctgccatacc cgcacatgac 120aatggaccaa atgtgccaca cgctcgctct tttttacacc cagtgcctct gactctgtcc 180ccatgggctg gtctccaaag ctctttccat tgcccaggga gggaaggttc tgagcaataa 240agtttcttag atcaatcaaa aaaaaa 266<210>493<211>483<212>DNA<213>智人(Homo sapiens)<400>493gccgctcgcg ctaggagagc gggcttcggg cacttgacat ggcggcagtg gcggcgactg 60cagcagcgaa ggggaatggg ggcggcggtg gcagggccgg ggccggggac gccagcggca 120cgcggaagaa gaagggcccg gggcccctgg ccacggcgta cctggtcatc tacaatgtgg 180tgatgacagc cgggtggctg gttatagcgg ttggtctggt ccgagcatac ctggctaagg 240gtagctacca tagcctttat tattcaattg aaaagccttt gaaattcttt caaactggag 300ccttattgga gattttacat tgtgctatag gaattgttcc atcttctgtt gtcctgactt 360ctttccaggt gatgtcaaga gtttttctaa tatgggcagt aacacatagc gtcaaagagg 420tacagagtga agacagtgtc ctcctgtttg ttattgcatg gacgatcacg gaaatcatcc 480gtt483<210>494<211>301<212>DNA<213>智人(Homo sapiens)<400>494gtggctattt tcatggaata tcttttatca gcctttcagt tttaatttat ttgtgtcttt 60ggatctaaag tcagtttgtt ttggacaatg tgtagtttga tcatgatttt aaaaaatcta 120ttctgaagct gggtggttca cacctgtaat cccagcactt tgggaggatc tcttgagccc 180aggagttgga gactagcctg gtctacaaag tgagactctg tttctacaaa aaaataaaat 240aaatagttgg gtgtggtggt atgcgcttgt ggttccagct acttgggagg atgagggagg 300a 301<210>495<211>496<212>DNA<213>智人(Homo sapiens)<400>495cgaagtgaag gctaggggcc cgtacgcgcc cgcctgactg tcgccagcag ctcctcggcg 60gccccaccgc agccgccgct ccctgaggcg cgggaggccc gcgccccgcg gctcgctgtg 120cgtgggaggg cgcgagcgaa cgcgggcgag gagcggccga gccgctgaag aggagctggg 180cgccggccgc ccggccgcgc tcggcccgcg gatcgcctcc gcccggtctt cgccggcccc 240ggcccctggc gagatgccgt gtggggagga ttggctcagc cacccgctgg gaatcgtgca 300gggattcttc gcccaaaatg gagttaatcc tgactgggag aagaaagtaa ttgagtattt 360taaggaaaag ctgaaggaaa ataatgctcc taagtgggta ccatcactga acgaagttcc 420ccttcattat ttgaaaccta atagttttgt gaaatttcgt tgcatgattc aggatatgtt 480tgaccctgag ttttac 496<210>496<211>494<212>DNA<213>智人(Homo sapiens)<400>496aaactatata aaaagtgatt tgtacagaac tttattttag ctctttttta aaaatgattt 60gcatggttag aaaacggcga ggacagccag gggagggaag ggcctctagg gaactttgca 120ctttctatac ctttgtacta tgcactgccc tattgattct acacccaata atgatattac 180ttgaacccat ctgtaagaaa ctgcttcgga aattcatttg tgtgtatgta aataacacaa 240catagaaaca ggaagggaaa aaagtctgca gtaatgcacg tatttttttt ctttcctgtt 300tattttcggt tttgctttaa gtccttttat ttttaattcc ctttttgttt ttctttttgg 360gttttggttc cttttgggtt tatgggtgcc ctgatactcc agcagagatc agaaggctac 420agatccattc tatccatccg ttatgtggct ttgccatccc agcttggagt gtctttacaa 480agataataac agtt494<210>497<211>184<212>DNA<213>智人(Homo sapiens)<400>497gcgcgccgcg gctggcaggg tgtgcgtgag tttggtggcg gccggctgtg cagagacgcc 60atgtaccggc tcctgtcagc agtgactgcc cgggctgccg cccccggggg cttggcctca 120agctgcggac gacgcggggt ccatcagcgc gccgggctgc cgcctctcgg ccacggctgg 180gtcg 184<210>498<211>471<212>DNA<213>智人(Homo sapiens)<400>498tcttactaca aatggagatg gctattatga aacagcatga gcatgagcct tttatctttt 60atacttagtg atatactttg cttgaaaatc actcagcaaa gtagttcaca tgatgtgtat 120catatttgaa gtgtggtttt tctcaaaatc attgacttta aggagctcat ttctgaacaa 180aaaggtttgc tctgtggaaa aatcaatcac tgccaggatt ctttcatttc tgtactattt 240tgtataattg aatttgttca cttctctcac accagcaagt gttttacagg tgccttggat 300taaaacaaaa ttgattttaa aatttttatg taagtcattg tgtctatgat gccactttta 360aaaggaaaat gcaattgcgt aatggcttat atccttattt aatgtaccta tttgtgttct 420aataattgtt tgaatgtttt attcagctta aaactttacc atgaagtcat a 471<210>499<211>478<212>DNA<213>智人(Homo sapiens)<400>499aggtgggaaa agcggaggag gacgcccagg aggaggcggc ggcggcggcc gggaagtgaa 60aggtctcgca aagttcagcg gcggctgcgg gcgccgagcc ccgggctagc ggcagacgag 120cccgcagggc cgctccgcgg ggcagcgcag ccaggccggc tatggtcccg gggctcccgc 180cgccccccag gtgcccggga cccgccaggc cggtgcgcga gggtcacccc acctccccgc 240gcggtcccgg cccctggctc ccagctgccg gcgaccgctg accgagcccg gcgccccagg 300aggaggaaga aaccagggcc ccgttccctc ccgaggacgg cggcgcttca tcccgcagcc 360cagaggtctc ggctccctcc ggcacccgcc cggcccggct gctcccggct cctcccggcc 420atggggagct gcgcgcggct gctgctgctc tggggctgca cggtggtggc cgcaagga478<210>500<211>495<212>DNA<213>智人(Homo sapiens)<400>500gggggcttct ggcttggtgt ggaccaggag ggggcagaag gcaccctgtc gtggctgggc 60accgtcttcg gcgtgctggc tagcctctgt gtctcgctca acgccatcta caccacgaag 120gtgctcccgg cggtggacgg cagcatctgg cgcctgactt tctacaacaa cgtcaacgcc 180tgcgtcctct tcctgcccct gctcctgctg ctcggggagc ttcaggccct gcgtgacttt 240gcccagctgg gcagtgccca cttctggggg atgatgacgc tgggcggcct gtttggcttt 300gccatcggct acgtgacagg actgcagatc aagttcacca gtccgctgac ccacaatgtg 360tcgggcacgg ccaaggcctg tgcccagaca gtgctggccg tgctctacta cgaggagacc 420aagagcttcc tctggtggac gagcaacatg atggtgctgg gcggctcctc cgcctacacc 480tgggtcaggg gctgg 495<210>501<211>494<212>DNA<213>智人(Homo sapiens)<400>501ctgcggtgtg gttggtggtg agatgacgac cttagtgctg gataatggag cttacaacgc 60caaaatcgtt acagccatga aaatgtgtcg gttattccta attgtcagtt ccggtcaaaa 120acagcacgtc ttaaaacttt tactgccaac cagatagatg aaataaaaga cccttctgga 180ctcttttaca tcctcccttt tcaaaagggc tacttggtga attgggatgt tcagagacaa 240gtttgggatt acctttttgg aaaagaaatg tatcaggttg attttttaga tactaatatt 300attatcactg aaccatactt taacttcact tcaattcaag aatcaatgaa tgaaattcta 360tttgaagaat accagtttca agcagtatta agagtaaatg ctggggctct cagtgcacat 420aggtatttcc gagataatcc ttccgaatta tgctgtatca ttgttgatag tggatattcc 480tttacacata tagt494<210>502<211>479<212>DNA<213>智人(Homo sapiens)<400>502ttgtataatg ctgaatgtgt ccagagggac aagtttgcag aacctcatat tggtatatta 60aagaaataat aaaataaaaa agcactttag gttattttat ctttaacccg attgctgcaa 120tttcttttgt gtgtatatat acatatatat actttccaca aagttttatt ttttgctcag 180aataaaaagt taaattgagg tgtgaaaaga aaagcactta ccttggtgca atatgtgtag 240cttgatggtc gttgtcccat gtggccctgg cctggcagcg tttttccgct caatcagccc 300tgtgctgtga gattgtccat agggaaacac tattatgcat tctcagcaac cgctcaatct 360atgcaagcct tccctgtgtg ccccagggcg ccccctcagg ctctctgaag aactgctgtg 420ggtcctgttt tctgctgact gttgaggccc tttttcatca cttcttggtc tctcgccat 479<210>503<211>451<212>DNA<213>智人(Homo sapiens)<400>503ttgtgggccg ggtgggtttc ctaatctggt ttcgtctgcc tggttcatct gtgtgcgatg 60gctccggact cggatccctt ccctgaaggg ccgctcttaa agctgctacc cttagacgct 120agagaccggg gcacccagcg ctgccgcctg ggcccggccg ccctccacgc cctgggcgcg 180cgcttgggct cggcagtgaa gatctcgcta cccgacggcg gctcctgcct ctgcactgcc 240tggcctcggc gggacggagc ggacggcttt gtgcagctgg acccgctgtg cgcgagcccc 300ggggcggcgg tcggggcgtc gagatcccgg aggagtctca gcctgaatcg cctcctccta 360gtgccctgtc cgcccctgcg gcgcgtcgcc gtgtggccgg tgttgcgaga gcgggcaggc 420gcgcccggtg cccggaatac agccgcggtg c 451<210>504<211>462<212>DNA<213>智人(Homo sapiens)<400>504cagtggggaa ggggagagat gccgaggtgg tcagtatcct gactttcaga ggcctttttt 60tgtttgtttt aatttttgct agattgatat taaaaactca tgtggaggaa ctcaaggaat 120gtttagaaga ccaaaagtcc ccaatgacag gaacaaaagc aaccaatttt taactttctc 180ttctcattcc tgttttcatt gatttcccac atgtagtcct tttgctcagg aagtctttgg 240ggaaattaag gatctttgaa gctctgaaat aggtgatcag gttagtggtg tctgtcagct 300gtctaagagg ttggaaaatg aactactcaa gatagtcacg aaaatactga aagtttgatt 360tttctttcca tatttgaatt aattttttct gtttgactgg aaggggtttt tgtataacta 420aaacctcagc gcataaagga gatttaaaag gagcacatga tt 462<210>505<211>136<212>DNA<213>智人(Homo sapiens)<400>505tcgattatat cacacatttc agttgggagg ttgtctcaac ctgtgaccac catctgagtt 60agctggcaga cttctaggag gtcctgtctg aggtagaatc agaaatggct tccctccttc 120tcccataaaa aaaaaa 136<210>506<211>466<212>DNA<213>智人(Homo sapiens)<400>506ggggtacaga gacagcagcc tgcggagcgt tctaggcagg acagggcagc aaacctgaca 60tgcggagctg ggggcagggg taatggggcc agggggtaat ggcaggtgag gccatggcct 120agagggttgc catgcttggt gcaggggagg agaggcccag gtgtggctgc agtggcagca 180ggagtcagtg tggctgtgcc cagtgggatg ttgtcagaga atggacctgg ctgctgggaa 240aggtgattgt gtttgtctga gccacactgg actcttctct gaccagcaag cacattctgg 300agatgcgggg cagagacgag gcctccgtga gaacctttga ggtgtgaggg ccttgatctg 360gggtgcagcc tccagctttc tgcttacaga gcaggacctg caggagctcg ctgactgcct 420gcacagtgga aggaagacct gtttctttta ctttccttga ggagaa 466<210>507<211>101<212>DNA<213>智人(Homo sapiens)<400>507atgatttaat tttttaaact gtagcaattg gatagataat tttatttgaa attttacaca 60ctgaaagctc taaataaaca gatacattca cattcaaaaa a 101<210>508<211>242<212>DNA<213>智人(Homo sapiens)<400>508gacaatgcaa gtaacctcaa atgagagtgt ggaaaggcgg gaaagcagcc agagcttcat 60tgttatgaaa aaagagtgaa atgtgctctg ttgaagagtt gaagaatgaa caaaggatat 120ttagtttgaa tggaagctca gtaatgagaa atgagaatgg ttgagttctt aaaagaagca 180agtaaagaag aggatttgtg ggctactatt ctcattcagt gaatctcatw ccacccttgc 240ct 242<210>509<211>101<212>DNA<213>智人(Homo sapiens)<400>509cctttgctcc ctttttccaa tttcttattg catatctttc tgtattacaa caaaatgata 60tgcaataaga aattggaaaa agggagcaaa ggcgaagggg y 101<210>510<211>461<212>DNA<213>智人(Homo sapiens)<400>510gcaggttcgg gaccatgagt tggattcctt ttaagattgg gcagcccaag aaacagattg 60tgcccaaaac agtggagaga gactttgaaa gggagtatgg aaaacttcag caccatgtca 120aaatctgccg tgaagatatc cttggactta ctctccaatc ccctctgtga gcaagaccag 180gaccttctga acatggtgac ggccctggac acggccatga agcggatgga tgccttcaat 240caggaaaagg tgaaccagat ccagaagact gtgatcgagc ccttaaaaaa gttcggcagt 300gtcttcccga gcctcaacat ggctgtgaag aggcgggaac aggccttgca ggactacagg 360aggctgcagg ccaaggtgga gaagtatgag gaaaaggaga agacggggcc agtgctggcc 420aagctccacc aggcacgaga ggagctgcgg cctgtgcggg a 461<210>511<211>461<212>DNA<213>智人(Homo sapiens)<400>511ggctttctga tatttctaaa attgacctgg aatcaaccat tgacatgtcc tgtgctaaat 60atgaattcac tgatgccctg ctgtgccatg atgatgagct ggaagggcgc cggattgcct 120tcatcctgta cctggttcct ccctgggaca ggagcatggg tggtaccctg gacctgtaca 180gcattgatga acactttcag ccgaagcaga ttgtcaagtc tcttatccct tcgtggaaca 240aactggtttt ctttgaagta tctcctgtgt cctttcacca ggtgtctgaa gtgctgtctg 300aagaaaagtc acgtttgtct ataagtggct ggtttcatgg tccatcattg actcggcctc 360ccaactactt tgaacccccc atacctcgga gccctcacat cccacaagat catgagattt 420tgtatgattg gatcaaccct acttatctgg acatggatta c 461<210>512<211>686<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(686)<223>n＝A、T、C或G<400>512actgacctga aggagaccta agagtccttt ccctttttga gtttgaatca tagccttgat 60gtggtctctt gttttatgtc cttgttccta atgtaaaagt gcttaactgc ttcttggttg 120tattgggtag cattgggata agattttaac tgggtattct tgaattgctt ttacaataaa 180ccaattttat aatctttaaa tttatcaact ttttacattt gtgttatttt cagtcagggc 240ttcttagatc tacttatggt tgatggagca cattgatttg gagtttcaga tcttccaaag 300cactatttgt tgtaataact tttctaaatg tagtgccttt aaaggaaaaa tgaacacagg 360gaagtgactt tgctacaaat aatgttgctg tgttaagtat tcatattaaa tacatgcctt 420ctatatggaa catggcagaa agactgaaaa ataacagtaa ttaattgtgt aattcagaat 480tcataccaat cagtgttgaa actcaaacat tgcaaaagtg ggtggcaata ttcagtgctt 540aacacttttc tagcgttggt acctcgccgc gaccacgctg gaattccgga agggcctgtc 600ctangatcca gtgtggtgga attctgcaga tatccagcac agtggcggnc gctcgagtct 660aaanggcccg tttaacccgc tgatca 686<210>513<211>429<212>DNA<213>智人(Homo sapiens)<400>513catgaacgac accgtaacta tccgcactag aaagttcatg accaaccgac tacttcagag 60gaaacaaatg gtcattgatg tccttcaccc cgggaaggcg acagtgccta agacagaaat 120tcgggaaaaa ctagccaaaa tgtacaagac cacaccggat gtcatctttg tatttggatt 180cagaactcat tttggtggtg gcaagacaac tggctttggc atgatttatg attccctgga 240ttatgcaaag aaaaatgaac ccaaacatag acttgcaaga catggcctgt atgagaagaa 300aaagacctca agaaagcaac gaaaggaacg caagaacaga atgaagaaag tcagggggac 360tgcaaaggcc aatgttggtg ctggcaaaaa gccgaaggag taaaggtgct gcaatgatgt 420tagctgtgg 429<210>514<211>346<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(346)<223>n＝A、T、C或G<400>514aaaactttct ctacttattt agttttntcc tctgagttca accgctgctg gattcgtttg 60gcataacttt gtgccatgga gttaatgata gataggatga agtaacacac catgacaacg 120accaactttt caaacatcca ggacaaccag ttttctccct gtggtgtgcc catttcgctt 180ttgtggtgaa gcttctgccg ttgagcctcc aggtactcct gaaatggctt ctgcagagat 240ggacctatgc cggggacagc actggaagca gggtacagta gcccaaagaa aaagacacat 300ttgggaagaa aagcaggaaa aacgttaaag aaaatgtact taccac 346<210>515<211>549<212>DNA<213>智人(Homo sapiens)<400>515ctgaccagga ctgtgaagat gcggttccgc tgcgaagatg gggagacatt ttccaggaac 60gtcatgatga tccagtcctg caaatgcaac tacaactgcc cgcatgccaa tgaagcagcg 120tttcccttct acaggctgtt caatgacatt cacaaattta gggactaaat gctacctggg 180tttccagggc acacctagac aaacaaggga gaagagtgtc agaatcagaa tcatggagaa 240aatgggcggg ggtggtgtgg gtgatggaac tcattgtaga aaggaagcct tgctcattct 300tgaggagcat taaggtattt cgaaactgcc aagggtgctg gtgcggatgg acactaatgc 360agccacgatt ggagaatact ttgcttcata gtattggagc acatgttact gcttcatttt 420ggagcttgtg gagttgatga ctttctgttt tctgtttgta aattatttgc taagcatatt 480ttctctaggc ttttttcctt ttggggttct acagtcgtaa aagagataat aagattagtt 540ggacagttt 549<210>516<211>382<212>DNA<213>智人(Homo sapiens)<400>516ccgctcgtca gactccagca gccaagatgg tgaagcagat cgagagcaag actgcttttc 60aggaagcctt ggacgctgca ggtgataaac ttgtagtagt tgacttctca gccacgtggt 120gtgggccttg caaaatgatc aagcctttct ttcattccct ctctgaaaag tattccaacg 180tgatactcct tgaagtagat gtggatgact gtcaggatgt tgcctcagag tgtgaagtca 240aatgcatgcc aacattccag ttttttaaga agggacaaaa ggtgggtgaa ttttctggag 300ccaataagga aaagcttgaa gccaccatta atgaattagt ctaatcatgt tttctgaaaa 360tataaccagc cattggctat tt 382<210>517<211>323<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(323)<223>n＝A、T、C或G<400>517acgagcgtag gacgatgctt ctcttntgtc agcctgcaac tgagtcagga ttgaatactt 60ggaccccagg tctggagatt gggatactgt aatgcttctt tgttattata acataaaagc 120accactgttc tgttcatttc ctagctgttc taattaagaa aactattaag atgagcaacc 180acatttagaa atgtttattg acaggtcttt tcaaataatg cttttctaat taatagccaa 240agatttcata tctaactttg taaccagaat tatacagtaa gttgacacca cttagattta 300aaggcagaca gttttgcttt agt 323<210>518<211>605<212>DNA<213>智人(Homo sapiens)<400>518ctggataccg aggctggggc cccacactgt ggaacaaacc cacagcttgc tcaggatcca 60tcccagaatc agcagacatc aaatccaacg cacagttcag aagatgtgaa gccaaaaacc 120ctcccgctgg ataaaagcat taaccatcag atcgagtctc ccagtgaaag gcggaagtct 180ataagtggaa agaagctgtg ctcttcctgt gggcttcctt tgggtaaagg agctgcaatg 240atcatcgaga ccctcaatct ctattttcac atccagtgtt tcaggtgtgg aatttgtaaa 300ggccagcttg gagatgcagt gagtgggacg gatgttagga ttcgaaatgg tctcctgaac 360tgtaatgatt gctacatgcg atccagaagt gccgggcagc ctacaacatt gtgacacggc 420tttcaagctt ccggatcact caccatttct ttactgagag tgtcccctgg caactgctta 480acaaaatccc aagctcaggg gcttctcagc atttacctaa tttctgaaag gctcttctga 540aaggtggtat ctgttctttc gtagcacagt gtttatgttt ttcctgttta ttggtttggt 600ttttt 605<210>519<211>462<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(462)<223>n＝A、T、C或G<400>519ctgctggtca tgnccttggc agtcttttgt gcaaaataag gcatattnga gctccacatt 60aaccttgcgg caggcgncta cttgctctgc atgctgtanc agngcacgtc ctccttcccc 120ttggtggtgt agcctgngan aggctgccca tacttatcca cacaccagca naagccccgc 180ttcctgcctt tggaagggcg acactgcttt ttcttataaa atcccttctt gtcacagttg 240ggaatgtgna cacccctggg actcagcaca ttgaggaact tcaagtgatt cagtgtgnct 300tccatttctc tacggcangn accatattct gtctcccgct tggactcgga ggagaagttc 360tgggtatctg tgctctgaga ctcgtagtca actttgtagc gctggctgnc tttagcatgc 420cctttcttga tgatgantat ctttgaatgg agggggtgga ac 462<210>520<211>565<212>DNA<213>智人(Homo sapiens)<400>520actcgtaata aatatgcatc cggaaacaag ataaaaggct acacctcgtc aggcatccta 60caaaaatgtc tcaagtttta tatactctgc agcatttctg tgcgggggca gaaggggctg 120ttgtgtattt tctgaagtgc tgtgacaaaa ggtcctttca catttctttg gagcattttt 180gaaattgctt aactataatt aaacaactta agaaaagtaa caccaagctt taaagccatt 240tttgctttgc tgtcattggt ccttatccaa tacagatcaa catatcatcc agcacagcca 300agcacccact gaggccaagc agccttgtgg gacatgggcc ctgtcagagc aggccctact 360ttcagttaaa tactttggag agtccaggat tctgtctctc tccctcaaca agattaatgc 420cataagggaa gttgcaagcg tgttagaaac atttttaacc tgaaagtaaa gtgaacagaa 480atattttttt ttccgagacc tctgctatgc accataatat taccatatca gggtttttag 540cttcaaagtt gaaaaacaga ttggt565<210>521<211>127<212>DNA<213>智人(Homo sapiens)<400>521acatggctga cgtcaccgtc cagtgcaaaa tcaaaaaaga aagaaagaaa aaccccaaag 60aaagaggatt tttcagtgga gaacatggtg ggctgattag gcttctatta gattacattc 120atttcac127<210>522<211>642<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(642)<223>n＝A、T、C或G<400>522actatgtttc gtaaattaaa taggtntggc ccagaagacc cactcaattg cctttgagat 60taaaaaaaaa aaaaaaaaag aaagaaaaat gcaagtttct ttcaaaataa agagacattt 120ttcctagttt caggaatccc ccaaatcact tcctcattgg cttagtttaa agccaggaga 180ctgataaaag ggctcagggt ttgttcttta attcattaac taaacattct gcttttatta 240cagttaaatg gttcaagatg taacaactag ttttaaaggt atttgctcat tggtctggct 300tagagacagg aagacatatg agcaataaaa aaaagattct tttgcattta ccaatttagc 360aaaaatttat taaaactgaa taaagtgctg ttcttaagtg cttgaaagac gtaaaccaaa 420gtgcacttta tctcatttat cttatggngg aaacacagga acaaattctc taagagactg 480tgtttcttta gttgagaaga aacttcattg agtagctgtg atatgttcga tactaaggaa 540aaactaaaca gatcaccttt gacatgcgtt gtagagtggg aataagagag ggctttttat 600tttttcgttc atacgagtat tgatgaagat gatactaaat gc 642<210>523<211>244<212>DNA<213>智人(Homo sapiens)<400>523ctgaaggagc tgatccagaa ggagctcacc attggctcga agctgcagga tgctgaaatt 60gcaaggctga tggaagactt ggaccggaac aaggaccagg aggtgaactt ccaggagtat 120gtcaccttcc tgggggcctt ggctttgatc tacaatgaag ccctcaaggg ctgaaaataa 180atagggaaga tggggacacc ctctgggggt cctctctgag tcaaatccag tggtgggtaa 240ttgt 244<210>524<211>407<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(407)<223>n＝A、T、C或G<400>524acgttagtgg tgatgtcacc caccctnnng ctggggccga ggatgctctc attgtgcact 60gcgtagatga ctctggccac tggggcagag gtggtttatt tacagctctg gaaaagcgat 120ccgctgagcc aagaaaaata tatgagctgg ctgggaaaat gaaagacctg agtttgggag 180gtgtcctttt atttcctgtt gatgataaag aatcaagaaa caaagggcaa gatttgttgg 240ccttgattgt ggctcagcat cgtgatcgtt ccaatgtcct gtctggcatt aagatggcag 300ccctagaaga gggcctgaag aagatatttt tagcagcaaa aaagaagaaa gcaagtgttc 360atcttccacg tattggacat gccacgaaag gttttaactg gtatggt407<210>525<211>276<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(276)<223>n＝A、T、C或G<400>525acacaggagg caacgtgttt cacatnatag acttcacttc caactccttg gaatgttcat 60ttctttggct tacaggagag actagacagg aaggccaggc aatgcttagg caactaaaat 120gaggttgggg gtaatgctaa cgtcaccctc acagggatgg ccacggggac tgttattcgc 180aagctggttt tctagacctg ttagctggaa gcatggtgag caccatttct ggacgctcag 240gccgtgtcgg gcttcagtca tctccaccac acaggt276<210>526<211>288<212>DNA<213>智人(Homo sapiens)<400>526acaattaccc accactggat ttgactcaga gaggaccccc agagggtgtc tccatcttcc 60ctatttattt tcagcccttg agggcttcat tgtagatcaa agccaaggcc cccaggaagg 120tgacatactc ctggaagttc acctcctggt ccttgttccg gtccaagtct tccatcagcc 180ttgcaatttc agcatcctgc agcttcgagc caatggtgag ctccttctgg atcagctcct 240tcagctcctt cttgctcagg gtgtgcttgt caccctccct gccggagt 288<210>527<211>412<212>DNA<213>智人(Homo sapiens)<400>527actttgagct tattgttttt attctgtatt aaatattttc agggttttaa acactaatca 60caaactgaat gacttgactt caaaagcaac aaccttaaag gccgtcattt cattagtatt 120cctcattctg catcctggct tgaaaaacag ctctgttgaa tcacagtatc agtattttca 180cacgtaagca cattcggacc atttccgtgg tttctcatga gctgtgttca cagacctcag 240cagggcatcg catggaccgc aggagggcag attcggacca ctaggcctga aatgacattt 300cactaaaagt ctccaaaaca tttctaagac tactaaggcc ttttatgtaa tttctttaaa 360tgtgtatttc ttaagaattc aaatttgtaa taaaactatt tgtgtaaaaa aa 412<210>528<211>489<212>DNA<213>智人(Homo sapiens)<400>528aaatgcaaaa agtcaaagta ggtaacaggt tggtaattaa agtgtcagga agactggaag 60aggcaaaaat caagcagagt tccaataagt gtatgaaaaa aaaaatcata actgaaggtt 120taagaaaagt ccccaaaggc agaatcacaa tatgagcagg aggaataaaa agcttttgga 180tataccaggc agctttctgt acgactcagg tttacaggtg aaattcctca gtttgagttc 240agaagaattt gaacttattc cagcaaaata cttcaatctt tttattactg cctcctcccc 300catcttcttt ctgggcaaag ggatgcttgg attaggtcca aagctcctgg cagggggagg 360ggccatgtgt cacagcataa cagacggttg caagtgcttt actgagcagg ggtcaggttt 420gcagcaactc tgataggctc acacaatggc ctccatttta cagcccctcc ttggaggccc 480actgatcag 489<210>529<211>631<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(631)<223>n＝A、T、C或G<400>529acttgcctaa agtttttata tctgnntctt ctgctgtaaa tcttcccttc ataaatgaaa 60attttaataa aatcaactat gtggaaatat ataattaaag gaattcacta actgtgattt 120tcataattta gggacattct cttctagtaa gcatggtgca ttatttacta gagatataat 180atgcattaaa acaaaaaatg ttttctatca tcatagaaaa gtttgaggtc cagggataat 240catctctgga tacattattt cctaccgtcg tggtacacac tgaacacatt tgaggcttat 300gactggttct tttacttaca aatattgttt agacacattt tcaaatgtca caccaatcaa 360taataataag gaatggattt tatctatatt gacagttctt tcaaccttaa gagtgaactg 420ctacaggtaa gattcaatca catttttcag gagaaagcta ttgagaccaa tatgctttgg 480ttatctaata ggggtggaat gacttataat gctatttact ccaggcaaag agaaaataca 540acagacatag gatcttgatt tcaacgtagt tctcctccat gtgcatttct ctgtccgttt 600aggcaatgcc aactggtcca ccagtgaaca t 631<210>530<211>316<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(316)<223>n＝A、T、C或G<400>530acacatttaa atgactcacg agantnaagt ttttttcaaa tatattaaga tcacaccacc 60ttgttgttta tcgaaagata ttcaaggaga aagatctgac tctccaaact gcatctgaga 120ttgccacttt aaacagacct catttcaaac atgcaacaac gccactggta ataaagcttt 180ggaatgggtg ctcattctat tatttcacta caaacagcat agaaagcaag agaagttggg 240aatttattct aaaatagaat ggaggttgtc atctacagca gcactcctca ctcctctgtt 300gccattttta gcaagt 316<210>531<211>296<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(296)<223>n＝A、T、C或G<400>531aaagtatcat ttatttgaaa aacatacatt atcattntgt ttttgatatt tgataatgaa 60aaaaatcttt gnttgtttat ttctgaaaaa gaactgtatt tagngattat tttagatagt 120gatattatan cattcatctg tgtgtaaatt atttcatata gggaagagtt ctgatctgta 180cctatggttc ttattgaaaa caacattgga tgtgcatttc tgtgatgtta tgaatacatt 240tctactttat tttgaaacat ttgccaaact aaatactgta acactgtata acattt 296<210>532<211>266<212>DNA<213>智人(Homo sapiens)<400>532acatatgcac caaattccat tttagaagtt tccatatcat tttcatagaa aacaaagttt 60gaaaacaagt aacatttaaa cacagcacgg tattctacca caactgaaac ttttttcttc 120ttcttcttta caggactcaa caaaatctaa aaatgaacta tgctgtagat ttacctcatg 180caaagatctt tatgttatct ctgaaaatga aaaggatggc cttttaagca cattttactg 240ttttatacta ttatggcaac ttgtgt 266<210>533<211>289<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(289)<223>n＝A、T、C或G<400>533actcagaagt cacttttaat atcancgaca gaaatatttc actaattcaa ctgaggcaaa 60tttcctttct agacaaagga cctagaaatt gagcatgcaa aacatccatc cattcattca 120ttcaaataat tagccaattt taccgtcatt taattccacc agaagcaaat actagaatat 180ctagaagtag tttgggtaaa gaaacattta cattttaata ttgtgtaatg tcataaattt 240ggggctaaaa taacaccagg tcaaatttga tccctttgta tgtgagggt 289<210>534<211>293<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(293)<223>n＝A、T、C或G<400>534aaaataaaag gttctttaca agatgatacc ttaattacac tcccgcaaca cagccattat 60tttattgtct anctccagtt atctgtattt tatgtaatgt aattgacagg atggctgctg 120cagaatgctg gttgacacag ggattattat actgctattt ttccctgaat ttttttcctt 180tgaattccaa ctgtggacct tttatatgtg ccttcacttt agctgtttgc cttaatctct 240acagccttgc tctccggggn ggttaataaa atgcaacact tggcattttt atg 293<210>535<211>408<212>DNA<213>智人(Homo sapiens)<400>535acttgaacac ttaaagagaa aaactctaaa taaagtcata gaggggatgg tagagatgac 60cacagaaaat gaccacggag agtattatga agattgcaag attagacatt gatgatgtaa 120attactccct ttctagataa aataatccat agatgtttat gaatcatatt tgtatgatta 180ttgctgttac tattattttg acacattatt tattattatt gttgtcacta ttattaccat 240taagatagca ggcgtaaaac tgtactggtt ccttcagtag tgagtatttc tcatagtgca 300gctttattta tctccaggat gtttttgtgg ctgtatttga ttgatatgtg cttcttctga 360ttcttgctaa tttccaacca tattgaataa atgtgatcaa gacaaaaa 408<210>536<211>184<212>DNA<213>智人(Homo sapiens)<400>536acctctcatc aaggctctgc ctacaggcac attgtgatgt atctctgcac tgatcaccta 60ggtcatgtaa cttttttcta ggctctacct acgatggcat tgtgacataa ctctgcacta 120atcatccacg tgatgtaact cttgtctagg atgtgcctaa attaactttt tgacgtaacc 180ctgt 184<210>537<211>311<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(311)<223>n＝A、T、C或G<400>537ccacagttgt atcatatagc atctntaaca tttcatctag gattatctag tatagatctt 60actatatttg gggctatgtt gtatacaatg ttaacaagaa catatcttct ctgcatatat 120gtgtgaatta taaagaaaag catgagaatg actctaagtt caacaaacat gggtgaatct 180ctatgtgctc ccagtgtcct ggatgggctc cccagcaagc cattcctcct tcctgttctg 240atattactat tcttttttac attgtgctaa ggaggacaaa aggtgagaga tgaaaataaa 300gccttgcctt t 311<210>538<211>302<212>DNA<213>智人(Homo sapiens)<400>538aaaataaaaa agcaaaaact cttgtggtac ctagtcagat ggtagacgag ctgtctgctg 60ccgcaggagc acctctatac aggacttaga agtagtatgt tattcctggt taagcaggca 120ttgctttgcc ctggagcagc tattttaagc catctcagat tctgtctaaa ggggtttttt 180gggaagacgt tttctttatc gccctgagaa gatctacccc agggagaatc tgagacatct 240tgcctacttt tctttattag ctttctcctc attcatttct tttatacctt tcctttttgg 300gg 302<210>539<211>396<212>DNA<213>智人(Homo sapiens)<400>539actgtttatt tgctccttct cttcatgcct gtggctggat gtcccacaac actataagaa 60atataagtca agccctttgt gttaagcaag aactacagac tccatctttt cacccaaatc 120atgaatgacc aataaaaagc aagttattcc agaggaagaa gcagcccttg aaatgttaag 180gcttaggctt gaaaggtgaa gagcaggaat tctctctttc aaatcctaga gcataaaccc 240atgtgtggcc aagtgagatc agccctcaag ggcacatgcc aagggcagag cagcccatgt 300agacagcttc ggagggcatg ggggtgtagg gagttcgggg tagctcctca ttaactattt 360gttgggtgag taaaggggtg aggctcagtg gcaggt396<210>540<211>634<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(634)<223>n＝A、T、C或G<400>540ccaaaaacaa gatgaccaga tttgntttna gcctgatgac cctacaggtc gtgctatgat 60atggagtcct catgggtaaa gcaggaagag agtgggaaag agaaccaccc cactctgtct 120tcatatttgc atttcatgtt taacctccgg ctggaaatag aaagcattcc cttagagatg 180aggataaaag aaagtttcag attcaacagg gggaagaaaa tggagattta atcctaaaac 240tgtgacttgg ggaggtcagt catttacagt tagtcctgtg tctttcgact tctgtgatta 300ttaaccccac tcactaccct gtttcagatg catttggaat accaaagatt aaatccttga 360cataagatct catttgcaga aagcagatta aagaccatca gaaggaaatt atttaggttg 420taatgcacag gcaactgtga gaaactgttg tgccaaaaat agaattcctt ctagtttttc 480ttgttctcat ttgaaaggag aaaattccac tttgtttagc atttcaagct tttatgtatc 540catcccatct aaaaactctt caaactccac ttgttcagtc tgaaatgcag ctccctgtcc 600aagtgccttg gagaactcac agcagcacgc ctta 634<210>541<211>221<212>DNA<213>智人(Homo sapiens)<400>541cacacaagca gcagagacca tgggaaccct ctcagcccct ccctgcacac agcgcatcaa 60atggaagggg ctcctgctca cagcatcact tttaaacttc tggaacctgc ccaccactgc 120ccaagtcacg attgaagccg agccaaccaa agtttccgag gggaaggatg ttcttctact 180tgtccacaat ttgccccaga atcttaccgg ctacatctgg t 221<210>542<211>287<212>DNA<213>智人(Homo sapiens)<400>542cctcttctac tatggcagga gatgtggcgt gctgttgcaa agttttcacg tcatcgtttc 60ctggctagtt catttcatta agtggctaca tcctaacata tgcatttggt caaggttgca 120gaagaggact gaagattgac tgccaagcta gtttgggtga agttcactcc agcaagtctc 180aggccacaat ggggtggttt ggtttggttt ccttttaact ttccttttgt tatttgcttt 240tctcctccac ctgtgtggta tattttttaa gcagaatttt atttttt287<210>543<211>274<212>DNA<213>智人(Homo sapiens)<400>543acttgtgaaa cacagctgtt cttctgttct gcagacacgc cttcccctca gccacaccca 60ggcacttaag cacaagcaga gtgcacagct gtccactggg ccattgtggt gtgagcttca 120gatggtgaag cattctcccc agtgtatgtc ttgtatccga tatctaacgc tttaaatggc 180tactttggtt tctgtctgta agttaagacc ttggatgtgg tttaattgtt tgtcctcaaa 240aggaataaaa cttttctgct gataagataa aaaa 274<210>544<211>307<212>DNA<213>智人(Homo sapiens)<400>544ccaggtggtt gtcttattgc accatactcc ttgcttcctg atgctgggca atgaggcaga 60tagcactggg tgtgagaatg atcaaggatc tggaccccaa agaatagact ggatggaaag 120acaaactgca caggcagatg tttgcctcat aatagtcgta agtggagtcc tggaatttgg 180acaagtgctg ttgggatata gtcaacttat tctttgagta atgtgactaa aggaaaaaac 240tttgactttg cccaggcatg aaattcttcc taatgtcaga acagagtgca acccagtcac 300actgtgg307<210>545<211>570<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(570)<223>n＝A、T、C或G<400>545accttagaaa tttgcaacca cctccctgaa agtcttctcc cacgttatta agtgcaatgt 60ttatggtaaa tgtagaagca tcatgatgag gacgaagaga acgctgtcgt tcaggggagt 120attttactac aaaattcagt agtgcaaatc ccttcgtata atagcctgca aagaccttca 180gtgtaactgg ngcaatgaac tcccggataa aatgaagcca tacattctcc agatcaactt 240gcttcatgtg gatatcatca gttgggacat tttcataacc accagatata cggctatcat 300gatgttttcc cccagaccat ttgccgtaat gttccatttc ttctaccaat tcatcacagg 360ctttttcaga aaatatgggg aaccaaaaga catctggaca gggctgttca actatatttt 420cagtgaaaat ctttgaataa tcacggttta tatacttttc cttccagtcc acaggatttt 480caaaaatctg ccagaggtca ttgttataat gggaagtatt gtaattagca gtggataata 540gccttccaaa ttcatgtcta ttagaaatgt 570<210>546<211>589<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(589)<223>n＝A、T、C或G<400>546aaaaatactt tttaccaaag gtgctatttc tctgtaaaac actttttttt ggcaagttga 60ctttattctt caattattat cattatatta ttgtttttta atattttatt ttcttgacta 120ggtattaagc ttttgtaatt atttttcagt agtcccacca cttcataggt ggaaggagtt 180tggggttctt cctggtgcag gggctgaaat aacccagatg cccccaccct gccacatact 240agatgcagcc catagttggc ccccctagct tccagcagtc cactatctgc cagaggagca 300agggtgcctt agaccgaagc caggggaaga agcatcttca taaaaaactt tcaagatcca 360aacattaatt tgtttttatt tattctgaga agttgaggca aatcagtatt cccaaggatg 420gcgacaaggg cagccaagca gggcttagga tatcccagcc taccaatatg ctcattcgac 480taactaggag ggtgagttgg ccctgtctct tcttttttct ggacctcagt ttccttcagt 540ggagcttggt aaaaatgcac taccntttga tttgataagg tataaatct 589<210>547<211>293<212>DNA<213>智人(Homo sapiens)<400>547actcctatta ttgactgtag tcaatcaaac ataaaaaggt gaaagtaaaa tttaattttt 60tacccttatt ttactgacca atatggaagt tcttggtatc tttaaggctg accttcctgg 120tattgtgtaa tgattgaatg tatctaaact gtaataattt gaaactgaca aacataacct 180tctcagactt acaaaactat gttctttcta aagatacaga tttttattat tttattttga 240ctaggaagga tttataaata aatgtaatga aaaatctttg atcttaataa agt 293<210>548<211>98<212>DNA<213>智人(Homo sapiens)<400>548aaacaaaggt tgagatgtaa aaggtattaa attgatgttg ctggactgtc atagaaatta 60cacccaaaga ggtatttatc tttacttttt tttgtaca 98<210>549<211>121<212>DNA<213>智人(Homo sapiens)<400>549acatgcatat ttcaaagacc tgttaatggc gtccactttg gattcttaca tgaaacgatt 60cagtgcacat tgtaagccta aggaccacgc aaaagggttt cccacatatt aagtattcag 120t 121<210>550<211>509<212>DNA<213>智人(Homo sapiens)<400>550acaatagtat acattttata atgatgaact tataatgatt aagggacatt tctataaaaa 60tactacaata gttttatgca caacttccca ttaaaaatga gatttcttat ttgtttgtct 120gtttttactc tgggagtaat actttttaaa ttacctttac atatatagtc actggcatac 180tgagaatata caatgatcct ggaaattgca gtaacaaaag cacacaacga ttatagtaac 240tataagatac aataaaacaa ataaatgtga aagtagattc atgaaaatgt attcctttaa 300aatattgttt tcctacaggc ctatttaaca agatgtttca ttttactgta tattttgtag 360ttaatataaa tgttgctcta atcagattgc ttaaaagcat ttttattata tttatgttgt 420tgaactaata tatgaaataa gtaaatgtag ctcccacaag gtaaacttca ttggtaagat 480tgcactgttc tgattatgta agcatttgt509<210>551<211>427<212>DNA<213>智人(Homo sapiens)<400>551accatggtta tatgattaat cttgggacaa agaattttat agaaattttt aaacatctgg 60aaaagaagct taagttttat catccttttt tttctcgtga attcttaaag gattatgctt 120taatgctgtt atctatctta ttgttcttga aaatacctgc attttttggt atcatgttca 180accaacatca ttatgaaatt aattagattc ccatggccat aaaatggctt taaagaatat 240atatatattt ttaaagtagc ttgagaagca aattggcagg taatatttca tacctaaatt 300aagactctga cttggattgt gaattataat gatatgcccc ttttcttata aaaacaaaaa 360aaaaaataat gaaacacagt gaatttgtag agtgggggta tttgacatat tttacagggt 420ggagtgc427<210>552<211>340<212>DNA<213>智人(Homo sapiens)<400>552cctcaaggcg gtccaattat ccacttgcag attctacaga aagagtgttt caaaactgct 60ctgtcaagag aaatggtcca ccgtgtgtgt ggaatgcagc catcacacat tagtttctga 120gattgcttct gtcttggttt tatggggaga tatttccatt tctagcatag gcttcaaggc 180gctctaaata tccgcttgga aatactacaa aaacagtgtt tcaaaactgc tgtatccaaa 240ggaaggtgcc actcgctgag ttgaatgcac acatcacaag gaagtttctg agaattcttc 300tgtctagatt catacgaaga aatcccgttt ccaacgaagg340<210>553<211>549<212>DNA<213>智人(Homo sapiens)<400>553acttgagctg tgaggtcatc ggaatcccga cacctgtcct catctggaac aaggtaaaaa 60ggggtcacta tggagttcaa aggacagaac tcctgcctgg tgaccgggac aacctggcca 120ttcagacccg gggtggccca gaaaagcatg aagtaactgg ctgggtgctg gtatctcctc 180taagtaagga agatgctgga gaatatgagt gccatgcatc caattcccaa ggacaggctt 240cagcatcagc aaaaattaca gtggttgatg ccttacatga aataccagtg aaaaaaggtg 300aaggtgccga gctataaacc tccagaatat tattagtctg catggttaaa agtagtcatg 360gataactaca ttacctgttc ttgcctaata agtttctttt aatccaatcc actaacactt 420tagttatatt cactggtttt acacagagaa atacaaaata aagatcacac atcaagacta 480tctacaaaaa tttattatat atttacagaa gaaaagcatg catatcatta aacaaataaa 540atacttttt 549<210>554<211>321<212>DNA<213>智人(Homo sapiens)<400>554acctaataat atgttaacat aaacataaca acacacatat tatttttcta ccccttggca 60actgaaaatg aagttaccat tcctaggcca aatttttaga caaagctttc taaaaccatc 120tttataaagt aaattcagat atgcttacaa taaaaagaca taaaagattc atcctgagat 180gaattctgag tcaataacta aaaaccattt ctaccagtgc atcactacca tgtaatccat 240tctacgcaag ctctacaaat attgagtcaa atcctgtctg tcagaaaatg aagacccaat 300aagtttgccg aagtattcag t321<210>555<211>322<212>DNA<213>智人(Homo sapiens)<400>555ctggatcccg agaatactgg aacaatagag ctcgacctta tctcttggct ctgtttctca 60gtactttgaa gttataacta atctgcctga agacttctca tgatggaaaa tcagccaagg 120actaagcttc catagaaata cactttgtat ctggacctca aaattatggg aacatttact 180taaacggatg atcatagctg aaaataatga tactgtcaat ttgagatagc agaagtttca 240cacatcaaag taaaagattt gcatatcatt atactaaatg caaatgagtc gcttaaccct 300tgacaaggtc aaagaaaact tt 322<210>556<211>286<212>DNA<213>智人(Homo sapiens)<400>556aaaaaatatg tatctaagaa tgttctaggg cactctggga acctataaag gcaggtattt 60cgggccctcc tcttcaggaa tcttcctgaa gacatggccc agtcgaaggc ccaggatggc 120ttttgctgcg gccccgtggg gtaggaggga cagagagaca gggagagtca gcctccacat 180tcagaggcat cacaagtaat ggcacaattc ttcggatgac tgcagaaaat agtgttttgt 240agttcaacaa ctcaagacga agcttatttc tgaggataag ctcttt 286<210>557<211>459<212>DNA<213>智人(Homo sapiens)<400>557acagaagatg aataataatg aaaaactgtg attttttgac tatcacatac attgtgttaa 60aaaacaggta aatataatga ctattactgt taagaaagac aaggaggaaa actgtttcaa 120tgttcaggtt taaatactaa gcacaaaaat ataacaaatt ctgtgtctac aataattttt 180gaagtgtata caagtgcatt gcaaatgagc tctttaaaat ttaaagtcca tttccccttt 240agccaagcat atgtctacat ttatgatttc tttctcttat tttaaagtct cttctggttt 300agttttttaa aaagtttcat catggctgtc atcttggaat ctagcctcca gctcaaagct 360gagacttcac gcatacatat tctcctttct gggtgcatct tcacctagtt tctccaagta 420ttcagagtta aatagcacaa cttcttttat atgttccct 459<210>558<211>303<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(303)<223>n＝A、T、C或G<400>558aaaaaataaa aaacaagaca acaatttagt agaagtaccn ctgggaggga ggggagggga 60aaaaaggata tacaggggca ggngtattct ctgtacagag gtgcananaa aatttcacat 120anctttanag aatgccttgt ggaaaaaaaa aaataggccc caatacttgt tactgccctt 180tatcaaaact gtgtgcatga cctgcacaaa taaaatcaca aaacagtgtt gccacattct 240tcaaggaaac aaagcaaaat ttagggggnt tcttttccct ctccttgtta aaagtcattt 300ttt303<210>559<211>232<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(232)<223>n＝A、T、C或G<400>559aaagcattta ttaagaattt actcaggcat gatggcccat acttgtaatc ccagctattg 60ggaaggatga gatgggagga tggcttgagg ccagaggttt gagaccgacc agccagggca 120acacagtgag accccttctc aaaaaaaaaa aaaaaaaaag agagagtgtg tgattagaag 180ctaaatagga aagttttgag cttcaagtca gngaggagta aaaaagattt tt 232<210>560<211>336<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(336)<223>n＝A、T、C或G<400>560ctctgcaaaa ataannataa aaaaataaat aaaattttaa aaataataaa attcactata 60tacacatata aagaaataaa aagaagtctc agttgcagct atttgtcaaa attaatatcc 120atttcttttt atatacggtg aatattgcgc aattatagat ctggattttg aaccacttaa 180tgaagcggca acaccaggtg ttttgaggtg ttggcattct tcgctgattt ggctgttccc 240aatgtttaca ttatttaatc ttgcaaaaat ggttctgtgc acttggatgn gaaatgctgn 300ccagntttat tttttttatg ttgntatcct tggatg336<210>561<211>636<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(636)<223>n＝A、T、C或G<400>561acattatggg ttttattgct ttcttttatg gtagacctgt taatggggaa aaaatacatc 60aaatcaaata gaatcttata tctgtatgtt aaaatagagc acttacctga agtcagtggc 120ctggatcata gccctggatc atttcccagt ctgtcctgtg ctgtgtgacc ttggacaagg 180cgcttcatct ctctgggcct ctatttctcc atttgtaaaa caagtggctg cagtagatga 240tggctgagag cccttcctgt tcccagatgc cttggtccaa agaccccacc cctctgctgg 300tcctgccaac gtgttggtgc tataagctgc ttcagatata aaattggttt atctataatg 360tttgttcatt taatagcttc taaaaggcct ttttgttata cagtgctttt tttctagttt 420tatggacttg gttactgtaa taatgtcttg tttttagcca tgtaactaca aacagatatt 480ctcttgatgt cttagtaaat ttgcatttga tatatcattg atgagatttt gttgttatgt 540aatattcttt ggctacgcat ctgtccagca tcttattaac cataatactg ngatcattat 600ttggaaatat gtcctatgga aagaataaaa gcatgt636<210>562<211>708<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(708)<223>n＝A、T、C或G<400>562acagtccacc ttttgataca tgccatgcct ttgatcaaag aacaggacat aaaaacaaag 60tcacaatgac attccatagt aaatttggaa tcagaactcc aaatgcaact tcgggctcgc 120tggagaacaa ctaaggggca ccaaaccctc tgaggtttta ctttaaggtt cgctgtatgt 180ttgccttgga caaaaaggct acctaccacg tgctatccag taatatactt aaataagcca 240atacttagat ctactgtaag gcagatgcta attataaggc attaagtaag caaatagtgc 300cctcagctac tgcagaagaa aagtcccact gaggaaaaga aagtcttgtg atttttaaag 360gcaagttttc aagtgctctc atagttctat cctctaattc cattaaatcc atactaggag 420cgtcagtgag ggttttcata gcttttggaa atactttggt ctctgaactg taattagcaa 480gaagtaaaaa cagaaacgtc aaacgtcaaa tgtttgcttt gttacctgga ggactaaatg 540tagatgtctt tagtatactt tgtatgttct taatattgga agataatttt gtgaatctgt 600agattttatt ttttcagtct taccttacaa atttcttttc tatgaataat agaggactta 660cngcactctg ccatttgtta atgaaaggaa ggcngangat ttagaaag 708<210>563<211>290<212>DNA<213>智人(Homo sapiens)<400>563ccagatgctc atccactttc agactttcat ctcttctgcc atctgccaaa gtcaacagag 60ctttccggaa gtcaccagat gtttcggaac taatgtcatc tccaagactc ttcttgtata 120ctgtataata ggcttgagag atatccttca tttgcctgct tgtcctggta gttaagattt 180caatcaaggc atcttcgttt gttcccgcgc ccttcatgga tttctttagc tgctttgcat 240caaagactgc tggtggagtc actagggcca ccatgagatg ctcaaagtgg 290<210>564<211>530<212>DNA<213>智人(Homo sapiens)<400>564accaccagat acttaaagct tcaaaaagac tgcccctacc accacaggag gaccagccta 60accatacgct ccaaaagatg gctgtgatag atcttgtgaa gcaattactg agcagatcaa 120gatctttggg aaggaacact aaagatgttt tgaatgaatt atagtccact ggcattttag 180tgtatttttt tttcttttta gaaacacaca tttctaaaaa tgtcatgtta cattcctgca 240tgtccctttt gatagcatta gtggatccat tggatttctt ttttcttttt gtgagacagc 300ttttagtctt acctgaattt atgtgtgttt ttccgacagt ggttaataat tatattggtg 360atgtagcagc aattgtgttg gcagggtttt catatattat tagtaattaa cactaactgt 420tggactgact tgtgtcgata gcgctcacgc aagcatggtt aacgtcccta aaacccgccg 480gactttctgt aagaagtgtg gcaagcacca accccataaa gtgacacagt 530<210>565<211>450<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(450)<223>n＝A、T、C或G<400>565ctgcttacgg aagcgctgnn tgactaggat gtgatttatt aacgaccaac ttctgttatt 60gtgtgttaag tttttcatct gtgcatcaaa tcacaaaaag aataaataga gctttttcct 120ttatcagtcc cttgggcaca gcaggtcctg aacaccctgc tctacaatgt tgcatcaaga 180gttcaaacaa caaaataaaa aatattaaga ggaaatcccc atcctgtgac ttgagtccct 240taagtctaca ggggctggtg acctcttttt gctaatagga aaatcacatt actacaaaat 300ggggagaaaa ctgtttgcct gtggtagaca cctgcacgca taggattgaa gacagtacag 360gctgctgtac agagaagcgc ctctcacatc tgaactgcat actgagcggg caagtcggtt 420gtaagttcag taaaaccctc tgatgatgcc 450<210>566<211>563<212>DNA<213>智人(Homo sapiens)<400>566acttgagctg tgaggtcatc ggaatcccga cacctgtcct catctggaac aaggtaaaaa 60ggggtcacta tggagttcaa aggacagaac tcctgcctgg tgaccgggac aacctggcca 120ttcagacccg gggtggccca gaaaagcatg aagtaactgg ctgggtgctg gtatctcctc 180taagtaagga agatgctgga gaatatgagt gccatgcatc caattcccaa ggacaggctt 240cagcatcagc aaaaattaca gtggttgatg ccttacatga aataccagtg aaaaaaggtg 300aaggtgccga gctataaacc tccagaatat tattagtctg catggttaaa agtagtcatg 360gataactaca ttacctgttc ttgcctaata agtttctttt aatccaatcc actaacactt 420tagttatatt cactggtttt acacagagaa atacaaaata aagatcacac atcaagacta 480tctacaaaaa tttattatat atttacagaa gaaaagcatg catatcatta aacaaataaa 540atacttttta tcacaaaaaa aaa 563<210>567<211>424<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(424)<223>n＝A、T、C或G<400>567ccagtgagca aattgaaaac caactgaaag caaatccaaa tgaggaagat tttaataaag 60gaataccctt ctccatagca ggtgcaatgc tgactgctca aggcgtgcgt gcgcgcgcac 120acacacacac acacacacac atacatactc tcacacacnc atctttccaa ttaaactgca 180ggtagaatga gattttgtgt tattcaaaaa atttgtaagt gatcaaaanc actgctatgg 240aatgcctgtt tatctgcctt tgntctggtt aaaatctcat aaaaatacat tcaacaggaa 300aacatanatt gtatgtgtat aaatatatat gtatatatat atattatata cacatgcaca 360caaatacttt tgttttttga agcataagat agttacataa atactcctat aattgctaaa 420gttt 424<210>568<211>392<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(392)<223>n＝A、T、C或G<400>568actggctcac tcagagagga cgtccttcaa ctatgccatg aaggaggctg ctgcagcggc 60tttgaagaag aaaggatggg aggtggtgga gtcggacctc tatgccatga acttcaatcc 120catcatttcc agaaaggaca tcacaggtaa actgaaggac cctgcgaact ttcagtatcc 180tgccgagtct gttctggctt ataaagaagg ccatctgagc ccagatattg tgggttganc 240aaaagaaagc ttggaagccn caagaacctt gtgatattcc agttccccct gcantgggtt 300tgggaagtcc ctgccntttt gaaagctggt ttgaagcgaa tgttcatagg aaagtttgct 360taccacttac cctgcccatg gtangacaaa ag392<210>569<211>559<212>DNA<213>智人(Homo sapiens)<400>569aaagagattt attaaatcat cttatcacaa agatggaaac atatacaaac tagaaacatg 60caaccatcat cttccacagt caagtcacaa tgtcaaatat ttttcttgcc tctgcagatg 120aaaagttcag atcttatacc caactactta ctcaccccga atatttaagt cagtcttcct 180gaaagtactc agggtagcaa gtaacaaaat gcaaacgatt atataaagaa agtgcagtta 240aaaaggaaac tatgtggcaa gtaccctctt tcccttccca ccccccaatt aaaggcaaac 300aatggcactt tgctcttgct taacctagat tgtcttcaaa aactattaaa atgtaaaaga 360cttaacaaaa aaacaaaaag acgtttaaca gatgtcaaaa agctccttag tgtttgaaaa 420taaatgctta aacaaaagac aacatatttt atatcaaaca agtttgaaga gccctgaatt 480gcagcattct gtaacataaa caaacaaaaa gctggtatag gatttattgg caaaggcaga 540atttcttcaa gcagggtaa 559<210>570<211>368<212>DNA<213>智人(Homo sapiens)<400>570agccgccgct ggatgctaag tccgatgtca ccaaccagct tgtagatttt cagtggaaac 60tgggtatggc tgtgagctca gacacttgca gatctcttaa gtatccttac gttgcagtga 120tgctaaaagt ggcagatcat tcaggccaag taaagaccaa gtgctttgaa atgacgattc 180cacagtttca gaatttctac agacagttca aggaaattgc tgcagttatt gaaacggtgt 240gaagacggat tctttggttg ataaattgct atcattctaa agtcatggac ttcactttcg 300gcaacaaaac taaataagga tggaacattt attgaatgaa aaatgcactt ttgtttttcc 360attttttt 368<210>571<211>261<212>DNA<213>智人(Homo sapiens)<400>571acacgattgc tgcttccgct atatttgtga tataggaatt aagaggatac acacgtttgt 60ttcttcgtgc ctgttttatg tgcacacatt aggcattgag acttcaagct tttctttttt 120tgtccacgta tctttgggtc tttgataaag aaaagaatcc ctgttcattg taagcacttt 180tacggggctg gtggggaggg gtgctctgct ggtcttcaat taccaagaat tctccaaaac 240aattttctgc aggatgattg t261<210>572<211>488<212>DNA<213>智人(Homo sapiens)<400>572ctctcagctc tcggcgcacg gcccagcttc cttcaaaatg tctactgttc acgaaatcct 60gtgcaagctc agcttggagg gtgatcactc tacaccccca agtgcatatg ggtctgtcaa 120agcctatact aactttgatg ctgagcggga tgctttgaac attgaaacag ccatcaagac 180caaaggtgtg gatgaggtca ccattgtcaa cattttgacc aaccgcagca atgcacagag 240acaggatatt gccttcgcct accagagaag gaccaaaaag gaacttgcat cagcactgaa 300gtcagcctta tctggccacc tggagacggt gattttgggc ctattgaaga cacctgctca 360gtatgacgct tctgagctaa aagcttccat gaaggggctg ggaaccgacg aggactctct 420cattgagatc atctgctcca gaaccaacca ggagctgcag gaaattaaca gagtctacaa 480ggaaatgt 488<210>573<211>619<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(619)<223>n＝A、T、C或G<400>573actttactga aagaacacta ntgttctttc ctttccgttg tgaaaaaagt tgtttctgag 60gaattgaaac cccagaagat aactacaaca aaaacatgtt aatttttttt taaaaatgat 120gattcaaagg cagatttgaa gggaagtaat atttaggtgg cagaagaagg caaatgcagc 180ctctgaaggg aactgttcta attattacct aaaaaataaa gttacacaac tatattcaag 240gacatgagat aaagcactgc ttgaaaacca gaatgactga acagttaggt gaaaaggaac 300agctgaaata ggaaggggaa atggactgaa gaataatttg aatcgggaca gtgatccatc 360agtcctagat gcttctggta tgtaaatatc ttgaatcaca ttgtttcctt tcttctgaaa 420tctcaaagga gaattctcac agcactacat taaggttgcc attttgttag gattcaaaat 480ttcaatccag tagccatcag gatcttgaat aaatgccagg cctttcattt taccatcatc 540aggtttcttc acaaatttga ctccagtctt caaccttttc aagcctgatc atcaggaaca 600caattccata tgaccgatc 619<210>574<211>202<212>DNA<213>智人(Homo sapiens)<400>574acatccaccc cactatttct tcacataccg aatcaggatt gaaatgtcaa aagatgcact 60tcctgagaag gcctgtcagt tggacagtcg ctattggaga ataacaaatg ctaagggtga 120cgtggaagaa gttcaaggac ctggagtagt tggtgaattt ccaatcatca gcccaggtcg 180ggtatatgaa tacacaagct gt 202<210>575<211>311<212>DNA<213>智人(Homo sapiens)<400>575ccacagttgt atcatatagc atctctaaca tttcatctag gattatctag tatagatctt 60actatatttg ggactatgtt gtatacaatg ttaacaagaa catatcttct ctgcatatat 120gtgtgaatta taaagaaaag catgagaatg actctaagtt caacaaacat gggtgaatct 180ctatgtgctc ccagtgtcct ggatgggctc cccagcaagc cattcctcct tcctgttctg 240atattactat tcttttttac attgtgctaa ggaggacaaa agatgagaga tgaaaataaa 300gctttgcctt t 311<210>576<211>134<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(134)<223>n＝A、T、C或G<400>576ttttttgcat caaaaagctt tatttccatt tggnccaagg cttgttagga tagttaaaaa 60agctgcctat tggctggagg ganaggctta ggcaaaancc ctattacttt gcaaggggcc 120cttcaaaagt cgct134<210>577<211>488<212>DNA<213>智人(Homo sapiens)<400>577ctgatcagtg ggcctccaag gaggggctgt aaaatggagg ccattgtgtg agcctatcag 60agttgctgca aacctgaccc ctgctcagta aagcacttgc aaccgtctgt tatgctgtga 120cacatggccc ctccccctgc caggagcttt ggacctaatc caagcatccc tttgcccaga 180aagaagatgg gggaggaggc agtaataaaa agattgaagt attttgctgg aataagttca 240aattcttctg aactcaaact gaggaatttc acctgtaaac ctgagtcgta cagaaagctg 300cctggtatat ccaaaagctt tttattcctc ctgctcatat tgtgattctg cctttgggga 360cttttcttaa accttcagtt atgatttttt tttcatacac ttattggaac tctgcttgat 420ttttgcctct tccagtcttc ctgacacttt aattaccaac ctgttaccta ctttgacttt 480ttgcattt 488<210>578<211>476<212>DNA<213>智人(Homo sapiens)<400>578accatgcatt aagagcttcc tgattgagat tcagtgcatc agccgtgtct attccatcta 60cgtccacacc gtctgtgacc cactctttga agctgttggg aaaatattca gcaatgtccg 120catcaacttg cagaaagaaa tataaatgac atttcaagga tagaagtata cctgattttt 180ttccttttaa ttttcctggt gccaatttca agttccaagt tgctaataca gcaacaattt 240atgaattgaa ttatcttggt tgaaaataaa aagatcactt tctcagtttt cataagtatt 300atgtctcttc tgagctattt catctatttt tggcagtctg aatttttaaa acccatttaa 360atttttttcc ttaccttttt atttgcatgt ggatcaacca tcgctttatt ggctgagata 420tgaacatatt gttgaaaggt aatttgagag aaatatgaag aactgaggaa aaaaaa 476<210>579<211>246<212>DNA<213>智人(Homo sapiens)<400>579ctggtgctca ctgagatggt aggttttcct attttcctgc tacatctgca caagctacat 60ctagaatgaa gccaccaatt tcaatgtgac caggcaatgg cagccagcac tgccttacac 120tggtttgatt ctgattccct aattctggcc actgcaggtg atgagtaagg gtggggatca 180gggaggaagt ccagaagcca gtctttgtct ccctttcctg cttatattta agtgcctatt 240tacatg 246<210>580<211>615<212>DNA<213>智人(Homo sapiens)<220><221>misc_feature<222>(1)...(615)<223>n＝A、T、C或G<400>580gtcttcacag taataactaa tggtggatcc taaggtgaaa ttatttcctt caaaatagnc 60atgaactgna ttcccaggag ggncacagtc cctacttttg canatgggaa agggaggtgc 120ccaggtgtgg tcctctagac actggctccg attgctgccc ttgaggatgt agtggtcatt 180gcacataaac gtgattttgt cacttacatt cacaggccct gaagaactga actctccatt 240caccagcaca ggatcaggac agtggcccaa gcggcactca gtagtggtgt tatcccactc 300cttagaggca ttgcaaaaaa gggtcttctt tcctaccagg tggtagccct tgatacaaac 360gtaagtcccc agaatctgtc cttccacctc ctttgcgaca aatatgctat tgtccactgg 420aggaagctct ggacagtgct catctgaagc agaaactcgc cacgcaacca taagacagca 480cgcacaccaa aaaaacatct ggtgatcaaa gtcctctccc caggctggaa ttcacccagc 540tcagacacct tacctgtctc tgtccctcca gagttagggc ttcccancaa ggaactgggc 600ttaactgact tccaa 615<210>581<211>576<212>DNA<213>智人(Homo sapiens)<400>581actcttgttg agttctgtag agccttctga tgtctctaaa gcactaccga ttctttggag 60ttgtcacatc agataagaca tatctctaat tccatccata aatccagttc tactatggct 120gagttctggt caaagaaaga aagtttagaa gctgagacac aaagggttgg gagctgatga 180aactcacaaa tgatggtagg aagaagctct cgacaatacc cgttggcaag gagtctgcct 240ccatgctgca gtgttcgagt ggattgtagg tgcaagatgg aaaggattgt aggtgcaagc 300tgtccagaga aaagagtcct tgttccagcc ctattctgcc actcctgaca gggtgacctt 360gggtatttgc aatattcctt tgggcctctg cttctctcac ctaaaaaaag agaattagat 420tatattggtg gttctcagca agagaaggag tatgtgtcca atgctgcctt cccatgaatc 480tgtctcccag ttatgaatca gtgggcagga taaactgaaa actcccattt acgtgtctga 540atcgagtgag acaaaatttt agtccaaata acaagt 576<210>582<211>939<212>DNA<213>智人(Homo sapiens)<400>582atgagcatcg gcctcctgtg ctgtgcagcc ttgtctctcc tgtgggcagg tccagtgaat 60gctggtgtca ctcagacccc aaaattccag gtcctgaaga caggacagag catgacactg 120cagtgtgccc aggatatgaa ccatgaatac atgtcctggt atcgacaaga cccaggcatg 180gggctgaggc tgattcatta ctcagttggt gctggtatca ctgaccaagg agaagtcccc 240aatggctaca atgtctccag atcaaccaca gaggatttcc cgctcaggct gctgtcggct 300gctccctccc agacatctgt gtacttctgt gccagcagtt actcagtcgg ggagggcggg 360gattcacccc tccactttgg gaatgggacc aggctcactg tgacagagga cctgaacaag 420gtgttcccac ccgaggtcgc tgtgtttgag ccatcagaag cagagatctc ccacacccaa 480aaggccacac tggtgtgcct ggccacaggc ttcttccctg accacgtgga gctgagctgg 540tgggtgaatg ggaaggaggt gcacagtggg gtcagcacgg acccgcagcc cctcaaggag 600cagcccgccc tcaatgactc cagatactgc ctgagcagcc gcctgagggt ctcggccacc 660ttctggcaga acccccgcaa ccacttccgc tgtcaagtcc agttctacgg gctctcggag 720aatgacgagt ggacccagga tagggccaaa cccgtcaccc agatcgtcag cgccgaggcc 780tggggtagag cagactgtgg ctttacctcg gtgtcctacc agcaaggggt cctgtctgcc 840accatcctct atgagatcct gctagggaag gccaccctgt atgctgtgct ggtcagcgcc 900cttgtgttga tggccatggt caagagaaag gatttctga 939<210>583<211>828<212>DNA<213>智人(Homo sapiens)<400>583atgaactatt ctccaggctt agtatctctg atactcttac tgcttggaag aacccgtgga 60aattcagtga cccagatgga agggccagtg actctctcag aagaggcctt cctgactata 120aactgcacgt acacagccac aggataccct tcccttttct ggtatgtcca atatcctgga 180gaaggtctac agctcctcct gaaagccacg aaggctgatg acaagggaag caacaaaggt 240tttgaagcca cataccgtaa agaaaccact tctttccact tggagaaagg ctcagttcaa 300gtgtcagact cagcggtgta cttctgtgct ccgaaccctt ctcttcaggg cggatctgaa 360aagctggtct ttggaaaggg aacgaaactg acagtaaacc catatatcca gaaccctgac 420cctgccgtgt accagctgag agactctaaa tccagtgaca agtctgtctg cctattcacc 480gattttgatt ctcaaacaaa tgtgtcacaa agtaaggatt ctgatgtgta tatcacagac 540aaaactgtgc tagacatgag gtctatggac ttcaagagca acagtgctgt ggcctggagc 600aacaaatctg actttgcatg tgcaaacgcc ttcaacaaca gcattattcc agaagacacc 660ttcttcccca gcccagaaag ttcctgtgat gtcaagctgg tcgagaaaag ctttgaaaca 720gatacgaacc taaactttca aaacctgtca gtgattgggt tccgaatcct cctcctgaaa 780gtggccgggt ttaatctgct catgacgctg cggctgtggt ccagctga 828<210>584<211>275<212>PRT<213>智人(Homo sapiens)<400>584Met Asn Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly5 10 15Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly35 40 45Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln50 55 60Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly65 70 75 80Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys85 90 95Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Pro Asn100 105 110Pro Ser Leu Gln Gly Gly Ser Glu Lys Leu Val Phe Gly Lys Gly Thr115 120 125Lys Leu Thr Val Asn Pro Tyr Ile Gln Asn Pro Asp Pro Ala Val Tyr130 135 140Gln Leu Arg Asp Ser Lys Ser Ser Asp Lys Ser Val Cys Leu Phe Thr145 150 155 160Asp Phe Asp Ser Gln Thr Asn Val Ser Gln Ser Lys Asp Ser Asp Val165 170 175Tyr Ile Thr Asp Lys Thr Val Leu Asp Met Arg Ser Met Asp Phe Lys180 185 190Ser Asn Ser Ala Val Ala Trp Ser Asn Lys Ser Asp Phe Ala Cys Ala195 200 205Asn Ala Phe Asn Asn Ser Ile Ile Pro Glu Asp Thr Phe Phe Pro Ser210 215 220Pro Glu Ser Ser Cys Asp Val Lys Leu Val Glu Lys Ser Phe Glu Thr225 230 235 240Asp Thr Asn Leu Asn Phe Gln Asn Leu Ser Val Ile Gly Phe Arg Ile245 250 255Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu260 265 270Trp Ser Ser275<210>585<211>312<212>PRT<213>智人(Homo sapiens)<400>585Met Ser Ile Gly Leu Leu Cys Cys Ala Ala Leu Ser Leu Leu Trp Ala5 10 15Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu20 25 30Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His35 40 45Glu Tyr Met Ser Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu50 55 60Ile His Tyr Ser Val Gly Ala Gly Ile Thr Asp Gln Gly Glu Val Pro65 70 75 80Asn Gly Tyr Asn Val Ser Arg Ser Thr Thr Glu Asp Phe Pro Leu Arg85 90 95Leu Leu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser100 105 110Ser Tyr Ser Val Gly Glu Gly Gly Asp Ser Pro Leu His Phe Gly Asn115 120 125Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Asn Lys Val Phe Pro Pro
130 135 140Glu Val Ala Val Phe Glu Pro Ser Glu Ala Glu Ile Ser His Thr Gln145 150 155 160Lys Ala Thr Leu Val Cys Leu Ala Thr Gly Phe Phe Pro Asp His Val165 170 175Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Ser180 185 190Thr Asp Pro Gln Pro Leu Lys Glu Gln Pro Ala Leu Asn Asp Ser Arg195 200 205Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp Gln Asn210 215 220Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe Tyr Gly Leu Ser Glu225 230 235 240Asn Asp Glu Trp Thr Gln Asp Arg Ala Lys Pro Val Thr Gln Ile Val245 250 255Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Phe Thr Ser Val Ser260 265 270Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu275 280 285Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Ala Leu Val Leu Met290 295 300Ala Met Val Lys Arg Lys Asp Phe305 310<210>586<211>97<212>PRT<213>智人(Homo sapiens)<400>586Glu Val Glu Val Ser Arg Asp His Ala Ser Leu Gly Asp Ser Glu Thr5 10 15Leu Ser Gln Thr Glu Leu Arg Lys Lys Glu Arg Lys Lys Lys Arg Glu20 25 30Arg Lys Phe Gln Ala Asn Cys Gly Ile Asp Phe Ile Ile Phe Trp Ile35 40 45Phe Trp Ile Leu Leu Phe Ser His His Trp Ile Gln Glu Ser Leu Leu50 55 60Cys Pro Pro Ser Pro Lys Glu Val Thr Cys Arg Glu Met Leu Thr Gly65 70 75 80Gly Cys Leu Pro Trp Ala Thr Arg Ser His Leu Gly Arg Arg Lys Cys85 90 95Ser<210>587<211>16<212>PRT<213>智人(Homo sapiens)<400>587Phe Gln Ala Asn Cys Gly Ile Asp Phe Ile Ile Phe Trp Ile Ph Trp1 5 10 1權(quán)利要求
1.分離的多核苷酸，其包含選自下組的序列(a)SEQ ID NO390；392，394，396，398-420，422-424，428-433和440-583提供的序列；(b)SEQ ID NO390，392，394，396，398-420，422-424，428-433和440-583提供序列的互補(bǔ)物；(c)由SEQ ID NO390，392，394，396，398-420，422-424，428-433和440-583提供序列的至少20個(gè)連續(xù)殘基組成的序列；(d)在中等嚴(yán)格條件下，與SEQ ID NO390，392，394，396，398-420，422-424，428-433和440-583提供序列雜交的序列；(e)與SEQ ID NO390，392，394，396，398-420，422-424，428-433和440-583的序列具有至少75％同一性的序列；(f)與SEQ ID NO390，392，394，396，398-420，422-424，428-433和440-583的序列具有至少90％同一性的序列；和(g)SEQ ID NO390，392，394，396，398-420，422-424，428-433和440-583提供序列的簡并變異體。
2.分離的多肽，其包含選自下組的氨基酸序列(a)SEQ ID NO584-587；(b)由權(quán)利要求1的多核苷酸編碼的序列；和(c)與由權(quán)利要求1的多核苷酸編碼的序列具有至少70％同一性的序列；和(d)與由權(quán)利要求1的多核苷酸編碼的序列具有至少90％同一性的序列。
3.表達(dá)載體，其包含與表達(dá)調(diào)控序列可操作連接的權(quán)利要求1的多核苷酸。
4.用權(quán)利要求3的表達(dá)載體轉(zhuǎn)化或轉(zhuǎn)染的宿主細(xì)胞。
5.特異性結(jié)合權(quán)利要求2的多肽的分離的抗體，或其抗原結(jié)合片段。
6.檢測患者是否存在癌癥的方法，包括以下步驟(a)從患者得到生物樣本；(b)使生物樣本接觸與權(quán)利要求2的多肽結(jié)合的結(jié)合劑；(c)檢測樣本中與結(jié)合劑結(jié)合的多肽量；和(d)將多肽量與預(yù)先確定的截?cái)嘀颠M(jìn)行比較并由此確定患者是否存在癌癥。
7.包含至少一種權(quán)利要求2的多肽的融合蛋白。
8.在中等嚴(yán)格條件下，與SEQ ID N0390，392，394，396，398-420，422-424，428-433和440-583引用的序列雜交的寡核苷酸。
9.刺激和/或擴(kuò)充對腫瘤蛋白特異性的T細(xì)胞的方法，包括在足以允許刺激和/或擴(kuò)充T細(xì)胞的條件和時(shí)間下，使T細(xì)胞與選自下組的至少一種成分接觸(a)權(quán)利要求2的多肽；(b)權(quán)利要求1的多核苷酸；和(c)表達(dá)權(quán)利要求2的多肽的抗原呈遞細(xì)胞。
10.分離的T細(xì)胞群，其包含根據(jù)權(quán)利要求9的方法制備的T細(xì)胞。
11.組合物，其包含選自生理可接受載體和免疫刺激劑的第一成分，和選自下組的第二成分(a)權(quán)利要求2的多肽；(b)權(quán)利要求1的多核苷酸；(c)權(quán)利要求5的抗體；(d)權(quán)利要求7的融合蛋白；(e)權(quán)利要求10的T細(xì)胞群；和(f)表達(dá)權(quán)利要求2的多肽的抗原呈遞細(xì)胞。
12.刺激患者免疫應(yīng)答的方法，包括給患者施用權(quán)利要求11的組合物。
13.治療患者癌癥的方法，包括給患者施用權(quán)利要求11的組合物。
14.確定患者是否存在癌癥的方法，包括以下步驟(a)從患者得到生物樣本；(b)使生物樣本接觸權(quán)利要求8的寡核苷酸；(c)檢測樣本中與寡核苷酸雜交的多核苷酸的量；和(d)將與該寡核苷酸雜交的多核苷酸的量與預(yù)先確定的截?cái)嘀颠M(jìn)行比較，并由此確定患者是否存在癌癥。
15.包含至少一種權(quán)利要求8的寡核苷酸的診斷試劑盒。
16.包含至少一種權(quán)利要求5的抗體和檢測試劑的診斷試劑盒，其中檢測試劑包含報(bào)道基團(tuán)。
17.抑制患者癌癥發(fā)生的方法，包括以下步驟(a)將從患者分離的CD4+和/或CD8+T細(xì)胞與選自下組的至少一種成分共同培養(yǎng)(i)權(quán)利要求2的多肽；(ii)權(quán)利要求1的多核苷酸；和(iii)表達(dá)權(quán)利要求2的多肽的抗原呈遞細(xì)胞，使得T細(xì)胞增殖；(b)給患者施用有效量的增殖T細(xì)胞，并由此抑制患者癌癥的發(fā)生。
全文摘要
本發(fā)明公開了治療和診斷癌癥特別是肺癌的組合物和方法。示例的組合物包含一種或多種肺腫瘤多肽，其免疫原性部分，編碼這種多肽的多核苷酸，表達(dá)這種多肽的抗原呈遞細(xì)胞，和對表達(dá)這種多肽的細(xì)胞特異性的T細(xì)胞。所公開的組合物可用于例如診斷、預(yù)防和/或治療疾病，特別是肺癌。
文檔編號C07K16/30GK1469926SQ01810358
公開日2004年1月21日 申請日期2001年3月28日 優(yōu)先權(quán)日2000年3月29日
發(fā)明者S·G·里德, M·J·洛迪斯, R·默哈瑪斯, H·塞克里斯特, D·R·本森, C·Y·茵迪里亞斯, R·A·漢德森, S·P·弗靈, P·A·阿爾蓋特, M·埃里奧特, J·瑪尼昂, M·D·卡洛斯, S G 里德, 卡洛斯, 嵐, 弗靈, 晁, 本森, 死鎪固, 漢德森, 洛迪斯, 茵迪里亞斯, 鋨綠, 阿爾蓋特 申請人:科里克薩有限公司