用于治疗和诊断卵巢癌的组合物及方法-j9九游会真人

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专利名称::用于治疗和诊断卵巢癌的组合物及方法用于治疗和诊断卵巢癌的组合物及方法
技术领域
概括地,本发明涉及卵巢癌的治疗。更具体地,本发明涉及包括至少卵巢癌蛋白质一部分的多肽,编码这些多肽的多核苷酸,及特异性识别这些多肽的抗体和免疫系统细胞。这样的多肽,多核苷酸、抗体及细胞可以用在用于卵巢癌治疗的疫苗及药物组合物中。发明背景在美国及全世界,对妇女而言,卵巢癌是严重的健康问题。尽管在这种癌症的检测和治疗方面已取得了进展,但是目前没有预防或治疗的疫苗或其它普遍成功的方法可用。目前这种疾病的治疗依靠早期,断和侵入性治疗的联合,这可汰包括各种治、疗中"秤或多种治疗,如手术,放射疗法,化学疗法及激素治疗。常常基于各种预后参数,包括特异肿瘤标记分析选择特定癌症的治疗疗程。然而,已建立的标记的应用常常导致难以解释的结果,而且在许多癌症患者中继续观察到高死亡率。免疫疗法有显著改进癌症治疗及存活的潜力。这种疗法可以涉及对卵巢癌抗原免疫应答的产生及增强。然而,目前为止,几乎没有卵巢癌抗原是已知的,而且也没有证明抗这种抗原的免疫应答的产生有治疗益处。因此,本领域需要鉴定卵巢肿瘤抗原及在卵巢癌治疗中使用这种抗原的改进的方法。本发明满足了这些需要而且进一步提供了其它的相关优点。发明概述简而言之,本发明提供了用于治疗癌症,如卯巢癌的组合物及方法。一方面,本发明提供了包含卵巢癌蛋白质免疫原性部分的多肽或其变异体,变异体的不同在于一个或多个置换、缺失、添加和/或插入,以致变异体与卵巢癌蛋白质特异抗血清的反应能力没有实质减弱。在一些实施方式中,卵巢癌蛋白质包括选自seqidn0:456-457,460-477和512-570及这些多核苷酸序列的互补序列的多核苷酸序列编码的序列。本发明进一步提供了编码上述多肽或其一部分的多核苷酸,包含这种多核苷酸的表达载体及用这种表达载体转化或转染的宿主细胞。本发明进一步提供了多肽组合物,其包含选自seqidn0s:394-455,458-459,478-511和571-596所述序列的氨基酸序列。另一方面,本发明提供了药物组合物及疫苗。药物组合物可以包括生理学上可接受的载体或赋形剂,联合以下物质中的一种或多种(i)包含卵巢癌蛋白质免疫原性部分的多肽,或其变异体,所述变异体的不同在于一个或多个置换、缺失、添加和/或插入,以致变异体与卵巢癌蛋白质特异抗血清的反应能力没有实质减弱,其中卵巢癌蛋白质包含如下多核苷酸编码的氨基酸序列,所述多核苷酸包含seqidn0s:456-457,460-477和512-570所迷的任一个序列;或(ii)编码这种多肽的多核苷酸;(iii)特异结合这种多肽的抗体;(iv)表达这种多肽的抗原呈递细胞,和/或(v)与这种多肽特异反应的t细胞。疫苗可以包括非特异性免疫应答增强剂,联合以下物质中的一种或多种(i)包含卵巢癌蛋白质免疫原性部分的多肽,或其变异体,所述变异体的不同在于一个或多个置换、缺失、添加和/或插入,以致变异体与卵巢癌蛋白质特异抗血清的反应能力没有实质减弱,其中卵巢癌蛋白质包含seqidnos:394-455,458-459,478-511,及571-596所述的氨基酸序列或以下多核苷酸编码的氨基酸序列,所述多核苷酸包含seqidno:456-457,460-477和512-570所述的任一个序列,或(ii)编码这种多肽的多核苷酸;(iii)特异结合这种多肽的抗体特异性结合的抗独特型抗体;(iv)表达这种多肽的抗原呈递细胞,和/或(v)与这种多肽特异反应的t细胞。另一方面,本发明进一步提供了包含至少一个上述多肽的融合蛋白质,及编码这种融合蛋白质的多核苷酸。在相关方面,提供了包含融合蛋白质或编码融合蛋白质的多核苷酸及生理学上可接受载体的药物组合物。另一方面,进一步提供了疫苗,其包含融合蛋白质或编码融合蛋白质的多核苷酸及非特异性免疫增强剂。另一方面,本发明提供了抑制患者癌症发展的方法,包括给患者施用上述药物组合物或疫苗。另一方面,本发明进一步提供了刺激和/或扩增t细胞的方法,包括用(a)包含卵巢癌蛋白质免疫原性部分的多肽,或其变异体,所述变异体的不同在于一个或多个置换、缺失、添加和/或插入,以致变异体与卵巢癌蛋白质特异的抗血清的反应能力没有实质減弱,其中卵巢癌蛋白质包含seqidnos:394-455,458-459,478-511,及571-596所述的氨基酸序列或如下多核苷酸编码的氨基酸序列,所述多核苷酸包含seqidno:456-457,460-477和512-570所迷的任一个序列;(b)编码这种多肽的多核苷酸,和/或(c)表达这种多肽的抗原呈递细胞,在足以允许t细胞刺激和/或扩增的条件和时间下接触t细胞。可以在药物组合物或疫苗中存在这样的多肽,多核苷酸和/或抗原呈递细胞以用于刺激和/或扩增哺乳动物的t细胞。另一方面,本发明提供了抑制患者卵巢癌发展的方法,包括给患者施用上述制备的t细胞。另一方面,本发明提供了抑制患者卵巢癌发展的方法,包括以下步骤(a)温育从患者分离的cd4 和/或cd8 t细胞和以下物质中的一种或多种(i)包含卵巢癌蛋白质免疫原性部分的多肽,或其变异体,变异体的不同在于一个或多个置换、缺失、添加和/或插入,以致变异体与卵巢癌蛋白质特异抗血清的反应能力没有明显减弱,其中卵巢癌蛋白质包含下述多核苷酸编码的氨基酸序列,所述多核苷酸包含seqidn0:456-457,460-477和512-570所述的任一个序列;(ii)编码这种多肽的多核苷酸;(iii)表达这种多肽的抗原呈递细胞;以使t细胞增殖;和(b)给患者施用有效量的增殖的t细胞,由此抑制患者卵巢癌的发育。在给患者施用前可以克隆所述增殖的细胞。另一方面,本发明也提供了鉴定分泌性肿瘤抗原的方法。这种方法包括以下步骤(a)在免疫缺陷的哺乳动物中植入肺瘤细胞;(b)在足以允许肿瘤抗原分泌进入血清的时间后,从所述免疫缺陷哺乳动物获得血清;(c)用血清免疫免疫活性的哺乳动物;(d)从免疫活性的哺乳动物获得抗血清;和(e)用抗血清筛选肺瘤表达文库,而且由此鉴定分泌性肿瘤抗原。鉴定分泌性卵巢癌抗原的优选方法包括以下步骤(a)在scid小鼠中植入卵巢癌细胞;(b)在足以允许卵巢癌抗原分泌进入血清的时间后,从该scid小鼠获得血清;(c)用该血清免疫具有免疫活性的小鼠;(d)从所述具有免疫活性的小鼠中获得抗血清;和(e)用抗血清筛选卵巢癌表达文库,和由此筌定分泌性卵巢癌抗原。本发明也公开了08e多克隆抗血清识别的抗体表位,所述抗体表位如本发明seqidno:394-415所示。本发明进一步公开了预测与hla-0201结合的10-mer(聚体)和9-mer肽,这些肽分别是seqidn0:416-435和seqidn0:436-455。当参考下面的详细说明及附图时,本发明的这些及其它方面是明显的。本发明公开的所有参考文献都被整体引入作为参考,如每篇文献单独被引用一样。本发明另一个方面,申请人意料外地鉴定出编码0772p基因5,-末端的一系列新重复序列元件。罔此,本发明提供了有xn-y所代表的结构的0772p多肽,其中x包含与seqidno:596所示0772p重复序列有至少50%同一性,优选至少70%同一性,更优选至少90%同一性的序列。通常y包含与seqidn0:594所示0772恒定区序列有至少80%同一性,优选至少90%的同一性,更优选至少95%的同一性的序列。根据这个实施方式,通常n是从1到35的整数,优选从15到25的整数,x可以相同或不同。在一个优选实施方式中,x包含选自seqidn0s:574-593的序列,y包含seqidno:594所示序列。在另一个优选实施方式中,示例性0772p多肽包含seqidn0:595所述序列,含有20个重复序列元件(即,x2。),其中x元件以下列顺序排列(在0772p重复区中从n-末端到c-末端移动)seqidn0:574-seqidno:575-seqidno:576-seqidno:577-seqidno:578_seqidn0:579-seqidn0:580-seqidn0:581-seqidno:582-seqidn0:583-seqidno:584-seqidno:585-seqidno:586-seqidn0:587-seqidno:588-seqidno:589-seqidno:590-seqidn0:591-seqidn0:592-seqidn0r593。根据本发明另一方面,提供了有xn-y结构的0772p多核香酸,其中x包含选自seqidnos:512—540,542-546和548—567任一个的0772p重复序列元件。通常y包含与seqidno:586所示0772p恒定区序列有至少80%同一性,优选至少90%同一性,更优选至少95%同一性的序列。在这个实施方式中,通常n是从l到35,优选从15到25的整数,x可以相同或不同。在另一个实施方式中,示例性0772p多核苷酸包含seqidno:569所述序列,含有20个重复序列元件(即,x2。)。根据本发明另一方面,提供了0772多肽,它包含至少seqidn0:490-511任一个所示的抗体表位(antibodyepitope)序列。根据本发明另一方面,提供了08e多肽,其包含至少seqidnos:394-415任一个所示的抗体表位序列。序列标识符和附图的简要说明seqidno:l-71是图1a-is所示的卵巢癌抗原多核苷酸。seqidn0:72-74是图2a-2c所示的卵巢癌抗原多核苷酸。seqidn0:75是卵巢癌多核苷酸3g(图4)。seqidn0:76是卵巢癌多核苷酸3f(图5)。seqidn0:77是卵巢癌多核苷酸6b(图6)。seqidn0:78是卵巢癌多核苷酸8e(图7a)。seqidn0:79是卵巢癌多核苷酸8h(图7b)。seqidn0:80是卵巢癌多核苷酸12e(图8)。seqidn0:81是卵巢癌多核苷酸12h(图9)。seqidn0:82-310是图15a_15eee所示的卵巢癌抗原多核苷酸。seqidn0:311是卵巢癌多核苷酸0772p的全长序列。seqidn0:312是0772p氨基酸序列。seqidn0:313-384是卵巢癌抗原多核苷酸。seqidno:385代表克隆0772p—种形式的cdna序列,命名为21013。seqidno:386代表克隆0772p—种形式的cdna序列,命名为21003。seqidno:387代表克隆0772p—种形式的cdna序列,命名为21008。seqidn0:388是与seqidno:385对应的氨基酸序列seqidno:389是与seqidno:386对应的氨基酸序列。seqidno:390是与seqidn0:387对应的氨基酸序列。seqidn0:391是卵巢癌多核苷酸08e的全长序列。seqidn0:392-393是08e编码的蛋白质序列。seqidno:394-415是与0e8抗体表位对应的肽序列。seqidn0:416-435是用0e8全长开放阅读框架预测的可能的hla-a2lomer结合欣。seqidn0:436-455是用0e8全长开放阅读框架预测的可能的歸-a29mer结合欣。seqidno:456是显示与0772p有同源性的全长genbank序列的截短核苷酸序列。seqidn0:457是显示与0772p有显著同源性的全长genbank序列。seqidn0:458是编码显示与0772p有同源性的全长genbank序列的截短形式的蛋白质。seqidn0:459是显示与0772p蛋白质序列有显著同源性的genbank的全长蛋白质序列。seqidn0:460编码包含在残基1-70中的0772p独特的n-末端部分。seqidn0:461包含单一序列并编码seqidno:456残基1-313。seqidno,462是克隆0772p的假设序列。seqidno'463是克隆flj14303的cdna序列。seqidno'464是克隆0772p的部分cdna序列。seqidno465是克隆0772p的部分cdna序列。seqidno:466是克隆0772p的部分cdna序列。seqidno467是克隆0772p的部分cdna序列。seqidno:468是克隆0772p的部分cdna序列。seqidno469是克隆0772p的部分cdna序列。seqidno.470是克隆0772p的部分cdna序列。seqidno.471是克隆0772p的部分cdna序列。seqidno:472是克隆0772p的部分cdna序列。seqidno:473是克隆0772p的部分cdna序列。seqidno:474是克隆0772p的部分cdm序列。seqidno:475是克隆0772p的部分cdna序列。seqidno:476是克隆0772p的部分cdna序列。seqidno:477代表卵巢胂瘤抗原0772p新的5,-末端。seqidno:478是seqidno:462编码的氨基酸序列。seqidno:479是seqidn0:463编码的氨基酸序列。seqidno:480是seqidn0:472编码的部分氨基酸序列。seqidno:481是seqidn0:471可能的开放阅读框架编码的部分氨基酸序列。seqidn0:482是seqidn0:471第二个可能的开放阅读框架编码的部分氨基酸序列。seqidn0:483是seqidn0:467编码的部分氨基酸序列。seqidn0:484是seqidn0:466可能的开放阅读框架编码的部分氨基酸序列。seqidn0:485是seqidno:466第二个可能的开放阅读框架编码的部分氨基酸序列。seqidn0:486是seqidno:465编码的部分氨基酸序列。seqidno:487是seqidno:464编码的部分氨基酸序列。seqidn0:488代表0772p的细胞外、跨膜和细胞质区。seqidn0:489代表0772p的预测细胞外结构域。seqidn0:490代表与0772p特异抗体表位对应的肽#2的氨基酸序列。seqidn0:491代表与0772p特异抗体表位对应的肽#6的氨基酸序列。seqidno:492代表与0772p特异抗体表位对应的肽#7的氨基酸序列。seqidno:493代表与0772p特异抗体表位对应的肽#8的氨基酸序列。seqidno:494代表与0772p特异抗体表位对应的肽#9的氨基酸序列。seqidno:495代表与0772p特异抗体表位对应的肽#11的氨基酸序列。seqidn0:496代表与0772p特异抗体表位对应的肽#13的氨基酸序列。seqidn0:497代表与0772p特异抗体表位对应的肽#22的氨基酸序列。seqidno:498代表与0772p特异抗体表位对应的肽#24的氨基酸序列。seqidn0:499代表与0772p特异抗体表位对应的肽#27的氨基酸序列。seqidno:500代表与0772p特异抗体表位对应的肽#40的氨基酸序列。seqidno:501代表与0772p特异抗体表位对应的肽#41的氨基酸序列。seqidno:502代表与0772p特异抗体表位对应的狀#47的氨基酸序列。seqidno:503代表与0772p特异抗体表位对应的肽#50的氨基酸序列。seqidn0:504代表与0772p特异抗体表位对应的肽#51的氨基酸序列。seqidno:505代表与0772p特异抗体表位对应的肽#52的氨基酸序列。seqidno:506代表与0772p特异抗体表位对应的欣#53的氨基酸序列。seqidno:507代表与0772p特异抗体表位对应的肽#58的氨基酸序列。seqidno:508代表与0772p特异抗体表位对应的欣#59的氨基酸序列。seqidno:509代表与0772p特异抗体表位对应的肽#60的氨基酸序列。seqidn0:510代表与0772p特异抗体表位对应的狀#61的氨基酸序列。seqidno:511代表与0772p特异抗体表位对应的肽#71的氨基酸序列。seqidno:512(0772p重复1)代表与0772p5,可变区重复号21对应的cdna序列实例。seqidn0:513(0772p重复2)代表与0772p5'可变区重复号20对应的cdna序列实例。seqidn0:514(0772p重复3)代表与0772p5,可变区重复号19对应的cdna序列实例。seqidn0:515(0772p重复4)代表与0772p5'可变区重复号18对应的cdna序列实例。seqidno:516(0772p重复5)代表与0772p5,可变区重复号17对应的cdna序列实例。seqidn0:517(hb重复1)代表与0772p5'可变区重复号21对应的cdna序歹i实例。seqidno:518(hb重复2)代表与0772p5,可变区重复号20对应的cdna序歹'实例。seqidn0:519(hb重复3)代表与0772p5'可变区重复号19对应的cdna序列实例。seqidn0:520(hb重复4)代表与0772p5,可变区重复号18对应的cdna序列实例。seqidn0:521(hb重复5)代表与0772p5,可变区重复号17对应的cdna序列实例。seqidn0:522(hb重复65,-末端)代表与0772p5'可变区重复号16对应的cdna序列实例。seqidno:523(1043400.1重复1)代表与0772p5,可变区重复号9对应的cdna序列实例。seqidno:524(1043400.1重复2)代表与0772p5,可变区重复号io对应的cdna序列实例。seqidno:525(1043400.1重复3)代表与0772p5,可变区重复号10/11对应的cdna序列实例。seqidno:526(1043400.1重复4)代表与0772p5,可变区重复号11对应的cdna序列实例。seqidn0:527(1043400.1重复5)代表与0772p5'可变区重复号14对应的cdna序列实例。seqidno:528(1043400.1重复6)代表与0772p5,可变区重复号17对应的cdna序列实例。seqidn0:529(1043400.3重复1)代表与0772p5'可变区重复号20对应的cdna序列实例。seqidno:530(1043400.3重复2)代表与0772p5,可变区重复号21对应的cdna序列实例。seqidno:531(1043400.5重复1)代表与0772p5'可变区重复号8对应的cdna序列实例。seqidn0:532(1043400.5重复2)代表与0772p5'可变区重复号9对应的cdna序列实例,此外还含有内含子序列。seqidn0:533(1043400.5重复2)代表与0772p5'可变区重复号9对应的cdna序列实例。seqidn0:534(1043400.8重复1)代表与0772p5,可变区重复号17对应的cdna序列实例。seqidno:535(1043400.8重复2)代表与0772p5,可变区重复号18对应的cdna序列实例。seqidn0:536(1043400.8重复3)代表与0772p5,可变区重复号19对应的cdna序列实例。seqidn0:537(1043400.9重复1)代表与0772p5,可变区重复号4对应的cdna序列实例。seqidn0:538(1043400.9重复2)代表与0772p5,可变区重复号5对应的cdna序列实例。seqidn0:539(1043400.9重复3)代表与0772p5'可变区重复号7对应的cdna序列实例。seqidno:540(1043400.9重复4)代表与0772p5,可变区重复号8对应的cdna序列实例。seqidn0:541(1043400.11重复1)代表与0772p5'可变区重复号1对应的cdna序列实例。seqidn0:542(1043400.11重复2)代表与0772p5,可变区重复号2对应的cdna序列实例。seqidn0:543(1043400.11重复3)代表与0772p5'可变区重复号3对应的cdna序列实例。seqidno:544(1043400.11复号11对应的cdna序列实例。seqidno:545(1043400.11复号12对应的cdna序列实例。seqidno:546(1043400.12复号20对应的cdna序列实例。seqidno:547(pb重复a)应的cdna序列实例。seqidno:548(pb重复b)应的cdna序列实例。seqidno:549(pb重复e)应的cdna序列实例。seqidno:550(pb重复g)应的cdna序列实例。seqidno:551(pb重复c)应的cdna序列实例。seqidn0:552(pb重复h)应的cdna序列实例。seqidn0:553(pb重复j)应的cdna序列实例。seqidno:554(pb重复k)应的cdna序列实例。seqidn0:555(pb重复d)应的cdna序列实例。seqidno:556(pb重复i)应的cdna序列实例。seqidn0:557(pb重复m)应的cdna序列实例。seqidn0:558(pb重复9)重复4)代表与0772p5,可变区重重复5)代表与0772p5'可变区重重复1)代表与0772p5'可变区重代表与0772p5,可变区重复号1对代表与0772p5,可变区重复号2对代表与0772p5'可变区重复号3对代表与0772p5'可变区重复号4对代表与0772p5,可变区重复号4对代表与0772p5,可变区重复号6对代表与0772p5,可变区重复号7对代表与0772p5,可变区重复号8对代表与0772p5'可变区重复号9对代表与0772p5'可变区重复号10对代表与0772p5,可变区重复号11对代表与0772p5,可变区重复号12对应的cdna序列实例。seqidno:559(pb重复8.5)代表与0772p5,可变区重复号13对应的cdna序列实例。seqidno:560(pb应的cdna序列实例。seqidn0:561(pb应的cdna序列实例。seqidno:562(pb应的cdna序列实例。seqidno:563(pb应的cdna序列实例。seqidno:564(pb应的cdna序列实例。seqidno:565(pb应的cdna序列实例。seqidno:566(pb应的cdna序列实例。seqidno:567(pb应的cdna序列实例。seqidn0:568代表3,恒定区cdna序列。seqidno:569代表含有21个重复之共有序列,3,恒定区和3,非翻译区的cdna序列。seqidno:570代表共有重复序列的cdna序列。seqidno:571代表0772p5'可变区重复号1的一个可能开放阅读框架的共有氨基酸序列。seqidno:572代表0772p5,可变区重复号1的第二个可能开放阅读框架的共有氨基酸序列。seqidn0:573代表0772p5'可变区重复号1的第三个可能开放阅读框架的共有氨基酸序列。重复8)代表与0772p5'可变区重复号u对重复7)代表与0772p5,可变区重复号15对重复6)代表与0772p5,可变区重复号16对重复5)代表与0772p5,可变区重复号17对重复4)代表与0772p5'可变区重复号18对重复3)代表与0772p5'可变区重复号19对重复2)代表与0772p5,可变区重复号20对重复1)代表与0772p5,可变区重复号21对seqidn0:574代表0772p5'可变区重复号2的共有氨基酸序列。seqidn0:575代表0772p5'可变区重复号3的共有氨基酸序列。seqidn0:576代表0772p5,可变区重复号4的共有氨基酸序列。seqidn0:577代表0772p5'可变区重复号5的共有氨基酸序列。seqidn0:578代表0772p5'可变区重复号6的共有氨基酸序列。seqidn0:579代表0772p5,可变区重复号7的共有氨基酸序列。seqidn0:580代表0772p5,可变区重复号8的共有氨基酸序列。seqidn0:581代表0772p5'可变区重复号9的共有氨基酸序列。seqidno:582代表0772p5'可变区重复号10的共有氨基酸序列。seqidn0:583代表0772p5,可变区重复号11的共有氨基酸序列。seqidn0:584代表0772p5,可变区重复号12的共有氨基酸序列。seqidno:585代表0772p5'可变区重复号13的共有氨基酸序列。seqidn0:586代表0772p5,可变区重复号14的共有氨基酸序列。seqidn0:587代表0772p5,可变区重复号15的共有氨基酸序列。seqidn0:588代表0772p5,可变区重复号16的共有氨基酸序列。seqidn0:589代表0772p5'可变区重复号17的共有氨基酸序列。seqidn0:590代表0772p5,可变区重复号18的共有氨基酸序列。seqidn0:591代表0772p5,可变区重复号19的共有氨基酸序列。seqidn0:592代表0772p5'可变区重复号20的共有氨基酸序列。seqidno:593代表0772p5,可变区重复号21的共有氨基酸序列。seqidn0:594代表3,恒定区的氨基酸序列。seqidn0:595代表含有21个重复之共有序列和3,恒定区的氨基酸序列。seqidno:596代表共有重复序列的氨基酸序列。图1a-is(seqidno:1-71)描述了编码代表性分泌型卵巢癌抗原的多核苷酸的部分序列。图2a-2c描述了图1的3个克隆的全部插入序列。图2表示命名为07e(11731;seqidno:72)的序列,图2b表示命名为09e(11785;seqidno:73)的序列,及图2c表示命名为08e(13695;seqidno:74)的序列。图3表示命名为08e的卵巢癌序列徵阵列表达分析结果。图4表示编码卵巢癌序列的多核苷酸的部分序列(命名为3g;seqidno:75),所述的卵巢癌序列是人t-细胞白血病病毒类型i癌蛋白质tax和骨粘连蛋白的剪接融合体。图5表示命名为3f(seqidn0:76)的卵巢癌多核苷酸。图6表示命名为6b(seqidn0:77)的卵巢癌多核苷酸。图7a和7b表示命名为8e(seqidn0:78)和8h(seqidn0:79)的卵巢癌多核苷酸。图8表示命名为12c(seqidn0:80)的卵巢癌多核香酸。图9表示命名为12h(seqidn0:81)的卵巢癌多核苷酸。图io描述了命名为3f的卵巢癌序列微阵列表达分析结果。图11描述了命名为6b的卵巢癌序列微阵列表达分析结果。图12描述了命名为8e的卵巢癌序列微阵列表达分析结果。图13描述了命名为12c的卵巢癌序列徵阵列表达分析的结果。图14描述了命名为12h的卵巢癌序列微阵列表达分析的结果。图15a-15eee描述了编码代表性分泌型卵巢癌抗原的附加多核苷酸的部分序列(seqidno:82-310)。图16是示例全长序列中各种部分08e序列的位置的图解。图17是示例对08e蛋白质的表位作图研究结果图。图18是08e细胞表面表达的荧光激活细胞分类术(facs)分析图。图19是08e细胞表面表达的荧光激活细胞分类术(facs)分析图。图20表示08e转染的hek293细胞的焚光激活细胞分类术(facs)分析,证明了08e的细胞表面表达。图21表示skbr3乳腺肺瘤细胞的荧光激活细胞分类术(facs)分析,证明了08e的细胞表面表达。图22表示hek293细胞中的08e表达。用抗08e兔多克隆抗血清并233l探测细胞。图23表示抗08e兔血清的elisa分析。图24表示亲和纯化的兔抗08e多克隆抗体的elisa分析。图25是测定抗08emab(单克隆抗体)的抗体内化的图,表示抗氨基酸61-80的mabs诱导了配体内化。发明详述如上所述,概括地,本发明涉及用于癌症(如卵巢癌)治疗的组合物和方法。本发明所述组合物可以包括免疫原性多肽,编码这种多肽的多核苷酸,结合多肽的结合剂如抗体,抗原呈递细胞(apcs)和/或免疫系统细胞(例如,t细胞)。本发明多肽通常包含至少卵巢癌蛋白质或其变异体的免疫原性部分。用免疫测定技术已鉴定出一些卵巢癌蛋白质,而且在本发明中被称为卵巢癌抗原。,巢癌抗原"是卵巢肿瘤细胞(优选人细胞)以至少高于正常卵巢细胞水平至少2倍的水平表达的蛋白质。某些卵巢癌抗原可检测地(在免疫测定中,如elisa或westernblot)与抗植入了人卵巢肿瘤的免疫缺陷动物血清产生的抗血清反应。这样的卵巢癌抗原从卵巢肿瘤流出或分泌进入免疫缺陷动物的血清。因此,本发明提供的一些卵巢癌抗原是分泌型抗原。本发明的一些核酸序列通常包含编码这种多肽全部或一部分的dna或rna序列,或是这种序列的互补序列。本发明进一步提供了用评估卯巢肿瘤中表达改变的技术鉴定的卵巢癌序列。这样的序列可以是多核苷酸或蛋白质序列。卵巢癌序列在卵巢肿瘤中通常以高于正常卵巢組织中表达水平至少2倍,优选至少5倍的水平表达,这是用这里提供的代表性测定法测定的。本发明提供了一些部分卵巢癌多核苷酸序列。包含这样的多核苷酸序列(或其互补序列)的基因编码的蛋白质也认为是卵巢癌蛋白质。抗体通常是免疫系统蛋白质,或其抗原结合片段,它们能结合本文所述卵巢癌多肽的至少一部分。本发明提供的组合物中可以应用的t细胞通常是对这种多肽特异的t细胞(例如,cd4 和/或cd8 )。本文所述的一些方法进一步利用了表达这里提供的卵巢癌多肽的抗原呈递细胞(如树突细胞或巨噬细胞)。卵巢癌多核苷酸编码本文所述卵巢癌蛋白质或其一部分或其它变异体的任何多核苷酸都包括在本发明中。优选的多核苷酸包含编码卵巢癌蛋白质一部分的至少15个连续核苷酸,优选至少30个连续核苷酸,更优选至少45个连续核苷酸。更优选,多核苷酸编码卵巢癌蛋白质,如卵巢癌抗原的免疫原性部分。与任何这样的序列互补的多核苷酸也包括在本发明中。多核苷酸可以是单链(编码链或反义链)或双链,而且可以是dna(基因组、cdna或合成的)或rna分子。附加的编码或非编码序列可以,但不是必需,存在于本发明多核苷酸中,而且多核苷酸可以,但不是必需,与其它分子和/或支持材料连接。多核苷酸可以包含天然序列(即,编码卵巢癌蛋白质或其部分的内源序列)或可以包含这样的序列的变异体。多核苷酸变异体可以包含一个或多个置换、添加、缺失和/或插入,使得与天然卵巢癌蛋白质比较,所述编码多肽的免疫原性不减少。通常可以如本文所述评估对编码多肽的免疫原性的影响。变异体优选显示与编码天然卵巢癌蛋白质或其部分的多核苷酸有至少约70%同一性,更优选有至少约80%同一性,最优选有至少约90%同一性。通过用本领域技术人员熟知的计算机算法,如megalign,用默认参数,比较序列可以容易地检测两个多核苷酸或多肽序列的同一性百分率。通常通过l匕较窗口"比较序列以鉴定和比较序列相似性的局部区域进行两个序列间比较。本文所用,匕较窗口"指至少约20个连续位置,通常30到约75个,或40到约50个,其中两个序列最佳对齐(aligned)后,序列可以与同样数目连续位置的参照序列比较。可以用,例如,lasergene这套生物信息学软件(dnastar,inc.,madison,wi)的megalign程序,用默认参数进行比较序列的最佳对齐。优选地,通过在至少20个位置的比较窗口比较两个最佳对齐序列检测序列同一性的百分数,其中窗口中多核苷酸或多肽序列部分与参照序列(不包含添加或缺失)比较可以包含20%或以下,通常5-15%,或10-12%的添加或缺少(即缺口)。可以通过测定在两个序列中出现相同核酸碱基或氨基酸残基的位置数得出匹配位置数,匹配位置数除以参照序列总位置数(即,窗口大小),用100乘以所得结果得出序列同一性的百分数,来计算同一性百分数。变异体也可以,或作为替代方案,与天然基因,或其部分或互补序列显著同源。在中度严格条件下,这样的多核苷酸变异体能与编码天然卵巢癌蛋白质(或互补序列)的天然存在的dna序列杂交。适合的中度严格条件包括在5xssc,0.5%sds,1.0mmedta(ph8.0)溶液中预洗;在50x:-5xssc中杂交过夜;随后65x:,用含有o.1%sds的2x,0.5x和0.2xssc各洗2次20分钟。本领域技术人员将理解,做为遗传密码简并的结果,存在许多编码本发明所述多肽的核苷酸序列。这些多核苷酸中一些与任何天然基因的核苷酸序列具有最小限度的同源性。因此,本发明特别考虑了由于密码子使用不同而改变的多核苷酸。而且,包含本文提供的多核苷酸序列的基因的等位基因在本发明范围内。等位基因是由于一个或多个突变,如核苷酸缺失、添加和/或置换而改变的内源基因。由此产生的mrna和蛋白质可以,但不是必需,有改变的结构或功能。可以用标准技术(例如杂交、扩增和/或数据库序列比较)鉴定等位基因。可以用各种技术中任一种制备多核苷酸。例如,如下文将详述的,可以通过用如下抗血清筛选晚期传代卵巢肺瘤表达文库鉴定卵巢癌多核苷酸,所述抗血清是在用植入晚期传代卵巢肿瘤的scid小鼠血清注射免疫活性的小鼠后用这种小鼠的血清产生的。卵巢癌多核苷酸也可以用目的是评估差异基因表达的各种技术中任一种鉴定。或者,可以从卵巢肺瘤细胞制备的cdna扩增多核苷酸。可以通过聚合酶链式反应(pcr)扩增这样的多核苷酸。对于这个方法而言,可以基于本发明提供的序列设计、可以购买或合成序列特异的引物。可以用扩增后的部分,利用公知技术,从合适文库(例如,卵巢癌cdna文库)分离全长基因。在这样的技术中,用一个或多个多核苷酸探针或适合扩增的引物筛选文库(cdna或基因组)优选地,按大小筛选文库以包括较大分子。也可以优选随机引物文库以筌定基因5,和上游区域。优选基因组文库以获得内含子和延伸5,序列。对于杂交技术,可以用公知技术标记(例如,通过用"p切口平移或末端标记)部分序列。随后通过用标记探针(参见sambrook等,#o7ecw7ar67o/7/n《y4z^力or"oryife/2wa7,coldspringharborlaboratories,coldspringharbor,ny,1989)杂交含有变性细菌菌落(或含有噬菌斑的菌苔)的滤膜筛选细菌或细菌噬菌体文库。筛选和扩大杂交菌落或噬菌斑,分离dna进行进一步分析。可以通过,例如,用部分序列上的引物和载体引物的pcr分析cdna克隆以检测附加序列的量。可以产生限制性图谱和部分序列上的以筌定一个和多个重叠克隆。然后可以用标准技术测定完整序列,这包括产生一系列缺失克隆。随后,装配由此产生的重叠序列为单一连续序列。用公知技术,通过连接适合片段可以产生全长cdna分子。作为替代方案,存在从部分cdna序列获得全长编码序列的大量扩增技术。在这些技术中,通常用pcr进行扩增。可以用各种商用试剂盒的任一个进行扩增步骤。可以用,例如,本领域公知的软件设计引物。优选22-30核苷酸长度,有至少50。/。gc含量和在约68-72"温度下与靶序列退火的引物。如上所述可以测序扩增区域,而且可以装配重叠序列为连续序列。这种扩增技术之一是反向pcr(参见triglia等,>4c/^5化s.7^8186,1988),其用限制性内切酶在基因已知区产生片段。然后通过分子内连接环化这个片段,用这个片段作为模板,用来源于已知区的不同方向的引物进行pcr。在可替换的方法中,可以通过用接列。扩增后的序列通常用同样的接头引物和对已知区域特异的第二个引物进行第二轮扩增。这个方法的改变是利用在已知序列相反方向开始延伸的两个引物,这在wo96/38591中描述了。另外的技术包括捕获pcr(capturepcr)(ugrstrom等,pcr淑aoc/s力//7/c.7:111-19,1991)和步行pcr(walkingpcr)(parker等,mucl.acids.res.19:3055-60,1991)。也可以利用其它采用扩增的方法以获得全长cdna序列。在一些情况下,通过已表达序列标志(est)数据库中提供的序列的分析可能获得全长cdna序列,可从genbank中得到已表达序列标志(est)数据库。用公知程序(例如,ncbiblast检索)通常可以进行重叠ests的检索,而且可以用这样的ests产生连续的全长序列。图1a-is(seqidn0:1-71)和图15a—15eee(seqidno:82-310)提供了编码部分卵巢癌抗原的cdna分子的一些核酸序列。图1a-1s提供的序列看来是新的。对于图15a-15eee的序列,数据库检索表明了有显箸同一性的配对。这些多核苷酸是用目的是鉴定分泌的肿瘤抗原的技术,通过卵巢肿瘤cdna表达文库的血清学筛选分离的。简而言之,在载体入-screen(novagen)中从衍生于scid的人卵巢肿瘤(0v9334)制备晚期传代卵巢肿瘤表达文库。通过用植入了晚期传代卵巢肿瘤的scid小鼠的血清注射免疫活性小鼠获得用于筛选的血清。这个技术允许编码分泌性胂瘤抗原免疫原性部分的cdna分子的鉴定。具体地,本发明包括这里所述的多核苷酸,及包含这种序列的全长多核苷酸,这种全长多核苷酸的其它部分,和与这样全长分子的全部或部分互补的序列。这个技术也可以用于其它类型肺瘤分泌的抗原的鉴定,这对本领域技术人员显而易见。图4-9(seqidno:75-81)及seqidno:313-384提供了编码部分卵巢癌蛋白质的cdna分子的其它核酸序列。这些序列是通过筛选肿瘤相关表达的微阵列cdna(即,用本文的代表性测定法测定,卵巢肿瘤中表达至少高于正常卵巢组织5倍)鉴定的。根据制造商说明(而且基本上如schena等,i°roc.淑丄v4cad5w.編93:10614-10619,1996和heller等,yvat丄/4cad5"c2..94:2150—2155所述)用synteni微阵列(paloaltoca)进行这样的筛选。seqidn0:311和319提供了包含这些核酸序列中一些的全长序列。各种公知技术中任何技术都可以用于评估cdna的肺瘤相关表达。例如,可以应用利用标记多核苷酸探针的杂交技术。可供选择地,或此外,可以用扩增技术,如实时(real-time)pcr(参见gibson等,6"e/o迈e/esearca6:995-1001,1996;heid等,ge/o范e/esearc力&986-994,1996)。实时pcr是评估扩增期间pcr产物积累水平的技术。这个技术允许多个样品中mrna水平的定量评估。简而言之,从肿瘤和正常组织提取mrna,而且用标准技术制备cdna。例如,用perkinelmer/appliedbiosystem(fostercity,ca)7700prism仪器可以ca)提供的primerexpress程序,可以为目的基因设计配对引物及荧光探针。本领域技术人员可以最初确定引物和探针的最佳浓度,而且得对照(例如p-肌动蛋白)引物和探针。为了测定样品中特定rna的量,同时用含有目的基因的质粒产生标准曲线。可以用实时pcr测定的ct值产生标准曲线,所迷值与用在测定法中的起始cdna浓度有关。通常范围为10-106目的基因拷贝的标准稀释是足够的。此外,产生对照序列的标准曲线。这允许组织样品起始rna含量相对于对照量的标准化,以便于比较。通常可以通过本领域公知的任何方法制备多核苷酸变异体,包括通过例如固相亚磷酰胺化学合成的化学合成。用标准诱变技术,如寡核苷酸定向位点特异诱变(参见adelman等,2:183,1983)也可以在核苷酸序列中引入修饰。或者,假如dna与适合的rna聚合酶启动子(如t7或sp6)—起被引入载体,那么通过编码卵巢癌抗原或其部份的dna序列体外或体内转录可以产生rna分子。如本发明所迷,一些部分可以用于制备编码多肽。此外,或作为替代方案,可以给患者施用一部分以便体内产生编码多肽。与编码序列互补的序列的一部分(即反义多核苷酸)也可以用做探针或调节基因表达。可以转录成反义rna的cdna构建体可以被引入细胞或组织以有利于反义rna产生。也可以用本发明所述反义多核苷酸抑制卵巢癌蛋白质的表达。可以用反义技术通过三股螺旋的形成控制基因表达,三股螺旋的形成损坏双螺旋充分打开以结合聚合酶、转录因子或调节分子的能力(参见gee等,在huber和carr,m>7eci/hjrawi"历迈w3o2o《icy4//roacae51,futurapublishingco.(mt.kisco,ny;1994)中的描述)。可备选地,可以,没计反义分子与基因控制区(例如,启动子、增强子或转录起始位点)杂交,而且阻止基因转录;或通过抑制转录物与核糖体结合阻止翻译。任何多核苷酸都可以进一步被修饰以增强体内稳定性。可能的修饰包括,但不限于,在5,和/或3,末端增加側翼序列;在主链中用硫代磷酸酯或2,0-甲基,而不是磷酸二酯酶键接;和/或包括非常规的减基如次黄噤吟核香,queosine,wybutosine,及腺噤呤,胞嘧咬核苷,鸟噤呤,胸腺嘧啶和脲嘧啶核普的乙酰-,甲基-,硫代和其它修饰形式。用已建立的重组dna技术可以将本发明所述的核苷酸序列和各种其它核苷酸序列连接。例如,可以克隆多核苷酸进入各种克隆载体,包括质粒、噬菌粒、入-噬菌体衍生物和粘粒。特别有用的载体包括表达载体,复制载体,探针产生载体和测序载体。一般地,载体将包含在至少一种生物中起作用的复制起点,方便的限制性内切酶位点和一个和多个筛选标记。其它元件取决于期望的用途,而且对本领域技术人员显而易见。在一些具体实施方式中,可以配制多核苷酸以允许进入哺乳动物细胞,并在其中表达。这样的制剂对治疗目的特别有用,如下文所述。本领域技术人员将理解存在许多使多核苷酸在靶细胞中表达的方法,而且可以利用任何合适的方法。例如,可以将多核苷酸引入病毒载体,如,但不限于腺病毒,腺相关病毒,反转录病毒,或痘苗或其它痘病毒(例如,禽痘病毒)。引入dna进入这类栽体的技术是本领域技术人员公知的。反转录病毒可以附加地转移或引入筛选标记基因(以帮助转导细胞的鉴定或筛选)和/或靶组成成分,如编码特定靶细胞之受体的配体的基因,以使栽体有耙特异性。也可以用抗体,通过本领域技术人员公知的方法完成靶向。其它用于治疗目的的制剂包括胶体分散系统,如大分子复合物、纳米胶嚢、微球体、珠粒和基于脂质的系统,包括水包油乳剂、微胶粒、混合微胶粒和脂质体。用做体外和体内递送载体的优选胶体系统是脂质体(即人工膜泡嚢)。这类系统的制备和用途是本领域公知的。卵巢癌多肷在本
发明内容中,多肽可以包含至少卵巢癌蛋白质或其变异体的免疫原性部分,如本文所述。如上所述,一些卵巢癌蛋白质是卵巢肿瘤细胞表达的卵巢癌抗原,而且在免疫测定(如elisa)中可检测地与如下抗血清反应,所述抗血清是针对植入了卵巢肿瘤的免疫缺陷动物的血清产生的。本文所述的卵巢癌多核苷酸编码其它卵巢癌蛋白质。本发明所述多肽可以是任何长度。可以存在衍生于天然蛋白质和/或异源序列的附加序列,而且这样的序列可以(但不是必须)有进一步的免疫原性或抗原性。本文所用免疫原性部分"是b细胞和/或t细胞表面抗原受体识别(即特异结合)的抗原部分。这样的免疫原性部分通常包含卵巢癌蛋白质或其变异体的至少5个氨基酸残基,更优选地至少10,而且更优选地至少20个氨基酸残基。优选的免疫原性部分是按本文所述分离的cdna分子编码的。更多的免疫原性部分通常可以用公知技术筌定,如在paul,fw/7cfe范e/7taj/鹏tf/7o2o^r,第三版,243-247(ravenpress,1993)中及其所引参考文献所概括的。这样的技术包括筛选能与卵巢癌蛋白质特异的抗体,抗血清和/或t细胞系或克隆反应的多肽。如果抗血清和抗体特异结合卵巢癌蛋白质(即在elisa或其它免疫测定中它们与卵巢癌蛋白质反应,而不与其它不相关蛋白质可检测地反应),那么如本文所用的抗血清和抗体是,巢癌蛋白质特异的"。用公知技术,可以如本文所述制备这样的抗血清、抗体和t细胞。天然卵巢癌蛋白质的免疫原性部分是与这样的抗血清、抗体和/或t细胞以不显著少于全长多肽反应性的水平(即在elisa和/或t细胞反应性测定法中)反应的部分。在这样的测定法中,这样的免疫原性部分可以以相似或高于全长蛋白质反应性的水平反应。通常可以用本领域技术人员公知的方法进行这样筛选,如在harlow和lane,y4/7tjf/>otableseeoriginaldocumentpage54
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这个筛选进一步鉴定了克隆0772p的多种形式,本发明称作21013,21003和21008。psort分析表明21003(seqidn0:386;翻译为seqidn0:389)和21008(seqidn0:387;翻译为seqidno:390)代表了0772p的类型la跨膜蛋白质形式。21013(seqidno:385;翻译为seqidn0:388)看似该蛋白质的截短形式,而且通过prort分析预测是分泌的蛋白质。其它序列分析产生了08e全长克隆(2627bp,符合northern分析观察到的信息大小;seqidn0:391)。如下所述获得这个核苷酸序列发现原始08e序列(0rig08econs)与est克隆(image#1987589)序列有33个核苷酸的重叠。这个克隆提供了原始08e序列上游的1042个附加核苷酸。用单一est和08e序列引物(estx08epcr),通过测序从卵巢原始肿瘤文库产生的多个pcr片段,证实了est和08e间的连接。当卵巢肿瘤文库锚定pcr给出了几个都终止在推定的起始甲硫氨酸上游,而不能产生任何附加序列信息的克隆(锚定pcrcons)时,进一步表明了全长状态。图16表示示例全长08e序列中每个部分序列位置的图。从全长08e序列可以翻译两个蛋白质序列。对于"a"(seqidn0:393)起始于推定的起始甲硫氨酸。第二个形式"b"seqidno:392)在核苷酸序列的5,末端包括27个附加上游残基。实施例3这个实施例/^开了08e多克隆抗血清识别的抗体表位(antibodyepitopes)的鉴定和表征。产生抗源于大肠杆菌(e.coli)的08e重组蛋白质的兔抗血清,而且检测对与08e氨基酸序列对应的20或21mer版的抗体表位识别。来源于亲和纯化抗08e血清的酸洗脱峰和/或盐洗脱峰识别全长08e蛋白质的跨越氨基酸区31到65,76到110,136到200和226到245的肽。因此上述肽对应的氨基酸序列构成了亲和纯化抗08e抗体识别的抗体表位。抗08e兔血清的elisa分析如图23所示,而且亲和纯化兔抗08e多克隆抗体的elisa分析如图24所示。为了表位作图,合成了对应于08e蛋白质的20或21mer肽。为了抗体亲和纯化,将兔抗08e血清过08e琼脂糖凝胶柱,然后用含有0.5mnacl和20mmp04的盐緩冲液洗脱抗体,随后用o.2m甘氨酸,ph2.3进行酸洗脱步骤。通过lmtris,ph8的添加中和纯化的抗体,并将缓冲液转换为磷酸緩冲盐水(pbs)。为了酶连免疫吸附测定法(elisa)分析,室温下(rt),在96孔平底板上以g/ml包被08e肽和08e重组蛋白质2小时。然后用pbs 0.1%tween20洗板5次,用pbs 1%牛血清白蛋白(bsa)封闭1小时。然后以1pg/ml加酸或盐洗脱部分的亲和纯化抗08e抗体到孔中,室温(rt)温育1小时。再一次洗板,接着加驴抗兔ig辣根过氧化物酶(hrp)抗体,室温1小时。洗板,然后通过添加生色底物3,,3,,5,,5,-四甲基联笨胺(tmb)(bos等,/0//迈冊雄雄y^:187-204(1981);可从sigma(st.louis,m0)得到)显色。室温温育反应15分钟,通过加1nh2s04停止反应。在自动板读数器上,在可见密度450(od450)下读取板。与oe8抗体表位对应的肽序列这里公开在seqidno:394-415。图17公开了08e多克隆抗血清识别的抗体表位。实施例4这个实施例公开了卵巢癌组织样品中08e表达的ihc分析。对于免疫组织化学研究,切石蜡包埋甲醛固定的卵巢癌组织为8微米切片。用在0.1m柠檬酸钠緩冲液(ph6.0)中蒸汽加热诱导表位恢复(steamheatinducedepitoperetrieval,shier)作为最佳染色条件。切片与10%血清/pbs温育5分钟。加入每个切片第一抗体(抗-08e兔亲和纯化多克隆抗体),25分钟,随后与抗兔生物素标记的抗体温育25分钟。通过用过氧化氬进行三个1.5分钟的温育封闭内源过氧化物酶活性。抗生物素蛋白-生物素复合物/辣根过氧化物系统与dab色原体一起使用以显现抗原表达。用苏木精复染载波片。六个卵巢癌组织切片中一个(乳头状浆液癌(papillaryserouscarcinoma))显示了08e免疫反应性。当优化染色条件时,用08e多克隆抗体,4/5卵巢癌样品染色阳性。08e表达定位到质膜。用抗08e兔多克隆抗体分析六个卵巢癌组织。六个卵巢癌组织样品中一个(乳头状浆液癌)染色为08e表达阳性。08e表达定位到表面膜。实施例5这个实施例公开了预测与hla-a2结合,同时对人cd8t细胞应答有免疫原性的08e肽。通过使用08e全长开放阅读框架(orf)和通过用episeek"(用于预测mhc结合肽的程序)运行它,预测08e可能的hla-a2结合肽。所用程序是以parker,k.c.等,//迈迈w/zo丄152(1):163-175(1994)(已整体引入本发明作为参考)公开的算法为基础。预测与hla-0201结合的10mer和9mer肽这里分别公开为seqidn0:416-435和seqidn0:436-455。实施例6这个实施例公开了通过荧光激活细胞分选(facs)检测08e表面表达。对于facs分析,用水冷的染色緩冲液(pbs/196bsa/叠氮化物)洗细胞。下一步,在冰上细胞与10pg/ml亲和纯化兔抗b305d多克隆抗体温育30分钟。用染色緩冲液洗细胞3次,然后冰上与1:ioo稀释的山羊抗兔ig(h l)-fitc试剂(southernbiotechnolgy)温育30分钟。洗3次后,在含有碘化丙锭(prodiumiodide)的染色緩冲液中重悬浮细胞,该活体染料允许可渗透细胞的鉴定,之后通过facs分析细胞。在稳定表达08ecdna的skbr3乳腺癌细胞和hek293细胞上证实了08e表面表达。用对照不相关质粒dna稳定转染的mb415细胞或hek293细胞均没有显示08e表面表达(图18和19)。实施例7这个实施例进一步评估了08e的表达和表面定位。为了表达和纯化用于免疫的抗原,37i:,在振荡培养箱中,在大肠杆菌(e.coli)重组表达系统中表达的08e在有适合抗生素的lb肉汤中过夜生长。第二天早上,在2l带挡板三角瓶中,加10ml过夜培养物到500ml加有适合抗生素的2xyt中。当培养物光密度(在560nni)达到0.4-0.6时,用iptg(lmm)诱导细胞。与iptg温育后4小时,离心收集细胞。然后用磷酸緩冲盐洗细胞,再一次离心。弃去上清液,或冷冻细胞备用或立刻处理。向细胞沉淀中20ml加入溶解緩冲液,涡旋。为了粉碎大肠杆菌细胞,然后在16,000psi压力下,将这个混合物通过弗氏压碎器。然后,再一次离心细胞,通过sds-page检查上清液和沉淀中重组蛋白质的分配。对于定位于细胞沉淀的蛋白质,在10mmtrisph8.0,1%chaps中重悬浮沉淀,而且洗包含体沉淀,再一次离心。再重复这个过程2次。用含有添加10mm咪唑的ph8.010mmtris的8m尿素或6m盐酸胍溶解洗过的包含体沉淀。加溶解蛋白质到5ml镍螯合物树脂(qiagen)中,室温下温育45分钟到1小时,同时持续搅拌。温育后,倾注树脂和蛋白质混合物通过一次性的柱子,收集流过物。然后用10-20倍柱体积的溶解緩沖液洗柱子。随后,用8m尿素,10mmtrisph8.0和300mm咪唑从柱子上洗脱抗原,收集在3ml级分中。进行sds-page凝胶以确定合并哪些级分以进一步纯化。做为最后纯化步骤,用适合緩冲液平衡强阴离子交换树脂,如hi-prepq(biorad),而且加样上面合并的级分到柱上。用逐步增加的盐梯度洗脱柱上抗原。当过柱时,收集级分,而且进行另一个sds-page凝胶以检测合并柱上的哪些级分。用10mmtrisph8.0透析合并的级分。然后评估这个物质的sds-page或hplc测定的可接受纯度,劳里(lowry)测定法或氨基酸分析测定的浓度,氨基酸末端蛋白质序列测定的同一性,及鲎(lal)测定法测定的内毒素水平。然后,通过o.22ym过滤器过滤后,装瓶蛋白质,并在需要免疫前冷冻抗原。为了产生多克隆抗血清,每种前列腺抗原400ng与loong胞壁酰二肽(mdp)混合。加入等体积不完全弗氏(freund,s)佐剂(ifa),然后混合。每4周,用100pg与等体积ifa混合的抗原加强免疫。每次加强免疫后7天,取动物血液。在4k温育血液12-24小时,离心,产生血清。为了表征多克隆抗血清,通过与50pl(典型地是lmg)抗原在4t:温育20小时包被96孔板。孔中加入250plbsa封闭緩冲液,室温温育2小时。用pbs/0.01%tween洗板6次。在pbs中稀释抗08e兔血清或亲和纯化抗08e抗体。每个孔加入50p1稀释抗体,室温下温育30分钟。如上述洗板,之后以1:10000稀释度加入50[i1山羊抗兔辣根过氧化物酶(hrp),室温下温育30分钟。如上述洗板,每个孔加入100yltmb微孔过氧化物酶底物。在暗处室温温育15分钟后,用ioom11nh2s04终止比色反应,在450nm下立即读数。所有多克隆抗体均显示了对08e抗原的免疫反应性。为了在哺乳动物hek293细胞中重组表达,亚克隆全长08ecdna进入哺乳动物表达载体pc醒3.1 和pcep4(invitrogen),所述载体被修饰分别含有组氨酸和flag表位标签。用fugene6试剂(roche)转染这些构建体进入hek293细胞(atcc,美国典型培养物保藏中心)。简而言之,hek293细胞以100,000细胞/ml密度在含有10�s(hyclone)的dmem(gibco)中接种并过夜培养。下一天,向100m1不含fbs的dmem中加入2ji1fugene6,室温温育15分钟。向1pg08e/pcep4或08e/pcdna3.1质粒dna中加入fugene6/匿m混合物。然后加fugene/dna混合物到hek293细胞,37"c,7%0)2中温育48-72小时。用pbs润洗细胞,然后通过离心收集和沉淀。为了western印迹分析,通过冰上在含有triton-x100的裂解緩冲液中温育细胞,产生全细胞裂解物。通过10,000rpm,4x:离心5分钟澄清裂解物。用含有p-巯基乙醇的sds-page上样緩冲液稀释样品,然后在加载至sds-page凝胶前煮沸10分钟。转移蛋白质到硝酸纤维素上,而且用以1:750稀释的抗08e兔多克隆血清#2333l探测。用与hrp偶联的山羊抗兔ig并随后在ecl底物中温育显示印迹。对于facs分析,进一步用水冷却染色緩冲液(pbs l先bsa 叠氮化物)洗细胞。下一步,在水上,细胞与10ng/ml蛋白质a纯化的抗08e多克隆血清温育30分钟。用染色緩冲液洗细胞3次,然后水上与1:100稀释的山羊抗兔ig(h u-fitc试剂(southernbiotehnology)温育30分钟。洗3次后,在含有碘化丙锭(pi)的染色緩冲液中重悬浮细胞,该活体染料允许可渗透细胞的鉴定,之后通过facs分析细胞。从这些试验中(图20-21示例了结果),用兔抗08e血清,通过facs分析检测到转染的hek293细胞和skbr3细胞表面上08e表达。通过westernblot分析,也在转染的hek293细胞裂解物中检测到表达(图22)。实施例8抗08emabs(单克隆抗体)的产生和表征如下所述,产生抗源于大肠杆菌(e.coli)的08e蛋白质的小鼠单克隆抗体。用含有50ng重组08e的完全弗氏佐剂(cfa)腹膜内(ip)免疫a/j小鼠,随后用含有10ng重组08e蛋白质的不完全弗氏佐剂(ifa)腹膜内(ip)加强免疫。切除脾脏前3天,用约50pg溶解的08e重组蛋白质静脉内免疫小鼠。除去对08e有阳性效价的小鼠的脾脏,制备单细胞悬浮液,用于与sp2/0骨髓瘤细胞融合以产生b细胞杂交瘤。通过elias检测杂种克隆上清液对重组08e的特异性,而且用跨整个08e序列的肽进行表位作图。还通过流式细胞术测试mabs检测稳定转染08e的细胞表面上和乳腺肿瘤细胞系表面上08e的能力。对于elisa分析,分别用重组08e蛋白质或跨整个08e分子的重叠20mer肽,在1-2fig/ml或10pg/ml浓度下包被96孑l板。包被后,用冲洗緩冲液(pbs 0.1%tween20)洗板5次,用含有0.5%bsa,0.4%tveen20的pbs封闭。然后加杂种上清液或纯化mabs,室温温育板60分钟。用冲洗緩冲液洗板5次,加与辣根过氧化物酶(hrp)连接的第二抗体,驴抗鼠ig(jacksonimmunoresearch),60分钟。在冲洗緩冲液中再一次洗板5次,随后加辣根过氧化物酶底物。产生的杂交瘤克隆中,有15个识别整个08e蛋白质的分泌的mabs。表位作图显示在这15个克隆中,14个分泌的mabs识别08e氨基酸残基61-80,一个克隆分泌识别氨基酸残基151-170的mab。对于流式细胞计量术分析,收集稳定转染08e的hek293细胞和表达08emrna的skbr3细胞,在流动染色緩沖液(pbs 1%bsa 叠氮化物)中洗涤。在水上,细胞与mab杂合体上清液温育30分钟,随后,用染色緩冲液洗3次。在水上,细胞与山羊抗鼠ig-fitc温育30分钟,随后在含有碘化丙锭的冲洗緩冲液中重悬浮前用染色緩冲液洗3次。流式细胞计量术分析表明15/15mabs能检测表达在08e转染的hek293细胞表面上的08e蛋白质。在skbr3细胞上试验的6/6mabs能识别表面表达的08e。实施例9序列0772p的延长dna和蛋白质序列分析通过筛选卵巢肿瘤(scid来源的)cdna文库获得包含克隆3f,6b,8e和12的全长序列,详细如实施例2所述。这个2996碱基对序列,命名为0722p,如序列seqidn0:311所示,而且编码的914氨基酸蛋白质序列如seqidn0:312所示。利用公共数据库,包括genbank,检索dna序列0772p,它显示了与genbank登记号ak024365(seqidn0:457)的显著命中。发现这个genbank序列长度是3557碱基对,编码长度为1156氨基酸的蛋白质(seqidn0:459)。这个序列的截短形式,残基25-3471(seqidn0:456),编码长度是1148个氨基酸的蛋白质(seqidn0:458),其中残基25对应于genbank序列中第一个atg起始密码子。公开的dna序列(seqidn0:457)与0772p不同在于它有与seqidno:457的碱基958-962对应的5个碱基对插入。这个插入引起读框移位,以致与0772p(seqidn0:312)相比,seqidn0:457编码附加的n-末端蛋白质序列。此外,0772p编码包含在残基1-79(seqidn0:460)中的单一n-末端部分。seqidno:456的n-末端部分残基1-313也含有单一序列(uniquesequence),如seqidno:術所列。实施例10产生多克隆抗体用于0772p分子细胞相关表达型式的免疫化学和流式细胞计量术分析在本申请实施例2和9中鉴定了0772p分子。为了评估在各种组织中抗原表达的亚细胞定位和特异性,产生抗0772p的多克隆抗体。为了产生这些抗体,在大肠杆菌(e.coli)重组表达系统中表达0772p-1(序列seqidn0:312的氨基酸44-772)和0772p-2(序列seqidno:312的氨基酸477-914),37x:在lb肉汤中过夜生长。下一天,加入10ml过夜培养物到500ml含有适合抗生素的2xyt中。当培养物光密度(在560nm)达到0.4-0.6时,用iptg(lmm)诱导细胞。温育后,收集,洗涤,裂解细胞,在16,ooopsi压力下,通过弗氏压碎器。然后,离心细胞,通过sds-page检查重组蛋白质的分配。对于定位于细胞沉淀的蛋白质,在10mmtrisph8.0,t/。chaps中重悬浮沉淀,而且洗涤包含体沉淀,离心。用含有添加10mm咪唑的ph8.010ramtris的8m尿素或6m胍hc1溶解洗过的包含体沉淀。加溶解蛋白质到5ml镍螯合树脂(qiagen)中,室温下温育45分钟。温育后,倾注树脂和蛋白质混合物通过柱子,收集通过的液流。然后用10-20倍柱体积的緩冲液洗柱子。随后,用8m尿素,10mmtrisph8.0和300mm咪唑从柱子上洗脱抗原,收集在3ml的级分中。进行sds-page凝胶以确定合并哪些级分以进一步纯化。做为最后纯化步骤,用适合緩冲液平衡强阴离子交换树脂,而且加样上面合并的级分到柱上。用逐步增加的盐梯度洗脱柱上抗原。收集级分并用sds-page凝胶分析以确定合并柱上的哪些级分。用10mmtrisph8.0透析合并的级份,呈上由此产生的蛋白质用于最后释放的质量控制。释放的标准是(a)sds-page或hplc测定的纯度,(b)劳里(lowry)测定法或氨基酸分析测定的浓度,(c)氨基酸末端蛋白质序列测定的同一性,及(d)鲎(lal)测定法测定的内毒素水平。然后,通过0.22nm过滤器过滤蛋白质后,在需要免疫前,冷冻抗原。为了产生多克隆抗血清,将400pg0772p-1或0772p-2与100pg胞壁酰二肽(mdp)混合。每4周,用100mg与等体积不完全弗氏(freund,s)佐剂(ifa)混合的抗原免疫兔。每次加强免疫后7天,取动物血液。在4c温育血液12-24小时,离心,产生血清。为了鉴定多克隆抗血清的特性,用抗原包被96孔板,随后用bsa封闭。在pbs中稀释抗兔血清,加入每个孔。然后洗板和加入山羊抗兔辣根过氧化物酶(hrp)。再一次洗板,每个孔加入tmb徵孔过氧化物酶底物。温育后,终止比色反应,在450nm下立即对板读数。所有多克隆抗体均显示了对合适抗原的免疫反应性。在石蜡包埋甲醛固定的组织上进行0772p表达的免疫组织化学分析。发现0772p在正常卵巢和卵巢癌中表达,而不在心脏,肾,结肠,肺或肝中表达。此外,免疫组织化学和流式细胞计量术分析表明0772p是质膜相关分子。0772p1含有预测由氨基酸859-880编码的跨质膜结构域1。0772p的n-末端是细胞外的,而且是通过氨基酸1-859编码,而c-末端是细胞内的。序列分析表明有17个可能的n-连接的糖基化作用位点。实施例110772p在原发卵巢胂瘤细胞表面上表达为了在哺乳动物细胞中重组表达,分别亚克隆0772p-21008(seqidn0:387)和0772p全长cdna(seqidn0:311,编码seqidno:312蛋白质)进入哺乳动物表达载体pbib或pcep4。用fugene6(roche)转染这些构建体进入hek293细胞。然后,hek293细胞以100,000细胞/ml密度在含有胎牛血清(fbs)的dmem中接种,过夜生长。第2天,加入1fugene6到loo[i1dmem中,dmem中不含有fbs,室温下温育15分钟。向1mg0772p/pbib或0772p/pcep4质粒dna中加入fugene6/dmem混合物,室温温育另外15分钟。然后,将fugene6/dna混合物加到hek293细胞中,37x:,7�2中培养48-72小时。洗涤细胞,然后通过离心沉淀。为了western印迹分析,通过在裂解緩冲液中温育细胞,产生全细胞裂解液,随后离心澄清。稀释样品,进行sds-page。然后转移凝胶到硝化纤维素上,而且用纯化抗0772p-2兔多克隆抗体探测。用与hrp结合的山羊抗兔ig在ecl底物中温育后显示印迹。westernblot分析表明能在0772p转染的hek293细胞中检测到0772p-21008。为了检测细胞中0772p的细胞表达分布图,在scid小鼠中生长原发卵巢癌肿瘤细胞。从小鼠中取回细胞,通过流式细胞计量术分析。简而言之,在含有pbs,1%bsa,和叠氮化钠的冷却染色緩冲液中洗细胞。细胞与10mg/ml纯化的抗0772p-1和0772p-2多克隆血清温育30分钟。温育后,在染色緩沖液中洗细胞3次,用与fitc缀合的山羊抗兔ig(h u(southernbiotechnology)温育。在含有跌化丙锭(pi)的染色緩冲液中洗涤和重悬浮细胞,该pi是鉴定非存活细胞的活体染料。然后用荧光激活细胞分类术(facs)分析细胞。facs分析表明,0772p在细胞表面存在。胂瘤细胞上的0772p表面表达允许通过治疗抗体进行免疫靶向。实施例12抗08e单克隆抗体的功能表征如实施例8所述,产生小鼠抗源于大肠杆菌(e.coli)的08e的单克隆抗体(mab),并检测该单克隆抗体促进08e抗原内在化的能力。体外用细胞毒性测定法测定抗体内在化。简而言之,在50ng/孔纯化抗08e或对照抗体存在的情况下,hek293和08e/hek转染细胞在含有添加10%热失活fbs的dme的96孔板中接种。抗08emab的同种型如下11a6-igg1/k,15c6-igg2b/k,18a8-igg2b/k,及14f1_igg2a/k。w6/32是用作阳性对照的黑猩猩(pan)抗人mhc类型i小鼠单克隆抗体,还包括做为阴性对照的两个不相关mab,ir-pharm和ir-crxa。与08e特异抗体或相关对照抗体温育后,以100ng/ml的浓度加mab-zap(—种山羊抗小鼠ig-皂草素缀合的第二抗体)(advancedtargetingsystems)到一半孑l中,37e,在7%(302培养箱中温育板48到72小时。这个测定法利用了皂草素(核酶失活蛋白质)的有毒特性,当其内在化时皂草素有细胞毒性作用。与mab-zap温育后,通过添加mts试剂,随后在微板elisa读数器上对板od490读数来定量内在化。图25描述了从这些测定得到的结果。上图代表没有被08e转染的hek细胞,因此08e抗体不应该结合和被内在化。无论样品是否与mab-zap温育,除了阳性对照ab,w6/32外,所有样品的增殖水平是同样的。下图代表被08e转染的hek细胞,因此应该结合08e特异抗体。来源于杂交瘤11h6,14fl,和15c6的,识别08e氨基酸61-80的抗体能促进08e表面蛋白质内在化,这是通过由于mab-zap的毒性引起增殖水平降低检测到的。实施例13卵巢肺瘤抗原0772p的表征上文(例如实施例2和9)已描述了卵巢胂瘤抗原0772p多种形式的cdna和蛋白质序列。genbank检索表明0772p同flj14303(登记号ak024365;seqidno:457和463)有高度相似性。在序列seqidno:478和479中分別公开了与0772p和flj14303对应的蛋白质序列。flj14303与0772p大部分相同,3,-末端大量序列,显示了100%同源性。然而,flj143035,-末端比0772p进一步延伸5,。此外,flj14303含有5bp插入序列(seqidn0:457),这个插入引起了氨基末端蛋白质序列的读框移位,以致与0772p比较,flj14303利用了不同起始甲疏氨基酸,因此编码不同蛋白质。在基因组序列中存在这个插入,而且在显示与这个区域有同一性的所有est克隆中可见这个插入,表明flj14303(seqidno:457)代表了0772p的剪接变体,同时有含有延伸和不同氨基末端的0rf。附加的5'核苷酸序列包括在0772p基因组作图期间鉴定的重复序列。0772p的5'末端和flj14303的相应区域显示90-100%的同源性。总的看来,这表明0772p和flj14303是相同基因不同剪接的变异体,不同单一重复序列被剪接进入基因的5,-末端。在染色体19的相同区域内另外10个或更多个重复序列的鉴定,表明由于不同重复序列的不同剪接,可以有许多种形式的0772p,每个都有不同的5,-末端。0772p的northern印迹分析证明了不同大小的多个与0772p杂交的转录物,一些超过了10kb。进一步分析鉴定了13个另外0772p相关序列,它们的cdm和氨基酸序列如表2所述。
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nd=未检测最初,认为这些序列代表了0772p剪接形式的重叠和/或不连续序列,其能编码0772p特定剪接形式所独特的多肽。然而,这些序列的核苷酸对齐(alignment)未能在重复元件内鉴定出相同区域。这表明这些序列可能代表单0772p基因的不同特定区域,该基因含有16或更多重复结构域,它们的全部形成了单一线性转录物。序列ls#104300.10(表2;seqidno:465)的5,-末端对0772p和flj14303都是唯一的,而且不含重复元件,表明这个序列可能代表0772p的5,-末端。以前,跨膜预测分析表明0772p含有1至3个跨膜的横跨结构域。通过用免疫组织化学和流式细胞计量术证实了这点,也证明了代表0772p的质膜相关分子的存在。然而免疫组织化学也表明了分泌形式的07mp的存在,它可能从0772p的可变剪接形式或从翻译后切割事件产生。表2所示几个序列的分析表明了序列1043400b.12,1043400.8b和1043400.11b都含有跨膜区域,而1043400.8a,1043400.10,1043400.1,1043400.11a和1043400.9都缺少跨膜区域,表明这些蛋白质可能是分泌的。分析表明,部分0772p被表达和/或保留在质膜上,使0772p成为定向抗这种蛋白质的特异免疫治疗,例如治疗性抗体的有吸引力的目标靶。在序列seqidn0:489中公开了预测的0772p细胞外结构域,而且由于在以下序列中的切割事件,0772p的分泌可能会出现slveqvflecrlnasfhwlgstyqlvdihvtemessvyqp.在seqidn0:489位置10的赖氨酸(k)处最可能出现蛋白酶切割。0772p的细胞外,跨膜和细胞质区域都在序列seqidn0:488中公开了细胞外的:ssvlvdgyfpnrnepltgnsdlpf跨膜的waviliglagllglitclicgvlvtt细胞质的rrrkkegeynvqqqcpgyyqshldledlq实施例14在卵巢癌和正常组织中08e表达的免疫组织化学(ihc)分析为了检测哪些组织表达卵巢癌抗原08e,用对08e特异的多克隆和单克隆抗体,在各种组织切片进行ihc分析。08e特异性单克隆抗体的产生如实施例8中详细所述。用于染色的单克隆抗体是11a6和14f1它们是08e的氨基酸61-80特异的,所用单克隆抗体还有18a8,它识别oe8的氨基酸151_170(其产生详见实施例12)。为了染色,在甲醛溶液中固定组织样品12-24小时,在切成8ym切片前在石蜡中包埋。用在0.1m柠檬酸钠緩冲液中蒸汽加热诱导表位恢复(sheir)做为最佳染色条件。切片与1(t/。血清/pbs温育5分钟。然后每个切片加入第一抗体,25分钟,随后与抗兔或抗小鼠生物素标记的抗体温育25分钟。通过用过氧化氢进行三个1.5分钟的温育封闭内源过氧化物酶活性。抗生物素蛋白-生物素复合物/辣根过氧化物酶(abc/hrp)系统与dab色原体一起使用以观察抗原表达。用苏木精复染载波片以观察细胞核。用08e兔亲和纯化多克隆抗体(氨基酸29-283;该抗体的产生细节,参见实施例3)得到的结果如表3所示。用3个单克隆抗体得到的结果如表4所示。表3
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表4用单克隆抗体进行的08e免疫组织化学分析
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0=没有染色,1=轻度染色,2=中度染色,n/a-没有得到实施例150772p多克隆抗体的表位作图为了进行0772p的表位作图,产生了肽,这些肽的序列来自0772p序列。这些肽是15mers,有5个氨基酸重叠,通过在膜载体上化学合成而产生。所述肽通过其c-末端与whatman50纤维素载体共价结合,而n-末端不结合。为了测定表位特异性,用100%乙醇湿润膜1分钟,随后在tbs/tween/triton緩冲液(50ramtris,137mmnacl,2.7mmkc1,0.5%bsa,0.05%tween20,0.05%tritonx-100,ph7.5)中封闭16小时。然后用两个0772p特异抗体,0772p-1(seqidn0:312的氨基酸44-772)和0772p-2(seqidno:312的477—914;参见实施例10中抗体产生的详述)及不相关兔抗体做为对照探测肽。稀释抗体为lpg/ml,室温下与膜温育2小时。然后在tbs/tween/triton緩冲液中洗膜30分钟,之后与1:10,000稀释的hrp-连接的抗兔第二抗体温育2小时。再一次在tbs/tween/triton中洗膜30分钟。用ecl观察抗肽反应性。在表5中描述了特定表位对每个0772p多克隆抗体的结合特异性表5
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*=相对的反应水平,-未结合,****最大结合实施例160772p相关的新n-末端重复结构的鉴定如上所述,已鉴定和表征了各种0772pcdna和蛋白质形式(例如,实施例1,2,9和14)。重要的是,相对于正常组织,证明了0772prna和蛋白质在卵巢癌组织中过量表达,因此是卵巢癌诊断和治疗应用的有吸引力的靶标。利用以前鉴定为与0772p有同源性的基因组核苷酸序列的开放阅读框架(0rfs)的生物信息学分析,在编码0772p蛋白质的基因的5,区域鉴定出了多个核苷酸重复序列。用对各重复特异的引物,通过rt-pcr证实了这些重复序列中的许多。从cdna扩增了含有多个重复的片段,因而证实了特定重复的存在及允许确定这些重复的顺序。意外地,当分析来源于不同数据库和实验室来源的各组0772p序列时,在0772p基因的5,-区域和0772p蛋白质的相应n-末端区域鉴定到了至少20个不同重复结构,每个重复结构相互之间都有实质水平的同一性(参见表6)。每个重复包含编码多肽单元的连续开放阅读框架,所述多肽单元能与一个或多个其它重复剪接,这样形成了不同数量和顺序的重复串连体。有趣地是,在科学文献中描述了有类似于本发明所述0772p的重复结构域的其它分子。例如蛋白质粘蛋白家族,它们是下述粘液的主要糖蛋白组分,所述粘液包被呼吸道,消化道和泌尿生殖道被覆细胞表面。已证明不同粘蛋白是由不同数量,长度和氨基酸序列的串连重复序列组成(perez-vilar和hill,/.a/o丄ca亂房"w..31751-31754,1999)。预期本文所述各种筌定的重复结构很可能通过可变剪接产生多种形式的0772p。已鉴定的重复的cdna序列如seqidno:513-540,542-546和548-567所述。所述重复的编码氨基酸序列如seqidn0s:574-593所述。在许多情况下,这些氨基酸序列代表共有序列,所述共有序列是从一个以上通过试验得到的序列的对齐得到的。这些剪接形式中每一个都能编码有多个重复结构域的唯一0772p蛋白质,所述多个重复结构域与含有跨膜区的0772p恒定羧基末端蛋白质部分连接。0772p恒定区的cdna序列如seqidn0:568所述,而且编码的氨基酸序列如seqidn0:594所述。分解所有得到的可用0772p序列为其可養定的重复。用加权残基重量表(weightedresideweighttable)及cluster方法(dnastar序列分析包中的megalign软件)比较这些序列以鉴定重复序列间关系。利用这个信息,通过rt-pcr提供的排序数据,和用seqman(dnastar)进行的序列对齐(自动和人工),鉴定出了一个包含20个明显不同重复单元的示例性共有序列全长0772p重叠群。这个0772pcdna重叠群的cdna如seqidn0:569所述,而且编码氨基酸序列如seqidn0:595所述。这种形式的0772p蛋白质包括按以下顺序的下述共有重复结构seqidn0:572-seqidno:574-seqidn0:575-seqidno:576-seqidn0:577-seqidno:578-seqidn0:579-seqidno:580_seqidn0:581-seqidno:582-seqidn0:583-seqidno:584-seqidno:585-seqidno:586-seqidn0:587-seqidno:588-seqidno:589-seqidn0:590-seqidn0:591-seqidno:592-seqidno:593。因此,seqidno:595代表了0772p蛋白质一个示例性全长共有序列。然而,如上所述,基于对这个蛋白质目前的知识和基于描述含有类似重复结构的蛋白质的科学文献,预期存在许多有或多或少重复的其它形式0772p。另外,预期许多形式的0772p有不同排列,例如不同顺序的这些n-末端重复结构。通过0772p的northern分析支持了有不同数量重复的多种形式0772p的存在。在这个研究中,0772p特异探针的northern杂交产生了多个0772p杂交性转录物的成片条带,一些超过了10kb。因此,0772p蛋白质的可变重复区可以用xn-y结构示例性地表示,其中x包含与seqidno:596所示共有重复序列有至少50%同一性的重复结构;n是蛋白质中存在的重复数,预期典型地是从1到约35的整数;y包含seqidn0:594所述的恒定区序列,或与seqidno:594有至少80%的同一性的序列。0772p分子xn重复区中存在的每个x是不同的。为了确定20个重复区中每个的共有序列,对齐经试验测定的分立重复区的序列并确定共有序列。除了确定每个重复区的共有序列外,也确定了共有重复序列。过对齐来源于各重复区每一个的共有氨基酸序列和总的重复共有序列,检测重复的变异性。同一性数据如表6所示。表6与共有重复序列比较,重复序列的同一性百分率
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从上述描述可以理解,尽管为了举例说明的目的这里描述本发明特定实施方式,但是可以进行各种修改,而不背离本发明的精神和范围。因此,本发明仅受所附权利要求书的限制。序列表<11g>corixacorporationmitcham,jenniferl.king,gordone.algate,paula.fling,stevenp.retter,marcw.fanger,garyrichardreed,steveng.vedvick,thomass.carter,darrickhill,paulalbone,earl<120〉用于治疗和诊断卵巢癌的组合物和方法<130>210121.46201pc<140〉pct'<141〉2001-07-17<160>596<170>fastseqforwindowsversion4,0<210〉1<211〉"1<212>dna<213〉人(homosapiens)<400>1ttagagaggcacagaaggaagaagagttaaaagcagcaaagccgggtttttttgttttgt60tttgttttgttttgttttgagatggagtctcactctgttgcccaagctggagtacaacgg120catgatctcagctcgctgcaacctccgcctcccacgttcaagtgattctcctgcctcagc180ctcccaagtagctgggattacaggcgcccgccaccacgctcagctaattttttttgtatt240tttagtagagacagggtttcaccaggttggccaggctgctcttgaactcctgacctcagg300tgatccacccgcctcggcctcccaaagtgctgggattacaggcgtgagccaccacgcccg360gcccccaaagctgtttcttttgtctt;tagcgtaaagctctcctgccatgcagtatctaca420taactgacgtgactgccagcaagctcagtcactccgtggtc461<210>2<211>540<212>dma<213>人<400>2taggatgtgttggaccctctgtgtcaaaaaaaacctcacaaagaatcccctgctcattac60agaagaagatgcatttaaaatatgggttattttcaactttttatctgaggacaagtatcc120attaattattgtgtcagaag-agattgaatacctgcttaagaagcttacagaagcta,tggg180
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ccagtattcctcccctaatgatgcctgctcccctagtgccttctgttagta531<210〉6<211>531<212>d船<213〉人<400>6aatagatttagttgagtaggccsgctccscgcaccagtgcatccgggcttttctccgagcgctgcagcctatgcagagtgtttctgaggsctcacttgtscaaggccsgccaccsctggttggcactgcctggcccsgggcgsgcccs3tcagctgcagctcaacttcaatgcaccctggggagaaaccagaagagcccagctggcactgactctcttggtccgatatcagcccattcgacttcaaatccttgattgatacttgaagagacaggcaccagaatgtgagaggcactggcacgctttggcttgcttcgtcccgctctaatctgcttccatcggtggctgcctaagactggcaagctgccacttggcggtcagtgttattggttsgcttctgcagttgcagggcggccctagccctctcggtaagagtgctgt60ggattaacaa120ggtgctggca180gctggcacca240actggtactg300tcccgcctgg360cccggcagca420cttggcttca480c531<210>7<211〉531<212〉dna<213>人<400>7agtcaggcttgcccgcagggttggctgcttaaggctcgcccgggatgtggactgatgtgtattcaattga<210>8<211>531<212>dna<213>人cccgaaaggtctgga3ccaccttcaagggggggcccggaggtagagctgccccttttgcaagattcccat3ccccga3atgaagcatctgaggtggccgatcccatagccagccttgctccaagctcc3gagggagggcacaagcgctcgcattgaacgataagaatgscgatggggasgagggtctcaattttgggccctccctgagattcatcccaagaatgatttgggaicatgctgagcaggctattcacttgtaca3gg3tggc3g3ggccct33tgcsgggcstccacctaaagcagcctgaagctgaagtacct3ggac3tcatccttggaig33ttcttctcagcagtgatcag60ggcctcaatg120aaggactcgg180ccgtaggggc2403ccscc3cct300tttggctaaa360caaag33tac420ggtatttggg480c531<220><221>misc—feature<222>481—<223>n-a,t,c或g<400>8gaggtctcacgttggtctcccaatcaggaaattgcttgcctagattttcttaaaataattgtttcttggaataagaacaantcttaattg<210>9<211>531<212〉dmatatgttgcccaaaagtgctggactttttcctgagggtgacgaatgcaaaa3ttc3c3t3tgtaaactccacaggsccttgaggctgttctggatcataggttcttca3gatacaaaattgataaaatgtgttcctg3tttttactcatcctc3t333ttccttgtccatctgaactcctgcgtgagccacagtg3agggtcttgctaaaaaactaatgaac33gs33cc3tggataagagttttagttcactcacccagcttccagagtsggttaggatgctttaggtaataatgtatgatattataagtaaatagtctcgaatcacaaaatccacccat60caccaatttt120tagctacact180ggtaaagsat240tacatattca300aatgctttga360atcactgata420tgggtgtttg480a531<213>人<221>raise—feature<222>528—<223>n=a,t,c或g"00>9aagcggaaatgagaaaggagagggctcagtcctgttggagggtgcacagaccagcacggcatacsctgagtataagggtttgtgcagtgaatctaagaaaatgttctgagttacctatttaagttaaaaacaaagcaggttccacccaaggagecagggaaggtacttgagttggaattgggaaaatcatgtggtattgaaactctgggtggtgctgtagtctgtgacctgtttgttacaggtttagaaactcttacagcaaaattggggctgtatttgtttattgeattttaicaaasgccctttatcacsgcactgtcggctgggctaaaccaaagaatttttaatcccatcattaccagcgg3a33ctgctggaitgsc60aacagggecactcacagtgg120ggtccatgatgaggtaaaca180aatttgacaaagtaatcttc240atgttcctttttttcatttc300atccttccatgaaggacegg360tagaacacagttcagagtta420tttgcttttggttaatcatc480ggctggangtg531<210>10<211>861<21'2>dma<213>人<400〉10ccgcggctcctgtc'cagaccgccagccttgtactgatgtcatcagaaaaggtgactaatagatcagataaaacagtttaatttttggactgtgttagagatcagaacattgcttacagaagaatatcatattcagcaga3cgatagagaagtcctgatgggaaatgaggactcatctgatgtcatgactgtttggcaaataatcacaatagaaggtcttatt3tg3ttc3gcagcttggtactgttaattttaaagcaacactcaaagtaaaataaatgg<210>11<211>541<212>dma<213〉人ctgaccctccctcccaaggcggctgegagagcctgtgcttttggacaactacttttccagaaggtaccag3agaatatggggaatttctggggacctacacttcacaacasgagaagtsaatatttaaaaatgacacaaatgaagccctggeagecaaagatgaacttttgatgaaagatagsatcccctgaaagcagtaggaaaccgetggagaaacaattgttcagtgaaataataagcacttgattagaaaaataaattatgtgttcgatcatgtat3tcaaccgtcccccaacaacc60aagtaagaatcaggecttat120aacagaaaggaaa.ctcatgc180ctgcacaaataccagaatct240ataaacttacagagacctgc300aacctgaagagaccacctgt360gaatatccatgagatttcag420caggactccttggccaacca480tgccaaceigctgctttattg540gccsccatgttcaaccatct600sattgetatttacc3ggaat660atgeaacatttgttgaggcc720ccattgtttcttcaattgtg780gagatagaaaaatttttatt840861<400>11caccaatataaatccaatttstgsagct3gc3algtg3tg3tggcataagatatatccacttgaaagcgttcctgatcttgagagtaa'cagaaaaagaaaacaaaacgaacaasgtgtcatacaaggcaccgtgatttttggaaaatcagatgagaaaact3ettttgegaaaacggtggcctttgatattaaacttgtga3cttgttctccatttcasataaagacatttttgcattttgagtct33ttctsgcctctgsstaattctaacctgaagaaatgtggtctttccaasgectgactaaaagaggaaaagaattt60tccaagaatcacttttgtaa120gg33ataaaaacacaagact180gcatattcttcgacaaattg240aggaggcatatcacatccca300gatgaaccaaagacacaaaa360ataaaccttgaacatctcct420gtgatgacttttgtggacat4803ctcccctgaaaacctttgc540541<210>12<211〉541<212>d船<213〉人<4o0〉12ctgggatcatcstcctcttcaagatgatgctggctgtttccsgcttccscctgattcagactttgctgtcttggtcgattttggtgaattttctcttgattgtacagtgcttctgtttcttctgacttca3gcatcttcaggtcgaagagtgtgctctcaaagtggcctgtccaggasacgtcataaaagtgccgggtaccctaccataaccttctttgttctggatgtttcactgtgatggc33cccatggtgtcccagataacaccatactcttcttcaacggctatcctgaagaaatcaaacctgagtatttttcaattttctcctcttgttgtcatgcccatttattcattcgattttcctcttcatttgtctttsttcgctggaatctttttaccagggctcactattttgctgcgggggctgscattagacctctaaactattgtcctcttctt60tcctgagatg120gtcgtttgac180tcatgcccct240gaggaaactt300aaatttgcct360aaagaaacct420tcagtatagc480gaattggttt540541<210>13<211>441<212>d肌<213>人<400〉13gagggttggtcttcccccggggsgggggaggggaggcggattgtcatgtatattttc33atcctcccaac<210〉14<211>131<212>dma<213〉人ggtagcggctctcccttcgtggcgtcggggggctgtgaggtttgag33gagccaagactgctggagaasgcctaatgtcgtgggg3ggtgttccccccccgggtgggggggactccgggagggggaaaaatg3tggatgactcgctctgtcggtcgcctgaggcgttccgagccatggacggaagtttgtgattcagtggtttcagsactcggtcttgctcgtgccggaggtccccssgagtcgagaggccctgtcctggtcccaatttstcagctcctgctctcgcacg60tgtgtgcgag120gacccgcgga180tccaggaggc240atcagtttct300aaggctattt360agccaagagg420441<220〉<221>raise<222>126<223>n=<400>14aagcaggeggtcgcccgccgtgccgntgccfeaturea,t,c或gctcccgcgctcgccgcgctggcgcagggccgtgccscctgcccgcccgcccccgaccgccagcatgctgccgagagtgggcgctcgctcgc60tgccccgcgc120131<210>15<211>692<212>dna<213>人<400>15atctcttgtatcaaagtttgtcagtatttttatgatacscggtaaaagattgsca_3333atgecaaatatcaaaaaegtgttttatttctaaaccagttttat33g3c3ccaatttggeettaatataaaaagattaactatgcaaaagttcaa3tagt3cttacacacatctcctaaaatctttgaaactaattgtcaaatgccttcaataagaacatgaagttcagatatattcctcaactgctt33atcttgcaeittcacacacgtg33gaccctt3ttgcccc33a120tgatatatga180gtaagaaata240tgc3cgccaa300attgetgeca360ggagggaacactgtgtcacccctccctacaaatctgggcatatttgagaggagtgattctatteatgtecacccactggtgecctgaaaactgctgtctcttccacatcctcacatagacgeattgetggtagagesagtcataggtctcattgcctggteggtcattgtcataaccaga<210>16<211>728<212〉dna<213〉人atccaggtagtttcctttaatccaatagca420gacagccacgttgaaatcctgtggggaacc480aatgecsataatttttcgetcccacttctg540cccagacccgctggcccctggctgggcatc600gtctttgacgtcacagaagcgattacaccaa660692"00〉16cagaeggggtcctgccttggtgatggtttcccggccatgcggtatgtcttagaggattctctttsaactggccaagct3tgtgctgccsctgctagcctctctgccct3ctccaaaggttc3ct3tgtcctccca^agatasggctttatgtttgctttgssctgtgatattagtagatcctggatccggagatagaaagatgacatgcc3cccc3ccaagtgtccccttctcttacctggctaggcttgctgggatttcccccttttccccttccaccagcacttcc33c3g3ttccggcagcctccagggecaagtaagccacagttttscccctcggtcttgaacgctcagcactcacgsttgtscctctttccttct:gaatgctatggctcagccctgaggccacctgtccttgggctagggggatacctccaatcctgacttcgccaictgcgctctccttcctagttgtttccttatassttacccttaaagg3ctg3cattcagcctgagagggtgtggccggagagecaagactcagggsaagtagaccataggtgatctg60ccggctgatc120gccgccatgt180tgaggcctcc240tccagttttg300agactgaegg360ttcttgaggra420cagggaggga480aacctgggca540cctcaatcac600cagttcccag660gttc3tg3gg720728<210>17<211〉531<212〉dma<213〉人<220><221>misc—feature<222>518,—528<223>n-a,t,c或g<细>17aagcgaggaagccactgcggctcctggctgaacgegaagaacaggageggaagctgeaggagctggcccgggaggctgaagcccgggctgagcaggaggctcgagagaaggcgcaggctgagaaagaggaagccgaagcccggtcccgggaaaagcactttcagaaggaggaacaggagataatgaagaggaeteggaaateagaagecgccgcagctaacaattccggcccagacccttcttccagaaaggattctattgcagaaagga<210>18<211>1041<212>dna<213>人<220><2j21>misc—feature<222>544—<223>n=a,t,c或ga3aagcggcgccsggctcgggaacagaggg60ctgaaagggacaagegaatgcgagaggagc120aacgtg3ggcegaggegegg3gacgggagg180agcaggaggageaggagegactgeagaage240aagaagctgagcgccagcgccaggageggg300gaeaagagegaagaaageggctggaggaga360ccgaaaccaagaagcaggatgcaaaggaga420gtgaaagctgtagagactcggccctctggg480aggagctnggccccccangga531<柳>18ctctgtggaaaactgatgaggaatgaatttaccattacccatgttctcatccccaagcaa60agtgctgggtctgattactgcaacacagagaacgaagaagaacttttcctcatacaggat120cagcagggcctcatcacactgggctggattcatactcaccccacacagaccgcgtttctc180tccagtgtcgacctacacactcactgctcttaccagatgatgttgccagagtcagtagcc240attgtttgctcccccaagttccaggaaactggattctttaaactaactgaccatggacta300gaggagatttcttcctgtcgccagaaaggatttcatccacacagcaaggatccacctctg360ttctgtagctgcagccacgtgactgttgtggacagagcagtgaccatcacagaccttcga420tgagcgtttgagtccascaccttccaagaacaacaaaaccatatcagtgtactgtagccc480cttaatttaagctttctagaaagctttggaagtttttgtagatagtagaaaggggggcat540cacntgagaaagagctgattttgtatttcaggtttgaaaagaaataactgaacatatttt600ttaggcaagtcagaaagagaacatggtcacccaaaagcaactgtaactcagaaattaagt660twtcagaaattaagtagctcagaaattaagaaagaatggtataatgaacccccatatac720ccttccttctggattcaccaattgttaacatttttttcctctcagctatccttctaattt780ctctctaatttcaatttgtttatatttacctctgggctcaatasgggcstctgtgcagaa840atttggaagccatttagaaaatcttttggattttcctgtggtttatggcaatatgaatgg900agcttattactggggtgagggacagcttactccatttgaccagattgtttggctaacaca960tcccgaagaatgattttgtcaggaattattgttatttaataaatatttcaggatattttt1020cctctacaataaagtaacaat1041<210〉19<211>1043<212>dna<213>人<400>19ctctgtggaaaactgatgaggaatgaatttaccattacccatgttctcatccccaagcaa60agtgctgggtctgattactgcaacacagagaacgaagaagaacttttcctcatacaggat120cagcagggcctcatcacactgggctggattcatactcaccccacacagaccgcgtttctc180tccagtgtcgacctac3cactcactgctcttaccagatgatgttgccagagtcagtagcc240attgtttgctcccccaagttccaggaaactggattctttaaactaactgaccatggac'ta300gaggagatttcttcctgtcgccagaaaggatttcatccacacagcaaggatccacctctg360ttctgtagctgcagcbacgtgactgttgtggacagagcagtgaccatcacagaccttcga420tgagcgtttgagtccaacaccttccaagaacaacaaaaccatatcagtgtactgtagccc480cttaatttaagctttctagaaagctttggaagtttttgtagatagtagaaaggggggcat540cacctgagaaagagctgattttgtatttcaggtttgaaaagaaataactgaacatatttt600ttaggcaagtcagaaagagaacatggtcacccaaaagcaactgtaactcagaaattaagt660tactcagaaattaagtagctcagaaattaagaaagaatggtataatgaacccccatatac720ccttccttctggattcaccaattgttaacatttttttcctctcagctatccttctaattt780ctctctaatttcaatttgtttatatttacctctgggctcaataagggcatctgtgcagaa840atttggaagccatttagaaaatcttttggattttcctgtggtttatggcaatatgaatgg900agcttattactggggtgagggacagcttactccatttgaccagattgtttggctaacaca960tcccgaagaatgattttgtcaggaattattgttatttaataaatatttcaggatattttt1020cctctatcaataaagtaacaatta1043<210>20<211>橘<212〉dna<213>人<400>20ggacgacaaggccatggcgatatcggatccgaattcaagcctttggaattaaataaacct60ggaacagggaaggtgaaagttggagtgagatgtcttccatatctatacctttgtgcacag120ttgaatgggaactgtttgggtttagggcatcttagagttgattgatggaaaaagcagaca180ggaactggtgggaggtcaagtggggaagttggtgaatgtggaataacttacctttgtgct240ccacttaaaccagatgtgttgcagctttcctgacatgcaaggatctactttaattccaca300ctctcattaataaattgaataaaagggaatgttttggcacctgatataatctgccaggct360atgtgacagtaggaaggaatggtttcccctaacaagcccaatgcactggtctgactttat420seqidn0:79是卵巢癌多核苷酸8h(图7b)。seqidn0:80是卵巢癌多核苷酸12e(图8)。seqidn0:81是卵巢癌多核苷酸12h(图9)。seqidn0:82-310是图15a_15eee所示的卵巢癌抗原多核苷酸。seqidn0:311是卵巢癌多核苷酸0772p的全长序列。seqidn0:312是0772p氨基酸序列。seqidn0:313-384是卵巢癌抗原多核苷酸。seqidno:385代表克隆0772p—种形式的cdna序列,命名为21013。seqidno:386代表克隆0772p—种形式的cdna序列,命名为21003。seqidno:387代表克隆0772p—种形式的cdna序列,命名为21008。seqidn0:388是与seqidno:385对应的氨基酸序列seqidno:389是与seqidno:386对应的氨基酸序列。seqidno:390是与seqidn0:387对应的氨基酸序列。seqidn0:391是卵巢癌多核苷酸08e的全长序列。seqidn0:392-393是08e编码的蛋白质序列。seqidno:394-415是与0e8抗体表位对应的肽序列。seqidn0:416-435是用0e8全长开放阅读框架预测的可能的hla-a2lomer结合欣。seqidn0:436-455是用0e8全长开放阅读框架预测的可能的歸-a29mer结合欣。seqidno:456是显示与0772p有同源性的全长genbank序列的截短核苷酸序列。seqidn0:457是显示与0772p有显著同源性的全长genbank序列。seqidn0:458是编码显示与0772p有同源性的全长genbank序列的截短形式的蛋白质。<221>xnisc—feature〈222〉472,—494〈223>n=w或gtgcaagtcacggctggsgtgattctcctgct33ttttt3tttctgacctcgctacccgtgggcggcsttt333gtcsgtcagccttgccaggg3gttt3tcaatggtgtgcacagcctccatttttsgt3aggtgstccaicctggccatgctcccccatcaagtga3gtctggangcctgctt3ttt33ttstcttggctccg3gtagctgcctgcctcggcactggagttgaasgcccgcctgctctaacatctgcs33atttttccccasctgcaacctggattacaggttccccatgtcctcccaaagggctcctgtatggccacccggaaaagttcagatggagsctccacctcctgtgcccgcc3ctggccaggcttgttgggatttcatgttggccctca333tagggccattggcttcctttccctgtcgccca60ggttcssgcg120cscacccagc180ggtcttgaac240acaggcgtga300tccagcctaa360gggcacctgt420cntctgacac480g531<210>25〈211〉471<212>dma<213>人〈221〉misc—feature<222>377—<223>n=a,t,c或g<400>25c3gatgs3tctkagas3g3tgccctgaatcattgagaaaaggggaicttggggagcgtgcagcctggggagcagatggaccc3ctccttgcctgataattgsggttctcacttcagtaitgctcctgtgttggatgttgngtcgt33tagtgggttc33tg33tcgcgttttcttttaatgaagcggcggtggcgacagcggcagacctctagctcgagcgcgtactggaagtcagttggattagsttctcsgcctgaasgccatctcgacaccttcctaatcc33tccttgaelcaaacagctcatttgaaagaaaaccaggttgagagaagcccatttgtat60gacctagggatcgatctgga120agggacctcccgccgggatg180cagatttctctcagcaagat240aggttctagaggatgattct300tccagacgcacaaagaaaat360ggagaagaacgaggagaccg420tgc3g3ccctg471<210〉26<211〉541<212〉dma〈:m〉人<400〉26gactgtcctggagtggaagcatactgttttgtgacttctgcttccatagcgtgg3ttttgccttgctggacagtattagcgctgctctttgaacaagggacc333g33c3cattgctctggaatctgcagtagcaacagatctcttttacsctgttctgcteltcca_catca_gtcc3cttcsctctgaccagccsccttccttcsaacaagtccactttccagctttggggc3tggggat3tgacagcctggagagctgcagcccttgaaggcttcctgagttaagttcttgccttactgggcttcgttgg3tataaccagagtattttcctgsgatgcagaiagtagagcaatgacaaaacctgcagacaacgtcctctgacctgtgctgtcctgttcttc3gttggtggttcaacatcctggtggtggcag60ccatcagaag120tcaggctctg180tgttcttttg240cttgcaggtg300acagggatgt360tgcttaattg420actgattgt3彻gctctgggas540541<210〉27<211〉461<212>dna<213〉人<220〉<221>misc一feature<222〉367—<223〉n=a,t,c或g〈400>27arcatgtaatagtgtgggsacctc3atteaatatgtttgtgtaagaaaaccataggccttttt3atcattacagtcaccggggggctggaagcagtcatttgccttaattctgagctagagcasctctgtctcttgaacgtggctccaaggtccttgctttgaattgtggactcaggc3tgaagctcaactcactgagagatcagaactcgtccaggaagtcttttccttccaggaagggttctcttatc3aagctgasgaatgttatcctgcsgtggttacaaagcttcagtgtgtgctttctggagatcgaacttggctt33tccc3tcgtttctataacttcctcaaggc3tgg33ggttasattcagatgcagggtag3ggc3tttcc60120180240300360420461<210>28<211>541<212>dna<213>人<400>28agtctggagttatgaacaagaactagacaagatctcagggtctttgtctcaagtctatccasgacgctgcataaatctatgtgtgtt3agacctcccccttgaatttttacaacatatcctaattgactgcactttttstgttgagaaaagagcaagaaacttcaaagacsgtgataagtgcctgtcaccgttatatgtg3cstcttatacc5lcttcgcelgatgcttccccaarragaagatattagaagaaaatgcacgtggggagtgactgtaatgttttcc3cssatactcaggggcaaggtgccttttttagcatattgggaaaattggagacaaggaggacaggagctctgaggataagctgtagggctgcatttggcttctcttaatccg3gc333sggctcc33603attc3tgtg120tgcatcccca180tagtgcatgt240agcccctgga300tatgtaccct360tagtsatggg420cccaactgac480tcggcgaccc540541<210〉29<211>411<212>dna<213>人<綱〉29tagctgtcttagtgtatttctgtcatccatagaggggcactacattacctagagccca3gcttgaattgtcctcactcttttacactctgattctgggacagtgcsttctctgttc3c33333tgt3gtcaagctcccattatctatcactcaggcgggagggggaatgcctc3ttgcccctgttgat3t33ttcccatgcccc3taitctcagasgctgsactttctggsacattggctcagcacc3gtcggttttgctgtgttgtgggat33tggattsggtgatagcc3t3ttgccagagcctgggt3ac33ggcccctgtccca3ccgggacctggtagataatgaa60cgcttgtcat120ggagcatggc180atgagtgata240sccaaatacc300caaatctcat360g411<210>30<211>511<212〉dna<213〉人<400〉30atcatgaggatgctttgaagacagttctgcggagcaaggcttataaaccatcatgstccaatt3gagggatgttaccaaaatactacctgatggctgaagatgtcttacattcagatctc3tc3cctccccacsgagscaggg3tggtscsg3ctgggtsaggcctcaggtgtcagtaggstaactccctgcc3ggtccc33cc3t3tc3taaaccatttatttataaacaaacttacagagagagagcgtccctcgacatcattcstgagtattcgtcttcatggtggaagagcaggaga33catggagcgtggggattgttttcacac60taattgactc120aggcaa3gga180aacctgccac240gaaaccaccc300ataattcagg360ctc3t3gtcc420aatcagctcctaccaggccccacctccaacgatggggacacagattcaaaccatatcata:tggggattgcsattcasc3tgag3tttg480511<210〉31<211〉827<213〉人<400>31c3tggcctttct3ccagctttcscagtgtcccctgggaacacctagtgtcgaggaagcagtccctctggtctggccacgctggcttacaaaacagtcttcgctttctaaaagataagtaaagactgcatg<210>32<211〉291<212>d船<213〉人<400〉32ccagaacctcttggatgaccccacagcagtcc33cc33tgctccttagagtcctgattttcactcasgggttgacccgggcgtcctcctctccttgtggcaggccccttggctcccacgtgggggcsgtgagtagagttgcttgccctgcc3catgcc3c3ggtgacttgctsaacaactggccagaggtgcccgtttggtcagcttggtcaacaacaggttctcctggagggggtgccctctgttcctcagaggcacsgggcccagtttccatca_tctggggaggcttgtctaaggcctcgaaccgaaaactgccctggccc3tgtg33gctcttgtcctggcccagagtccagtcttgacccctctgctcctgaagagaccctccatctctcagggtggcttccacctgggtggctggc3gggcatcttccagcaccctc3tgcctc3gtgggagtga3agctaccacggcagaggcaggagtgtggccgtttaasggcgataaagctcgcgtcaggccctgggagcagccgggctaccaggggagcactgtcaagaaaccaggtggggtgaitcttggagctccaggca60agccccagcc120gctggtgtga180tggcccctca240attaagtgtt300agggggcact360atcagctctg420ctgcacctga480tggcacccta540tctgactcct600ggccgggcat660aaacagtctt720gtctcscagc780827cttctctttggagaatggggaggcctcttggagacacagatctagagaaattgcccaagaagcccaccttctggtcccaacagttggtcaggccctgctgtagaaggtcacttggctccaggcaggagagaaggcctttatttctcgcccacccattctcgggtttcacc60cctgcagacc120ttgcctgctt180ctgtaccagc240acctccgttttcagtcagygttgtccagcaacggtaccgtttacacagtca<210>33<211>491<212>dma<213>人291<400>33tgcatgtagtttccaaacaccccaracgcttcccatgaacctgacacttgatagq:atcacaaa3atgctgttaagcgggt<210>34<211>521<212>dma<213>人tttatttatgcacttcccctactgcacgaggttacgtggc3gttacctgc33t33tccc3tttacgacaggggtgggcc3gtgttttsgtcacttgatctaastattgtggacatgactgtcatgtatctatcaaaaaccg33tc3tctggggcacagcttatccgctgtcacagtgccaccatgattcagt3aaatc3ctcacgcctgt3agtgtcccaggccgagagccaggtaagtgtgtaacagcacaacattttgattgatgtttgatcccagcaccagcatgact60cagaccagga120ccgtcactga180tgtacttttc240acagttaatt300taacgacaac3603t3c3tc七t3420tttgggaggc480491<220>〈221>misc—feature<222>453,—476,487<223>n=a,t,c或g<400〉34tggggcggaaagcagaiggaatggatggaaaactgaagccg3aggacgggccctgaangtg3g3agcc33gtgaasaittaccaacagtgagtgccsccagtatgcagtctcccttccttctgtgtaccccggccaaggagccggcagagtgccgtgtcttgctgcagatttgtacactttatgg3c3己cttggtggtgg33tccaaggccgtggtgcggc3tgtcgggccttggatgcagagc33gg3tgtccagatcccacangtcccggaccttggccagctgcsgctgcggtgatgtggscttctgatcatggatgccaggaaggatctggtgg3tctgaggccgagg60cttcacttgc120atttccttcc180ttgtttttgg240ctcattctga300actctcagat360cagtgctgga420tggaanggaa480521<210>35<211>161<212>dna<213>人<220〉<221〉misc—feature<222>18—<223>ii=t,c或g<400〉35tcccgcgctcgcagggcncgtgccacctgccygtccgcccgctcgctcgctcgcccgccg60cgccgcgctgccgaccgycagcatgctgccgagagtgggctgccccgcgctgccgctgcc120gccgccgccgctgctgccgctgctgccgctgctgctgctgc161<210>36<211>341<212>dna<213〉人<4o0>36ggcgggtaggctattattagagctcaagagacactgctttgttcaccagccatggsactg33ttatcgcccagtgaggagattggaagaagaaaagacattgatgacactagaagaacgaaagattcsgccagaagcagc33tgatg3tgtttcatggagtccaaagagaagssgctttcaasggggacatgstgctgtsatgcctatttttagctcaccagactacgtggggagctcca333ctc3cc3aaagtggagagggaagaatg60gcccgsgagc120agacasgagg180tgggcggata240ccaagatgaa300341<210>37<211>521<212〉dma<213>人<220><221>misc—feature<222>516—<223>n=a,t,c或g<■>37tctgaaggttsaatgtttcatctaaatagggtttgagattaaatgagataatacatgtaatgttgttgttgatgatgatgatgatgatgacttgaacctattagataatcaatacatgttgataatgrtaaacacctatagcatagagtt60aattatgtgcctggcatacagcaagattgt120taatatttttctatccccagtgc3caactg180tcttgaactgag3tc3atttccccatgttg240attttcttctagaggagatgacatttgagcaagatcttaa300agaaaatcagatgccttcacctgaccactgcttggtgatcccatggcactttgtacatct360ctccattagctctcatctcaccagcccatcattattgtatgtgctgccttctgaagcttg420cagctggctaccatcmggtagaataaaastcatcctttcataaaatagtgaccctccttt480tttatttgcatttcccaaagccaagcaccgtggganggtag521<210〉38<:2ll〉461<212>d隐<213〉人<4o0〉38tatgaagaagggaaaagaagataatttgtgaaagggtcagtctgtagctcttcttaatgagatttccttagtggtgtatctaatcacaggtgggggacttgggcccacttctcatttcatatttactgttgtttaacaatgccacaaagaaaaatgctgtttttgtgtgctcataatggttactgttacagaagccagcaagaagacctcattgactccagtgtgtgcaaatccagtttgaaagaaatgggtccagttactagtctttga60gaataggcagctttcagttgctcagggtca120aaacatctgtggttccctccagtctctttc180ttaattagaggsaatagaactcaaagtaca240catggttgggagctatttcttgatttgtgt300tccaaaaattgggtgctggccaaagagaga360tgtteatteacacccccggggatatcagga420gectatettct461<210〉39.<211>769<212〉dna<213>人<400〉39tgagggactgattggtttgctetctgetatcgtcctccttctcattccctttagttgtacgatgtcgecttttcttcttcttgctttttctctcatctgcatcattccttteagatgetgtctttttcttttttttggggggcttgetetggectttgagaegagecaggaaggectgettcattgtgatcccaagacgggeagecttgtgcatctcatcagtcagaatctttggggacttctccaagtctttgtttggcttctctccactctgatacagcaagttgggcttgggatgatttatctgtactccatcctgcccagtttccagctcattccaccagtggtttgtgaactcctettgettcagygtcaccctgagagectgag<210>40<211>292<212>d船<213>人tcaattccccaagecpaettgttcctgcag60cctctctttcatctgagacctttccttctt120tgatgttct.gctcagcatgttctgggtgct180tsgcttcttcctcctctttctgcctccttt240ctgactgcagttgaggggeeccagggtcct300cctgggcctctaggegageaagettggect360gtgctgttcgcccctcacaggcttggagca420tggacccctggttgtcgtcatcactgcagc480ctgaagtcaatgtagecatettcacaaact540tataaegggtggtctccttagaaaggctcc600ctaccaagttggccgcagtcttgtt,gaaga660tggcagggtcatgtcctaccccatgagtgt720tgataccattctccttccg769<400>40gacaacatgaaataaatcctagaggacaaaaaactcgaaaaatgagcaagtctggtgggatgggcctcctgatcttaacaagccatgctccctttacgcaggaaacagggcttggaacttctaacctacctgeegggtaggtaccatcccattaaactc3atagagtgtagtctagttaa60gtggaggaagggctatactataaatccaag120attatacacatctctgaactggacatscca180ctaagggaaattaacatgeaccacccacat240tgcttcgctgaaatcagtgctc292<210>41<211>406<212>dma<213>人<400〉41ttggaattaactataccttttgatggasaaataacttaccatctactttagc3ctggtct<210>42<211〉381<212>dna<213〉人<400〉42aa3ctgg3cctacctcaggggtctctgcaai.tcgcatccsgccctccsagggccctgctgggactctgaaaa<210〉43<211〉451<212>dma<213>人<40o>43catgcgtttccgcctcagccctatattccttgstgt3tataatcctgataaaggcgcata<210>44<211〉521<212>dna<213>人<400>44gttggsccccgttcctttttagccgt3tcagatgasttagcagaccaitaaataataggagttttgscstgatggtatctcggtactggtg<210>45<211>585<212>dma<213>人ataaacctgggtgcsceigttagcagacaggtttgtgctccattccacactgccaggctatgactttataaaacagggasgaactggtgggacttaaaccactcattaatagtgacagtagattatttaatgtg3aagttgtgtttgggttaggtcaagtggatgtgttgcgaaggaatgggagtgagstgtagggcatctgggaagttggagctttcctgaagggaatgttttcccctaa3tt3tctcttccstat60t3g3gttg3t120tgastgtggai180acatgcaagg240tttggcscct300caagcccaat360406tgcaacagggccccscsgccgtggagccagcaagccttaascaggaaggccaasatcttgacatga3tttatgactacctctgcctgccttgggggagggcatca3gctgsctgcarggtccccc3gg3gtgagctctgagsccctg3elcctsacasttgctgaigcaagccgggagggtgagacacagcacagaacccagccaagccattgggg33ggggtcagcccctc60aagggggcct120cccagccttc180ctg33ctgcc240ccsccccctc300aaggaagaaa360381accactgttgtccaaaagtgggctctgtgttttt3ttc3tattactttcaggttctttatatgagaatacgccaggctggctgggattacttccgsgactggtcaatctgaggcacaattacttaataactttttcaaaacccaaactggtctcgaactcag3tgtgagcgetttt33tcttt3tc333ttaattgacattatatttgccctggcctcaacatggcaccaccascttctc3ctgc3tcttctagtagagttcctcaaaag3tgggstgctgcaatccacc60tgccaaaagg120tacatttaga180aagtttccac240aaccsaacat300agctgttttc3603stttgcaat420451cagggactggaaagacacttcttgcccgagctgtggcgggagaagctgat60attatgcttctggatccgaatttgatgagatgtttgtgggtgtgggagcc120gaaatctttttagggaagcaaaggcgsatgctccttgtgttatstttatt180attctgttggtgggaagagaattgaatctccaatgcatccatattcaagg240atcaacttcttgctgaaatggatggttttaaacccaatgaaggagttatc300ccaicaaacttcccagaggcattagataatgccttaataccgtcctggtcg360caagttacagttccaaggccagatgtaaaaggtcgaacagaaattttgaa420aataaaataaagtttgatcaatcccgttgatccagaaattatagcctcga480gcttttccggaagcagagttgggag3atctt521<400>45gcctacaacacagatcttcgaccatygagaaggttgatctcagaaagagtaagaccctgagtcaaggcaagctgggaaacactctgcactacaaatttcatccagaaagatgaagaccctacgtcaa^gcttgccggaaacyaccctgcactggtaagacagatccaagaagctggaagatggtcctgcgttgcactttcgtctsccctgg3ctggt33gaaagatccsrgcsgctggaacctggtgctccstcaccctctggacgcacccttgsgggggctttc33t33cacctggtgcacc3tca^ctcgatggdcgcacgtctcagaggaggtggagcstccctcctgctgtctgactggtgtctaagagttgttgcatscgtctcaggcrtycctccccctgtctgagtgggatgcsccagtgacacatcagcagag3c33c3tcc3tttcccctttttcccaggtgggatggccgagtgactgaccsgcagctacascatcratcttcgtgcatcgagaatgttgatctttgaaagagtcctsaggtttcm60120180240300360420480540585<210〉46<211〉481<212>dna<2u>人<400〉46ga3ctgggccctgcccctcacttcctgcaagt3ggagagagcelgcagaccgcacctgatgggcacctgggaactcctcaactgagcccaacccctccctctgaatagaggc3gcggc3gcggcctca_tctccgagcagagtcttgcctgcgtcatgccttctggtcttctcatgcgggcccccatacatttgaggtgcatcgtgwtcctcaggagactgcccctagtatgtgtccgcatgsgccsgcscscacat3cctgtacagaaggggagcacggtcgaggcagcg3gggtc3g3ggaagccccctctgccgtgtccatctgctgccctggaggggcsggttggggccggcccacsgcagatggaggctaatcctgcccctacctctgtkc60tagcctattc120sgatggggas180gcagataaaa2403ttgggctg3300ggagttaagt360gctgccctgg420acaattcctg480481<210>47<211>461<212>dna<213>人<220><221>raise—^feature<222>128—<223>n=a,t,c或g<400>47atggatcttacttaacctccggtacacngccacgttgcccaegtgetaggtcsccsgttcttatgaaggggtcaagaaagctttgccscccaggctcaagc3cc3c3cccaggctggtccattacaggcgccctccgtgtgaacttccatcctcagactccaggttggagctstcctcctcatcctgacctgagccaccgctcagcagcsgctgsatgagcagcatgatatgcsgtgctggccassgccttttgtatttttcaagcagatcacccsgcctgctgtgagaaggtaggattaagcagggtgacaatcttggctccacatagcttgtagag3cctgcccacctttgttttgctatgetttgeacatgctcctggtcactgcagc60tggg3ctac3120gggatctcgq:180cagcccccca240ttt33tggas300tctgtgacct360tttcccgggg420461<210>48<211>571<212>dna<213>人<400>48ataggggcttaggatgeatetaaggagggaattcaggttcgggtccttagatgagaaagaaagaaggeggccgtctgcaaaatgaggtcgtaaggecagggctcttatcc60gacacccgaggtccttctctctgccgtgtg120gcgaaggagaggccgcaccagaaaccgaca180ccttcatcttcccagtttgttttgcagttttagttcatggctctgctcaccccgtgccsg<210>49<211〉511<212〉dma<213>人<400〉49ggataatgaa5lcccc3gccctggttttttct3agata3tgctcaccccgt<210〉50<211>561<212〉dna<213>人<400>50ccactgcacttc33c3gaittcaagaggttcccsggc3tgg3cttgggcccgggcaacagagtgctgtaaaggctcscgccgaattttggc<210>51<211>451<212〉d肌<213>人<400>51agaatccattatacagggatcttaggtctgtaaggaagacgagagatgca<210>52<211>682ggacttgcagcctctagaactgagaaaataactgtctgttggttaagcca240agtattctcttatggcttcctaagcagactaacaaacaaacacccaaaat300cttcgctgtcttctgtaaaaattgctatgagagaacttttcac仁cactgt360ctccctcagtccctggttctttcttctcacataatcccaatttcaattta420cccaggcagagtcattcatcacggcatctcctgagctaaaccagcacctg480ttcttgactggctgctcatcatcagccctcttgcagagatttcatttcct540gtacttcacgcaccaagctca571gttgttttatttagcttggacaaaaaggcatattcctctattttcttata60ccccaaaat33agcaagcatatatatcttgaatgtgtaataatccagtga120cagtactttaaaagaaaaaaaaatatgtatttctgtcaggttaaaatgag180stttactctgctaactcattattttttgctttctttttggttaagagagg240cactgaaaaaggtttttatcttatctggcaittggaattagacatattcaa300ccatttccaaactttaagaccacaaacaagtaatttacttttctgaacat360tggaaaatgggaattatasaatagactttgcagactcttatgagattaaa420t3tgaaattctttcttcttttttacttctttttcctttttgagatggagt480cacccaggctggagtacagtg511ccagcctgggtgacggagtgagactctgtctcaaasaaacaaacaaacaa60aactgaaaaggaaatagagttcctctttcctcatatatgaatatattatt120gttgatcacctaccatatgcttggtattgttctaattgctggggatacag180tgcagaacttcatggagcatgaaagtaaataaacaaagttaatttcaagg240ttgctcacacctttagtcccagcactttgggaggctgaggcaggtggatc300aggagttcaaggctgcagtgagccaagattgtgccactactctccaggct360gcaagaccctgtctcagggggaacaaaaagttaatttcagattttgttaa420ggaagtaaataggttgatattcaagagagcacctgaaggccaggcgtggt480tgtggtctaacgctttgggaagcccgagcgggcggatcacaaggtcagga540caggcatggtg561tattgggttttaaactagttacacaactgaaatcagtttggcactscttt60tacgcctgtgtatgccgacacttaaatactgtaccaggaccsctgctgtg120tattcagtcattcagcatgtagatactaaaaatatactgtagtgttcctt180tgtacagggtgtgttgcaagatgacattcaccaatttgtgaattatttca240tacctttcactctataaacttgtcataggcaaacatgtggtgttagcatt300cacaaaaatgttacataaaagttcagacattctaatgataagtgaactga360aaccccacatctcaatttttgtaacaagataaagaaaataatttaaaaac420gcattcagtgggtacaaagcc451<212>d船<213〉人<4o0>52caaatatttatatttctatgccagttttca33gacaccttaacaatttggcactgtgtcacstatttgagtccacccactctcttccscatggtagagcaggtcggtcatattaacttaacaaaagtatgaatagtaaagcctctcc七3acccctccctaaggagtgattggtgccctgatcctcacataagtcataggttgtcataaccttgaaacaagttgtcaaataccttcaaactccagtcatctc33tccaggtctgscagccagaccccagacctcgtctttgttcagakgaattcctcattggett333tgatgcaattgtatgaagaccctagtttcctttcsgttgaaatstaatttttcccgctggcccaegtcacagatatatgatatagaaataggtgtgcaccgcctaattgctgcaatccaatagcctgtggggagctcccacttctggctgggc3gcg3tacacsagtttgeasgtatttttttgatacacaaaaaaagattatcaggagggaaca33tctgggaccattcatgctgctgctgtatcgcattgcc333ttgcct60120180240300360420480540600660682<210>53<211>311<212>dma<213>人<220><221>misc—feature<222>208—<223>n-a,t,c或g<400>53tttgactttagtaggggtcttatatctttcattatgecattetgeattwatcacattaaatcttttavagccatcatttagagctgtgaactctggctgaagbgtgagttagaactatttattttactttgcttatcttctaatgbcaaggaatggctttcttggaaaatcaagcmggnttctctccaacaaggctttcccatacacactgcciugtaatatttaraccyta60gaacagwtgctaaiuctggct120ttcttgatatgaataaagga180egagtctgetsasggggggk240caatgacratggtttctgacc300<210>54<211>561<212>dma<213〉人<權>54agagaagececataaatgeacctccatcategggttcatactttggttttaactctcatctgtttgtaatgagtgeggeaagttcacactggggagaagcctcccagctcaccctacatc3ctgtgggaaggccttcagcgagagactcgtaagtgcagacagatggacagattcccsctteattctgegctggacagttatcagtgtgggaaggecttectggagagaaaccctatgtattactgaacacgtaaggattaagectttegteggagtteccctaccagtgcgttgaatgtagecgagtteacactggagaeggaggtcaaccctcattca3aacatggtccagectttgtggagagaagcaeggcagaacc3gtcag3gctcaagectttt60tgtaatgaatgeggcagage120cacacaggagaaaaacccta180actcttgttcagcatcgaag240gggaaagcttteagecagag300gaagecctatgactgtggtg360gcatcagaaagttcacagcg420tcatggctccagcctcscag480ctttaaccatggtgcaaatc540561<210>55<211>811<212>dma<213>人<400〉5592gagacagggtactgcagcccggactgtgggtttgccatgtcctcccagaattagcatccaatttttactattagttttccgaggtgcaggcctgttgcctacgctgtcaagtcctttggcgaacccctggctcactttgttgacctcctgtgcatgccactgcac3tgcttgttgggattcttgctcactggctttggattttaactgatggcatcsctcataaaggccttttttccaccgaccaggactcscccaggctg3ctc3aacacstgcctggcggtcttgaacgagattaatcatttttttccaataaaacatccttgctcs5ttsgtctgcteittg3cagcgaatcccttgtgc己acttcttgg33tgcsgtattctcctgctascttttgttcctgagctc3cc3ccacgcataagagatgtttttcagcttgaaaggasattccagtcttttcgcacttttatgccatgactctctttggctaggtattcgggtgcgatctctcagccctgagtttttgtaaaacgatctgctggccccatataagcactgttatacagagtaagtttacct3cc3c3tc3ttcttccactctattccattagagatcttctattgtccgttscgt3gctccaagtagctgaagstggggtcccacctcggt3gggtsttcgattggatcttgagattcac3ttattttcatttttgt333tgtcaggcatttatcagctatccactggtg60120180240300360柳540600660720780811<210><211><212><213〉56591dna人<220><"221>m丄sc一feat:ure<222>45,!"77,490,561<223>n=a,t,c或g<400>56atctcatata.tatatttcttcctgactttatcacagagaccaaaatagagcggctttctg3c33a3ct3gggggctctgtcttctcatactacaaagagctactctatctgaaaaaaaatcatcctaggaagaaagaatgggaagaaagactgttcccagggaccactaccttcctgccatcacagggcaagtgcc3gggtaggtggggatggcctggaagataaggagaaagtctcagacgtgccccangagcttcccacctgctgctggcaggcccttttgggtggggnccaactgggtttgcttgcttctgncacgcaxttaaaata60gtggaacgcatggcagtcacaggacaaaat120atcatacaattttcaagtattttttttatg18dtaaaaaataaatgagacaagatagtttatg240acggggcagttgggtacagattcctgtccc300ctgagttcccccacagcctcacccatcatg360ccagtggagacaggaaccagcaacata'ctt420aacacactggtggg33gcaatcccacnggc480gctccctgggtggctttgggaacagcttgg540cctttgggcccgtgtggaasg591<210>s7<211>481<212>dna<213>人<彻>57aaacattgagatggaatgatagggtttcccaattatgatttatagccttctcaaataccttttscctctttacassttaaataagcaagtattttttctgtattaaacctctstcatagtaataaacaggtttaaaatcacctcaataggaaacaatctgaatgcttaagattttccactctgtattccagacttcttaaattatagaaaagcagggccgggaggcaacatcatctacca3agaatcaggtccatattttasctasatgaa60gccatacttg3tatctcaaccagagctaat120aactggatccacastttataatacctgtca180ttaagcctattagggtacttaatccttaca240caactgcccttctggttttcttctttgact300ttgggtgctagcagtacacagtgttacact360aaggaatgtacactttttgtattctttctg420tggtagggacttgtatgcatggactacttt480481<210>58<211>141<212>dma<213〉人<40o>58actctgtcgcacaggwtcatcaccatgccc<210>59<211〉191<213>人<40q>593cctt333gaiccttacaagtcaggcaattc<210>60<211>480<212>dma<213〉人<400〉60agtcaggatctattacatctaggttacataggttttagct3gagttctct3gtcctcccttgggatggga3gc33c3ccc<210>61<211>381<212〉dma<213〉人<400〉61ctttcgsttt■tgtgtattat3gctt3gatgtcttcctttt3gctgc3tgtttattttgatcactggttat<210>62<211>90(5<212〉d肌<213〉人<彻〉62gtggaggtgatgaggcaccttaggggaaggcgggccgtcggcggagggaggsggaactctccaggctggagcccabtggmgcgatctcgactccctgcaagctmcgcctc60gccattctcctgcctcagcatctggagtagctgggactacaggcgccagc1203gcta3ttttt141cataggagaatttatactgggagagaaagcttacaaatgtaaggtttctg60ggagtgattcacacctggaacaacatactggacttcacactggabagaaa120gtaatgagtgtggcaaagcctttggcaagcagtcaacacttattcaccat180a191atgatggctcag七ttcccacagcgatgaatggagggccaaatatgtgggc60gaagaacgtactaagcatgataaacagtttgataacctcaccttcagg120acaggtgatcaagcccgtacttttttcctacagtcaggtctgccggcccc180gaaatatgggccttatcagatctgaacaaggatgggaaga'tggaccagca240atagctatgaaactcatcaagttaaagttgcagggccaacagctgcctgt300cctatcstgaaacaaccccctatgttctctccactaatctctgctcgttt360agcatgcccaatctgtccattcatcagccattgcctccagttgcacctat420ttgtcttctgctacttcagggaccagtattcctccctaatgatgcctgct480ccttcaatttgtcacgtttgattttatgaagttgttcaagggctaactgc60agctttctctgagttccttcagctgattgttaaatgaatccatttctgag120cagtttctttttcaagagcatctaattgttctttasgtctttggcataat180ctgatgactttctatgaagtaaactgatccctgaatcaggtgtgttactg240ttttaattctttcgtttaatagctgcttctcagggaccagatagataagc300attccttaagctcttggtga3gttgttcg3tttccatastttccaggtca360cccaaacttct381aacggaggcaagaaagggggctacctcaggagcgagggacaaagggggcg60aggccgcggcaccccggcgacaggaagccgtcctgaaccgggctaccggg120gcccgcgtagtcctcgcagggccccagagctgg3gtcggctccacagccc180gcttctcacttcctggacctccccggcgcccgggcctgaggsctggctcg240aagaggaaacagacttgagcagctccccgttgtctcgcaactccactgcc300catttcttccctcgctccttcaccccccacctcatgtagaaaggtgctga360agcgtccggagcgctttggtctggggaactatgggggcaagcggcagctccc333c3ctctcaaaccttttggccttcaagcctgcacaaagaccg<210>63<211〉491<212〉dna<213〉人<400>63gacatgtttgtgcttccagaggttgggggctcaggcttggaacctagaaatgctggtgacagtggcctctggtggggtgacactgtggtc<210〉64<211>511<212〉dma<213〉人<400>64gatggcatgggggacccgccgctgcsgccagggactgctcaggtgcctggtcattaaagcc33ccccctcccagcatctcggtcatctgg<210>65<211〉394<212〉dna<213>人<400〉65taaaaaagtgatgta33ccggcttasctgaggcggggatctggcactcataagctgaaggaagggtcggg<210>66gggaagaagaacctgggctaccgtcctggccttcccmcccccttcccggg420gggcgtggagttggggttgggggggtgggtgggggttcttttttggagtg480tttttcccttcttcaggtcaggggaaagggaatgcccaattcagagagac540gaaggacgggagtggaggagcttctggaactttgcagccgtcatcgggag600taacagcagagagcgtcsccgcttggtatcgaagcacaagcggcataagt660caaagacatggggttggtgacccccgaagcagcatccctgggcacagtta720ggtggagtatgatgatatcagctctgattccgacaccttctccgatgaca780actagaccgaagggagaacgacgaacgtcgtggatcagatcggagcgacc840acatcgtcaccaccagcacaggcgttcccgggacttactaaaagctaaac900906cctgcagggggaggatggggccccggaagcggtacc333caagattggtcaacatattccggaggctcgtgggtttctgaacagctctcaacggtccggatcatgctctggtgctaaggactctcccaggggcctaaggccccttcgcttatgggattagggtcag33tctcctccctggtactgttttgatcagctgcc3c3cagactcagggctccgtcccatcccatccagtgctcacaggctgagacatc3gcgt3gccccstgcgccctcatcctggtgactccaaaggctgatcaaccgctgtcctgttcttta60aggccatgct120gacccgctgc180gtgagaggaa240ccgcatccaa300cactgggctg360ggctgaactg4203atg3gctca480491tcgttgctaatgtgcctgctgggatggagcacttcctcctgtgagcccag60tgtccctggagcttggggcaaggagggaagagtgataccaggaaggtggg120ggggccagagtcagttcagggagtggtcctcggccctcaaagctcctccg180aggagtgatggtgccctggagtttgccccaacttccctggccaccctgga240ctgctccaggcctctaggctgggctgatgggtttctccaggacacaagta300c3ccctctcctcagcttgtcaggccgcacatgtgggacaggctgtgctca360gcctgccctgccctccatcaggaggagccagtggaaccttcggaaagctc420agcagccctcaaaagtcgtcctggggcaagctctggttctcctgactgga480gcttggcctgctctctctcgc511taacaaaggtttatcttac3aatagcgtccctgcsgtttgggggacsggctatcgaccstgagaggcctcttatttagacaagaaagcacatccaa33gtgactgcttgcatcctgctcgagggggctctttgggctatgtttcttcatgaatatttggtgggttt33ggcgggtttgtctctgtggggcagggcagtggtgggcccccagatcataaactaagtaaaactacccagggttccgcccgctggaggaccttcatccaggatgtct60tcagtgactt120tgacgatatt180ggtctgttct240cccttacgtg300cggaactaac360394<211>359<212〉dna<213>人<400〉66caatgcgttcctt仁atggatgtaaattcaaatcacgttwaagacactaggtcgggcgccacatttttccatgaagatgtacggaaatctgaattccaaaaggttaccacaggggctgtaagaa_tggagaa_tsgtatttctgatgc3tc33ggaaggaaaattccatatccaatatgagttt<210〉67<211>450<212>dma<213>人cagteatgetgagccatcccgggctgacag60agtgccacccaagga^gaagaagaatttgga120tgttgaatatgaaaatggcccccaaatgga180acctagtgaccctcctaagtgggaaagagg240aacatcagaatataaaactgagatcataat300actcagagacagtagsaactattcccagg359<220><221>misc—feature<222〉425—<223>n=a,t,c或g<400〉67taggaataacaaatgtttattcagaaatggtsatgccccttcctctccttctgcacaggaagtggaggaggacacaggactagcccaccacttatagagtggaggaggesaacaggtccccagctccagatggccacgtggttgcagctgatacctgetttgggatgagagggaggataataccctaagcacagtgeaageagtgagccccactgncttttggatgetetcttgggccacg<210〉68<211〉511<212>dna<213〉人ataagtaatacataatcscccttcatctct60gacacagatgggtaacatagaggcatggga120ccttctcttcccggtctcccaagatgactg180ctcaaitgtsccagatggtcacctatagcac240gactcaatgaaactctgtgacaaccagaag300agecatgeagggaggat3tttaccatccct360cggctcccagtacctgaaaaaccaaggcct420450aagcctcctgccctggaaatctggagccccgctgagaggcaagacegtetccctcctgctcacagcagaaacgccagcagagaaaatgggctgcctctgggctgacccgctggctgtacgcatttgaggccagggtggaggaaagggaggcaac^cagcc;cttgtcccacgeagectaaggtcggggaggacgaggtaactcagcagcaaceggaggggeagcaaccccccgcacacgtcgagagegatgatggacttgagcgccgtgtt<210>69<211>511<212〉d贴<213>人ttggagctgagctggacggggcagggagrgg60geagctgettccccagcagccactgctggg120agecgagagtccttagccctggagctgagg180tggecagaactggggttggcatctggcatc240ccsacagaggaaaacctattcctgctgtga300tgeagggagegtgatgaagtcaggcagcca360tgtcaccttgtagectatgegctcaatggc420agccaacagcagtgcctctgcaggcaccaa480c511<400〉69gtttggcagaagacatgtttaataacattttatctgtccaccatcttgccttgcccttccgaggttagggcccccaggcgggctaagtgctagecagctgggcacggccccctagccccttcatatttaa3aaatacagcaacaattctc60tggggctgaggcagacaaagga33ggta3t120tattggcctgctcc七getcaaagagagecajl80ecsggttgetgaggeggcagcggtggtaga240gttcttcactct3cggcccgcctccagggcccaggtagtcctataggagc<210>70<211:>511<212〉dna<213>人<400>70c33gttga己csagaggatgt3ctttt3cct3gt3tgsttcgattagcaagatctcsgagcgcsttccctcgc3gggctg3gtgctgggct<210>71<211〉511<212>dna<213〉人<400>71tggcctgggctat3gggtaitgccicctggagctccacgacaggtgssctgttggccagtgtcttggtggactcagagccgctctcacgggg<210〉72<211>2017<212>dna<213>人<400>72agccagatggcg3tgastggaacagtttgattttcctacataaagttgcatgttctctccatcagcca.ttccagtattcctaccaaatggtgcctcatgc3ggccc3gtccagggaactcagtatcggcagagccgtgggctgcagtctcgcagggagaacttctgcaccagccctggct300aaagaggtggagccctgagaaccggaggaaaacatccatcacctccagcc360ttcctcctcttcctggcctgccagttcacctgccagccgggctcgggccg420agcgtt:gtagaagcagccctccgcagaagcctgccggtcaaatctccccg480cccccgggaggggtcagcacc511gtcaggcttggcagaggtggagtgtagatgaaaacaaaggtgtgattatg60gagtcctttgggtgtaggagagaaatggctgttgagcttctatttcaagat120gtgcaaaaagcacattttccacctccttctcatggcatttgtgtaaggtg180ctattccatctgcattttagaggtgaagaataacgtacsagggattcagt240ggacccctcactaagtgttgatggagttaggacagagctcagctgtttga300ccaggcagctggsgctgggtaggatcctggagctggcactaatgtgaggt360caacccaggctcagatccgga^cctgaccgtgctgacccccgasggggag420gct卯cccgttgggctccctgctcct:ttcacaecaetctegetttgag480gggactacttcacagagcagc511aggattgggagagaggtagctacccggatgcagtcctttgggatgaagac60gaccccatcatttccccsgsggtctcggcctcctttggtgttcagcagct120gagatctggcctctctgtgatttcatcactgtgcacactcctctcctgcc180ggcttgctgaatgacaacacctttgcccagtgcaagaagggggtgcgtgt240gcccgtggagggatcgtggacgaaggcgccctgctccgggccctgcagtc300geeggggctgcactggacgtgtttacggaagagccgccacgggaceggge360catgagaatgtcatcagctgtccccacctgggtgccagcaccaaggaggc420tgtggggaggaaattgctgttcagttcgtggacatggtgaaggggaaatc480gttgtgaatgcccaggccctt511ctgagagctgcaagatagsagtcaggatcatgatggctcagtttcccacag60agggecaaatatgtgggctattacatctgaagaacgtactaagcatgata120taacctcaaaccttcaggaggttacataacaggtgatcaagcccgtactt180gtcaggtctgccggccccggttttagctgaaatatgggccttatcagatc240tgggaagatggaccagcaagagttctctatagctatgaaactcatcaagt300gggccaacagctgcctgtagtcctccctcctatcatgaaacaacccccta360actaatctctgctcgttttgggatgggaagcatgcccaatctgtccattc420gcctccagttgescctstagcaacaicccttgtcttctgetacttcaggga480tcccctaatg3tgcctgctcccctagtgccttctgttagtacatccteat540aactgecagtctcattcagcctttatccattccttattcttcttcaacat600atcatcttacagectgatgatggg3ggatttggtggtgctagtatccaga660tctgattgatttaggatctagtagctcaacttcctcaactgcttccctct720acctaagacagggacctcagagtgggcagttcctcagccttcsagattaa780aaaatttaatagtctagacaaaggcatgagcggatacctctcaggttttc840aagctagaaactctggctgaacctcactgatccctccstcatcagaaaacagcagcagcaagaaacagagg3gaggcagcggcaggagctgcagactacaataaacagtg3catgcsgctc3tctaagctata3t3caca<210〉73<212〉dna<213〉人<400>73atggcagtgatgg3agag3gtaatcagtat3caaaggcatacaagtgaga<210>74.<211>1567<212>dma<213〉人<彻>74atatctagaaaggctccaatattcatgtgagcatccccsg3gtgc3tgttgcccctggaaatgtaccctaagtsatgggtccaactgacacggcgacacctt3tttctcatatggcatta3gacctc3gtcatctccgggacagtgctac3caggacgtcaaccctggtttgcccttcttcatcgatggtcatggcca_aa_tttc3g3gggctatgaacgagagggaggctactgcaagagagagctggaggctcagtcagtctccacctgagatgtccaatgacctggaagcttatctatattatgccaactcagaaatggcagtt3gccg3cgg3c3gtgctggacagcgga3agcaaggsgcctcagagaacgcaaagcaagaatggaagacagcgggcttgagagacaagaccaggggsactggaagatcagaaagcattatggaaactggtccctgcctgattcagagacttaaaggattcatttacttgaacaactctctc333ctgaaagctgac3ct3ccactttgsttctgtagaaactgccagctggaga3cccagaaagaagasgcagctaggaagagagaacgccgtttcsgtg33tggtcaaacaactagaagcagctggatcagtttacaatcagcttcagctagct3g33ttt3ttgacgttgcct3gttacttttgcgscgcc33ga3gg33g3gggagttggaggagfaaaggagagaatgggaacattgtcagg'gactgagctatcaacaagag3cttc3t333tgctcttgaagal5lggaalctcc333cgtgscactstttggsctggcgatgccccgsgcttgctgccttcatgtgttgatggtgggagcggaaaacgcttggagactccgtcctgagctcc3cagatctcaggaagttttggcttaaggaataagtcatcagaaagaaactgaaattgaagg900960102010801140120012601320138014401500156016201680174018001860192019802017cattcaccatcaccc3gtgtctcagagggcactttcggaactcasgagtcagcaattagacatgggaacctgggctgaaatctaiaggtgctcgccaagtct3ctgcttt3aatggttccatttcttctctaccttcccttacatctgaaacaagasgtctaaaactttctgtggcaactaatatttcaaattcctttctctt'cttcaggagt3ggg3g33cactggacataacttctgtcgctccgcs33tttattaaccttctctgtag60gaacctaaaa120ttaagtgcca180tctctcagag240gtgttaccca300caggatgtgc360acta414gtctggagtgagcaaacaagagcaagaaacaaaaagaagccaaaagcaga60atgaacaagataaatctatcttcaaagacatattagaagttgggaaaata120actagacasgtgtgttaagagtgataagtaaaatgcacgtggagacaagt180atctcagggacctccccctgcctgtcacctggggagtgagaggacaggat240ctttgtctctgaatttttagttatatgtgctgtaatgttgctctgaggaa300agtctatcccaacatatccacatcttatattccacaaattaagctgtagt360agacgctgctaattgactgccacttcgcaactcaggggcggctgcatttt420caaatgattcactttttatgatgcttccaaaggtgccttggcttctcttc480aatgccaaagttgagaaaaatgatcataattttagcataaacagagcagt540gattttataaataaactgagcaccttctttttaaacaaacaaatgcgggt600gatgatgttcatccgtgaatggtccagggaaggacctttcaccttgacta660tgtcatcacaagctctgaggcttctcctttccatcctgcgtggacagcta720tttcaatagcatctagagcagtgggactcagctggggtgatttcgccccc780ggaatgtctgaagacaattttgttacctcaatgagggagtggaggaggat840taccaactagtggataaaggccagggatgctgctcaacctcctaccatgt900tccccattacaactacccaatccgaagtgtcaactgtgtcaggactaaga960ttgagtag3aaagggcctggaaagaggggagccascaaatctgtctgctt1020cctcacattagtcattggcaaataagcattgagccagaactctatcgggcaccaggataatatgggaaatgcctgatgggattatcttcacattctaccctgcaagccaagttctgtaagttactctgaatttagatetccagacccttcatataccttccatgaagcacacacagacttgaggccttgaggaatgaagctttgaaggaacactcttcatgtgttaaccactgccttccttgttgtt:atagaaaactga仁11tagagttctttcct3<210〉75<211>240<212>dma<213〉人ctgtctctttggctgctgcctcagcacaga1080catctctcagtgaacagagttgacaaggee1140gcttgttgagcttctaagtttctttccctt1200agaaatgectgagttctagctcaggttttc1260ctggccacaattcaaattaaggcaacaaac1320ttgaaagcaaggacaatgactgcttgaatt1380aagaatactttgtttccagcccccttccca1440ggaccttggagccacggtgactgtattaca1500tgatcgttcaagagaatgattaaatataca15601567<■>75tcgagcggccgcccgggcaggtccttcagagggctccaacttgeagaeggcctgttgtggggaagacctgggggaaaacaccatggttttctctcagcgtgeggagggaggctctggactcttggactgtgtcacactgccaggcttcca60gacagtctctgtaatcgegaaagcaaccat120atccaccctgagatctttgaacaacttcat180ggatatttctacctcggccgcgaccacgct240<210>76<211>330<212>dna<213〉人<220><221>misc—feature<222>288—<223>n=a,t,c或g<400>76tagegyggtcgcggccgaggyctgcttytctgtccagcccagggcctgtggggtcagggc60ggtgggtgcagatggcatccactccggtggcttccccatctttctctggcctgagcaagg120tcagcctgcagecagagtaeagagggecaacactggtgttcttgaacaagggccttagca180ggccctgaaggrccctctctgt3gtgttgaacttcctggagccaggccacatgttctcct240cataccgcaggytagygatggtgaagttgagggtgaaatagtattmangragatggctgg300caracctgcccgggcggccgctcsaaatcc'330<210>77<211>361<212>d肌<213〉人<秦>77agcgtggtcgeggecgaggtgtccttcagggtgtcagctctctgtactctggttgcagaccsgccsccagagtggstgctgtctgcacccacagagagcggctgtactggaagctgageecctacaccctggacagggacagtctctatgccaccaccagcaceggggtggtcagegagg3gtctgettatgcccttgttcaagaacacca60tgsccttgetcaggectgagaaggatgggg120ategtcctgaccccaaaagccctggactgg180agctgacccacggcatcactgagctgggee240tcsatggtttcacccatcggagctctgtac300agecattcaacctgcccgggcggccgctcg360361<210>78<211〉356<212>dna〈213〉人<220><221>raise—feature<222>7,3;6,350,353<223>n=a,t,c或g<40o〉78ttggggnttt3ctgsaicttcgaagttcaaccagtgttggcggc3gcc3ctggacagagagaccacggag己cctctgtactgg3gtgg3cgeggctatactcccgggcaggacctgeggtagggtccttcactggctgcagccatctgcacgggagctgsgtaceggggtgtgaggagaacgggcctgctcactgactttgcctccgccttccsgtcctctgtcagegagg3tgc3gcaccaggtccctgtctcagscttggatcccactgggeggngaen3gccattcac60ctggctccag120tc33g3gc3c180agaaacatgg240gtcctggact300ccrictt356<210>79<211>226<212〉dma<213〉人<400>79agcgtggtcggaggaagatcc3ttt33t3ccagaacacttcggccgaggttetgetgtea3cct33cgt3ccsgtcgcaggtgagaaggctcg33cstcagcagacctgccatgetcttttgtcatccactagcttggeeccgggcggccctcctgcccatgsgstggcscsggttstctgctcgactggcacagt60gtcaaaagtg120catatgtgct180226<210>80<211〉4"<212>肌a<213〉人<220><221〉misc—feature<222〉23—<223>n-a,t,c或g<400>80tgtggtgttgaacttcctggagncagggtggatggtgaagttgagggtgaatggtaccaggsmgmssgaggmwggwgtyycwgaggttcyggtggtgggcacagagstcygatgggtgaaggtgtaggggcccagctcttyratgycattctctcicgyygmgwccagsgcttttggggtcagtggctgctccatccttcteggacctgaggccaacactggtgttctttgaata<210>81<211〉310<212>dma<213>人acccatgtcctccccatactgcaggttggt60gagagggecsgeagecataattgtsgrgck120rarrtccactgtggaggtcccaggagtget180accattgacatagagactgttcctgtccag240ggycagttkgctyagctcccagtacagcer300aagatgatggatgcagatggcatccactcc360agaggtcagtctgcagccagagtacagagg420444<〉81tcgagcggccttccacctgtgatcagtcagacagagggeetccgtggtgtttggtgatgggcccgggcaggctgcggacaactggctgttaacactggtgtgaacttcctgtcaggaagctctccagggactcagttctcttcttgaacaggaaaccagg3cattggtctgtgeagaaggacctgagcaaagggcttgaggtgttgcatgtagagecactgaagcaggtcggtc3gtctgc3gsccctgctttttcctcagcctcctgga60aaactgetea120cagecagagt180agaaccctct240taatgeaagg300310<210>82<211〉571<212>dna<213>人<220><221>misc—feature<222>202—<223>n=a,t,c或g<400>82acggtttcaatggacacttttacaaatggaatttcatcttaa_tataiaiait3ltatgcactctatcttgaagaatgtatgcaatgtttaagggttcctggcactttagctaatgccaagtggagaactaaaaggcaggaaagtaccttccaggsgctccaaaccgtgttccatttggcacagctattgtttscttastggat:cgtttccatgctgagtagtgagaact33gct3acactgctcanaatgcacaatggtttagtatccagggtgcagtgaagattgcatctcttggccactagcgatgcagaaaatgctaagttactaaatattgctgagagcatggcaccacccccagtgctcaagtggcagtgatcaattttgtctcactacc60aacagtgacaaagctaatca120actttctttttaacaggcaa180cactaaasaattcaaatggg240gagctgaigatgctgtgca3c300tgaatcttgacatggaaggt360gacttaggggctgtgcacag420tccaccccaggaagrgacttt480acatggctgactttatcctc540571<210>83<211>551<212>dma<213>人<400>83aaggctggtgggtttttgatcctgctggagaagggaaaagatgcttctgggaacaaggttcgagcttcactttccaagctaggggatgtcagagcccacagetccatggtaggagtcaat3ag3aggagctg3actactttgcaaaggccatcctgggcggagctaaagttgcagacaaggtcaatgagatgattattggtggtggaatgatggagattggcacttctctgtttgatgaatccaaagctg3g3agaatggtgtgaagatt33gtttg3tg3<210>84<211>5"u<212>d贴〈213〉人aacctccgctttcatgtggaggaagaaggg60saagccgaigccagecaaaatsgaagctttc120tatgtcaatgatgcttttggcactgctcac180ctgccacagaaggctggtgggtttttgatg240ttggagagcccagagcgacccttcctggcc300atccagctcatcaataatatgctggacaaa360gcttttaccttccttaaggtgctcaacaac420gagggagecaagattgtcaaagacctaatg480accttgcctgttgactttgtcactgctgac540551<400>84tttgttccttacatttttctaaagagttactaagttctgattccaacttagetaatteatcttctagctgggacaaaagttctttgttttgaagctggacctctgtctgggccttggactaaatgttaatctttaattcttccatatggacactgeaattatcttctttgagtctaatttacttcctctcccatttcttagcttcatctaacatgetettagtaaaggctgcaagctggggctgaacttccttgtctttcttgttcaaagagtggactttttctctgcgcaaagcatcca<210〉85ttaaatcagtcaactggtctttgagactct60tctgagaactgtggtataggtggcgtgtct120ccccctgtag3gt3tcac3g3ccttctgct180cccaaatctgcttgtcatgtteaagectgg240tggacatctgtctaagttgatcctttagaa300cttcttctttgctttgaatcgcatcactaa360tcaccctgtcacgatcatcctggagggaag420tcacagtactgtccaagttttcctgaagtt480taacctgaatctctccaattgtctcttcca540g571<211>561<212>dma<213>人〈400>85.tcattgcctgaagtta&gaa3tcct3g3gcgaaagggtcaaaagsctctcggsacatcagt<210〉86<211>795<212>dna<2'13>人<400>86aagccaataaaattctcacccacagctcaatagaaggaaaggttcaatgtcctctggtgttttctctcttttggtagttttacatcctgtttctaacctctgatgcagaatttctcttcccaggagcttc<210>87<211>594<212>dna<213>人<秦>87caagctttttcaactgggttcttcaagcttactggsatgtcatct3cttctgatc3ttttctgcagcgtcctgctggsgtgagcttcaag<210>88<211>557<212〉d船<213>人tgatggcatctggaatgtgatgagcagccaggaagttgtagatttcattc60ttcagcatgtggtggaagctgtgaggcaagagaaacaagaactgtatggc120gcacagaggcaaacaagaaggagacagaaaagcagttgcaggaagctgag180aggaaatgaaag33a3gatgagaaagtttgctaaatctaa3c3gc3g3a3240tggaagaagagaatgaccggcttagggcagaggtgcaccctgcaggagat300agtgtatggaaacacttctttcttccaatgccagcatgaaggaagaactt360aaatggagt3tgaaaccctttctaagaagtttcagtctttaatgtctgag420taagtgaagaggttcaagatttaaagcatcagatagaaggtaatgtatct480acctagaggccaccgagaaacatgataaccaaacgaatgtcactgaagag540ctataccaggt561tcaccatt—tattacttaatatatgccaaccactgtacttggcagttcaca60gttacaacaaccccatgaggtatttattcccattctatagatagggaaac120gtaagttaggaaactgagccaagtatacacagaat己cgaagtggcaaaac180gactgacactgctatctgctggcctccagtgtcctggctcttttcacacg240ctccagcgctgctgctgctgctgcattaccatgccctcattgtttttctt300tcaactgcatccttcaaagaatctaactcattccagagaccacttatttc360tctgaaattacttttaataattcttcatgagggggaaaagaagatgcctg420tgttgtttaagctgctcaatttgggacttaaacaatttgttttcatcttg480aacagctgtgttttgctagaaagaitcsctctccctctcttttagcatggc540ttcaattcattttccttttctttcaacacaatctcaagttcttcaaactg600gaggcctctttcaagttatgttgtgctacttcctgaacatgtgcttttaa660tcttcttgaagatcctgtaaccacttccctgtattggctaggtctttctc720aaaacagccttcatggtattcatctgttcctcttttccttttaataagtt780aga_a_c795ttttttttttaaa.aagtgttagcattaatgttttattgtcacgcagatgg60tatgtcttcatattttatatttttgtaaattaaaaaaattacaagtttta120ggctggttatattttcagaaaacatgattagactaattcattaatggtgg180ttccttattggctccagaaaattcacccaccttttgtcccttcttaaaaa240tggcatgcatttgacttcacactctgaagcaacatcctgacagtcatcca300aaggaatatcacgttggsatacttttcagagagggaatgaaagasaggct360gcaaggcccacaccacgtggctgagaagtcaactactacaagtttatcac420caaggcttcctgaaaagcagtcttgctctcgatctgcttcaccatcttgg480ctgacgagcggctgtaaggsccgatggaaatggatccaaagcaccsaaca540actcgctgcttggcttgaattcggatccgatatcgccatggcct594imageseeoriginaldocumentpage103<221〉misc—feature<222〉480,—491<223〉n=a,t,c或g<400>91gaatcacctttctggtttagctagtactttgtctccctgggctctgtttggctctcggtatggagaggggaatatgcattaaggtgaaaaattgctgcttcsggactgtggaatta仁仁tgacaaaaaaggtaattacaaaatgtgtacattgtgctcacattcccttaaatgttgtttcctctccgggaagaggcagagacagtttggcgaaggagaaagcsgccttccagttaaalgatcgctggcctcangcggeigtctgggtcsgaggtatgaggtttcccacagcgga60aggcagg、cctacaccttttcctctcctcts120gtcaccttccaaaagtgagaaagggattcg180gaatgttttacaaatggttg240cacaacatgctttttaaagacattatgcat300aaaggtgctcagcctctagcccagctggat360agggaaggagggggtggtga420a_gccctcagtt3aaggtc3gcttcccgcan480gaggagcagcsgc3gggtggg3ctggggcg5405"<210>92<211〉551<212>d肌〈213>人<400>9233ccggsgcggtgaagcgcacgcctccagcgcctccttgactggccactgggt3tgssggatcca_actcagctcgtaagtgc3g3gtccctgtctg3gtgcgagcagtagagatccaggtgagaagttgaaccgtsggatccctgcaaaattattgaaaatggtgatcatgttgccgagactgggtgggctctgc3gcsggggagaaaggccsgctggttccgggccttagcsc3ttgc3tgaaggagacgatggatgagaccatggctgcaggcagatgcgggcccggggctgaaaaaggaagaggcagttggascgcscagsttsgscggaitc3ccacatgcagagga33c3ggctgatggaccgtgcctgctgatgacagaggaacgtg3tggaccacatcgaggcg60gcgagctgag120ggctgaggtg180tcaggagcgc240gagtgagaga300actccaggaa360tgaagaggtg420agctgagctg480gaacctgaag540551<210>93<211>531<212>dna<213>人<400〉93gagaacttggcctttattgtgggcccaggagatctggttttctggstsgccaggtcataggcacaggcctcacttgctgcagttccggggctcgtggtscacgscsg3gccsttggtgcacgagggcaggcagcaggagcattgctcctgtttgctggcacactttccctggcagtaatgtcccactttgatgt3ctgcaccttggctgtgtcacagcaggtgcctggaattttcacgatatcsaatggtgggcagcccgtgaccctctt〈210>94<211>531<212>d船<213>人gggcacaaaggtcaggaggcccaagggagg60catgggtatcagtaggaatccgctgtagct120agaacacctgcactgcatggcgttgatgac180gtgcaagggcacgcgcatgggctccgtcct240cacatcctcgstgtcaatggagtacacagc300aatgtccacttcctcttgggacttacaatc360gatgtctttgcastcaggctcctcacatgt420tttgcctccttcagccagacacttgtgttc480ctcccsgatgtactctcctct531<220><221〉misc一festure<222〉517一<223〉n-a,t,c或g1<400〉94gcctggacctctgcagagtctctcctgttcggcagttccatgctcctatggcctgcagccgtctctgctgccgtacgttgttt3ccc3tctgccggatcaatcgtgtcaagggtggaggactcggcacattcaitctttcaccggggcaaaagctgcacaggtgaaaacatttggccacatgtgccacacattgtgaccatgacgtgtggccgtcaccttcacaagcctgctaacatggagggaagtcagccctcacatacgtgacttgctggaccccggctgccgctggsgatgggcagacaggacctggatgaagtccaatggcagtgg3tct3cggcg3ccgccnc33tggcaaatggcttcatgtgccctgcccttgatttcaagctaagtgctcctttgagattaaatgggsgactcta_tc3tgta_aacaacgagtccagaccttg60caacagccag120tgtgtgcacg180tactggtagc240ccacaatggg300gcatgctggc360ggtccttgcc420tga3gtc3gg480t531<210〉95<211〉605<212〉dma<213〉人<400>953g3tca^ccttctcgatagtrsgraraytttggatgttgtctctgctgatgtgtcactggtgcatcccactcagacaggg3gg3ggratgctccacttcgtct3actgctggtcarwcaactkkr3g3c3ycccmagtcagacagcaggagggatgctccacctcctctgagacgtgcgyccatcccttccttgtagagtgatggggagg33tgcytsramskmacctcwgagacggtgcgtccagccttccttagagggtgatggagcaccaggttccagctgccytggatctttcttaccagtcttccttgtcagkgyratgrgsaglcaccartcttccagcttcttggatctgtcttaccagtgcagggtrgtttccsagcatgcyttgacrcagggtcttcttggatctttwmttksywgwgtgcagaggtgtttcccagcttgccttgactcagggtcttsctctttctgaagatcaaccttctcratggacgaagatctgctttgacgt60rasyktmwwm120ggactctttc180aaagatcaac240sttctcgatg300cacgaagaty360gatgttgtag420tctgctggtc430tgtcsctcgg540gcatcccacc600605<210>96<2ll>531<212>dna<213〉人<400>96aagtcacaaagacagaggtcgaggaggtgacaagacatgcgctcgtttaaatggaaaaaacagattgagagaacatttgaatgattctgsagcatctcaattsatcactccattacaacactgacaascaaacagtgttcctggaaataattattaccagacataatctcagaaaaggaatcaatctattcatgctagac3g3aaggatgctgcaagctagaccttcaaggaaaaagtgg33gaataattcaagaggtaagaagaggcaagctcgagagagttgatctgagaggatgaagtattagaagcctcgaattactagagatagaagtctgtggcaggctgaaaaagcaatctcattaagaatcttgaacgaag360atctttaca3120alaaaigaggct180tttaaactac240agtaaccaa3300aatgtgtgag360tcgggttgtt420gcagaaacta480a531<210>9"7<211>1017<212>d<213>人<220〉<221>ruisc—feature<222>963,—995,1001,<223>n=a,t,c或g1008,1010<400〉97cgcctccaccatgtccatcagggtgacccagaagtcctacaaggtgtccacctctggccc60ccgggccttccttctcccgacagcggcatgcctggaggtgcctc33c33cgatgctggagcaacatgttcgaagctgaagcaagtatgaggaaggatgtggaccgscgagccagatctcgcagcatcattggctgsgagcggatgacctgctncaggctg<210〉98<211>561<212>dma<213>人<400〉98tgggtctggsggcagggggcggcttatcctagcacctgcatggacsgccagccactgattgaatgatgttttgcastaca<210〉99<211>636<212〉dna<213>人<400>99gggaatgcaaggaaacttagtgttgtagtcgctgatcsggcactgggctctcccacctctacagggtgcgggratgccttacttcgagagagacggagcatccatcttcc<210>100<211〉697<212〉dna<213〉人<400〉100agcagccgctgtgggcagcaggaggcatcag3cccc33c3aagtttgcctgagagct3cactggaggcgggatgagatcagatgaagcttatcaacttccgacacatctggctgaggtcaatgtaccsggcggcgc3c33agattgagggcctacacgsggcaactttcgccgcagttactccaggccgtccttcatagagcctcctgcatcaacarcctagcttggcaa3taagcgt3ctcaggcagcttggtgctgtcaggcacagtatcaagtatgsagactgagatcctcaaaggctgggcccggtcggtggcctgggtcaaccsgcaaggt3cggtaggcggcagcatgcagggg3g3gatggagggtagagctgcatggacaaccgaggatattggagctgcagctctgagatgcaganggctttcccgcstc3ggcggcggctagcctgctgagagaaggagcttcctggagcacggctcg3actggagactcctggtggaggascgaatttggagtctcgccgagstccgggagccgctcccgccaaccgcaagcctggctgaacccggaacncctggsngngctcctcgagatggtggggcgcccccttgtgcaac3tgg3tgggccaggatcctc3tc3atggaagggctsgctgcagtctggacatggagccgggctgsggsagcacggatcagcccggccgccat120180240300360420糊54060066072078084090096010173accc333cctacccaggggggacaggcaccctggagtctagtgccaccggtgcctt3taggcacggtgagccttccsctaagctggattactcaaggatgcttcctaitccctccaggcgcscccagggcc3cctgcctttagcccaatgctt3accc3cgagacaattttgcctggcgcatggggcctacctaccctgga3cccagcggctgccactggcgcctgggggacttcaatgagtcgctccatgtgggggaacccccgggcagggcacctggagcctggggcctccctatggcggtggtgcctcgctttaigattatgcgttatc60agcctgctgg120cacccccagg180cttatcccgg240acccatcttc300cccctgctgg360gcstgctgat420tcc333g3gg480gagtcattgg540561caactttattgaaaggaaagtgcaatgaaatttg七tgaaaccttaaaagg60acaccccccctcragcgmagkaccargtgcaraggtggactctttctgga120agacagggtrcgwccatcttccagctgtttyccrgcaaagatcaacctct180aggratgccttccttatcttggatctttgccttgacattctcgatggtgt240cacctcgagggtgatggtcttaccagtcagggtcttcacgaagatytgca300gagacggagcaccaggtgcagggtrgactctttctggatgttgtagtcag360yccatcttccagctgctttccsagcaaagatcaacctctgctggtcagga420ccttgtcytggatctttgcyttgacrttctcaatggtgtcactcggctcc480tgatggtcttaccagtc3gggtcttcacgaagatctgcatcccacctcta540ccaggtgcsgggtggactctttctggatggttgtagtcagacagggtgcg600agctgtttcccagcaaagatcaacct636
tableseeoriginaldocumentpage107
aggcacagtcccagaggtgatatcaaggcc451〈210〉104<211〉441<212〉d隨<213>人<400>104actcacggtgacggcccccacaatggcctcccgtcatgctttgtcacctcgccsgatgcacccgcgccct<210>105<211〉509<212>dma<213〉人ggtctgctc3asggtgc3cagccggatccatggggctagtgctgcgcggcagaccatcgtgcaaggtgcgtcatcstccacttgctggctctgcgaacccctcagcctcaggtaatggctgcccatgttgggsgggcct3cgsctcgccttgcgcatcgttaagtccgtccaggtcctgcatcgcgctggcgcgtgactstggatgaatgctggcactaggactggcttccccsgcgccaactcccgtggccgtcctgggccttcatcctgcgtggtggccgcaggacttatctcctg60ttggaatcct120ggacgctgaa180ggctggctgg240ggcagcaaca300cagagcaccg360ctgcaggcgg420441<220〉<221>misc—feature<222>195—<223〉n=a,t,c或g<400>105tgcaaaagggccccagctccggcatctgcaccaaatataactccgttttcctgcggtctaagagatgacatggggttcalcggttgtscag<210〉106<211>571<212>dma<213>人acacaggggtccg3cc3c33gctggga^gsatacntgtgttgccggtgttctgcatccgcctcggggtcc3caccsigc3cgccatgcttgtcaaaaataacccccttccttggagaggggtgggtgtgcaccccggatggtccccacgcttc3c3gttgaaatttctctcccccggggaggaggtgccg3aatcctccacg,ggcagccccgcgagctgggggctccgcccgttcsgtccccctcccaagcaagaagagctcggtgcgc3ccc3cc3gggcgccaggctcctgctgcctggatcagcagacatcttgcaaacctgta60gagcaggtgt120tggtctcttt180ccc33gceict240caccggctgg300tcsttgtaga360ttcccggtgt420cactgtttga430509<400〉106gggttggaggagttgc3ct3gtacattttagsctgcsgsgtttcaaaataactgactgatctttctttctatgatccatt<210〉107<211>555<212〉d船gactggttctttgatttctcagccaataagggsctgggt3gctgtcaicagatat3333tttgagatgagtttcaaggaggctgtaagcagttatttcaaatttctccca3ctgcaggatggggaaggaaaccsgatggggtaaaaagtttattgagatggttcacatggccaggsaagcattgtgaagggsagacacttgtcggcccc33t3cacct3accttaaaagattggcc3gggttgtacat33gcacttctsgaattaagtggtgtcaat3ttcaagaigaccacaagscctcct3caacaaactggcc3c333ccctsttc33g3gacagcagctgc3333ac3ccscctcai3c3gtatcaaaac60tsaaaggaga120gaaaccttac180ccagcccacg240csaagcasag300tttctccagc360tcaaacccag420sgtcttcttt糊taagggggac540571<>107caggaaccggggcggtgwgtg3gcgcctcggtggcctccgcgcctggccgagaggtatgggtggctcgtgctggcsgaggaagtgtctg<210>108<211>541<212>dna<213>人<400>108atctscgtcaggctttcasgctcattccgagttgcaatgggctctcagtaggaggagaagccaaatgctgcccsatcctcttgsactcacc<210>109<211>411<212>d船<213>人<400>109ctsgacctctcac3gcga_aitggagaacaatgtcagttcttgttctgccagacgctgacct<210>110<211>451<212>dma<213〉人<400〉110ccgaattcaatgaacctacgattattcctagattgaagccccccac3ttacgctacscgatttcatgcccagcgcgagcacgcaagatcccagcgagaagttgaaccgtsactgccctgcaaggttattgsagttggtg3tcccgttgccgtagctgggtaggttctgcattgagggagaggatccagctaaaagctggaaaaaccgggcctaagcacattcattgaagggagagatggagggcaccatggcagcaggcaaaggcgggccggttgaagaaagaagctgaacttaaaagattgcagsagagagacttggaatgagcagattgctgggstcagatgatgcagcgggaac3gggagctggaccaaagctgctggaagaasagagcagat3ggacgcacagaggagactg3tggccsccatcgactgaggctgagtgctcaggaatgagagtgatggaactcca60120180240300360420480540555tcaatcaggctggagacaccatgttc3atcgagctaagctgctcaatatt60aggccttgaaggactatgattacaactgctttgtgttcagtgatgtggac120tggacgaccgtaatgcctacaggtgtttttcgcagccacggcacatttct180acaagttqgggtttagcctgccatat^ttcagtattttggaggtgtctct240aacaacagtttcttgccatcaatggattccctaataattattggggttgg300atgacgacatttttaacagattagttcataaaggcatgtctatatcacgt360tagtagggaggtgtcgaatgatccggcattcaagagacaagaaaaatgag420agaggtttgaccggatcgcacatscaaaggaaacgatgcgcttcgatggt480ttacctacaaggtgttggatgtcagagatacccgttatatacccaaatca540541sattaaaaggcacaatcatgctggagaat^aacagtctgaccccgagggc60tttagggaaggaggcaaagaggtgagaagggaaaggaaagaaggaaggaa120aagaactggagacgttgggtgggtcagggagtgtggtggaggctcggaga180aaacctgactgctatgagttttcaaccccatagtctagggccatgagggc240ggtggctgagggtccttccacccagcccacctgggggagtggagtgggga300gtaagcagatgttgtctcccaagttcctgacccsgatgtctggcaggata360gttccctcaacaagggacctgaaagtaattttgctctttac411gcgtcaacgatccytcccttaccatcaaatcaattggccaccaatggtac60agtacaccgactacgggcggactaatcttcaactcctacatacttccccc120gaaccaggcgacctgcgactccttgacgttgacaatcgagtagtactccc180cccattcgtataataattacatcacaagacgtcttgcactcatgagctgt240ggcttaaaaacagatgcaattcccggacgtctaagccaaaccactttcac300ccgggggtatactacggtcaatgctctgaaatctgtggagcaaaccacag360atcgtcctagaattaattcccctaaaaatctttga3atagggcccgtatt420taccctatagcaccccctctaccccctctag451<210〉111<211>541<212>dna<213>人<400>111gctcttcaca3g3cc3cc3caacagttttc3aaggagtgacttgccaggtctgsgaggccggataaggaaggattcc3gta33ctgtgatcttttattgttgaccaggaactgaccgtctccccaaggccttggggttcgggggtatgctcagccacagctt3tg3333tgtcggccaattaattctctt3tgccsctttgggagcgttgtc33cc5lc3ctgagctttcctcatgagtgtacttcatgctgacc3ccattcacatggcag33gggtg3ccttcccsgaigcttgctgctgct33c3tttsctgtgagggttcaacggtttttttctgcccatcccccctttagc3catttgtcaccatgggggtggggagggggacaaaagagctgtaggatagctgggtgtgtgaaggtcgtcgtcttga60tcatgattgg120cacatgcaaa180ctgcaggtga240ccctcasgaa300cgcatcatta360gcgggtgaaa420ggaaacagga4日0cccatgaaac540541<210>112〈211〉521<212〉dma<213>人<400>112caagcgcttggcgtttggactttggtttgacccaggggtccagtaccacccctctctccc6ttattgacacgttggagccgccttccttgcctaaggtgtctcatcagtccattgctcttgaagactttgtccccacttacggtgtatggaggggaagggaacatctttagtgtctgagctccagttcagtgaggttcttgagccttaggaaggi:cttcagcactttccctctcccggcaaagcctgsacatgcccctcggtgagtttctggctcttgaggagtctttgcagatgaacctcaagstctatctcctcccttggtctcctgcgcccttcattgctctcaaattactgcaataggggttttgtgcctttggggat60g3gg3ggccgagttcccctt120catctctgggaatcaacagc180ccccagcacatggaaaaccc240c3tttcc3gacttgaaisttc300gatcaggtgcacctgggaga360gaagggcagggaatggggac420cacacttggtgggaccatga4803521<210〉113<211〉568<212>d船<213>人<400>113agcgtcaaatcagaatggaaaagactcaaaagratccttcaagaaacaggaaaaaactccagacattaaagcaaaaatgcaagcaagtatagccaaattcatcaattatgtgaagaattgagatctctggcagtggaggaagtctctttattttccgtcttatttcatttctgtaacagtagtgagaactttccctaccgtgtttgataagttgtccaaaatgcctgtttagtttttaaagtatgtatggaatgttatgataggacataggqsmgacaaaaatatacatgtgaaataa<210>114<211>483<212>dma<213〉人<400>114accaitcstcascaccaagatcaaiaaggaca60taaaacsccaaaaggacctagttctgtaga120agaaaaaggtggttctcttcccaaagtgga180cttccggatgactgaccaagaggctattca240agaaaatagtttaaacaatttgttaaaaaa300tgatatctggctgtcctttttatastgcag360atgttgtccaggttctattgccaagastgt420gatggaactccaccctttgcttggttttaa480tagtagcggtggtcagacatggaaatggtg540568tccgaattcctcggttttagttgtggaatgctttcatttccacgtttctttttaasactgtgtattttcttattgtgtactgcaagcgaattataatctaggctgtttaaaggtttactgttttwttttttttagcagtagtttcttatagaaacctttaaatggscaaacgtttgcctgtsattgattctagcagttaatg3gattttcctttacsgttctggcttctaaaacatcaatgtattccttttagaacctttgtttcstgttctggatgtatagagcaaagagg33ggtsttttttggatcaaagagg3ttactcgatggatttatatttgatagctatgcaatttta33c33caaagttgtggtatatgttcttttttcastt60taaat3ctgt120gtatttctaa180cgtttatatg240aaaaagtcta300ggtteaactt360ttttaacaaa420gcttattttc480483<210〉115<211>521《212〉dma<213>人<彻>115tgtggtggcgggcccccggcgctgaatgaa3gga3atgtgtctgtgcttgtgcttcaaatgaccgacggattcgcccttgcgggctgaggagcgccggccsttgtcgggacqcaacatcagcccgggcccgacaggggcacttcccaaaggcccagcaagcttgtaatgctggaggcccaactacgaactatgaagacactcattgcgggtgctgggcccttgacgttgtgccgacatsaccttgaggagggactctgacgccgtgggttcgtgagcaggccctccaggaagcactcasagstcstcsttatcatcgagccctgcccctggaaaaatatactagaggtctaccggcaagagatgccatgtattaaaatgtctggatgaagatctsctctaccttcagcaaggccagtaaattgc33ggg3ccac3sgc3ttggaactcaattgctcaacacagacagcataaaccactcg60120180240300360420480521<210〉116<211〉501<212〉d船<213>人<400〉116ctttgcaaagctgtgaaggaagctgccttcaaacagagtcaaattaaaagcgtgactgcaccatggtttacttttatttcgaaagcagtgcagcagcctgtcttcacagcligtgcatagtgcaggcaggtgagggtttttactttcccttataagctgatatgtctgcggcacgagaaggcc33ggcc3ttggagtctgaccatt3c3tgccagctccaccatatgtaatcatggaatccaatgagtgggggcagagagaaagctcatagc3tcactgccctctctttt3ttcatgttacaaaacctgcscatcggaaccaacgactgcaaactggcatgtgtctgcc3catctgtaaaaggttctgtsttatggcatcttag60ggcctccac3120aaacacaagc180gaatctgaca240cctgtttacs300acatcaagtg360aacaaaatat420cacttggata480501<210〉117<211〉451<212>dna<213>人<220><221>misc—feature<222>320—<223>n=a,t,c或g<400>117caagggatattt3gttctctgagattgtcccgtatccaat3ggagagtttatgttgagggtacrgrgtgacactgaacagatcacaaagcacgagaaaca60ccctccccagcgtctccttcgtctccctggttttccgatgtccacagagt120ctaagtaactgcatgatcagagtgctgkctttataagactcttcattcag180tcagcaattgctteatcaaatgccgtttttgecaggetacaggccttttc240agaatctcatagtaaaagsctgsgaaatttagtgccagaccaagacgaat300tgggtgtgtaggctgcattnctttcttactaatttcaaatgcttcctggtaagcctgctg360ggagttcgacacaagtggtttgtttgttgctccagatgccacttcagaaagatacctaaa420ataatctcctttcattttcaaagtagaacac451<210〉118<211〉501<212>dna<213>人<400>118tccggagccggccgcctgaggggtctttgtagaaagccaacagtcacagaacaagaatgtgaaaacagagggcagaactgcaatgctacagggtagtcgctagtgggctttccctgcagcsctcgctgagacaggggcatggtaaggccgaggaatgagacaggscatctc33ccc3g33cgccgccgccaggaaggaagcctcccacggcaggctgagcg33ctctccacccgccgctcagaagcagcagcsaitgatgtgccggtgcagaggtcatctcgaatgacaatacgaagagagttcctggcgtgatgggcaaatctggagcttccactgc3gggctcggagctggataaaagttatggctgcaaaatctgctcgtcatctccagagtaccgtggttggacaaacaccgctgcc60tcgctcggaa120gagctggtac180gccatgaagg240tctgttgcct300gcattgagca360agaagataga420tatcttattc480501<210〉119<211〉391<212>dna<213>人<400>119tgtgtgagggagggttccccagsgtcagggtctggaggcttctctgstcacacttgacagargttcaalcagggasgcaactctcctctgggtgttcattctagggaccaaggggaaaggaaatgggacagagcaaaaggaggactgactcttttttgggaggctggtctcgctcgaatgaactccttcccatctcaaatgagaaatgagagtaagaaaagtttcccccctggg3ggtag3tgttgc3333gtggcagtatgtggggatt3ccc33cccccgttggaaaggaagstggagg120acscc3ttcc180agaagacgtt240ttgatccctt300gaaaggattc360391<210〉120<211〉421<212〉dna<213〉人<220><221>misc<222>409<223>nfeaturea,t,c或g<400>120tggcaatsgcgttccgccggcaccgaggctccaccgcsgaccccc3tc3ctccctcagaactagaacaigtacagcc3tccaaggccttecg3gagcaacactcaggcttctttgtgtttggcctggc3c3aggagctctttccactggtatgsacgacctgatttcggtgtcagttccctctgcctctattagtaggegecargcgcatccacaggegsgcgtctctgagaggaggccg3tagcegtettcttgttttttteggagcagtggcatggacgtatcaagcagagaggaggeeactcaactgcgttttttcttcttggttgnttcactgccat60eigstggaigtt120taccaggatg180taaggcagag240ccctttcctc300ctgggggggt360gaatgtctcc420421<210〉121<211>206<212〉dma<213>人<鄉>121agctggcgct33ccc3cgcc3gcc3c3333gtttccaataagggctcggttgtaaggtcgctgtaacctcaaacggtttatgtga3at3cagcgtrgtcsgtcttcgtccatc七gcttttaagg33accataaagcttggctacctgcccttgcgctcagtgtaga6qttctgaaatacactaagagc120agtgccttaatttttaacca180206<210>122<211〉131<212〉d肌<213〉人<鋼〉122ggagatgaaggatgscgatgatgaggaagctgagtcagctacgggcargctcgataccaagaagcagaagaccgacgagggggcagctgaagatgatgag60atgactagacagcaaaaaag120131<210>123<211>231<212〉dna<213>人<220><221>misc—feature<222>166,—202,222,225<223>n=a,t,c或g<400>123cctcagtggcgca3ttscatggccc33gag<210>124<211>521<212>dma<213>人<220><221>raise—feature<222>284,—"2,513〈223>n=a,t,c或gaaatacttaaattaatcaaaaggcactacgagtakgctaakgaagatcaagctacagsacalccargaagcatgtttgctttccagaagacgatatttggccnggaaaggatcaagataga<400>124gagtagcaacagcsgccgtgatcttcagcaggagct3ggcttactgcagtgccgccaatcatc3cc3tgggcs33gcgctatcgcttagtggcsgctcccaaggtggtgaccgtggagagggagcttttgc3tcccatgctcagccaagcacctacatgctggtattgagggagtgcttaaccaggacttct3ag3aattg3tgtct3c3atcatgattattcccttatgttggtgcaaattctcaaatttctgtgggsggggtagttggatctcasaaacagcaaccagttgttc3gagatgcctgcaaccccggcsggtatgctatctcanggcttttataccacctaaaacctactg60atyatctaatatgaatgtta120tatggnacaatggtcattwg180tnaangtaaag231acttcggttcccsggatgccattgctgaccgagacctgtgtggntgtggcgattgcttcaataagaaagagtagcsgtgccggtctctgc60gaatatcaaa120gcctgggcct180tggaaattgg240gaaatcaatg300gccagccggg360tnagagccgg420agatcatatt480521<210〉125<211>341<212〉dna<213〉人<220><22l〉misc—feature<222〉277—<223>n=a,t,c或g<400>125atgcaaaagggtaccccagctgtggcstcttttccaaataactctccgtttggctgcggtggacacagggtccccgaccagcsgctgggstsaat3cgtgttctgccggtctactgcatcggttcaacccccttagagagaggctgtcagaactgtttggsgsgcgctgggtgt<210〉126<211>521<212〉dma<213〉人<220〉<221>misc—feature<222>353,—399,455<223>n=a,t,c或g<400>126aggttggsgacaggcccsgaggagagatccgcccagcctggctcascagacc3gccc3tgccggcgactgcagcccccag<210>127<211>351<212>dma<213〉人<400>127tgsgatttataatgcatttagtccctgggatctcttaaattcagagcaagttccatctga<210>128<211〉521<212〉dna<213〉人aggtcatgcagtggcactggagcagatccctstc3ggca_cttscscag3cgcsgctctacttcatccagtaagggcctgagcaatgggcacctcccccggcggggaggtgggaaaatcctgggcggnggggcaccccgcgggtgcagattacagaccatgggtgcagctgtcaagttgtgagaggtccagcagatccagcca3gcca_3ccgctggcaaggcagcctttctgtccsggskccaggtgatgctgccggcccagggacagac33ggac3gcaagtcaccatagcccttcnacc33ng3c3ctcccagaggatgcatttcatg33aagagtggcaaagaatgggatggggaggcagcttgaagggaggtgggtggcsatgaatttccatggcaggaccacgaaacgtggcaagtccatgcaatccacccactctctggatgcgtg3a3a3gcgtcttgggggtcttccccctggaaagcsagccgagctcggccagc3cccscaggggcgccccccaaacct60aaggagcagg120tgctggtctc180ccacccaagc240aggcaccggc300341.agccacsgggagcagatcatagctgcsgtatccagacact3gc3gttcaagcctgcgggccgggcaggcccc33c3c33ttcasgcccaa60cactaacaca120tatccgctta180tgccaccaat240gccagttcac300cang3cctcg360ccccaggtga420ttttgccata480521aggrgactagacaaagtcctctccacagggagctacacact3gc3gctgtcacagttttt60sgtttcctgg120aataaatctg180agctctgggg240attcacctsa300t351<400〉128tccagscatgagagttaaggtaaatatactgagcttgctactcctgtcctgaaggtttcc33t3gct33gaggcggggagtttcattccttcatttgccattgctgttttc3gga3ccaggttccttctcgccaggtccctcaccccattacctgctatgttttgcttttggtgascagtcd33c3gagcggaagcagaagascaigttttagagaacaagtgccctgttc60120180240cctgatggagttccattcctgcgggtgtgaastcsctgccgcgctacttaataaatatatcatcctaagggcacttgccagccagggcacggctgagtaacacgaagcca3ccccstggscag3cccctc3ctcttccttttatactttgaaattatgataaccgattttgctcttatccggacagtcaagcactgttgtgaaaacaaccgcaacttctgtttcaagaaag300cttagccgca360tcccatgcgg420tggacaacag480521<210>129<211>521<212>dma<213>人<400>129tgagacggaccagatctagtagagcaattaagcttcacattcaccggcct3gtgcgag3tagtgtctatgcaacagagggcactggcctgggcagagaggatgaagcttacgggaaaggtattccatcatgtttctaccg'tsccagacacccc33c3tgtccgs33ccaagtcccccctcactcaggcctcatctctgttctaaaactgcacttcgctcsttccagatggtggaaccaaa3tctc3g3gsatktgctgtcggaacttctggggscagttgagccsgtcgcatctctccctgtataacagcccac3tgcctgatatttccaggtggacsgsgtaggacctgagacgtcggcstcttgaaaigtacgattctcggctatggaatatggggatgtatgaaatgcacatgaaacg60agcttcaaga120ssgatgatggs180ccatcaactc240gaaatgggct300tcagcggggg360tggaccgagg420tcatggtgac480521<210>130<211>270<212>dma<213〉人<400>130tcactttatttttcttgtatctgcacggagactctggtgtcttggtgaatacagtctcctggcatcaaaggtggccttgggt3gcagtcatcgataccagccatcatgaga3aaaccctatgttgtagccgggtcttgacgaggtggtcatccagsggtcgggggtcaggcg33gttgcccagggtggc3acagctggaggtgaactccttagctgtagggtgcagcccccctgagtccggatagggagatcttagaaatgggctgaggt60120180240270<210>131<211>341<212〉dma<213>人<400>131ctggaatataccsgccattcttatgt3t33ctggggaaga3acccsgtgg3t3a^3ctgggacccgtgatgctcctactgtagctcatgcagg3gtacatccagggagcggcacagctctcgacaaaactatgtgtccattgaagggagatggcacttacttgaacgaggaitgtggtg3tgtcat3actgttggcscctsctttgtccctctgactgtgccaccgtcccggacagaatcagcttttgtaatcttcatacgcttctgcactgtggctgggagcttgccaggtgcttcattcttgtgagatg60120180240300341<210〉132<211>8"<212>dma<213>人<220〉<221〉misc—feature<222>37—<223〉n=a,t,c或g〈秦>132tgaatggggagaaccttccagccatgtggactccttcatctggtcatcctaaggaggggagtsaagtgtgtcctgtgacactgcgggctcccctgcactgggacatctgcgag3at3ataaaggtcctgactaataccct<210>133<211〉601<212>dna<213〉人<■〉133ggccgggcgc3gcsagc3gccagccgctcgttcagg3agcggtgtgggcc3cgtg3tatttcasatgcatg3gcc33tasaatatgaaga<210〉134<211>421<212>dna<213>人<400夕134agagaagaaggtgattaggtattgcttatttccctcacaggggcaatcttg<210>135<211〉511<212〉dma<213>人<400>135ggaaaggattgctgacagactgactatg3aggagctgaccgaagtgggcaacatgaggggcaccaagacttggagctgtgctatgctctga3gacagctgtccag3gaccaaagtgaagaccctgtgttcagcctgtcagatttgaatgtgttc333tcccttctgcagtcaggaaatggtctgtggtggctgcctg3gc33c3c3gt333tggcttttggctccaggctcctggtgtggtcsgttctctactgtggagcccttccsc3gctccatgctagggtggctggc3gc33cc3cgtctg3agscagcttgnggatgcctcttggccctcacccttcsttgctgttgatgasgagcccagagctcacttggtgacttagtcaagtccatgtccaccccaaccttgcccctgaccttagagatggct3tggtggctc3sctacagtggaccaggcctgaaggagcaggagatggggctccggttgtcgaggagaaactgststgtctagacaatgtcgtctgatgttcctgcacacctgctccagccc33ctcctc3cagcgctgacacaaccatctgcaggggatgaagtacacataaggaggagccttggeigctgacaggtggaactcccagattttc3c3c3tcccctgtgagtaggaccctatasacattggtcttccacacttgctcttccagtaatgggat60120180240300360420480540600660720780輔8"gcgcgcccccgccacacgcacgccgggcgtgccagtttata3agggagag60g3gtcttgaagctctgtttggtgctttgg3tccatttccatcggtcctta120tcagactccagcagccaagatggt^aagcagatcgagagcaagactgctt180cttggacgctgcaggtgataaacttgtagtagttgacttctcagccacgt240ttgcaaaatgatcaagcctttctttcattccctctctgaaaagtattcca300ccttgaagtagatgtggatgactgtcaggatgttgcttcagagtgtgaag360gccaacattccagttttttaagaagggacaaaaggtgggtgaattttctg420ggaaaagcttgaagccaccattaatgaattagtctaatcatgttttctga480agccattggctatttasaacttgtaatttttttaatttacaaaaatataa540cataaacccmgttgccatctgcgtgacaataaaacattaatgctaacact600601aatttaagcaagttacrctatcttaaaaaacacsacgaatgcattttaat60ttccctccctccacctccctcccccaccctcctcatgaattaagaatcta120_taaccataaaaccaagttttgtggaatccatcatccagagtgcttacatg180taatattgccttctt3caaaatttctattttaaaaaaaattataaccttg240acaaaaaaattcagtacaaaagttcaat:atattgaaaaatgcttttcccc300caccgttttatatatagcagagaataatgaagagattgctagtctagatg360c3aattacaccaagacgcacagtggtttatttaccctccccttctcataa420421caagaattagaggacttgcttgctrragaaaaagacaactctcgtcgcat60aaagagagagagatggcggaaataagggatcaaatgcagcaacagctgaa120cagcttcttgatgtaaagttagccctggacatggasatc3gtgcttacag180gaaactcttagaaggcgaagaagagaggttgaatgcligtctccaagcccttcttcccgtgt240gacagtatcccgagcatcctcaagtcgtagtgtaccgtacaactagaggaaagcggaaga300gggttgatgtggaagaatcagaggcgaagtagtagtgttagcatctctcattccgcctca360accactggaaatgtttgcatcgaagaaattgatgttgatgggaaatttatcccgcttgaa420gsacacttctgaacaggatcaaccaatgggaaggcttgggagatgatcagaaaaattgga480gacacatcagtcagttataaatatacctcaa511<210>136<211〉341<212〉dna<213>人<400〉136catgggtttcgcctcggcctctgtttctttgactgccagcttcaagttctttgascctggaccaggttggcccssagtgctgtctttagcaagctcagtcgqctcagtgattctatcagtccaggctgcttgggattacagt333gctctactccgtggtaagctgcaggcgaattaatccttgasctscggcgtgagcccctgccatgcctttttctcttccccagttacttcstgstgtgacctcaggaccacgcccgsgtatctacattccagttctagtgatcaggtgatccacccgcccccaaagtaactgacgttctctctctctgagggttct60120180240300341<210>137<211〉551<212>dna<213>人<400〉137gatgtgttggagaagatgcaaattattgtgaggttggcsgcctttttgcaccggcagactagacattctcaaatgcctttaccctctgtgtttaaaatatgtgtctatggttggatgaaagggttattttttgaatacctttgaacattattgagcttatcaattaatgatttcttactaattgctgtgtcctcacaaagcasctttttagcttaagaagtggaaatggasgtctttaatcagacggaaatgtgagtgagagaagtccttaatcccctgctctgaggacatttgatgacacagtttagcaaactggactggatctgaagggcctgacaaatcattacaga60agtatccatt120ctatgggagg180gtaaaaatgg240aaggcatgga300tagatgtgtt360aaagatggtt420ataagsaagg480agatggaaag540551<210>138<211〉531<212〉dna<213>人!<220〉<221>raise—feature<222〉490—<223〉n=a,t,c或g<400>138gactggttctttgatttctcggactgggtagctgtc3c3gtttcaaggantt3tttc333tttctcccaactgcaggatggggaaggaaaccagatggggt33333gtttattgagatggtttcacatggaagacacttgtcggccccaatscacctssccttaasagattggccagggttgtacataagcacttctagactaaatcagt3att3agtggtc33t3ttc3agagaccaca3g3cctcct3c33c333ctggcc3c333ccctattcaagagacagcagctggcaaaaacatc3cctt33cgtrtcaaaactaaaaggagagaaaccttacccagcccacgtttctccagctcaaacccagcagtcttcttagttgcacta60gtacatttta120cagaasatgg180gactgcag3g240tttcsaasta300actgactgat360aaasgggtga420tctttctttc480c531<210〉139<211〉521<212〉dna〈213>人<220〉<221〉m丄sc一feature<222〉51*7一<223〉n=a,t,c或g<400〉139tgggtgggcactgcagcagcggagaaaggccagctggttgctggaagaagcgggcctt3acacattgcaggsaggagactcagagatggg〈210>140<211>571<212>dma<213>人<220><221〉misc一feature<222〉7—<223〉n=a,t,c或gccatggctggaggcagatgagggcccgggaaagaagagctaagatgaagaaagaggcagatggaaccgcagstc3ccacctgcagaggagacaggctgagggaccgtgcttgctgatgagt3gg33gt3tcagaaggaacttagactg3tatcgaggcggcgagctgagcgctgaggtggcaggagcgccagtgagagagctccaggaaagaagaggtgggagcttgagcggaccanaactgaagcgcaagcctccagcgcctccttgaatggccactgcgtatgaaggttccaactcaiactcgtaagttttggc3a33ggatccaggtt60agaagttgag120ccgtaggatc180cctgcaaaag240tattgasaac300agaagctaag360ggtgatcatt420tcccgttgcc480521<400>140aggggcngcgctggaagcgctaaactctgcgcgagaagaaacattcacaaagattcggaatcaacaaagcctgtccagaatatgtacctgctgatcgtcaggtgcgtgggcccgagagtgtctgagcctcaaagggccgtgcgcstccatatttgccstgtgtctgggccaacgtaatgattaccactttccactgggtgacagcgtgsgcttgtcgccttctgccatcaggagtgggctaaaggaataaggatgaaigatc33333tct3accgacttaggctgggaggggcatttagatacg3agtggttcaagaagcgg3actccagaggaatgtgcctcacc33atacagscagtcacctggccagaaggacttggcggctcccgcaaacccgagaatgcacctcggtgtgcgc3ttataccgaatcagctatatacatgtggatgactctc3gc3c60ttgagcttgt120aagaagggtg180t3c3cc3tc3240gcactcaaag300gacaccaggc360cggtgtgcgg420tttggttacc480gaactaatcg540571<210〉141<211〉531<212>d船<213〉人<彻>141tcgggagccaaatggggaggcccaagaagccctgctgtaggcctttatttgtccagcaac3gctgttagctcagtccatttgtttacaagcacttggccccctcttggagccaccttctg33ggtc3cttctcgcccaccggtsccgtttcttagagtgaccagttggcagtggagtcggtcttcctctc3c3c3gaggggtccc33cctggctccattgcattcctcct3c3c3gtc3cttgcagtgaaccagcctgaaggcttgctgacaaagsgccatttcaccttggcagaccccacctgcttccagtaccagcacctcagacacacactgtttacccatttggtacttctcttcagascctccttgatgacctctcagcagtcagacca3tgggcctccgttttcccatttcaccacaccgtgaacctggtgtt3tttgagggcactctttggagagagaaattgttggtcaggcaggagagaagagtcagtgtttcccttgccstccattcccaactggagtcc60120180240300360420480531<210>142<211><212〉dna<213>人<220><221>misc<222〉410'<223>n=.a,t,c或<彻〉142acctagacagttgtcctgaaasctgctgacagagtggaaggtgggaagagaggcaagggcstttgttgcacaggaaagtgcttgtaaagtaaggtgggtgaccctactggtgcatctgttcgtctcaaggtg33gccc3ttgtgctctctg33gtgatttgagggaggactagsagtcageaagagttaacgtcccscagtgaagaactgagc3gc3gggacccgg3tactgatggsgagcggtaggaggcaitg3ggcaccagt3aagaggggaggtccctgatgaagcaagccccacgagagcggaaaacag3gaagccttgaggcaatttactgagagatagaagtgtggagctacctcggatggggtttcaga3ga3atggaggcggn3tgcacsgtgccttggtagt60agtgcccaga120tttctgaatc180ccttccgtga240cctgggctcc300agaactaatc360ggtgggggcs420gccgagtcca480491<210〉143<211〉515<212>d船<213〉人"00〉143tttccagttgtcaccggccccgggcgtgtgacaaaaattagcagaagaatcactctagcc<210〉1"<211>340<212>dn7v<213>人<400>144tgtgccagtcc3gccc33ccctacaaggccccttctccaccagccttctcgcccaggccatgt33c33gtctattttcca3tt3t3ttatctccttccgctcatgcctgaittgagsccgctgggcatgcgcttgaacctgggcgacagtacaggcctaccatgagcccagcagatcccggccacagtccac3tcacgtaccccatggaaattgttctgtgacaagaaatctttttcctgt33tccc3gatcctggccagtggcgcatgcgggaggcag3ctg3g3ctcac3attttca60taatgtcgtta333tt3ctt120gccatccctacattaatctt3cttttcc3c1803actatgcc3tctactgggc240cattttgggaggcc33ggcsggcggatcat3003catggtgsaaccccgcctc360cctgtagtctcagct3ctcgggsggctgag420sggatgcagtgagccccgatcgcgccactg480tgctc515tcagcagcgaccagcagc3ttaattctctccc3gccccccttccccacagctccttcagc3tgctcccaatccsatcaagcactccagtc3c6l3gttccctttgccagccatcsggccc3tgcgctctcccttccccaagcacatcctgggtcccctgtt60gtccccacac120ccagcctgtc180gatgcagcct240.actggtagtt300340<210〉145<211>630<212>dna<213>人<400〉145tgtaaaaacttgtttttaattttgtataaaataaaggtggtccatgcccacgggggctgt60seqidn0:79是卵巢癌多核苷酸8h(图7b)。seqidn0:80是卵巢癌多核苷酸12e(图8)。seqidn0:81是卵巢癌多核苷酸12h(图9)。seqidn0:82-310是图15a_15eee所示的卵巢癌抗原多核苷酸。seqidn0:311是卵巢癌多核苷酸0772p的全长序列。seqidn0:312是0772p氨基酸序列。seqidn0:313-384是卵巢癌抗原多核苷酸。seqidno:385代表克隆0772p—种形式的cdna序列,命名为21013。seqidno:386代表克隆0772p—种形式的cdna序列,命名为21003。seqidno:387代表克隆0772p—种形式的cdna序列,命名为21008。seqidn0:388是与seqidno:385对应的氨基酸序列seqidno:389是与seqidno:386对应的氨基酸序列。seqidno:390是与seqidn0:387对应的氨基酸序列。seqidn0:391是卵巢癌多核苷酸08e的全长序列。seqidn0:392-393是08e编码的蛋白质序列。seqidno:394-415是与0e8抗体表位对应的肽序列。seqidn0:416-435是用0e8全长开放阅读框架预测的可能的hla-a2lomer结合欣。seqidn0:436-455是用0e8全长开放阅读框架预测的可能的歸-a29mer结合欣。seqidno:456是显示与0772p有同源性的全长genbank序列的截短核苷酸序列。seqidn0:457是显示与0772p有显著同源性的全长genbank序列。seqidn0:458是编码显示与0772p有同源性的全长genbank序列的截短形式的蛋白质。gaggggtggtggggcgaggggcggccaccatccagggccgcggcttcgtctcccasccgcccccaccgcgcctcgttcttcgsgcgtcagggagcgcsgctccgtcctctaccctagcttgccgccggcacctl;tgtcgcgsttsgcaccccattcagcacgttacctgcccccgcgcggccattgctgcttccgtttgtgcgtcggcgcccacgggtccgttcggcgtctccagaggacagatgcggaacgccgctaggcggaasaagccagcaacggt540gaagccgcag600cctcatggtc660agccgcggct720tcagccscgg780820<210〉149<211>501<212〉d船<213〉人<40o>149cagatttttatgctcttcc3tgcttggctttctggctgctttgagctcttctggacatctccgttagagcccactgtgggtcacaggsgctttgc3gtcggctgcatggcgctgggccagcggtcatctcccatagccttgggaagacagaggcttccatggctcsgctctt3tgcctggtcactggggccaggcgcaagagcagattccagagagctcactcctccagcttcctcctctctcttctgttcttgaccctgcgtttcttgcgccttgatgagctttgtteaagecagtctgtccctgatcttccttggatatccdtttg33ctgeatatettgcttatttgcatctcgcagcaaaggtctcgtccttgctggagtcstggcaattgcctggtcaactgctctaagggtgtttctgctagcc60ggctgagaaa120caggtcatag180tstgatctcc240ttcgtt333g30033tc3gcgcc360tccactgggc420taaaggatat480501<210>150<211>511<212〉dna<213〉人<220〉<221>misc—<222〉457,—<223〉festiiirea,t,c或g<幅〉150ctcctcttgggeattctgetacagcaaggcggccagacag3a_tgc3tccacctgctaccgagctgtttgacaggtgcaagcaagatgatct3c3tg3accttgactttgccactggtacag3agtggc3agaagttgggccctgctcaactggtgggggcgacatgggcacasgttgaaagacaatctttgacacatacttgccatggccctggaagtctttgcaggaacgcgcctgcaggtggacttaa3csgcttcgagaaggtggaastgggeggatgttccgggscgstgtgac.attagettgegegatctggntaacaaagtaitctatgaagttgtaagcaacttgacctctctggtcttcttctgcttcgagatctgctggsagaetctgettgaggagasccaa60ctacaggttc120ttttgeatat180gaaagcccag240aagaatcaac300tscsatggga360eggcasgcaa420tgatggcant480511<210〉151<211>566<212〉dna<213>人<>151tcccgaattccaaatcttttttcacaatca.tgggtggcggc3cctct3ggccatgagtgg33gcg3ca3agegecasgstagaaatgeagggaagagatg3agttac3gcaggtggtggtttccatgatgttggawagtgctgatgagacatgsttcgtccgaatgggctggc3t3ggttggaagtgacagacaggaagaaaatgeaatt33cgtgagst;ac3tggatccatccctatggstgaagctaatgcgtsctg3tgectatcattattaagaegegaggesagagggaagaacaaaegggaaagattcaggsggctcctggcgttgcgctttggggaacstcagg60atggaagaac120gaggaacgac180atgsggcgcc240gaeatgegaa300cagaaatttc360ccaccagcas420cagggaggtg480cggggcctgtgggtggacagggtcctagaggaatggggcctggaactccagcaggatatg540gtagagggagagaagagtacgaaggc566<210>152<211>518<212>d隐〈213〉人"00〉152ttcgtgaagatgagaatgtcgatctttigctagsgtccacccctgactggtggcaaagatcgcacttggtctttc3ttgcaccctgactggggga33cagcctgcacctggaagaccatcagaagatggacctgcgcttgactttcctttct3ag3cc3tctggaagatggtgctccgtctccctcgaggt33ggcatcccgcaccctgtcgggggggtgt3ctctcg33gggaaggcatc3cgc3ccctgcagaggtgggggsgcccsgtticctgatcagtg3ct3c33cctaagtttecttgeattetggagcccgacctcctgacctctgactacaatgeaaatetgacaccatcgcagaggttgaatccagaaagccttttaagggtgacaccat60agca)caggtt120acatccagaa180tcgtgaagac240agaatgtcaa300tetttgetgg360agtccactct420tttcaacaaa480518<210>153<211〉542<212〉dma<213>人<400>153gcgcgggtgcagcgccccgatetgetctgaqacsagegeacgg333tttga.aagctgtctcctgttsccagtgggccactgagtgacagcgcctccttgtgccgttctgctcc.atggagt.ccstgaaggagggecaaaggctttc3asaaigggtgaccgagtg3ggctggcgcctgcattcatcaacgaagggcttcssggatgggaactagsttcaccatctatcag3caicttsgcctgggagggsgg3ctagatggctcgtggtaacccaagcgtgcacccagatgtgcgtgccat3ccaataagct3tgtcaatgtggccag3ctctcttggcttgaggagaatacacctcgggcactgcattgatcaicgastccgtgtatactttggtagcacctgga60cttgttaaac120gggtggcgag180catcaacatt240caaagagatt300caggctcaac360gcggctgtcc420tacctatgt3480atcgctgatc540542<210>154<211〉411<212>dma<213>人<細>154aattctttatctccctctccgcc3cg3ggggctgtggctgcagctgtggggccaggggga3tcccctc3ccccctgccsggggcaigcagcagaagcatacaictcccagccaaac七catctcccsccccttggaaggctgctgccacaggcttgtagaagctcctcaagccsgccscsgtgcccagatgtgtcctccctataaggccagtccggaggacacccagggcatgccagaccatgaagggaatggtggtgagcaccagcatcagaagagctcagagcggtgaggggtaggcagcc60aaaatgagsa120agtcagtgcat180cctgcagcca240aggcagaggc300gacagaacag360a411<210〉155<211>421<212>dna<213〉人<220><221〉misc—<222>173—fe3ture<223>a,t,c或g〈400〉155tgstgaatct3ctggttcccagggcaagaatgactggctactcccacgaaccccsgagctctgaagtgccgggtgggctgcgtgatcgggcgggatgccatggttsatatctcaagctcctgctggcatcgcagtagcccaaggagaatcttacagatggcgccagatcc3tatgtsg3ttttctgtcsgctctcccccactcgg33cttgcaccaaccgtctgatcccaatatattttaggtggggggttgcttsct33gctcttctctctcggsta3ccggggcgtctcccc3ggcctgcagtgacattcaagcctgttacattccctggggstcccs60c3gctgc3ag120cangcaggca180tgcccctgcc240tcccagsgag300cctgtcacct360tccccstagc420421<210〉156<211>670<212〉d船<213>人<400>156agcggagctcaactccagcgacacaggtggtacctgaaggtcc3cc3agactactgagcaatcctcaaccacttcgtcggcctcctgcagatcttttcccttcctgtaccgtttggtctacctcccctggactgggtaactgggacagacttgatggtgatccgcttcctatgaagagtgggctsggcggtccctggtgctcctccccsctggctacaaccactgacatt3ggtgtcatcggttgtcagcgaaagtgatcggstggc3ttggggaagctc3tcctccttcattgttctggtcattggaat3gcttgctttcc3cac3cgccaggtgsaggcgcagtgtcaatttccagtgctgggcgagggtccgtatggctggaagcctcttccctggc3tttcctttttgttgtaccgcsggctcaggtgcgggacaccggggggcatagcacctggaatcgggaagcaccttgatgagaagcaggcaccttggctgtgtttttcctttctggggg.agtctttcaatacatcgagcag60ctacctggat120gtgctctgtg180gcctatcacc240cacgggcgtc300gcagctcaag360gggccggtgg420g3c3c33gat480ttaggtttcc540ggtccccacc600aaaagaagct660670<210〉157<211〉421<212>dna<213>人<400>157ggttcacagcttagc3gctcaag3atcgagatttacacggg3c33gt3tgtccgtggagaaaasctcaggactgctgcttgttctccggtttgaaatcsagg3aggctccccctggagcgacgctgcagacagtggatttgtgtgttgccttttagtgcctgatgtggagaascctcgaccttaaaggtcaattctcatcc3tc3act3tggccaggaatatgtttgaaccctgaagtttaaaatggctgatgtgtgaggctggccgacccatgcttcggtccaggctcaatgaaatggattaaggaaatatgatttgctatgccctctgtccacagtgcatgtcttggacaaggctatc60ggagagcaaa120gatgtgcttc180ggcagctgct240cagtaacctg300agatcagttg360gacctcttgg420421<210>.158<212>dna<213>人<400〉158tcgtagccatgttccstgcctcatcsacgggcassgaggttcctctgctgatc3cttcc3ttttctgcttaattggtgaatgatggtgcgtgtgacaaagtgtactctcccccctggcttctttgg3g3aatagaacctcatttggagcaaggagagata3ctgcccagcgtgacgcc3c33tccggtagttaccagagctcggcatgcctcggaggggctctgactgctcggagccggagtggtgttctcgtgcagccctccctgtccgaattgtcgttg60ggacatcttg120gccatacagg180gatgcacagt240cagatagaag300321<210>159<211〉596<212>dma<213〉人<4o0〉159tggcacactgcttttgsgtggggaatj:catcttcaagttgactg3t3agaaaatgagacttgtgtgtgtgttgaaattacgvctgtataactt3333ttg<210>160<211>515<212〉dna<213>人<40o〉160gggggtaggccagtgtcagatgggtgggtttggssctggagagatgcccaagccgcacgcgtctgagtccacagctccattaaggggcgc<210>161<211>936<212>dma<213>人<400>161tastttcttaatccacatcaapc3cgcccaaaaattgatcaaccgaatctccactgcccacttattttgactcttcaactaggtgtttecccagttgtgatccactatgctccacgtccaaataatcggtgaatcttcgtctgaagttgt<210>162ctcttaagaaactatgawgatctgagatttttttgtgtatgtttttgact60gtaatcatatgtgtctttatagatgtacatacctccttgcacaaatggag120tttcatcactgggagtgtccttagtgtataaaa&catgctggtatatgg180taaaaatgaaagtgactttaaaagaaaatsggggatggtccaggatctcc240ctgtttttaagtaacttaaggacctttgggtctacaagtatatgtgaaaa300tactgggtgaggaaattcattgtttaaagatggtcgtgtgtgtgtgtgtg360ttgtgttgtgttttgttttttaagggagggaatttattatttaccgttgc420tgkgtaaatatatgtytgataatgatttgctytttgvcmactaaaattag480gtwctaoratgcmtccctgggkgttgatyttccmagatattgatgatamcc540taaccygcctttttccctttgctytcruattaaagtctattcmaaag596tctttattagacggttattgctgtactacagggtcagagtgcagtgtaag60ggcccgcgttcagcccaagaatgtggattttctctccctattgatcacag120tcttcagaaaagccccagaggcagggaccagt'gagctccaaggttagaag180aggcttcagtcscatgctgcttccacgcttccaggctgggcagc33ggag240tgacgtgccaggtctccccatctgacaccagtgaagtctggtaggacagc300ctgcctctgccaggaggecaatcatggtaggeagcattgeagggtcagag360ggaataggagcaggggcaggtccctgcggagaggcacttctggcctgaag420tgagcccctgcagtacaggygtagtgccttggaccaagcccacagcctgg480ctgccagggccacggccaggaggca515gtcgtttggaatccttaagcatgeaaaagetttgaacagaagggttcaca60ggttgtcttatggcatccagttaagecagagctgggaatgcctctgggtc120ggagcagaagcacttgacttgtcggtcctgctgccacggtttgggcgccc180cgtccacctcgtcctcccctgccgccacgtcctgggcggccaaggtctcc240tccagctgagacgttatatcatttgctggcttccggaaatgatggtccat300tcagcatgagcctcttcactctttgatttatgaagaacaaatcccttctt360tcagcaccttcatttggtttteggatattaaattctacttttgcccggtc420atagccttccactcatccaaagtcatctcttttggaccctcctcttttac480tcattctccttattttcagtgtctgccactggatgatgttcttcaccttc540tcagtcacatttgattgatccaagtcagttaattegtetttgacagttcc600gatccgctacctccacgtttgtcctcgtgcttcaggccagatctstcact660ctatcaaattcacgtttgccacgagaatcaaatccatctcctcggcccat720cggccccctcgacctcttccaagaccaccacgacctcgaataggtcggtc780ctatcaactgaaaattcgeetccttcacccttttcttcaagtggcttttc840tcacgaggtggtcgcctttctggtcttctatcaattattttcccttcacc900tgatcaggtcttcttccaactcgtgc936<211>950<212>dna<213〉人<400〉162aagcggstggacctgagtc3gccgastcct.agccccttcccttgggcctgcgacatcagtgacagacggaagcagcagaccatcaaggctacgggaggccgcgaagatgaagtttggctgcctctccttccggcagccttatgctggcttggaatcaagactgtggagacgcgctggcgtcctctgctgagcagccagcgatcgccgtccaicattgctcscagggactgggaaggcgatgcctgtcgggagagagactcgggatgactcctgctcagattcaggccttgctcaggaaaggggtcgaggagtgatagcgggactcgttgacatfggggaaactttgcaatgttsactcccgatgaggttgtggaactagaaaatcaagctgcactgaccaaaagt3cctgactgtgatttcaaaccccaggtggttactggagcccataccggcaaggatgtattccaggtagacatcccagagcacctgatccctttgggtgacaagtgtgggctcctgaaaggaatgttccrgagaaaccagctaaatccaatttgccatcgtgacgcagacctgtataaattaggttaaagatgaatttggagagtcccacccactaagcact^tgcatgtaaacaggttcctttgctaagtagggggtggggctttccttgtgtgatgcctccttaggcacacaggcgtactttgaccttagggtagaaggcaaagctgccagtaaatgtctcagcattttggtcctgctagtttctggattgtacaaataaatgtgttgtagatga<210〉163<211〉475<212>dna<213>人ctgtggtgct60cggggcgctt120tgtcttaaat180g33ctgtacc240gctgctggtg300ggaaaagttt360ccccgasgsc420cctgaagcag480taggaaagga540gcatgaagtg600atggcacctt660tccsctgctt720cagatgaagg"780aatgtctcaa840ttgctgctaa900950<220><221〉misc—feature<222〉301,—317,331,458,<223>n=a,t,c或g464,470<咖>163tcgaigcggcctctccggctgccaggcaggtacacctgtggggagggctttngacggtgagtcttggcattcgtggctcac<210>164<211>476<212〉dma<213>人<400〉164agcgtggtcgccctgaggtcgccgcgggagcc3ggactggccccatcgagcctgcccccaaggcttctatgcccgggcsgcccattgctccsggctgaccttctcggggcgttggag3ccgacgctnaccatgcacctccgtccaccaccgtgtcggagttcccactccatggttcttggtgccctttggttgcacttgtacscggtacgacgccgtccaaicgc3tgt33cggccgaggtgsgcagtacsctgaatggcaaaaaccatcttcccgggaggcccagcgacacacgcctcccccagc3cgggcggcgatgtctcaitctcctcctttggaigstactccttgccngctggtgt3cgt3cc33ttcctca3snctaggcgtggtcgctgggatagcc^iggatgggggttttctcgattca3cc3gctgctcctccgaacttgacc'cggncgcgarictg3ggtt3cggtacgtgga3c3gc3cgtaaggagtacaacc333gcc33agatgaccaatcgcccgtgggtgctggactttgtsgttgt60aagcctttga120ggcagggtgt180atgggggctg240tcctggtgca300cgcggctttg360tcagggtctt420cacgc475atgcgtggtgcggcgtggagccgtgtggtcgtgcaaggtcagggcagcccgaaccaggtcccgacacctggtggacgtgagtgcataatgagcgtcctcacgagaiaicc3c3gcctgacctcaatgggcagccgggcggccgccacgaaga60ccaagscaaa120ccgtcctgca180ccctcccagc240aggtgtacac300gcctggtcaa360ccgg3ga3c3420gctcga476<210〉165<211>256<212>dna<213〉人<220><221>misc<222〉10,:<223>n=,<400〉165agcgtggttngcsacatggaactggtacatccgatggattccgggcggric249cggccgaggtgactggtgagcagcaaigaacqcsgttcgsggctcg3cccaaccaaggctgcancctggatgccatcaaagtcttctacctgcgtgtaccccactcagcccagtgtggcccagaagacccaaggacaagaggcatgtctggttcggcgagagcatgatatggcggccagggctccgaccctgccgatgtggacctgc60120180240256<210〉166<211〉332<212〉d船<213>人<400>166agcgtggtcgcactctgactgccatcaaagagtgtggcccttcggcgagagccg3tgtggcggccgaggtggaagsgtggtcttctgcaaagaagaactggcstgsccgaacctgcccggcai3gaaccccagagtactggcatggagacttggattccsggcggccgctcgcccgcscctattgaccccaiggtgagacctttcgagtatggccgtgeiccta_cca_a_ggctggcgtgtacccgcggccagggc33g3tgtgc60caacctggat120cactcagccc180gcatgtctgg240ctccgaccct300332<210〉167<211>332<212〉dna〈213>人<220〉<221>misc—feature<222>77,i09,136,184,<223〉n-a,t,c或g198<400〉167tcgagcggtcaactggaatcttgctgatgtcc3ntctccaatccagt3ctgcggggttctgcccgggcagcatcggncataccagntctttgttgcanaactccactctttgacctcggtgtccacatcggctctcgccgctgggccacagactttgatgccagacagagcgcg3cc3cggcagggtcggaaccagacatctgggctgaggcatccaggttggcacatctctagccctggccgcctcttgnctggggt3cactgcagccttgtgsggtcacggccatactcgcttggggttcgcaggtctcagttggggtcagcaggtgcgg60120180240300332<210〉<211〉<212><213>168276人<220><221><222〉<223>misc一feature"72,百4n-a,t,c或g<400〉168tcgagcggccgcccgggcaggtcctcctcagagcggtagctgttcttattgccccggcag60cctccatagatnaagttattgcangagttcctctccacgtcaaagtaccagcgtgggaag120gatgcacggcaaggcccagtgactgcgttggcggtgcagtattcttcatagttgaacata180tcgctggagtggacttcagaatcctgccttctgggagcacttgggacagaggaatccgct240gcattcctgctggtggacctcggccgcgaccacgct276<210〉169、<211〉276、〈212〉dna'<213>人'<400〉169agcgtggtcgtccc3g3aggcaccgcca3cggagaggaaccggccgaggtcaggattctggcagtcactgtcctgcaataccaccsgcagaag3cc3ctcggccttgccgacttcatctagaatgcagcgcagcgatatgtgcatccttctggaggctgcgattcctctgtcccaagtgcttcaactatgaagaatactgccacgctggtactttgacgtcggggcaataagaacagctaccgctctgaggaggacctgcccgggcggccgctcga60120180240276<210>170<211〉332<212>dna<213〉人<220〉<221〉raise<222>294■<223〉nfeaturea,t,c或g<400>170tcgagcggccaactggaatcttgctgatgtcc3gtctcc33tccagt3ctgcggggttctgcccgggcagcateggtcataccagttctttgttgcagaactccsctctttgacctcggcgtccacatcggctctcgccgctgggccacagactttgatgccsgccagsacgcgaccacggeagggteggaaccagscstctgggctgngtggcacatctcta^gccctggccgcctcttgtctggggtacactgcagccttgtgaggtcacggccatactcgcttggggttcgcaggtctc3gttggggtcagcangtgcgg60120180240300332<210>171<211>333<212>dna<213>人<400>jl71agcgtggtcgccactctggctgccatcsaacagtgtggccgeteggegsgtgccgatgtgeggecgaggttggaagagtgg^:cttctgcacagaagaactagcatgaccggacctgcccggagagtactgggt3cstc3gatggattccaggcggccgctcgcccgcaccgattgacccctggtgagaccc33g33ccccgttcgagtatcgsitgccgtgacctgcgtgtaccaaggacaagaggcggc.caggtcaagatgtggcascctggacc3ctc3g、ccggcatgtctggctccgaccc60120180240300333<210>172<211〉527<212〉dna、<213>人<220〉<221>misc—feature<222〉化了25,140,148,220,229,291,388,<223〉n=a,t,c或g456
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<211>372<212>dma<213〉人<220〉<221>misc一feature<222〉247一<223〉n=a,t,c或g<4qo〉175agcgtggtcgctgaaagaccaacgaaggcttatgccgttgtgcttangctggtgtg3actgcggccgctccggccgaggtsgcagsggcatgaaccaaccg3gatgagtgttggaagtggacaagattggg3cctcaccagataaggttcggtacggatgacggaacgaatgagagaagtggggt3ccscctgaagaggttgtcgtgctttgtctgaatcagtgtgattcatg3ccgtcaggacaacatcatttaccgtggg3cccct3c3cgctttaaactctagatggtgagtggaggca60c33ctctgtc120agtttcccat180gttgtgccag240ccatgacaat300acctgcccgg360372<210>176<211〉372<2〗2>d船<213>人<220〉<221〉misc—feature<222〉251—<223>n-a,t,c或g<權〉176tcgagcggccgtagttcaca3aagcctaagtccaacggcacaagccttcgctggtctttccgcgaccacggcccgggcagccattgtcatc3ctggc3cantgacagagtagtgcctccactgtccsttttcggcaccatctctgtgt3gggtgcccscggtetatgatgtttccctgacggag3tg33tc3gectgatteagtcaaagcacaacaacctctgtaggtggtatcccacttctcatctgsaatgaeattegttgagtcatccgtcccg33cctcctctggtgsctccaatctt60gaccacttcc120cccactcatc180taggttggtt240tatgectctg300ggacctcggc360372<210〉177<211〉269<212>dna<213>人<220〉<221>raise—feature<222>94,^25<223〉n-a,t,c或g<400〉1"agcgtggccgcggccgaggtccattggctgtctcagccttggttctccagcta3tggtg3cccttcttggtgggctgacattctccagagtcaaagtgtccttaagagcatagacactcaatacaaccacggaatgacctgtcaggaac<210>178〈211〉529<212〉dma<213>人gaaeggcateaacttggaagccagtgatcg60tggnggtctcagtagcatctgtcacacgag120tggtgacaacaccctgagctggtctgcttg180cttcatatttggcgnccaccataagtcctg240269<400〉178tcgsgcggccccttgcacgac3cca3ctg3cacccsatgtcggccaccaactcagggtgt3tgct3ctgsgcccgggcagtgatatggagcctga3gttctcagctcactastcasccttatatgaagtgtgtcaccactgaccaccatctgccgttccagtcctcagacagccagccccactcaggtcaggatatcgaggctcctgacaagtgtctatgctggagaatgsccattagctgccaatggaccgggttctgatg3ttgg33ccacccacasgtgcgggtgacgetcatccgtctcttaaggatcsgcccdccctcggccgcggtacacagtcccagtcceicacctgagcgccccccaaggagggttgtatcacactttgacaaagaagggctgactgagacg3cc3cgcttagtgtggttg60gct3ttcctg120cagtggacac180aagaceggae240ggacttatgg300agcagaccag360cgtgtgacag420atcactggct480529<210〉179<212>dma<213>人<220><221>misc<222〉64<223>n=<400〉1793gcgtggtcgtagntcttctttctcattcttcctcatcccgggaatteggtccaagtggatggcagg3agggggctgggcfeaturea,t,c或geggecgaggtcgaagtcccgcatggatctttctcstscagtcagctcagagcttgtggccagtcgaaggtagacctgcccctggccgascggccagcagccttcacccgcggtg3cc3gggtccaggesacttcttggtgcttgttgtcagggcggccgctgccagtgtatecaeggggtagettctgetscgttcttgaggggggatgtccctccaaggttgetgeacatcgacagggaagatggtctcctgctctcagtcaggcc3gtcccgatttgeaaggtgcactttgtccttctcaaagtacatgtta60ctccaggcgc120aaggttgttg180catgegcagg240cccgstgtag300ggcaaagaag360ctcgccaatg420454<210>180<211>454<212>dma<213>人<220><221〉misc—feature<222>55,;99,317,332,<223>n-a,t,cdma<213>人<220><221〉misc—feature〈222>8,47,60,67<223>n=a,t,c或g<糊〉181agcgtggntgcggacgacgcccacaaagccattgtatgtagttttanttcagctgcaaan603ataccnccagcatccacctta_ctaa_cca'gcstatgcagaca102<210〉182<211〉337<212>d肌<213>人<220〉<221〉misc<222〉169/<223>n=<4o0〉182tcgagcggtcggtctggcacggatagtatgggcgctggcttgcatatacttacastggctfeature195,253,a,t,c或g314gcccgggcagcctgagcsgccsgcscggttggtangggttggntagtgagttgnggscctgtctgggcggccagcgaggactgagtctgtgattacaggggcgagcctggcggccgcgacatagcaccggcttggtcttagggatagctgctgggaacagcgctcttcttcacgcttgcatattttggttg3gc33tccatgaagnactcgt3c3cttgcgctga_gcgaatggatga60ttggctagga120acctgaagga180tgccattctc240taaagctaca300337<210〉183<211〉374<212〉dma<213>人<400>183tcgagcggccgtsgttcacatccaacggcacaaigccttcggctggtctttgccgcgaccagcccgggcagccattgtcatcsctggcacataatgggaaacaagtgcctccgctgtccattttcgacaccatctacagtttaaactgtgtagggttgcccacggcactatgatgtccctgscggagatgaatcagcctgattcagtcaaagcacta3c3acctcttgt3ggtggtcccacttctgacattcgttg3gtc3tccgttcccgaacccacctctggtctccaatctt60gaccacttcc120cccactcatc180taggttggtt240ttatgcctct300gaggacctcg360374<210>184<211〉375<212>dna<213〉人;<220><221〉misc—feature<222>30,"174,248,285,306,332,345,368<223>n-a,t,c或g<400>184agcgtggtttactgaaagaccaacgaaggcttatgccgttgtgcttangctggtgngaacgggcggcncggcggccgaggcagcagaggcttgaaccaacggagatgagttttggaagtgtacaagattgctcgatcctcaccanataa_ggttcgct3cggatg3gggaacgaatgtcstttcaggagagaagtgaggtgccaccggaagaggttctcgtgctttgtctgaatcaatgtgattcagnaccgtcagtacaacatcagttaccgtgggacccctacaggctttaaactctanatggtggganaaaattagtggaggc60gcaactctgt120cagnttcccs180tgttgtgcc3240gtcatgacaa300ggacctgccc360375<210〉185<211〉148<212〉dma<213>人<220〉〈221〉misc—feature<222〉28,;6,86<223〉n=a,t,c或g<彻〉185agcgtggtcgcaaataagcgtttgctgagccggccgaggtctggcttnct-gctcangtgattatcctgaaccggctatgcccctgnattggattgccacacggctcacattga3gga333g3ttgatcccatccaggc60tgcatgcaag120148<210〉186<211〉397<212>d肌〈213〉人<220><221〉misc<222>78<223>rfeaturea,t,c或g<400〉186tcgsgcggccactgattaag3cccaccgc3tgagaagctccagacttcaatccttcsgctgcccgggcsgagtggggnggttggtgacctactgtctgtctcaacacacsgaatttaaggcagcaaacttgtccasttgacgggtattagtgcciagctcctcatatcacgtgggcttgccgccatcttccgc3tgc33tgasc33ac3gtggataatattagcagccttcaacagcaaagaggaaccataagctttttactgagccgtctgagaccgcattt3gccttggtccsctgcgaiccc33agtcaacaatggcagaacggcgttcttccacc60tctgagcttt120ctttgatgac180gtggatagtc240gcagcatcac300atcaatcttt360397<210>187<211〉584<212〉dma<213>人<220〉<221〉misc_<222〉145,一feature■286,363,365,425,433,452,462^471,512,53$,540,565,583<2^3〉n=a,t,c或g<御>187tcgagcggccccactccaattccgggagccaggcatcttaatgtggeicattggatgctgggangric3tgcgctgnttgctccgctcctgagggccctctggcccgggcagtgctggccgcacggcttctttgttaacctatgccatcccactcgggasgtctgatctggaganaaagcaaattcactgctggcctatttagtccagsgggttcactcctggtggntactgcctsccsttgtctgcgcatgcttctacagsgtgaccaaggactcaacctgagcancttcgctgtgctgaagaaccttcacaccccagggccgctgtgtsaagggagctcacgtggcaccagatcct:g3agangaaatttcangntgcagagtcgcgaacagtttgctgcttaaccsgatcc3c3g3ttctctcagnggggtttcccgtgaangggtgaaactggtcttgacgnt514,534,gccactggag60caggcagcct120cctctcacgg180cctctgcgct240tttgatgtgg3003c3cccatgg360agaagaacag420nggactgctc480aggngnacan540584<:210〉188<211>579<212〉dma<213〉人<220〉<221〉misc—feature<222>7,1^6,486<223>n-a,t,c或g<400〉188agcgtgngtcagtctgcaacgaaattcctccaggatctcttgccacgcatctcccttgttcacagcgcaactggggtcsagaaggntccatcagcacaaggcggccgsggctcaggctgacttggncactgtagaagtacgcgcag33ctgttgcatgggtggtaggtaggtaaccacaaggagtg33gcccctctggactgctgaataggtagc3gtg3gccttctcagaga±ca_ggcatcccgagccsatgggcaatggttaacataag33gccgtggggccasc3atctgcccggcggcacagagggactc3gg3gccagcagcctgtgacctcccagcatccaccatccacatagcg3tgcctccgctcccggaagtggagtggq;tgccgctcgacacctgtacaggg3gcagtcctcttctttttgggtgttcac3tc333cccgcagaggagacgagaagctggctgcctggatcagtggcaaccttcagacc60c3ttc3ccct120tc33tctctt180cgggaaatgg240actgagtgag300atctgtgtta360gtggtcagcc420tctggttagt480gcsgcaaact540579<210〉189<211〉374<212>dma<213>人〈220><221〉misc—feature<222>41,;80,314,330,<223〉n-a,t,c气g350,353<400>189tcgagcggccgtagttcscaaaagcctaagtccaacggcacaagccttcggctgggctttgccgcgaccagcccgggcagcc3ttgtcatcactggcscataatggga.aattgacagagtcagngcctcccgctgtccattttcggcaccatctacagtttaaactgtgtagggtgcccacggttccctgacggagatgaatcagcctgattcagtcaaagcac33c33cctctltgtaggggggncccacttctcatctgaaatgacattcgttgagtcstccgtccccgaacccacctctggnctccastctt60gaccacttcc120cccactcatc180taggttggtt240ttatgcctct300gangacctcg360374<210>190<211>373<212>dma<213>人<220><221>misc一feature<222>247,—304,306,332,337<223>n-a,t,.c或g<權〉190agcgtggtcgcggccgaggtcctcaccagactgaaagaccagcagaggcataaggctcggaacgaaggcttgaaccaacctacggatgactatgccgttggagatgagtgggaacgaatgtgcttangctttggaagtgggtcatttcagtggngngaactacaagattggagagaagtgggtgccacctacaacatcatagtggaggca60gaagaggttgttaccgtgggcaactctgtc120tcgtgctttgacccctacacagtttcccat180tctgaatcaggctttaaactgttgtgccag240atgtgattcatctagatggtgccatgacaa300gnaccgncagggagaaaatggacctgcccg360ggcggccgct<210>191<211>354<212>dna<213>人<220><221〉misc<222>218,.<223>n=.373299,306,326,a,t,c或g333,337,341<彻〉191agcgtggtcggctgatgtacsgtctccatgccagtactctgggggnttttcggccgaggttcggtcatgccagttcttctttgcsgasgaccactcttccgcggctgcccccacatcggctctcgccgaagggccacsctctttgatggcagccagagtgtctggncttcagggtcggagccagacatgcgggctgagtgatccaggntggcacatcttgggntgtrictcccctggccgcctcttgtcctgggtacacgcca3ccttggtaggtcacggcnatctgctggcstsctcg33tggggttcttaggtctcacctggggtcaataggtgcggncctc360120180240300354<210>192<211>587<212>dna<213>人〕<220><221>misc—feature<222〉276—<223>n=a,t,c或g<400〉192tcgagcggcccccggccctcttcctgccccgatgccaatgcagc3g3tcgcgtgacctcacaagctgcaatgtaccccacacaagaagcaggcagggctc<210>193<211>98<212>dna<213>人gcccgggcagctggacctccagccacctcatggttcgtgaagaacatccgagatgtgccacctggatgcctcagcccagttgtctggttccgaccctgccgtctcgcggttggcccccctagagaaggctccgtgacctcgagcccagagctctgactggatcaasgtctgtggcccaaaggcgagaacagatggggacccgcactggtgggtcctcccacacgatggtggaggtggacaggcagncgcaaagagtggagtctgcaacatsgaaictggtatgaccgatggttggccgcgaatgctggtccgcgctggtttgccgctactacc3ccctc33ag33ccccgcagtsctggatggsgsctggtcatcsgcssgattccagttcsicacgcttgttggtccccgacttcagcccgggctgatgagcctgagcccgcacctgctgaccccaacga^g3cctgcgaaccccaagggagtatggcg60120180240300360420480540587<220><221〉misc<222>8,9;<223>rfeature33,58,a,t,c或g71,90<權〉193agcgtggnngcggccgaggtataaiatatccatgaagctgtncaaagatctcagggtggan<210〉194<211〉240agnccatatcctccctccacacgctganag6098<212〉d船<213>人<40g>194tcgagcggccgcccgggcaggtccttcagagggctccaacttgcagacggcctgttgtggggaagacctgggggaaaacaccatggttttctctcagcgtgcggagggaggctctggactcttggactgtgtcacactgccaggcttcca60gacagtctctgtaatcgcgaaagcaaccat120atccaccctgagatctttgaacaacttcat180ggatatttctacctcggccgcgaccacgct240<210〉195<211〉400<212〉d贴<213>人<220〉<221>rnisc—feature<222>22,57,39,105,268,276,302,323,331,335,347,351371,373<223〉n=a,t,c或g<400〉195cg3gcgggcgasgctscaccgastgacaatatccaacctgacgtgccagggnggtccctcaaccgatatcaccgggcaggatcacaggttgctcggagctcgtttcctggstt3ccggtaggccccgcccnsttttgncatncagactcctacaaccaggcccctgtggtccaiccaicscccatcatcnagtgntgtcccsttggccttca33tccananscactgactaccatcgacgcccaattccttgnaggntactaaccatcaagctccactgccactggtatcatctgggcctccttactgrigcccagatgtcag60tgc3c3cctt120ttgatgcacc180ggcagccgcc240tccc3gag3a300ngcaaccggc360400<210><211〉<212〉<213〉196人<220〉<221〉<222〉<223>misc_feature19,百3,168,252,271,n=a,t,c或g292,43.0<400〉196agcgtggttcaactgtaaggtcctggaatgcttccsatcatcgggtcccgaccscttctcgcacgtggcggttggatggntgtcattcaagcggccganggttcttcstcgggcccatgaggggctcgctgntccsggcctgggaggagagctgccatgagc3tca_atggggtgtcctgtcagaagngccaacagatggttgtccttctg3tt3cccaggcttctaccsgcaaggtggca_ctggggatgacatgtgagagagagttcttc3gggncctctgtgatcatacttgagaattggggtcagtggaggc."cgtcgatgactagaagttccaggaaccctg603a3tgatgt3ctcsgaagtg120cttcttgncctgtctttttc180240caccagggcggngccgaggg300tg3tgta3ccggt33tcctg360gtggtggccaggaaacgcag420cacagggggagctccgacat494<210>197<211>118<212>dna<213>人<220><221>raisefeature<222>8,71,96<223〉n-a,t,c或g<400>197agcgtggncgcggccgaggtgcagcgcgggctgtgccaccttctgctctctgcccaacga60taaggagggtncctgcccccaggagaacattaactntccccagctcggcctctgccgg118<210>198<211〉403<212〉dma<213>人<220><221〉misc—feature<222〉41,"^3,98,195,350<223〉n=a,t,c或g<400>198tcgagcggccgggagsagctgggctggsacgtggctggagcstttcatctg33ggtggc3gcccgggcsggtggtcagcccagscgcaggctc311333ttggccaggacattaaitgttcacsgcccgcgcgttttttttggcc3ggcagaggg3gtgacactggctgtcccctgggggcatgcacctcggctgaaagtggtacagagncccaggacacctacctggcactgga3ccctccccgcgscc3cntacttt.attcctcactgcttcccacagccggtcccg3c3ttatcattgngetgagggcsggt120cagcctggtg180attgcggcgg240gaagcccgag300gcagagagca360403<210〉199<211〉167<212>dna<213>人<220〉<221〉miscfeature<222>92,10*7<223〉n=a,t,c氛g<400〉199tcgagcggccgcccgggcagggagcaaggttgatttcttttatccagtgagctgaacattgtccaccataagtcctgatacaaccacggatgagctgtca60cattggtccggncttctccttgggggncacccgcactcga120gggtggcgtccactgggcgctcaggct167<210>200<211〉252<212〉dna<213〉人<220〉<221〉misc—feature<222〉210,226,227,230,236<223〉n=aft,c或g<400>200tcgagcggttcgcccgggcaggtccaccacgccacgtgccaggattaccggctacatcatagaagcggtccctcggccccgccctggtgtgggaaccgaatataca.atttatgtcattgntgattggaaggaacccaattccttgctggtatcatggcagcc60caagtatgagaagcctgggtctcctcccag120cacagaggctactattactggcctggaacc180cctgaagaataatcarmaanagcgancccc240252<210>201<211>91<212〉dna<213>人<4o0>201agcgtggtcgcggccgaggttgtacaagcttttttttttttttttttttttttttttttt60ttttttttttttttttttttttttttttttt91<210〉202<211〉368<212>dma<213>人<220〉<221〉misc—feature<222〉9,3&<223〉n=a,t,c或g<4o0〉202tcgagcggncgcccgggcaggtctgccaacgtccgtgtgcggggaggtaacaagaaatactcctggggctcagagtgttgtactcgtaaatctaataacgagctggttcgtsccaagaccagcacaccgtaccgacagtggtacgagtccggagccaagctgactcctgaggaagaagagaccaagattggcccccgccgcatccacaca60cgtgccctgaggttggscgtggggaatttc120acaaggatcatcgatgttgtctacaatgca180ctggtgaagaattgcatcgtgctcatcgac240cactatgcgctgcccctgggccgcaagaag300attttaaacaaaaaacgatctaanaaaaaa360368<210>203<211〉340<212〉dma<213>人<4o0>203agcgtggtcgcggccgaggtgaaatggtatcagtgttgggcaacaaatgatctttgaggaaacggccacccccataaggcataggccaagtctctctcagacsaccstctcstgggccccatgtcatcctgttggcactgatgaagaacccagtgccactctgacaggacctgcccgggctcagcttcctggcacttctggtcagcaacc60acatggttttaggcggaccacaccgcccac120accatacccgccgaatgtaggacaagaagc180attccaggacacttctgagtacatcatttc240cttscagttcagggttcctggaacttctac300ggccgctcg3340<210〉204<211〉341<212>dma<213>人<400>204tcgagcggccgcccgggcaggtcctgtcaggaactgtaagggttcttcatcagtgccaacgtcctggaatggggcccatgagatggttgtcgggtatggtcttggcctatgccttatgggaaaaccatgttcctcaaagatcatttgttgaggaagctgaataccatttcacctcggccgagtggcactggtagaagttccaggaaccct60aggatgacatgaaatgatgtactcagaagt120ctgagagagagcttcttgtcctacattcgg180ggtggccgttgtgggcggtgtggtccgcct240cccaacactgggttgctgaccagaagtgcc300cgsccacgct3341<210〉205<211〉770<212>dna<213>人<221〉misc—feature<222〉529,—591,623,626,746,749,759,762,766<223〉n-a,t,c或g629,630,656,702,709,712,717,743,<400〉205tcgagcggcctcgtaccactttggtacgaacgagtacaacttcttgttacaggaagaagaggaaaaagaattgcgtgcstgcaasgaagtatccaaagggttattggtgcgctttggcagcggaccccttgcccgggcsggtcggtacggccagctcgttactctgsgccctccccgcacgattttaaactgccaaaatccgcttcaaggggagttctatgagtttcag3agggcttgcaccttttctttaaccgattccgtctcccttctgtgctgtcgattagatgcaccaggagaaaacggactgtgagcagtctccccgggscagtcttaagaaaaccagtgcaatcantangannggttttgccaacnccnggngttgcggcccaatgagcacgattccccacgttggatgcggctggsggsgc3gtg3ccgagctcagggcccaggctgggtctgcgttctangggggcagcgctgcaattcttcatcg3tgstccaacctcsggggggcc33gtc3g33g333gttcc3gcaigagatggctatgaatggtgng3ttg3t3ctgtggggcttgggncccncttgatagtgggaccaccsgggtcccttgtttt3ggcacggtatctgactcctgtatgatgaaaggcssgcttcgtgctagaggtcttcaactantggccaaatattggnacaaanacctnggg60120180240300360420480540600660720770<210>206<211>810<212>d船<213>人<220><221>misc—<222〉574,—feature621,625,636,668,673,704,728,743,767,772,786,789,807,809,810<223〉n=a,t,c或g<400>206agcgtggtcgaggctgccaacctgcaccsatccctttggaaactctttgc3tgc3cgc33ttctttttcctcttcttcctggtgtactcggtcggacccaacaggggnacggcggccritctgcatntana3g3ctgttcctaaatttggcttagctgagacctct3gc3cgaagcttgcctttcatcatacaggagtcagataccgtgcctaaaacaaggaagaacctgggantcccactgaaagcccaaggggcccattctgctgcttcaataccagcaagcsgtatcac3c3ccattcatagccatctctgctggaactttcttctgacttggcccccctg3ggttggaitcstcgatgatgcgcttgcttntggaaaaccccctnsnnagcgasgggtccsg33cc3gatgtctctgctgggccctgsgctcggtcactgctcctccaatttttttaggccgcatccaacgtggggaagtgnctacaagatcgnctcelccctgggccg33tccatc3cttctggcstsccactcctactgattgcactttttcctaagactgtcccggggagactgctatcgttttttcacagtccgttttctcctggtgcatctaattcgacatggacactgggnggcaicc33tg3t360tgttgcagca120ggtctgsaac180atag3actcc240ccttgaagcg300gattttggca360gtttaaaatc420gtgcggggag480ggctcagagt5403acgsigctgg600accgtacccg6603a3ctgcccg720cngtcgsgca780810<210〉207<211>257<212>dna<213>人<權〉207tcgagcggcctctgcaacatagaactggtagcccgggcatggg3g3ctggtcatcsgc33ggtccccaaccgagacctgcgaaccccaaggaaggctgcaatgtaccccacacaagaggcscctgg3tgcctcagcccagttgtctggttctgaccgatggattccagttcgagtatggcggccagggctccgaccctgccgatgtggacc240tcggccgcgaccacgct257<210〉208<211>25"<212>dna<213>人<400〉208agcgtggtcgctggaatccagctgatgtacagtctccatgcccgggcggccggccgaggt七cggtcatgccsgttcttctttgcagaagacgctcgaccacatcggctctcgccgaagggccacactctttgstggcsgggtcggagccagacatgcgggctgagtgatccaggttgccctggccgcctcttgtcctgggtacacgccagccttggtcatactcgaa60tggggttctt1203ggtctc3cc180tggggacctg240257<210>209<211〉747<212>dma<213>人<220〉<221〉misc—feature<222〉453,—538,540,542,546,693,711,723,724,731,747<223〉n=a,t,c或g554,556,598,659,670,679,689,<400>209tcgsgcggccccacgtgccagaagtggtccggasccgaatattggaaggacatggaccagcctgggtatggttgggcaacgcc3cccccatntcanacactctgtggcactacsggactncgnncactgggcccgggcagggattaccggctcggccccgatscaatttaagatcttggaacactggaaasaatgatcttt3aggcatagcatntnatggttgatgaaaaggccggacncngaaaatggcgtcc3cc3c3ctacatcatcccctggtgtctgtcattgcccgagcttccctgttccttcctggtattcagtgsggsacstgccsagaccagccccattcccccttacagtcttaagccnatactgtncccaattcctacagaggctactgaagaatacaactggtaascagttcaaacttcctggcaggntttaggct3cccgccgaiaggacacttctcagggttctttncaccctgtgctggtstcsgcctgggtcctattactggatcagaagagcccttccacsagacccctttcttctggtcaggaccscsccatgtag.gacatgsgtscstcgg己actttt3gggcgttctaatggcsgccg60tcctcccaga120cctggaaccg180cgsgcccctg240ccccaatctt300cgtcacccac360gcaacccagt420gcccacaacg480agaagctntn540atttatgnca600ccaggcctnt660nggtcccact720747<210>210<211〉872<212>dma<213>人<220〉,<221〉misc一feature<222>165,—174,181,256,260,269,271,277,286,289,294,298,300,301,303,308,311,321,325,328,329,333,338,342,3化349,351,357,359,364,366,379,385,395,396,397,術,408,410,414,415,429,431,434,435,440,443<223>n-a,t,c或g<221>misc一feature<222>4",—"6,"7,"8,449,450,451,464,470,472,475,479,483,484,485,488,494,"6,497,504,508,509,511,513,517,522,524,526,532,533,542,543,553,559,566,567,571,572,578,582,588,591,594,595,59(5,600,606<223〉n=a,t,c或g<221>misc—feature<222〉612,—614,617,618,664,666,671,673,678,707,708,714,719,721,770,778,779,781,782,<223〉n=a,t,c或g<221〉misc一feature<222〉815,—820,827,828,872<223>n=a,t,c或g629,6"9,723,785,630,681,726,791,631,688,741,802,652,690,807,654,691z761,808,655,698,762,812661,663,706,769,838,841,8化851,857,864,866,869,<400>210agcgtggtcggcgttac333catc3tggagngagggctaataactactscntncttgncccc3n3nttggaaccctatnactnnnaantccnnagctcttcccccnccccncnn3nttccncnctncei3crmttncattantcnctct3ccggccgaggtctcctsggagagtggggccaattccatgaacgtctnaccnntccttgggtcctttaaananttnnattancttnannccttcnttt33riacnaricgrmttncnttccnnctt3ttttcctnatttgaaacnta3t3ntttccactagaggggcttgctgtaaggctgcgagtttgtggatcctgctgtncngaanatrmaatccnccttgatnntnnnnncccncccrmttaatgrmgcctttgacctnnntttcggritnntcatccctttnccacnnctaatnanttnttctgtgtgccgcggagggccggttgtggtgggcctgstgancccccnttt3tngcctnccccttnnncacnctcacccccnciictcntacrmgctctnc3naacctccttntcccatnctnttctttacaanttncctcnattgccc3ggtgctstggtgtctgngaaactccacaatcgtgttcanntnctcntcattntnantncttctritctacnattcctcttcccttccsrmnctrmccccctrmctctacnnttcagagtctct60tgctgcggtt120tccnaggaca180gagaccctgt240catngggntn300nctactngnt360tttrmtcgta420anccnatang480trmcccatt3540ntgrmnaatn600tncrmaaatt660tcantctanc720tctactcrmc780ttattttncg840872<210><211〉<212><213>211517d肌人<220〉<221><222><223>misc462/featurea,t,c或g<400>211tcgsgcggccgggcatggcatatctcatctcttaccagttgagc33c3cgatcetcaggc3cc3c33cctgccctccgc3gcccgggc3gggcggctctgttgggttccagggtcccaggtggcgcacaacgcsgcctttcaagcaagcctctagtggacgtctgccaaggettcccacccastgctcacgcagcatgatgcsgtgtcaacttcatggatggccccsctcctcctaagaactcggncgcg,gagaccctgtcttctgttctgtggtcaggccttcaccttgcgtagtaagtttagccctcttccatgstgatttgtsscgcsccscgctatgctgtgggagatgggggaggggcttctatgcccsgc3t33c3gggtcgtccteggagaccgcagcscananactctgggactggctg60tggtgggcsg120tagggecaat180caccctgtct240tccgctgtgg300tttcccagac360accatagcag420ctggcaatgg480517<210>212<211〉695dma<213〉人<220〉<221>misc—feature<222〉432,476,522,547,<223〉n=a,t,c或g621,624,647,679<4o0>212tcgagcggccccsgacttgagattcacagagggtcaccatccttgsccattctccaaatgatcgcagagaatctctatcctgtgccaaaacaaagcntcaccccgttata<210〉213<211〉804■<212>dma<213〉人<220><221>misc—feature<222〉552,—555,592,624,629,633,658,695,697,698,745,753,755,762,773,786,788,793,795<223〉n-a,t,c或ggcccgggcagcatc3t3tg3ttccagggggttctcccaggtaggsgggcggaaitttctggacggatcctggncataggacataatagtggtcatgtctaagttcaaagtaasacacctnggtctggtccsatcatactgggccsggagsaaataccaggaagtaggagcagttggggcagagtcacagac■tgaccaagatgatgaagcagatatcag3c3nccncc3tc3ggccggacccggatagcctgggagaatagtccaggggeccgggcctggstgttggaggcttct33ttcttacatatttgggggaacatcctgagacttctagttggttcccccttcgagtcctcctctgaggaccctggttgtccctcccttggggtgggcaaacg3tccgtc3ccatggttctgtccttc33c3anccagctccttgggcaaasttgcccnttctactgctactagtagggcattggaataccagccttgaggtat3tt3tgtcgcttccsga_cagcttnctgtcctttttgcsaaggagaaaaagcacccggg<400〉213agcgtggtcgtgatggtgctgatstttagaatcccactatagtcctatgcc3ggstccgtcagaaattccgccctcctaactgggagaaacccctggaattatgatg七cactgccggggggagctgctttttttanancgcggccgaggtatctttgaactcatgstgsgctattttggcaggatagagattctctgcgatatttggagsatggtcaaggatggtgaccctcnggngaatcagtctgggatggcgttcgaaa333gggccacgngnctggggttttatgacgcttttcttttttgtgcaasca3cagg33ggtctggssgcgacataatattgttgtgcagcctcaaggccggtattccagatgccctactagcnagtangagcccgwtcttccncctttgggcccggtgtctcctttttsgggga^gctgctgttg33ggcagaaccatggtgacgstcatttgcccscaccaagggagaggtcctcaaaganggactcgtgcarianntnagngngggggctgaagggcagctscttctcaggatgttccgcctccsscttccaggccctgtcccctggtctattctccccaggctattccnttcacactantacaatta60120180240300360420480540600660695700,702,gggaacaact60tctcstgtct120gctctgcttc180catcttggtc240gtctgtgact300tgccccaacc360gctcctsctc420cctggtattc480tctcctggcc540anatgattca600tggaccanac660ggcggccgtc720ctnggcggcg"780<210>214<211>594<212>d船<213〉人<220><221>misc—feature<222〉452,509,585<223〉n=a,t,c或g<400〉214agcgtggtcgcggccgaggt.ccacatcggcagggtcggagccctggccgccatactcgaa60agtctccatgccagtactctggggttcttggagggtggtggtagcggcca_ccagcgctggggsccsgc3ttcggtcatgccagttcttctttgcagaagaccactcttcccggctgcccttccacctcgaccatcgtgaggaggaccaggcaccaa:gtgctctcgccgsagggccacactctttgatggcagtcagagtgctgggctccgggtcacggtcccttctcttggggaccaanagacccgcgsgccsgacatgcgggctgagtgatccaggttggcscatcttggstgttctcg3cgaaccac3angtggctggggtccaggaa3acctgcccgctcttgtcctgggtacacgccsgccttggtaggtcacggcatctgctggcttggcatcatggcaggaactgggcccgggggccgnccgcttggggttctt120aggtctcacc180tggggtcaat240sggtgcgggc300tcaggctctt360c3gcccggts420gaagtcgaaa480gggsccaacs540cgaa594<210〉215<211〉590<212>d,<213>人<220〉<221〉misc一feature<222〉8,9—<223>n=a,t,c或g<400>215tcgagcgnnccccggccctcttcctgccccgatgccaatgcagcagatcgcgtgacctcacaaggctgcagtgtaccccaggccagggctgcccgggcagctggacctccagccacctcatggttcgtgsagaacstccgagatgtgccaacctggatgcctcagcccagatgtctggttcccaccctgcgtctcgcggttggtccccctagagaaggctccgtgacctcgagcccagagctctgactggcatcaaagtctgtggcccagcggcgagagccgatgtggaccgcactggtgggtcctcccacacgatggtggaggtggacaggcagccgcattctgcaacaaagaactggt3tg3ccg3tgctccggccgcatgctggtccgcgctggtttgccgct3ct3cc3ccctc33agaaccccgcagtactggattggagactggacatcagcaagattcca_gttgaccaccctttgttggtccc60cgacttcagc120ccgggctgat180gagcctgagc.240ccgcacctgc300tgaccccaac360tgagacctgc420gaaccccaag480cgagtatggc540590<210>216<211>801<212>dna<213>人<220><221〉miscfeature<222>2,22,'25,26,328,373,385,440,,473,534,571,572,582,587,589,593,600,605,617,633,642,653,672,681,685,696,699,709,715,717,726,731,739,742,745,758,"769,772,778,780,788,789,791,793,796<223>n=:a,t,c或g<400>216tngagcggccgtgsagatggagggtgctcgacaatggtctgtgcccctgggaggaccgtgccagcacacttggtcatsgcagccggaaagattgcgttgctt33ntgaa3cctttcctcggcccgggcsgtcaccctggatggtttccctggatggattgtgaaaatggattggtgccccggnggccgtttgtttcctgncataaagtgtgctcactgcctccgccnaccgnttacttgagntgnnaacgaaacccggacggaactcctgaagggacagc3ctccaggtctggcccanscactantggatgtgaaattgtaaagccttggcgcttttccacccggggaaanttantgggcctggtcctgcgacctggtgagacttcctggccggtgctcc3aacaggagcctcggccgcgccgagctcggtatccgctcaggtgct33tgrmngggaaacagncggtttgtttggncgnttggtcctcctgagaggagttcttcaaaggctggtgtgaagccgtgggcttacc3cgctaataccaagcttcaatttcacaagtgagctsacntggcntngcngtattgggtcgggttgngggcaaggctg60gttggaccac120attaggggac180ggtgaacctg240cctggtgaga300gcccgaattt360ggcgtastca420cancatacga480ctcncattaa540ccngcttgcn600gcnctttttc660gcgancnggt720
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seqidn0:79是卵巢癌多核苷酸8h(图7b)。seqidn0:80是卵巢癌多核苷酸12e(图8)。seqidn0:81是卵巢癌多核苷酸12h(图9)。seqidn0:82-310是图15a_15eee所示的卵巢癌抗原多核苷酸。seqidn0:311是卵巢癌多核苷酸0772p的全长序列。seqidn0:312是0772p氨基酸序列。seqidn0:313-384是卵巢癌抗原多核苷酸。seqidno:385代表克隆0772p—种形式的cdna序列,命名为21013。seqidno:386代表克隆0772p—种形式的cdna序列,命名为21003。seqidno:387代表克隆0772p—种形式的cdna序列,命名为21008。seqidn0:388是与seqidno:385对应的氨基酸序列seqidno:389是与seqidno:386对应的氨基酸序列。seqidno:390是与seqidn0:387对应的氨基酸序列。seqidn0:391是卵巢癌多核苷酸08e的全长序列。seqidn0:392-393是08e编码的蛋白质序列。seqidno:394-415是与0e8抗体表位对应的肽序列。seqidn0:416-435是用0e8全长开放阅读框架预测的可能的hla-a2lomer结合欣。seqidn0:436-455是用0e8全长开放阅读框架预测的可能的歸-a29mer结合欣。seqidno:456是显示与0772p有同源性的全长genbank序列的截短核苷酸序列。seqidn0:457是显示与0772p有显著同源性的全长genbank序列。seqidn0:458是编码显示与0772p有同源性的全长genbank序列的截短形式的蛋白质。tccagtccaggcccc3tcctctggtgttcttggcttttgggtctcsggccttgsacaaggggtcagg3cg3g3gc33ggtctgggtgcagaagtctgca^cccctgaaggacagcatccaccacctcggcctctggtggct240agagctgaca300gcgaccacgc360361<210>224<211>361<212>dna<213〉人<400〉224agcgtggtcggtgtcagctccagccaccagacagagagcgcctacaccctcc3cc3cc3gcggccgaggttctgtactctagtggatgctgctgtactggggscsgggsccaccggggtggtccttcaggggttgcagscgtctgcaccc33gctgagccagtctctatggtcagcgagggtctgcttattgaccttgct3tcgtcctg3atgctgacccatcaatggtttsgccattc33gcccttgttcc3ggcctgagcccc3333gccggcatcactc3ccc3tcggcctgcccggg3aggatgggg120cctggactgg180gsgctgggcc240agctctgtac300cggccgctcg360361<210〉225<211〉766.<212〉dna<213>人<220><221〉misc一<222>574,_<223><400〉225agcgtggtcgactgtaagggcctggaatggggtatggtctaaccatgttcctgtggaagggttggggaagtcagggcaattgtgacaccag3tg3tg3gngggggnggactatggatcccfeature610,631,a,t,c或g643,657,660,666,688,712,735,747cggccgaggtttcttcatcaggcccatgagtggcctatgcctcaaagatcaccatttccaaacatccaagctcgtctgtcgacataaattgggcggggccccggtaatccctgcccggcgactcngtccacctgtcagaggtgccaacagatggttgtctcttatgggggatttgttgccgtgtcstsccaitctctggtctttttccttcgtatattcgggagggacccttggcacgtgggccgttcr13aacttggnggatggcactggtgagagagagctggccgttgtcaacactgggcsgggtgggtcatgaagattcai3tcaggggtcccggttcctctnttggaariggttgcatgagcccaattcaatgatgtacttcttgtcctgggcggtgtgttgctgaccaggggtgtggactcgctcttcaggccagtaag3gaccagct3tncc3cc33cacacacttgacttttggaaccctga60tcagaagtgt120acattcggcg180gtccgcctaa240gsagtgccag300gtcttttgaa360agggttacca420tgattattct480tagtagcctc540tctc3tactt600ggaaatnggn660gnggccgtac720766<210>22(5<211>364<212〉dma<213>人<400>226tcgagcggcctccacagacaacagttgggtcgagaatgcatcgaacacctagcgtggcttcgctgcccgggcagaggccaggacagccaatctggagtttcctcgctggatgaccgctggctccgtccttgacctcgtttgtsccagacagacatgtgatatcac3gcccasagcactttgtctttttc3gc33ccgttgatgactggcaacatagcacttcaggagaagggggccagtcttgagtgggaaggttagaatggggtgcggacaccggttgt3gatagatgttgagtcagacctcggtaatccgtc60tactgatgca120ctccaggaag130gctgccattg240catgttcagc300gccgcgacca360364<210>227<211>275<212>dna<213>人<400>2273gcgtggtcgggtgaccgtggcccagcaacatgcccaccgcatcccccttcggccgsggtctgtcctacagtcctcaggaccctccagcaacttcggcacccagacctacaccaaggtggacaagagagt:tgagcccaaatgcccsgcscctgsactcctggggggaccgccaaacctgcccgggcggccgctcgctctactccctcagcagcgt60acctgcaacgtagatcacaa120tcttgtgacaaaactcacac180tcagtcttcctcttcccccg240275<210>228<211〉275<212〉dma<213>人<400〉2'28cgsgcggccgcccccaggaggctcsactcttctgggtgccaggactgtagcccgggcaggtttggaagggggatgcggggttcaggtgctgggcacggtgggcatgtgtgcttgtccaccttggtgttgctgggcttgtggaagttgctgg3gggcacggtcaccacgctgacagacctcggccgcgaccacgctgasgaggsagactgacggtc60agttttgtcacaagatttgg120atctacgttgcaggtgtagg180gctgagggagtagagtcctg240275<210〉229<211〉40<212>dma<213>人<220〉<221>raise—<222>1,4:<223>ifesture5,13,15,17,29:a,t,c或g<400>229nggrmggtccggncngricaggaccactcntcttcgaaate40<210>230<211>20b<212〉d肌<213>人<400>230sgcgtggtcgtttgegaate3cc3ggaccteggecgaggtcctcacttgcctcctgcaaatctgttttaaagtcctgagcaatttctegeagaagttcagtggacttctgataaegtctagcccgggcggccgctcgagcaccgatagctgcgctctg60accagacgctggaagggaag120atttcacggagcgccacagt180208<210>231<211〉208<212〉d船<213>人<220〉<221>misc<222〉33<223>nfeaturea,t,c或g<400〉231tcgagcggccgaagtccacttcaggactttasgtgaggacgcccgggcagg3acttctg33333c3g3tcctcggccgcggtcctggtatcttcgcasacttgcgcttccasccacgcttgriggcgctccgtgaaattatcccttccagcgtctggtgcgagcgcagctateggtgettgagaaattgc120tgeaggagge180208〈210>232<211〉332<212〉dna<213>人<400〉232tcgagcggccaactggaatcttgctgatgtccagtctccaatccsgtactgcggggttctgcccgggcsgesteggtcataccagttctttgttgcagaactccactctttgacctcggcgtccacatcggctctcgccgctgggccscagactttgatgccagtcagagcgcgaccacggcagggteggctgggctgaggc3tcc3ggttggcacatctct3gccctggccgcctcttgtctggggtacactgcagccttgtgaggtcacggccatactcg60cttggggttc120gcaggtctca180gttggggtca240geaggtgegg300332<210>233<211>415<212>dna<213〉人<220><221〉misc—feature<222>6,19,21<223〉n=a,t,c或gacccntttnatggatatteggcctcaagstgctgcaacct'gccccactcagg3ggcatgtcgggctccgac<■>233gtgggnttgagccagtgtgccctgccgtgacctgcgtgtaccaaggacaa3tggcggcca<210>234<211>776<212>dna<213>人<220><221>iuisc一feature<222>505,—550,574,750,776<223>n-a,t,c或gnctccgcttgcttagcgtggtgccactctggatgecateacccsgtgtggtggttcggcgcctgccgatggtaccgagcttcgcggccgsactggaagagaagtcttctgcccagaagaaag3gcatg3ctggacctgcccggstccsctggtcaagaactggagagtaccaacatggagctggtacatccgatggattccgggcggccgagtaseggeecccgcccgcatggattgaccactggtgagacagttbgagtctcga601,604,608,612,649,656,657,680,711,60120180240300360415<400>2343gcgtggtcgacttaeggagtctacagctagtcactggccgaaattgacaaagtggctgcggaccaggacggcttgeageeggcegsggtcc3tcagcgggtggagacag33cc3tccc3cttcaagttcccacagtggactgggatgctaaatagcectccttaaacctccccgc33gcgatgeaagtgccctgttacttaaaactgeagtatgtggttcct.gctgtcagtccaggagtgg3gttg3ttageaagecaaaccgatgttcggttacagagggtccagatcaagtgtctstcagtgagatatcactgtgccataccatcactttccattsaaggacaacagt33cc3cc3caaacagaaatgctcagastcttacaggatc60tgggagcaag120tgtgtatgct180ttaccgaaca240cattagtgtc300tcccaaaaat360gactattgaa420casgeggaga480agcgtccggagcgctttggtctggggaactatgggggcaagcggcagctccc333c3ctctcaaaccttttggccttcaagcctgcacaaagaccg<210>63<211〉491<212〉dna<213〉人<400>63gacatgtttgtgcttccagaggttgggggctcaggcttggaacctagaaatgctggtgacagtggcctctggtggggtgacactgtggtc<210〉64<211>511<212〉dma<213〉人<400>64gatggcatgggggacccgccgctgcsgccagggactgctcaggtgcctggtcattaaagcc33ccccctcccagcatctcggtcatctgg<210>65<211〉394<212〉dna<213>人<400〉65taaaaaagtgatgta33ccggcttasctgaggcggggatctggcactcataagctgaaggaagggtcggg<210>66gggaagaagaacctgggctaccgtcctggccttcccmcccccttcccggg420gggcgtggagttggggttgggggggtgggtgggggttcttttttggagtg480tttttcccttcttcaggtcaggggaaagggaatgcccaattcagagagac540gaaggacgggagtggaggagcttctggaactttgcagccgtcatcgggag600taacagcagagagcgtcsccgcttggtatcgaagcacaagcggcataagt660caaagacatggggttggtgacccccgaagcagcatccctgggcacagtta720ggtggagtatgatgatatcagctctgattccgacaccttctccgatgaca780actagaccgaagggagaacgacgaacgtcgtggatcagatcggagcgacc840acatcgtcaccaccagcacaggcgttcccgggacttactaaaagctaaac900906cctgcagggggaggatggggccccggaagcggtacc333caagattggtcaacatattccggaggctcgtgggtttctgaacagctctcaacggtccggatcatgctctggtgctaaggactctcccaggggcctaaggccccttcgcttatgggattagggtcag33tctcctccctggtactgttttgatcagctgcc3c3cagactcagggctccgtcccatcccatccagtgctcacaggctgagacatc3gcgt3gccccstgcgccctcatcctggtgactccaaaggctgatcaaccgctgtcctgttcttta60aggccatgct120gacccgctgc180gtgagaggaa240ccgcatccaa300cactgggctg360ggctgaactg4203atg3gctca480491tcgttgctaatgtgcctgctgggatggagcacttcctcctgtgagcccag60tgtccctggagcttggggcaaggagggaagagtgataccaggaaggtggg120ggggccagagtcagttcagggagtggtcctcggccctcaaagctcctccg180aggagtgatggtgccctggagtttgccccaacttccctggccaccctgga240ctgctccaggcctctaggctgggctgatgggtttctccaggacacaagta300c3ccctctcctcagcttgtcaggccgcacatgtgggacaggctgtgctca360gcctgccctgccctccatcaggaggagccagtggaaccttcggaaagctc420agcagccctcaaaagtcgtcctggggcaagctctggttctcctgactgga480gcttggcctgctctctctcgc511taacaaaggtttatcttac3aatagcgtccctgcsgtttgggggacsggctatcgaccstgagaggcctcttatttagacaagaaagcacatccaa33gtgactgcttgcatcctgctcgagggggctctttgggctatgtttcttcatgaatatttggtgggttt33ggcgggtttgtctctgtggggcagggcagtggtgggcccccagatcataaactaagtaaaactacccagggttccgcccgctggaggaccttcatccaggatgtct60tcagtgactt120tgacgatatt180ggtctgttct240cccttacgtg300cggaactaac360394<210>238<211〉372〈213〉人<400〉238tcgagcggccaaagcctaagtccaa_cggcacaagccttegctggtctttccgcgaccacggcccgggcsgccattgtcatcactggcacattgacagagtagtgcctccactgtccsttttcggcaccatctacagttta3actgtgt3gggtgcccacggtct3tgaitgtttccctgacggagatgaatcagectgstteagtcaaagcacaacaacctctgtatggtggcatcccacttctgaeattegttgagtcatccg■tcccgaacctcctctggtgactccaatctt60gaccacttcc120cccactcatc180tsggttggtt240tatgectctg300ggacctcggc360372<210>239<211>720<212>dma<213〉人<220〉<221〉misc一feature<222>478,*~557,563,5",620,660,663,672,6",684」<223>n=a,t,c或g<400>239tcgagcggccggagcsaggttatccsgtgatgagtgaacttgactctctcaagccttcaaggtccattttcacttgacacatttctgttcgtg3c3gcattaaacttgetgcccgggcagtg3tttctttgctgaacatttcaggtcagtcgcttggatttagtcatttctgggagtggttaatgctgttggtaatta3tcccagccagntrmtctccttgtcc3ccatac3ttggtccggggtggtgtctggtgcaggactgagcatagtgtttgstctggttactctggtcctgaacaggaaattggcggnatnatcagaacttccggggancagaagagtcctgatagtcttctcctcactgggcgcatagtggtts3c3cttaaccagtaatcggtcacttttgctgcttg3ctcc33gttacagggtattgancntccasc3acc3cggatgggggtcactcaggcttgtctgcagtctgc3t3ctcc3cttttagttttcaggggaactgcatctgggacggggctgtctaaggccctgtcttctggttaacttgggee。3,695tgagctgtca60ccgcactcga120gggtgtgacc180aaccsgsggc240tgtgggctgc300tgttggtcct360tgaaggcagc420tggtttgnca480tccacggcca540atggtasctt600ttccgaaagn660gg3acccctt720<210>240<211>691<212>dma<213>人<220><221〉misc—feature<222>564,582,640,651,666,669,690<223>n=a,t,c或g<400〉240.agcgtggtcgeggecgaggtcctgtcagagactgtaagggttcttcatcagtgccaacagcctggaatggggeccatgagatggttgtctggtatggtcttggcctatgccttatgggggaaccatgttcctcaaagatcatttgttgccga3gctgaataccatttccagtgtcataccctgtggaaggaacatccaagatctctggtcgttggggaagctcgtctgtctttttccttctggcactggtagaagttccaggaaccctga60gatgacatgaaatgatgtactcagaagtgt120gagagagagcttcttgtcctacatteggeg180tggccgttgtgggcggtgtggtccgcctaa240caacactgggttgetgaccagaagtgccag300cagggtgggtgacgaaaggggtcttttgaa360catgaagattggggtgtggaagggttacca420caatcaggggctcgctcttctgattattct480tcagggcaatgacataaattgtatattcggcttgtgacaccaggcggggcccanggaccacttgatgatgtaacccggtaatcctgcacggggtgnggnggacctgcccggcggccctcn<210〉241<211〉謂<212〉dna<213〉人ttcccggttccaggccagtaatagtagcct540cttctctgggangagacccagcttctcata600tggcggctgncatgataccancaaggaatt6603691<220〉<221〉misc一feature<222〉680,—715,721,728,735,749,757,762,772,776,779,781792,796,800,謂<223>n=a,t,c或g<權>241agcgtggtcgacttscggsgtctacaigctagtcactggccgsaattgscaaagtggctgcggaccaggacggcttgcsgcagtcagcctcactcaggtcagstatcgsgtgctcctg3cantcgaaancgnggcccaattcggccgaggtccatcagcgggtggagacaig33cc3tccc3cttcaagttcccacagtggatggttcsgscc3ccc3c33ggcgggtgaccgctcatccgnaattntgaaacncctntagnctgggatgct33atagccctcctt333cctccccgcaagcgatgcaagtgccctgttacttsaaactgcagt3tgtggtttgcagtaacccctgagccgccccaaggagagggtgt3tc3tttccttcncgggtcgtncctgctgtcagtccaggagtggagttgattagcaagccaaaccgatgttcggttacagagggtcc3g3tcagtgtctatgactattcctgcsgtggacscagacccggacggacttatggactgggnggcc3gtg3gatatcactgtgcctttcc3tt33t33cc3cc3cctcags3tcccaccsactgscacccaatgtccatgaaagagggactgcccgnttcgagctttacaggatctgggagcaagtgtgtatgcttt3ccgaacacattagtgtctcccaaaaatgactattgaaaagcggagagcctgaagttctcactcactgaatcaaccttcggcnggccgtncttntana60120180240300360420480540600660720780<210>242<211>26<212>dma<213>人<220><221>misc—feature<222>22—<223>n-a,t,c或g<400>242agcgtggtcgpggccgaggtcnagga26<210〉243<211>697<212〉dna<213>人<220><221>raise—feature<222>496,—541,624,662,679,688<223>n-a,t,c或g.<權>243tcgagcggccgcccgggcaggtccaccacacccaattccttgctggtatcatggcagccg60ccacgtgccaggattaccggctacatcatcaagtatgagaagcctgggtctcctcccaga120gaagtggtccggaaccgsatattggaaggacatggaccagcctgggtatggttgggcaacggcacccccantctcascaacatcctgg仁ggngccacttcctcggccccgatacaatttaagatcttggaaaatgatcttccatctcatgggcacttgattgacaggancccctggtgtctgtcattgcccgaigcttccctgttccttcctggtattcagtg3gg33c3tgccaagaccaggccccsttcg3a_ri33ccctttgggcgrigaacagaggctactgaagaatacaactggtaaacagttcaaacttcctggcsggttttaggctaccccgccgcaggacactttacagttcagcc3ccctctattactggatcagaagagcccttcc3c3agacccctttcttctggtcaggaccacaccaatgtaggacctgagtsicatggttcctggacctggaaccgcgagcccctgccccaatcttcgtcscccscgcaacccagtgcccscaacg33ga3gctctcatttcatgtacttctacca180240300360420480540600660697<210〉2"<211〉373〈212〉dna<213>人<400〉244agcgtggtcgagttcacaccagcctaagcacaacggcataagccttcgttggtctttcaggcggcccgctcggccgaggtattgtcatggctggc3cssvcgacagagttgtgcctccactccattttctccctgscggtcccacttctctccaatcttgt60caccatctagatgaatcacatctgaaatgaccacttccaa1203gttta3agcctgsttcagacsttcgttcccsctcatctc180gtgtaggggtgtcatccgtaggttggttca240cccacggtaacascctcttcccgaaccttatgcctctgct300atgatgttgtaggtggcacctctggtgaggacctgcccgg360373<210:>245<211>307<212〉d,<213>人<400〉245agcgtggtcgctgcttcctgcccaacccggaigacaeit'ttc3gttttt己tccgctcg3cggccgaggttaaactcccttttgaccaacgtgcccc3gacc3tccc33ctggaaaatatccaggaattcctggctccctctga3cccccttttttccttggcttcg3cgccc3ccc33ctgcattcatcaagtgacctgttggccctgt60caactttccc120333a33tggg180tctcaaactt240cccgggcggc300307<210>246<212>dna<213>人<400>246tcgagcggcccactgaaagaattatgccgtagtgcttaggatggtgtgaacgcgaccacggcccgggcagccagcsgaggcttgsaccaatggagatgagctttggaagtctacaagattctgtcctcaccacataaggttccctacggatgtgggaacgaaggtcatttcagg3gag33gtgaggtgccacgggaagaggtactcgtgctttgtctgaatcgatgtgattcgggaccgtcactacaacatctgttaccgtgtgacccctacaggctttaaaatctagatgggggagaaaatatagtggagg60ggcaactctg120acsgtttccc180ctgttgtgcc240tgcc3tg3c3300ggacctcggc360372<210〉247<211>348<212>dna<213>人<220>
tableseeoriginaldocumentpage152
<400>250tcgagcggccgaactgtaaggtcctggaatcgggtatggtaggaagctgangscctggnggcccgggcagggttcttcatggggcccatgcttggcctattcctcaaagaataccait11cgtcctgtcagcagtgccaacagatggttgtgccttatgggtcatttgttgcagtgtcatatccaaaanctagtggcactgaggatgacatggtggccgttcccaacactgcccagggnggctgncccatggtagaagttcgaaatgatgtgcttcttgtcgtgggcggtgggttgctgacgtgaccaaagcaggaaccct60actc3gaagt120ctacsttcgg180tggtccgcct240cagaagtgcc300ggggtcnt仁t360400<210>251<211〉5"<212>.駕a〈213〉人<220><22l>misc—feature<222〉8,1^7,312,338,351,352,357,363,421,444,508<223>n-a,t,c或g366,373,380,405,<■〉251agcgtggncggaccatggtgtsctgtagattaccgtttctgaaatcttecttctcctaattgncantgganggtaccgaattcaaacaaaeggecgaggtctactgggtcggtgaagtct■tcttttgetacrictctgaaaaantggatanaagctccaag3ctttcccc3ctgaggatgtcttctg3gtcgggtgtcccttgggatgagaaacctgtggatcactatttca3agatccca33ct3ta1n3aaaactcttccagatatgtgaaaatgetgeacsctgttgsgaaagccccttcctggaangtccsttttaccgagggaagtaccc3caggggaaggctgatgngaatctccagagctsttctctaaatttctgcccttgggaaaaacaacriagcagaaggtcaagtctg33gtgct60ctgaagtagg120cttccatcat180agtcaccact240c3t3atttgg300nngggcriacc360aaagtgggaa420gggcsccagt480514<210>252<211〉501<212〉d船<213>人<220〉<221〉miscfeature<222〉20,21,25,44,430,453,494<223>n-a,t,c或g<细>252aagcggccgcggcagttgtccgagatattcttgcctcatgtttggctggcctccttctctcntcttatca3ttg3ttncncttttccacaccgggcaggnacagcgccagcttctgccacagggtcacactctatagtttactggagcttatttcsttggagageggattggtnttttcc343,347,356,362,38*7,391,398,409,428,nc3gn3gtgcccccgctggctgttctcctattgaattctcggggaaagtttccgtaccttacagtancccettegggactctccaaagcacgtggtatgtettttcegtttgttgaaactccacttctgcnctttctnccccnaattatggggntcaccctgtgcaggagcttcccatcacccaagacatgtgcc3ctg3tgntggnaaac3333c3tricggggccagaaccaggtctgc60ca33tggcac120tegtaacacg180gtgcaigctc3240cctttacttc300aagggnggaa36033ggga3aat4203ta33ggggg480501<210>253<211〉226<212〉dma<213>人imageseeoriginaldocumentpage154seqidn0:79是卵巢癌多核苷酸8h(图7b)。seqidn0:80是卵巢癌多核苷酸12e(图8)。seqidn0:81是卵巢癌多核苷酸12h(图9)。seqidn0:82-310是图15a_15eee所示的卵巢癌抗原多核苷酸。seqidn0:311是卵巢癌多核苷酸0772p的全长序列。seqidn0:312是0772p氨基酸序列。seqidn0:313-384是卵巢癌抗原多核苷酸。seqidno:385代表克隆0772p—种形式的cdna序列,命名为21013。seqidno:386代表克隆0772p—种形式的cdna序列,命名为21003。seqidno:387代表克隆0772p—种形式的cdna序列,命名为21008。seqidn0:388是与seqidno:385对应的氨基酸序列seqidno:389是与seqidno:386对应的氨基酸序列。seqidno:390是与seqidn0:387对应的氨基酸序列。seqidn0:391是卵巢癌多核苷酸08e的全长序列。seqidn0:392-393是08e编码的蛋白质序列。seqidno:394-415是与0e8抗体表位对应的肽序列。seqidn0:416-435是用0e8全长开放阅读框架预测的可能的hla-a2lomer结合欣。seqidn0:436-455是用0e8全长开放阅读框架预测的可能的歸-a29mer结合欣。seqidno:456是显示与0772p有同源性的全长genbank序列的截短核苷酸序列。seqidn0:457是显示与0772p有显著同源性的全长genbank序列。seqidn0:458是编码显示与0772p有同源性的全长genbank序列的截短形式的蛋白质。<212〉dna〈213〉人<400;>260tcgagcggcc3actggaatcttgctgatgtccagtctccaatccagtactgcggggttctgcccgggcagcat'cggtcataccagttcttctccactctttgacctcggcgtccacatcggetctcgccgctgggecacagactttgstgccagtcagsgcgcgaccacggcagggtcgg3accagac3tctgggctgsggcatccaggttggcacatctct3gccctggccgcctcttgtctggggtacsctgcagccttgtgaggtcacggccatactcgcttggggttcgcaggtctcagttggggtcageaggtgegg60120180240300332<210〉261<211〉94<212〉dma<213>人<400>261cgagcggccgttttttttttcccgggcaggtccccccccttttttttttttttttttttttttttttttt60tttttttttttttttttttttttt94<210>262<211>650<212>dna<213>人—,<220><221>miscfeature<222>412,—582,612,<223>n=a,t,c或g6"eggecgaggtteactgeaaagaagctgatgcacagttctgatatcgaacatggtcctgatctatctgaaaggcasccagtagtataatttattcaaaagggngcttataa<400>262agcgtggtcgacatcacata3ga3ggccct3attcacctacagtctttgaatgacattggttctaatcttgtttggsaactgtctcaatg<210>263<211>573<212〉dna<213>人<220〉<221>raise—feature<222〉453,—458,5"<223>n=a,t,c或g<>263agcgtggtcgeggecgaggtacttaeggagaaacaggaggtctacagctaccatcagcgggtcactggccgtggagacagctggcattccaatagcattggggtcaaatggaggatggttcgcaaggctgcaaigaatttgtccc33c333gesagtgacectttttggtttaaaataaacctgggatgctaa3tagccctccttaaacctccccgcssgcttcgacttctaaggtgaattgcacgaaacatgsgsctaccgtgtggacgtaaaaatttaagacaaaattcaaaggatacttt3ttttttttttcacccttcctgctgtcagtccsggsgtggagttgsttctccagccg3tcaggccagtcaaggctgaacactggggsatattgtagsttggccctgttctccat3tgtcagttatttatctcttttttanccaattccnttttntgatgcttcccagai60ggaaatgtaa120ggaaatagca180tggagcsaaa2403ttgcaccct300tgctttttat360gntcctcttg420tttccasast480tggctggtcc5403atttcaaaa600650cagtgagstatcsctgtgcc3t3cc3tc3ctttcc3tt33ttacaggatc60tgggagcsag120tgtgtatgct180gaaattgacaaaccatcccagatgcaagtgaccgatgttcaggacaacagaagtggctgccttcaagttcccctgttactggttaca_gaagtaaccaccatggaccaggaccaacaaaaactaaaactgcaggtccagatcaaacagaaagaaggcttgcagcccacagtggaagtatgtggntaggngtetatgctcageggagaaagtcagccttctggtttagactgcagtaaccaacattgategetggncattcacttggatggtggatgtccaattccattagtgtc300ctccc333aa360atggactatt420a3tccc33gc480cctaaaggac540573<210〉264<211〉550<212〉dna<213>人<220〉<221〉misc一feature<222〉39,352,526<223〉n=a,t,c或g<400>264tcgagcggccagggaatagcttgcccctgtcagtcctttagctt'ggattcagtcatttcttgggaagtggactaatgetgggttcggcaagacagcatacgcccgggcagtcatggsttcgggctt.tcccgggcgatcaatgsgcatagagtttgatctgggggttactcttgtcctgsaattaat'ggaagtccttgcagcatcctcaggaagcaatttttgttggttacc3ct33cc3cgaectgeagttgtaaccagtcatcggtcacattggcttgcetctgeagnggctcgagt3ggatggaatcgtgcagtctgaatactccscttttsagttttaacaggggaattgcatctggtgcttggcggtcttcttc3cgtcaccctgt3c3tcc3c3taccagaggctgtgggctgcatggtggtcctcttgasggcaggatggttttggctgnctcccatcaggtgc60acctggasac120cagngaatgc180gactctctcc240agecttcaat300gncccatttt360gccacttgac420gacaatttct480aegggecagt540550<210>265<211>596<212〉dma<213〉人<220><221>raisc一feature'<222>347,—352,35.3,534,<223〉n=a,t,c或g555,587<400>265tcgagcggccagggaatagcttgcccctgtcagtcctttagcttggattcagtcatttcttggggsagggactaatgetgtteggtaattc33gc3t3c3gcccgggcsgtcatggattcgggctttcccgggcgatcaatgagcatagagtttgatctggtggttactcgtggcctgaaaatgggaaatcaggngatgggtccttgcagcatcctc3ggaagcaatttttgttggttacc3ctaaccscgaectgeagtttgtaaccagcatcggtc3ctggcttactggtataatcaactctgcagtggctcg3gt3ggatggaatcgtgcagtctga3t3ctcc3cttttsagtttttaacaggggattgcatctgggcttgcggggctccaggttttcttcttcscgtcaccctgtacatccacataccagaggctgtgggctgcatgttggncctacttgsagcagatggtttgggctgtctccaaaggccnctgcatcaggtgc60acctggaaae120cagtgaatgc180gactctctcc240agecttcsat300grmccatttt360gccacttgac420tc33tttctg480cggncagtga540atggta596<210>266<211>506<212〉dma<213>人<220><221>miscfeature<221〉misc—feature<222〉480,—491<223〉n=a,t,c或g<400>91gaatcacctttctggtttagctagtactttgtctccctgggctctgtttggctctcggtatggagaggggaatatgcattaaggtgaaaaattgctgcttcsggactgtggaatta仁仁tgacaaaaaaggtaattacaaaatgtgtacattgtgctcacattcccttaaatgttgtttcctctccgggaagaggcagagacagtttggcgaaggagaaagcsgccttccagttaaalgatcgctggcctcangcggeigtctgggtcsgaggtatgaggtttcccacagcgga60aggcagg、cctacaccttttcctctcctcts120gtcaccttccaaaagtgagaaagggattcg180gaatgttttacaaatggttg240cacaacatgctttttaaagacattatgcat300aaaggtgctcagcctctagcccagctggat360agggaaggagggggtggtga420a_gccctcagtt3aaggtc3gcttcccgcan480gaggagcagcsgc3gggtggg3ctggggcg5405"<210>92<211〉551<212>d肌〈213>人<400>9233ccggsgcggtgaagcgcacgcctccagcgcctccttgactggccactgggt3tgssggatcca_actcagctcgtaagtgc3g3gtccctgtctg3gtgcgagcagtagagatccaggtgagaagttgaaccgtsggatccctgcaaaattattgaaaatggtgatcatgttgccgagactgggtgggctctgc3gcsggggagaaaggccsgctggttccgggccttagcsc3ttgc3tgaaggagacgatggatgagaccatggctgcaggcagatgcgggcccggggctgaaaaaggaagaggcagttggascgcscagsttsgscggaitc3ccacatgcagagga33c3ggctgatggaccgtgcctgctgatgacagaggaacgtg3tggaccacatcgaggcg60gcgagctgag120ggctgaggtg180tcaggagcgc240gagtgagaga300actccaggaa360tgaagaggtg420agctgagctg480gaacctgaag540551<210>93<211>531<212>dna<213>人<400〉93gagaacttggcctttattgtgggcccaggagatctggttttctggstsgccaggtcataggcacaggcctcacttgctgcagttccggggctcgtggtscacgscsg3gccsttggtgcacgagggcaggcagcaggagcattgctcctgtttgctggcacactttccctggcagtaatgtcccactttgatgt3ctgcaccttggctgtgtcacagcaggtgcctggaattttcacgatatcsaatggtgggcagcccgtgaccctctt〈210>94<211>531<212>d船<213>人gggcacaaaggtcaggaggcccaagggagg60catgggtatcagtaggaatccgctgtagct120agaacacctgcactgcatggcgttgatgac180gtgcaagggcacgcgcatgggctccgtcct240cacatcctcgstgtcaatggagtacacagc300aatgtccacttcctcttgggacttacaatc360gatgtctttgcastcaggctcctcacatgt420tttgcctccttcagccagacacttgtgttc480ctcccsgatgtactctcctct531<220><221〉misc一festure<222〉517一<223〉n-a,t,c或g<210>269<211〉368<212>dma<213>人<220><221〉misc—feature<222〉265,329<223〉n=a,t,c或g〈400〉269agcgtggtcgctttctttttctgctgtcttgcttggcccgtacgaggaatccgctcgacggccgaggtgtggcctgaaataagtctgcagtscccgtcaagggaggtagacctctaggccsgcstc3gacgntgtc3tagcttcscsgtcaccatttsgcctgggcnagsgccccgcccaattcgcagccaatggctccaccccaggttggtgctggtcaagccctgtttgcdggctcccatatgcccctcacagttccccacagttcatggacctgctggtcatcgc60gccgtctcca120agttccttca180tcctgggtgt240tggatcaggg300cc(3ggcgggc360368<210>270<211〉368<212〉dna<213>人<221〉rniscfeature<222〉54,163,219,229,316<223〉n=a,t,c或g"00〉270tcgagcggccttgt3ccctgc3agcaic3ccggacatgaagagcagtggaggaaaggcgatccacgcttgcccgggcagatccagaactcaggagaactgaactgggcaacggqagttcgaccanagccgtccatscaggtgggaiccsggtg3g3cctgtstgggsgcc.tgctactgcgggc33ggcggggctgttgcccaccatccgtgggtgtasatattggctgngaattgatgacggcttcctgacaggccctagctacttacctaagctgcana3tcgtttc3gtgctggacctaggncattcc60cccttcgggc120gtactttggt180ctt3t33g3c240gccacaasaa300cggccgccga36q368<210>271<211〉424<212>d船<213>人<220><221〉misc一feature<222>279,—329,362,384,<223〉n-a,t,c或g■<400>271agcgtggtcggcgttacaaacatcatggaggagggctaaactsctscgttggtgaagatccntgacc3cgattccggccgaggtctcctaggagagtggggccatccatgsagtgacsctgctgatgctgcccttgaaccatttccactagaggggcttgctgtaaggctgcgattgtggatggtgcgccacgtgggacccancgtgngaaccctctgtgtgccgcggagggccggttgtggtgcctga仁gatcgttgctcanatggcaaaaatcaagatgaansttgcccaggtgctatggtgtctgggaaaccacagcggagcagggtgtgcggccctta33atacttgccccagagtctct60tgctgcggtt120tccgaggaca180accctgttsa240tgggcatcaa300aaccccttgc360accacccccc420424<210>272<211>541<212>dna<213〉人<220><221>misc<222〉<223〉n=,<400〉272a,t,c或gtcgagcggccgggcatggcatatctcatctcttaccagttg3gc33cscgcstcsggccacc3c33cctcancaaggcccttgcctgggggcccgggcagggcggctctgttgggttccagggtcccaggtggcgcacsgtccacaaactgccagcctttttccgcacsgc333tgggcagtctgccaaggettcccaccca3tgctcaicgc3gc3tgstcagtgtcaactcatggatttgggccccactgnaagcccttcacaigacctngagaccctgtcttctgttctgtggtcaggccttcaccttggtagtagttaagcc6tctgttcttcatgaacctaaggagttantnggacctatgctgtgggagatgggggaggggcttctatgcccagcaacagggtctccctcggagtttgaaaccgcatttgta33cgttggnccgcgggactggctg60tggtgggcag120tsgggcca3t180caccctgtct240cgctgtggat300tcccaaaaca36qgcscaccatt420caasaaactc480aaccaccgct540541<210〉273<211〉579<212〉dma-<213>人j<220〉<221>misc—feature<222〉223,—265,277,531,578<223〉n=a,t,c或g308,329,346,360,366,429,"8,517,524,<,>2733gcgtggtcgaaaacccggatggaactcctatactcc3ggttggccc3nsctactantggaccctggggngcattaaagtgggcgttgcgccggccgaggtcgscctggtgggacttcctgcccggtgctccaaacsggagctgcccgggcatccgaacttg333ttggt3ttcactgcccctggccctccagagaggagtgcttcaaaggctggtgtgaacccgngggctggccgctcnacggtaccaaattccgctnccgggggggcctcgcttttecstggcaaggcttgttggaccacattagggg3gggtgaaccttcctggngaggcttggccgt33ttcc3c3caaatgarigtggtcegggnaggtgaagatgcagggtgetccscsatggtcggngcccctgagsggacgtgtccagnacacaatcatggccasc3t3ccgaagentaaetcgtcaccctgg60gtggtttccc120tggatggatt180gtgaaaatgg240ttggtgcccc300tggcggccgn360atagcttgtt420acceggsaag480ncsttt33tt540579<210〉<211〉<212〉<213><220><221〉<222〉<223〉"4330dma人misc171■festuren-a,t,c或g<>274tcgagcggccgcccgggcaggtctgggccaagcccacgggctcctgtttgacctggagttggggcaccaacacgtcctctccattttcaccaggggcaccctcsccagga603ggttc3ccc120ttcacaccagcctttgaagcactcctctctggatgggccaggsgcaccgggcaggaagtcccaccaggtcgacctcggccgctgtcccttcaggagttccatccgggttttcga_ccacgct3atccatcc3gsccattgtggggaaaccacgagcaccctgccsgggtgaccatcttcaccncccctaatg180tggtccaaca240agccttgcca300330<210〉275<211>97<212〉dna〈213〉人i<220〉<221〉misc一feature<222〉2,3百,72<223〉n-a,t,c或g<400〉275ancgtggtcgcggccgaggtcctcaccagaggtgrxcacctacaacatcatagtggaggca60ctgaaagaccancagaggcataaggttcgggaagagg97<210〉27(5<211〉610<212>dna<213>人<220><221>misc<222>358,558^584,588,590<223〉n=a,t,c或gfesture360,363,382,424,433,464,.468r477,491'<400>276tcgagcggccgtagttcaca333gccta3gtccaacggcac33gccttcgctggtctttccgancatgcaatttcactggacccaacttttaaccgaaaa<210>277<211〉38<212>dna<213〉人<220><221>misc一<222〉2,5;<223>igcccgggcagccattgtcatcactggcacataatgggaaattgacagsgtagtgcctccagcttaagccctcntaaaaggncccgccgntaatcgccnttgtccattttcggc3ccatctacagtttaaactgtgtagggtgtcc3cggtctatgatgttgnattctgcaggccccaatttttacaaacgtccctgacggagstgsatgcctg3ttc3gtcaaagcacaacascctctgtaggtggcagastaatccctcccccttatncggtgaacttccccccttttccc3cttctcatctg33stgacattcgttgsgtc'atccgtcccgaacctcctctggtgaatcacacttgtcgnccancn499,511,ctccaatctt60gaccacttcc120ccc3ctc3tc180taggttggtt240tatgcctctg300ggacctcngn360gcggccgctt420gtatttnccai480cctggcggtt540tgggcgtaaa600610—feature3718,21,31a,t,c或g<,>277ancgnggtcgcggccgangtnttttttcttnttttttt38<210>278<211〉443<212>dma<213〉人<220〉<221〉misc—feature<222〉156,—212,233,419,437<223〉n=a,t,c或g245,327,331,336,361,364,381,391,397,<鄉〉278agcgtggtcgccctgsggtcgccgcgggagcc3ga3ttggccccntcgaacctgcccccanaangctttt<210〉279<211>348<212>dna<213>人<220〉<221〉misc_<222>219,_cggccgaggtaagttcaactgagcagtacattg3atggc3aaaacc3七tttcccgggaggtatcccascgctgaggttscggtacgtggaacagcacgtacc333gcc33nacttccccccccstgcgtggtgcggcgtggagccgggnggtcgngcaaggtt3gggca1gcccnaaccnggttntggaantgggtggacgtgsgtgcatsatgagcgtcctcatccaacaaagcg3gaacc3ccagcctt33cgccacgsaga60ccaagacaaa120ccgtcctgca180ccntcccagc240aggtgtacac300ttgcttggtc360tgggccaanc420443feature256,291,297,307,314,317<223〉r"00〉279tcgagcggcctctccggctgccsggcaggtacacctggggggaagggcttggacggngaga,t,c或ggcccgggcsgcccattgctccaggctgaccttctcggggctgttgnaascgacnctnaccgtgtcggagttcccactccatggttcttggttgccctttgcttgcacttgacacggaaccccagcacgggcggcgatgtctc3tctcctcgttt七gaanasctccttgccgggctggtggaggcgtggtcgctgggatagccgggatgggtggttttct'cattcacccagactgctccttgtsgttgtaagcctttgaggcagggtgagatgggggctncctggngca60120180240300348<210〉280<211〉149<212〉dna<213>人<220><221>misc—feature<222>18,34,51,118,120,140<223〉n=a,t,c或'g<400〉280agcgtggtcgcggacgangtcctgtcagagtggnactggtagaagttccaactgtaagggttcttcatcagtgccaacaggatgacatgaaatgatgtaccctggaatggggcccatganatggttgcc<210>281<211〉404<212〉dna<213>人ngaaccctga60tcagaagngn120149<220〉<221>misc—feature<222〉383,386,388,393<223〉n=a,丁,c或g<4o0〉281tcgagcggccccscgtgccagssgtggtccggsaccgaatattggaaggacctgggtatggcccgggcagggattaccggctcggccccgaaaagacagaagatcttggaaacctgggaagtccscc3c3cta^caitc3tcccctggtgtctgtcattgcccgagcttccctgttccttccaanggnanttcccaattcctacagaggctactgaagaatacaactggtaaaanctttccttgctggtatcagcctgggtcctattt3ctggatcagasgagcccttccacaagacccctttggcaatggcagccg60tcctcccaga120cctggaaccg180cgagcccctg240ccccaatctt300cggcaccccc360404<210〉282<211〉507<212〉dna<213>人<220〉-<221>misc—<222〉320,—feature341,424,45〇,459,487,498<223〉n-a,t,c或g<400〉282agcgtggtcgscttacggagtctacagctagtcactggccgasattgacaaagtggctgctggaccaggag33ngcttgcgaaaaangtccggccgaggtaaacaggaggccatcagcgg33cc3tccc3cttcaaggtnagcccacagtaagccttntgctggg3tgct333t3gccctccttaaacctccccgcaagcgaitgcsagtgccctggtactcttaaactgcgggagtatgnggttcaacctgctgtcagtccaggagtggagttgattagcaagccaaaccgatgttcgggttacagaagggtccagagggtagtgnccagtgagatatcactgtgcctttccat;taant33ccaicc3tatgcttcagttacaggatc60tgggagcaag120tgtgtatgct180ttsccgaaca240cattagtgtc300ctcccaaaaa360aatgactstt420aatccaagcg480507〈210〉283<211〉325<212>d船<213>人<220〉<221>misc—feature<222〉216,—292,303,304<223〉n-a,t,c或g<,〉283tcgagcggccgcccgggcaggtccttgcagagggaatagctcatggattccatcctcaggttgcccctgtgggctttcccaagcaattttcagtcctttagggcgatcaatgttggttacgcttggattctgagcatagacactaaccacaanncatttctgtttgatctggaccctctgcagtgtcttcttcaccatcaggtgc-60gctcgagtaggtcaccctgtacctggaaac120gatggaatcgacatccacatcagtgaatgc180tgcagnctgaaccagaggctgactctctcc240atactccactgtgggctgcaanccttcaat300325<210〉284<211〉331<212>dna<213〉人<220〉<221>misc—feature<222〉54,亏9,63,121,<223〉n=a,t,c或g312,327<400>284tcgagcggccctriatccagcnaccttcgacgggccscaagctctgagctgcccttgtatggcccgggcaggtctggtggggtcctggcacacgcacatgggggngttgnt60七gcccagcccccattggcgagtttgagaaggtgtgcagcaatgacaacaa120tcttcctgccacttctttgccacaaagtgcaccctggagggcaccaagaa180ctccacctggactacatogggccttgcaaatacatccccccttgcctgga240accgaattcccccttgcgcatgcgggactggctcaagaaccgtcctggca300anagggatgaagacacnaccc331<210><211〉<212〉<213><220〉<221〉<222〉478<223〉285509人m工sc316,'feature-319,327,329,339,3化357,384,398,427,443,450,n=a,t,c或g<400〉285agcgtggtcgggtgaccgtggcccagcaacatgcccaccgc3tcccccttgccggtactatttctgggggt3a33gngtagttgccgctccggccgaggtccctccagcaaccaaggtggtgccc3gc3ccca33cctgcgtgganccnagaaat仁ggtaaasgcctgggactggcccgcctgtcctacs3cttcggc3cacaagagagtctgaactcctccgggcggccacttggnanctccngtttateggnggcct3nttttccagcgtcctcaggsccsgacct3ctgagcccaaaggggggaccggctcgasagccaacctggngaattcccncatgaagtgasgctctactccctcttgtgacatcagtcttcccgaattccagcaacatacgactaaactcactcsgcagcgt60tagatcacaa120aa3ctcac3c180tcttcccccg240cacactggcg300gcataanctg360.gccggaagca420attaattngc480509<210>286<211〉336<212〉dna<213>人<220〉<221>raise—feature<222〉188,~251f267<223〉n-a,t,c氛g<400>286tcgagcggccccccccaggaggctcaactcgtctgggrigcgaggactgtacacactggcggcccgggcaggttcaggtgctcttgtcc3cegaagttgetngacagacctgccgctccgagtttggaaggtgggcacggtcttggtgttgggagggcacgcggccgngacgc3tgcstttgggatgcgggggaa_gagggialgaetgaeggt60gggcatgtgtgagttttgtcacaagatttg120ctgggcttgtgatctaegttgcaggtgtag180gtcaccacgctgctgagggagtagagtcct240cacgctaagcegaattctgeagatatccat300tagagg336<210〉287<211〉30<212>dna<213>人<220><221>n\isc_feature<222〉8,l百<223〉n-a,t,c或g<〉287agcgtggncgcggacgangacaacaacccc30<210>288<211〉316<212〉d贴〈213〉人<220〉<221〉misc—feature<222>22,130<223〉n=a,t,c或g<400>288tcgagcggccasctggaatcttgctgatgnccagtctccaatccsgtactgcggggttctgcccgggcsgcatcggtcataccagttctttgttgcagaactccactctttgacctgnccacateggctcttgccgctgggccscagactttgatgccagtcagsggeagggteggaaccagscatctgggctgaggcatccsggttggcacatctagccctggccgcctcttgtctggggtacactgcagccttgtgaggtcscggccatsctcg60cttggggttc120gcaggtctca180gttggggtca240geaggtgegg300316<210〉289.<211>308<212>d船<213〉人<220><221>misc—feature<222>36,165,191,195,<223>n=a,t,q或g:35<400>239agcgtggtcgeggecgaggtccagcctggaccaggtatagctggacctcgtggtagccctcctgctggtttccctggtgctcctggacagggggctceggntganaaaggtgaaggaggcagaggtggagctggcccccctggccccgaaccacctgg<210>290<211>324<212>dna<213>人<220><221〉misc—feature<222>m—<223>n=a,t,c或ggataanggtgaaggtggtgcccccggactt60ggtgagagaggtgaaactggccctccagga120aatggtgaacctggnggtaaaggagaaaga180cctcctgnattggcaggggccccangactt240ggaggaaagggtgctgctggtcctcctggg300308<400〉290tcgagcggccgcccgggcaggtctgggccagggecatetttccctgggacaccatcagcatttggaccaggacttccaagacctcctcttccancagcaccaggtggcccaggaggaccaggaggaccaataggaccagtaggacccctt60cctggaccgcctggttcacccttgtcaccc120tctccaggcattccttgcagaccaggagta180gcagcaccctttcctccttcgggaccaggg240tccgaattcctcggttttagttgtggaatgctttcatttccacgtttctttttaasactgtgtattttcttattgtgtactgcaagcgaattataatctaggctgtttaaaggtttactgttttwttttttttagcagtagtttcttatagaaacctttaaatggscaaacgtttgcctgtsattgattctagcagttaatg3gattttcctttacsgttctggcttctaaaacatcaatgtattccttttagaacctttgtttcstgttctggatgtatagagcaaagagg33ggtsttttttggatcaaagagg3ttactcgatggatttatatttgatagctatgcaatttta33c33caaagttgtggtatatgttcttttttcastt60taaat3ctgt120gtatttctaa180cgtttatatg240aaaaagtcta300ggtteaactt360ttttaacaaa420gcttattttc480483<210〉115<211>521《212〉dma<213>人<彻>115tgtggtggcgggcccccggcgctgaatgaa3gga3atgtgtctgtgcttgtgcttcaaatgaccgacggattcgcccttgcgggctgaggagcgccggccsttgtcgggacqcaacatcagcccgggcccgacaggggcacttcccaaaggcccagcaagcttgtaatgctggaggcccaactacgaactatgaagacactcattgcgggtgctgggcccttgacgttgtgccgacatsaccttgaggagggactctgacgccgtgggttcgtgagcaggccctccaggaagcactcasagstcstcsttatcatcgagccctgcccctggaaaaatatactagaggtctaccggcaagagatgccatgtattaaaatgtctggatgaagatctsctctaccttcagcaaggccagtaaattgc33ggg3ccac3sgc3ttggaactcaattgctcaacacagacagcataaaccactcg60120180240300360420480521<210〉116<211〉501<212〉d船<213>人<400〉116ctttgcaaagctgtgaaggaagctgccttcaaacagagtcaaattaaaagcgtgactgcaccatggtttacttttatttcgaaagcagtgcagcagcctgtcttcacagcligtgcatagtgcaggcaggtgagggtttttactttcccttataagctgatatgtctgcggcacgagaaggcc33ggcc3ttggagtctgaccatt3c3tgccagctccaccatatgtaatcatggaatccaatgagtgggggcagagagaaagctcatagc3tcactgccctctctttt3ttcatgttacaaaacctgcscatcggaaccaacgactgcaaactggcatgtgtctgcc3catctgtaaaaggttctgtsttatggcatcttag60ggcctccac3120aaacacaagc180gaatctgaca240cctgtttacs300acatcaagtg360aacaaaatat420cacttggata480501<210〉117<211〉451<212>dna<213>人<220><221>misc—feature<222>320—<223>n=a,t,c或g<400>117caagggatattt3gttctctgagattgtcccgtatccaat3ggagagtttatgttgagggtacrgrgtgacactgaacagatcacaaagcacgagaaaca60ccctccccagcgtctccttcgtctccctggttttccgatgtccacagagt120ctaagtaactgcatgatcagagtgctgkctttataagactcttcattcag180tcagcaattgctteatcaaatgccgtttttgecaggetacaggccttttc240agaatctcatagtaaaagsctgsgaaatttagtgccagaccaagacgaat300gttngtgtgcggggaggtaacaagaaataccgtgccctgaggntggacgnggggaatttc120tcctggggctcagagtgttgtactcgtaaaacaaggatcatcgatgttgtctacaatgca180tctaataacgagctggttcgtaccaagaccctggtgaagaattgcatcgtgctcatngac240agcacaccgtaccgacagtgggtaccgaagtcccactstgcncct285<210〉295<211〉216<212〉d腦<213〉人<4o0〉295tcgagcggcccc3cgtgcc3gssgtggtccggaaccgaatgcccgggcaggtccaccacacccaattccttgctggtatcatggcagccg60ggattaccggctacatcatcaagtatgagaagcctgggtctcctcccaga120ctcggccccgccctggtgtcacsgaggctactattactggcctggaaccg180atacaatttatgtcattgccctgaag216<210〉296<211〉414<212〉dma<213>人<220><221〉misc—feature<222>7,33,61,62,63,88,355,386,393<223>n-a,t,c或g109,122,255,298,307,340,<4o0>296agcgtgntcnnnntcttctggnccagtaatgagacccaggcstgataccagaattcntgcgggccccaatcggccgaggaattattcttcagtsgcctctcttctcatacttcccccctatggggssgctagggcaangagtgacaccstgttgatgatgsgggtgtggtgatcacacttgttaggngaagcgnctgtcttcataaattgtggcggggccgagccggtaatgacctgcccgggcgggccgnccric3ttt33tttccttccaatattcggntagggaccactcctggcacgtggcgggccgctcgaaccatgcsasttcc3c3tc3ggggct60cccggttccs120tctctgggag180gggcggctgc240tcgaaaancc300catcntaaaa360ttgg414<210〉297<211〉376<212〉dna<213>人<220〉<221〉misc—feature<222>312,—326,335,361<223〉n-a,t,c或g<4o0〉297tcgagcggcccccggccctcttcctgccccccagcagaatgcacctggccntacttggaagcccgggcagctggacctccagccacctcatggttcgtgacg33aac3ttgngaacctccttggacgtctcgcggttggtccccctagagaaggctccgtgacctccggaacccgaaa_gaangtgccgcactggtgggtcctccc3cacgatggtggaggtggacagaagggcaagccacntcttgatgctggtccgcgctggtttgccgctactscc3ccctc33cccgcaaagaactgggsaaatgttggtccc60cgacttcagc120ccgggctgat180gagccttgag240aaccccgccc300aaagggaaaa360376<210〉298<211〉357<212>dna<213>人<220〉〈221>misc—feature<222〉345,—346<223〉n=a,t,c或g"00〉298agcgtggtcgctggaatccagctgatgtacagtctccatgccagtactctgcggggttctcggccgaggttcggtcatgccagttcttctttgc3ga3gaccsctcttcctgcgggctgcccacatcggctctcgccgaagggccaicactctttgatggcagtcagaagtccttctgggcagggtcggagccagacstgcgggctgggtgatccaggttgggcacatctttcccggaatgccctggccgcctcttgtcctgggtacacgccagccttggtgaggtcacggttctnngaaccatactcgaa60tggggttctt120aggtctcacc180tggggtcaat240cagggtgcgg300ttgctgg357<210><211><212〉<213>299307dna人<220〉<221〉<222〉<223〉misc231/feature—285,306=a,t,c或g<40o〉299agcgtggtcggcgttaca33catcatggaggagggctaaactactacgttcaaggngcggccgaggtctcctaggagagtggggcc3tccatgssgtgacacttgctccactagaggggcttgctgtaaggctgcgattgtggatggtgtgcgccactctgtgtgccgcggagggccggttgtggtgcctgstgstcgtgttgctcsattgcccaggtgctatggtgtctgggsaaccacagcggagnscangggtgcagagtctct60tgctgcggtt120tccgaggaca180accctgttaa240ggctgggcat300307<210〉300<211〉351<212〉dna<213>人<400>300tcgsgcggccgggcatggcatatctcatctctt3ccagttgagcaacacggatcatcagggcccgggcagggcggctctgttgggttccagggtcccaggtggcgcacagcc3tcc3c33gtctgccaaggcttcccacccaatgctcacgcagcatgatcaagtgtcaaacttcatggagagatcctgtcttctgttctgtggtcaggccttcaccttgcgtasgtaagtttaaccctctatgctgtggg3gatgggggaggggcttctatgcccagcatt33csgggttgtcctcggaggactggctg60tggtgggcag120tagggccaat180caccctgtct240ctccgctgtg300g351<210〉301<211〉330<212〉dna<213〉人<400〉301tcgagcggccagtgctggtggtccsgggtgcagccgctctc3ctcc3gtgcagagggccagcccgggc3ggtgggcacagtaggggcccactgttgagtcgctgctcc3tacactggtgtgtgtttcagaaggtccgatggctctttg3tc3gggcttttccttctcggatctttgaataggttccsaggtccactgtgg3ggtcccaggggtgaaaccattgacatagagactgttcctgccattggccagttggctcagctcccagtaggggtcaagatgatggatgcagatggcatccctgagagaggtcagtctgcagccagagta60120180240300330<210〉302<211〉317<212>dma<213〉人<220〉<221〉ruisc—feature<222〉129,—295<223〉n=a,t,c或g<400〉302agcgtggtcgcggccgaggtagctgggcccctacaccctggctctgtgnccaccaccagcctccatcctccctctccagcccctc3acttcaecateaccggaagttcaacaccacactgtactgggagctaagcaagacaggaacagtctctatgteictcctgggacctccacagtcccacsattatggctgctggaacctgeagtatggggaggaactgaccaatgacattgaag60caatggtttcacccatcaga120gg3tt"tcsga3cctcaggg3180ccctctcctggtscc3ttc3240c3tgggtc3ccctgnctcca300317<210〉303<211〉283<212〉dna<213〉人<220〉<221〉misc—feature<222>139,—"6,195<223〉n=a,t,c或<400>303tcg3gcggccgcccggacaggtctgggcggggtctggcaccctgagcagtecagegaggaggatagtatgcagcaeggntctgagnctgtggtgctggctggtangggttgattacagggtgcat3tsctggttagtgsggtgagcctggatagcacegggcatattttggaatggatga60cttggtcttagttgagcaatttggctagga120gggatagctgccatgaagtaacctgaagga180ttgggaacagctcgtacacttgccattctc240ccctcttcttttg283<210>304<211>72<212>dma<213>人<220〉<221>misc<222>59.<223>n=.feature<400>304agcgtggtcgeggecgaggtgagecacaggctgctggtcctgtgaceggggetgaagctggggetgetggne6072<210>305<211>245<212>dma<213>人<220><221>misc一feature<222>5,lt,22,98,102formulaseeoriginaldocumentpage170人<彻〉309agcgtggtegctggaatccagctgstgtaccsgtctccattcc3gtactcegggceggggcaggctcttgcccgctcgaeggecgaggtteggtestgcgttgcagaagtccactcttcgttcttgeggagggtgggtgccacatcggctctcgccgaagggcc430<212〉dna<213>人<220〉<221>misc—feature<222〉342—<223〉n=a,t,c或g<400>310tegsgeggtcagcctgagcccgcscctgccg3cccc33ccgsgacctgcgaggaaiccccaccagtttcgagsccsccgctgcccgggcag3gc3g3tcgagtgacctcaatgtaccccacagg3ca3gaggtattggcgggtttegtgacg33catccgggatgtgccaccctggatgcctcagcccagtgc3ttgtcttccsgggcttccgtgacctcgagccc3gaggtctgsctgga3tcsa3gtctgtgggcccagggttcggcgaccgacccttgaggtggacacgcagccgcaistctgcaacatccgstgtggacaccctcaag60gaaccccgcc120gtactggatt180ggagactggt240ccgatggatt360cctcggccgc420430<210>311<211〉2996<212〉dma<213>人<彻>311cagccaccggac3g3gagcacctacaccctccacc3ctagct33acctggtc3cc33cctcgg3g3gggttctggctgcagccstctgcatgggsgctgagacsgcctctgggacccccagctgccagccctgctaaggcaccttgctcacgccctgaccctgacccacaagtggatgccgctgtstttggg3c3gggaccattcctgggtccctcggctgcggt3tg3gccttcagggcgactgactttccc3cc5lcccgccagctgacttgtcaatggcagtgtatctatctcctgattgtggcctggccttgttcaaccacaggcccgcatcactgaatctgcscccgagctgagccagtctctatg3ccccc3c3ggccsgccctcg3g33c3tgcctggtccctggctcaggccttgaccccaaaccacaatatctttcactc3tgggsgcatctactattcaccctccagg33ggaacaccagt3g3tggggs3tgggctggacgctgggccccaccgccctgatcaatggttttggacctgggtcctggtgctagcaccctggttcaagagcagaaaaggatgagccctaggcactgagctggcggagctctgaagactccagctc33cttc3ttcaacactagttggccctcgccaccggagag3gagc3gctacacactggccccacaggccsgc3tcactcacacagcggaacatctgggattcactctcctccaigg3agccagtgttggggacagccactggscagagagcccctatgctgtccsccaccctcgatattcc3tcactaacagagagggttgtactctggtggstgccattgtatttggaacagggacagcctgggctgggagctgggccagctctgtgcactccagttt3scttcacc3ccctctgtactggagtggatgcagctgtatcctggacaaccagcactccttggcccttcacctgcggtatccttcagggcctgcaggctgctgcacccacgctgagccagtctctatgtc6012018024030036042048054060066072078084090096010201080aatggttteaccattcacscggctccctcacagaggagcaccaggtctgccggctgggccggtccagatggaagccacaaaatctccsgtgtccttcagcggttgccaacacctgcacctgagctgagtcagcctcttcaaatttccacaaccctgctgagacacattcc33ggc3ttgtaccctgaatgacag3aatggctg33tttcaaattaccagaagc3tca3gacsccacaccggttgccatct3ccctggacaactgggaattggactcatcaggsgaatacagstctgc33tagaagcttggcccatcggagtgaacttcacagttcaacstgcctgggtgcctgagacacgctatcaagcacctactctctagcctcctaccagccatgggattcaccagaacctgctcagtgatctccctaccaccctgaagctgacccatcaatggctattgtcaactggggacatccagcttctgccttctcctccsacctc3ttcc3agtcatcagtcc3tgttatttttcgggtggactcatgaggaattggagcagtgtctgaccttccacgtccagcagactggaactctggggcagactctgtacccc3c3g3c33cacggtacacaggtggscctcggtgttccstasctcccaaggtaccscctgtstgggcssgacccttgttccaggcctgagccctgtgggctggtgtcacctgc3cccc3ggaacctcagtggsc33ggtcggtcaccaactttggaccccttggctgggcttatcsaccacctaccatattgactgtcaacctgtgtaactctgcggstgccttgtggatcttctgggctctgcggtgtcacagtgcccatgccggtgcc3cc3ccagcactgcgctacagtcatgaagcggctgcagggctctgcacctgagctgagccagcctctaccccsgccscc3aagaccctcaggctcagctacagaagagcaaaggatggggcccgggctggcaactgggct33ttt3tc33aatccagacc3cc3c3ctctttgacgatggagcctggtggtccacctaccacaagcagcttcccsggac3gatgcgctcagtttc33c3tttctcgccacacccggaatggggtattttcgtcatcctcactggtgaccaggctactacctggggtgcct3ttggtcggaccggggtggttggcggac3tacctgctcsgtcatcgc3ctacctgcagccagcagacccattaacggtt3cattcctgccc3ctzc33cttcattcaactcgcatgggccccagccactggac3tacsgc3tctstgtccttccggggcgaccscatcctcac33aggcatgactccgtgttagcaagtcttagttggtggacc3gc3ccc3aagcccagccaccaactctttcsggtctgttggctcggaggtsccc3gcttcggcttggccccgccggcgagtcacacctttcccccsgccagcgaggaggggccaaccctcctttgttcaaggtctgtgcctcagcggctggcatcacctcctctgtcac3ccatctcccaccgaggggcttctacttgtgtggacaccgctttactggggacagggatgtaccagataagagtacatctcaactacatggtcactgtccatccatgtggcacttctacsggcaccaccccgaaacagcccccaacaggagtagacagatgagccctta3gg3ctcctggaagaaggaasgacctggagcagggtccaa1140120012601320;380i"o15001560162016801740180018601920198020402100216022202280234024002460252025802640270027602820288029402996<210〉312<211>914<212〉prt<213>人<400〉312metsermetvalserhisserglyalaleucyspropro!leualaphe11015leuglypropro20gintrpthrtrpgluhisleuglyleugin30pheleuleuserserasn340pheginleuthrphe420tyrglypro■leugly500glyglyleuval580asnval165serleugluleuleu245gluglythrleuthr325asnasnargargtyr405hisserproprothr485lysleucysvalasp565thrglyphe150serlyslieasngin230tyralaprohistyr310glyleulieserser390leugluleuaspleu470leuglyargginasp550liegintyrhisthrthrleumet215glyserthrglyser295valvalargthrser375valginleuaspgluserasnserproleu535thrginleualaliethrprophe200trplieuglyglyleu280工leasn.valtyrasp360leuargldna<213>人<400〉313acagccagtcggagctgcaattgt333gga33gcc3ca3ctgcagtttgtctacgactccagcacacagccaactcgcacagtgtcaagctcaacaaacctg3tcctgtctgcggtccacaagagcataaatgcccagtgtggggctcatcttgggcctca33tg3ctgccaaccaggtgagaggccgttaggcaggcacaaaagcacttttccatcttggtgttctgggtggatcgcgyatgtccaagggacctgaggctcggagaaaacccacttcaacacctctctgccttggtcacatttcactggcctctagtgaatccaaccttttgacattatgatgagcgggagcaactggagtcatcatggtaacactcgccagatccctcgggacagatccccctattcctgctcccccatacacgagstac3ccs3c3tatatgcactcaaaatgctct60gacttggaggctgagcaaag120agacgcagtcagtgctggga180ccccgctgggsagtcctatg240tccgcagaagacggtcscca300ctcagattttgtcttcagtg360agaaaccttgcccctgattt420gatttaccacgtccaccaca480ccagtataagcacatgggct540actggatcaggtagaacaac600agctac33tc3s3c3g656<210〉314<211〉519<212>dma<213>人<400〉314tgtgcgtggagtcactttgcgtttaaggatcagttatgttaascttcaatcattcattagtt3tgtttsgctaccsgggagstaggccac<210>315<211〉"1<212>dna<213>人<400>315cacagagcgtaaaagttccccagaggcaacttgtcaaacgttccttctttatgatttaaagctcgctctc<210>316<211>247<212〉dma<213〉人<400>316tggcgcggctggcgggst3ccc3gtct3gc3tctgctgtctgctgac<210>317<211>409<212〉dna<213>人<400〉317tgacagggctcscgatgtgggaatgctcccggaggagtggttgcattctactgtcaggaaccaaagggtaccagtcagcttccgggtgtgactggagcagggcttgtcgtcttcttcaga60aggggttggtgaagctgctcccatccatgtacagctcccagtctactgat120ggtctcggtggttaggcccactagaataaactgagtccaatacctctaca180taactgggctctctgacaccgggaggaaggtggcggggtttaggtgttgc240ggttatgcggggatgttcacagagcaagctttggtatctagctagtctag300ctaatggtgtcctttggtatttattaaaatcaecacagcatagggggact360gttttgtctaagagttagcttatctgettettgtgctaacagggctattg420ctttggacatgggggccagcgtttggaaacctcatctagtttttttgaga480tggccttggacctcggccgcgaccacgct519ttattgacacatgttgattacagggtttattctctgesetgtgacaaacc33ttcc33tgtccgttttcctgcsttttgtcaccactcctcatgtaaata3gtgcta1ggtgttttcagccactttcgccctttgtgagctggsa33ttggggtcacatataaaaitgtcatctctecaegttgaggatttagttgggagaaatctgggggagatttctt3tttacaatgaagtcttttgtgcgectctgtccaacaggactgtttccaaggaggttagtggtatggttcccct60gcagtttctt120tactgactca180tgcttcttsg240cttttcccct300astctctctc360gactttttga420441gctggatttcaccttcttgcacctgccggtgagegectggggtctaaagg60tccattatggcccctcgccctgtagggctggaatagttagaaaaggcaac120ttggtaagaagagagacatgcccccaacctcggcgccctttttcctcacg180cttacttcagegactgeaggagcttcacctgcaagaaaacagcattgagc240247cctggagttgttaagtcaccaagtagctgcaggggatggacactgcccca60gatgaacagcagccttggtttgtagcccagggtgtccatggatttgaccc120tggaggcectgtggcgaggacaggcactggatggtccagaccctctggct180tggagecaggactgggccttcagccatgagggcta'gaataacctgacctc240acactgggtcattaatgacacctttccagtggatgttgca3aaaccaaca300cctggccctgggagggctcaggtgageteacaaggagaggteaagecaag360ggkaacacacaacaccaggggaaaccagcccccaaacca409<210〉318<211〉320<212>dna<213〉人<220〉<221>inisc—feature<222〉6,l7,24,271<223〉n=a,t,c或g"00〉318caaggnagatcctcacgsgggtcattggtcgtcactgggcgcctgggttggctggagccccttaagngggtcaggggaac3gg33gctgtctttgctcggccagaatagttgcagccgcagtcntatgtaccttgtagaacctggacgtag3gg3ggc3taaggggagcaagtgtgctccctccaccagcggccatctccc3ccc3g3a3rmgcagggcgtggctccagg3gc3tc3tctacatccatggggcgagatctaggcagggctgttcctggag60cgtgaaggat120gg3tgccat3180tggactcggg240gg33gcc3tt300320<210〉319<211〉212<212〉dna<213>人<220〉<221〉misc—feature<222>172—,<223>n=a,t,c或g<400>319tgaagcaatagcgcccccatagggggtccttccctggctcggcctcagagccctggtaaaaccctgctgcagscctcggc<210>320<211>769<212〉dna<213〉人<糊〉320tggaggtgtatcc33ctcactggagggcgtcctacaaggatgcctgccatcattcataggcccctctgttacttggtatg3gagtggc3gttccsgctccgccbcttacccagcggtatctgggtgctggtttacaggcggagcatggaaaggcagatgggaagatgaggtgtgaccctttttggggtctcgcgaccacgctgcsgtgagagcagtgagagactttctccatagagaagcscgggaggtggaccc33tt3ccctg33ccctcttccagagat333c3gcccc3tstgagaaattgagctcctccaactggaaggagaagggagagatyt.cagtgsgactgcccagcgcatacactggaagggaagtaagggaccctctctggtcttcccggagccacatcataggttgacaggccatgtgcactatagtaggggsaggaagataigctggasggccag3gaggaagccgctg己ttttcsaccctgggtggggg60agacgctgtc120anacctggtc180212gcaagsgtgtcagtactcagtgagcaggggtcattctccttgagtgagtctcctacatgcgcctcccstttcaggttgaactctgagaccttgatgcaatgtgaagcac3gggl:gtggaacacsgcagagccttcatctctactcagatctcagggcatctgcagggcccattcttcttcatattgcagggacaatgatgactgctcattc3cct3ccccgcatttgaacggtatgtatcgcactcacaccctaaascc60ctgggccacc120cttcttggaa180ggccagccac240ctcccsctga300ttcctgacca3603tgctcactt420atggcttgga480tcccc3atcc540acttcaccca600ctctcctgcc660ttggggggtg"720769<210〉321<211>690<212>dna<213>人<220><221〉misc—feature<222〉633,—666<223〉n=a,t,c或g<400>321tgggctgtggcctactccccgtgcctggtgcaggggggctgtctcaacat33gtg3ggtgtctgtgacatcctgtgacctacagaagccaaaagtgcagggacagtgacttccttncgct<210>322<211〉1ch<212〉dma<213>人<400>322gtcgcsagccacgctcacatgcggcacctgcggaggc33cttcgctctgcctgtgaggtccagcacctgccagcctgcsgcggctscggggaggatcgacggatgaaatgacatcctcgcttgagsccsggggccacaggtgctctgcagtgggaggtcascsgccagtgcccaggaatccactgcc3cttgtgtgcacgggagc'ccagtggagactgcttcagaggaatcttctatctggaacttctgggg3gcaccaggccagacagc3cggga3gactctcaggctgcttgtcgcatgtccccctgggccggttccggtgccaccastcatggtgtcggcggggtgcggccgcctggatngggctcagatagaagcc33tc3tcccccttcaaagccgagctgccagctacscgggcgg3ggaggagggtgcattttttcagaggcatggcccagat3gacc3ccaacctacaagactttgtctgtg60tataagaagg120tgggaccatg180aaccatggac240agatactgcc300tgctcgtgcg360cccttccaca420gacacctatt480caagagccag540cgaggtgact600cgccaaggac660690ggagcaccaccatgtagcctttcccgaagtaccggaccttcacggacatcatgg3gc3ggaccaccacctggtcctcctcctcc60104<210〉323<2.11〉118<212>dna<213〉人<400>323gggccctgggcgcttccaaatgacccaggaggtggtctgcgacgaatgccctaatgtcaa60actagtgaatgaagaacgaacactggaagtagaaatagagcctggggtgagagacgga118<210〉324<211〉354<212>dna<213>人<400>324tgctctccggagcggtctgt.ggaagtcattagaacatctctgcaaagccagagcttgaagatggacccagtctttacccaacagtggsicgtttgaagtgcaagaaactgggcttgtcaaaacgcaaggccagaatgacctccagggtctaccttcttgaactacaaagggctgtactatagctgcag3g3ttcctacgctattttaagccgacattgccgcacatcgtgaccaggggatgcttgatgctcctagcgctgscaaatatgacaatgttctcc60cagtcaccat120gagsgtttgt180tggtagctga240aacatgcaaa300actg354<210〉325<211>"2<212〉dma<213〉人<220〉<221〉miscfeature<222><223〉a,t,c或gatgggctcctcc33g3ccsataggtcgctgaaattcaggtcatccacttcggtggtctctccctgcatttgctggagatcgatctgaaggctttgccagattcctgagtatgagcttcgatctcgctcttggcccattctcagcggactctctccaattccaaaigtagacccgtc3agtgaaacgccctg<:■〉325ncatgcttgaccc3ctgat3ggcscttc33gagaggtctgccatcttcatgagttatctgtggcctcssaacatgtaacttgttagtcagcccattcagaaatggcctag<210>326<211>455<212〉dma<213〉人<,〉326tccgtgaggaaccttcacctacgatgatga3tc3gccgg3tccctctgctcggtgcatgg3g33gctggtsctttgagag<210〉327<211〉321<212〉dna<213〉人<4o0>327ttcactgtgactctctgagtaagccaccctggatatttct3tttctg3cagtcttaagga<210〉328<211〉476<212〉dma<213>人<220〉<221〉misc—feature<222〉302,—311<223〉n=a,t,c或g<400〉328tgcaggaggggccatgggggcagtgtgcagtctgatgaagccaagaggtaatgcactcctggtgagagattg33ag3g3cattggtcctttcttagtttgtgcttacagt3gcc3tctggggtttaggggttattctattctgtcattcagtcaagcc3acctggaaaccgtccttcacccctgctcttgggactcttctcgcctcttgccttctctttccactagaggcaatagggaagtgg3actccaactcgcagtctctcttcaatcttcccgcaggacacagggctgaaggaggagggtggtgattgccccctggacagtt33gcgcaccagcagccsgggscagttgctgcttsgcagtgtggtcta3cag3gcatgaataagagataacccagggattgcttttggtgasacaagcaatccattggtagtcgtgccctaccttcaataacttatctgtctaactcctcagatacttttccttttttgct3csgatcgtgtgtgctcatttcca3cct3tttc3atstttttttatgatggattcaaagggcatatcttcacacttttcc333gtggcttttagttttctgcca60120180240300360420柳600642aggcactgcatcattgacaagcctc33ttattcttctgcstgagccctgacccacggtggaagtatgtctacgctggggc3csgtacttcccgt3tccttcggacgc3catcggtggtatggtttcatagaacatgactggccctcacgtcaatc60ccaggcattg120agattcctgc180ggcggcgctt240gatgatcaga300ggcgctgggc360gttgagcttg420455ctcgatgaacgstgctgatgcatggtgaacactgatggccgatctgcttcgtcgcacagatatgcagtccaaggaagttcatggacaaccaatgaggcggtgtgacagccccgaitsgcgcgtaaggacggcccaccttgaacgatgctgcttgtctccttg60cttatactc3120gtgtttgcg3180ttcatccgag240ctcgctgccc300321ctgtgaatggtctgggtgggtttcccatctgatgcagccccatggtgtccctgataaatc60tgtggtctacgggctggcagctaccatgat120ctccaccatctgtatcctggccmagaaaaa180cttcccttcaaaccaaccaaaatttcctttcaaaggcataccggtctaataaagcctcccccatttttcccctggtatgctncagggcttrictgtctgtgggtcatagtttatctcctccaaggcaaagactctactgcctccatctatccagtggaagtgttag^:atgtatgactgtcatctctcccaacagggcctgaacccaaatgccatccttggt240sttcccaggctccctggcct300cacttgctgggagctccttg360ggctcttcagagggtgccaa420cttggsagggcttcca476<210>329<211〉340<212〉dna<213>人<400〉329cgagggagatctaagggtgaaatatgggctgctcatgcactggtggctgggttctgagtctgccagcacccc3csgcccttatccaacccacgctacctacatgccc33t3gcggccacgctgatggagagtcacaagggaaccaagatgttgtggcacgactcttgcccttcagtcacagtgagatgatctgctgcagcgagagtgagggagagtaaggatcctcgcttcagccctgctggagatcttgctgcctggacgggttgtcccgctgccctagtcagtgctag60aaagcagtgg120tgggcccaag180ctttggctgg240gatgtcctct300340〈210>330<211>277<212>dma<213>人〈400〉330tgtcaccatcacattggtgccaaatacccacaggatgcsgccagtgctgacattgttgagggccaggccaaaaaggttgttggcaatccagatgctgctcaggcccaggcac^ccaggtcctccttgttttcccagaaccctgtgtgaaggaagacatcggtgcaggagcgtgcttcctccttggtgtca3gcag3ct3gatgaag3gtccgcccagtctactccattaagggagaaagcaggtaccagacgccaacaattcataattgatgatctc60120180240277<210>331<211>136<212〉dna<213〉人<400>331ttgcttcct:acctcctttctctgtcctctcatacaaaccacacacacaatgaggatgaaaccgggcggccgctcgactgaggttctgccttacaatggggacactg60acagataacaggtaaaatgacctcacctgc120136<210〉332<211〉184<212>dna<213〉人<400>332ttgtgagataaacgcagatactgcaatgcattgctgatcttattgttgtctaagtagagaagtctggctatctgattgaagctcaagtcagcsgttaaaacgcttgaaatactcatcagggatg60gttagaagagagacagggagaccagaaggc120aggtattcgagtgatttaagacctttaaaa180184<210>333<211>384<212>d船<213>人<400>333cggaaaacttcgaggaattgctcaaagtgcctgtggctgcagcgtccaagccagcagtggtcaaaiacctccaccsccgt:gcgcaccacagaggagcagactgtggatgggaggccctgtaaaatggtctgtgagcagaagctcctgaaggaactgaccaacgatggggaactgatcctgagggtctacgtccgagagtgagcggtgggggtga'atgtgatgctgaggaagattg60agatcaaacaggagggagacactttctaca120agattaacttcaaggttggggaggagtttg180agagcctggtgaaatgggagagtgagaata240gagagggccccaagacctcgtggaccagag300ccstgacggcggatgacgttgtgtgcaccat360384<210〉334<211〉169<212〉dna<213>人<220〉<221〉misc—feature<222>2,<223〉n=a,t,c或g<400>334cnacaaacagagcagacaccctggatccggaaaattgaatttccacttcctgaccgccgcagcaagatgaacctctctgaggaggttgactcctgctactggccaggacggctggaccgt60cagaagagattgattttctccactatcact120ttggaagactatgtngccc169<210〉335<211〉185<212>dna〈213〉人<彻〉335ccaggtttgcagcccaggctgcacatcaggtgctgactgatggtgctgtgacggatgtggcgaacctgcccatgtcagtgatcattgtggagcagggsctgcctcgcal3tacttcatgctgttgc60aagccacacgtgaggctgtggtgcgtgcct120gtgtgggtggtgctgactttgaggccatgg180185<210>336<211>358<212>dna<213>人<220><221〉misc—feature<222>26—<223>n=a,t,c或g<化0〉336ctgcccctgccttacggcggccaganacactttgttctcagtcccatccaactccagcatagagagacctgagctgatgagggctggcgocaggac3cctttgcctaagtaacgctgtttgatgcccgtagaggctccactgggcactgcatccacctccactgtggggttcccgcggga<210〉337<211>271<212〉dna<213〉人<220>acccaggatggcattggccccaaacttgga60caggttgtccagtttctcttgctccaccac120gatggtggagttgatgtggtccactgcctt180gtctccatccctcagctccagggcctcata240agcccggaaaagacctttggcagtatagag300gtccaggatctcccgggcccagatcttc358<221>raisc一feature<222>17—<223〉n=a,t,c或g<400>337cacaaagccaccagccngggaaatcagaatgaaatcctgcccagcatgggattcagaacccatacaggataaaacaaattcaattgccttcaaagccaaagttgccaccgcacaaaaagaaaaagtagatttttcacsttcccatgaagcatt己cttgatgcaactgacttgtaatagcca60tggtctgcaaccaaatccaccgtcaaagtt120ttccacattaatagcatcaagcttccccaa180gaatcttgtgtcaatttctccctactttat240g271<210>338<211〉326<212>dna<213>人<220〉<221>misc—feature<222>15,"17,18<223>n=a,t,c或g<400>338ctgtgctcccgggaaaggctaatcaggtcatcgacgaaactgtggactgctgccatctgggactngnncaccscggggcaaagattttgcagsagaactttagctgtagatctcaggtacgggatscatcccaactggtcagatacagcccgggagctcgttctggcaccgsctgctcgaggccagggcttcagaggtsccsgsgtactgggcgggtcatcctctgtttccscsgaatgtcc3c3ggtaac3accag。cctctggg60gaggcsgccc120agagaggctt180gtgttgcata240cgggtgtaag300326<210>339<211>260<212>dna<213>人<220><221>misc—feature<222〉仏化60,69,<223>n-a,t,c或g<400>339ttcacctgagcaaggacgncccaagtgctgctttsggacgcctcggccgcgactcatttcacatttccacgatcccagactccanctaptgaccacgcta<210>340<211〉220<212>dma<213〉人<220〉<221>misc—feature<222〉15,丁8<223>n=a,t,c或g90,91,96,113,117,119,195gtgccctttgttgacttcaagcaaagnccttcanggtctn60ttgcgaatgnnctcanggctcatcttg^agaanaagnanc120tcgggggtaaccttgtgggtaagagctcatccagtttatg180cgggggagctggaagcctgcgtggatgcggccctgctgga240260<400>340ctggaagcccggctnggnctggcagcggaaggsgccaggcaggttcacgcagcggtgctg60gcagtagcggtsgcggcactcgtctatgtccacacactcgggcccgatcttgcggtaacc120atcagggcaggtgcactgataggagccaggcaagttatggcagtcctggctggggcgaca180gtcgtgcagggcctgggcacactcgtccacatccacaciag220<210〉341<21i〉384<212>dma<213〉人<400>341ctgctaccaggatggsgcttggcgtcaccatttcccaggacccgttggctggcaattatasagtgccactgggagcgagacacacgatttgtggcccgtctcsaggccsct3c3g3agtctcacattgagggtttaccaggctgactatccctcctgcggtgcctcaggaagggaggaagatggtgttcaacagaaattcccagcctcggcsgcggcgaaactcctccgaattgcacgggtaccagatgtctaatgtattggtcctctacgtgagggaggcactgttctggggtagccatcc3gcc3cccctacgccatg60tgctacsccg120sgggggctcc180aggaggaagc240cctga_3tggt300tggggcagtg360384<210>342<211〉245<212〉dma<213>人<400〉342ctggctaagctgtaaccaaccacagctctgcggctgttctggcagtcatcattgttactggtgggcaccatgtccttgaagcttcaggcaagcaa3agaatgaccccaagtccatcaactctcgagtcttcattggaaacctcaagtg3agaa3tcagatgtggagaccatcttctcta3gtatggccgtgtggcgtgcacaagggctatgcctttgttcagtactccaatgagcgccatgcccg60120180240245<210〉343<211〉611<212〉dma<213>人<400〉343tctcagccattttcctgccatgcatcacactttttttaaccsaaagaaatagcagcagaattttacctcsatagcccgtataaatsccccctttgaagctgtgtcagaaataattacaaataata3tggcgattgacttgggttagttttatttga3c3gctagatcttgttttttt3tttgaaagaagaatcctatttaa_t3catgagtat3csagttctttgaasgaaagggtctctga3tt3tgtag3t3a_gtttgcggaacatggatgcactgaaagtctttggtatgaatcctgttatttctaaggaggctt33ttttggtaagacttctgttaactgcatgctgtcttagagtcaactaatcatttttgtassccggtattccttttgaaaaatatttttcttcttgggggtggatacatcatttattaagtgtgacatgcctcaactgttaat60gttagcagac120tggtatctga18033a3agaa3t2403ttttaa3ac300taactaaaat360tttttgtctg480agaaccatga540agttcttata600611<210〉3"<211>311<212〉dna<213>人<220〉<221>misc<222〉<223〉feature275,284,296,297,300a,t,c或g<400>344nctcgaaaaa3acctg3ctg3gctgsctcaagtgcaatgatttggggctt<210〉345<211>201<212>dna<213>人345c3cacggtcaaatgtcaccattctactccctctgcctatg<210〉346<211>370<212>dna<213>人<400〉346ctgctccaggtctcttcagactcccggaaagttggtgacaacstacttggggcgctgacggcccaagacacagaaaagagcggtgttatgggcsgs3gcag3tgtcccagtagaatt3ccsacacctccagtcatcgtccacaactgaagatgasgtactgaggantacattgaactagcagtgcctgaaccttt333c3ttaagaatccttaanaagtacaagaaaagca60cctt3ccgg3120ctggctcgca180gaggscctgg240atgcannaan300311tcccgactgccaacctggaggcccaggccctgtggaaggagccgggcagc60tgagtgtggatgctgagtgtgtgcccatggtcagggaccttctcaggtac120gaaggattgacatcaccctgtcgtcagtcaagtgcttccacaagctggcc180gggccaggcag201gcgtggtgtgatgttctggattgctgttgctaaggcaggtccttcgtggcgcagcagtttggcgctggcatattcatcagagacccggcgt3ttgttctc<210>347<211〉416<212>dma<213>人<220><221>misc—feature<222>416—<223>n=a,t,c或g<400>347ctgttgtgctccccatttgaagaacaaggactggtggggaatttgctgga3tgcactaat<210>348<211〉351<212〉dna<213〉人gtgtatggacacaagcaaagtg3gsttgcttcagtatcagggacattga3cgtgagcatgttgaaatattgtgggctttaasggtgait33ttagtcctgtaacstcscagagc3333tccgaitgtgattccactgacctcctctgcctccgaggcgggtggscggggtcggetctggaaggaagtctgggaaagttctcttccgaggagcatgcgttggactctccagctgtgcgttcctgcgtggttcatccaggtctgcaggctgtgt60agggcagaat120tctccaagac180gataggtctg240ggactacgtc300aaaggaacgt360370ccatgagtaaccstgtttgtttggt3csg3tgcacagaca3scc3ggttcaagcagcccgctccattcctacsgcg3c3gtggcactgactctgatgctatca3c3ggcta3t3ggaaagattcagcaaaggtatagaat60gtgtttgctg120a3tccccttt1b0ccagattttg240gacttcctgg300aagtttggag360agtcan416<400〉348gtacaggagacagttggatgtctacagcagcttgtctc33ctttacgggt3ggctgtctc<210〉3"<211〉207<212〉dma<213>人ggatggcaggctctcctggaaagaaacggcctgc3aagaggtcaggctggagtggggggatgc3g3gcggggctctgaaa3ggcagtgccgcgtt:ccttcgggscsgtaaaaccttggacgcactgagctttgaaacgggcagggacgagctctttcactggtctttcccaatacccgggctgcaggtgacaggaaatagcaggagacaga3tcctcctcttccc3ca:agctttcttgggaagggctcgg60tctggcagcc120atgccttcct180agcacagacc240gccatstctc300c351<220><221>misc一feature<222〉1一<223〉n=a,t,c或g<400〉349nccgggacaittgaccagtga3cagagtg3gcggtggaggcctccaccctcaacagtggcaagaagagcctggagactgaagattgcactgctgcagtccaggctgaagacagagggctctcgaaatgcagaagctggatgcacaggtcaaggagctggtgtgagcgcctggtggctgcacaaggcct60gatctgtgcg120ctgaagtcgg180207<210〉350<211〉323<212>dma<213>人<400>350ccatacagggggggccagc3gagacctgggtggg3gcc3tctactgcgaaca3ggcggggctgttgcccaccatccgtctgtgtaaatggtggctgtg33ttg3tgacatctcctgatgcggccctsg3gacttacctcctgagacgggtgctgcagactcgtttcaggctgggtcattcctccttcgggccaactttggtggtataagacaggt3ccctgat3gc3c3ccc3acatgaaggacsgtggagacaaggcg3tgaccagaactgt60ggagaactgt1203ctgggcats180ggcagttctg240ccagagccgg300323<210〉351<211>353<212>dna<213>人<220〉<221>misc一feature<222>12,55,39.42<223>n=a,t,c或g<權〉351cgccgcatcctgtttttgttttgtccgttttccggactcgttttgttgcgttctgasacccntggtccctttgtagggttctgtggggttcctgcttggtaatctgagccatacttttactccsntcccttttttccttcaggtttatgtggcgattctcttcttcctccctgagtttcctttcctttnttccacctctcttttaatcatc3ccggtt33agcttctgccgtgaggctgacngggaacgtcctgtctcttctgaggtcactatggtgcgtttttgaacttggctgtgtgcgtatgcggtt60ttgctccatg120gtctatttcc180cccttttttc240tgttcttcgg300caa353<210>352<211>467<212〉ona<213>人<400〉352ctgcccacacaatttgagcagtcaagagcagaatcgaaca33ctctggctctsctatccctcacccaagcaagagaccct<210>353<211>350<212〉dma<213〉人<400〉353ctgctgcagcgaaatctgtcgaaatgctgcctgattgtgtgsgttacaacttgaagatgc<210>354<211〉351<212〉dra<213〉人<400>354atttagatgattttaggtttsgcagatgatgaatggcagtaaagagctgaagttgtatat<210〉355<2ll〉308<212〉dma<213>人<400>355ttttggcgcaatgcaaatgttcgtgagaattcactcag<210〉356<211〉207<212〉dna<213〉人<400>356ctgtcccaagatgaagaatatgatcacttgcgagatgtccttagggtacaagaacaggaattgaagtctg60gaacctgtctgagaaactctctgaacaagaattacaatttcgtcgtctca120agttgacaactttactctggatataaatactgcctatgccagactcagag180ggctgttcag3gccatgcsgttgctgaagagga3gcc3g33s3gcccscc240ttcagtggaggcattaaagtacagcatgaagacctcatctgcagaaacac300gctgggtagtgcagttgaggc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258026402*700276028202880formulaseeoriginaldocumentpage217305vallysaspserasn385thrthrleumetglyserthrglyser"valvalargthrse;rval625ginleuaspgluser705asnserproleuglyaspprogin370aspthrprophetrpl>euglyglyljeulie530asnvaltyraspleu610ijysproserliyspro690gluphealaleulieproglylys355leuserseralathr435proservalasp515thrglysermetasn595glyasnlieuginasp675proalathrthirphe755lieuthr340serthrleuthrsex!leuglya巧argasp50qarggluphegluiua580valalaglysergin660serthrthrliephe740ginljeutyr325alaprohisphepro工leasnserproleu485alagluleuthrgluaspmetargalaglythrleuthrthrser725asnlysarg310serthrargasnval390glyphepheargleu470th:rlieginglyhis550pxometlystyrglu630prohistyrproala710asnserserproglyglyleu工le375asnthrglythrlyspheleucysleupro535argpheglyhisthr615thrglyglyleu!lys695metleuthrserglucysvalasp360thrglyproprolie440phelysi^euthrtyr520tyrserthrginleu600glyargleulieasn680proglyginglumet760lysargasp345arggluphethrser425thjrasnasnarghis505;leuthrserpro585!leucysvalprothrglyalatyrtyrgly745glyaspleu330alagluleuthrvalalathrthrproarggluleuvalasn570glyseraxgasplie650argtyrthrhisser730valprogly315thr工leginglyh丄s395tyralaleuthrser475gluproleuasppro555pheserproval!leu635lysleuasnthrlieu715proleuphealaleucysleuhis380argleuser■arggluvallysaspserarg540thrthrlieuleulie620!leuginglygluphe700lysaspgintyralaleuthrtyr365tyrserglyhistyrargglyaspptogin525aspthrlielysphe605alacysvalpropro685leuthrmethisleu765thrarghis350trpalasermagluvalproglythr510ljeuserserasnphe590ginleuthrphetyr670glyproleuglyleu750glygly320proglu335kisprogluleuleuaspva丄ser400serlys415leuliegluasnleuginleutyr彻gluma495glyprothrhisleutyrthrgly560asnl^eu5*75asnlieargserargsertyrleu640hisglu655serleuleuasppro!leuthrlieu720lysgly735cysginvalasp770775780thrthrcysthrhisproaspprovalglyproglyleuasp工le785790800ginginleutyrtrpg丄uleuserginieuthrhisglyvalthrgin805810815leuglyphetyrvalleuaspargaspserleuphelieasnglytyr820825830alaproginasnleuserlieargglyglutyrgin工丄easnphehis835840845lievalasntrpasnleuserasnproaspprothrserserglutyr850855860liethr!euthrthrarg110511101115112[argarg乃yslysgluglyglutyrasnvalgingingincysprogly112511301135tyrtyrginserhisleuaspleugluaspleugin11401145<210>459<211>1156<212>prt<213〉人<40o>459gluargvalleuginglyleuleumetproleuphelysasnthrser151015serserleutyrserglycysargleuthrleuleuproglulysaspasppro50sergin65arghisthrthrthrproleuphe130methisginglytyrseralathrpj:ogly210hisser225tyrvalproglylysproasnphe290glyser305argserargljeuaspalaargg丄u370gluleu385phethrthrvalseralathrasnasnthrasnthr20glyalaala35lysserproleuthrhisserleutyr85argthrpro100alaserleu115thrlieasnhisproglyleuleuarg165glycysarg180lysvalasp195leuaspargliethrgluasnglyphe245thrprothr260glyproser275thr工lethrarglyspheleuphelys325thrlieuleu340工lecysthr355ginleutyrglyhistyrhisargser405tyrleugly420alaserhis435leuargtyrthrgluargservalglyglygly70valaspserpheser150proleualagluleu230thrvslalaasnasn310serarghistrpala390seralaleugluv3l470proleu55lieasnthrglythr135argvalthrliegin215glyginaspalaleu295thrthrprohisglu375leuvalser]jeugluleuleu25valaspala40asparggluthrgluleuglyphethr90serthrmet105prothrthr120工lethrasnlyspheasnphelysasn170leuleuarg185cysthrtyr200leutyrtrpprotyrthrargserser250leuglythr265serproleu280argtyrgluthrgluargservalgly330glulysasp345proasppro360!leuserginaspasnaspserthrthr410lysthrpro425lieleupheasnmettrpginglyleutyrserglyvalarggly75hishisalaleuthr155thrproarggluleu235cysleu60progin!eu!leuargprog丄ulys500hisargproasp515lieugluleuser530thrleuasparg545servalprothrleuasnphethr580proglyserleu595leuserproleu610cysargval工le625valaspleuleupi:o工lelysgin660thrargleugly675glytyrasnglu690alathrthrphe705tyrhisleulystyrserproasp740glyvalleugin755glyprophetyr770aspglyalaala785provalglyproginleuthrhis820aspserleuphe835glyglutyrgin850proaspprothr865asplysvalthrargphecysleu900vallysalai^eu915valpheleuasp930thrtyrginleu485aspproginaspthr565工lelysphealacysvalproproleuthr725methisjoeuthrgly805glylielieserthr885valpheiiysva丄glythr乙euser550serasnpheginleu630thrphetyrglypro710lieuglyijeuglygly790leuvalasnasnser870leuthrserthraspgluglyth_r535leuthrasnasnarg615argtyrhisserleu695prothrlysleucys775valaspthrglyphe855giutyrasnserleu935工lealapro520histyrglyijeulie600serserlieuglu!leuaspleuleuglyarg760ginaspliegintyrhistyr!>ysleuasn920asnhis丁hr505glyservalvalarg585thrservalginl>eu665aspgluserasnser745pro!leuthrginleu825alalie工leglythr905leualaval490glyleu工leasnval570tyraspleulyspro650serlysprogluphe730alaleu工lethrgin810glyprovalthrser890metaspserthrvalaspthrgly555sermetasnglyasn635leuginaspproala715thrthrphesercys795lieupheginasnleu875ginaspprophegluaspargglu540pheglumavalala620glyserginser:thr700thrliepheginleu780thrtyrtyrasntrp,leuleuserserhismetalaglu525leuthrgluaspmet605argalaglythrjleu685thrthrserasnlys765argtyrtrpvalleu845asna:rghisvallieu925trpglulie510ginglyhispromet590lystyrgluprohis670tyrproalaasnser750serprohisgluleu830serleuaspaspijeu910valleu495cysthrleutyrprotyrargser560phethr575glyginhisleuthrglythrarg640glyijeu655glylielysprometgly720leugin735thrglusermetglulysproaspjoeuserb15asparg工leargserasnliegin880thrphe895valthrgluginglyser945ty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tableseeoriginaldocumentpage226
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tableseeoriginaldocumentpage248
formulaseeoriginaldocumentpage249tgccattcacctggatctagagaaggatgggacctgggctctgagctggg<210>525<211〉470<212〉dna<213〉人<400〉525gtttcacccsgggcaaccactacc3ttc3cctggttcc3gtc3ag33ctcagsaggstgggg3cctgggc3ctg3gctgg<210〉526<211〉467<212〉dna<213〉人"00〉526gtttc3cccagggc33ccsctaccattcactggttccaggc33g33c3ccgaagcaggagccctggactgcgagctgggc<210>527<212〉dna<213>人<400〉527gtttcacccataggascctctgcc3ttc3cctggctccagtcaagaatacgccctggactctgagctggg<210〉528<211〉537<212〉dna'<213>人<400〉528ccta33cttcaccatcsccaacctgcagtatgaggaggacatgcatcgcc180gaagttcaacgccacagagagggtcctgcagggtctgcttagtcccatat240cagtgttggccctctgtactctggctgcagactgacctctctcaggcccg300ggcagcaactggaatggatgctgtctgcctctaccaccctaatcccaaaa360ggacagagagcagctgtactgggagctaagccagctgacccacaacatca420cccctacagcctggacagggacagtctctatgtcaatg468tcagaactctgtgcccaccaccagtactcctgggacctccacagtgtact60tgggactccatcctccttccccggccacacagagcctggccctctcctga120attcaactttaccatcaecaacctgeattatgaggaaaacatgcaacacc180gaagttcaacgecacagagagggtcctgcagggtctgcttagtcccatat240cagtgttggccctctgtactctggctgcagactgacctctctcaggcccg300ggcagcaactggaatggatgctgtctgtctctaccgaccctaatcccatc360tggacagagagcagctgtactgggagctgagccagctgacccacgacatc420gcccctacagccctggacagggacagtctctatgtcaatg470tcagaactctgtgcccaccaccagtactcctgggacctccacagtgtact60tgggactccatcctccttccccggccacacagsgcctggccctctcctga120tttcaactttaccatcaecaacctgeattatgaggaaaacatgcaacacc180aagttcaacaecaeggagagggttctgcagggtctgeteacgcccttgtt240agtgttggccctctgtactctggctgeagactgaccttgctcagacctga300gcagccactggagtggacaccatctgcact,caccgccttg3ccctctaa3360gacagagagcagctatactgggagctgagcaaactgacccgtggcatcat420ccctacctcctggacagaggcagtctctatgtcaatg467teggaacttt.gtgcccatcaccagcactcctgggacctccacagtacacc60tgaaactccatcctccctacctagacccatagtgcctggccctctcctgg120cctcaacttcaccatcaccaacttgeagtatgaggaggeeatgcgacacc180gaagttcaataccaeggagagggtcctacagggtctgetcaggeccttgt240cagtateggecctctgtactccagctgcagactgaccttgctcaggccag300ggcagccaccagagtggatgccatctgtacccaccaccctgaccctcaaa360gagcagagagcagctgtactgggagctgagccagctgacccacggcatca420cccctacaccctggacaggcac3gtctctatgtcaatg468gi:ttc3ccc3tgggaacctctgctattcacgctggctctattcaaagaaccgagaaggataaagccctggctcctcatatggcggtcatgtcagagccccgagaactccagaaagttt3aaccagtgttgggggcagccaactggscsgacgcaggttagggtccagaca3t3cc33cc3gcctccctgtaccatcactacaccacggaggccctctgtacgcaaagtgggagcagctattgatggtgsagggagcctggccagcactccctggacctacacctgcggtaagagtccttcctctggctgcatgccatctgactgggagctgttaattgtgagttctcgagtgatacctccgaccgccagctgaggagaacagggtctgctagactgacctcacctaccgcgagccagggtaatagcaccagttgccaggtacaatgcacc60cctctcctgg120atgcatcacc180caggcctgtg240tgctcaggcc300cctgatccca360gatgcatgtt420ggsgagggct480gcatgtc537<210>529<211〉231〈212〉dma<213>人<529tgttccsgagctgtgaagaagcggcccaggtc3cccggctgagcagcctgcggtgctg3gtctgcct3tcgggcccctacggtgcacggtscacgggtggaagcaggtgttctctggacaacacaggctgacctcctctgtccatgagctaagacagcctcaigggtcaitccacctacctggagccagcagctaccttsacgcactaaggt60cagcccctca120scccatggca180g231<210>530<211>376<212>dma<213〉人<400>530gttacaatgatgcctcctct3cttc3cc3tactccaccgagacaccaccttactgggagc3gcgatagct3cctggtcc3gtcagaagccctccsstctcgggggtccttgcacctaccatgagtcagctcttcaitgatgagcctccsgtattcaccagcacctggccctgaccctgscccatggtc七3c33ctcctggggtaccacctgagaagggtgggccccggtc3cccsacc33gccagcccctgaagacccsagggctca3tggggc3gcggctggacattgggcttctaacc3cattcc60ctcacactca120gctacattca180cactggtgtg240acagcagctt300tgtcctggac3603"6<210>531<211>75<212〉dna<213>人<则>531ggtaaccacagctgacccatggcatcaaagagctgggcccctacaccctggacaggaaca60gtctctatgtcaatg75<210>532<211>906<212>dma<213〉人<秦〉532gtttcacccattgggacctctgccgttcacctggctccagtcaagaactc3ga3ggatgggccctggacttatcacctattcggagctctagggactccacctcaactttgaagttcaaccagtgtcggcggcagccactggacagggagtctgagacacgtggcccccatcctccctcc3cc3tc3cc3accacagagacctctgtactgg3gtgg3tgcagctgtact3c3c33gttcccagcactcccc3gcccc3catctgc3gtagggtcctgcactggctgc3gccatctgcacggcagctgag3gcc3ttcc3tgggacctccaacagctgtttggggsggacgggtctgcttactgatctctcc3ccaccttcc3g3gaccaactctccctgacagtggacc60cctctcctgg120atgcgtcacc180ggtcccttgt240ctcaggtctg300aaccctcaaat360caacctcatt420tctccccctg480gtgcatcaaatcccaaceictctgcagagaic3c3cc3c3ctcg3c33ct3tcagacaccagccacgtggct11tccc<210〉533<212〉dna<213>人<400>533gtttcacccattgggacctctgccgttcacctggctccaigtcaagaactcagaaggatgggccctggsct<210〉534<211〉157<212>dna<213>人<锡>534gcagccsccsgacagagagcccct3c3ccc<210〉535<211〉468<212〉dna<213>人<秦>535gtttc3c3c3tgggaiac3tctgctattcacctggctccagtcaagagcscaaaaggatgggccctaggctctgagctggg<210>536<211>334<212>dna<213>人<糊>536gtttcactcatgggagcatctact3ttc3cgctccagga3gatgctgacctcactggtcatcagttctgggacagacagcactacaactt540gacggagaccccatatgaaccagagacaacagcc3tacagctcattcatc600caacacaatggttcccaggacaactcccaagttttcccatagtaagtcag660cccagtagccatcaccagtcctgggccagaagccagttcagctgtttcaa720ctcacctgatatgtcagatctggtgacctcactggtccctagttctggga780tacaaccttcccaacattgagtgag^ccccatatgaaccagagactacag840cactcatcctgcagaaaccagaacaacggtttctgggacaattcccaact900906tcggagctctgtggcccccaccagcactcctgggacctccacagtggacc60agggactccatcctccctccccagccccacaacagctgttcctctcctgg120cctcaactttaccatcaecaatetgeagtatggggaggacatgcgtcacc180gaagttcaacaccacagagagggtcctgeagggtctgettggtcccttgt240cagtgtcggccctctgtactctggctgcagactgatctctctcaggtctg300ggcagccaictggagtggatgccs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cagtgttggccct5700ctgtactctggctgcagactgaccttgctcaggcctgaaaaacgtggggcagccaccggc5"760gtggacaccatctgcactcaccgccttgaccctctaaaccctggactggacagagagcag5820ctatactgggagctgagcaaactgacctgtggcatcatcgagctgggcccctacctcctg5880gscagaggcagtctctatgtcaatggtttcacccatcggaactttgtgcccatcaccagc5940actcctgggacctccacagtacacctaggaacctctgaaa'ctccatcctccctacctaga6000cccatagtgcctggccctctcctggtgccattcaccctcaacttcaecatcaccaacttg6060cagtatgaggcta_c3gggtctgcagactgatgtacccaccctgagccagcctctatgtcrtccatagtgaggccctctccaacatgggtcctcaagccctttgctcaggccctgacccca3ccc3c3gc3ggtttcacccccgg333cctctgccattcacctggctccattcaagaacagagaaggatgagccctggacactgagctggcagagctcta3g33ctccagattaacttcaagtgttggccgc3gcc3cc3g3c3g3gagcccct3c3cccccc3cc3ct3tcta33cctg3tc3cc33ccacggagagggctgtactctggtggstgccactgtattgggaictcctgggaccttcagctgcggtstgaggcagggcctgcaggctgacctsccc3ccgccagccagctgatatgtcaatggaggagccatcaacccggctttgttccagatctgtgaaga3gcggccc3gatcacccggcgaacctggtcct570<211>469<212〉dma<213>人<220><221〉misc—feature<222〉71,9!,93,120,124,168,178,218,230,300,321,350,387,412,414,415,422,423r451<223〉n=a,t,c或gtcggagctctwgggactcc;acctcaacttcgaagttcaacccsgtgttgggggcagccactggacagagagcccctacacgtgcccsccatcctccctccaccacgg3gaccctctgtacyggagtggatgc3gctrt3ccctggacaggccagcactcccyrgccccacacctgc3gtagggtcctkcatctggctgcaigccatctgcatgggagctgarac3gtctct<400>570gtttc3ccc3tgggsacctctgcyattcacctggctccagttcsagaacagagaaggatgagccctggscamwgagctgg<210>571<211〉130<212>prt<213>人<220〉<221>variant<222>69,107,110〈223〉xaa:任何氨基酸<400>571hisproginleugluginginproginserhis510tgggacctccagctgctggctgaggagracgggtctgctygactgsccttccc3ccgccygccagctgac3tgtcsaitgacagtggacc60cctctcctgr120atgcatcrcc180aggtcccttg240gctcaggccy300tgaccccaaa360cmayrgcatc420469sertrpcyshisser15proserthrserthrhishisginproalavalargglyglyhisala202530alaproglyserarglyspheasnalahisarggluargthralagly3540—45sercysserasnproargserglyliealavaltrpasnthrserlie505560ginalaalaaspxaaprohisserglyginargarg工丄ealaginpro65707580arggintrpmetproseralahisliealaleuthrleulysthrser859095asptrpthrgluseraspcysthrglyserxaaalaliexaaginmet100105110alaserargsertrpalaprothrprotrpthrglythrvalsermet115120125sermet130<210>572<211〉130<212〉prt<213〉人<220><221>variant<222〉1,58,78,92,94〈223〉xaa:任何氨基酸<400〉572xaalieproserserasnserserhisserproliehisglyalalie51015hisproginleuginleu工lethrasn!>eugintyrglugluaspmet202530arghisleuvalproglyserserthrargthrgluarggluleugin3540'45glyargalaginthrleuaspgingluxaaginserglylieproleu505560phearg!leuginthrserleuthrginalaarggluglyxaai>euser65707580hisglyserglycyshisleuhisthrserproxaaproxaaargpro859095argthrglyginargalathrvalleuglyalagluginserasplys100105110trphisproglyalaglyproleuhisproglyprogluginserleu115120125cysgin130<210>573<211>130<212>prt<213>人<220><221〉variant<222>1,54〈223〉xaa-任何氨基酸<400〉573serprothrleuasnalaargthralaalathrval10prophemetvalglythrvalval50sergly6535leucysthralavalglyleuaspglyliegin115pheasnserserpro20phegingluvalgin40lysproxaaliearg55argleualaserleu70aspala工lecysthr85arggluargleutyr100gluleuglyprotyr12025cysseirthrargargalaginarg30pro15thrpheasnserserargprohis10590glu75pro60lysaspcysasncysargglutyrleutyrglu45aspserse:rprogluala80lieugluleuserasnleu110asp95thrasnthrleuaspargasnserleutyr125valasn130<210>574<21i>156<212〉prt<213>人<220><221>variant<222>101〈223〉xaa-任何氨基酸'<400>574glyphethrhisargsersermetprothrthrserthrrproglythr51015serthrvalaspvalglythrserglythrproserserserproser202530
tableseeoriginaldocumentpage267
alaliecysliehishisleuaspprolysserpro115120glyleuasrrarg125gluargleutyrtrpgluleuserginleuthrasngly工lelysglu130135140leuglyprotyrthrleuaspargasnserleutyrvalasn145150155<210〉<211〉<212〉<213〉576122prt人<400>576alaalaglyproleuleu'valleuphethrleuasn510asnleu.lystyrglugluaspmethisargprogly2025asnthrthrgluargvalleuginthrleuarggly3540asnthrserglyglyleuleutyrserglycysarg505560argserg丄ulysaspglyalaalathrglyvalasp657075hisargleuaspprolysserproglyvalasparg8590trpgluleuserginleuthrasnglylielysglu100105thrleuaspargasnserleutyrvalasn115120phethrliethr15seraxglysphe30pro.metphelys45leuthrleuleualaliecysthr80gluginleutyr95leuglyprotyr110<210〉577<211>156<212〉prt<213>人<220〉<221>variant<222〉11,106,151<223〉xaa=任何氨基酸<權>577glyphethrhisargthrservalserthrvalaspleuglythrser20prothrxaaserthrproglythr1015glythrpropheserleuproser2530proalathralaglypro乙euleuvalleuphethrleuasnphethr354045工lethrasnleulystyrglugluasp&ethisargproglyserarg505560lyspheasnthrthrgluargvalleuginthrleuleuglypromet65707580phelysasnthrservalglyleuleutyrserglycysargleuthr859095leuleuargserglulysaspglyalaxaathrglyvalaspala工le100105110cysthrhisargleuaspprolysserproglyvalaspargglugin115120125leutyrttpglul>euserglrvleuthrasnglylielysgluleugly130135140protyrthrl>euaspargxaaserlevityrvalasn145150155<210〉578<211〉155<212〉prt<213>人<400〉578glyphethrhistrp工leprovalprothrsex:serthrproglythr51015serthrvalaspleuglyserglythrproserserleuproserpro202530thrthralaglyproleuleuvalprophethrleuasnphethrlie354045thrasnleugintyrglugluaspmethishisproglyserarglys505560pheasnthrthrgluargvalleuginglyleuleuglyprometphe65707580lysasnthrservalglyleuleutyrserglycysargleuthrleu859095leuargproglulysasnglyalaalathrglymetaspalaliecys100105110serhisargleuaspprolysserproglyleuasnarggluginleu115120125tyrtrpgluleuserginleuthrhisglylielysgluleuglypro130135140页tyrthrleuaspflxghisserleutyrvalasn145150155<210>579<211〉155<212>prt<213>人<220><221〉variant<222>52,138<223>xaa=任何氨基酸<400>579glyphethrhistrp工leprovalprothrserserthrproglythr51015serthrvalaspleuglyserglythrproserserleuproserpro202530thrthralaglyproleuleuvalpro.phethrleuas.n-phethrlie354045thrasnleuxaatyrglugluaspmethiscysproglyserarglys505560pheasnthrthrgluargvalleuginserleuleuglyprometphe65707580lysasnthrservalglyproleutyrserglycysaxgleuthrleu859095leuargserglulysaspglyalamathrglyvalaspalaliecys100105110thrhisargleuaspprolysserproglyvalasparggluginleu115120125tyrtrpgluleuserginleuthrasnxaalielysgluleugly'pro130135140tyrthrleuaspserasnserleutyrvalasn145150155<210>580<211>156<212>prt<213>人<220><221>variant<222>23<223〉xaa=任何氨基酸<400〉580glyphethrhisginthrseralaproasnthrserthrproglythr51015serthrvalaspleuglyxaaserglythrproserserleuproser202530prothrseralag丄yproleuleuvalprophethrleuasnphethr354045liethrasnleugintyrglugluaspmethishisproglyserarg505560lyspheasnthrthrgluargvalleuginglyleuleuglypromet65707580phelysasnthrservalglyleuleutyrserglycysargleuthr859095leuleuargproglulysasnglyalaalathrglymetaspalalie100105110cysserhisargleuaspprolysserproglyleuasnarggj_ugin115120125leutyrtrpgluleuserginleuthrhisgly工lelysgluleugly130135140protyrthrleuaspargasnserleutyrvalasn145150155<210〉<212〉581156prt<213>人<400〉581glyphethrhisargserservalalaprothrserthrproglythr51015serthrvalaspleuglythrserglythrproserserleuproser202530prothrthralavalproleuleuvalprophethrleuasnphethr3540.45liethrasnleugintyrglygluaspmetarghisproglyserarg505560lyspheasnthrthrgluargvalleuginglyleuleuglyproleu65707580phe]lysasnserservalglyproleutyrserglycysargleulie859095serleuargserglulysaspglyalaalathrglyvalaspmalie_100105110cysthrhishisleuasnproginserproglyleuaspargglugin115120125leutyrtrpginleuserginmetthrasngly工lelysgluleugly130135140protyrthrleuaspargasnserleutyrvalasn145150155<210><211><212><213><220〉<221><222>582156prt人v3ri3nt151<223>xaa-任何氨基酸<400>582glyphethrhisargserserglyleuthrthrserthrprotrpthr51015serthrvalaspleuglythrserglythrproserprovalprose:r202530prothrthralaglyproleuleuvalprophethrleuasnphethr354045工lethrasnleugintyrglugluaspmethisargproglyserarg505560lyspheasnalathrgluargvalleuginglyleuleuserprolie6570"7580phelysasnserservalglyproleutyrserglycysargleuthr859095serleuargproglul>ysaspglyalaalathrglymetaspalaval100105110cysleutyxhisproasnprolysargproglyleuaspargglugin115120125leutyrtrpgluleuserginleuthrhisasnliethrgluleugly130135140protyrserleuaspargxaaserleutyrvalasn145150155<210>583<211>156<212>prt<213>人<220><221>variant<222>109,114,117,128,139〈223〉xaa-任何氨基酸<■>583glyphethrhisginasnservalprothrthrserthrproglythr51015serthrvaltyrtrpalathrthrglythrproserserpheprogly202530histhrgluproglyproleuleulieprophethrpheasnphethr354045liethrasni^uhistyrglugluasnmetginhisproglyserarg505560phelysasnthrservalglyproleutyrserglycys8590leuleuargproglulysginglualaalathrglyxaa100105cysxaahisaxgxaaaspprolieglyproglyleuasp115120125leutyrtrpgluleuserginleuthrhisxaa工jlethr130135140argleuthr95aspthrlie110arggluxaagluleuglypro145tyrthrleuaspargaspserleutyrvalasn150serthrhisthrvalhisleuala20alaproval35proliethrasnleuhistyr5065pheasnthrthrphelysserthrser85gjlu70val155<210〉584<211〉156<212〉prt<213〉人<400〉584glypheasnprotrpser5servalprothrthrserthrproglythr1015thrserglythrproserserleuprogly2530leuleulieprophethrleuasnphethrglugluasnmetginhisproglyserarg5560argvalleuginglyleuleulysproleu7580glyproleutyrserglycysargleuthr9095pheasnthrthrgluargvalleuginglyleuleuthrproleu'707580leuleuargproglu.lyshisglyalaalathrglyvalaspalalie100105110cysthrleuargleuaspprothrglyproglyleuasparggluarg115120125trpg丄uleuserginleuthrasnservalthrgluleugly135140l>eutyr130pro145tyrthrleuaspargaspserleutyrvalasn150155<:210>585<211>156<212〉prt<213〉人eugintyrglu55thrthrgluarg"70thrservalgly85proglulysarg100cysthrhisargleuasppro115leutyrtrp130pro145tyrleugluleuserlys135lexiasparggly150valprothr10serglythr25leuvalpro40gluaspmetvalleuginproleutyr90glyalaala105leuasnpro120leuthrcysserleutyrthrserlieprogly15promaserleupro30phethrleuasnphe45arghisproglyser60glyleuleulyspro75serglycysargijeu95thrglyvalaspthr110glyleuaspargglu125glylieliegluleu1.40valasn155thrglythrargleu80thr工legingly<210><211><212><213〉586156人<220〉<221>variantformulaseeoriginaldocumentpage275leuleuargproglulysasp100glyvalalathrargvalaspalalie105110cysthrhisargproasppro115'lyslieproglyleuasparggingin120125leutyrtrpgluleusergin130135leuthrhisser工lethrgluleugly140protyrthrleuaspargasp145150se^leutyrvalasn155<210>588<211>156<212〉prt<213〉人<彻>588glyphethrphethrvalginargsersergingluthr20prothralathrglyproval35lie工le50ljysphe65phelysasnlieuleuargleugintyrgluthrthrgluarg70thrservalser85proglwlysasp100cysthrhisargproasppro115leutyrtrplysi>euseirgin130135protyrthrleuasparghis145150valprothrthi:serthrproglythr1015sergluthrproserserleuprogly2530leuleuprophe丁hrleuasnphethr4045gluaspmethisargprog丄yserarg60valleuging丄yleuleumetprol>eu7580serleutyrserglycysargleuthr9095glyalaalathrargvalaspalaval105110lysserproglyleuasparggluarg120125leuthrhisglyliethrgluleugly140serleutyrvalasn155<210〉589<211〉156<212〉prt<213>人<400>589glyftiethrhisginsersermetthrthrthrargthrproaspthrserthrprothrliethr50lysphe65phelysmethisleu20thralaser35asnlieuargcysthrleutyr130protyr145asnthrthrasnthrser85argprolys100tyrargpro115trpgluleuthrleuasp1015alathrserargthrproalaser乙eusergly2530proleuleuvalleuphethrlieasnphethr4045tyrglugluasnmethishisproglyserarg60gluargvalleuginglyleuleuargproval707580valglyproleutyrserglycysargleuthr9095lysaspglymaalathrlysvalaspalalie105110aspprolysserproglyleuaspargglugin120125serginleuthrhisserliethrgluleugly135140argaspserleutyrvalasn150155<210〉<211><212><213><220><221><222>5.90156prt人variant145〈223〉xaa:任何氨基酸<400>590glyphethrprothrvalginasp20proseralaala35liethr50lysphe65asnleuasnthrphelysserthrargserservalprothrthrser工leproglythr51015leuglythrserglythrprovalserlysprogly2530serproleuleuvalleuphethrleuasnphethr4045argtyrglugluasnmet,ginhisproglyserarg5560thrgluargvalleuginglyleuleuargserleu70"7580servalglyproleutyrserglycysargleuthr859095leuleuargproglulysaspg丄ythra丄athrglyvalaspala工le100105110cysthrhishisproaspprolysserproarg"leuaspargglugin115120125leutyrtrpgluleuserginleuthrhisasn工lethrgluleugly130135140xaatyralaleuaspasnaspserleuphevalasn145150155<210〉591<211>155<212〉prt〈213〉人<400〉591glyphethrhisargserservalserthrthrserthrproglythr5'—.1015proseralaalaserhisleuleu工leleuphethrleuasnphethr354045工lethrasnleuargtyrglugluasnmettrpproglyserarglys505560pheasnthrthrgluargvalleuginglyleuleuargproleuphe65707580lysasnthrservalglyproleutyrserglycysargleuthrleu859095leuargproglulysaspglyglualathrglyvalaspalaliecys100105110thrhisargproaspprothrglyproglyleuasparggluginleu115120125tyrjleugluleuserg丄nleuthrhisserliethrgluleuglypro130135140tyxthrleuaspargaspserleutyrvalasn145150155<210>592<211>134<212>prt<213>人<400>592glyphethrhisargserservalprothrthrserthrglyvalvalprothrvaltyrleuglyalaser20y1gh1pjhts5y2sergluglupro20metalaaspmet35asnvalmetlys50phethrleuasn10phethrlie253015argtyrglyginproglyserleulyspheasni丄ethrasp4045glyalaargtyr65histhrleul593150prt人<220><221>variant<222>7〈223〉xaa-任何氨基酸<秦〉593glytyrasngluproalathrthrpheleu20glyxaaaspglupropi:othrthrprolyspro1015proproleuserglualathrthralametgly2530tyrhistyrser50glyval65gly,proaspglyleu35lysproaspmetleuginhisthrleuthrleuasnphethrlieserasnleuginphetyrleu85alaalathr10040glylysgly55leulaeuarg70glycysginglyvalasp45sermathrpheasnserthrglu60proleupheginlyssersermet"7580leulieserleuargproglulys9095provalglyproglyleuasplieginginleutyrtrpgluleuser115120125ginleuthrhisglyvalthrginleuglyphetyrvalleuasparg130135140<210〉594〈211〉318<212>prt<213>人<220〉<221〉variant<222〉136,248,268〈223〉xaa-任何氨基酸<400〉594glytyralaproginasnleuserlieargglyglutyrginlieasn51015phehislievalasntrpasnleuserasnproaspprothrserser202530glutyr工lethrleuleuargasp工leginasplysvalthrthrleu354045asnleuthrmetaspservalleuvalthrval657075serasnleuaspproserleuvalgluginval8590leuasnalaserphehistrpleuglyserthr100105liehisvalthrglumetgluserservaltyr115120serser130tyrser145lysarglielysthrginhisphetyrxaaasnphethr135ginasplysalaginproglythrthr150155asnliegluaspalaleuasnginleu165170sertyrpheseraspcysginvalser180185iysalaleupheleuasptyrginleu110ginprothr125liethrasn140asntyrginphea:rgasnthrphearg190pheser80lysthr95valaspserserleup:co160serser175servalserleuphe工leasn150glyserginleuhisaspthrpheargphecysleuvalthr5560p5a1lytproasnarghishisthrglyvalaspserleucysasnpheserproleumet225ala210thr195argargglyglythrpro305leu290glyleu275tyr200205argvalaspargvalalalietyrgluglupheleuarg220servalleuasnserasnglythr230valaspgly245aspleuproglyleu工learglyslystyrginser310215ginleugintyrxaaproglu295asnphe235asnarg250thrleuaspasngluproargser240leuthr255phetrpalavalliexaalieglyleuala265270leuvalthrthrcys280leuglygluh丄sleuasp工lecystyrasnleuglu315glyval285val300gingingincysaspleugin<210〉59,5<211〉3451<212〉prt<213>人<220〉<221〉variant<222〉177,335,523,618,663,875,961,1001,1441,1555,1560,1563,1574,1585,2065,2070-2683,2990,3269,3381,3401〈223〉xaa-任何氨基酸<400〉595lieargasnsersergluleutyrglycysargleuala151015se:rleuargpiro20glulysaspsersei:25mathralavatlasp30alaliecysthrhis35axgproaspprogluasp!leuglyleuasparggluargleutyr50trpgluleuserasn55leuthrasnglyliegingluleuglyprotyrthrleuaspargasnserleutyrvalasnglyphethrhis65707580argsersermetpro85thrthrserthrpro90glythrserthrval95aspvalglythrser100glythrproserser105serproserprothr110thralaglyproleu115ijeumetprophethr120leuasnphethrlie125thrasnleugintyr130glugluaspmetarg135argthrg丄yse:rarg140lyspheasnthrmetgluserv3lleuginglyleuleulysproleuphelysasnthr145150155160serglyproleutyrserglycysargleuthrleuleuargproseqidn0:79是卵巢癌多核苷酸8h(图7b)。seqidn0:80是卵巢癌多核苷酸12e(图8)。seqidn0:81是卵巢癌多核苷酸12h(图9)。seqidn0:82-310是图15a_15eee所示的卵巢癌抗原多核苷酸。seqidn0:311是卵巢癌多核苷酸0772p的全长序列。seqidn0:312是0772p氨基酸序列。seqidn0:313-384是卵巢癌抗原多核苷酸。seqidno:385代表克隆0772p—种形式的cdna序列,命名为21013。seqidno:386代表克隆0772p—种形式的cdna序列,命名为21003。seqidno:387代表克隆0772p—种形式的cdna序列,命名为21008。seqidn0:388是与seqidno:385对应的氨基酸序列seqidno:389是与seqidno:386对应的氨基酸序列。seqidno:390是与seqidn0:387对应的氨基酸序列。seqidn0:391是卵巢癌多核苷酸08e的全长序列。seqidn0:392-393是08e编码的蛋白质序列。seqidno:394-415是与0e8抗体表位对应的肽序列。seqidn0:416-435是用0e8全长开放阅读框架预测的可能的hla-a2lomer结合欣。seqidn0:436-455是用0e8全长开放阅读框架预测的可能的歸-a29mer结合欣。seqidno:456是显示与0772p有同源性的全长genbank序列的截短核苷酸序列。seqidn0:457是显示与0772p有显著同源性的全长genbank序列。seqidn0:458是编码显示与0772p有同源性的全长genbank序列的截短形式的蛋白质。625leuprotrplieupro705tyrgluvallysasp785serargthrprophe865hisserserthrgly945valglyprotyr工legly690leugluargglyasn770proginhisserser850thrcysleviglygly930vallieasnthrsertrpthrpro675serl>eugluvalleu755glylysleuserser835serleuproleucys915valasplysg丄ysejr995proglu!leu660valglyvalasp!leu740leualaserthrleu820thrleuasnglygly900argasparggluphe980thr645aspprothrpromet725gintyralaprohis805tyrpropropheser885proleualaglul*euthr1010phethrlie1025一serarglysprometphethrleuthrthrphelysvalserasnasn630serargth:rprophe710hisglyserthrgly790glyvalglyserthr870argmetthr工legin950glyhisaspalalieuginxaaserser695thrhisleuglygly775leulieasnthrpro855lielyspheijeucys935leuproginlieuleuserser680serleuproljeucys760mbtasnlysgl;yser840thrthrphelysleu920tl"u:tyrtyrthrleu665thrleuasnglygly745axgasparggluphe825thrthrasnasn905arghistrpthrser985asn650tyrpropropheser730proleualaglulieu810thrvalalaleuthr890thrserarggjlulieumagly1000glyprol>eu1015gintyrglu1030thrthrgluarg1045asnthrservalglyserlieugluval635glyvalglyserthr715argmetthrliegin795glymsaspgly875thrserglulieuleu955aspprog丄yvalasp工leasnthrpro700工leleugluargglyasp925proginasnthrprogluphe670thrthrasnasn750arghistrpthrparo830ser'leugluval910glylysleuserser990serleu655thrvalalaleuthr735thrproajcggluleu815valglyvalaspleu895leuserthrleu975thrserleuproleu640glyhisaspglygin720thrsergluleuleu800aspprothrpromet880gintyralaproasn960tyrproleuasngly1040gly1005phethr1020methishis1035leuginglyleu10501055leu"leutyrserglycysarg106010651070leuargproglulysasnglyalaalathrglymetasp107510801085alaliecysserhisargleuaspprolysserproglyleuasnarg109010951100gluginleutyrtrpgluleuserginleuthrhisglylielysglu1105111011151120leuglyprotyrthrleuaspargasnserleutyrvalasng丄yphe112511301135thrhisargserservalalaprothrserthrproglythrserthr11451150va丄aspleug丄ythrserglythrproserserleuproserprothr115511601165thr7uavajlproleuleuvalprophethrleuasnphethr工lethr117011751180asnleugintyrglygluaspmetarghisproglyserarglysphe1185119011951200asnthrthrgluvalleuginglyleuleuglyproleuphe!lys120512101215asnserservalglyproleutyrserglycysargleu工leserleu122012251230argserglulysaspglyalaalathrglyvalaspala工lecysthr123512401245hishisleuasnproginserproglyleuasparggluginleutyr125012551260trpginleuserginmetthrasnglylielysgluleuglyprotyr1265127012751280thrleuaspargasnserleutyrvalasnglyphethrhisargser128512901295serglyleuthrthrserthrprotrpthrserthrvalaspleugly1300.13051310thrserglythrproserprovalproserprothrthralaglypro131513201325leuleuvalprophe.thrleuasnphethrliethrasnleugintyr133013351340glugluaspmethisargproglyserarglyspheasnalathrg丄u1345135013551360argvalleuginglyleuleuserpro工lephelysasnserserval136513701375glyproleutyrserglycysaxgleuthi:serleuargproglulys138013851390aspglymamathrglymetaspalavalcysleutyrhisproasn1395'14001405prolysargproglyleuasparggluginleutyrtrpgluleuser141014151420ginleuthrhisasnliethrgluleuglyprotyrserleuasparg1425143014351"0xaaserleutyrvalasnglyphethrhisginasnservalprothr144514501455thrserthrproglythrserthrvaltyrtrpalathrthrglythr146014651470proserserpheprogl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qidn0s:464-477和512-569中提供的序列的简并变异体。21.分离的多肽,其包含选自如下序列的氨基酸序列(a)权利要求20的多核苷酸编码的序列;和(b)与权利要求20的多核苷酸编码的序列有至少80%同一性的序列;和(c)与权利要求20的多核香酸编码的序列有至少90%同一性的序列。22.表达载体,其包含可操作地与表达控制序列连接的权利要求20的多核苷酸。23.用权利要求22的表达载体转化或转染的宿主细胞。24.特异地与权利要求21的多肽结合的分离的抗体或其抗原结合部分。25.检测患者中癌症存在的方法,包括以下步骤(a)从患者获得生物样品;(b)用与权利要求21的多肽结合的结合剂接触生物样品;(c)检测样品中与结合剂结合的多肽的量;和(d)比较该多肽的量和预先确定的截断值,由此确定患者中癌症存在与否。26.包括至少一个权利要求21的多肽的融合蛋白质。27.刺激和/或扩增对肿瘤蛋白质特异的t细胞的方法,包括在足以允许t细胞刺激和/或扩增的条件下和时间内,用选自以下组的至少一个成分接触t细胞(a)权利要求21所述的多肽;(b)权利要求20所述的多核苷酸;和(c)表达权利要求20所述的多核苷酸的抗原呈递细胞。28.分离的t细胞群,包含根据权利要求27的方法制备的t细胞。29.药物组合物,包含选自生理学上可接受载体和免疫剌激剂的第一組分,和选自以下物质的第二組分(a)权利要求21所述的多肽;(b)权利要求20所述的多核苷酸;(c)权利要求24所述的抗体;(d)权利要求26所述的融合蛋白质;和(e)权利要求28所述的t细胞群;和(f)表达权利要求21所述的多肽的抗原呈递细胞。30.刺激患者免疫应答的方法,包括给患者施用权利要求29的组合物。31.用于治疗患者卵巢癌的方法,包括给患者施用权利要求29的组合物。32.确定患者中癌症存在与否的方法,包括以下步骤(a)从患者获得生物样品;(b)用与权利要求21所述的多核苷酸序列杂交的寡核苷酸在中度严格条件下接触生物样品;(c)检测样品中与所述寡核苷酸杂交的所迷多核苷酸的量;和(d)比较与寡核苷酸杂交的所述多核苷酸的量和预先确定的截断值,而且由此确定患者中癌症的存在与否。33.0772p多肽,至少包含seqidn0s:490-511任一个中所示的抗体表位序列。34.08e多肽,至少包含seqidn0s:394-415任一个中所示的抗体表位序列。35.特异地与权利要求1的多肽结合的分离的抗体或其抗原结合片段。全文摘要本发明公开了用于癌症(如卵巢癌)治疗和诊断的组合物和方法。组合物可以包括一个或多个卵巢癌蛋白质,其免疫原性部分,编码这样的部分的多肽,或对这样蛋白质特异的免疫系统细胞或抗体。这样的组合物可以用于,例如,疾病如卵巢癌的诊断和预防。进一步提供了鉴定从卵巢癌和/或其它肿瘤分泌的肿瘤抗原的方法。本发明进一步提供了用于卵巢癌诊断和检测的多肽和多核苷酸。文档编号c07k14/47gk101230100sq20071019322公开日2008年7月30日申请日期2001年7月17日优先权日2000年7月17日发明者d·卡特,e·奥博尼,g·e·金,g·r·范戈,j·l·米特沙姆,m·w·勒特,p·a·奥噶特,p·赫尔,s·g·利德,s·p·弗灵,t·s·维德韦克申请人:科里克萨有限公司
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