CN1315998A - 用于治疗和诊断前列腺癌的组合物和方法 - Google Patents
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Abstract
此处公开了用于治疗和诊断癌症(诸如前列腺癌)的组合物和方法。组合物可以包含一种或多种前列腺肿瘤蛋白、其免疫原性部分、或编码这些部分的多核苷酸。或者,治疗组合物可以包含表达前列腺肿瘤蛋白的抗原呈递细胞,或对表达这种蛋白质的细胞特异的T细胞。这样的组合物可以用于例如预防和治疗疾病(诸如前列腺癌)。此处还提供了基于检测样品中的前列腺肿瘤蛋白或编码这种蛋白质的mRNA的诊断方法。
Description
技术领域
本发明主要涉及癌症(诸如前列腺癌)的治疗和诊断。本发明更具体的涉及至少包含前列腺肿瘤蛋白的一部分的多肽和编码这些多肽的多核苷酸。这些多肽和多核苷酸可以在疫苗和药物组合物中使用，从而预防和治疗前列腺癌，和诊断和监控这些癌症。
发明背景
前列腺癌是男性中最常见的癌症，在50岁以上的男性中估计发病率为30％。相当多的临床证据显示人前列腺癌有向骨转移的倾向，且此病呈现为不可避免的从雄性激素依赖状态发展为雄性激素不应性状态，导致患者死亡率的提高。这种普遍的疾病当前正成为美国男性中癌症致死的第二高病因。
尽管对此疾病的疗法进行了许多研究，但前列腺癌仍然是难以治疗的。通常情况下，治疗是基于外科手术和/或放射疗法进行的，但在相当大部分的病例中这些方法都是无效的。两种先前鉴定的前列腺特异性蛋白--前列腺特异抗原(PSA)和前列腺酸性磷酸酶(PAP)--具有有限的治疗和诊断潜力。例如，PSA水平并不总是能很好的与前列腺癌的出现相关联，在一部分非前列腺癌中也呈阳性，包括良性前列腺增生(BPH)。此外，PSA测量值与前列腺体积大小有关，且不显示转移水平。
尽管对这些和其它癌症的疗法进行了许多研究，但前列腺癌仍然是难以有效诊断和治疗的。相应的，本领域中仍需要用于检测和治疗这些癌症的改进方法。本发明满足了这些要求，并进一步提供其它相关优势。
发明概述
简单的说，本发明提供了用于诊断和治疗癌症(诸如前列腺癌)的组合物和方法。一方面，本发明提供了至少包含前列腺肿瘤蛋白的一部分或其变体的多肽。某些部分和变体具有免疫原性，从而变体与抗原特异的抗血清的反应能力基本上没有降低。在某些实施方案中，多肽至少包含前列腺肿瘤蛋白的免疫原性部分或其变体，其中肿瘤蛋白包含下列多核苷酸序列编码的氨基酸序列：(a)SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472任一记录的序列；(b)与任何上述序列在中等严谨条件下杂交的序列；和(c)(a)或(b)的任何序列的互补序列。在某些特定的实施方案中，这样的多肽至少包含肿瘤蛋白的一部分或其变体，其中肿瘤蛋白包含SEQ ID NO:112-114、172、176、178、327、329、331、336、339、376-380和383任一记录的氨基酸序列。
本发明还提供了编码上述多肽的多核苷酸或它们的一部分(诸如至少编码前列腺肿瘤蛋白的15个氨基酸残基的部分)、包含这些多核苷酸的表达载体和用这些表达载体转化或转染的宿主细胞。
另一方面，本发明提供了包含上述多肽或多核苷酸和生理学可接受的载体的药物组合物。
在本发明的相关方面，提供了包含上述多肽或多核苷酸和非特异免疫应答增强剂的疫苗。
本发明还提供了包含：(a)与前列腺肿瘤蛋白可特异结合的抗体或它们的抗原结合片段；和(b)生理学可接受的载体的药物组合物。
在其它方面，本发明提供了包含：(a)表达上述多肽的抗原呈递细胞；和(b)药学可接受的载体或赋形剂的药物组合物。抗原呈递细胞包括树突状细胞、巨噬细胞、单核细胞、成纤维细胞和B细胞。
在相关方面，提供了包含：(a)表达上述多肽的抗原呈递细胞；和(b)非特异免疫应答增强剂的疫苗。
在其它方面，本发明还提供了至少包含一种上述多肽的融合蛋白，以及编码这些融合蛋白的多核苷酸。
在相关方面，提供了包含与生理学可接受的载体相组合的融合蛋白或编码融合蛋白的多核苷酸的药物组合物。
在其它方面，还提供了包含与非特异免疫应答增强剂相组合的融合蛋白或编码融合蛋白的多核苷酸的疫苗。
在其它方面，本发明提供了抑制癌症在患者体内发展的方法，包括给患者施用上述药物组合物或疫苗。
在其它方面，本发明还提供了从生物学样品中除去肿瘤细胞的方法，包括将生物学样品和能与前列腺肿瘤蛋白发生特异反应的T细胞在足以从样品中除去表达该蛋白质的细胞的条件和时间下接触。
在相关方面，提供了抑制癌症在患者体内发展的方法，包括给患者施用经上述处理的生物学样品。
在其它方面，还提供了用于刺激和/或扩增对前列腺肿瘤蛋白特异的T细胞的方法，包括将T细胞与下列一种或多种物质在足以刺激和/或扩增T细胞的条件和时间下接触：(a)上述多肽；(b)编码这样的多肽的多核苷酸；和/或(c)表达这样的多肽的抗原呈递细胞。还提供了包含如上制备的T细胞的分离T细胞群。
在其它方面，本发明提供了抑制癌症在患者体内发展的方法，包括给患者施用有效量的上述T细胞群。
本发明还提供了抑制癌症在患者体内发展的方法，包括下列步骤：(a)将从患者分离得到的CD4+和/或CD8+T细胞与下列一种或多种组分一起温育：(ⅰ)至少包含前列腺肿瘤蛋白免疫原性部分的多肽；(ⅱ)编码这样的多肽的多核苷酸；和(ⅲ)表达这样的多肽的抗原呈递细胞；并(b)给患者施用有效量的增殖T细胞，并由此抑制癌症在患者体内的发展。增殖细胞可以(但不必)在给患者施用之前进行克隆。
在其它方面，本发明提供了测定患者体内是否存在癌症的方法，包括：(a)将从患者得到的生物学样品与结合剂(能与上述多肽结合)接触：(b)检测样品中与结合剂结合的多肽的量；并(c)将多肽的量与预先测定的临界值进行比较，并由此测定患者体内是否存在癌症。在优选的实施方案中，结合剂是抗体，更优选单克隆抗体。癌症可以是前列腺癌。
在其它方面，本发明还提供了监控癌症在患者体内发展的方法。这种方法包括下列步骤：(a)将第一时间点从患者得到的生物学样品与结合剂(能与上述多肽结合)接触；(b)检测样品中与结合剂结合的多肽的量；(c)使用随后第二时间点从患者得到的生物学样品，重复步骤(a)和(b)；并(d)将步骤(c)检测得到的多肽的量与步骤(b)检测得到的量进行比较，由此监控患者体内癌症的发展。
在其它方面，本发明还提供了测定患者体内是否存在癌症的方法，包括下列步骤：(a)将从患者得到的生物学样品与寡核苷酸(能与编码前列腺肿瘤蛋白的多核苷酸杂交)接触；(b)检测样品中与寡核苷酸杂交的多核苷酸(优选mRNA)的量；并(c)将与寡核苷酸杂交的多核苷酸的量与预先测定的临界值进行比较，并由此测定患者体内是否存在癌症。在某些实施方案中，mRNA的量是使用(例如)至少一种可与编码上述多肽的多核苷酸或其互补物杂交的寡核苷酸引物，通过聚合酶链式反应进行检测的。在其它实施方案中，mRNA的量是采用可与编码上述多肽的多核苷酸或其互补物杂交的寡核苷酸探针，通过杂交技术进行检测的。
在相关方面，提供了监控癌症在患者体内发展的方法，包括下列步骤：(a)将从患者得到的生物学样品首先与寡核苷酸(能与编码前列腺肿瘤蛋白的多核苷酸杂交)接触；(b)检测样品中与寡核苷酸杂交的多核苷酸的量；(c)使用第二时间点从患者得到的生物学样品，重复步骤(a)和(b)；并(d)将步骤(c)检测得到的多核苷酸的量与步骤(b)检测得到的量进行比较，并由此监控患者体内癌症的发展。
在其它方面，本发明提供了可与上述多肽结合的抗体，诸如单克隆抗体，以及包含这些抗体的诊断试剂盒。还提供了包含一种或多种上述寡核苷酸探针或者引物的诊断试剂盒。
参照以下详述及附图，本发明的这些及其它方面是显而易见的。在此公开的所有文献是作为独立每篇全文收入作为参考文献的。
图和序列标识符的简述
图1图解了T细胞杀死表达代表性前列腺肿瘤多肽P502S的成纤维细胞的能力，与对照成纤维细胞进行比较。溶解的百分比显示为效应物：靶细胞的一系列比率。
图2A和2B图解了T细胞识别表达代表性前列腺肿瘤多肽P502S的细胞的能力。在每一例中，显示了不同数目响应物的γ-干扰素斑点的数目。在图2A中，展示了P2S-12肽脉冲的成纤维细胞的数据，与对照E75肽脉冲的成纤维细胞进行比较。在图2B中，展示了表达P502S的成纤维细胞的数据，与表达HER-2/neu的成纤维细胞进行比较。
图3展示了肽竞争结合实验，显示由P501S衍生的P1S#10肽可与HLA-A2结合。在TNF释放生物实验中，P1S#10肽抑制HLA-A2限制的将fluM58肽呈递给CTL克隆D150M58。D150M58 CTL对HLA-A2结合流感基质肽fluM58是特异的。
图4图解了由P1S#10免疫的小鼠建立的T细胞系特异溶解P1S#10脉冲的Jurkat A2Kb靶细胞和P501S转导的Jurkat A2Kb靶细胞的能力，与EGFP转导的Jurkat A2Kb进行比较。溶解百分比显示为效应物：靶细胞的一系列比率。
图5图解了T细胞克隆识别并特异溶解表达代表性前列腺肿瘤多肽P501S的Jurkat A2Kb细胞的能力，并由此说明P1S#10肽可能是P501S多肽的天然加工表位。
图6A和6B图解了CD8+细胞系(3A-1)对代表性前列腺肿瘤抗原(P501S)的特异性。图6A显示了51Cr释放实验的结果。特异溶解百分比显示为效应物：靶细胞的一系列比率。图6B显示了各种效应物：靶细胞比率下，用经P501S转导的自身B-LCL刺激的3A-1细胞产生γ-干扰素的水平。
SEQ ID NO:1是F1-13经测定的cDNA序列
SEQ ID NO:2是F1-12经测定的3’cDNA序列
SEQ ID NO:3是F1-12经测定的5’cDNA序列
SEQ ID NO:4是F1-16经测定的3’cDNA序列
SEQ ID NO:5是H1-1经测定的3’cDNA序列
SEQ ID NO:6是H1-9经测定的3’cDNA序列
SEQ ID NO:7是H1-4经测定的3’cDNA序列
SEQ ID NO:8是J1-17经测定的3’cDNA序列
SEQ ID NO:9是J1-17经测定的5’cDNA序列
SEQ ID NO:10是L1-12经测定的3’cDNA序列
SEQ ID NO:11是L1-12经测定的5’cDNA序列
SEQ ID NO:12是N1-1862经测定的3’cDNA序列
SEQ ID NO:13是N1-1862经测定的5’cDNA序列
SEQ ID NO:14是J1-13经测定的3’cDNA序列
SEQ ID NO:1 5是J1-13经测定的5’cDNA序列
SEQ ID NO:16是J1-19经测定的3’cDNA序列
SEQ ID NO:17是J1-19经测定的5’cDNA序列
SEQ ID NO:18是J1-25经测定的3’cDNA序列
SEQ ID NO:19是J1-25经测定的5’cDNA序列
SEQ ID NO:20是J1-24经测定的5’cDNA序列
SEQ ID NO:21是J1-24经测定的3’cDNA序列
SEQ ID NO:22是K1-58经测定的5’cDNA序列
SEQ ID NO:23是K1-58经测定的3’cDNA序列
SEQ ID NO:24是K1-63经测定的5’cDNA序列
SEQ ID NO:25是K1-63经测定的3’cDNA序列
SEQ ID NO:26是L1-4经测定的5’cDNA序列
SEQ ID NO:27是L1-4经测定的3’cDNA序列
SEQ ID NO:28是L1-14经测定的5’cDNA序列
SEQ ID NO:29是L1-14经测定的3’cDNA序列
SEQ ID NO:30是J1-12经测定的3’cDNA序列
SEQ ID NO:31是J1-16经测定的3’cDNA序列
SEQ ID NO:32是J1-21经测定的3’cDNA序列
SEQ ID NO:33是K1-48经测定的3’cDNA序列
SEQ ID NO:34是K1-55经测定的3’cDNA序列
SEQ ID NO:35是L1-2经测定的3’cDNA序列
SEQ ID NO:36是L1-6经测定的3’cDNA序列
SEQ ID NO:37是N1-1858经测定的3’cDNA序列
SEQ ID NO:38是N1-1860经测定的3’cDNA序列
SEQ ID NO:39是N1-1861经测定的3’cDNA序列
SEQ ID NO:40是N1-1864经测定的3’cDNA序列
SEQ ID NO:41是P5经测定的cDNA序列
SEQ ID NO:42是P8经测定的cDNA序列
SEQ ID NO:43是P9经测定的cDNA序列
SEQ ID NO:44是P18经测定的cDNA序列
SEQ ID NO:45是P20经测定的cDNA序列
SEQ ID NO:46是P29经测定的cDNA序列
SEQ ID NO:47是P30经测定的cDNA序列
SEQ ID NO:48是P34经测定的cDNA序列
SEQ ID NO:49是P36经测定的cDNA序列
SEQ ID NO:50是P38经测定的cDNA序列
SEQ ID NO:51是P39经测定的cDNA序列
SEQ ID NO:52是P42经测定的cDNA序列
SEQ ID NO:53是P47经测定的cDNA序列
SEQ ID NO:54是P49经测定的cDNA序列
SEQ ID NO:55是P50经测定的cDNA序列
SEQ ID NO:56是P53经测定的cDNA序列
SEQ ID NO:57是P55经测定的cDNA序列
SEQ ID NO:58是P60经测定的cDNA序列
SEQ ID NO:59是P64经测定的cDNA序列
SEQ ID NO:60是P65经测定的cDNA序列
SEQ ID NO:61是P73经测定的cDNA序列
SEQ ID NO:62是P75经测定的cDNA序列
SEQ ID NO:63是P76经测定的cDNA序列
SEQ ID NO:64是P79经测定的cDNA序列
SEQ ID NO:65是P84经测定的cDNA序列
SEQ ID NO:66是P68经测定的cDNA序列
SEQ ID NO:67是P80经测定的cDNA序列
SEQ ID NO:68是P82经测定的cDNA序列
SEQ ID NO:69是U1-3064经测定的cDNA序列
SEQ ID NO:70是U1-3065经测定的cDNA序列
SEQ ID NO:71是V1-3692经测定的cDNA序列
SEQ ID NO:72是1A-3905经测定的cDNA序列
SEQ ID NO:73是V1-3686经测定的cDNA序列
SEQ ID NO:74是R1-2330经测定的cDNA序列
SEQ ID NO:75是1B-3976经测定的cDNA序列
SEQ ID NO:76是V1-3679经测定的cDNA序列
SEQ ID NO:77是1G-4736经测定的cDNA序列
SEQ ID NO:78是1G-4738经测定的cDNA序列
SEQ ID NO:79是1G-4741经测定的cDNA序列
SEQ ID NO:80是1G-4744经测定的cDNA序列
SEQ ID NO:81是1G-4734经测定的cDNA序列
SEQ ID NO:82是1H-4774经测定的cDNA序列
SEQ ID NO:83是1H-4781经测定的cDNA序列
SEQ ID NO:84是1H-4785经测定的cDNA序列
SEQ ID NO:85是1H-4787经测定的cDNA序列
SEQ ID NO:86是1H-4796经测定的cDNA序列
SEQ ID NO:87是1I-4807经测定的cDNA序列
SEQ ID NO:88是1I-4810经测定的cDNA序列
SEQ ID NO:89是1I-4811经测定的cDNA序列
SEQ ID NO:90是1J-4876经测定的cDNA序列
SEQ ID NO:91是1K-4884经测定的cDNA序列
SEQ ID NO:92是1K-4896经测定的cDNA序列
SEQ ID NO:93是1G-4761经测定的cDNA序列
SEQ ID NO:94是1G-4762经测定的cDNA序列
SEQ ID NO:95是1H-4766经测定的cDNA序列
SEQ ID NO:96是1H-4770经测定的cDNA序列
SEQ ID NO:97是1H-4771经测定的cDNA序列
SEQ ID NO:98是1H-4772经测定的cDNA序列
SEQ ID NO:99是1D-4297经测定的cDNA序列
SEQ ID NO:100是1D-4309经测定的cDNA序列
SEQ ID NO:101是1D.1-4278经测定的cDNA序列
SEQ ID NO:102是1D-4288经测定的cDNA序列
SEQ ID NO:103是1D-4283经测定的cDNA序列
SEQ ID NO:104是1D-4304经测定的cDNA序列
SEQ ID NO:105是1D-4296经测定的cDNA序列
SEQ ID NO:106是1D-4280经测定的cDNA序列
SEQ ID NO:107是F1-12(也称为P504S)经测定的全长cDNA序列
SEQ ID NO:108是F1-12预测的氨基酸序列
SEQ ID NO:109是J1-17经测定的全长cDNA序列
SEQ ID NO:110是L1-12经测定的全长cDNA序列
SEQ ID NO:111是N1-1862经测定的全长cDNA序列
SEQ ID NO:112是J1-17预测的氨基酸序列
SEQ ID NO:113是L1-12预测的氨基酸序列
SEQ ID NO:114是N1-1862预测的氨基酸序列
SEQ ID NO:115是P89经测定的cDNA序列
SEQ ID NO:116是P90经测定的cDNA序列
SEQ ID NO:117是P92经测定的cDNA序列
SEQ ID NO:118是P95经测定的cDNA序列
SEQ ID NO:119是P98经测定的cDNA序列
SEQ ID NO:120是P102经测定的cDNA序列
SEQ ID NO:121是P110经测定的cDNA序列
SEQ ID NO:122是P111经测定的cDNA序列
SEQ ID NO:123是P114经测定的cDNA序列
SEQ ID NO:124是P115经测定的cDNA序列
SEQ ID NO:1 25是P116经测定的cDNA序列
SEQ ID NO:126是P124经测定的cDNA序列
SEQ ID NO:127是P126经测定的cDNA序列
SEQ ID NO:128是P130经测定的cDNA序列
SEQ ID NO:129是P133经测定的cDNA序列
SEQ ID NO:130是P138经测定的cDNA序列
SEQ ID NO:131是P143经测定的cDNA序列
SEQ ID NO:1 32是P151经测定的cDNA序列
SEQ ID NO:1 33是P156经测定的cDNA序列
SEQ ID NO:134是P157经测定的cDNA序列
SEQ ID NO:135是P166经测定的cDNA序列
SEQ ID NO:136是P176经测定的cDNA序列
SEQ ID NO:137是P178经测定的cDNA序列
SEQ ID NO:138是P179经测定的cDNA序列
SEQ ID NO:139是P185经测定的cDNA序列
SEQ ID NO:140是P192经测定的cDNA序列
SEQ ID NO:141是P201经测定的cDNA序列
SEQ ID NO:142是P204经测定的cDNA序列
SEQ ID NO:143是P208经测定的cDNA序列
SEQ ID NO:144是P211经测定的cDNA序列
SEQ ID NO:145是P213经测定的cDNA序列
SEQ ID NO:146是P219经测定的cDNA序列
SEQ ID NO:147是P237经测定的cDNA序列
SEQ ID NO:148是P239经测定的cDNA序列
SEQ ID NO:149是P248经测定的cDNA序列
SEQ ID NO:150是P251经测定的cDNA序列
SEQ ID NO:151是P255经测定的cDNA序列
SEQ ID NO:152是P256经测定的cDNA序列
SEQ ID NO:153是P259经测定的cDNA序列
SEQ ID NO:154是P260经测定的cDNA序列
SEQ ID NO:155是P263经测定的cDNA序列
SEQ ID NO:156是P264经测定的cDNA序列
SEQ ID NO:157是P266经测定的cDNA序列
SEQ ID NO:158是P270经测定的cDNA序列
SEQ ID NO:159是P272经测定的cDNA序列
SEQ ID NO:160是P278经测定的cDNA序列
SEQ ID NO:161是P105经测定的cDNA序列
SEQ ID NO:162是P107经测定的cDNA序列
SEQ ID NO:163是P137经测定的cDNA序列
SEQ ID NO:164是P194经测定的cDNA序列
SEQ ID NO:165是P195经测定的cDNA序列
SEQ ID NO:166是P196经测定的cDNA序列
SEQ ID NO:167是P220经测定的cDNA序列
SEQ ID NO:168是P234经测定的cDNA序列
SEQ ID NO:169是P235经测定的cDNA序列
SEQ ID NO:170是P243经测定的cDNA序列
SEQ ID NO:171是P703P-DE1经测定的cDNA序列
SEQ ID NO:172是P703P-DE1预测的氨基酸序列
SEQ ID NO:173是P703P-DE2经测定的cDNA序列
SEQ ID NO:174是P703P-DE6经测定的cDNA序列
SEQ ID NO:175是P703P-DE13经测定的cDNA序列
SEQ ID NO:176是P703P-DE13预测的氨基酸序列
SEQ ID NO:177是P703P-DE14经测定的cDNA序列
SEQ ID NO:178是P703P-DE14预测的氨基酸序列
SEQ ID NO:179是1G-4736经测定的延续cDNA序列
SEQ ID NO:180是1G-4738经测定的延续cDNA序列
SEQ ID NO:181是1G-4741经测定的延续cDNA序列
SEQ ID NO:182是1G-4744经测定的延续cDNA序列
SEQ ID NO:183是1H-4774经测定的延续cDNA序列
SEQ ID NO:184是1H-4781经测定的延续cDNA序列
SEQ ID NO:185是1H-4785经测定的延续cDNA序列
SEQ ID NO:186是1H-4787经测定的延续cDNA序列
SEQ ID NO:187是1H-4796经测定的延续cDNA序列
SEQ ID NO:188是1I-4807经测定的延续cDNA序列
SEQ ID NO:189是1I-4810经测定的3’cDNA序列
SEQ ID NO:190是1I-4811经测定的3’cDNA序列
SEQ ID NO:191是1J-4876经测定的延续cDNA序列
SEQ ID NO:192是1K-4884经测定的延续cDNA序列
SEQ ID NO:193是1K-4896经测定的延续cDNA序列
SEQ ID NO:194是1G-4761经测定的延续cDNA序列
SEQ ID NO:195是1G-4762经测定的延续cDNA序列
SEQ ID NO:196是1H-4766经测定的延续cDNA序列
SEQ ID NO:197是1H-4770经测定的3’cDNA序列
SEQ ID NO:198是1H-4771经测定的3’cDNA序列
SEQ ID NO:199是1H-4772经测定的延续cDNA序列
SEQ ID NO:200是19-4309经测定的延续cDNA序列
SEQ ID NO:201是1D.1-4278经测定的延续cDNA序列
SEQ ID NO:202是1D-4288经测定的延续cDNA序列
SEQ ID NO:203是1D-4283经测定的延续cDNA序列
SEQ ID NO:204是1D-4304经测定的延续cDNA序列
SEQ ID NO:205是1D-4296经测定的延续cDNA序列
SEQ ID NO:206是1D-4280经测定的延续cDNA序列
SEQ ID NO:207是10-d8fwd经测定的cDNA序列
SEQ ID NO:208是10-H10con经测定的cDNA序列
SEQ ID NO:209是11-C8rev经测定的cDNA序列
SEQ ID NO:210是7.g6fwd经测定的cDNA序列
SEQ ID NO:211是7.g6rev经测定的cDNA序列
SEQ ID NO:212是8-b5fwd经测定的cDNA序列
SEQ ID NO:213是8-b5rev经测定的cDNA序列
SEQ ID NO:214是8-b6fwd经测定的cDNA序列
SEQ ID NO:215是8-b6rev经测定的cDNA序列
SEQ ID NO:216是8-d4fwd经测定的cDNA序列
SEQ ID NO:217是8-d9rev经测定的cDNA序列
SEQ ID NO:218是8-g3fwd经测定的cDNA序列
SEQ ID NO:219是8-g3rev经测定的cDNA序列
SEQ ID NO:220是8-h11rev经测定的cDNA序列
SEQ ID NO:221是g-f12fwd经测定的cDNA序列
SEQ ID NO:222是g-f3rev经测定的cDNA序列
SEQ ID NO:223是P509S经测定的cDNA序列
SEQ ID NO:224是P510S经测定的cDNA序列
SEQ ID NO:225是P703DE5经测定的cDNA序列
SEQ ID NO:226是9-A11经测定的cDNA序列
SEQ ID NO:227是8-C6经测定的cDNA序列
SEQ ID NO:228是8-H7经测定的cDNA序列
SEQ ID NO:229是JPTPN13经测定的cDNA序列
SEQ ID NO:230是JPTPN14经测定的cDNA序列
SEQ ID NO:231是JPTPN23经测定的cDNA序列
SEQ ID NO:232是JPTPN24经测定的cDNA序列
SEQ ID NO:233是JPTPN25经测定的cDNA序列
SEQ ID NO:234是JPTPN30经测定的cDNA序列
SEQ ID NO:235是JPTPN34经测定的cDNA序列
SEQ ID NO:236是PTPN35经测定的cDNA序列
SEQ ID NO:237是JPTPN36经测定的cDNA序列
SEQ ID NO:238是JPTPN38经测定的cDNA序列
SEQ ID NO:239是JPTPN39经测定的cDNA序列
SEQ ID NO:240是JPTPN40经测定的cDNA序列
SEQ ID NO:241是JPTPN41经测定的cDNA序列
SEQ ID NO:242是JPTPN42经测定的cDNA序列
SEQ ID NO:243是JPTPN45经测定的cDNA序列
SEQ ID NO:244是JPTPN46经测定的cDNA序列
SEQ ID NO:245是JPTPN51经测定的cDNA序列
SEQ ID NO:246是JPTPN56经测定的cDNA序列
SEQ ID NO:247是PTPN64经测定的cDNA序列
SEQ ID NO:248是JPTPN65经测定的cDNA序列
SEQ ID NO:249是JPTPN67经测定的cDNA序列
SEQ ID NO:250是JPTPN76经测定的cDNA序列
SEQ ID NO:251是JPTPN84经测定的cDNA序列
SEQ ID NO:252是JPTPN85经测定的cDNA序列
SEQ ID NO:253是JPTPN86经测定的cDNA序列
SEQ ID NO:254是JPTPN87经测定的cDNA序列
SEQ ID NO:255是JPTPN88经测定的cDNA序列
SEQ ID NO:256是JP1F1经测定的cDNA序列
SEQ ID NO:257是JP1F2经测定的cDNA序列
SEQ ID NO:258是JP1C2经测定的cDNA序列
SEQ ID NO:259是JP1B1经测定的cDNA序列
SEQ ID NO:260是JP1B2经测定的cDNA序列
SEQ ID NO:261是JP1D3经测定的cDNA序列
SEQ ID NO:262是JP1A4经测定的cDNA序列
SEQ ID NO:263是JP1F5经测定的cDNA序列
SEQ ID NO:264是JP1E6经测定的cDNA序列
SEQ ID NO:265是JP1D6经测定的cDNA序列
SEQ ID NO:266是JP1B5经测定的cDNA序列
SEQ ID NO:267是JP1A6经测定的cDNA序列
SEQ ID NO:268是JP1E8经测定的cDNA序列
SEQ ID NO:269是JP1D7经测定的cDNA序列
SEQ ID NO:270是JP1D9经测定的cDNA序列
SEQ ID NO:271是JP1C10经测定的cDNA序列
SEQ ID NO:272是JP1A9经测定的cDNA序列
SEQ ID NO:273是JP1F12经测定的cDNA序列
SEQ ID NO:274是JP1E12经测定的cDNA序列
SEQ ID NO:275是JP1D11经测定的cDNA序列
SEQ ID NO:276是JP1C11经测定的cDNA序列
SEQ ID NO:277是JP1C12经测定的cDNA序列
SEQ ID NO:278是JP1B12经测定的cDNA序列
SEQ ID NO:279是JP1A12经测定的cDNA序列
SEQ ID NO:280是JP8G2经测定的cDNA序列
SEQ ID NO:281是JP8H1经测定的cDNA序列
SEQ ID NO:282是JP8H2经测定的cDNA序列
SEQ ID NO:283是JP8A3经测定的cDNA序列
SEQ ID NO:284是JP8A4经测定的cDNA序列
SEQ ID NO:285是JP8C3经测定的cDNA序列
SEQ ID NO:286是JP8G4经测定的cDNA序列
SEQ ID NO:287是JP8B6经测定的cDNA序列
SEQ ID NO:288是JP8D6经测定的cDNA序列
SEQ ID NO:289是JP8F5经测定的cDNA序列
SEQ ID NO:290是JP8A8经测定的cDNA序列
SEQ ID NO:291是JP8C7经测定的cDNA序列
SEQ ID NO:292是JP8D7经测定的cDNA序列
SEQ ID NO:293是P8D8经测定的cDNA序列
SEQ ID NO:294是JP8E7经测定的cDNA序列
SEQ ID NO:295是JP8F8经测定的cDNA序列
SEQ ID NO:296是JP8G8经测定的cDNA序列
SEQ ID NO:297是JP8B10经测定的cDNA序列
SEQ ID NO:298是JP8C10经测定的cDNA序列
SEQ ID NO:299是JP8E9经测定的cDNA序列
SEQ ID NO:300是JP8E10经测定的cDNA序列
SEQ ID NO:301是JP8F9经测定的cDNA序列
SEQ ID NO:302是JP8H9经测定的cDNA序列
SEQ ID NO:303是JP8C12经测定的cDNA序列
SEQ ID NO:304是JP8E11经测定的cDNA序列
SEQ ID NO:305是JP8E12经测定的cDNA序列
SEQ ID NO:306是肽PS2#12的氨基酸序列
SEQ ID NO:307是P711P经测定的cDNA序列
SEQ ID NO:308是P712P经测定的cDNA序列
SEQ ID NO:309是CLONE23经测定的cDNA序列
SEQ ID NO:310是P774P经测定的cDNA序列
SEQ ID NO:311是P775P经测定的cDNA序列
SEQ ID NO:312是P71 5P经测定的cDNA序列
SEQ ID NO:313是P710P经测定的cDNA序列
SEQ ID NO:314是P767P经测定的cDNA序列
SEQ ID NO:315是P768P经测定的cDNA序列
SEQ ID NO:316-325是先前分离的基因经测定的cDNA序列
SEQ ID NO:326是P703PDE5经测定的cDNA序列
SEQ ID NO:327是P703PDE5预测的氨基酸序列
SEQ ID NO:328是P703P6.26经测定的cDNA序列
SEQ ID NO:329是P703P6.26预测的氨基酸序列
SEQ ID NO:330是P703PX-23经测定的cDNA序列
SEQ ID NO:331是P703PX-23预测的氨基酸序列
SEQ ID NO:332是P509S经测定的全长cDNA序列
SEQ ID NO:333是P707P(也称为11-C9)经测定的延续cDNA序列
SEQ ID NO:334是P714P经测定的cDNA序列
SEQ ID NO:335是P705P(也称为9-F3)经测定的cDNA序列
SEQ ID NO:336是P705P预测的氨基酸序列
SEQ ID NO:337是肽P1S#10的氨基酸序列
SEQ ID NO:338是肽p5的氨基酸序列
SEQ ID NO:339是P509S预测的氨基酸序列
SEQ ID NO:340是P778P经测定的cDNA序列
SEQ ID NO:341是P786P经测定的cDNA序列
SEQ ID NO:342是P789P经测定的cDNA序列
SEQ ID NO:343是显示与人MM46的mRNA有同源性的克隆经测定的cDNA序列
SEQ ID NO:344是显示与人α-TNF刺激的ABC蛋白(ABC50)的mRNA有同源性的克隆经测定的cDNA序列
SEQ ID NO:345是显示与人E-钙粘着蛋白的mRNA有同源性的克隆经测定的cDNA序列
SEQ ID NO:346是显示与人细胞核编码的线粒体丝氨酸羟甲基转移酶(SHMT)的mRNA有同源性的克隆经测定的cDNA序列
SEQ ID NO:347是显示与人天然抗性相关的巨噬细胞蛋白2(NRAMP2)有同源性的克隆经测定的cDNA序列
SEQ ID NO:348是显示与人葡糖磷酸变位酶相关蛋白(PGMRP)有同源性的克隆经测定的cDNA序列
SEQ ID NO:349是显示与人蛋白酶体亚基p40的mRNA有同源性的克隆经测定的cDNA序列
SEQ ID NO:350是P777P经测定的cDNA序列
SEQ ID NO:351是P779P经测定的cDNA序列
SEQ ID NO:352是P790P经测定的cDNA序列
SEQ ID NO:353是P784P经测定的cDNA序列
SEQ ID NO:354是P776P经测定的cDNA序列
SEQ ID NO:355是P780P经测定的cDNA序列
SEQ ID NO:356是P544S经测定的cDNA序列
SEQ ID NO:357是P745S经测定的cDNA序列
SEQ ID NO:358是P782P经测定的cDNA序列
SEQ ID NO:359是P783P经测定的cDNA序列
SEQ ID NO:360是未知的17984经测定的cDNA序列
SEQ ID NO:361是P787P经测定的cDNA序列
SEQ ID NO:362是P788P经测定的cDNA序列
SEQ ID NO:363是未知的17994经测定的cDNA序列
SEQ ID NO:364是P781P经测定的cDNA序列
SEQ ID NO:365是P785P经测定的cDNA序列
SEQ ID NO:366-375是B305D和各种剪接变体经测定的cDNA序列
SEQ ID NO:376是SEQ ID NO:366的序列编码的预测氨基酸序列
SEQ ID NO:377是SEQ ID NO:372的序列编码的预测氨基酸序列
SEQ ID NO:378是SEQ ID NO:373的序列编码的预测氨基酸序列
SEQ ID NO:379是SEQ ID NO:374的序列编码的预测氨基酸序列
SEQ ID NO:380是SEQ ID NO:375的序列编码的预测氨基酸序列
SEQ ID NO:381是B716P经测定的cDNA序列
SEQ ID NO:382是P711P经测定的全长cDNA序列
SEQ ID NO:383是P711P预测的氨基酸序列
SEQ ID NO:384是P1000C的cDNA序列
SEQ ID NO:385是CGI-82的cDNA序列
SEQ ID NO:386是23320的cDNA序列
SEQ ID NO:387是CGI-69的cDNA序列
SEQ ID NO:388是L-艾杜糖醇-2-脱氢酶的cDNA序列
SEQ ID NO:389是23379的cDNA序列
SEQ ID NO:390是23381的cDNA序列
SEQ ID NO:391是KIAA0122的cDNA序列
SEQ ID NO:392是23399的cDNA序列
SEQ ID NO:393是先前鉴定的基因的cDNA序列
SEQ ID NO:394是HCLBP的cDNA序列
SEQ ID NO:395是转谷氨酰胺酶(transglutaminase)的cDNA序列
SEQ ID NO:396是先前鉴定的基因的cDNA序列
SEQ ID NO:397是PAP的cDNA序列
SEQ ID NO:398是Ets转录因子PDEF的cDNA序列
SEQ ID NO:399是hTGR的cDNA序列
SEQ ID NO:400是KIAA0295的cDNA序列
SEQ ID NO:401是22545的cDNA序列
SEQ ID NO:402是22547的cDNA序列
SEQ ID NO:403是22548的cDNA序列
SEQ ID NO:404是22550的cDNA序列
SEQ ID NO:405是22551的cDNA序列
SEQ ID NO:406是22552的cDNA序列
SEQ ID NO:407是22553的cDNA序列
SEQ ID NO:408是22558的cDNA序列
SEQ ID NO:409是22562的cDNA序列
SEQ ID NO:410是22565的cDNA序列
SEQ ID NO:411是22567的cDNA序列
SEQ ID NO:412是22568的cDNA序列
SEQ ID NO:413是22570的cDNA序列
SEQ ID NO:414是22571的cDNA序列
SEQ ID NO:415是22572的cDNA序列
SEQ ID NO:416是22573的cDNA序列
SEQ ID NO:417是22573的cDNA序列
SEQ ID NO:418是22575的cDNA序列
SEQ ID NO:419是22580的cDNA序列
SEQ ID NO:420是22581的cDNA序列
SEQ ID NO:421是22582的cDNA序列
SEQ ID NO:422是22583的cDNA序列
SEQ ID NO:423是22584的cDNA序列
SEQ ID NO:424是22585的cDNA序列
SEQ ID NO:425是22586的cDNA序列
SEQ ID NO:426是22587的cDNA序列
SEQ ID NO:427是22588的cDNA序列
SEQ ID NO:428是22589的cDNA序列
SEQ ID NO:429是22590的cDNA序列
SEQ ID NO:430是22591的cDNA序列
SEQ ID NO:431是22592的cDNA序列
SEQ ID NO:432是22593的cDNA序列
SEQ ID NO:433是22594的cDNA序列
SEQ ID NO:434是22595的cDNA序列
SEQ ID NO:435是22596的cDNA序列
SEQ ID NO:436是22847的cDNA序列
SEQ ID NO:437是22848的cDNA序列
SEQ ID NO:438是22849的cDNA序列
SEQ ID NO:439是22851的cDNA序列
SEQ ID NO:440是22852的cDNA序列
SEQ ID NO:441是22853的cDNA序列
SEQ ID NO:442是22854的cDNA序列
SEQ ID NO:443是22855的cDNA序列
SEQ ID NO:444是22856的cDNA序列
SEQ ID NO:445是22857的cDNA序列
SEQ ID NO:446是23601的cDNA序列
SEQ ID NO:447是23602的cDNA序列
SEQ ID NO:448是23605的cDNA序列
SEQ ID NO:449是23606的cDNA序列
SEQ ID NO:450是23612的cDNA序列
SEQ ID NO:451是23614的cDNA序列
SEQ ID NO:452是23618的cDNA序列
SEQ ID NO:453是23622的cDNA序列
SEQ ID NO:454是叶酸水解酶的cDNA序列
SEQ ID NO:455是LIM蛋白的cDNA序列
SEQ ID NO:456是已知基因的cDNA序列
SEQ ID NO:457是已知基因的cDNA序列
SEQ ID NO:458是先前鉴定的基因的cDNA序列
SEQ ID NO459是23045的cDNA序列
SEQ ID NO:460是23032的cDNA序列
SEQ ID NO:461是23054的cDNA序列
SEQ ID NO:462-467是已知基因的cDNA序列
SEQ ID NO:468-471是P710P的cDNA序列
SEQ ID NO:472是P1001C的cDNA序列
发明详述
如上所述，本发明主要涉及用于治疗和诊断癌症(诸如前列腺癌)的组合物和方法。此处描述的组合物可以包括前列腺肿瘤多肽、编码这些多肽的多核苷酸、结合剂(诸如抗体)、抗原呈递细胞(APC)和/或免疫系统细胞(如T细胞)。本发明的多肽通常至少包含前列腺肿瘤蛋白的一部分(诸如免疫原性部分)或其变体。“前列腺肿瘤蛋白”指使用此处提供的代表性实验测定，在前列腺肿瘤细胞中的表达水平比在正常组织中的表达水平至少高2倍(优选至少5倍)的蛋白质。某些前列腺肿瘤蛋白是与前列腺癌患者的抗血清发生可检测反应(在免疫实验中，诸如ELISA或Western印渍)的肿瘤蛋白。本发明的多核苷酸通常包含编码这样的多肽的全部或一部分的DNA或RNA序列。抗体通常是能够与上述多肽结合的免疫系统蛋白质或它们的抗原结合片段。抗原呈递细胞包括表达上述多肽的树突状细胞、巨噬细胞、单核细胞、成纤维细胞和B细胞。在这些组合物中可以采用的T细胞，通常是对上述多肽特异的T细胞。
本发明的基础是人前列腺肿瘤蛋白的发现。编码某些肿瘤蛋白的多核苷酸序列或它们的一部分，提供于SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472。至少包含肿瘤蛋白的一部分的多肽序列提供于SEQ ID NO:112-114、172、176、178、327、329、331、336、339、376-380和383。前列腺肿瘤蛋白多核苷酸
本发明包括此处所述编码前列腺肿瘤蛋白或者它们的一部分的任何多核苷酸或其变体。优选的多核苷酸包含编码前列腺肿瘤蛋白的一部分的至少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。更优选的，多核苷酸编码前列腺肿瘤蛋白的免疫原性部分。本发明还包括与任何这些序列互补的多核苷酸。多核苷酸可以是单链(编码链或反义链)或双链，而且可以是(基因组的、cDNA或合成的)DNA或RNA分子。RNA分子包括含有内含子并与DNA分子一一对应的HnRNA分子和不含内含子的mRNA分子。本发明的多核苷酸可以(但不必)含有其它编码或非编码序列，而且多核苷酸可以(但不必)与其它分子和/或支持物相连。
多核苷酸可以包含天然序列(即编码前列腺肿瘤蛋白或它们的一部分的内源序列)或可以包含这样的序列的变体。多核苷酸变体可以含有一个或多个取代、加入、缺失和/或插入，但是相对于天然肿瘤多肽，所编码的多肽的免疫原性并没有降低。对编码的多肽的免疫原性的影响通常可以如此处所述进行评估。变体与编码天然前列腺肿瘤蛋白或它们的一部分的多核苷酸具有同一性，优选同一性至少大约70％，更优选至少大约80％，最优选至少大约90％。
如下文所述进行最大对应排列时，如果两种多核苷酸或多肽序列中的核苷酸或氨基酸序列是相同的，那么这两种多核苷酸或多肽序列称为“同一的”。两种序列之间的比较通常在比较窗口上进行，以鉴定并比较序列相似性的局部区域。本文中使用的“比较窗口”指至少大约20个，通常30-大约75个，40-大约50个连续位置的一段，其中的，序列可以与相同数目连续位置的参考序列在最佳排列后进行比较。
用于比较的序列的最佳排列可以使用生物信息学软件(DNASTAR,Inc.,Madison,WI)的Lasergene组件中的Megalign程序，种用系统参数进行。此程序收录了下列参考文献描述的多种排列设计：M.O.Dayhoff(1978)A model of evolutionary change in proteins-Matrices for detecting distant relationships.M.O.Dayhoff(编)Atlas of Protein Sequence and Structure,NationalBiomedical Research Foundation,Washington DC,Vol.5,Suppl.3,pp.345-358；J.Hein(1990)Unified Approach to Alignment andPhylogenes，酶学方法(Methods in Enzymology)，183卷，pp.626-645,Academic Press,Inc.,San Diego,CA；D.G.Higgins和P.M.Sharp(1989)CABIOS 5:151-153；E.W.Myers和W.Muller(1988)CABIOS 4:11-17；E.D.Robinson(1971)Comb.Theor 11:105；N.Santou和M.Nes(1987)Mol.Biol.Evol.4:406-425；P.H.A.Sneath和R.R.Sokal(1973)Numerical Taxonomy-the Principles andPractice of Numerical Taxonomy,Freeman Press,San Francisco,CA；W.J.Wilbur和D.J.Lipman(1983)Proc.Natl.Acad.Sci.USA 80:726-730。
优选的，“序列同一性百分比”在至少20个位置的比较窗口上比较两种最佳排列的序列进行测定，其中比较窗口中的多核苷酸或多肽序列部分，与进行最佳排列且不包含加入或缺失的参考序列相比，可以包含20％或更少的加入或缺失(即缺口)，通常5-15％，或10-12％。这一百分比如下计算：测定两种序列中核酸碱基或氨基酸残基相同的位置的数目，得到匹配位置数目；将匹配位置数目除以参考序列(即窗口大小)的位置总数，并将结果乘以100，从而得到序列同一性百分比。
变体可以还/或与天然基因或者它们的一部分或互补物在基本上是同源的。这些多核苷酸变体能够与天然产生的编码天然前列腺肿瘤蛋白的DNA序列(或互补序列)在中等严谨条件下杂交。合适的中等严谨条件包括在溶液5xSSC、0.5％SDS、1.0mM EDTA(pH8.0)中预洗；于50-65℃在5xSSC中杂交过夜；随后于65℃用含0.1％SDS的2x、0.5x和0.2xSSC各清洗两次，每次20分钟。
本领域普通技术人员将会理解，由于遗传密码的简并性，有许多种核苷酸序列编码此处所述的多肽。这些多核苷酸中的一些与任何天然基因的核苷酸序列具有最小同源性。虽然如此，本发明明确包括由于密码子使用的差异而变化的多核苷酸。此外，包含此处提供的多核苷酸序列的基因的等位基因属于本发明的范围之内。等位基因是由于一个或多个突变(诸如核苷酸的缺失、加入和/或取代)而改变的内源基因。得到的mRNA和蛋白质可以(但不必)具有改变的结构或功能。等位基因可以使用常规技术(诸如杂交、扩增和/或数据库序列比较)进行鉴定。
多核苷酸可以使用多种技术进行制备。例如，多核苷酸可以通过对cDNA微阵(microarray)筛选肿瘤相关表达(即使用此处提供的代表性实验进行测定，在前列腺肿瘤中的表达比在正常组织中高至少5倍)而进行鉴定，下文描述更为详细。这些筛选可以使用Synteni微阵(Palo Alto,CA)，根据制造商的说明书(并基本上如Schena等人[Proc.Natl.Acad.Sci.USA 93:10614-10619,1996]和Heller等人[Proc.Natl Acad.Sci.USA 94:2150-2155,1997]所述)进行。或者，多肽可以由从表达此处所述蛋白质的细胞(诸如前列腺肿瘤细胞)制备的cDNA进行扩增。这些多核苷酸可以通过聚合酶链式反应(PCR)进行扩增。对于此方法，可以根据此处提供的序列设计序列特异的引物，而且可以购买或合成。
使用众所周知的技术，可以将经扩增的部分用于从合适的文库(如前列腺肿瘤cDNA文库)分离全长基因。在这些技术中，使用一种或多种适合于扩增的多核苷酸探针或引物对(cDNA或基因组)文库进行筛选。优选的，文库经大小选择而包含较大的分子。随机引发文库也可以优选用于鉴定基因的5’和上游区域。基因组文库优选用于获取内含子和延续的5’序列。
对于杂交技术，可以使用众所周知的技术对部分序列进行标记(如通过缺刻翻译或用32P末端标记)。然后将含有变性细菌菌落(或含有噬菌体噬斑的菌苔)的滤膜与经标记探针(见Sambrook等人，Molecular Cloning:A Laboratory Manual,Cold Spring HarborLaboratories,Cold Spring Harbor,NY,1989)杂交，从而对细菌或噬菌体文库进行筛选。选择并扩增杂交菌落或噬斑，并分离DNA用于进一步的分析。可以对cDNA克隆进行分析，例如使用来自部分序列的一种引物和来自载体的一种引物进行PCR，以测定其它序列的量。可以构建限制性图谱和部分序列以鉴定一种或多种重叠克隆。然后可以使用常规技术(可能涉及构建一系列缺失克隆)测定完整序列。然后将得到的重叠序列装配成单一连续序列。可以使用众所周知的技术，通过连接合适的片段构建全长cDNA分子。
或者，有大量的扩增技术可以用于由部分cDNA序列得到全长编码序列。在这些技术中，通常通过PCR进行扩增。可以使用多种可购买的试剂盒进行扩增步骤。可以使用(例如)本领域众所周知的软件进行引物设计。引物优选长度为22-30个核苷酸，GC含量为至少50％，并于大约68-72℃的温度下与靶序列退火。可以如上所述对扩增区域进行测序，并将重叠序列装配成连续序列。
这样一种扩增技术是用限制酶产生基因已知区域的片段的反向PCR(见Triglia等人，Nucl.Acids Res.16:8186,1988)。然后通过分子内连接将片段环化，并作为模板和由已知区域得到的趋异引物用于PCR。在另一种方法中，可以使用接头序列的引物和已知区域特异的引物进行扩增，获得部分序列的邻近序列。通常使用相同的接头引物和特异于已知区域的第二引物，对扩增序列进行第二轮扩增。此步骤的一种变动是采用由已知区域起始相反方向延伸的两种引物，其描述于WO 96/38591。另一种这样的技术是“cDNA末端的快速扩增”或RACE。此技术涉及使用一种内部引物和可与polyA区域或载体序列杂交的一种外部引物，以鉴定已知序列的5’和3’序列。另外的技术包括俘获PCR(Lagerstrom等人，PCR Methods Applic.1:111-19,1991)和行走PCR(Parker等人，Nucl.Acids Res.19:3055-60,1991)。使用扩增的其它方法也可以用于得到全长cDNA序列。
在某些实例中，通过分析表达序列标签(EST)数据库(诸如GenBank)提供的序列，可能得到全长cDNA序列。对重叠EST的搜索通常可以使用众所周知的程序(如NCBI BLAST搜索)进行，而且这些EST可以用于构建连续的全长序列。
至少编码前列腺肿瘤蛋白的一部分的cDNA分子某些核酸序列提供于：SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472。下文描述了这些多核苷酸的分离方法。这些前列腺肿瘤蛋白的每一种在前列腺肿瘤组织中均过度表达。
多核苷酸变体通常可以通过本领域已知的任何方法制备，包括化学合成，例如固相亚磷酰胺化学合成法。也可以使用常规诱变技术，诸如寡核苷酸介导的位点特异的诱变(见Adelman等人，DNA 2:183，1983)，在多核苷酸序列中引入修饰。或者，倘若编码前列腺肿瘤蛋白或它们的一部分的DNA已经插入到含有合适的RNA聚合酶启动子(诸如T7或SP6)的载体中，则可以通过DNA序列的体外或体内转录产生RNA分子。如此处所述，某些部分可以用于制备编码的多肽。此外，可以给病人施用一部分多核苷酸，以在体内合成编码的多肽(如通过用编码前列腺肿瘤多肽的cDNA构建物转染抗原呈递细胞，诸如树突状细胞，并给病人施用经转染细胞)。
与编码序列互补的序列(即反义多核苷酸)的一部分也可以作为探针使用，或用于调控基因表达。可以转录成反义RNA的cDNA构建物也可以导入组织细胞中，以有助于产生反义RNA。如此处所述，可以使用反义多核苷酸以抑制肿瘤蛋白的表达。反义技术可以用于控制基因表达，其机理是形成三股螺旋，削弱两股螺旋打开以结合聚合酶、转录因子或调控分子的能力(见Gee等人，Huber和Carr中的Molecular and Immunologic Approaches,Futura Publishing Co.(Mt.Kisco,NY；1994))。或者，可以设计反义分子，使其与基因的控制区域(如启动子、增强子或转录起始位点)杂交，并阻断基因的转录；或通过抑制转录本与核糖体的结合而阻断翻译。
编码序列或互补序列的一部分，也可以设计为检测基因表达的探针或引物。探针可以用各种报导基团(诸如放射性核素和酶)进行标记，且长度优选至少10个核苷酸，更优选至少20个核苷酸，更更优选至少30个核苷酸。如上所述，引物长度优选22-30个核苷酸。
任何多核苷酸可以进行进一步的修饰以增加体内稳定性。可能的修饰包括(但不限于)在5’和/或3’末端加入侧翼序列；主链中使用磷酸硫酯或2’O-甲基而非磷酸二酯键；和/或包含非常见碱基，诸如次黄核苷、queosine和wybutosine，以及腺嘌呤、胞嘧啶、鸟嘌呤、胸腺嘧啶和尿嘧啶的乙酰基-、甲基-、硫代-和其它修饰形式。
此处所述核苷酸序列可以使用已建立的重组DNA技术与多种其它核苷酸序列进行连接。例如，可以将多核苷酸克隆到多种克隆载体中，包括质粒、噬菌粒、λ噬菌体衍生物和粘粒。特别感兴趣的载体包括表达载体、复制载体、探针产生载体和测序载体。通常，载体含有在至少一种生物体中有功能的复制起点、方便的限制性内切酶位点、和一种或多种可选择标记。其它元件取决于设计用途，且对本领域普通技术人员是明显的。
在某些实施方案中，可以将多核苷酸配成制剂，以能够进入哺乳动物细胞并在其中表达。如下文所述，这些制剂对于治疗目的特别有用。本领域普通技术人员可以理解，有许多方法可以实现多核苷酸在靶细胞中的表达，而且可以采用任何合适的方法。例如，可以将多核苷酸插入病毒载体，诸如(但不限于)腺病毒、腺伴随病毒、逆转录病毒、或者牛痘或其它痘病毒(如鸟类痘病毒)。用于将DNA插入这些载体的技术对于本领域普通技术人员是众所周知的。逆转录病毒载体还可以转移或插入一个基因，作为可选择标记(以帮助鉴定或选择经转导的细胞)和/或靶向模块(诸如编码特异靶细胞上的受体的配基，使得载体具有目标特异性)。靶向作用还可以使用抗体通过本领域普通技术人员已知的方法来实现。
用于治疗目的的其它制剂包括胶状体分散系统，诸如高分子复合物、微囊、微球体、珠、和基于脂类的系统(包括水包油乳状液、微团、混和微团、和脂质体)。作为体外和体内投递载体使用的优选胶状系统是脂质体(即人工膜泡)。这些系统的制备和使用在本领域中是众所周知的。前列腺肿瘤多肽
如上所述，在本发明的内容中，多肽可以至少包含前列腺肿瘤多肽的免疫原性部分或其变体。如上所述，“前列腺肿瘤蛋白”指由前列腺肿瘤细胞表达的蛋白质。称作前列腺肿瘤蛋白的蛋白质还可在免疫实验(诸如ELISA)中与来自前列腺癌患者的抗血清发生可检测反应。上述多肽可以是任何长度的。可以有由天然蛋白质和/或异源序列得到的其它序列，而且这些序列可以(但不必)具有其它免疫原或抗原特性。
“免疫原性部分”，如此处使用的，指蛋白质中由B细胞和/或T细胞表面抗原受体识别(即特异结合)的一部分。这些免疫原性部分通常包含前列腺肿瘤蛋白或其变体的至少5个氨基酸残基，更优选至少10个氨基酸残基，更更优选至少20个氨基酸残基。某些优选的免疫原性部分包括已经缺失了N-末端前导序列和/或跨膜结构域的肽。其它优选的免疫原性部分可以含有相对于成熟蛋白质较短的N-和/或C-末端缺失(如1-30个氨基酸，优选5-15个氨基酸)。
免疫原性部分通常可以使用众所周知的技术进行鉴定，诸如Paul在Fundamental Immunology，第三版，243-247(Raven Press,1993)中总结的技术及其参考文献。这些技术包括对多肽筛选与抗原特异的抗体、抗血清和/或T细胞系或克隆反应的能力。如此处使用的，若抗血清和抗体可与抗原特异结合(即它们在ELISA或其它免疫实验中与该蛋白质发生反应，而且与不相关的蛋白质不发生可检测反应)，则它们是“抗原特异的”。这些抗血清和抗体，如此处所述，可使用众所周知的技术进行制备。天然前列腺肿瘤蛋白的免疫原性部分是与这些抗血清和/或T细胞的反应水平基本上不低于全长多肽的反应性(如在ELISA和/或T细胞反应实验中)的部分。这些免疫原性部分可以在这些实验中以与全长多肽反应性相似或更高的水平发生反应。这些筛选通常可以使用本领域普通技术人员众所周知的方法进行，诸如在Harlow和Lane,Antibodies:A Laboratory Manual,Cold SpringHarbor Laboratory,1988中描述的方法。例如，可以将多肽固定在固体支持物上，并与患者血清接触，使血清中的抗体与经固定的多肽结合。然后可以除去未结合的多肽，并使用(例如)125I标记的蛋白A检测结合的抗体。
如上所述，组合物可以包含天然前列腺肿瘤蛋白的变体。多肽“变体”，如此处所用，指与天然前列腺肿瘤多肽因一个或多个取代、缺失、加入和/或插入而不同，但是多肽的免疫原性没有实质性降低的多肽。换句话说，变体与抗原特异的抗血清反应的能力，与天然蛋白质相比，可能增强或不变，或者可以降低少于50％，优选少于20％。这些变体通常可以通过修饰一种上述多肽序列并评价经修饰的多肽与此处所述抗原特异的抗体或抗血清的反应性而进行鉴定。优选的变体包括已经除去一个或多个部分(诸如N-末端前导序列或跨膜结构域)的变体。其它优选的变体包括已经从成熟蛋白质的N-和/或C-末端除去一小部分(如1-30个氨基酸，优选5-15个氨基酸)的变体。多肽变体优选展示与经鉴定的多肽至少大约70％，更优选至少大约90％，更优选至少大约95％的同一性(如上测定)。
优选的，变体含有保守取代。“保守取代”指一种氨基酸被另一种有相似特性的氨基酸取代，而且肽化学领域技术人员预测多肽的二级结构和亲水特性基本上不变。氨基酸取代通常可以根据残基的极性、电荷、溶解性、疏水性、亲水性和/或两性性质的相似性进行。例如，带负电荷的氨基酸包括天冬氨酸和谷氨酸；带正电荷的氨基酸包括赖氨酸和精氨酸；而具有不带电荷的极性头基团、可能代表相似亲水性值的氨基酸包括亮氨酸、异亮氨酸和缬氨酸；甘氨酸和丙氨酸；天冬酰胺和谷氨酰胺；和丝氨酸、苏氨酸、苯丙氨酸和酪氨酸。可能代表保守改变的其它组氨基酸包括：(1)ala、pro、gly、glu、asp、gln、asn、ser、thr；(2)cys、ser、tyr、thr；(3)val、ile、leu、met、ala、phe；(4)lys、arg、his；和(5)phe、tyr、trp、his。变体可以还/或者含有非保守改变。在优选的实施方案中，变体多肽因5个或更少氨基酸的取代、缺失或加入而与天然序列不同。变体可以还/或者通过(例如)缺失或加入对多肽的免疫原性、二级结构和亲水特性影响很小的氨基酸而进行修饰。
如上所述，多肽可以在蛋白质的N-末端包含在翻译时或翻译后引导蛋白质转移的信号(或前导)序列。多肽还可以与接头或其它序列缀合，以便于多肽的合成、纯化或鉴定(如多聚组氨酸)，或增强多肽与固体支持物的结合。例如，多肽可以与免疫球蛋白Fc区缀合。
多肽可以使用多种众所周知的技术进行制备。由上述DNA序列编码的重组多肽可以由DNA序列使用本领域普通技术人员已知的多种表达载体容易的制备。表达可以在任何适当的、用含编码重组多肽的DNA分子的表达载体转化或转染了的宿主细胞中进行。合适的宿主细胞包括原核细胞、酵母和高等真核细胞。优选的，采用的宿主细胞是大肠杆菌、酵母或哺乳动物细胞系(诸如COS或CHO)。首先对来自合适的将重组蛋白质或多肽分泌到培养基中的宿主/载体系统的上清液使用可购买的滤器进行浓缩。然后，将浓缩液用合适的纯化基质(诸如亲和基质或离子交换树脂)进行纯化。最后，可以进行一轮或多轮反相HPLC以进一步纯化重组多肽。
少于大约100个氨基酸、通常少于大约50个氨基酸的多肽部分和其它变体，还可以使用本领域普通技术人员众所周知的技术，通过合成方法产生。例如，这些多肽可以使用任何可购买的固相技术进行合成，诸如Merrifield固相合成方法，其中氨基酸被依次加到正在延伸的氨基酸链上。见Merrifield,J.Am.Chem.Soc.85:2149-2146,1963。用于多肽自动合成的设备可以从供应商，诸如Perkin Elmer/Applied BioSystems Division(Foster City,CA)购买，而且可以根据制造商的说明书进行操作。
在某些特殊的实施方案中，多肽可以是包含多种上述多肽，或包含至少一种上述多肽和无关序列(诸如已知肿瘤蛋白)的融合蛋白。例如，融合配偶体可以帮助提供T辅助表位(免疫学融合配偶体)，优选人识别的T辅助表位，或者可以帮助以高于天然重组蛋白的产量表达蛋白质(表达增强子)。某些优选的融合配偶体既是免疫学又是表达增强融合配偶体。可以选择其它融合配偶体，以增加蛋白质的溶解性，或使得蛋白质靶向到目的细胞内区室。还有的融合配偶体包括有助于蛋白质纯化的亲和标签。
融合蛋白通常可以使用常规技术进行制备，包括化学缀合。优选的，融合蛋白作为重组蛋白在表达系统中表达，使得能够相对于非融合蛋白以升高水平进行生产。简单的说，可以分开装配编码多肽成分的DNA序列，并连接到适当的表达载体中。编码一种多肽成分的DNA序列的3’末端，以肽接头或无肽接头，与编码第二种多肽成分的DNA序列的5’末端进行连接，使得序列的阅读框架是相同的。这使得翻译得到单一融合蛋白，该蛋白质保留了两种成分多肽的生物学活性。
可以用肽接头序列将第一种和第二种多肽成分分开足够距离，以确保每种多肽折叠成各自的二级和三级结构。使用本领域众所周知的技术，将这样的肽接头序列插入融合蛋白。可以根据下列因素选择合适的肽接头序列：(1)形成柔性伸展构象的能力；(2)不会形成可以与第一种和第二种多肽上的功能表位发生相互作用的二级结构的能力；和(3)缺乏会与多肽的功能表位发生反应的疏水的或带电荷的残基。优选的肽接头序列含有甘氨酸、天冬酰胺和丝氨酸残基。其它近乎中性的氨基酸，诸如苏氨酸和丙氨酸也可以在接头序列中使用。可以作为接头有效使用的氨基酸序列包括在Maratea等人，Gene 40:39-46,1985；Murphy等人，Proc.Natl.Acad.Sci.USA 83:8258-8262,1986；美国专利号4,935,233和美国专利号4,751,180中公开的那些序列。接头序列的长度通常可以为1-大约50个氨基酸。当第一和第二多肽具有可用来隔开它们的功能性结构域和阻止空间干扰的非必需N-末端氨基酸区域时，就不需要这样的肽序列。
将经连接的DNA序列与合适的转录或翻译调控元件进行可操作连接。负责DNA表达的调控元件只位于编码第一种多肽的DNA序列的5’端。相似的，用于终止翻译的终止密码子和转录终止信号只位于编码第二种多肽的DNA序列的3’端。
还提供了包含本发明多肽和无关免疫原性蛋白质的融合蛋白。优选的免疫原性蛋白质能够引起记忆应答。这些蛋白质的实例包括破伤风、结核和肝炎蛋白质(见例如Stoute等人，New Engl.J.Med.336:86-91,1997)。
在优选的实施方案中，免疫学融合配偶体由蛋白D(革兰氏阴性细菌流感嗜血杆菌B的表面蛋白，WO91/18926)得到。优选的，蛋白D衍生物大致包含该蛋白质的前三分之一(如N-末端前100-110个氨基酸)，而且蛋白D衍生物可以进行脂化。在某些优选的实施方案中，N-末端包括脂蛋白D融合配偶体的前109个残基，从而为多肽提供额外的外源T细胞表位，并增加在大肠杆菌中的表达水平(由此作为表达增强子发挥功能)。脂尾确保了向抗原呈递细胞最佳展示抗原。其它融合配偶体包括来自流感病毒的非结构蛋白质，NS1(血细胞凝集素)。通常，使用N-末端的81个氨基酸，但是也可以使用包括T辅助表位的不同片段。
在另一个实施方案中，免疫学融合配偶体是称为LYTA的蛋白质或它的一部分(优选C-末端部分)。LYTA是由合成N-乙酰基-L-丙氨酸酰胺酶(称为酰胺酶LYTA，由LytA基因编码，Gene 43:265-292,1986)的肺炎链球菌得到的。LYTA是一种自溶素，可特异降解肽聚糖主链中的某些键。LYTA蛋白的C-末端结构域负责与胆碱或一些胆碱类似物(诸如DEAE)的亲和力。此特性已经被应用于发展可用于表达融合蛋白的大肠杆菌C-LYTA表达质粒。在氨基末端含有C-LYTA片段的杂合蛋白的纯化已经描述于Biotechnology 10:795-798,1992。在优选的实施方案中，可以将LYTA的重复部分插入融合蛋白。一个重复部分发现于C-末端区域，于第178位残基开始。特别优选的重复部分包括第188-305位残基。
通常，此处所述的多肽(包括融合蛋白)和多核苷酸是分离的。“分离的”多肽或多核苷酸指与其最初的环境是分开的。例如，如果将天然产生的蛋白质与一些或所有在天然系统中共存的物质分开，那么该蛋白质就是分离的。优选的，这些多肽是至少大约90％纯，更优选至少大约95％纯，最优选至少大约99％纯。例如，如果将多核苷酸克隆到并非天然环境一部分的载体中，那么可以认为该多核苷酸是分离的。结合剂
本发明还提供了可与前列腺肿瘤蛋白特异结合的药剂，诸如抗体和它们的抗原结合片段。如此处使用的，如果抗体或它们的抗原结合片段以可检测的水平(在例如ELISA中)与前列腺肿瘤蛋白发生反应，而与无关蛋白质在相似条件下不发生可检测反应，那么称它们与前列腺肿瘤蛋白是可“特异结合”的。如此处使用的，“结合”指两个分开的分子之间的非共价结合，以至于形成复合物。结合能力可以通过，例如测定复合物形成的结合常数，进行评价。结合常数是将复合物浓度除以各成分浓度的乘积得到的数值。通常，当复合物形成的结合常数超过大约103L/mol时，则称此两种成分“结合”。结合常数可以使用本领域众所周知的方法进行测定。
使用此处提供的代表性实验，结合剂还可以区分患者是否患有癌症(诸如前列腺癌)。换句话说，可与前列腺肿瘤蛋白结合的抗体或其它结合剂，对至少大约20％的患病患者将产生显示存在癌症的信号，对至少大约90％的未患该癌症的个体将产生显示不存在癌症的阴性信号。为了测定结合剂是否满足此需要，对来自患有或未患癌症的患者(使用常规诊断测试测定)的生物学样品(如血液、血清、尿液和/或肿瘤活组织标本)可以如此处描述的检测可与该结合剂结合的多肽的存在。显然应当对统计学有意义的数量的患病或未患病样品进行实验。每种结合剂应当满足上述标准；然而，本领域普通技术人员将认识到结合剂可以进行组合以提高灵敏度。
满足上述要求的任何试剂可以作为结合剂。例如，结合剂可以是带有或不带肽成分的核糖体、RNA分子或多肽。在优选的实施方案中，结合剂是抗体或它们的抗原结合片段。抗体可以本领域普通技术人员知道的多种技术进行制备。见例如Harlow和Lane,Antibodies:ALaboratory Manual,Cold Spring Harbor Laboratory,1988。通常，抗体可以通过细胞培养技术进行生产，包括本文所述单克隆抗体的产生，或用抗体基因转染合适的细菌或哺乳动物细胞宿主，从而产生重组抗体。在一种技术中，首先将包含多肽的免疫原注射到多种哺乳动物(如小鼠、大鼠、兔、绵羊或山羊)的任一种中。在此步骤中，本发明的多肽可以作为不经修饰的免疫原。或者，特别是对于相对较短的多肽，如果将多肽与载体蛋白(诸如牛血清清蛋白或匙孔_血蓝蛋白)进行连接，可以引起较好的免疫应答。将免疫原注射到动物宿主中，优选根据预先排定的包括一次或多次加强免疫的时间表进行，并对动物定期取血。然后可以(例如)使用与合适固体支持物偶联的多肽的亲和层析，由该抗血清纯化对多肽特异的多克隆抗体。
可以(例如)使用Kohler和Milstein,Eur.J.Immunol.6:511-519,1976的技术及其改进，制备对感兴趣的抗原多肽特异的单克隆抗体。简单的说，这些方法涉及制备能够产生具有想要的特异性(即与感兴趣的多肽的反应性)的抗体的永生细胞系。这些细胞系可以(例如)由从上述经免疫的动物得到的脾细胞产生。然后通过例如与骨髓瘤细胞融合配偶体，优选与被免疫动物同基因的融合配偶体融合，使脾细胞永生化。可以采用多种融合技术。例如，可以将非离子去污剂与脾细胞和骨髓瘤细胞混合几分钟，然后以低密度在支持杂合细胞而非骨髓瘤细胞生长的选择性平板上进行铺板。优选的选择技术使用HAT(次黄嘌呤、氨基喋呤、胸苷)选择。足够时间，通常大约1-2周后，可观察到杂合体的集落。选择单集落，并测试它们的培养物上清液对多肽的结合活性。优选具有高反应性和特异性的杂交瘤细胞。
可以由正在生长的杂交瘤细胞集落上清液分离单克隆抗体。此外，可以采用多种技术来提高产量，诸如将杂交瘤细胞系注射到合适的脊椎动物宿主(诸如小鼠)的腹膜腔中。然后可以由腹水或血液收获单克隆抗体。可以通过传统技术，诸如层析、凝胶过滤、沉淀、和抽提，从抗体中除去污染物。本发明的多肽可以用于例如亲和层析步骤的纯化过程。
在某些实施方案中，使用抗体的抗原结合片段可能是优选的。这些片段包括可以使用常规技术制备的Fab片段。简单的说，可以通过蛋白A珠层析柱上的亲和层析，由兔血清纯化免疫球蛋白(Harlow和Lane,Antibodies:A Laboratory Manual,Cold Spring HarborLaboratory,1988)，并用木瓜蛋白酶进行消化，以产生Fab和Fc片段。可以通过在蛋白A珠层析柱上亲和层析，将Fab和Fc片段分开。
本发明的单克隆抗体可以与一种或多种治疗剂进行偶联。这方面合适的试剂包括放射性核素、分化诱导剂、药物、毒素、和它们的衍生物。优选的放射性核素包括90Y、123I、125I、131I、186Re、188Re、221At、和212Bi。优选的药物包括氨甲喋呤、以及嘧啶和嘌呤类似物。优选的分化诱导剂包括佛波醇酯和丁酸。优选的毒素包括蓖麻毒蛋白、相思豆毒蛋白、白喉毒素、霍乱毒素、白树毒素(gelonin)、假单胞菌外毒素、志贺氏菌毒素、和美洲商陆抗病毒蛋白。
治疗剂可以与合适的单克隆抗体直接或间接(如通过连接基团)进行偶联(如共价键结合)。若试剂和抗体都含有能够相互反应的取代基，则它们之间的直接反应是可能的。例如，二者之一上的亲核基团(诸如氨基或巯基)可以与二者之另一上的含羰基基团(诸如酸酐或酸卤化物)或含易离去基团的烷基(如卤化物)发生反应。
或者，可能比较理想的是将治疗剂和抗体通过连接基团进行偶联。连接基团可以作为间隔抗体与试剂的间隔子发挥功能，以避免对结合能力的影响。连接基团还可以用来增加试剂或抗体上的取代基的化学反应性，并由此增加偶联效率。化学反应性的增加还可以有助于原本不可能使用的试剂或试剂上的功能基团的使用。
对于本领域技术人员明显的是，可以采用多种双功能或多功能试剂(同和异功能的，诸如Pierce Chemical Co.,Rockford,IL的产品目录中描述的)作为连接基团。偶联可以(例如)通过氨基、羧基、巯基或经氧化后的糖类残基实现。有大量参考文献描述这些方法学，如授予Rodwell的美国专利号4,671,958。
若治疗剂不含本发明免疫缀合物的抗体部分时更有效，则可能需要使用在进入细胞过程中或其后可被切割的连接基团。已经描述了大量不同的可切割的连接基团。试剂在细胞内从连接基团释放的机制，包括通过还原双硫键(如授予Spitler的美国专利号4,489,710)、通过照射光不稳定键(授予Senter等人的美国专利号4,625,014)、衍生氨基酸侧链的水解(如授予Kohn等人的美国专利4,638,045)、血清补体介导的水解(如授予Rodwell等人的美国专利4,671,958)以及酸催化的水解(如授予Blattler等人的美国专利号4,569,789)进行裂解。
可能需要将多于一种试剂与抗体进行偶联。在一个实施方案中，将多分子试剂与单分子抗体偶联。在另一个实施方案中，多于一种试剂可以与一种抗体偶联。不管具体实施例如何，含有多于一种试剂的免疫缀合物可以有多种方法进行制备。例如，一种以上试剂可以与一个抗体分子直接进行偶联，或者可以使用提供多个附着位点的接头。或者，可以使用载体。
载体可以以多种方式携带试剂，包括直接的或通过连接基团的共价结合。合适的载体包括蛋白质诸如清蛋白(如授予Kato等人的美国专利号4,507,234)、肽和多糖诸如氨基葡聚糖(如授予Shih等人的美国专利号4,699,784)。载体还可以通过非共价结合或通过包裹(诸如在脂质体囊泡中，如美国专利号4,429,008和4,873,088)携带试剂。对放射性核素试剂特异的载体包括放射性卤化的小分子和螯合化合物。例如，美国专利号4,735,792公开了代表性的放射性卤化小分子和它们的合成方法。放射性核素螯合物可以由螯合化合物(包括含有氮和硫原子作为结合金属或金属氧化物放射性核素的供体原子的那些螯合化合物)构成。例如，授予Dayison等人的美国专利号4,673,562公开了代表性螯合化合物和它们的合成方法。
对于抗体和免疫缀合物可以使用多种施用途径。通常，施用方法可以是静脉内、肌肉内、皮下或对切除肿瘤病灶进行。显然抗体/免疫缀合物的准确剂量将随使用的抗体、肿瘤上的抗原密度、和抗体的清除速率而变化。T细胞
免疫治疗组合物可以还/或包含对前列腺肿瘤蛋白特异的T细胞。这些细胞通常可以在体外或离体，使用常规步骤进行制备。例如，T细胞可以由患者的骨髓、外周血、或一部分骨髓或外周血，使用可以由CellPro Inc.,Bothell WA购买的细胞分离系统诸如CEPRATETM分离得到(也见美国专利号5,240,856；美国专利号5,215,926；WO89/06280；WO91/16116和WO92/07243)。或者，T细胞可以由相关或无关人、非人哺乳动物、细胞系或培养物衍生得到。
T细胞可以用前列腺肿瘤多肽、编码前列腺肿瘤多肽的多核苷酸和/或表达这样的多肽的抗原呈递细胞(APC)进行刺激。这样的刺激在足够产生对多肽特异的T细胞的条件和时间下进行。优选的，前列腺肿瘤多肽和多核苷酸存在于投递载体(诸如微球体)中，有助于产生特异T细胞。
如果T细胞可杀死前列腺肿瘤多肽包被的或表达编码该多肽的基因的靶细胞，那么认为T细胞对该多肽是特异的。T细胞特异性可以使用多种常规技术进行评估。例如，在铬释放实验或增殖实验中，与阴性对照相比，溶解和/或增殖增加超过2倍的刺激指数指示有T细胞特异性。这些实验可以如Chen等人，Cancer Res.54:1065-1070，1994中描述的进行。或者，T细胞增殖的检测可以通过多种已知技术实现。例如，T细胞增殖可以通过测量DNA合成的增加速率(如通过用氚标记胸苷脉冲标记T细胞的培养物并测量掺入DNA的氚标记胸苷的量)进行检测。与前列腺肿瘤多肽(100ng/ml-100μg/ml，优选200ng/ml-25μg/ml)接触3-7天，应当导致T细胞增殖至少增加2倍。如上述接触2-3小时，应当导致T细胞的激活，这种激活可使用常规细胞因子实验进行测量，其中细胞因子释放水平(如TNF或TNF-γ)增加2倍是T细胞活化的指征(见Coligan等人，CurrentProtocols in Immunology，第一卷，Wiley Interscience(Greene1998))。应答前列腺肿瘤多肽、多核苷酸或表达多肽的APC而已经激活的T细胞可以是CD4-和/或CD8+。前列腺肿瘤蛋白特异的T细胞可以使用常规技术进行扩增。在优选的实施方案中，T细胞由患者或者相关或无关供体得到，并在激活和扩增后给患者施用。
为了治疗目的，应答前列腺肿瘤多肽、多核苷酸或APC而增殖的CD4+或CD8+T细胞，其数量可以在体外或体内扩增。这些T细胞的体外增殖可以多种方式进行。例如，可以将T细胞在加有或未加T细胞生长因子(诸如白介素-2)的条件下，再暴露于前列腺肿瘤多肽、或相当于这些多肽的免疫原性部分的短肽、和/或合成前列腺肿瘤多肽的刺激细胞。或者，可以通过克隆扩增在前列腺肿瘤蛋白存在条件下增殖的一个或多个T细胞。克隆细胞的方法在本领域是众所周知的，并且包括有限稀释。药物组合物和疫苗
在某些方面，可以将此处公开的多肽、多核苷酸、T细胞和/或结合剂掺入药物组合物或免疫原组合物(即疫苗)。药物组合物包含一种或多种这样的化合物和生理学可接受的载体。疫苗可以包含一种或多种这样的组合物和非特异免疫应答增强剂。非特异免疫应答增强剂可以是能增强对外源抗原的免疫应答的任何物质。非特异免疫应答增强剂的实例包括佐剂、可生物降解的微球体(如polylacticgalactide)和脂质体(其中掺入化合物；见如Fullerton，美国专利号4,235,877)。疫苗制备物描述于(例如)M.F.Powell和M.J.Newman，编，“Vaccine Design(the subunit and adjuvant approach)”，Plenum Press(NY,1995)。本发明范围内的药物组合物和疫苗还可以含有生物学有活性的和无活性的其它化合物。例如，在组合物或疫苗中，可以掺入融合多肽或作为分开的化合物的形式，存在其它肿瘤抗原的一或多个免疫原性部分。
药物组合物或疫苗可以含有编码上述一种或多种多肽的DNA，使得多肽可以原位合成。如上所述，DNA可以存在于本领域普通技术人员知道的多种投递系统中，包括核酸表达系统、细菌和病毒表达系统。大量基因投递技术在本领域是众所周知的，诸如Rolland描述的那些方法(Crit.Rev.Therap.Drug Carrier Systems 15:143-198,1998)及其引用的参考文献。适当的核酸表达系统含有在患者体内表达需要的DNA序列(诸如合适的启动子和终止信号)。细菌投递系统涉及施用在其细胞表面表达多肽的免疫原性部分或分泌这样的表位的细菌(诸如卡介菌)。在优选的实施方案中，可以使用可能涉及非致病的(有缺陷的)、能复制的病毒的病毒表达系统(如牛痘或其它痘病毒、逆转录病毒、或腺病毒)导入DNA。合适的系统公开于(例如)Fisher-Hoch等人，Proc.Natl.Acad.Sci.USA 86:317-321,1989；Flexner等人，Ann.N.Y.Acad.Sci.569:86-103,1989；Flexner等人，Vaccine8:17-21,1990；美国专利号4,603,112、4,769,330、和5,017,487；WO89/01973；美国专利号4,777,127；GB 2,200,651；EP 0,345,242；WO91/02805；Berkner,Biotechniques 6:616-627,1988；Rosenfeld等人，Science 252:431-434,1991；Kolls等人，Proc.Natl.Acad.Sci.USA 91:215-219,1994；Kass-Eisler等人，Proc.Natl.Acad.Sci.USA 90:11498-11502,1993；Guzman等人，Circulation88:2838-2848,1993；和Guzman等人，Cir.Res.73:1202-1207,1993。用于将DNA掺入这些表达系统的技术对本领域普通技术人员是众所周知的。DNA还可以是“裸露的”，如Ulmer等人，Science259:1745-1749,1993中描述的，Cohen,Science 259:1691-1692,1993中进行了综述。裸露DNA的摄取可以通过将DNA包被到能够有效转运到细胞中的、可生物降解的小珠上而增加。
虽然可以在本发明的药物组合物中采用本领域普通技术人员知道的任何合适的载体，但载体的类型随施用方式而变化。本发明的组合物可以配制成用于任何适当的施用方式，包括(例如)局部、口腔、鼻腔、静脉内、颅内、腹膜内、皮下、或肌内施用。对于非肠道施用，诸如皮下注射，载体优选包含水、盐水、醇、脂肪、蜡或缓冲液。对于口服施用，可以采用任何上述载体或固体载体，诸如甘露糖醇、乳糖、淀粉、硬脂酸镁、糖精钠(sodium saccharine)、滑石、纤维素、葡萄糖、蔗糖、和碳酸镁。还可以采用可生物降解的微球体(如polylactate polyglycolate)作为载体用于本发明的药物组合物。合适的可生物降解的微球体公开于(例如)美国专利号4,897,268和5,075,109。
这些组合物还可以包含缓冲液(如中性缓冲盐水或磷酸缓冲盐水)、糖类(如葡萄糖、甘露糖、蔗糖、或葡聚糖)、甘露糖醇、蛋白质、多肽或氨基酸(诸如甘氨酸)、抗氧化剂、螯合剂(诸如EDTA)或谷胱甘肽、佐剂(如氢氧化铝)和/或防腐剂。或者，本发明的组合物可以配制成冻干剂。化合物还可以使用众所周知的技术包被于脂质体内。
在本发明的疫苗中可以采用多种非特异免疫应答增强剂。例如，可以包括佐剂。大部分佐剂含有设计用于保护抗原免于快速代谢的物质，诸如氢氧化铝或矿物油，和免疫应答刺激物，诸如脂质A、百日咳杆菌或结核分枝杆菌衍生的蛋白质。合适的佐剂是可购买的，例如弗氏不完全佐剂和完全佐剂(Difco Laboratories,Inc.,Detroit,MI)；MerckAd juvant 65(Merck and Company,Inc.,Rahway,NJ)；铝盐，诸如氢氧化铝凝胶或磷酸铝；钙、铁或锌盐；酰化酪氨酸的不溶性悬浮液；酰化的糖；阳离子或阴离子衍生的多糖；polyphosphazene；可生物降解的微球体；单磷酰脂质A和quil A。细胞因子，诸如GM-CSF或白介素-2、-7、或-12，也可以作为佐剂使用。
在此处提供的疫苗中，佐剂组合物优选设计用来诱导Th1型占优势的免疫应答。高水平的Th1型细胞因子(如IFN-γ、IL-2和IL-12)趋向于诱导对所施用抗原的细胞介导免疫应答。相反的，高水平的Th2型细胞因子(如IL-4、IL-5、IL-6、IL-10、和TNF-β)趋向于诱导体液免疫应答。应用此处提供的疫苗之后，患者将产生包括Th1和Th2型应答的免疫应答。在优选的实施方案中，其中Th1型应答占优势，Th1型细胞因子的水平比Th2型细胞因子的水平将大大增加。使用常规技术可以容易的评估这些细胞因子的水平。有关细胞因子家族的综述，见Mosmann和Coffman,Ann.Rev.Immunol.7:145-173,1989。
用于引起主要为Th1型的应答的优选佐剂包括(例如)单磷酰脂质A，优选3-脱氧-酰化单磷酰脂质A(3D-MPL)与铝盐的组合。MPL佐剂可以由Ribi ImmunoChem Research Inc.(Hamilton,MT；见美国专利号4,436,727；4,877,611；4,866,034和4,912,094)购买。含CpG的寡核苷酸(其中CpG二核苷酸未甲基化)也诱导主要为Th1型的应答。这些寡核苷酸是众所周知的，而且描述于(例如)WO96/02555。另一种优选的佐剂是皂苷，优选QS21，其可以单独或与其它佐剂组合使用。例如，一种增强系统涉及单磷酰脂质A与皂苷衍生物的组合，诸如WO94/00153中描述的QS21与3D-MPL的组合，或WO96/33739中描述的反应原性较低的组合物，其中QS21用胆固醇淬灭。其它优选的制剂包含水包油乳剂和生育酚。水包油乳剂中涉及QS21、3D-MPL和生育酚的特别有效的佐剂制剂描述于WO95/17210。此处提供的任何疫苗可以使用使抗原、免疫应答增强剂和合适的载体或赋形剂组合在一起的众所周知的方法进行制备。
此处描述的组合物可以作为缓释制剂(如诸如施用后缓慢释放化合物的胶囊或海绵体等制剂)的一部分施用。这些制剂通常可以使用众所周知的技术进行制备，并通过(例如)口腔、直肠、或皮下灌输，或者通过在设计的靶位点灌输施用。缓释制剂可以含有散布于载体基质中和/或包含于由速率控制膜包围的贮槽内的多肽、多核苷酸或抗体。用于这些制剂的载体是生物相容性的，而且还可以是可生物降解的；优选制剂可以使活性成分的释放水平相对稳定。缓释制剂内含有的活性成分的量取决于灌输位点、释放速率和预期持续时间、和治疗或预防的状况的本质。
在药物组合物和疫苗中可以采用多种投递载体，以有助于产生针对靶肿瘤细胞的抗原特异的免疫应答。投递载体包括抗原呈递细胞(APC)，诸如树突状细胞、巨噬细胞、B细胞、单核细胞和可以加工成有效APC的其它细胞。这些细胞可以(但不必)进行遗传修饰，以增强呈递抗原的能力，提高T细胞应答的激活和/或维持，本身具有抗肿瘤作用，和/或与受体在免疫学上相容(即HLA单倍体型匹配)。APC通常可以由多种生物学流体和器官分离得到，包括肿瘤和肿瘤周围组织，而且可以是自身的、同种异体的、同基因的或异基因的细胞。
本发明的某些优选实施方案使用树突状细胞或它们的始祖细胞作为抗原呈递细胞。树突状细胞是高度有效的APC(Banchereau和Steinman,Nature 392:245-251,1998)，而且显示是引起预防或治疗性抗肿瘤免疫力的有效生理学佐剂(见Timmeran和Levy,Ann.Rev.Med.50:507-529,1999)。通常，树突状细胞可以根据它们的典型形状(原位为星形，具有体外可见的显著的细胞质突起(树突))，和根据缺失B细胞(CD19和CD20)、T细胞(CD3)、单核细胞(CD14)和天然杀伤细胞(CD56)的分化标志进行鉴定，可使用常规实验鉴定。树突状细胞当然可以进行改造，以表达通常不会在体外或离体树突状细胞上存在的特异细胞表面受体或配基，而且本发明包括这些经修饰的树突状细胞。作为树突状细胞的替代，载有分泌泡抗原的树突状细胞(称为外来体)可以用于疫苗(见Zitvogel等人，Nature Med.4:594-600,1998)。
树突状细胞及其始祖细胞可以由外周血、骨髓、肿瘤渗透细胞、肿瘤周围组织渗透细胞、淋巴结、脾、皮肤、脐带血或任何其它合适的组织或流体得到。例如，树突状细胞可以通过向由外周血收获的单核细胞培养物中组合加入细胞因子(诸如GM-CSF、IL-4、IL-13和/或TNF-α)而离体分化。或者，可以向培养基中加入GM-CSG、IL-3、TNF-α、CD40配基、LPS、flt3配基和/或可诱导树突状细胞成熟和增殖的其它化合物的各种组合，将由外周血、脐带血或骨髓收获的CD34阳性细胞分化成树突状细胞。
可将树突状细胞方便的分为“未成熟”和“成熟”细胞，从而以简单的方式区别两种已很好表征过的表型。然而，这种分类不应当解释为不包括所有可能的分化中间阶段。未成熟树突状细胞的特征为具有较好的抗原摄取和加工能力的APC，与Fcγ受体、甘露糖受体和DEC-205标记的高表达一致。成熟表型的典型特征为这些标记的表达较低，而负责T细胞活化的细胞表面分子(诸如Ⅰ型和Ⅱ型MHC)、粘连分子(如CD54和CD11)和共刺激因子(如CD40、CD80和CD86)的表达较高。
APC通常可以用编码前列腺肿瘤蛋白(或者它们的一部分或其它变体)的多核苷酸进行转染，使得前列腺肿瘤多肽或它们的免疫原性部分表达于细胞表面。这种转染可以离体发生，然后如此处描述的可以将包含这些经转染细胞的组合物或疫苗用于治疗目的。或者，可以给患者施用以树突状细胞或其它抗原呈递细胞为靶细胞的基因投递载体，导致体内发生转染。例如，树突状细胞的体内和离体转染通常可以使用本领域知道的任何方法(诸如WO97/24447中描述的那些)，或Mahvi等人(Immunology and Cell Biology 75:456-460,1997)描述的基因枪方法进行。树突状细胞的抗原装载通过将树突状细胞或其始祖细胞与前列腺肿瘤多肽、DNA(裸露的或包含于质粒载体中)或RNA；或与表达抗原的重组细菌或病毒(如牛痘、家禽痘病毒、腺病毒或慢病毒载体)一起温育来实现。在装载之前，多肽可以与提供T细胞辅助的免疫学配偶体(如载体分子)进行共价缀合。或者，树突状细胞可以单独地或在有多肽存在下用非缀合的免疫学配偶体进行脉冲。癌症治疗
在本发明的其它方面中，此处描述的组合物可以用于癌症(诸如前列腺癌)的免疫治疗。在这些方法中，通常给患者施用药物组合物和疫苗。如此处使用的，“患者”指任何温血动物，优选人。患者可能患有或未患有癌症。相应的，上述药物组合物和疫苗可以用来预防癌症的发展或治疗患有癌症的患者。癌症可以使用本领域普遍接受的标准进行诊断，包括恶性肿瘤的存在。药物组合物和疫苗可以在外科切除原发性肿瘤和/或治疗(诸如放疗或施用传统化疗药物)之前或之后施用。
在某些实施方案中，免疫治疗可以是积极的免疫治疗，其中治疗依赖于内源性宿主免疫系统的体内刺激，从而与施用的免疫应答修饰剂(诸如此处公开的多肽和多核苷酸)一起与肿瘤发生反应。
在其它实施方案中，免疫治疗可以是消极的免疫治疗，其中治疗涉及具有确定的肿瘤免疫反应性、能够直接或间接介导抗肿瘤作用、且不必依赖完整宿主免疫系统的试剂(诸如效应细胞或抗体)的投递。效应细胞的实例包括上述T细胞、T淋巴细胞(诸如CD8+细胞毒性T淋巴细胞和CD4+T辅助肿瘤渗透淋巴细胞)、杀伤细胞(诸如天然杀伤细胞和淋巴因子激活的杀伤细胞)、B细胞和表达此处提供的多肽的抗原呈递细胞(诸如树突状细胞和巨噬细胞)。对此处记录的多肽特异的T细胞受体和抗体受体可以进行克隆、表达并转移到用于继承性免疫治疗的其它载体或效应细胞中。此处提供的多肽还可以用于产生用于被动免疫治疗的抗体或抗独特型抗体(如上所述和美国专利号4,918,164)。
通常可以通过此处所述的体外培养，得到足够量的效应细胞用于继承性免疫治疗。将单个抗原特异的效应细胞扩增成数以十亿记的保持体内抗原识别能力的细胞的培养条件，在本领域是众所周知的。这些体外培养条件通常使用抗原间歇刺激，通常在细胞因子(诸如IL-2)和不分裂的饲养细胞存在下进行。如上所述，此处提供的具有免疫反应性的多肽可以用于抗原特异的T细胞培养物的快速扩增，以产生足够数目的细胞用于免疫治疗。具体地说，抗原呈递细胞，诸如树突状细胞、巨噬细胞、单核细胞、成纤维细胞或B细胞，可以用具有免疫反应性的多肽进行脉冲，或用一种或多种多核苷酸使用本领域众所周知的常规技术进行转染。例如，抗原呈递细胞可以用具有适合于增加在重组病毒或其它表达系统中的表达的启动子的多核苷酸进行转染。用于治疗的培养效应细胞必须能够在体内生长、广泛散布、并长时间存活。研究表明，培养的效应细胞可以通过用IL-2补充的抗原重复刺激，在体内诱导生长，并以显著数目长时间存活(见例如Cheever等人，Immunological Reviews 157:177,1997)。
或者，表达此处记录的多肽的载体可以导入取自患者并离体无性繁殖的抗原呈递细胞，用于返回移植同一患者。经转染细胞可以使用本领域知道的任何方法再导入患者，优选通过静脉内、体腔内、腹膜内或肿瘤内以无菌形式给予。
此处公开的治疗组合物的施用途径、频率、以及剂量，将随个体变化，而且可以使用常规方法容易的建立。通常，药物组合物和疫苗可以通过注射(如皮内、肌肉内、静脉内或皮下)、鼻内(如通过呼吸)或口腔施用。优选的，可以在52周施用1-10个剂量。优选的，施用6个剂量，每次间隔一个月，而且可以在此后定期进行加强接种。其它方案可能适合于个别患者。化合物合适的剂量是，当如上所述施用后，能够促进抗肿瘤免疫应答，而且比基础(即未处理)水平高至少10-50％。这些应答可以通过测量患者体内的抗肿瘤抗体或通过能够在体外杀死患者肿瘤细胞的细胞溶解效应细胞的疫苗依赖性产生进行监控。这些疫苗还应当能够在接种疫苗的患者体内引起，与未接种疫苗的患者相比，导致改进的临床效果(如更频繁的缓解、完全或部分或更长的无疾病存活)的免疫应答。通常，对于包含一种或多种多肽的药物组合物和疫苗，一剂中每种多肽的量的范围为100μg-5mg/kg宿主。合适的剂量大小将随患者的大小而变化，但是通常范围为大约0.1-大约5mL。
通常，适当的剂量和治疗方案能提供足够量的活性化合物，以提供治疗和/或预防作用。这样的应答可以通过在治疗患者体内，与未治疗患者相比，获得改进的临床效果(如更频繁的缓解、完全或部分或更长的无疾病存活)进行监控。对前列腺肿瘤蛋白的先前存在的免疫应答的增加通常与改进的临床效果有关。这些免疫应答通常可以使用常规增殖、细胞毒性或细胞因子实验进行评估，可以使用患者治疗之前和之后得到的样品进行。检测癌症的方法
通常，可以根据由患者得到的生物学样品(例如血液、血清、尿液和/或肿瘤活组织标本)中一种或多种前列腺肿瘤蛋白和/或编码这些蛋白质的多核苷酸的存在，检测患者体内是否存在癌症。换言之，这些蛋白质可以作为标记，指示癌症(诸如前列腺癌)的存在与否。此外，这些蛋白质可以用于检测其它癌症。此处提供的结合剂通常能够检测生物学样品中与该试剂结合的抗原水平。多核苷酸引物和探针可以用于检测编码肿瘤蛋白的mRNA水平，这也指示癌症的存在与否。通常，前列腺肿瘤序列在肿瘤组织中的存在水平至少比正常组织中高3倍。
本领域那些普通技术人员知道多种使用结合剂来检测样品中的多肽标记的实验方案。见Harlow和Lane,Antibodies:A LaboratoryManual,Cold Spring Harbor Laboratory,1988。通常，患者体内是否存在癌症，可以如下测定：(a)将由患者得到的生物学样品与结合剂接触；(b)检测样品中与结合剂结合的多肽的水平；并(c)将多肽水平与预先测定的临界值进行比较。
在优选的实施方案中，实验涉及使用固定在固体支持物上的结合剂结合多肽，并与样品的其它部分分开。然后可以使用含有报导基团并可与结合剂/多肽复合物特异结合的检测剂检测结合的多肽。这些检测剂可以包含(例如)可与多肽特异结合的结合剂或抗体或可与结合剂特异结合的其它试剂，诸如抗-免疫球蛋白、蛋白G、蛋白A或植物凝血素。或者，可以利用竞争实验，其中多肽用报导基团进行标记，并使其在结合剂与样品一起温育后和经固定的结合剂结合。样品成分抑制经标记的多肽与结合剂的结合程度，是样品与经固定的结合剂的反应性的指示。如上所述，在这些实验中使用的合适的多肽包括全长前列腺肿瘤蛋白和结合剂可结合的一部分。
固体支持物可以是本领域普通技术人员知道的可附着肿瘤蛋白的任何材料。例如，固体支持物可以是微量滴定板中的测试孔或硝酸纤维素或其它合适的膜。或者，支持物可以是珠子或圆片，诸如玻璃、玻璃纤维、乳胶或塑料材料诸如聚苯乙烯或聚氯乙稀。支持物还可以是磁性颗粒或光纤传感器，诸如美国专利号5,359,681中公开的那些。结合剂可以使用本领域技术人员知道的多种技术(详细描述于专利和科学文献中)固定在固体支持物上。在本发明中，术语“固定化”指非共价结合(诸如吸附)和共价结合(可以是试剂和支持物上的官能团之间的直接连接，或者可以是通过交联剂的连接)。优选通过吸附在微量滴定板的孔中或膜上的固定。在这些情况中，吸附可以通过将合适缓冲液中的结合剂与固体支持物接触适当时间。接触时间随温度而变化，但是通常是大约1小时-大约1天。通常，塑料微量滴定板(诸如聚苯乙烯或聚氯乙稀)的一个孔与大约10ng-10μg，优选约100ng-1μg结合剂的接触，足够固定合适量的结合剂。
结合剂与固体支持物的共价结合，通常可以通过首先将支持物与能够与支持物和结合剂上的功能基团(诸如羟基或氨基)反应的双功能试剂发生反应而进行。例如，可以使用苯醌或通过支持物上的醛基与结合配偶体上的胺和活泼H的缩合，将结合剂共价附着到具有适当聚合物覆层的支持物上，见Pierce Immunotechnology Catalog andHandbook,1991,A12-A13。
在某些实施方案中，实验是双抗体三明治实验。此实验可以如下进行，首先将已固定在固体支持物(通常是微量滴定板的孔)上的抗体与样品接触，使得样品中的抗体能够结合经固定的抗体。然后由经固定的多肽-抗体复合物除去未结合的样品，并加入含有报导基团的检测剂(优选能够与多肽上的不同位点结合的二抗)。然后使用适合于特异报导基团的方法，测定仍然与固体支持物结合的检测剂的量。
更具体的说，一旦抗体如上所述固定在支持物上了，通常要封闭支持物上剩余的蛋白质结合位点。本领域普通技术人员知道任何合适的封闭剂，诸如牛血清清蛋白或吐温20TM(Sigma Chemical Co.,St.Louis,MO)。然后将经固定的抗体与样品一起温育，使多肽与抗体结合。温育前，样品可以用合适的稀释液进行稀释，诸如磷酸缓冲盐水(PBS)。通常，适当的接触时间(即温育时间)是足够检测由患有前列腺癌的个体得到的样品中的多肽存在情况的一段时间。优选的，接触时间足够使结合水平达到结合和未结合多肽平衡时结合水平的至少大约95％)。本领域普通技术人员认识到，达到平衡需要的时间可以通过试验一段时间后发生的结合水平容易的测定。室温下大约30分钟的温育时间通常是足够的。
然后可以通过用适当缓冲液(诸如含0.1％吐温20TM的PBS)清洗固体支持物，除去未结合的样品。然后可以向固体支持物中加入含有报导基团的二抗。优选的报导基团包括上文记录的那些基团。
然后将检测剂与经固定的抗体-多肽复合物一起温育足够检测结合多肽的一段时间。适当量的时间通常可以通过试验一段时间后发生的结合水平进行测定。然后除去未结合的检测剂，并使用报导基团检测结合的检测剂。检测报导基团采用的方法取决于报导基团的性质。对于放射性基团，闪烁计数或放射自显影方法通常是适当的。分光光度法可以用于检测染料、发光基团和荧光基团。生物素可以使用与不同报导基团(通常是放射性或荧光基团或酶)偶联的抗生物素蛋白进行检测。酶报导基团通常可以通过加入底物(通常是特殊长度的时间)，随后进行反应产物的分光光度法或其它分析从而进行检测。
为了测定癌症(诸如前列腺癌)的存在与否，通常将由仍然与固体支持物结合的报导基团检测得到的信号与相应于预先测定的临界值的信号进行比较。在优选的实施方案中，用于癌症检测的临界值是将经固定的抗体与未患癌症的患者样品一起温育得到的平均信号。通常，产生的信号超过预先测定的临界值3倍标准偏差的样品认为是癌症阳性的。在另一个优选的实施方案中，临界值使用Receiver OperatorCurve，根据Sackett等人的方法(Clinical Epidemiology:A BasicScience for Clinical Medicine,Little Brown and Co.,1985,p.106-7)进行测定。简单的说，在此实施方案中，临界值可以由相应于诊断试剂结果的每个可能临界值的真阳性率(即灵敏度)和假阳性率(100％特异性)配对绘图进行测定。图上的临界值中，与左上角最近的点(即包围最大面积的值)是最精确的临界值，通过此方法测定产生的信号比临界值高的样品可以认为是阳性的。或者，临界值可以沿着图向左漂移，以使假阳性率最小化，或向右漂移，以使假阴性率最小化。通常，通过此方法测定产生的信号比临界值高的样品认为是癌症阳性的。
在相关的实施方案中，实验以流式或色条测试形式进行，其中结合剂固定在膜(诸如硝酸纤维素)上。在流式测试中，当样品流经膜时，样品中的多肽将与经固定的结合剂结合。然后，当含有第二种经标记的结合剂的溶液流经膜时，该第二种结合剂将与结合剂-多肽复合物结合。然后可以如上所述进行结合的第二种结合剂的检测。在色条测试形式中，将结合剂结合的膜的一端浸入含有样品的溶液中。样品沿着膜移动，经过含有第二种结合剂的区域，至经固定的结合剂的区域。第二种结合剂在经固定的抗体区域的浓缩指示癌症的存在。通常，该位点处第二种结合剂的浓缩产生图案，诸如可以容易看见的线。这种图案的缺失指示阴性结果。通常，固定在膜上的结合剂的量选择为当生物学样品中含有在双抗体三明治实验中足够产生阳性信号的水平的多肽时，将在上述测试形式中产生视觉上可辨别的图案。用于这些实验的优选结合剂是抗体和它们的抗原结合片段。优选的，固定在膜上的抗体的量为大约25ng-大约1μg，更优选大约50-500ng。这些测试通常可以很少量的生物学样品进行。
当然，存在大量的其它实验方案，合适用于本发明的肿瘤蛋白或结合剂。上述描述意欲只作为例示。例如，对于本领域那些普通技术人员很显然的是，上述方案可以容易的进行改动，以使用前列腺肿瘤多肽来检测生物学样品中与这些多肽结合的抗体。这些前列腺肿瘤蛋白特异抗体的检测可能与癌症的存在有关。
肿瘤可以也/或根据生物学样品中能与前列腺肿瘤蛋白特异反应的T细胞的存在进行检测。在某些方法中，将由患者分离得到的、包含CD4+和/或CD8+T细胞的生物学样品与前列腺肿瘤多肽、编码这样的多肽的多核苷酸和/或至少表达这样的多肽的免疫原性部分的APC一起温育，然后检测T细胞特异激活的情况。合适的生物学样品包括(但不限于)分离的T细胞。例如，T细胞可以由患者通过常规技术(诸如通过外周血淋巴细胞的Ficoll/Hypaque密梯度离心)进行分离。可以将T细胞与前列腺肿瘤多肽(如，5-25μg/ml)在体外于37℃一起温育2-9天(通常4天)。可能需要将另一部分T细胞在不存在前列腺肿瘤多肽的情况下温育，作为对照。对于CD4+T细胞，激活优选通过评价T细胞的增殖进行检测。对于CD8+T细胞，激活优选通过评价细胞溶解活性进行检测。比无疾病患者至少高2倍的增殖水平和/或至少高20％的细胞溶解活性水平，指示患者体内存在癌症。
如上所述，癌症可以也/或者根据生物学样品中编码前列腺肿瘤蛋白的mRNA水平进行检测。例如，可以在基于聚合酶链式反应(PCR)的实验中采用至少两种寡核苷酸引物以扩增衍生自生物学样品的前列腺肿瘤cDNA的一部分，其中至少一种寡核苷酸引物对编码前列腺肿瘤蛋白的多核苷酸是特异的(即能够发生杂交)。然后分离经扩增的cDNA，并使用本领域众所周知的技术(诸如电泳)进行检测。相似的，可与编码前列腺肿瘤蛋白的多核苷酸特异杂交的寡核苷酸探针可以用于杂交实验，以检测生物学样品中编码肿瘤蛋白的多核苷酸的存在。
为了能够在实验条件下杂交，寡核苷酸引物和探针应当包含与编码前列腺肿瘤蛋白的多核苷酸的一部分(长度为至少10个核苷酸，优选至少20个核苷酸)有至少大约60％，优选至少75％，更优选至少90％同一性的寡核苷酸序列。优选的，寡核苷酸引物和/或探针可与编码此处公开的多肽的多核苷酸在上文定义的中等严谨条件下杂交。可以有效用于此处描述的诊断方法的寡核苷酸引物和/或探针优选长度为至少10-40个核苷酸。在优选的实施方案中，寡核苷酸引物包含具有SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375和381记录的序列的DNA分子中至少10个连续核苷酸，更优选至少15个连续核苷酸。用于基于PCR的实验和杂交实验的技术在本领域是众所周知的(见，例如，Mullis等人，Cold Spring Harbor Symp.Quant.Biol.15:263,1987；Erlich编，PCR Technology,Stockton Press,NY,1989)。
一个优选的实验采用RT-PCR，其中PCR与逆转录结合应用。通常，RNA由生物学样品(诸如活组织标本)抽提，并逆转录产生cDNA分子。使用至少一种特异引物的PCR扩增产生cDNA分子，可以使用(例如)凝胶电泳进行分离和可视化。可以在取自测试患者和取自未患有癌症的个体的生物学样品上进行扩增。可以在跨越两个数量级的多个稀释度cDNA上进行扩增反应。在各个稀释度下，与相同稀释度的非癌症样品相比，待测患者样品中的表达增加2倍或更多，通常认为是阳性的。
在另一个实施方案中，公开的组合物可以作为癌症发展的标记使用。在此实施方案中，用于癌症诊断的上述实验可以随时间进行，并且评价反应性多肽或多核苷酸水平的变化。例如，可以在6个月-1年内每24-72个小时进行实验，此后根据需要进行。通常，在检测到多肽或多核苷酸水平随时间增加的患者体内，癌症正在发展。相反的，若反应性多肽或多核苷酸水平保持稳定或随时间降低，则癌症不在发展。
某些体内诊断实验可以在肿瘤上直接进行。这样一种实验涉及将肿瘤细胞与结合剂接触。然后可以直接或间接通过报导基团检测结合的结合剂。这些结合剂也可以用于组织学应用。或者，多核苷酸探针可以用于这些应用。
如上所述，为了提高灵敏度，可以测定给定样品中的多种前列腺肿瘤蛋白标记。显然，对此处提供的不同蛋白质特异的结合剂可以在单个实验中相结合使用。而且，多种引物或探针可以同时使用。可以根据常规实验选择肿瘤蛋白标记，以确定产生最佳灵敏度的各种组合。此外，用于此处提供的肿瘤蛋白的实验可以与用于其它已知肿瘤抗原的实验相结合。诊断试剂盒
本发明还提供了在任何上述诊断方法中使用的试剂盒。这些试剂盒通常包含两种或多种进行诊断实验必需的成分。这些成分可以是化合物、试剂、容器和/或设备。例如，试剂盒中的一个容器内可以含有可与前列腺肿瘤蛋白特异结合的单克隆抗体或它们的片段。这些抗体或片段可以如上所述吸附在支持物上而提供。另外的一或多个容器中可以装入实验中将要使用的成分，诸如试剂或缓冲液。这些试剂盒可以还/或者含有包含报导基团(适用于直接或间接检测抗体结合)的上述检测剂。
或者，试剂盒可以设计用来监测生物学样品中编码前列腺肿瘤蛋白的mRNA水平。这些试剂盒通常包含至少一种可与编码前列腺肿瘤蛋白的多核苷酸杂交的上述寡核苷酸探针或引物。这样的寡核苷酸可以用于(例如)PCR或杂交实验。这些试剂盒中可以存在的其它成分，包括有助于检测编码前列腺肿瘤蛋白的多核苷酸的第二种寡核苷酸和/或诊断剂或容器。提供下列实施例作为说明而非限制。
实施例
实施例1
前列腺肿瘤多肽的分离和鉴定
此实施例描述了从前列腺肿瘤cDNA文库分离某些前列腺肿瘤多肽。
以用于cDNA合成和质粒克隆试剂盒的Superscript质粒系统(BRLLife Technologies,Gaithersburg,MD 20897)，依照生产商推荐的方法，从前列腺肿瘤polyA+RNA构建人前列腺肿瘤cDNA表达文库。具体的说，用polytron(Kinematica，瑞士)匀浆前列腺肿瘤组织，依照生产商的指示，用Trizol试剂(BRL Life Technologies)提取总RNA。然后，用Qiagen oligotex旋转柱mRNA纯化试剂盒(Qiagen,Santa Clarita,CA 91355)，依照生产商推荐的方法纯化poly A+RNA。第一链cDNA用Not Ⅰ/Oligo-dT18引物合成。合成双链cDNA，与EcoRⅠ/BaⅪ衔接头(Invitrogen,San Diego,CA)连接并用Not Ⅰ消化。将cDNA用Chroma Spin-1000柱(Clontech,Palo Alto,CA)大小分离后，连接到pCDNA3.1(Invitrogen)的EcoRI/NotⅠ位点，并用电穿孔法转化到Electro Max大肠杆菌DH10B细胞(BRL LifeTechnologies)内。
用同样步骤，由一组六组织标本(Clontech)建立正常人胰腺cDNA表达文库。通过测定独立克隆数、带有插入片段的克隆所占百分比、平均插入片段大小以及序列分析来表征cDNA文库。前列腺肿瘤文库中有1.64×107个独立克隆，其中70％的克隆带有插入片段，平均插入片段大小为1745个碱基对。正常胰腺cDNA文库有3.3×106个独立克隆，其中69％的克隆带有插入片段，平均插入片段大小为1120个碱基对。对于两个文库，序列分析表明大多数克隆带有全长cDNA序列，是合成自mRNA的、而混有最低限度的rRNA和线粒体DNA污染。
利用上述前列腺肿瘤和正常人胰腺cDNA文库，参照Hara等人所述(Blood,84:189-199,1994)略做改动，进行cDNA文库扣除(subtraction)。具体的说，如下所述构建前列腺肿瘤特异性扣除cDNA文库。取70μg正常人胰腺cDNA文库用EcoRⅠ、NotⅠ和SfuⅠ消化，随后用DNA聚合酶Klenow片段补平。经酚一氯仿抽提、乙醇沉淀后，将DNA溶于100μl水中，热变性，并加入100μl(100μg)光学探针生物素(Vector Laboratories,Burlingame,CA)混匀，依照生产商推荐的方法，将所得混和物置于冰上用270瓦日光灯照射20分钟。再加入50μl光学探针生物素，重复生物素化反应。用丁醇抽提五次后，经乙醇沉淀DNA，再溶于23μl水中作为驱动DNA(driverDNA)。
为制备示踪DNA(tracer DNA)，取10μg前列腺肿瘤cDNA文库，用BamHⅠ和XhoⅠ消化，酚-氯仿抽提，走Chroma spin-400柱(Clontech)。乙醇沉淀后，将示踪DNA溶于5μl水中。将示踪DNA与15μl驱动DNA和20μ12X杂交缓冲液(1.5M NaCl/10mM EDTA/50mMHEPES pH7.5/0.2％SDS)混匀，用矿物油覆盖，充分热变性。将样品立即转移至68℃水浴保温20小时(长时间杂交[LH])。然后将反应混合物进行链霉抗生物素蛋白处理，接着酚-氯仿抽提。此步骤再重复三次。将扣除后的DNA沉淀，溶解于12μl水中，加入8μl驱动DNA和20μl2X杂交缓冲液混匀，68℃杂交2小时(短时间杂交[SH])。除去生物素化双链DNA后，将扣除后的DNA插入氯霉素抗性质粒pBCSK+(Stratagene,La Jolla,CA 92037)的BamHⅠ/XhoⅠ位点，并用电穿孔法转化到Electro Max大肠杆菌DHI0B细胞内，建立前列腺肿瘤特异性扣除cDNA文库(前列腺扣除1)。
为了分析扣除cDNA文库，从扣除前列腺肿瘤特异性文库中随机挑取100个独立克隆制备质粒DNA，并根据插入片段大小进行分组。通过用Perkin Elmer/Applied Biosystems Division自动测序仪373A型(Foster City,CA)进行测序，对具有代表性的cDNA克隆进行进一步鉴定。6个cDNA克隆，即下文中的F1-13、F1-12、F1-16、H1-1、H1-9和H1-4，显示在扣除前列腺特异性cDNA文库中含量丰富。经测定F1-12的3’和5’cDNA序列分别提供于SEQ ID NO:2和3中；F1-13、F1-16、H1-1、H1-9和H1-4的3’cDNA序列分别提供于SEQ ID NO:1和4-7。
将分离克隆的cDNA序列与EMBL和GeneBank数据库(发布至96年)中的已知序列进行比较。4个前列腺肿瘤cDNA克隆：F1-13、F1-16、H1-1和H1-4，确定为编码以下已经确认的蛋白质：前列腺特异性抗原(PSA)，人腺体激肽释放酶，人肿瘤表达增强基因，和线粒体细胞色素C氧化酶亚基Ⅱ。H1-9与已经确认的人自主复制序列相同。没有发现F1-12 cDNA序列的同源序列。
经过随后的研究，分离出了F1-12的全长cDNA序列。此序列提供于SEQ ID NO:107，相应推测的氨基酸序列提供于SEQ ID NO:108。
为了克隆含量较少的前列腺肿瘤特异性基因，通过用正常胰腺cDNA文库和上述扣除前列腺肿瘤特异性cDNA文库中的3种含量最丰富的基因：人腺体激肽释放酶、前列腺特异性抗原(PSA)，和线粒体细胞素C氧化酶亚基Ⅱ，对上述前列腺肿瘤cDNA文库进行cDNA文库的扣除。具体的说，向驱动DNA中加入于pcDNA3.1中的人腺体激肽释放酶、前列腺特异性抗原和线粒体细胞色素C氧化酶亚基Ⅱ cDNA各1μg，如上所述进行扣除，以提供再次扣除的cDNA文库，此后将其称为增效的前列腺肿瘤特异性扣除cDNA文库(substracted prostatetumor specific cDNA library with spike)。
从增效的前列腺肿瘤特异性扣除cDNA文库中分离得到22个cDNA克隆。经测定，克隆J1-17、L1-12、N1-1862、J1-13、J1-19、J1-25、J1-24、K1-58、K1-63、L1-4和L1-14的3’和5’cDNA序列依次提供于SEQ ID NO:8-9、10-11、12-13、14-15、16-17、18-19、20-21、22-23、24-25、26-27和28-29。克隆J1-12、J1-16、J1-21、K1-48、K1-55、L1-2、L1-6、N1-1858、N1-1860、N1-1861和N1-1864经测定的3’cDNA序列依次提供于SEQ ID NO:30-40。将这些序列与上述基因库中的序列进行比较，显示出与5个含量最丰富的DNA种类中的3个(J1-17、L1-12和N1-1862；SEQ ID NO:8-9、10-11和12-13)没有明显同源性。剩下的两个含量最丰富的种类，一个(J1-12；SEQ ID NO:30)与已经确认的人肺表面活性剂相关蛋白相同，另一个(K1-48；SEQ ID NO:33)与R.norvegicus的2-芳基丙酰辅酶A差向异构酶mRNA有一定同源性。从增效的前列腺肿瘤特异性扣除cDNA文库中分离的17个含量较少的cDNA克隆中，4个(J1-16、K1-55、L1-6和N1-1864；分别为SEQID NO:31、34、36和40)与已经确认的序列相同，2个(J1-21和N1-1860；分别为SEQ ID NO:32和38)显示与非人序列有一定同源性，2个(L1-2和N1-1861；分别为SEQ ID NO:35和39)显示与已知的人序列有一定同源性。对多肽J1-13、J1-19、J1-24、J1-25、K1-58、K1-63、L1-4和L1-14(SEQ ID NO:14-15、16-17、20-21、18-19、22-23、24-25、26-27和28-29)没有发现明显同源性。
经随后的研究，分离出了J1-17、L1-12和N1-1862的全长cDNA序列(分别为SEQ ID NO:109-111)。相应推测的氨基酸序列提供于SEQID NO:112-114。L1-12也被称为P501S。
在进一步的实验中，通过用由三种正常前列腺polyA+RNA的汇集物制得的正常前列腺cDNA对前列腺肿瘤cDNA文库进行扣除(前列腺扣除2)，鉴定出了另外4个克隆。这些克隆(下面称作U1-3064、U1-3065、V1-3692和1A-3905)经测定的cDNA序列依次提供于SEQ IDNO:69-72。将测定的序列与基因库中的序列进行比较，显示出与U1-3065没有明显同源性。
通过用正常胰腺cDNA文库对增效的前列腺肿瘤特异性cDNA文库进行扣除，完成再次增效扣除(前列腺扣除增效2)，并用PSA、J1-17、肺表面活性剂相关蛋白、线粒体DNA、细胞色素C氧化酶亚基Ⅱ、N1-1862、自主复制序列、L1-12和肿瘤表达增强基因进一步增效扣除。分离得到另外4个克隆，此后称为V1-3686、R1-2330、1B-3976和V1-3679。这些克隆经测定的cDNA序列依次提供于SEQ ID NO:73-76。将这些序列与基因库内的序列进行比较，显示出与V1-3686和R1-2330没有明显同源性。
对上述三次前列腺扣除(前列腺扣除2，增效的前列腺肿瘤特异性扣除cDNA文库和前列腺扣除增效2)进一步分析，鉴定得到了另外16个克隆，即1G-4736、1G-4738、1G-4741、1G-4744、1G-4734、1H-4774、1H-4781、1H-4785、1H-4787、1H-4796、1I-4810、1I-4811、1J-4876、1K-4884和1K-4896。这些克隆经测定的cDNA序列依次提供于SEQ ID NO:77-92。将这些序列与上述基因库中的序列进行比较，显示与1G-4741、1G-4734、1I-4807、1J-4876和1K-4896(SEQ ID NO:79、81、87、90和92)没有明显同源性。对分离克隆进一步分析，确定了1G-4736、1G-4738、1G-4741、1G-4744、1H-4774、1H-4781、1H-4785、1H-4787、1H-4796、1I-4807、1J-4876、1K-4884和1K-4896的延伸cDNA序列，依次提供于SEQ ID NO:179-188和191-193，并确定了1I-4810和1I-4811的另外部分cDNA序列，分别提供于SEQ IDNO:189和190。
经对前列腺扣除增效2的另外的研究，分离出了另外3个克隆。如上所述测定它们的序列，并与最新的GenBank进行比较。所有三个克隆显示与已知基因的同源性，它们是富含半胱氨酸的蛋白质、KIAA0242和KIAA0280(依次提供于SEQ ID NO:317、319和320)。通过Synteni微阵(Synteni,Palo Alto,CA)对这些克隆进行的进一步分析表明所有3个克隆均在大多数前列腺肿瘤和前列腺BPH，以及大多数测试的正常前列腺组织中过度表达，但是在所有其它正常组织中低水平表达。
通过用正常胰腺cDNA对正常前列腺cDNA文库进行扣除，又进行了一次扣除(前列腺扣除3)。这样鉴定得到了另外6个克隆，即1G-4761、16-4762、1H-4766、1H-4770、1H-4771和1H-4772(SEQ IDNO:93-98)。将这些序列与基因库中的序列进行比较，显示出与1G-4761和1H-4771(SEQ ID NO:93和97)没有明显同源性。对分离克隆进一步分析，确定了1G-4761、1G-4762、1H-4766和1H-4772的延续cDNA序列，依次提供于SEQ ID NO:194-196和199，并确定了1H-4770和1H-4771的另外部分cDNA序列，分别提供于SEQ ID NO:197和198。
对由3位前列腺癌患者的polyA+RNA汇集物制得的前列腺肿瘤cDNA文库，用正常胰腺cDNA文库进行扣除(前列腺扣除4)，鉴定出了8个克隆，即1D-4297、1D-4309、1D.1-4278、1D-4288、1D-4283、1D-4304、1D-4296和1D-4280(SEQ ID NO:99-107)。将这些序列与基因库中的序列进行比较，发现与1D-4283和1D-4304(SEQ ID NO:103和104)没有明显同源性。对分离克隆进一步分析，确定了1D-4309、1D.1-4278、1D-4288、1D-4283、1D-4304、1D-4296和1D-4280的延续cDNA序列，依次提供于SEQ ID NO:200-206。
将由上述前列腺扣除1和前列腺扣除2分离得到的cDNA克隆进行集落PCR扩增，并用微阵技术(Synteni,Palo Alto,CA)确定它们在前列腺肿瘤、正常前列腺和各种其它正常组织中的mRNA表达水平。简单的说，将PCR扩增产物点到载片上成点阵形式，每种产物在点阵中占据唯一位置。从待测组织样品中提取mRNA，逆转录，并制备荧光标记cDNA探针。用标记的cDNA探针探查微阵，扫描载片并测量荧光强度。此强度与杂交强度相关。发现两个克隆(P509S和P510S)在前列腺肿瘤和正常前列腺中过度表达，而在检测的其它所有正常组织(肝、胰、皮肤、骨髓、脑、乳腺、肾上腺、膀胱、睾丸、唾液腺、大肠、肾、卵巢、肺、脊髓、骨骼肌和结肠)中低水平表达。经测定P509S和P510S的cDNA序列分别提供于SEQ ID No:223和224。将这些序列与基因库中的序列进行比较，发现与先前确认的EST有一定同源性。
此外，经研究，分离出了P509S的全长cDNA序列。此序列提供于SEQ ID No:332，相应推测的氨基酸序列提供于SEQ ID NO:339。
实施例2
前列腺肿瘤多肽的组织特异性的测定
用基因特异引物，采用逆转录PCR检测多种正常和肿瘤组织中具有代表性的前列腺肿瘤多肽F1-16、H1-1、J1-17(也称为P502S)、L1-12(也称为P501S)、F1-12(也称为P504S)和N1-1862(也称为P503S)的mRNA表达水平。
简单的说，使用Trizol试剂，如上所述从多种正常和肿瘤组织中提取总RNA。取1-2μg总RNA，使用SuperScriptⅡ逆转录酶(BRL LifeTechnologies)于42℃进行第一链的合成1小时。接着用基因特异引物通过PCR扩增cDNA。为了确保逆转录PCR半定量的本性，使用β肌动蛋白作为各个检测组织的内在对照。首先，制备第一链cDNA的系列稀释物，利用β肌动蛋白特异引物进行逆转录PCR检测。接着，选择一个能使β肌动蛋白模板线性扩增并且足够灵敏反映初始拷贝数差异的稀释度。使用这些条件，测定各组织各个逆转录反应中的β肌动蛋白水平。通过用DNA酶处理，并且确保使用未加入逆转录酶而制备的第一链cDNA时得到阴性PCR结果，使DNA污染降到最低。
测定4种不同类型的肿瘤组织(来自2位患者的前列腺肿瘤，来自3位患者的乳腺肿瘤、结肠肿瘤和肺肿瘤)和16种不同的正常组织(包括前列腺、结肠、肾、肝、肺、卵巢、胰、骨骼肌、皮肤、胃、睾丸、骨髓和脑)中mRNA的表达水平，发现F1-16在前列腺肿瘤组织、结肠肿瘤和正常前列腺中高水平表达，在正常肝、皮肤和睾丸中低水平表达，而在其它检测组织中检测不到表达；H1-1在前列腺肿瘤、肺肿瘤、乳腺肿瘤、正常前列腺、正常结肠和正常脑中高水平表达，在正常肺、胰脏、骨骼肌、皮肤、小肠和骨髓中表达低得多，而在其它检测组织中检测不到表达。J1-17(P502S)和L1-12(P501S)似乎在前列腺中特异性地过度表达，两个基因在前列腺肿瘤和正常前列腺中都高水平表达，而在其它所有检测组织中表达水平很低，甚至检测不到。N1-1862(P503S)在60％的前列腺肿瘤中过度表达，在正常结肠和肾中能检测到表达。因此，逆转录PCR结果揭示，F1-16、H1-1、J1-17(P502S)、N1-1862(P503S)和L1-12(P501S)要么具有前列腺特异性，要么在前列腺中表达水平显著提高。
进一步的逆转录PCR结果显示，F1-12(P504S)在60％的前列腺肿瘤中过度表达，在正常肾中能检测到表达，而在其它所有检测组织中不能检测到表达。类似的，R1-2330在40％的前列腺肿瘤中过度表达，在正常肾脏和肝脏中能检测到表达，而在其它所有检测组织中不能检测到表达。U1-3064在60％的前列腺肿瘤中过度表达，在乳腺和结肠肿瘤中也表达，但在正常组织中检测不到表达。
对R1-2330、U1-3064和1D-4279的逆转录PCR鉴定表明，这3种抗原在前列腺和/或前列腺肿瘤中过度表达。
对4个前列腺肿瘤、2个正常前列腺样品、2个BPH前列腺和正常结肠、肾、肝、肺、胰、骨骼肌、脑、胃、睾丸、小肠和骨髓的Northern分析表明，L1-12(P501S)在前列腺肿瘤和正常前列腺中过度表达，而在检测的其它正常组织中检测不到。J1-17(P502S)在2个前列腺肿瘤中检测到，而在其它检测组织中检测不到。N1-1862(P503S)在3个前列腺肿瘤中过度表达，在正常前列腺、结肠和肾脏中表达，而在其它检测组织中不表达。F1-12(P504S)在2个前列腺肿瘤中高度表达，而在其它所有检测组织中检测不到。
用上述微阵技术测定此处所述代表性抗原在前列腺肿瘤、乳腺肿瘤和下列正常组织：前列腺、肝、胰、皮肤、骨髓、脑、乳腺、肾上腺、膀胱、睾丸、唾液腺、大肠、肾、卵巢、肺、脊髓、骨骼肌和结肠中的表达水平。发现L1-12(P501S)在正常前列腺和前列腺肿瘤中过度表达，在正常骨骼肌中有一些表达。J1-12和F1-12(P504S)在前列腺肿瘤中都过度表达，在其它所有检测组织中表达较低或检测不到。N1-1862(P503S)在前列腺肿瘤和正常前列腺中高水平表达，在正常大肠和正常结肠中低水平表达，在其它所有检测组织中检测不到表达。R1-2330在前列腺肿瘤和正常前列腺中过度表达，在其它所有检测组织中较低水平表达。1D-4279在前列腺肿瘤和正常前列腺中过度表达，在正常脊髓中较低水平表达，在其它所有检测组织中检测不到。
为了具体确定P501S(SEQ ID NO:110)在乳腺肿瘤中的表达水平而进行的进一步微阵分析揭示，不仅在乳腺肿瘤中，而且在转移性乳腺肿瘤中(2/31)中等过度表达，而在正常组织中表达可忽略或低水平表达。此数据说明P501S可能在各种乳腺肿瘤中以及在前列腺肿瘤中过度表达。
如上所述，通过微阵技术检验Vasmatzis等人(Proc.Natl.Acad.Sci.USA 95:300-304，1998)描述的32种EST(表达序列标签)在多种肿瘤和正常组织中的表达水平。这些克隆中的2个(P1000C和P1001C)在前列腺肿瘤和正常前列腺中过度表达，而在所有其它测试的组织(正常主动脉、胸腺、休眠的和激活的PBMC、上皮细胞、脊髓、肾上腺、胎儿组织、皮肤、唾液腺、大肠、骨髓、肝、肺、树突状细胞、胃、淋巴结、脑、心脏、小肠、骨骼肌、结肠和肾)中低水平表达，甚至检测不到。测定的P1000C和P1001C的cDNA序列分别提供于SEQ ID NO:384和472。P1001C的序列显示与已经分离的JM27蛋白的人mRNA有一定同源性。发现与P1000C的序列没有明显同源性。
通过免疫组织化学分析研究了F1-12(P504S,SEQ ID NO:108)全长cDNA序列编码的多肽的表达。通过常规技术制备了针对全长P504S蛋白的兔抗P504S多克隆抗体。随后通过本领域众所周知的技术还进行了多克隆抗体的分离和鉴定。免疫组织化学分析显示，P504S多肽在100％测试的前列腺癌样品(n=5)中表达。
兔抗P504S多克隆抗体似乎不以相同的细胞质颗粒染色标记良性前列腺细胞，但有轻微的细胞核染色。对正常组织的分析揭示，编码的多肽在一些而非所有正常人组织中表达。兔抗P504S多克隆抗体的阳性细胞质染色发现存在于正常人肾，肝，脑，结肠和肺相关的巨噬细胞，然而心脏和骨髓是阴性的。
此数据说明P504S多肽存在于前列腺癌组织中，而且在良性前列腺增生组织和前列腺癌组织的染色之间存在性质和数量的差异，说明此多肽可以在前列腺肿瘤中选择性检测，并因此可用于前列腺癌的诊断。
实施例3
通过基于PCR的扣除，分离和鉴定前列腺肿瘤多肽
cDNA扣除文库购自Clontech公司，该文库中含有用10种其它正常组织cDNA(脑，心脏，肾，肝，肺，卵巢，胎盘，骨骼肌，脾和胸腺)进行扣除、接着又进行了第一轮PCR扩增的正常前列腺cDNA。依照生产商推荐的方法，对此文库进行第二轮PCR扩增。将所得cDNA片段亚克隆到载体pT7 Blue T-vector(Novagen,Madison,WI)中，并转化到XL-1Blue MRF’大肠杆菌(Stratagene)内。从独立克隆中分离DNA，并用Perkin Elmer/Applied Biosystems Division自动测序仪373A型进行测序。
将59个阳性克隆测序。将这些克隆的DNA序列与上述基因库中的序列进行比较，显示与其中25个克隆没有明显同源性，即P5、P8、P9、P18、P20、P30、P34、P36、P38、P39、P42、P49、P50、P53、P55、P60、P64、P65、P73、P75、P76、P79和P84。这些克隆经测定的cDNA序列依次提供于SEQ ID No:41-45、47-52和54-65。发现P29、P47、P68、P80和P82(分别为SEQ ID No:46、53和66-68)与先前确认的DNA序列有一定程度同源性。就发明者所知，这些序列从未发现存在于前列腺中。
以上述基于PCR的方法学进一步研究，分离得到了180多个其它克隆，发现其中23个克隆与已知序列没有明显同源性。这些克隆经测定的cDNA序列提供于SEQ ID No:115-123、127、131、137、145、147-151、153、156-158和160。23个克隆(SEQ ID No:124-126、128-130、132-136、138-144、146、152、154、155和159)与先前确认的EST有一定同源性。另有10个克隆(SEQ ID No:161-170)与已知基因有一定程度同源性。含有P20序列的较大cDNA克隆代表基因P703P的剪接变体。变体DE1、DE13和DE14经测定的DNA序列依次提供于SEQ IDNo:171、175和177，相应推测的氨基酸序列依次提供于SEQ IDNo:172、176和178。P703的延续剪接形式经测定的cDNA序列提供于SEQ ID No:225。剪接变体DE2和DE6的DNA序列依次提供于SEQ IDNo:173和174。
用上述逆转录PCR方法测定在肿瘤组织[前列腺(n=5)、乳腺(n=2)、结肠和肺]、正常组织[前列腺(n=5)、结肠、肾、肝、肺(n=2)、卵巢(n=2)、骨骼肌、皮肤、胃、小肠和脑]、激活和未激活的PBMC中各代表性克隆的mRNA表达水平。除另外指明，每种组织均只测定一个样品中的表达。
发现P9在正常前列腺和前列腺肿瘤中，与检测的所有正常组织相比，有高度表达(正常结肠除外，其中有相当水平的表达)。与检测的所有12种正常组织相比，P20(P703P基因的一部分)在正常前列腺和前列腺肿瘤中有高度表达。与除肺(2个样品中的1个)外的所有正常组织相比，P20在乳腺肿瘤(n=2)、结肠肿瘤和肺肿瘤中的表达有适度提高。与除肺、胃外的其它正常组织相比，P18在正常前列腺，前列腺肿瘤和乳腺肿瘤中的表达提高。与大多数其它正常组织相比，P5在正常前列腺中的表达有适度提高。然而，在正常肺和PBMC中观察到表达有一定提高。也观察到P5在前列腺肿瘤(5个样品中的2个)、乳腺肿瘤和1个肺肿瘤样品中的表达有提高。至于P30，与检测的12个其它正常组织中的6个相比，它在正常前列腺和前列腺肿瘤中有相似表达水平。发现在乳腺肿瘤、1个肺肿瘤样品，1个结肠肿瘤样品，还有正常PBMC中表达提高。与大多数正常组织相比，P29在所有5个前列腺肿瘤和所有5个正常前列腺中过度表达。然而，观察到P29在正常结肠和正常肺(2个样品均如此)中有显著的表达。与检测的所有其它正常组织相比，P80在所有5个前列腺肿瘤和所有5个正常前列腺中过度表达，在结肠肿瘤中表达提高。
进一步研究分离得到了下列12个其它克隆：10-d8、10-h10、11-c8、7-g6、8-b5、8-b6、8-d4、8-d9、8-g3、8-h11、9-f12和9-f3。10-d8、10-h10、11-c8、8-d4、8-d9、8-h11、9-f12和9-f3经测定的DNA序列依次提供于SEQ ID No:207、208、209、216、217、220、221和222。7-g6、8-b5、8-b6和8-g3经测定的正向和反向DAN序列提供于SEQ ID No:210和211、212和213、214和215、218和219。将这些序列与基因库中的序列进行比较，显示与9-f3的序列没有明显同源性。发现克隆10-d8、11-c8和8-h11与先前分离的EST有一定同源性，而10-h10、8-b5、8-b6、8-d4、8-d9、8-g3和9-f12与先前确认的基因有一定同源性。7-66和8-63的进一步鉴定显示分别与已知基因PAP和PSA相同。
使用上述微阵技术测定这些克隆的mRNA表达水平。发现克隆7-66、8-63、8-B5、8-B6、8-D4、8-D9、9-F3、9-F12、9-H3、10-A2、10-A4、11-C9和11-F2在前列腺肿瘤和正常前列腺中过度表达，而在测试的其它组织中表达水平低或检测不到。8-F11在前列腺肿瘤和正常前列腺、膀胱、骨骼肌和结肠中表达提高。10-H10在前列腺肿瘤和正常前列腺、膀胱、肺、结肠、脑和大肠中表达提高。9-B1在前列腺肿瘤、乳腺肿瘤，和正常前列腺、唾液腺、大肠和皮肤中表达提高。11-C8在前列腺肿瘤以及正常前列腺和大肠中表达提高。
通过微阵技术和逆转录PCR均发现，由上述基于PCR的正常前列腺扣除得到的其它cDNA片段是前列腺特异的。此克隆(9-A11)经测定的cDNA序列提供于SEQ ID NO:226。将此序列与公开数据库进行比较，揭示与已知基因HOXB13有99％的同一性。
经进一步分析，分离出了克隆8-C6和8-H7。这些克隆经测定的cDNA序列依次提供于SEQ ID NO:227和228。这些序列显示与已经分离的EST有一定同源性。
运用基于PCR和杂交的方法学以得到克隆P20(也称为P703P)更长的cDNA序列，由此获得逐渐延伸该基因的5’末端的其它3个cDNA片段。这些片段(P703PDE5,P703P6.26和P703PX-23；SEQ ID NO:326、328和330；推测的相应氨基酸序列依次提供于SEQ ID NO:327、329和331)含有额外的5’序列。P703PDE5通过用P703P的一部分作为探针筛选cDNA文库(#141-26)回收。从三种前列腺肿瘤cDNA的混和物中回收到P703P6.26，而从cDNA文库(#438-48)回收到P703PX-23。总的来说，额外序列包括了推测的成熟丝氨酸蛋白酶全部序列以及部分推测的信号序列。对将前列腺肿瘤合并物扣除一组正常组织的基于PCR的扣除文库(称作JP:PCR扣除)的进一步研究，分离得到另外13个克隆，其中7个与已知的GenBank序列没有任何明显同源性。这7个克隆(P711P、P712P、新23、P774P、P775P、P710P和P768P)经测定的cDNA序列依次提供于SEQ ID NO:307-311、313和315。其余6个克隆(SEQ ID NO:316和321-325)显示与已知基因有一定同源性。通过微阵分析，所有13个克隆均显示，与正常非前列腺组织相比，它们在前列腺组织中，包括前列腺肿瘤、BPH和正常前列腺中，3或更多倍过度表达。克隆P711P、P712P、新23和P768P显示在测试的大多数前列腺肿瘤和BPH组织(n=29)，和大多数正常前列腺组织(n=4)中过度表达，但是在所有正常组织中为背景水平至低水平表达。克隆P774P、P775P和P710P显示且在较少的前列腺肿瘤和BPH样品中相对较低表达，在正常前列腺中为阴性或低水平表达。
使用SEQ ID NO:307的部分序列筛选前列腺cDNA文库，得到P711P的全长cDNA。具体的说，使用常规技术，构建了定向克隆的前列腺cDNA文库。将此文库的一百万个菌落铺在LB/Amp平板上。使用尼龙滤膜浸提这些菌落，将这些滤膜沾取的cDNA变性并通过紫外光交联到滤膜上。将SEQ ID NO:307的P711P cDNA片段进行放射性标记，并与这些滤膜杂交。选择阳性克隆，制备cDNA，并使用自动PerkinElmer/Applied Biosystems测序仪进行测序。P711P经测定的全长序列提供于SEQ ID NO:382，相应推测的氨基酸序列提供于SEQ IDNO:383。
使用基于PCR和杂交的方法学，得到上述两个克隆(11-C9和9-F3，下文依次称为P707P和P714P,SEQ ID NO:333和334)的另外的cDNA序列信息。与最近的GenBank进行比较之后，发现P707P是已知基因HoxB13的剪接变体。相比之下，未发现与P714P有明显同源性。
发现克隆8-B3、P89、P98、P130和P201(公开于1998年2月9日提交的美国专利申请号09/020,956中包含有一毗连)序列P705P(SEQ ID NO:335,相应推测的氨基酸序列提供于SEQ ID NO:336)内，P705P经测定是已知基因NKX3.1的剪接变体。
实施例4
多肽合成
在Perkin Elmer/Applied Biosystems 430A多肽合成仪上采用FMOC化学，用HPTU(O-苯并三唑-N,N,N’,N’-四甲基脲鎓六氟磷酸盐)活化法合成多肽。可将Gly-Cys-Gly序列加在肽的氨基末端，以便于缀合、与固定表面结合或标记该肽。可用下述裂解混合物：三氟乙酸∶乙二硫醇∶苯甲硫醚∶水∶苯酚(40∶1∶2∶2∶3)，从固相支持物上将肽裂解下来。裂解2小时后，可在冷甲基-叔丁基醚中沉淀肽。然后将肽沉淀物溶于含0.1％三氟乙酸(TFA)的水中，冷冻干燥后经C18反相HPLC纯化。可用于水(含0.1％TFA)中的0％-60％乙腈(含0.1％三氟乙酸)梯度洗脱肽。冻干纯级分后，可通过电喷射或其它类型的质谱法以及氨基酸分析鉴定肽。
实施例5
通过基于PCR的扣除，进一步分离和鉴定前列腺肿瘤多肽
将如上所述由前列腺原发性肿瘤mRNA构建的cDNA文库用来自正常前列腺的cDNA进行扣除。扣除使用基于PCR的方案(Clontech)进行，对该方案作些改动以产生更大的片段。在此方案中，将测试(tester)和驱动双链cDNA分别用五种识别六核苷酸限制性位点的限制酶(MluⅠ、MscⅠ、PvuⅡ、SalⅠ和StuⅠ)进行消化。此消化产生cDNA平均大小为600bp，而非根据Clontech方案用RsaⅠ消化产生的平均大小300bp。此改动不影响扣除效率。然后用不同的衔接头产生两种测试群，而驱动文库仍然不含衔接头。
然后使用过量驱动cDNA，进行测试和驱动文库的杂交。在杂交第一步，将驱动cDNA分别与两种测试cDNA群之一进行杂交。此步骤产生(a)未杂交的测试cDNA群，(b)与其它测试cDNA杂交的测试cDNA群，(c)与驱动cDNA杂交的测试cDNA群，和(d)未杂交的驱动cDNA群。然后将两个分别进行的杂交反应物混和，并在额外的变性驱动cDNA存在的条件下进行再次杂交。随此第二轮杂交后，除了(a)-(d)群，还产生了第五群(e)，其中含有一种衔接头的测试cDNA与含有第二种衔接头的测试cDNA发生杂交。相应的，第二杂交步骤导致差异表达序列的富集，可以在PCR扩增(使用衔接头特异引物)中作为模板使用。
然后补平末端，并使用衔接头特异引物进行PCR扩增。只有含有不与驱动cDNA杂交的测试cDNA的(e)群指数扩增。然后进行第二轮PCR扩增，以减小背景并进一步富集差异表达序列。
此基于PCR的扣除技术使差异表达的cDNA标准化，使得可以回收在前列腺肿瘤组织中过度表达的稀有转录本。而通过传统扣除方法回收这些转录本将是困难的。
除了已知在前列腺肿瘤中过度表达的基因，还鉴定了77个克隆。这些部分cDNA的序列提供于SEQ ID NO:29-305。这些克隆中的大多数与数据库序列没有明显同源性。例外有JPTPN23(SEQ ID NO:231；与猪含缬酪肽的蛋白质相似)、JPTPN30(SEQ ID NO:234；与大鼠蛋白酶体亚基的mRNA相似)、JPTPN45(SEQ ID NO:243；与大鼠norvegicus胞质NADP依赖型异柠檬酸脱氢酶相似)、JPTPN46(SEQ ID NO:244；与人亚克隆H8 4 d4 DNA序列相似)、JP1D6(SEQ ID NO:265；与G.gallus动力蛋白轻链A相似)、JP8D6(SEQ ID NO:288；与人BAC克隆RG016J04相似)、JP8F5(SEQ ID NO:289；与人亚克隆H83 b5 DNA序列相似)、和JP8E9(SEQ ID NO:299；与人Alu序列相似)。
对由前列腺肿瘤合并物扣除正常前列腺合并物后组成的基于PCR的扣除文库(称PT-PN PCR扣除)的其它研究，得到另外3个克隆。将这些克隆的cDNA序列与最近版本的GenBank进行比较，揭示与两个克隆(P715P和P767P；SEQ ID NO:312和314)没有明显同源性。发现另一克隆与已知基因KIAA0056(SEQ ID NO:318)有一定同源性。使用微阵分析测量mRNA在各种组织中的表达水平，发现所有3个克隆在前列腺肿瘤和BPH组织中过度表达。具体的说，克隆P715P在大多数前列腺肿瘤和BPH组织中过度表达3倍或更多，而在大多数正常前列腺样品中和在胎儿组织中表达提高，但是在所有其它正常组织中为阴性至低水平表达。克隆P767P在多个前列腺肿瘤和BPH组织中过度表达，而在半数正常前列腺样品中中度表达，且在所有其它测试的正常组织中为背景至低水平表达。
通过上述微阵对PT-PN PCR扣除文库和含扣除了一组正常组织cDNA的前列腺肿瘤cDNA的DNA扣除文库进一步分析，分离得到经测定在前列腺肿瘤中过度表达的另外27个克隆(SEQ ID NO:340-365和381)。还发现SEQ ID NO:341、342、345、347、348、349、351、355-359、361、362和364的克隆在正常前列腺中表达。发现所有26个克隆在多种正常组织中低水平表达或检测不到，而P544S(SEQ IDNO:356)是例外，发现它在小肠中表达。发现26个克隆中的10个(SEQID NO:340-349)显示与已经鉴定的序列有一定同源性。没有发现与SEQ ID NO:350-365的克隆有明显同源性。
实施例6
小鼠的肽致敏和CTL细胞系的增殖
6.1此实施例阐述对表达P502S基因的细胞特异的CTL细胞系的制备。
如Theobald等人(Proc.Natl.Acad.Sci.USA92:11993-11997,1995)描述的，做下列改动，用P502S基因(此处也称为J1-17,SEQ ID NO:8)衍生的P2S#12肽(VLGWVAEL；SEQ IDNO:306)免疫表达人HLA A2.1转基因的小鼠(由L.Sherman博士提供，The Scripps Research Institute,La Jolla,CA)。用不完全弗氏佐剂乳化的100μg P2S#12和120μg乙肝病毒蛋白衍生的I-Ab结合肽免疫小鼠。三周后，处死这些小鼠，并使用尼龙筛制备单细胞悬液。然后将细胞以6×106个细胞/ml重悬于含下述成分的完全培养基(RPMI-1640；Gibco BRL,Gaithersburg,MD)中:10％FCS，2mM谷氨酰胺(Gibco BRL)，丙酮酸钠(Gibco BRL)，非必需氨基酸(Gibco BRL),2×10-5M 2-巯基乙醇，50U/ml青霉素和链霉素，并在经照射(3000拉德)的P2S#12脉冲(5mg/ml P2S#12和10mg/mlβ2-微球蛋白)LPS未成熟细胞(A2转基因脾细胞在有7μg/ml硫酸葡聚糖和25μg/ml LPS存在下培养3天)中培养。6天后，细胞(5×105个/ml)用2.5×106/ml肽脉冲的照射(20,000拉德)EL4A2Kb细胞(Sherman等人，Science 258:815-818,1992)和3×106个/ml A2转基因脾饲养细胞进行再刺激。将细胞在存在20U/ml IL-2的条件下培养。在制备克隆系的过程中，如上所述继续每周一次对细胞进行再刺激。
通过用肽脉冲的EL4A2Kb肿瘤细胞(1×104个细胞/孔)作为刺激物和A2转基因脾细胞(5×105个细胞/孔)作为饲养物(在30U/ml IL-2中培养)的有限稀释分析，克隆得到P2S#12系。第14天，如上对细胞进行再刺激。第21天，分离并维持正在生长的克隆。这些克隆中的多个显示对P502S转导的人成纤维细胞(表达HLA A2.1)的反应性(溶解)明显比对对照成纤维细胞高。
此数据说明P2S#12展示在人HLA A2.1分子中表达的P502S蛋白天然加工的表位。
6.2此实施例阐述鼠CTL系和对表达P501S基因的细胞特异的CTL克隆的制备。
与上述相似进行这一系列实验。用P501S基因(此处也称为L1-12，SEQ ID NO:110)衍生的P1S#10肽(SEQ ID NO:337)免疫小鼠。P1S#10肽是通过分析P501S预测的多肽序列中由发表的HLA-A2结合基元(K.C.Parker等人，J.Immunol.,152:163,1994)定义的潜在HLA-A2结合序列而得到的。P1S#10肽如实施例4所述合成，并根据经验使用基于T细胞的竞争实验测试HLA-A2结合。测试了预测的A2结合肽与HLA-A2特异肽竞争向HLA-A2结合流感基质肽fluM58特异的HLA-A2限制性CTL克隆(D150M58)呈递的能力。D150M58 CTL应答fluM58肽的自身呈递而分泌TNF。在竞争实验中，向D150M58 CTL培养物中加入100-200μg/ml检测肽，以结合CTL上的HLA-A2。30分钟后，测试与检测肽或对照肽一起培养的CTL在标准TNF生物实验中对fluM58肽的抗原剂量应答。如图3所示，P1S#10肽竞争fluM58的HLA-A2限制性呈递，证明P1S#10肽结合HLA-A2。
如Theobald等人所述(Proc.Natl.Acad.Sci.USA92:11993-11997,1995)，做下列改动，免疫接种表达人HLA A2.1转基因的小鼠。用不完全弗氏佐剂乳化的62.5μg P1S#10和120μg由乙肝病毒蛋白质衍生得到的I-Ab结合肽免疫小鼠。3周后，处死这些小鼠，并使用尼龙网制备单细胞悬液。然后将细胞以6×106细胞/ml浓度重悬于完全培养基(如上所述)中，并在存在经照射(3000拉德)的P1S#10脉冲(2μg/ml P1S#10和10mg/ml β2-微球蛋白)的LPS未成熟细胞(在7μg/ml硫酸葡聚糖和25μg/mlLPS存在下培养了3天的A2转基因脾细胞)的条件下培养。6天后，如上所述将细胞(5×105/细胞)用2.5×106/ml经肽脉冲的照射过(20,000拉德)的EL4A2Kb细胞和3×106/ml A2转基因脾饲养细胞再刺激。在存在20U/ml IL-2的条件下培养细胞。在制备克隆的过程中每周再刺激细胞一次。3轮体外刺激后，产生识别P1S#10脉冲的Jurkat A2Kb靶细胞和P501S转导的Jurkat靶细胞的细胞系，如图4所示。
用在存在30U/ml IL-2的条件下生长的肽脉冲的EL4 A2Kb肿瘤细胞(1×104细胞/孔)作为刺激细胞、A2转基因脾细胞作为饲养细胞(5×105细胞/孔)，通过有限稀释分析克隆了P1S#10特异的CTL系。第14天，如上进行再刺激。第21天，分离存活的克隆，并维持培养。如图5所示，这些克隆中的5个证明有对P501S转导的Jurkat A2Kb靶细胞的特异溶细胞反应性。此资料说明P1S#10代表了在人HLA-A2.1分子中表达的P501S蛋白质的天然加工表位。
实施例7
人T细胞识别前列腺肿瘤多肽的能力
此实施例例示了前列腺肿瘤多肽特异的T细胞识别人肿瘤的能力。
使用树突状细胞，根据Van Tsai等人的方案(Critical Reviewsin Immunology 18:65-75,1998)，用由P502S(也称为J1-17)衍生得到的P2S-12肽(SEQ ID NO:306)体外致敏人CD8+T细胞。在γ-干扰素ELISPOT实验(见Lalvani等人，J.Exp.Med.186:859-865，1997)中测试得到的CD8+T细胞小量培养物识别由自身成纤维细胞或经转导表达P502S基因的成纤维细胞呈递的P2S-12肽的能力。简单的说，在存在3μg/ml人β2-微球蛋白和1μg/ml P2S-12肽或对照E75肽的条件下，在104个成纤维细胞上平行滴定测量T细胞数目两份。此外，同时在用P502S基因转导的自身成纤维细胞，或者作为对照，在用HER-2/neu转导的成纤维细胞上测定T细胞。在实验前，将成纤维细胞用10ng/ml γ-干扰素处理48小时，以上调Ⅰ类MHC应答。小量培养物之一(#5)证明在γ-干扰素ELISPOT实验中显著识别肽脉冲的成纤维细胞，以及经转导的成纤维细胞。图2A证明在用P2S-12肽(实心柱)脉冲的成纤维细胞上，γ-干扰素斑点的数目随T细胞数目的增加而显著增加，对照E75肽(空心柱)则不然。这显示了这些T细胞具有特异识别P2S-12肽的能力。如图2B所示，此小量培养物也证明在经转导表达P502S基因的成纤维细胞上，γ-干扰素斑点的数目随T细胞数目的增加而增加，在经转导表达HER-2/neu基因的成纤维细胞上则不然。这些结果提供了额外的确凿证据表明P2S-12肽是P502S蛋白质的天然加工表位。此外，这也证明了在人T细胞集合中存在能够识别此表位的高亲和力T细胞。这些T细胞也应该能够识别表达P502S基因的人肿瘤。
实施例8
用前列腺抗原通过裸露DNA免疫在体内致敏CTL
上述前列腺肿瘤抗原L1-12，也称为P501S。用100μg VR10132-P501S肌肉内或皮内免疫HLA A2Kb Tg小鼠(由L.Sherman博士提供，The Scripps Research Institute,La Jolla,CA)。对小鼠进行了3次免疫，各次免疫间隔2周。最后一次免疫2周后，将免疫脾细胞与Jurkat A2Kb-P501S转导的刺激细胞一起培养。每周刺激CTL系一次。体外刺激2周后，评定针对P501S转导的靶细胞的CTL活性。8只小鼠中的2只显示强抗P501S CTL应答。这些结果证明P501S含有至少一种天然加工的A2限制性CTL表位。
实施例9使用前列腺肿瘤抗原通过完整基因致敏和刺激技术在体外产生人CTL
使用P501S逆转录病毒转导的自身成纤维细胞进行体外全基因致敏(见(例如)Yee等人，The Journal of Immunology 157(9):4079-86，1996)，衍生得到如上所述通过γ-干扰素ELISPOT实验鉴定能特异识别用P501S(也称为L1-12)转导的自身成纤维细胞的人CTL系。使用用P501S转导的HLA错配的成纤维细胞系系列，这些CTL系显示为限制性HLA-A2 Ⅰ型等位基因。具体的说，从在RPMI培养基(含10％人血清、50ng/ml人GM-CSF和30ng/ml人IL-4)中培养5天，由正常人供体的PBMC衍生得到的单核细胞培养物分化出树突状细胞(DC)通过。培养后，将DC用重组P501S痘病毒感染过夜，感染复数(M.O.I)为5，并加入3μg/ml CD40配基成熟过夜。通过UV照射灭活病毒。使用磁珠系统分离CD8+T细胞，并使用常规培养技术开始致敏培养。每7-10天，用P501S逆转录病毒转导的自身原代成纤维细胞再刺激培养物。4个刺激循环后，鉴定出用P501S转导的自身成纤维细胞刺激时特异产生γ-干扰素的CD8+T细胞系。通过在存在IL-15的条件下用P501S转导的成纤维细胞继续刺激培养物，可以维持P501S特异活性。制备用P501S转导的HLA错配的成纤维细胞系系列，以定义应答的限制性等位基因。通过在ELISPOT实验中测量γ-干扰素，P501S特异应答显示受HLA-A2限制。这些结果证明可以引发对P501S的CD8+CTL应答。
实施例10
鉴定前列腺肿瘤抗原内含有的天然加工的CTL表位
九聚肽p5(SEQ ID NO:338)由P703P抗原(也称为P20)衍生得到。p5肽在人HLA-A2供体中是免疫原性的，而且是天然加工表位。抗原特异性CD8+T细胞可以在用p5肽脉冲的单核细胞体外重复刺激后致敏。这些CTL在ELISPOT(如上所述)和铬释放实验中特异识别p5脉冲的靶细胞。此外，用p5免疫HLA-A2转基因小鼠产生可识别多种P703P转导的、表达HLA-A2Kb或HLA-A2的靶细胞的CTL系。具体的说，HLA-A2转基因小鼠爪垫上皮下免疫接种含100μg p5肽和140μg乙肝病毒核心肽(Th肽)的弗氏不完全佐剂。免疫3周后，用肽脉冲的LPS未成熟细胞体外刺激来自免疫小鼠的脾细胞。初次体外刺激5天后，通过铬释放实验评估CTL活性。将表达对照抗原P703P和HLA-A2Kb的逆转录病毒转导细胞作为靶细胞使用。鉴定出可特异识别p5脉冲的靶细胞以及表达P703P的靶细胞的CTL系。
人体外致敏实验证明p5肽在人体内具有免疫原性。通过在RPMI培养基(含10％人血清、50ng/ml人GM-CSF和30ng/ml人IL-4)中培养5天，由正常人供体的PBMC衍生得到的单核细胞培养物分化出树突状细胞(DC)。培养后，用p5肽对DC进行脉冲，并与GM-CSF和IL-4一起与CD8+T细胞富集的PBMC培养。每周用p5脉冲的单核细胞再刺激CTL系一次。CTL培养起始5-6周后，证明CTL对p5脉冲的靶细胞的识别。
实施例11
前列腺中乳腺肿瘤衍生的抗原的表达
1996年8月20日提出申请的美国专利申请编号08/700,014中描述了通过差异显示由乳腺肿瘤分离抗原B305D。分离得到此抗原的多种不同剪接形式。这些剪接形式经测定的cDNA序列提供于SEQ ID NO:366-375，相应于SEQ ID NO:292、298和301-303序列的预测的氨基酸序列依次提供于SEQ ID NO:299-306。
通过实时PCR和通过Northern分析检查了B305D在多种肿瘤和正常组织中的表达水平。结果表明B305D在乳腺肿瘤、前列腺肿瘤、正常前列腺组织和正常睾丸中高水平表达，在所有其它检查的组织(结肠肿瘤、肺肿瘤、卵巢肿瘤、和正常骨髓、结肠、肾、肝、肺、卵巢、皮肤、小肠、胃)中低水平表达或检测不到。
实施例12
在人血液中激发前列腺肿瘤抗原特异的CTL应答
此实施例例示了前列腺肿瘤抗原在正常人血液中诱发CTL应答的能力。
通过在RPMI培养基(含10％人血清、50ng/ml GMCSF和30ng/mlIL-4)中培养5天，由正常供体的PBMC衍生得到的单核细胞培养物分化出自身树突状细胞(DC)。培养后，将DC用表达P501S的重组痘病毒感染(M.O.I.=5)过夜，并通过加入2μg/ml CD40配基成熟8小时。UV照射灭活病毒，使用磁珠通过正选择分离CD8+细胞，并在24孔板中开始致敏培养。5个刺激循环后，鉴定出用自身P501S转导的成纤维细胞刺激后特异产生γ-干扰素的CD8+系。在P501S转导的自身B-LCL上进行额外刺激之后，细胞系3A-1能够维持其P501S特异活性。3A-1系显示能特异识别经转导表达P501S的自身B-LCL，但不识别EGFP转导的自身B-LCL(通过细胞毒性实验(51Cr释放)和γ-干扰素产生(Interferon-gamma Elispot；见上文和Lalvani等人，J.Exp.Med.186:859-865,1997)测得)。这些实验的结果呈现于图6A和6B。
实施例13
通过微阵分析鉴定前列腺肿瘤抗原
此实施例描述了由前列腺肿瘤cDNA文库分离某些前列腺肿瘤多肽。
使用微阵分析筛选上述人前列腺肿瘤cDNA表达文库，以鉴定与非前列腺的正常组织(不包括睾丸)相比，在前列腺肿瘤和/或正常前列腺组织中显示至少3倍过量表达的克隆。鉴定出372个克隆，并成功的对其中319个克隆进行了测序。表Ⅰ给出了这些克隆(显示于SEQ IDNO:385-400)的概述。这些序列中，SEQ ID NO:386、389、390和392对应于新基因，而SEQ ID NO:393和396对应于先前鉴定的序列。其它序列(SEQ ID NO:385、387、388、391、394、395和397-400)对应于已知序列，显示于表Ⅰ。
表Ⅰ
前列腺肿瘤抗原概述
| 已知基因 先前鉴定的基因 新基因 | ||
| T细胞γ链激肽释放酶载体CGI-82蛋白质mRNA(23319；SEQ ID NO:385)PSAAld.6 Dehyd.L-艾杜糖醇-2脱氢酶(23376；SEQ ID NO:388)Ets转录因子PDEF(22672；SEQ ID NO:398)hTGR(22678；SEQ ID NO:399)KIAA0295(22685；SEQ IDNO:400)前列腺酸性磷酸酶(22655；SEQ ID NO:397)转谷氨酰胺酶(22611；SEQID NO:395)HDLBP(23508；SEQ ID NO:394)CGI-69蛋白质(23367；SEQID NO:387)KIAA0122(23383；SEQ IDNO:391)TEEG | P504SP1000CP501SP503SP510SP784PP502SP706P19142.2, bangur.seq(22621；SEQ ID NO:396)5566.1 Wang(23404；SEQ IDNO:393)P712PP778P | 23379(SEQ ID NO:389)23399(SEQ ID NO:392)23320(SEQ ID NO:386)23381(SEQ ID NO:390) |
CGI-82在前列腺组织中，与测试的其它正常组织相比，显示4.06倍过量表达。它在43％的前列腺肿瘤、25％的正常前列腺中过量表达，而在测试的其它正常组织中检测不到。L-艾杜糖醇-2脱氢酶在前列腺组织中，与测试的其它正常组织相比，显示4.94倍过量表达。它在90％的前列腺肿瘤、100％的正常前列腺中过量表达，而在测试的其它正常组织中检测不到。Ets转录因子PDEF在前列腺组织中，与测试的其它正常组织相比，显示5.55倍过量表达。它在47％的前列腺肿瘤、25％的正常前列腺中过量表达，而在测试的其它正常组织中检测不到。hTGR1在前列腺组织中，与测试的其它正常组织相比，显示9.11倍过量表达。它在63％的前列腺肿瘤中过量表达，而在测试的正常组织(包括正常前列腺)中检测不到。KIAA0295在前列腺组织中，与测试的其它正常组织相比，显示5.59倍过量表达。它在47％的前列腺肿瘤中过量表达，而在测试的正常组织(包括正常前列腺组织)中低水平表达或检测不到。前列腺酸性磷酸酶在前列腺组织中，与测试的其它正常组织相比，显示9.14倍过量表达。它在67％的前列腺肿瘤、50％的正常前列腺中过量表达，而在测试的其它所有正常组织中检测不到。转谷氨酰胺酶在前列腺组织中，与测试的其它正常组织相比，显示14.84倍过量表达。它在30％的前列腺肿瘤、50％的正常前列腺中过量表达，而在测试的其它正常组织中检测不到。高密度脂蛋白结合蛋白(HDLBP)在前列腺组织中，与测试的其它正常组织相比，显示28.06倍过量表达。它在97％的前列腺肿瘤、75％的正常前列腺中过量表达，而在测试的其它正常组织中检测不到。CGI-69在前列腺组织中，与测试的其它所有正常组织相比，显示3.56倍过量表达。它是低丰度基因，在超过90％的前列腺肿瘤和在75％的正常前列腺组织中可检测到。此基因在正常组织中的表达很低。KIAA0122在前列腺组织中，与测试的其它正常组织相比，显示4.24倍过量表达。它在57％的前列腺肿瘤中过量表达，而在测试的所有正常组织(包括正常前列腺组织)中检测不到。19142.2bangur在前列腺组织中，与测试的其它正常组织相比，显示23.25倍过量表达。它在97％的前列腺肿瘤、100％的正常前列腺中过量表达，而在测试的其它正常组织中检测不到。5566.1Wang在前列腺组织中，与测试的其它正常组织相比，显示3.31倍过量表达。它在97％的前列腺肿瘤、75％的正常前列腺中过量表达，在正常骨髓、胰腺和激活的PBMC中也过量表达。新克隆23379在前列腺组织中，与测试的其它正常组织相比，显示4.86倍过量表达。它在97％的前列腺肿瘤、75％的正常前列腺中可检测到，而在测试的所有其它正常组织中检测不到。新克隆23399在前列腺组织中，与测试的其它正常组织相比，显示4.09倍过量表达。它在27％的前列腺肿瘤中过量表达，而在测试的所有正常组织(包括正常前列腺组织)中检测不到。新克隆23320在前列腺组织中，与测试的其它正常组织相比，显示3.15倍过量表达。它可在所有前列腺肿瘤、50％的正常前列腺中检测到。它也在正常结肠和气管中表达。其它正常组织不以高水平表达此基因。
实施例14
通过电子扣除法鉴定前列腺肿瘤抗原
此实施例描述了使用电子扣除技术鉴定前列腺肿瘤抗原。
通过电子扣除(与Vasmatizis等人，Proc.Natl.Acad.Sci.USA95:300-304,1998描述的相似)鉴定GenBank人EST数据库中可能的前列腺特异基因。由GenBank公开的人EST数据库得到多种前列腺文库衍生的EST克隆(43,482)的序列。将每种前列腺EST序列作为查询序列使用，在BLASTN(National Center for BiotechnologyInformation)搜索人EST数据库。将视为相同的所有匹配(匹配序列长度＞100碱基对，此区域的同一匹配率＞70％)排列在一起成簇。由于含有多于200个EST的簇可能代表重复元件或者高表达基因(诸如核糖体蛋白基因)，所以将它们放弃。如果两个或多个簇具有共同EST,则将那些簇排列在一起成“超簇”(supercluster)，产生了4,345个前列腺超簇。
下载GenBank中479个人cDNA文库的记录，以产生这些cDNA文库记录的数据库。将这479个cDNA文库分成3组，“+”组(正常前列腺和前列腺肿瘤文库，以及乳腺细胞系，其中希望有表达)，“-”组(来自其它正常成人组织的文库，其中不希望有表达)，和其它组(胎儿组织、婴儿组织、只在女性中发现的组织、非前列腺肿瘤和非前列腺细胞系的细胞系，其中表达认为是不相关的)。这些文库组的概述呈现于表Ⅱ。
表Ⅱ
前列腺cDNA文库和EST
| 文库 | 文库数目 | EST数目 |
| +组 | 25 | 43,482 |
| 正常 | 11 | 18,875 |
| 肿瘤 | 11 | 21,769 |
| 细胞系 | 3 | 2,838 |
| -组 | 166 | |
| 其它 | 287 |
就超簇中的EST分析每个超簇。记录每个EST克隆的组织来源，并由此将超簇分成4组：1型-只发现于“+”组文库的EST克隆；在“-”组或其它组文库中没有检测到表达；2型-只发现于“+”组和其它组文库的EST克隆；在“-”组中检测不到表达；3型-发现于“+”组、“-”组和其它组文库中的EST克隆，但是在“+”组中的表达高于“-”组或其它组中；4型-发现于“+”组、“-”组和其它组文库中的EST克隆，但是在“+”组中的表达高于在“-”组中的表达。此分析鉴定出了4,345个乳腺簇(见表Ⅲ)。由这些簇，向Research Genetics,Inc.定购了3,172个EST克隆，并收到96孔板中的甘油冻存物。
表Ⅲ
前列腺簇概述
| 类型 | 超簇数目 | 定购的EST数目 |
| 1 | 688 | 677 |
| 2 | 2899 | 2484 |
| 3 | 85 | 11 |
| 4 | 673 | 0 |
| 总计 | 4345 | 3172 |
使用连接了氨基的PCR引物PCR扩增插入片段，用于Synteni微阵分析。当对一个特定克隆得到多于一种PCR产物时，该PCR产物不用于表达分析。总计，通过微阵分析对来自电子扣除方法的2,528个克隆进行了分析，以鉴定相对正常组织在肿瘤中mRNA较高的电子扣除乳腺克隆。使用Synteni(Palo Alto,CA)微阵，根据制造商的说明书(而且基本上如Schena等人，Proc.Natl.Acad.Sci.USA93:10614-10619,1996和Heller等人，Proc.Natl.Acad.Sci.USA94:2150-2155,1997描述的)进行这些筛选。在这些分析中，将克隆排列在芯片上，然后用由正常和肿瘤前列腺cDNA，以及多种其它正常组织产生的荧光探针进行探查。对载片进行扫描，并测量荧光强度。
具有超过3的表达比率(即前列腺肿瘤cDNA的水平至少是正常前列腺cDNA的水平的3倍)的克隆鉴定为前列腺肿瘤特异序列(表Ⅳ)。这些克隆的序列提供于SEQ ID NO:401-453，某些新序列提供于SEQID NO:407、413、416-419、422、426、427和450。
表IV前列腺肿瘤特异克隆
| SEQ ID NO | 序列名称 | 注释 |
| 401 | 22545 | 先前鉴定的P1000C |
| 402 | 22547 | 先前鉴定的P704P |
| 403 | 22548 | 已知 |
| 404 | 22550 | 已知 |
| 405 | 22551 | PSA |
| 406 | 22552 | 前列腺分泌蛋白94 |
| 407 | 22553 | 新 |
| 408 | 22558 | 先前鉴定的P509S |
| 409 | 22562 | 腺激肤释放酶 |
| 410 | 22565 | 先前鉴定的P1000C |
| 411 | 22567 | PAP |
| 412 | 22568 | B1006C(乳腺肿瘤抗原) |
| 413 | 22570 | 新 |
| 414 | 22571 | PSA |
| 415 | 22572 | 先前鉴定的P706P |
| 416 | 22573 | 新 |
| 417 | 22574 | 新 |
| 418 | 22575 | 新 |
| 419 | 22580 | 新 |
| 420 | 22581 | PAP |
| 421 | 22582 | 前列腺分泌蛋白94 |
| 422 | 22583 | 新 |
| 423 | 22584 | 前列腺分泌蛋白94 |
| 424 | 22585 | 前列腺分泌蛋白94 |
| 425 | 22586 | 已知 |
| 426 | 22587 | 新 |
| 427 | 22588 | 新 |
| 428 | 22589 | PAP |
| 429 | 22590 | 已知 |
| 430 | 22591 | PSA |
| 431 | 22592 | 已知 |
| 432 | 22593 | 先前鉴定的P777P |
| 433 | 22594 | T细胞受体γ链 |
| 434 | 22595 | 先前鉴定的P705P |
| 435 | 22596 | 先前鉴定的P707P |
| 436 | 22847 | PAP |
| 437 | 22848 | 已知 |
| 438 | 22849 | 前列腺分泌蛋白57 |
| 439 | 22851 | PAP |
| 440 | 22852 | PAP |
| 441 | 22853 | PAP |
| 442 | 22854 | 先前鉴定的P509S |
| 443 | 22855 | 先前鉴定的P705P |
| 444 | 22856 | 先前鉴定的P774P |
| 445 | 22857 | PSA |
| 446 | 23601 | 先前鉴定的P777P |
| 447 | 23602 | PSA |
| 448 | 23605 | PSA |
| 449 | 23606 | PSA |
| 450 | 23612 | 新 |
| 451 | 23614 | PSA |
| 452 | 23618 | 先前鉴定的P1000C |
| 453 | 23622 | 先前鉴定的P705P |
实施例15
通过微阵分析进一步鉴定前列腺肿瘤抗原
此实施例描述了由前列腺肿瘤cDNA文库分离其它前列腺肿瘤多肽。
使用微阵分析筛选上述人前列腺肿瘤cDNA表达文库，以鉴定与非前列腺的正常组织(不包括睾丸)相比，在前列腺肿瘤和/或正常前列腺组织中显示至少3倍过量表达的克隆。对142个克隆进行了鉴定和测序。这些克隆中的某些显示于SEQ ID NO:454-467。这些序列中，SEQ ID NO:459-461对应于新基因。其它(SEQ ID NO:454-458和461-467)对应于已知序列。
实施例16
进一步鉴定前列腺肿瘤抗原P710P
此实施例描述了P710P的全长克隆。
用上述P710P片段筛选上述前列腺cDNA文库。将1百万个菌落在LB/氨苄青霉素平板上铺板。使用尼龙滤膜浸提这些菌落，然后将这些滤膜沾取的cDNA变性，并通过UV光与滤膜交联。将P710P片段进行放射性标记，并用于与滤膜杂交。选择阳性cDNA克隆，回收它们的cDNA，并通过自动ABI测序仪进行测序。得到4个序列，列于SEQ IDNO:468-471。
根据上述内容，可以理解，尽管本发明为了阐述目的而描述了一些特定实施方案，但可做各种改动，而仍不偏离本发明的精神和范围。相应的，本发明只受所附权利要求的限制。
序列表<110> Corixa Corporation<120> 用于治疗和诊断前列腺癌的组合物和方法<130> 210121.42701PC<140> PCT<141> 1999-07-08<160> 472<170> FastSEQ for Windows Version 3.0<210> 1<211> 814<212> DNA<213> Homo sapien<220><221> misc feature<222> (1)...(814)<223> n=A,T,C or G<400> 1tttttttttt tttttcacag tataacagct ctttatttct gtgagttcta ctaggaaatc 60atcaaatctg agggttgtct ggaggacttc aatacacctc cccccatagt gaatcagctt 120ccagggggtc cagtccctct ccttacttca tccccatccc atgccaaagg aagaccctcc 180ctccttggct cacagccttc tctaggcttc ccagtgcctc caggacagag tgggttatgt 240tttcagctcc atccttgctg tgagtgtctg gtgcgttgtg cctccagctt ctgctcagtg 300cttcatggac agtgtccagc acatgtcact ctccactctc tcagtgtgga tccactagtt 360ctagagcggc cgccaccgcg gtggagctcc agcttttgtt ccctttagtg agggttaatt 420gcgcgcttgg cgtaatcatg gtcataactg tttcctgtgt gaaattgtta tccgctcaca 480attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc ctaatgagtg 540anctaactca cattaattgc gttgcgctca ctgnccgctt tccagtcngg aaaactgtcg 600tgccagctgc attaatgaat cggccaacgc ncggggaaaa gcggtttgcg ttttgggggc 660tcttccgctt ctcgctcact nantcctgcg ctcggtcntt cggctgcggg gaacggtatc 720actcctcaaa ggnggtatta cggttatccn naaatcnggg gatacccngg aaaaaanttt 780aacaaaaggg cancaaaggg cngaaacgta aaaa 814<210> 2<211> 816<212> DNA<213> Homo sapien<220><221> misc_feature<222> (1)...(816)<223> n = A,T,C or G<400> 2acagaaatgt tggatggtgg agcacctttc tatacgactt acaggacagc agatggggaa 60ttcatggctg ttggagcaat agaaccccag ttctacgagc tgctgatcaa aggacttgga 120ctaaagtctg atgaacttcc caatcagatg agcatggatg attggccaga aatgaagaag 180aagtttgcag atgtatttgc aaagaagacg aaggcagagt ggtgtcaaat ctttgacggc 240acagatgcct gtgtgactcc ggttctgact tttgaggagg ttgttcatca tgatcacaac 300aaggaacggg gctcgtttat caccagtgag gagcaggacg tgagcccccg ccctgcacct 360ctgctgttaa acaccccagc catcccttct ttcaaaaggg atccactagt tctagaagcg 420gccgccaccg cggtggagct ccagcttttg ttccctttag tgagggttaa ttgcgcgctt 480ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca caattccccc 540aacatacgag ccggaacata aagtgttaag cctggggtgc ctaatgantg agctaactcn 600cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaaactgtcg tgccactgcn 660ttantgaatc ngccaccccc cgggaaaagg cggttgcntt ttgggcctct tccgctttcc 720tcgctcattg atcctngcnc ccggtcttcg gctgcggnga acggttcact cctcaaaggc 780ggtntnccgg ttatccccaa acnggggata cccnga 816
<210> 3
<211> 773
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(773)
<223> n = A,T,C or G
<400> 3cttttgaaag aagggatggc tggggtgttt aacagcagag gtgcagggcg ggggctcacg 60tcctgctcct cactggtgat aaacgagccc cgttccttgt tgtgatcatg atgaacaacc 120tcctcaaaag tcagaaccgg agtcacacag gcatctgtgc cgtcaaagat ttgacaccac 180tctgccttcg tcttctttgc aaatacatct gcaaacttct tcttcatttc tggccaatca 240tccatgctca tctgattggg aagttcatca gactttagtc canntccttt gatcagcagc 300tcgtagaact ggggttctat tgctccaaca gccatgaatt ccccatctgc tgtcctgtaa 360gtcgtataga aaggtgctcc accatccaac atgttctgtc ctcgaggggg ggcccggtac 420ccaattcgcc ctatantgag tcgtattacg cgcgctcact ggccgtcgtt ttacaacgtc 480gtgactggga aaaccctggg cgttaccaac ttaatcgcct tgcagcacat ccccctttcg 540ccagctgggc gtaatancga aaaggcccgc accgatcgcc cttccaacag ttgcgcacct 600gaatgggnaa atgggacccc cctgttaccg cgcattnaac ccccgcnggg tttngttgtt 660acccccacnt nnaccgctta cactttgcca gcgccttanc gcccgctccc tttcnccttt 720cttcccttcc tttcncnccn ctttcccccg gggtttcccc cntcaaaccc cna 773
<210> 4
<211> 828
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(828)
<223> n = A,T,C or G
<400> 4cctcctgagt cctactgacc tgtgctttct ggtgtggagt ccagggctgc taggaaaagg 60aatgggcaga cacaggtgta tgccaatgtt tctgaaatgg gtataatttc gtcctctcct 120tcggaacact ggctgtctct gaagacttct cgctcagttt cagtgaggac acacacaaag 180acgtgggtga ccatgttgtt tgtggggtgc agagatggga ggggtggggc ccaccctgga 240agagtggaca gtgacacaag gtggacactc tctacagatc actgaggata agctggagcc 300acaatgcatg aggcacacac acagcaagga tgacnctgta aacatagccc acgctgtcct 360gngggcactg ggaagcctan atnaggccgt gagcanaaag aaggggagga tccactagtt 420ctanagcggc cgccaccgcg gtgganctcc ancttttgtt ccctttagtg agggttaatt 480gcgcgcttgg cntaatcatg gtcatanctn tttcctgtgt gaaattgtta tccgctcaca 540attccacaca acatacganc cggaaacata aantgtaaac ctggggtgcc taatgantga 600ctaactcaca ttaattgcgt tgcgctcact gcccgctttc caatcnggaa acctgtcttg 660ccncttgcat tnatgaatcn gccaaccccc ggggaaaagc gtttgcgttt tgggcgctct 720tccgcttcct cnctcantta ntccctncnc tcggtcattc cggctgcngc aaaccggttc 780accncctcca aagggggtat tccggtttcc ccnaatccgg gganancc 828
<210> 5
<211> 834
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(834)
<223> n = A,T,C or G
<400> 5tttttttttt tttttactga tagatggaat ttattaagct tttcacatgt gatagcacat 60agttttaatt gcatccaaag tactaacaaa aactctagca atcaagaatg gcagcatgtt 120attttataac aatcaacacc tgtggctttt aaaatttggt tttcataaga taatttatac 180tgaagtaaat ctagccatgc ttttaaaaaa tgctttaggt cactccaagc ttggcagtta 240acatttggca taaacaataa taaaacaatc acaatttaat aaataacaaa tacaacattg 300taggccataa tcatatacag tataaggaaa aggtggtagt gttgagtaag cagttattag 360aatagaatac cttggcctct atgcaaatat gtctagacac tttgattcac tcagccctga 420cattcagttt tcaaagtagg agacaggttc tacagtatca ttttacagtt tccaacacat 480tgaaaacaag tagaaaatga tgagttgatt tttattaatg cattacatcc tcaagagtta 540tcaccaaccc ctcagttata aaaaattttc aagttatatt agtcatataa cttggtgtgc 600ttattttaaa ttagtgctaa atggattaag tgaagacaac aatggtcccc taatgtgatt 660gatattggtc atttttacca gcttctaaat ctnaactttc aggcttttga actggaacat 720tgnatnacag tgttccanag ttncaaccta ctggaacatt acagtgtgct tgattcaaaa 780tgttattttg ttaaaaatta aattttaacc tggtggaaaa ataatttgaa atna 834
<210> 6
<211> 818
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (818)
<223> n = A,T,C or G
<400> 6tttttttttt tttttttttt aagaccctca tcaatagatg gagacataca gaaatagtca 60aaccacatct acaaaatgcc agtatcaggc ggcggcttcg aagccaaagt gatgtttgga 120tgtaaagtga aatattagtt ggcggatgaa gcagatagtg aggaaagttg agccaataat 180gacgtgaagt ccgtggaagc ctgtggctac aaaaaatgtt gagccgtaga tgccgtcgga 240aatggtgaag ggagactcga agtactctga ggcttgtagg agggtaaaat agagacccag 300taaaattgta ataagcagtg cttgaattat ttggtttcgg ttgttttcta ttagactatg 360gtgagctcag gtgattgata ctcctgatgc gagtaatacg gatgtgttta ggagtgggac 420ttctagggga tttagcgggg tgatgcctgt tgggggccag tgccctccta gttggggggt 480aggggctagg ctggagtggt aaaaggctca gaaaaatcct gcgaagaaaa aaacttctga 540ggtaataaat aggattatcc cgtatcgaag gcctttttgg acaggtggtg tgtggtggcc 600ttggtatgtg ctttctcgtg ttacatcgcg ccatcattgg tatatggtta gtgtgttggg 660ttantanggc ctantatgaa gaacttttgg antggaatta aatcaatngc ttggccggaa 720gtcattanga nggctnaaaa ggccctgtta ngggtctggg ctnggtttta cccnacccat 780ggaatncncc ccccggacna ntgnatccct attcttaa 818
<210> 7
<211> 817
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(817)
<223> n = A,T,C or G
<400> 7tttttttttt tttttttttt tggctctaga gggggtagag ggggtgctat agggtaaata 60cgggccctat ttcaaagatt tttaggggaa ttaattctag gacgatgggt atgaaactgt 120ggtttgctcc acagatttca gagcattgac cgtagtatac ccccggtcgt gtagcggtga 180aagtggtttg gtttagacgt ccgggaattg catctgtttt taagcctaat gtgggacag 240ctcatgagtg caagacgtct tgtgatgtaa ttattatacn aatgggggct tcaatcggga 300gtactactcg attgtcaacg tcaaggagtc gcaggtcgcc tggttctagg aataatgggg 360gaagtatgta ggaattgaag attaatccgc cgtagtcggt gttctcctag gttcaatacc 420attggtggcc aattgatttg atggtaaggg gagggatcgt tgaactcgtc tgttatgtaa 480aggatncctt ngggatggga aggcnatnaa ggactangga tnaatggcgg gcangatatt 540tcaaacngtc tctanttcct gaaacgtctg aaatgttaat aanaattaan tttngttatt 600gaatnttnng gaaaagggct tacaggacta gaaaccaaat angaaaanta atnntaangg 660cnttatcntn aaaggtnata accnctccta tnatcccacc caatngnatt ccccacncnn 720acnattggat nccccanttc canaaanggc cnccccccgg tgnannccnc cttttgttcc 780cttnantgan ggttattcnc ccctngcntt atcancc 817
<210> 8
<211> 799
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (799)
<223> n = A,T,C or G
<400> 8catttccggg tttactttct aaggaaagcc gagcggaagc tgctaacgtg ggaatcggtg 60cataaggaga actttctgct ggcacgcgct agggacaagc gggagagcga ctccgagcgt 120ctgaagcgca cgtcccagaa ggtggacttg gcactgaaac agctgggaca catccgcgag 180tacgaacagc gcctgaaagt gctggagcgg gaggtccagc agtgtagccg cgtcctgggg 240tgggtggccg angcctganc cgctctgcct tgctgccccc angtgggccg ccaccccctg 300acctgcctgg gtccaaacac tgagccctgc tggcggactt caagganaac ccccacangg 360ggattttgct cctanantaa ggctcatctg ggcctcggcc cccccacctg gttggccttg 420tctttgangt gagccccatg tccatctggg ccactgtcng gaccaccttt ngggagtgtt 480ctccttacaa ccacannatg cccggctcct cccggaaacc antcccancc tgngaaggat 540caagncctgn atccactnnt nctanaaccg gccnccnccg cngtggaacc cnccttntgt 600tccttttcnt tnagggttaa tnncgccttg gccttnccan ngtcctncnc nttttccnnt 660gttnaaattg ttangcnccc nccnntcccn cnncnncnan cccgacccnn annttnnann 720ncctgggggt nccnncngat tgacccnncc nccctntant tgcnttnggg nncnntgccc 780ctttccctct nggganncg 799
<210> 9
<211> 801
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(801)
<223> n = A,T,C or G
<400> 9acgccttgat cctcccaggc tgggactggt tctgggagga gccgggcatg ctgtggtttg 60taangatgac actcccaaag gtggtcctga cagtggccca gatggacatg gggctcacct 120caaggacaag gccaccaggt gcgggggccg aagcccacat gatccttact ctatgagcaa 180aatcccctgt gggggcttct ccttgaagtc cgccancagg gctcagtctt tggacccang 240caggtcatgg ggttgtngnc caactggggg ccncaacgca aaanggcnca gggcctcngn 300cacccatccc angacgcggc tacactnctg gacctcccnc tccaccactt tcatgcgctg 360ttcntacccg cgnatntgtc ccanctgttt cngtgccnac tccancttct nggacgtgcg 420ctacatacgc ccggantcnc nctcccgctt tgtccctatc cacgtnccan caacaaattt 480cnccntantg caccnattcc cacntttnnc agntttccnc nncgngcttc cttntaaaag 540ggttganccc cggaaaatnc cccaaagggg gggggccngg tacccaactn ccccctnata 600gctgaantcc ccatnaccnn gnctcnatgg anccntccnt tttaannacn ttctnaactt 660gggaanancc ctcgnccntn cccccnttaa tcccnccttg cnangnncnt cccccnntcc 720ncccnnntng gcntntnann cnaaaaaggc ccnnnancaa tctcctnncn cctcanttcg 780ccanccctcg aaatcggccn c 801
<210> 10
<211> 789
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(789)
<223> n = A,T,C or G
<400> 10cagtctatnt ggccagtgtg gcagctttcc ctgtggctgc cggtgccaca tgcctgtccc 60acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg gttcaccttc tcagccctgc 120agatcctgcc ctacacactg gcctccctct accaccggga gaagcaggtg ttcctgccca 180aataccgagg ggacactgga ggtgctagca gtgaggacag cctgatgacc agcttcctgc 240caggccctaa gcctggagct cccttcccta atggacacgt gggtgctgga ggcagtggcc 300tgctcccacc tccacccgcg ctctgcgggg cctctgcctg tgatgtctcc gtacgtgtgg 360tggtgggtga gcccaccgan gccagggtgg ttccgggccg gggcatctgc ctggacctcg 420ccatcctgga tagtgcttcc tgctgtccca ngtggcccca tccctgttta tgggctccat 480tgtccagctc agccagtctg tcactgccta tatggtgtct gccgcaggcc tgggtctggt 540cccatttact ttgctacaca ggtantattt gacaagaacg anttggccaa atactcagcg 600ttaaaaaatt ccagcaacat tgggggtgga aggcctgcct cactgggtcc aactccccgc 660tcctgttaac cccatggggc tgccggcttg gccgccaatt tctgttgctg ccaaantnat 720gtggctctct gctgccacct gttgctggct gaagtgcnta cngcncanct nggggggtng 780ggngttccc 789
<210> 11
<211> 772
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(772)
<223> n = A,T,C or G
<400> 11cccaccctac ccaaatatta gacaccaaca cagaaaagct agcaatggat tcccttctac 60tttgttaaat aaataagtta aatatttaaa tgcctgtgtc tctgtgatgg caacagaag 120accaacaggc cacatcctga taaaaggtaa gaggggggtg gatcagcaaa aagacagtgc 180tgtgggctga ggggacctgg ttcttgtgtg ttgcccctca ggactcttcc cctacaaata 240actttcatat gttcaaatcc catggaggag tgtttcatcc tagaaactcc catgcaagag 300ctacattaaa cgaagctgca ggttaagggg cttanagatg ggaaaccagg tgactgagtt 360tattcagctc ccaaaaaccc ttctctaggt gtgtctcaac taggaggcta gctgttaacc 420ctgagcctgg gtaatccacc tgcagagtcc ccgcattcca gtgcatggaa cccttctggc 480ctccctgtat aagtccagac tgaaaccccc ttggaaggnc tccagtcagg cagccctana 540aactggggaa aaaagaaaag gacgccccan cccccagctg tgcanctacg cacctcaaca 600gcacagggtg gcagcaaaaa aaccacttta ctttggcaca aacaaaaact ngggggggca 660accccggcac cccnangggg gttaacagga ancngggnaa cntggaaccc aattnaggca 720ggcccnccac cccnaatntt gctgggaaat ttttcctccc ctaaattntt tc 772
<210> 12
<211> 751
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (751)
<223> n = A,T,C or G
<400> 12gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa 60agctgattga agcaaccctc tactttttgg tcgtgagcct tttgcttggt gcaggtttca 120ttggctgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg 180aagtanggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatcttt cttgatggca 300ggcactacca gcaacgtcag ggaagtgctc agccattgtg gtgtacacca aggcgaccac 360agcagctgcn acctcagcaa tgaagatgan gaggangatg aagaagaacg tcncgagggc 420acacttgctc tcagtcttan caccatanca gcccntgaaa accaananca aagaccacna 480cnccggctgc gatgaagaaa tnaccccncg ttgacaaact tgcatggcac tggganccac 540agtggcccna aaaatcttca aaaaggatgc cccatcnatt gaccccccaa atgcccactg 600ccaacagggg ctgccccacn cncnnaacga tganccnatt gnacaagatc tncntggtct 660tnatnaacnt gaaccctgcn tngtggctcc tgttcaggnc cnnggcctga cttctnaann 720aangaactcn gaagncccca cngganannc g 751
<210> 13
<211> 729
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(729)
<223> n = A,T,C or G
<400> 13gagccaggcg tccctctgcc tgcccactca gtggcaacac ccgggagctg ttttgtcctt 60tgtggancct cagcagtncc ctctttcaga actcantgcc aaganccctg aacaggagcc 120accatgcagt gcttcagctt cattaagacc atgatgatcc tcttcaattt gctcatcttt 180ctgtgtggtg cagccctgtt ggcagtgggc atctgggtgt caatcgatgg ggcatccttt 240ctgaagatct tcgggccact gtcgtccagt gccatgcagt ttgtcaacgt gggctacttc 300ctcatcgcag ccggcgttgt ggtcttagct ctaggtttcc tgggctgcta tggtgctaag 360actgagagca agtgtgccct cgtgacgttc ttcttcatcc tcctcctcat cttcattgct 420gaggttgcaa tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt 480tgctggtaat gcctgccatc aanaaaagat tatgggttcc caggaanact tcactcaagt 540gttggaacac caccatgaaa gggctcaagt gctgtggctt cnnccaacta tacggatttt 600gaagantcac ctacttcaaa gaaaanagtg cctttccccc atttctgttg caattgacaa 660acgtccccaa cacagccaat tgaaaacctg cacccaaccc aaangggtcc ccaaccanaa 720attnaaggg 729
<210> 14
<211> 816
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (816)
<223> n = A,T,C or G
<400> 14tgctcttcct caaagttgtt cttgttgcca taacaaccac cataggtaaa gcgggcgcag 60tgttcgctga aggggttgta gtaccagcgc gggatgctct ccttgcagag tcctgtgtct 120ggcaggtcca cgcagtgccc tttgtcactg gggaaatgga tgcgctggag ctcgtcaaag 180ccactcgtgt atttttcaca ggcagcctcg tccgacgcgt cggggcagtt gggggtgtct 240tcacactcca ggaaactgtc natgcagcag ccattgctgc agcggaactg ggtgggctga 300cangtgccag agcacactgg atggcgcctt tccatgnnan gggccctgng ggaaagtccc 360tganccccan anctgcctct caaangcccc accttgcaca ccccgacagg ctagaatgga 420atcttcttcc cgaaaggtag ttnttcttgt tgcccaancc anccccntaa acaaactctt 480gcanatctgc tccgnggggg tcntantacc ancgtgggaa aagaacccca ggcngcgaac 540caancttgtt tggatncgaa gcnataatct nctnttctgc ttggtggaca gcaccantna 600ctgtnnanct ttagnccntg gtcctcntgg gttgnncttg aacctaatcn ccnntcaact 660gggacaaggt aantngccnt cctttnaatt cccnancntn ccccctggtt tggggttttn 720cncnctccta ccccagaaan nccgtgttcc cccccaacta ggggccnaaa ccnnttnttc 780cacaaccctn ccccacccac gggttcngnt ggttng 816
<210> 15
<211> 783
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (783)
<223> n = A,T,C or G
<400> 15ccaaggcctg ggcaggcata nacttgaagg tacaacccca ggaacccctg gtgctgaagg 60atgtggaaaa cacagattgg cgcctactgc ggggtgacac ggatgtcagg gtagagagga 120aagacccaaa ccaggtggaa ctgtggggac tcaaggaang cacctacctg ttccagctga 180cagtgactag ctcagaccac ccagaggaca cggccaacgt cacagtcact gtgctgtcca 240ccaagcagac agaagactac tgcctcgcat ccaacaangt gggtcgctgc cggggctctt 300tcccacgctg gtactatgac cccacggagc agatctgcaa gagtttcgtt tatggaggct 360gcttgggcaa caagaacaac taccttcggg aagaagagtg cattctancc tgtcngggtg 420tgcaaggtgg gcctttgana ngcanctctg gggctcangc gactttcccc cagggcccct 480ccatggaaag gcgccatcca ntgttctctg gcacctgtca gcccacccag ttccgctgca 540ncaatggctg ctgcatcnac antttcctng aattgtgaca acacccccca ntgcccccaa 600ccctcccaac aaagcttccc tgttnaaaaatacnccantt ggcttttnac aaacncccgg 660cncctccntt ttccccnntn aacaaagggc nctngcnttt gaactgcccn aacccnggaa 720tctnccnngg aaaaantncc ccccctggtt cctnnaancc cctccncnaa anctnccccc 780ccc 783
<210> 16
<211> 801
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (801)
<223> n = A,T,C or G
<400> 16gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa 60agctgattga agcaaccctc tactttttgg tcgtgagcct tttgcttggt gcaggtttca 120ttggctgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg 180aagtagggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatcttt cttgatggca 300ggcactacca gcaacgtcag gaagtgctca gccattgtgg tgtacaccaa ggcgaccaca 360gcagctgcaa cctcagcaat gaagatgagg aggaggatga agaagaacgt cncgagggca 420cacttgctct ccgtcttagc accatagcag cccangaaac caagagcaaa gaccacaacg 480ccngctgcga atgaaagaaa ncacccacgt tgacaaactg catggccact ggacgacagt 540tggcccgaan atcttcagaa aagggatgcc ccatcgattg aacacccana tgcccactgc 600cnacagggct gcnccncncn gaaagaatga gccattgaag aaggatcntc ntggtcttaa 660tgaactgaaa ccntgcatgg tggcccctgt tcagggctct tggcagtgaa ttctganaaa 720aaggaacngc ntnagccccc ccaaangana aaacaccccc gggtgttgcc ctgaattggc 780ggccaaggan ccctgccccn g 801
<210> 17
<211> 740
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (740)
<223> n = A,T,C or G
<400> 17gtgagagcca ggcgtccctc tgcctgccca ctcagtggca acacccggga gctgttttgt 60cctttgtgga gcctcagcag ttccctcttt cagaactcac tgccaagagc cctgaacagg 120agccaccatg cagtgcttca gcttcattaa gaccatgatg atcctcttca atttgctcat 180ctttctgtgt ggtgcagccc tgttggcagt gggcatctgg gtgtcaatcg atggggcatc 240ctttctgaag atcttcgggc cactgtcgtc cagtgccatg cagtttgtca acgtgggcta 300cttcctcatc gcagccggcg ttgtggtctt tgctcttggt ttcctgggct gctatggtgc 360taagacggag agcaagtgtg ccctcgtgac gttcttcttc atcctcctcc tcatcttcat 420tgctgaagtt gcagctgctg tggtcgcctt ggtgtacacc acaatggctg aaccattcct 480gacgttgctg gtantgcctg ccatcaanaa agattatggg ttcccaggaa aaattcactc 540aantntggaa caccnccatg aaaagggctc caatttctgn tggcttcccc aactataccg 600gaattttgaa agantcnccc tacttccaaa aaaaaanant tgcctttncc cccnttctgt 660tgcaatgaaa acntcccaan acngccaatn aaaacctgcc cnnncaaaaa ggntcncaaa 720caaaaaaant nnaagggttn 740
<210> 18
<211> 802
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(802)
<223> n = A,T,C or G
<400> 18ccgctggttg cgctggtcca gngnagccac gaagcacgtc agcatacaca gcctcaatca 60caaggtcttc cagctgccgc acattacgca gggcaagagc ctccagcaac actgcatatg 120ggatacactt tactttagca gccagggtga caactgagag gtgtcgaagc ttattcttct 180gagcctctgt tagtggagga agattccggg cttcagctaa gtagtcagcg tatgtcccat 240aagcaaacac tgtgagcagc cggaaggtag aggcaaagtc actctcagcc agctctctaa 300cattgggcat gtccagcagt tctccaaaca cgtagacacc agnggcctcc agcacctgat 360ggatgagtgt ggccagcgct gcccccttgg ccgacttggc taggagcaga aattgctcct 420ggttctgccc tgtcaccttc acttccgcac tcatcactgc actgagtgtg ggggacttgg 480gctcaggatg tccagagacg tggttccgcc ccctcnctta atgacaccgn ccanncaacc 540gtcggctccc gccgantgng ttcgtcgtnc ctgggtcagg gtctgctggc cnctacttgc 600aancttcgtc nggcccatgg aattcaccnc accggaactn gtangatcca ctnnttctat 660aaccggncgc caccgcnnnt ggaactccac tcttnttncc tttacttgag ggttaaggtc 720acccttnncg ttaccttggt ccaaaccntn ccntgtgtcg anatngtnaa tcnggnccna 780tnccanccnc atangaagcc ng 802
<210> 19
<211> 731
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(731)
<223> n = A,T,C or G
<400> 19cnaagcttcc aggtnacggg ccgcnaancc tgacccnagg tancanaang cagncngcgg 60gagcccaccg tcacgnggng gngtctttat nggagggggc ggagccacat cnctggacnt 120cntgacccca actccccncc ncncantgca gtgatgagtg cagaactgaa ggtnacgtgg 180caggaaccaa gancaaannc tgctccnntc caagtcggcn nagggggcgg ggctggccac 240gcncatccnt cnagtgctgn aaagccccnn cctgtctact tgtttggaga acngcnnnga 300catgcccagn gttanataac nggcngagag tnantttgcc tctcccttcc ggctgcgcan 360cgngtntgct tagnggacat aacctgacta cttaactgaa cccnngaatc tnccncccct 420ccactaagct cagaacaaaa aacttcgaca ccactcantt gtcacctgnc tgctcaagta 480aagtgtaccc catncccaat gtntgctnga ngctctgncc tgcnttangt tcggtcctgg 540gaagacctat caattnaagc tatgtttctg actgcctctt gctccctgna acaancnacc 600cnncnntcca agggggggnc ggcccccaat ccccccaacc ntnaattnan tttanccccn 660cccccnggcc cggcctttta cnancntcnn nnacngggna aaaccnnngc tttncccaac 720nnaatccncc t 731
<210> 20
<211> 754
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(754)
<223> n = A,T,C or G
<400> 20tttttttttt tttttttttt taaaaacccc ctccattnaa tgnaaacttc cgaaattgtc 60caaccccctc ntccaaatnn ccntttccgg gngggggttc caaacccaan ttanntttgg 120annttaaatt aaatnttnnt tggnggnnna anccnaatgt nangaaagtt naacccanta 180tnancttnaa tncctggaaa ccngtngntt ccaaaaatnt ttaaccctta antccctccg 240aaatngttna nggaaaaccc aanttctcnt aaggttgttt gaaggntnaa tnaaaanccc 300nnccaattgt ttttngccac gcctgaatta attggnttcc gntgttttcc nttaaaanaa 360ggnnancccc ggttantnaa tccccccnnc cccaattata ccganttttt ttngaattgg 420gancccncgg gaattaacgg ggnnnntccc tnttgggggg cnggnncccc ccccntcggg 480ggttngggnc aggncnnaat tgtttaaggg tccgaaaaat ccctccnaga aaaaaanctc 540ccaggntgag nntngggttt nccccccccc canggcccct ctcgnanagt tggggtttgg 600ggggcctggg attttntttc ccctnttncc tccccccccc ccnggganag aggttngngt 660tttgntcnnc ggccccnccn aaganctttn ccganttnan ttaaatccnt gcctnggcga 720agtccnttgn agggntaaan ggccccctnn cggg 754
<210> 21
<211> 755
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(755)
<223> n = A,T,C or G
<400> 21atcancccat gaccccnaac nngggaccnc tcanccggnc nnncnaccnc cggccnatca 60nngtnagnnc actncnnttn natcacnccc cnccnactac gcccncnanc cnacgcncta 120nncanatncc actganngcg cgangtngan ngagaaanct nataccanag ncaccanacn 180ccagctgtcc nanaangcct nnnatacngg nnnatccaat ntgnancctc cnaagtattn 240nncnncanat gattttcctn anccgattac ccntnccccc tancccctcc cccccaacna 300cgaaggcnct ggnccnaagg nngcgncncc ccgctagntc cccnncaagt cncncnccta 360aactcanccn nattacncgc ttcntgagta tcactccccg aatctcaccc tactcaactc 420aaaaanatcn gatacaaaat aatncaagcc tgnttatnac actntgactg ggtctctatt 480ttagnggtcc ntnaancntc ctaatacttc cagtctncct tcnccaattt ccnaanggct 540ctttcngaca gcatnttttg gttcccnntt gggttcttan ngaattgccc ttcntngaac 600gggctcntct tttccttcgg ttancctggn ttcnnccggc cagttattat ttcccntttt 660aaattcntnc cntttanttt tggcnttcna aacccccggc cttgaaaacg gccccctggt 720aaaaggttgt tttganaaaa tttttgtttt gttcc 755
<210> 22
<211> 849
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(849)
<223> n = A,T,C or G
<400> 22tttttttttt tttttangtg tngtcgtgca ggtagaggct tactacaant gtgaanacgt 60acgctnggan taangcgacc cganttctag ganncnccct aaaatcanac tgtgaagatn 120atcctgnnna cggaanggtc accggnngat nntgctaggg tgnccnctcc cannncnttn 180cataactcng nggccctgcc caccaccttc ggcggcccng ngnccgggcc cgggtcattn 240gnnttaaccn cactnngcna ncggtttccn nccccnncng acccnggcga tccggggtnc 300tctgtcttcc cctgnagncn anaaantggg ccncggnccc ctttacccct nnacaagcca 360cngccntcta nccncngccc cccctccant nngggggact gccnanngct ccgttnctng 420nnaccccnnn gggtncctcg gttgtcgant cnaccgnang ccanggattc cnaaggaagg 480tgcgttnttg gcccctaccc ttcgctncgg nncacccttc ccgacnanga nccgctcccg 540cncnncgnng cctcncctcg caacacccgc nctcntcngt ncggnnnccc ccccacccgc 600nccctcncnc ngncgnancn ctccnccncc gtctcannca ccaccccgcc ccgccaggcc 660ntcanccacn ggnngacnng nagcncnntc gcnccgcgcn gcgncnccct cgccncngaa 720ctncntcngg ccantnncgc tcaanccnna cnaaacgccg ctgcgcggcc cgnagcgncc 780ncctccncga gtcctcccgn cttccnaccc angnnttccn cgaggacacn nnaccccgcc 840nncangcgg 849
<210> 23
<211> 872
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(872)
<223> n = A,T,C or G
<400> 23gcgcaaacta tacttcgctc gnactcgtgc gcctcgctnc tcttttcctc cgcaaccatg 60tctgacnanc ccgattnggc ngatatcnan aagntcganc agtccaaact gantaacaca 120cacacncnan aganaaatcc nctgccttcc anagtanacn attgaacnng agaaccangc 180nggcgaatcg taatnaggcg tgcgccgcca atntgtcncc gtttattntn ccagcntcnc 240ctnccnaccc tacntcttcn nagctgtcnn acccctngtn cgnacccccc naggtcggga 300tcgggtttnn nntgaccgng cnncccctcc ccccntccat nacganccnc ccgcaccacc 360nanngcncgc nccccgnnct cttcgccncc ctgtcctntn cccctgtngc ctggcncngn 420accgcattga ccctcgccnn ctncnngaaa ncgnanacgt ccgggttgnn annancgctg 480tgggnnngcg tctgcnccgc gttccttccn ncnncttcca ccatcttcnt tacngggtct 540ccncgccntc tcnnncacnc cctgggacgc tntcctntgc cccccttnac tccccccctt 600cgncgtgncc cgnccccacc ntcatttnca nacgntcttc acaannncct ggntnnctcc 660cnancngncn gtcanccnag ggaagggngg ggnnccnntg nttgacgttg nggngangtc 720cgaanantcc tcnccntcan cnctacccct cgggcgnnct ctcngttncc aacttancaa 780ntctcccccg ngngcncntc tcagcctcnc ccnccccnct ctctgcantg tnctctgctc 840tnaccnntac gantnttcgn cnccctcttt cc 872
<210> 24
<211> 815
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(815)
<223> n = A,T,C or G
<400> 24gcatgcaagc ttgagtattc tatagngtca cctaaatanc ttggcntaat catggtcnta 60nctgncttcc tgtgtcaaat gtatacnaan tanatatgaa tctnatntga caaganngta 120tcntncatta gtaacaantg tnntgtccat cctgtcngan canattccca tnnattncgn 180cgcattcncn gcncantatn taatngggaa ntcnnntnnn ncaccnncat ctatcntncc 240gcnccctgac tggnagagat ggatnanttc tnntntgacc nacatgttca tcttggattn 300aananccccc cgcngnccac cggttngnng cnagccnntc ccaagacctc ctgtggaggt 360aacctgcgtc aganncatca aacntgggaa acccgcnncc angtnnaagt ngnnncanan 420gatcccgtcc aggnttnacc atcccttcnc agcgccccct ttngtgcctt anagngnagc 480gtgtccnanc cnctcaacat ganacgcgcc agnccanccg caattnggca caatgtcgnc 540gaacccccta gggggantna tncaaanccc caggattgtc cncncangaa atcccncanc 600cccnccctac ccnnctttgg gacngtgacc aantcccgga gtnccagtcc ggccngnctc 660ccccaccggt nnccntgggg gggtgaanct cngnntcanc cngncgaggn ntcgnaagga 720accggncctn ggncgaanng ancnntcnga agngccncnt cgtataaccc cccctcncca 780nccnacngnt agntcccccc cngggtncgg aangg 815
<210> 25
<211> 775
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(775)
<223> n = A,T,C or G
<400> 25ccgagatgtc tcgctccgtg gccttagctg tgctcgcgct actctctctt tctggcctgg 60aggctatcca gcgtactcca aagattcagg tttactcacg tcatccagca gagaatggaa 120agtcaaattt cctgaattgc tatgtgtctg ggtttcatcc atccgacatt gaanttgact 180tactgaagaa tgganagaga attgaaaaag tggagcattc agacttgtct ttcagcaagg 240actggtcttt ctatctcntg tactacactg aattcacccc cactgaaaaa gatgagtatg 300cctgccgtgt gaaccatgtg actttgtcac agcccaagat agttaagtgg gatcgagaca 360tgtaagcagn cnncatggaa gtttgaagat gccgcatttg gattggatga attccaaatt 420ctgcttgctt gcnttttaat antgatatgc ntatacaccc taccctttat gnccccaaat 480tgtaggggtt acatnantgt tcncntngga catgatcttc ctttataant ccnccnttcg 540aattgcccgt cncccngttn ngaatgtttc cnnaaccacg gttggctccc ccaggtcncc 600tcttacggaa gggcctgggc cnctttncaa ggttggggga accnaaaatt tcncttntgc 660ccncccncca cnntcttgng nncncanttt ggaacccttc cnattcccct tggcctcnna 720nccttnncta anaaaacttn aaancgtngc naaanntttn acttcccccc ttacc 775
<210> 26
<211> 820
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(820)
<223> n = A,T,C or G
<400> 26anattantac agtgtaatct tttcccagag gtgtgtanag ggaacggggc ctagaggcat 60cccanagata ncttatanca acagtgcttt gaccaagagc tgctgggcac atttcctgca 120gaaaaggtgg cggtccccat cactcctcct ctcccatagc catcccagag gggtgagtag 180ccatcangcc ttcggtggga gggagtcang gaaacaacan accacagagc anacagacca 240ntgatgacca tgggcgggag cgagcctctt ccctgnaccg gggtggcana nganagccta 300nctgaggggt cacactataa acgttaacga ccnagatnan cacctgcttc aagtgcaccc 360ttcctacctg acnaccagng accnnnaact gcngcctggg gacagcnctg ggancagcta 420acnnagcact cacctgcccc cccatggccg tncgcntccc tggtcctgnc aagggaagct 480ccctgttgga attncgggga naccaaggga nccccctcct ccanctgtga aggaaaaann 540gatggaattt tncccttccg gccnntcccc tcttccttta cacgccccct nntactcntc 600tccctctntt ntcctgncnc acttttnacc ccnnnatttc ccttnattga tcggannctn 660ganattccac tnncgcctnc cntcnatcng naanacnaaa nactntctna cccnggggat 720gggnncctcg ntcatcctct ctttttcnct accnccnntt ctttgcctct ccttngatca780tccaaccntc gntggccntn cccccccnnn tcctttnccc820
<210> 27
<211> 818
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(818)
<223> n = A,T,C or G
<400> 27tctgggtgat ggcctcttcc tcctcaggga cctctgactg ctctgggcca aagaatctct 60tgtttcttct ccgagcccca ggcagcggtg attcagccct gcccaacctg attctgatga 120ctgcggatgc tgtgacggac ccaaggggca aatagggtcc cagggtccag ggaggggcgc 180ctgctgagca cttccgcccc tcaccctgcc cagcccctgc catgagctct gggctgggtc 240tccgcctcca gggttctgct cttccangca ngccancaag tggcgctggg ccacactggc 300ttcttcctgc cccntccctg gctctgantc tctgtcttcc tgtcctgtgc angcnccttg 360gatctcagtt tccctcnctc anngaactct gtttctgann tcttcantta actntgantt 420tatnaccnan tggnctgtnc tgtcnnactt taatgggccn gaccggctaa tccctccctc 480nctcccttcc anttcnnnna accngcttnc cntcntctcc ccntancccg ccngggaanc 540ctcctttgcc ctnaccangg gccnnnaccg cccntnnctn ggggggcnng gtnnctncnc 600ctgntnnccc cnctcncnnt tncctcgtcc cnncnncgcn nngcannttc ncngtcccnn 660tnnctcttcn ngtntcgnaa ngntcncntn tnnnnngncn ngntnntncn tccctctcnc 720cnnntgnang tnnttnnnnc ncngnncccc nnnncnnnnn nggnnntnnn tctncncngc 780cccnnccccc ngnattaagg cctccnntct ccggccnc 818
<210> 28
<211> 731
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (731)
<223> n = A,T,C or G
<400> 28aggaagggcg gagggatatt gtangggatt gagggatagg agnataangg gggaggtgtg 60tcccaacatg anggtgnngt tctcttttga angagggttg ngtttttann ccnggtgggt 120gattnaaccc cattgtatgg agnnaaaggn tttnagggat ttttcggctc ttatcagtat 180ntanattcct gtnaatcgga aaatnatntt tcnncnggaa aatnttgctc ccatccgnaa 240attnctcccg ggtagtgcat nttngggggn cngccangtt tcccaggctg ctanaatcgt 300actaaagntt naagtgggan tncaaatgaa aacctnncac agagnatccn tacccgactg 360tnnnttncct tcgccctntg actctgcnng agcccaatac ccnngngnat gtcncccngn 420nnngcgncnc tgaaannnnc tcgnggctnn gancatcang gggtttcgca tcaaaagcnn 480cgtttcncat naaggcactt tngcctcatc caaccnctng ccctcnncca tttngccgtc 540nggttcncct acgctnntng cncctnnntn ganattttnc ccgcctnggg naancctcct 600gnaacgggta gggncttntc ttttnaccnn gnggtntact aatcnnctnc acgcntnctt 660tctcnacccc cccccttttt caatcccanc ggcnaatggg gtctccccnn cgangggggg 720nnncccannc c 731
<210> 29
<211> 822
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(822)
<223> n = A,T,C or G
<400> 29actagtccag tgtggtggaa ttccattgtg ttggggncnc ttctatgant antnttagat 60cgctcanacc tcacancctc ccnacnangc ctataangaa nannaataga nctgtncnnt 120atntntacnc tcatanncct cnnnacccac tccctcttaa cccntactgt gcctatngcn 180tnnctantct ntgccgcctn cnanccaccn gtgggccnac cncnngnatt ctcnatctcc 240tcnccatntn gcctananta ngtncatacc ctatacctac nccaatgcta nnnctaancn 300tccatnantt annntaacta ccactgacnt ngactttcnc atnanctcct aatttgaatc 360tactctgact cccacngcct annnattagc ancntccccc nacnatntct caaccaaatc 420ntcaacaacc tatctanctg ttcnccaacc nttncctccg atccccnnac aacccccctc 480ccaaataccc nccacctgac ncctaacccn caccatcccg gcaagccnan ggncatttan 540ccactggaat cacnatngganaaaaaaaac ccnaactctc tancncnnat ctccctaana 600aatnctcctn naatttactn ncantnccat caancccacn tgaaacnnaa cccctgtttt 660tanatccctt ctttcgaaaa ccnacccttt annncccaac ctttngggcc cccccnctnc 720ccnaatgaag gncncccaat cnangaaacg nccntgaaaa ancnaggcna anannntccg 780canatcctat cccttanttn ggggnccctt ncccngggcc cc 822
<210> 30
<211> 787
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(787)
<223> n = A,T,C or G
<400> 30cggccgcctg ctctggcaca tgcctcctga atggcatcaa aagtgatgga ctgcccattg 60ctagagaaga ccttctctcc tactgtcatt atggagccct gcagactgag ggctcccctt 120gtctgcagga tttgatgtct gaagtcgtgg agtgtggctt ggagctcctc atctacatna 180gctggaagcc ctggagggcc tctctcgcca gcctccccct tctctccacg ctctccangg 240acaccagggg ctccaggcag cccattattc ccagnangac atggtgtttc tccacgcgga 300cccatggggc ctgnaaggcc agggtctcct ttgacaccat ctctcccgtc ctgcctggca 360ggccgtggga tccactantt ctanaacggn cgccaccncg gtgggagctc cagcttttgt 420tcccnttaat gaaggttaat tgcncgcttg gcgtaatcat nggtcanaac tntttcctgt 480gtgaaattgt ttntcccctc ncnattccnc ncnacatacn aacccggaan cataaagtgt 540taaagcctgg gggtngcctn nngaatnaac tnaactcaat taattgcgtt ggctcatggc 600ccgctttccn ttcnggaaaa ctgtcntccc ctgcnttnnt gaatcggcca ccccccnggg 660aaaagcggtt tgcnttttng ggggntcctt ccncttcccc cctcnctaan ccctncgcct 720cggtcgttnc nggtngcggg gaangggnat nnnctcccnc naagggggng agnnngntat 780ccccaaa 787
<210> 31
<211> 799
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (799)
<223> n = A,T,C or G
<400> 31tttttttttt tttttttggc gatgctactg tttaattgca ggaggtgggg gtgtgtgtac 60catgtaccag ggctattaga agcaagaagg aaggagggag ggcagagcgc cctgctgagc 120aacaaaggac tcctgcagcc ttctctgtct gtctcttggc gcaggcacat ggggaggcct 180cccgcagggt gggggccacc agtccagggg tgggagcact acanggggtg ggagtgggtg 240gtggctggtn cnaatggcct gncacanatc cctacgattc ttgacacctg gatttcacca 300ggggaccttc tgttctccca nggnaacttc ntnnatctcn aaagaacaca actgtttctt 360cngcanttct ggctgttcat ggaaagcaca ggtgtccnat ttnggctggg acttggtaca 420tatggttccg gcccacctct cccntcnaan aagtaattca cccccccccn ccntctnttg 480cctgggccct taantaccca caccggaact canttantta ttcatcttng gntgggcttg 540ntnatcnccn cctgaangcg ccaagttgaa aggccacgcc gtncccnctc cccatagnan 600nttttnncnt canctaatgc ccccccnggc aacnatccaa tccccccccn tgggggcccc 660agcccanggc ccccgnctcg ggnnnccngn cncgnantcc ccaggntctc ccantcngnc 720ccnnngcncc cccgcacgca gaacanaagg ntngagccnc cgcannnnnn nggtnncnac 780ctcgcccccc ccnncgnng 799
<210> 32
<211> 789
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(789)
<223> n = A,T,C or G
<400> 32tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60ttttnccnag ggcaggttta ttgacaacct cncgggacac aancaggctg gggacaggac 120ggcaacaggc tccggcggcg gcggcggcgg ccctacctgc ggtaccaaat ntgcagcctc 180cgctcccgct tgatnttcct ctgcagctgc aggatgccnt aaaacagggc ctcggccntn 240ggtgggcacc ctgggatttn aatttccacg ggcacaatgc ggtcgcancc cctcaccacc 300nattaggaat agtggtntta cccnccnccg ttggcncact ccccntggaa accacttntc 360gcggctccgg catctggtct taaaccttgc aaacnctggg gccctctttt tggttantnt 420nccngccaca atcatnactc agacggcnc gggctggccc caaaaaancn ccccaaaacc 480ggnccatgtc ttnncggggt tgctgcnatn tncatcacct cccgggcnca ncaggncaac 540ccaaaagttc ttgnggcccn caaaaaanct ccggggggnc ccagtttcaa caaagtcatc 600ccccttggcc cccaaatcct ccccccgntt nctgggtttg ggaacccacg cctctnnctt 660tggnnggcaa gntggntccc ccttcgggcc cccggtgggc ccnnctctaa ngaaaacncc 720ntcctnnnca ccatcccccc nngnnacgnc tancaangna tccctttttt tanaaacggg 780ccccccncg 789
<210> 33
<211> 793
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(793)
<223> n = A,T,C or G
<400> 33gacagaacat gttggatggt ggagcacctt tctatacgac ttacaggaca gcagatgggg 60aattcatggc tgttggagca atanaacccc agttctacga gctgctgatc aaaggacttg 120gactaaagtc tgatgaactt cccaatcaga tgagcatgga tgattggcca gaaatgaana 180agaagtttgc agatgtattt gcaaagaaga cgaaggcaga gtggtgtcaa atctttgacg 240gcacagatgc ctgtgtgact ccggttctga cttttgagga ggttgttcat catgatcaca 300acaangaacg gggctcgttt atcaccantg aggagcagga cgtgagcccc cgccctgcac 360ctctgctgtt aaacacccca gccatccctt ctttcaaaag ggatccacta cttctagagc 420ggncgccacc gcggtggagc tccagctttt gttcccttta gtgagggtta attgcgcgct 480tggcgtaatc atggtcatan ctgtttcctg tgtgaaattg ttatccgctc acaattccac 540acaacatacg anccggaagc atnaaatttt aaagcctggn ggtngcctaa tgantgaact 600nactcacatt aattggcttt gcgctcactg cccgctttcc agtccggaaa acctgtcctt 660gccagctgcc nttaatgaat cnggccaccc cccggggaaa aggcngtttg cttnttgggg 720cgcncttccc gctttctcgc ttcctgaant ccttcccccc ggtctttcgg cttgcggcna 780acggtatcna cct 793
<210> 34
<211> 756
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(756)
<223> n = A,T,C or G
<400> 34gccgcgaccg gcatgtacga gcaactcaag ggcgagtgga accgtaaaag ccccaatctt 60ancaagtgcg gggaanagct gggtcgactc aagctagttc ttctggagct caacttcttg 120ccaaccacag ggaccaagct gaccaaacag cagctaattc tggcccgtga catactggag 180atcggggccc aatggagcat cctacgcaan gacatcccct ccttcgagcg ctacatggcc 240cagctcaaat gctactactt tgattacaan gagcagctcc ccgagtcagc ctatatgcac 300cagctcttgg gcctcaacct cctcttcctg ctgtcccaga accgggtggc tgantnccac 360acgganttgg ancggctgcc tgcccaanga catacanacc aatgtctaca tcnaccacca 420gtgtcctgga gcaatactga tgganggcag ctaccncaaa gtnttcctgg ccnagggtaa 480catcccccgc cgagagctac accttcttca ttgacatcct gctcgacact atcagggatg 540aaaatcgcng ggttgctcca gaaaggctnc aanaanatcc ttttcnctga aggcccccgg 600atncnctagt nctagaatcg gcccgccatc gcggtgganc ctccaacctt tcgttnccct 660ttactgaggg ttnattgccg cccttggcgt tatcatggtc acnccngttn cctgtgttga 720aattnttaac cccccacaat tccacgccna cattng 756
<210> 35
<211> 834
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (834)
<223> n = A,T,C or G
<400> 35ggggatctct anatcnacct gnatgcatgg ttgtcggtgt ggtcgctgtc gatgaanatg 60aacaggatct tgcccttgaa gctctcggct gctgtnttta agttgctcag tctgccgtca 120tagtcagaca cnctcttggg caaaaaacan caggatntga gtcttgattt cacctccaat 180aatcttcngg gctgtctgct cggtgaactc gatgacnang ggcagctggt tgtgtntgat 240aaantccanc angttctcct tggtgacctc cccttcaaagttgttccggc cttcatcaaa 300cttctnnaan angannancc canctttgtc gagctggnat ttgganaaca cgtcaccgtt 360ggaaactgat cccaaatggt atgtcatcca tcgcctctgc tgcctgcaaa aaacttgctt 420ggcncaaatc cgactccccn tccttgaaag aagccnatca cacccccctc cctggactcc 480nncaangact ctnccgctnc cccntccnng cagggttggt ggcannccgg gcccntgcgc 540ttcttcagcc agttcacnat nttcatcagc ccctctgcca gctgttntat tccttggggg 600ggaanccgtc tctcccttcc tgaannaact ttgaccgtng gaatagccgc gcntcnccnt 660acntnctggg ccgggttcaa antccctccn ttgncnntcn cctcgggcca ttctggattt 720nccnaacttt ttccttcccc cnccccncgg ngtttggntt tttcatnggg ccccaactct 780gctnttggcc antcccctgg gggcntntan cnccccctnt ggtcccntng ggcc 834
<210> 36
<211> 814
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(814)
<223> n = A,T,C or G
<400> 36cggncgcttt ccngccgcgc cccgtttcca tgacnaaggc tcccttcang ttaaatacnn 60cctagnaaac attaatgggt tgctctacta atacatcata cnaaccagta agcctgccca 120naacgccaac tcaggccatt cctaccaaag gaagaaaggc tggtctctcc accccctgta 180ggaaaggcct gccttgtaag acaccacaat ncggctgaat ctnaagtctt gtgttttact 240aatggaaaaa aaaaataaac aanaggtttt gttctcatgg ctgcccaccg cagcctggca 300ctaaaacanc ccagcgctca cttctgcttg ganaaatatt ctttgctctt ttggacatca 360ggcttgatgg tatcactgcc acntttccac ccagctgggc ncccttcccc catntttgtc 420antganctgg aaggcctgaa ncttagtctc caaaagtctc ngcccacaag accggccacc 480aggggangtc ntttncagtg gatctgccaa anantacccn tatcatcnnt gaataaaaag 540gcccctgaac ganatgcttc cancancctt taagacccat aatcctngaa ccatggtgcc 600cttccggtct gatccnaaag gaatgttcct gggtcccant ccctcctttg ttncttacgt 660tgtnttggac ccntgctngn atnacccaan tganatcccc ngaagcaccc tncccctggc 720atttganttt cntaaattct ctgccctacn nctgaaagca cnattccctn ggcnccnaan 780ggngaactca agaaggtctn ngaaaaacca cncn 814
<210> 37
<211> 760
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(760)
<223> n = A,T,C or G
<400> 37gcatgctgct cttcctcaaa gttgttcttg ttgccataac aaccaccata ggtaaagcgg 60gcgcagtgtt cgctgaaggg gttgtagtac cagcgcggga tgctctcctt gcagagtcct 120gtgtctggca ggtccacgca atgccctttg tcactgggga aatggatgcg ctggagctcg 180tcnaanccac tcgtgtattt ttcacangca gcctcctccg aagcntccgg gcagttgggg 240gtgtcgtcac actccactaa actgtcgatn cancagccca ttgctgcagc ggaactgggt 300gggctgacag gtgccagaac acactggatn ggcctttcca tggaagggcc tgggggaaat 360cncctnancc caaactgcct ctcaaaggcc accttgcaca ccccgacagg ctagaaatgc 420actcttcttc ccaaaggtag ttgttcttgt tgcccaagca ncctccanca aaccaaaanc 480ttgcaaaatc tgctccgtgg gggtcatnnn taccanggtt ggggaaanaa acccggcngn 540ganccncctt gtttgaatgc naaggnaata atcctcctgt cttgcttggg tggaanagca 600caattgaact gttaacnttg ggccgngttc cnctngggtg gtctgaaact aatcaccgtc 660actggaaaaa ggtangtgcc ttccttgaat tcccaaantt cccctngntt tgggtnnttt 720ctcctctncc ctaaaaatcg tnttcccccc ccntanggcg 760
<210> 38
<211> 724
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(724)
<223> n = A,T,C or G
<400> 38tttttttttt tttttttttt tttttttttt tttttaaaaa ccccctccat tgaatgaaaa 60cttccnaaat tgtccaaccc cctcnnccaa atnnccattt ccgggggggg gttccaaacc 120caaattaatt ttgganttta aattaaatnt tnattngggg aanaanccaa atgtnaagaa 180aatttaaccc attatnaact taaatncctn gaaacccntg gnttccaaaa atttttaacc 240cttaaatccc tccgaaattg ntaanggaaa accaaattcn cctaaggctn tttgaaggtt 300ngatttaaac ccccttnant tnttttnacc cnngnctnaa ntatttngnt tccggtgttt 360tcctnttaan cntnggtaac tcccgntaat gaannnccct aanccaatta aaccgaattt 420tttttgaatt ggaaattccn ngggaattna ccggggtttt tcccntttgg gggccatncc 480cccnctttcg gggtttgggn ntaggttgaa tttttnnang ncccaaaaaa ncccccaana 540aaaaaactcc caagnnttaa ttngaatntc ccccttccca ggccttttgg gaaaggnggg 600tttntggggg ccngggantt cnttcccccn ttnccncccc ccccccnggt aaanggttat 660ngnntttggt ttttgggccc cttnanggac cttccggatn gaaattaaat ccccgggncg 720gccg 724
<210> 39
<211> 751
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(751)
<223> n = A,T,C or G
<400> 39tttttttttt tttttctttg ctcacattta atttttattt tgattttttt taatgctgca 60caacacaata tttatttcat ttgtttcttt tatttcattt tatttgtttg ctgctgctgt 120tttatttatt tttactgaaa gtgagaggga acttttgtgg ccttttttcc tttttctgta 180ggccgcctta agctttctaa atttggaaca tctaagcaag ctgaanggaa aagggggttt 240cgcaaaatca ctcgggggaa nggaaaggtt gctttgttaa tcatgcccta tggtgggtga 300ttaactgctt gtacaattac ntttcacttt taattaattg tgctnaangc tttaattana 360cttgggggtt ccctccccan accaaccccn ctgacaaaaa gtgccngccc tcaaatnatg 420tcccggcnnt cnttgaaaca cacngcngaa ngttctcatt ntccccncnc caggtnaaaa 480tgaagggtta ccatntttaa cnccacctcc acntggcnnn gcctgaatcc tcnaaaancn 540ccctcaancn aattnctnng ccccggtcnc gcntnngtcc cncccgggct ccgggaantn 600cacccccnga anncnntnnc naacnaaatt ccgaaaatat tcccnntcnc tcaattcccc 660cnnagactnt cctcnncnan cncaattttc ttttnntcac gaacncgnnc cnnaaaatgn 720nnnncncctc cnctngtccn naatcnccan c 751
<210> 40
<211> 753
<212> DNA
<213> Homo sapien
<220>
<221> misc_featu
<222> (1)...(753)
<223> n = A,T,C or G
<400> 40gtggtatttt ctgtaagatc aggtgttcct ccctcgtagg tttagaggaa acaccctcat 60agatgaaaac ccccccgaga cagcagcact gcaactgcca agcagccggg gtaggagggg 120cgccctatgc acagctgggc ccttgagaca gcagggcttc gatgtcaggc tcgatgtcaa 180tggtctggaa gcggcggctg tacctgcgta ggggcacacc gtcagggccc accaggaact 240tctcaaagtt ccaggcaacn tcgttgcgac acaccggaga ccaggtgatn agcttggggt 300cggtcataan cgcggtggcg tcgtcgctgg gagctggcag ggcctcccgc aggaaggcna 360ataaaaggtg cgcccccgca ccgttcanct cgcacttctc naanaccatg angttgggct 420cnaacccacc accannccgg acttccttga nggaattccc aaatctcttc gntcttgggc 480ttctnctgat gccctanctg gttgcccngn atgccaanca nccccaancc ccggggtcct 540aaancacccn cctcctcntt tcatctgggt tnttntcccc ggaccntggt tcctctcaag 600ggancccata tctcnaccan tactcaccnt ncccccccnt gnnacccanc cttctanngn 660ttcccncccg ncctctggcc cntcaaanan gcttncacna cctgggtctg ccttcccccc 720tnccctatct gnaccccncn tttgtctcan tnt 753
<210> 41
<211> 341
<212> DNA
<213> Homo sapien
<400> 41actatatcca tcacaacaga catgcttcat cccatagact tcttgacata gcttcaaatg 60agtgaaccca tccttgattt atatacatat atgttctcag tattttggga gcctttccac 120ttctttaaac cttgttcatt acgaacactg aaaataggaa tttgtgaaga gttaaaaagt 180tatagcttgt ttacgtagta agtttttgaa gtctacattc aatccagaca cttagttgag 240tgttaaactg tgatttttaa aaaatatcat ttgagaatat tctttcagag gtattttcat 300ttttactttt tgattaattg tgttttatat attagggtag t 341
<210> 42
<211> 101
<212> DNA
<213> Homo sapien
<400> 42acttactgaa tttagttctg tgctcttcct tatttagtgt tgtatcataa atactttgat 60gtttcaaaca ttctaaataa ataattttca gtggcttcat a 101
<210> 43
<211> 305
<212> DNA
<213> Homo sapien
<400> 43acatctttgt tacagtctaa gatgtgttct taaatcacca ttccttcctg gtcctcaccc 60tccagggtgg tctcacactg taattagagc tattgaggag tctttacagc aaattaagat 120tcagatgcct tgctaagtct agagttctag agttatgttt cagaaagtct aagaaaccca 180cctcttgaga ggtcagtaaa gaggacttaa tatttcatat ctacaaaatg accacaggat 240tggatacaga acgagagtta tcctggataa ctcagagctg agtacctgcc cgggggccgc 300tcgaa 305
<210> 44
<211> 852
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(852)
<223> n = A,T,C or G
<400> 44acataaatat cagagaaaag tagtctttga aatatttacg tccaggagtt ctttgtttct 60gattatttgg tgtgtgtttt ggtttgtgtc caaagtattg gcagcttcag ttttcatttt 120ctctccatcc tcgggcattc ttcccaaatt tatataccag tcttcgtcca tccacacgct 180ccagaatttc tcttttgtag taatatctca tagctcggct gagcttttca taggtcatgc 240tgctgttgtt cttcttttta ccccatagct gagccactgc ctctgatttc aagaacctga 300agacgccctc agatcggtct tcccatttta ttaatcctgg gttcttgtct gggttcaaga 360ggatgtcgcg gatgaattcc cataagtgag tccctctcgg gttgtgcttt ttggtgtggc 420acttggcagg ggggtcttgc tcctttttca tatcaggtga ctctgcaaca ggaaggtgac 480tggtggttgt catggagatc tgagcccggc agaaagtttt gctgtccaac aaatctactg 540tgctaccata gttggtgtca tataaatagt tctngtcttt ccaggtgttc atgatggaag 600gctcagtttg ttcagtcttg acaatgacat tgtgtgtgga ctggaacagg tcactactgc 660actggccgtt ccacttcaga tgctgcaagt tgctgtagag gagntgcccc gccgtccctg 720ccgcccgggt gaactcctgc aaactcatgc tgcaaaggtg ctcgccgttg atgtcgaact 780cntggaaagg gatacaattg gcatccagct ggttggtgtc caggaggtga tggagccact 840cccacacctg gt 852
<210> 45
<211> 234
<212> DNA
<213> Homo sapien
<400> 45acaacagacc cttgctcgct aacgacctca tgctcatcaa gttggacgaa tccgtgtccg 60agtctgacac catccggagc atcagcattg cctcgcagtg ccctaccgcg gggaactctt 120gcctcgtttc tggctggggt ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg 180tgaacgtgtc ggtggtgtct gaggaggtct gcagtaagct ctatgacccg ctgt 234
<210> 46
<211> 590
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222>(1)...(590)
<223> n = A,T,C or G
<400> 46actttttatt taaatgttta taaggcagat ctatgagaat gatagaaaac atggtgtgta 60atttgatagc aatattttgg agattacaga gttttagtaa ttaccaatta cacagttaaa 120aagaagataa tatattccaa gcanatacaa aatatctaat gaaagatcaa ggcaggaaaa 180tgantataac taattgacaa tggaaaatca attttaatgt gaattgcaca ttatccttta 240aaagctttca aaanaaanaa ttattgcagt ctanttaatt caaacagtgt taaatggtat 300caggataaan aactgaaggg canaaagaat taattttcac ttcatgtaac ncacccanat 360ttacaatggc ttaaatgcan ggaaaaagca gtggaagtag ggaagtantc aaggtctttc 420tggtctctaa tctgccttac tctttgggtg tggctttgat cctctggaga cagctgccag 480ggctcctgtt atatccacaa tcccagcagc aagatgaagg gatgaaaaag gacacatgct 540gccttccttt gaggagactt catctcactg gccaacactc agtcacatgt 590
<210> 47
<211> 774
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(774)
<223> n = A,T,C or G
<400> 47acaagggggc ataatgaagg agtggggana gattttaaag aaggaaaaaa aacgaggccc 60tgaacagaat tttcctgnac aacggggctt caaaataatt ttcttgggga ggttcaagac 120gcttcactgc ttgaaactta aatggatgtg ggacanaatt ttctgtaatg accctgaggg 180cattacagac gggactctgg gaggaaggat aaacagaaag gggacaaagg ctaatcccaa 240aacatcaaag aaaggaaggt ggcgtcatac ctcccagcct acacagttct ccagggctct 300cctcatccct ggaggacgac agtggaggaa caactgacca tgtccccagg ctcctgtgtg 360ctggctcctg gtcttcagcc cccagctctg gaagcccacc ctctgctgat cctgcgtggc 420ccacactcct tgaacacaca tccccaggtt atattcctgg acatggctga acctcctatt 480cctacttccg agatgccttg ctccctgcag cctgtcaaaa tcccactcac cctccaaacc 540acggcatggg aagcctttct gacttgcctg attactccag catcttggaa caatccctga 600ttccccactc cttagaggca agatagggtg gttaagagta gggctggacc acttggagcc 660aggctgctgg cttcaaattn tggctcattt acgagctatg ggaccttggg caagtnatct 720tcacttctat gggcntcatt ttgttctacc tgcaaaatgg gggataataa tagt 774
<210> 48
<211> 124
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(124)
<223> n = A,T,C or G
<400> 48canaaattga aattttataa aaaggcattt ttctcttata tccataaaat gatataattt 60ttgcaantat anaaatgtgt cataaattat aatgttcctt aattacagct caacgcaact 120tggt 124
<210> 49
<211> 147
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(147)
<223> n = A,T,C or G
<400> 49gccgatgcta ctattttatt gcaggaggtg ggggtgtttt tattattctc tcaacagctt 60tgtggctaca ggtggtgtct gactgcatna aaaanttttt tacgggtgat tgcaaaaatt 120ttagggcacc catatcccaa gcantgt 147
<210> 50
<211> 107
<212> DNA
<213> Homo sapien
<400> 50acattaaatt aataaaagga ctgttggggt tctgctaaaa cacatggctt gatatattgc 60atggtttgag gttaggagga gttaggcata tgttttggga gaggggt 107
<210> 51
<211> 204
<212> DNA
<213> Homo sapien
<400> 51gtcctaggaa gtctagggga cacacgactc tggggtcacg gggccgacac acttgcacgg 60cgggaaggaa aggcagagaa gtgacaccgt cagggggaaa tgacagaaag gaaaatcaag 120gccttgcaag gtcagaaagg ggactcaggg cttccaccac agccctgccc cacttggcca 180cctccctttt gggaccagca atgt 204
<210> 52
<211> 491
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(491)
<223> n = A,T,C or G
<400> 52acaaagataa catttatctt ataacaaaaa tttgatagtt ttaaaggtta gtattgtgta 60gggtattttc caaaagacta aagagataac tcaggtaaaa agttagaaat gtataaaaca 120ccatcagaca ggtttttaaa aaacaacata ttacaaaatt agacaatcat ccttaaaaaa 180aaaacttctt gtatcaattt cttttgttca aaatgactga cttaantatt tttaaatatt 240tcanaaacac ttcctcaaaa attttcaana tggtagcttt canatgtncc ctcagtccca 300atgttgctca gataaataaa tctcgtgaga acttaccacc caccacaagc tttctggggc 360atgcaacagt gtcttttctt tnctttttct tttttttttt ttacaggcac agaaactcat 420caattttatt tggataacaa agggtctcca aattatattg aaaaataaat ccaagttaat 480atcactcttg t 491
<210> 53
<211> 484
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(484)
<223> n = A,T,C or G
<400> 53acataattta gcagggctaa ttaccataag atgctattta ttaanaggtn tatgatctga 60gtattaacag ttgctgaagt ttggtatttt tatgcagcat tttctttttg ctttgataac 120actacagaac ccttaaggac actgaaaatt agtaagtaaa gttcagaaac attagctgct 180caatcaaatc tctacataac actatagtaa ttaaaacgtt aaaaaaaagt gttgaaatct 240gcactagtat anaccgctcc tgtcaggata anactgcttt ggaacagaaa gggaaaaanc 300agctttgant ttctttgtgc tgatangagg aaaggctgaa ttaccttgtt gcctctccct 360aatgattggc aggtcnggta aatnccaaaa catattccaa ctcaacactt cttttccncg 420tancttgant ctgtgtattc caggancagg cggatggaat gggccagccc ncggatgttc 480cant 484
<210> 54
<211> 151
<212> DNA
<213> Homo sapien
<400> 54actaaacctc gtgcttgtga actccataca gaaaacggtg ccatccctga acacggctgg 60ccactgggta tactgctgac aaccgcaaca acaaaaacac aaatccttgg cactggctag 120tctatgtcct ctcaagtgcc tttttgtttg t 151 <210> 55
<211> 91
<212> DNA
<213> Homo sapien
<400> 55acctggcttg tctccgggtg gttcccggcg ccccccacgg tccccagaac ggacactttc 60gccctccagt ggatactcga gccaaagtgg t 91
<210> 56
<211> 133
<212> DNA
<213> Homo sapien
<400> 56ggcggatgtg cgttggttat atacaaatat gtcattttat gtaagggact tgagtatact 60tggatttttg gtatctgtgg gttgggggga cggtccagga accaataccc catggatacc 120aagggacaac tgt 133
<210> 57
<211> 147
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (147)
<223> n = A,T,C or G
<400> 57actctggaga acctgagccg ctgctccgcc tctgggatga ggtgatgcan gcngtggcgc 60gactgggagc tgagcccttc cctttgcgcc tgcctcagag gattgttgcc gacntgcana 120tctcantggg ctggatncat gcagggt 147
<210> 58
<211> 198
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (198)
<223> n = A,T,C or G
<400> 58acagggatat aggtttnaag ttattgtnat tgtaaaatac attgaatttt ctgtatactc 60tgattacata catttatcct ttaaaaaaga tgtaaatctt aatttttatg ccatctatta 120atttaccaat gagttacctt gtaaatgaga agtcatgata gcactgaatt ttaactagtt 180ttgacttcta agtttggt 198
<210> 59
<211> 330
<212> DNA
<213> Homo sapien
<400> 59acaacaaatg ggttgtgagg aagtcttatc agcaaaactg gtgatggcta ctgaaaagat 60ccattgaaaa ttatcattaa tgattttaaa tgacaagtta tcaaaaactc actcaatttt 120cacctgtgct agcttgctaa aatgggagtt aactctagag caaatatagt atcttctgaa 180tacagtcaat aaatgacaaa gccagggcct acaggtggtt tccagacttt ccagacccag 240cagaaggaat ctattttatc acatggatct ccgtctgtgc tcaaaatacc taatgatatt 300tttcgtcttt attggacttc tttgaagagt 330
<210> 60
<211> 175
<212> DNA
<213> Homo sapien
<400> 60accgtgggtg ccttctacat tcctgacggc tccttcacca acatctggtt ctacttcggc 60gtcgtgggct ccttcctctt catcctcatc cagctggtgc tgctcatcga ctttgcgcac 120tcctggaacc agcggtggct gggcaaggcc gaggagtgcg attcccgtgc ctggt 175
<210> 61
<211> 154
<212> DNA
<213> Homo sapien
<400> 61accccacttt tcctcctgtg agcagtctgg acttctcact gctacatgat gagggtgagt 60ggttgttgct cttcaacagt atcctcccct ttccggatct gctgagccgg acagcagtgc 120tggactgcac agccccgggg ctccacattg ctgt 154
<210> 62
<211> 30
<212> DNA
<213> Homo sapien
<400> 62cgctcgagcc ctatagtgag tcgtattaga 30
<210> 63
<211> 89
<212> DNA
<213> Homo sapien
<400> 63acaagtcatt tcagcaccct ttgctcttca aaactgacca tcttttatat ttaatgcttc 60ctgtatgaat aaaaatggtt atgtcaagt 89
<210> 64
<211> 97
<212> DNA
<213> Homo sapien
<400> 64accggagtaa ctgagtcggg acgctgaatc tgaatccacc aataaataaa ggttctgcag 60aatcagtgca tccaggattg gtccttggat ctggggt 97
<210> 65
<211> 377
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(377)
<223> n = A,T,C or G
<400> 65acaacaanaa ntcccttctt taggccactg atggaaacct ggaaccccct tttgatggca 60gcatggcgtc ctaggccttg acacagcggc tggggtttgg gctntcccaa accgcacacc 120ccaaccctgg tctacccaca nttctggcta tgggctgtct ctgccactga acatcagggt 180tcggtcataa natgaaatcc caanggggac agaggtcagt agaggaagct caatgagaaa 240ggtgctgttt gctcagccag aaaacagctg cctggcattc gccgctgaac tatgaacccg 300tgggggtgaa ctacccccan gaggaatcat gcctgggcga tgcaanggtg ccaacaggag 360gggcgggagg agcatgt 377
<210> 66
<211> 305
<212> DNA
<213> Homo sapien
<400> 66acgcctttcc ctcagaattc agggaagaga ctgtcgcctg ccttcctccg ttgttgcgtg 60agaacccgtg tgccccttcc caccatatcc accctcgctc catctttgaa ctcaaacacg 120aggaactaac tgcaccctgg tcctctcccc agtccccagt tcaccctcca tccctcacct 180tcctccactc taagggatat caacactgcc cagcacaggg gccctgaatt tatgtggttt 240ttatatattt tttaataaga tgcactttat gtcatttttt aataaagtct gaagaattac 300tgttt 305
<210> 67
<211> 385
<212> DNA
<213> Homo sapien
<400> 67actacacaca ctccacttgc ccttgtgaga cactttgtcc cagcacttta ggaatgctga 60ggtcggacca gccacatctc atgtgcaaga ttgcccagca gacatcaggt ctgagagttc 120cccttttaaa aaaggggact tgcttaaaaa agaagtctag ccacgattgt gtagagcagc 180tgtgctgtgc tggagattca cttttgagag agttctcctc tgagacctga tctttagagg 240ctgggcagtc ttgcacatga gatggggctg gtctgatctc agcactcctt agtctgcttg 300cctctcccag ggccccagcc tggccacacc tgcttacagg gcactctcag atgcccatac 360catagtttct gtgctagtgg accgt 385
<210> 68
<211> 73
<212> DNA
<213> Homo sapien
<400> 68acttaaccag atatattttt accccagatg gggatattct ttgtaaaaaa tgaaaataaa 60gtttttttaa tgg 73
<210> 69
<211> 536
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(536)
<223> n = A,T,C or G
<400> 69actagtccag tgtggtggaa ttccattgtg ttgggggctc tcaccctcct ctcctgcagc 60tccagctttg tgctctgcct ctgaggagac catggcccag catctgagta ccctgctgct 120cctgctggcc accctagctg tggccctggc ctggagcccc aaggaggagg ataggataat 180cccgggtggc atctataacg cagacctcaa tgatgagtgg gtacagcgtg cccttcactt 240cgccatcagc gagtataaca aggccaccaa agatgactac tacagacgtc cgctgcgggt 300actaagagcc aggcaacaga ccgttggggg ggtgaattac ttcttcgacg tagaggtggg 360ccgaaccata tgtaccaagt cccagcccaa cttggacacc tgtgccttcc atgaacagcc 420agaactgcag aagaaacagt tgtgctcttt cgagatctac gaagttccct ggggagaaca 480gaangtccct gggtgaaatc caggtgtcaa gaaatcctan ggatctgttg ccaggc 536
<210> 70
<211> 477
<212> DNA
<213> Homo sapien
<400> 70atgaccccta acaggggccc tctcagccct cctaatgacc tccggcctag ccatgtgatt 60tcacttccac tccataacgc tcctcatact aggcctacta accaacacac taaccatata 120ccaatgatgg cgcgatgtaa cacgagaaag cacataccaa ggccaccaca caccacctgt 180ccaaaaaggc cttcgatacg ggataatcct atttattacc tcagaagttt ttttcttcgc 240agggattttt ctgagccttt taccactcca gcctagcccc taccccccaa ctaggagggc 300actggccccc aacaggcatc accccgctaa atcccctaga agtcccactc ctaaacacat 360ccgtattact cgcatcagga gtatcaatca cctgagctca ccatagtcta atagaaaaca 420accgaaacca aattattcaa agcactgctt attacaattt tactgggtct ctatttt 477
<210> 71
<211> 533
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(533)
<223> n = A,T,C or G
<400> 71agagctatag gtacagtgtg atctcagctt tgcaaacaca ttttctacat agatagtact 60aggtattaat agatatgtaa agaaagaaat cacaccatta ataatggtaa gattggttta 120tgtgatttta gtggtatttt tggcaccctt atatatgttt tccaaacttt cagcagtgat 180attatttcca taacttaaaa agtgagtttg aaaaagaaaa tctccagcaa gcatctcatt 240taaataaagg tttgtcatct ttaaaaatac agcaatatgt gactttttaa aaaagctgtc 300aaataggtgt gaccctacta ataattatta gaaatacatt taaaaacatc gagtacctca 360agtcagtttg ccttgaaaaa tatcaaatat aactcttaga gaaatgtaca taaaagaatg 420cttcgtaatt ttggagtang aggttccctc ctcaattttg tatttttaaa aagtacatgg 480taaaaaaaaa aattcacaac agtatataag gctgtaaaat gaagaattct gcc 533
<210> 72
<211> 511
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (511)
<223> n = A,T,C or G
<400> 72tattacggaa aaacacacca cataattcaa ctancaaaga anactgcttc agggcgtgta 60aaatgaaagg cttccaggca gttatctgat taaagaacac taaaagaggg acaaggctaa 120aagccgcagg atgtctacac tatancaggc gctatttggg ttggctggag gagctgtgga 180aaacatggan agattggtgc tgganatcgc cgtggctatt cctcattgtt attacanagt 240gaggttctct gtgtgcccac tggtttgaaa accgttctnc aataatgata gaatagtaca 300cacatgagaa ctgaaatggc ccaaacccag aaagaaagcc caactagatc ctcagaanac 360gcttctaggg acaataaccg atgaagaaaa gatggcctcc ttgtgccccc gtctgttatg 420atttctctcc attgcagcna naaacccgtt cttctaagca aacncaggtg atgatggcna 480aaatacaccc cctcttgaag naccnggagg a 511
<210> 73
<211> 499
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (499)
<223> n = A,T,C or G
<400> 73cagtgccagc actggtgcca gtaccagtac caataacagt gccagtgcca gtgccagcac 60cagtggtggc ttcagtgctg gtgccagcct gaccgccact ctcacatttg ggctcttcgc 120tggccttggt ggagctggtg ccagcaccag tggcagctct ggtgcctgtg gtttctccta 180caagtgagat tttagatatt gttaatcctg ccagtctttc tcttcaagcc agggtgcatc 240ctcagaaacc tactcaacac agcactctag gcagccacta tcaatcaatt gaagttgaca 300ctctgcatta aatctatttg ccatttctga aaaaaaaaaa aaaaaaaggg cggccgctcg 360antctagagg gcccgtttaa acccgctgat cagcctcgac tgtgccttct anttgccagc 420catctgttgt ttgcccctcc cccgntgcct tccttgaccc tggaaagtgc cactcccact 480gtcctttcct aantaaaat 499
<210> 74
<211> 537
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(537)
<223> n = A,T,C or G
<400> 74tttcatagga gaacacactg aggagatact tgaagaattt ggattcagcc gcgaagagat 60ttatcagctt aactcagata aaatcattga aagtaataag gtaaaagcta gtctctaact 120tccaggccca cggctcaagt gaatttgaat actgcattta cagtgtagag taacacataa 180cattgtatgc atggaaacat ggaggaacag tattacagtg tcctaccact ctaatcaaga 240aaagaattac agactctgat tctacagtga tgattgaatt ctaaaaatgg taatcattag 300ggcttttgat ttataanact ttgggtactt atactaaatt atggtagtta tactgccttc 360cagtttgctt gatatatttg ttgatattaa gattcttgac ttatattttg aatgggttct 420actgaaaaan gaatgatata ttcttgaaga catcgatata catttattta cactcttgat 480tctacaatgt agaaaatgaa ggaaatgccc caaattgtat ggtgataaaa gtcccgt 537
<210> 75
<211> 467
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(467)
<223> n = A,T,C or G
<400> 75caaanacaat tgttcaaaag atgcaaatga tacactactg ctgcagctca caaacacctc 60tgcatattac acgtacctcc tcctgctcct caagtagtgt ggtctatttt gccatcatca 120cctgctgtct gcttagaaga acggctttct gctgcaangg agagaaatca taacagacgg 180tggcacaagg aggccatctt ttcctcatcg gttattgtcc ctagaagcgt cttctgagga 240tctagttggg ctttctttct gggtttgggc catttcantt ctcatgtgtg tactattcta 300tcattattgt ataacggttt tcaaaccngt gggcacncag agaacctcac tctgtaataa 360caatgaggaa tagccacggt gatctccagc accaaatctc tccatgttnt tccagagctc 420ctccagccaa cccaaatagc cgctgctatn gtgtagaaca tccctgn 467
<210> 76
<211> 400
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (400)
<223> n = A,T,C or G
<400> 76aagctgacag cattcgggcc gagatgtctc gctccgtggc cttagctgtg ctcgcgctac 60tctctctttc tggcctggag gctatccagc gtactccaaa gattcaggtt tactcacgtc 120atccagcaga gaatggaaag tcaaatttcc tgaattgcta tgtgtctggg tttcatccat 180ccgacattga agttgactta ctgaagaatg gagagagaat tgaaaaagtg gagcattcag 240acttgtcttt cagcaaggac tggtctttct atctcttgta ctacactgaa ttcaccccca 300ctgaaaaaga tgagtatgcc tgccgtgtgaaccatgtgac tttgtcacag cccaagatng 360ttnagtggga tcganacatg taagcagcan catgggaggt 400
<210> 77
<211> 248
<212> DNA
<213> Homo sapien
<400> 77ctggagtgcc ttggtgtttcaagcccctgc aggaagcaga atgcaccttc tgaggcacct 60ccagctgccc cggcggggga tgcgaggctc ggagcaccct tgcccggctg tgattgctgc 120caggcactgt tcatctcagc ttttctgtcc ctttgctccc ggcaagcgct tctgctgaaa 180gttcatatct ggagcctgat gtcttaacga ataaaggtcc catgctccac ccgaaaaaaa 240aaaaaaaa 248
<210> 78
<211> 201
<212> DNA
<213> Homo sapien
<400> 78actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca 60tcacccagac cccgccctgc ccgtgcccca cgctgctgct aacgacagta tgatgcttac 120tctgctactc ggaaactatt tttatgtaat taatgtatgc tttcttgttt ataaatgcct 180gatttaaaaa aaaaaaaaaa a 201
<210> 79
<211> 552
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (552)
<223> n = A,T,C or G
<400> 79tccttttgtt aggtttttga gacaacccta gacctaaact gtgtcacaga cttctgaatg 60tttaggcagt gctagtaatt tcctcgtaat gattctgtta tcactttcct attctttatt 120cctctttctt ctgaagatta atgaagttga aaattgaggt ggataaatac aaaaaggtag 180tgtgatagta taagtatcta agtgcagatg aaagtgtgtt atatatatcc attcaaaatt 240atgcaagtta gtaattactc agggttaact aaattacttt aatatgctgt tgaacctact 300ctgttccttg gctagaaaaa attataaaca ggactttgtt agtttgggaa gccaaattga 360taatattcta tgttctaaaa gttgggctat acataaanta tnaagaaata tggaatttta 420ttcccaggaa tatggggttc atttatgaat antacccggg anagaagttt tgantnaaac 480cngttttggt taatacgtta atatgtcctn aatnaacaag gcntgactta tttccaaaaa 540aaaaaaaaaa aa 552
<210> 80
<211> 476
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(476)
<223> n = A,T,C or G
<400> 80acagggattt gagatgctaa ggccccagag atcgtttgat ccaaccctct tattttcaga 60ggggaaaatg gggcctagaa gttacagagc atctagctgg tgcgctggca cccctggcct 120cacacagact cccgagtagc tgggactaca ggcacacagt cactgaagca ggccctgttt 180gcaattcacg ttgccacctc caacttaaac attcttcata tgtgatgtcc ttagtcacta 240aggttaaact ttcccaccca gaaaaggcaa cttagataaa atcttagagt actttcatac 300tcttctaagt cctcttccag cctcactttg agtcctcctt gggggttgat aggaantntc 360tcttggcttt ctcaataaaa tctctatcca tctcatgttt aatttggtac gcntaaaaat 420gctgaaaaaa ttaaaatgtt ctggtttcnc tttaaaaaaa aaaaaaaaaa aaaaaa 476
<210> 81
<211> 232
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(232)
<223> n = A,T,C or G
<400> 81tttttttttg tatgccntcn ctgtggngtt attgttgctg ccaccctgga ggagcccagt 60ttcttctgta tctttctttt ctgggggatc ttcctggctc tgcccctcca ttcccagcct 120ctcatcccca tcttgcactt ttgctagggt tggaggcgct ttcctggtag cccctcagag 180actcagtcag cgggaataag tcctaggggt ggggggtgtg gcaagccggc ct 232
<210> 82
<211> 383
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(383)
<223> n = A,T,C or G
<400> 82aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60agtaccagta ccaataacat gccagtgcca gtgccagcac cagtggtggc ttcagtgctg 120gtgccagcct gaccgccact ctcacatttg ggctcttcgc tggccttggt ggagctggtg 180ccagcaccag tggcagctct ggtgcctgtg gtttctccta caagtgagat tttagatatt 240gttaatcctg ccagtctttc tcttcaagcc agggtgcatc ctcagaaacc tactcaacac 300agcactctng gcagccacta tcaatcaatt gaagttgaca ctctgcatta aatctatttg 360ccatttcaaa aaaaaaaaaa aaa 383
<210> 83
<211> 494
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(494)
<223> n = A,T,C or G
<400> 83accgaattgg gaccgctggc ttataagcga tcatgtcctc cagtattacc tcaacgagca 60gggagatcga gtctatacgc tgaagaaatt tgacccgatg ggacaacaga cctgctcagc 120ccatcctgct cggttctccc cagatgacaa atactctcga caccgaatca ccatcaagaa 180acgcttcaag gtgctcatga cccagcaacc gcgccctgtc ctctgagggt ccttaaactg 240atgtcttttc tgccacctgt tacccctcgg agactccgta accaaactct tcggactgtg 300agccctgatg cctttttgcc agccatactc tttggcntcc agtctctcgt ggcgattgat 360tatgcttgtg tgaggcaatc atggtggcat cacccatnaa gggaacacat ttganttttt 420tttcncatat tttaaattac naccagaata nttcagaata aatgaattga aaaactctta 480aaaaaaaaaa aaaa 494
<210> 84
<211> 380
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(380)
<223> n = A,T,C or G
<400> 84gctggtagcc tatggcgtgg ccacggangg gctcctgagg cacgggacag tgacttccca 60agtatcctgc gccgcgtctt ctaccgtccc tacctgcaga tcttcgggca gattccccag 120gaggacatgg acgtggccct catggagcac agcaactgct cgtcggagcc cggcttctgg 180gcacaccctc ctggggccca ggcgggcacc tgcgtctccc agtatgccaa ctggctggtg 240gtgctgctcc tcgtcatctt cctgctcgtg gccaacatcc tgctggtcac ttgctcattg 300ccatgttcag ttacacattc ggcaaagtac agggcaacag cnatctctac tgggaaggcc 260agcgttnccg cctcatccgg 380
<210> 85
<211> 481
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (481)
<223> n = A,T,C or G
<400> 85gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc 60tnccatcgtc atactgtagg tttgccacca cctcctgcat cttggggcgg ctaatatcca 120ggaaactctc aatcaagtca ccgtcnatna aacctgtggc tggttctgtc ttccgctcgg 180tgtgaaagga tctccagaag gagtgctcga tcttccccac acttttgatg actttattga 240gtcgattctg catgtccagc aggaggttgt accagctctc tgacagtgag gtcaccagcc 300ctatcatgcc nttgaacgtg ccgaagaaca ccgagccttg tgtggggggt gnagtctcac 360ccagattctg cattaccaga nagccgtggc aaaaganatt gacaactcgc ccaggnngaa 420aaagaacacc tcctggaagt gctngccgct cctcgtccnt tggtggnngc gcntnccttt 480t 481
<210> 86
<211> 472
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(472)
<223> n = A,T,C or G
<400> 86aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgctg agaattcatt 60acttggaaaa gcaacttnaa gcctggacac tggtattaaa attcacaata tgcaacactt 120taaacagtgt gtcaatctgc tcccttactt tgtcatcacc agtctgggaa taagggtatg 180ccctattcac acctgttaaa agggcgctaa gcatttttga ttcaacatct ttttttttga 240cacaagtccg aaaaaagcaa aagtaaacag ttnttaattt gttagccaat tcactttctt 300catgggacag agccatttga tttaaaaagc aaattgcata atattgagct ttgggagctg 360atatntgagc ggaagantag cctttctact tcaccagaca caactccttt catattggga 420tgttnacnaa agttatgtct cttacagatg ggatgctttt gtggcaattc tg 472
<210> 87
<211> 413
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(413)
<223> n = A,T,C or G
<400> 87agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg 60tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg 120cctctttggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180ttgtcttctg tgtaaatggt actagagaaa acacctatnt tatgagtcaa tctagttngt 240tttattcgac atgaaggaaa tttccagatn acaacactna caaactctcc cttgactagg 300ggggacaaag aaaagcanaa ctgaacatna gaaacaattn cctggtgaga aatcncataa 360acagaaattg ggtngtatat tgaaananng catcattnaa acgttttttt ttt 413
<210> 88
<211> 448
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(448)
<223> n = A,T,C or G
<400> 88cgcagcgggt cctctctatc tagctccagc ctctcgcctg ccccactccc cgcgtcccgc 60gtcctagccn accatggccg ggcccctgcg cgccccgctg ctcctgctgg ccatcctggc 120cgtggccctg gccgtgagcc ccgcggccgg ctccagtccc ggcaagccgc cgcgcctggt 180gggaggccca tggaccccgc gtggaagaag aaggtgtgcg gcgtgcactg gactttgccg 240tcggcnanta caacaaaccc gcaacnactt ttaccnagcn cgcgctgcag gttgtgccgc 300cccaancaaa ttgttactng gggtaantaa ttcttggaag ttgaacctgg gccaaacnng 360tttaccagaa ccnagccaat tngaacaatt ncccctccat aacagcccct tttaaaaagg 420gaancantcc tgntcttttc caaatttt 448
<210> 89
<211> 463
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(463)
<223> n = A,T,C or G
<400> 89gaattttgtg cactggccac tgtgatggaa ccattgggcc aggatgcttt gagtttatca 60gtagtgattc tgccaaagtt ggtgttgtaa catgagtatg taaaatgtca aaaaattagc 120agaggtctag gtctgcatat cagcagacag tttgtccgtg tattttgtag ccttgaagtt 180ctcagtgaca agttnnttct gatgcgaagt tctnattcca gtgttttagt cctttgcatc 240tttnatgttn agacttgcct ctntnaaatt gcttttgtnt tctgcaggta ctatctgtgg 300tttaacaaaa tagaannact tctctgcttn gaanatttga atatcttaca tctnaaaatn 360aattctctcc ccatannaaa acccangccc ttggganaat ttgaaaaang gntccttcnn 420aattcnnana anttcagntn tcatacaaca naacngganc ccc 463
<210> 90
<211> 400
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(400)
<223> n = A,T,C or G
<400> 90agggattgaa ggtctnttnt actgtcggac tgttcancca ccaactctac aagctgctgt 60cttccactca ctgtctgtaa gcntnttaac ccagactgta tcttcataaa tagaacaaat 120tcttcaccag tcacatcttc taggaccttt ttggattcag ttagtataag ctcttccact 180tcctttgtta agacttcatc tggtaaagtc ttaagttttg tagaaaggaa tttaattgct 240cgttctctaa caatgtcctc tccttgaagt atttggctga acaacccacc tnaagtccct 300ttgtgcatcc attttaaata tacttaatag ggcattggtn cactaggtta aattctgcaa 360gagtcatctg tctgcaaaag ttgcgttagt atatctgcca 400
<210> 91
<211> 480
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(480)
<223> n = A,T,C or G
<400> 91gagctcggat ccaataatct ttgtctgagg gcagcacaca tatncagtgc catggnaact 60ggtctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac 120atgcctcttt gactaccgtg tgccagtgct ggtgattctc acacacctcc nnccgctctt 180tgtggaaaaa ctggcacttg nctggaacta gcaagacatc acttacaaat tcacccacga 240gacacttgaa aggtgtaaca aagcgactct tgcattgctt tttgtccctc cggcaccagt 300tgtcaatacc aacccgctgg tttgcctcca tcacatttgt gatctgtagc tctggataca 360tctcctgaca gtactgaaga acttcttctt ttgtttcaaa agcaactctt ggtgcctgtt 420ngatcaggtt cccatttccc agtccgaatg ttcacatggc atatnttact tcccacaaaa 480
<210> 92
<211> 477
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(477)
<223> n = A,T,C or G
<400> 92atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcctt 120cccacgcagg cagcagcggg gccggtcaat gaactccact cgtggcttgg ggttgacggt 180taantgcagg aagaggctga ccacctcgcg gtccaccagg acgcccgact gtgcgggacc 240tgcagcgaaa ctcctcgatg gtcatgagcg ggaagcgaat gangcccagg gccttgccca 300gaaccttccg cctgttctct ggcgtcacct gcagctgctg ccgctnacac tcggcctcgg 360accagcggac aaacggcgtt gaacagccgc acctcacgga tgcccantgt gtcgcgctcc 420aggaacggcn ccagcgtgtc caggtcaatg tcggtgaanc ctccgcgggt aatggcg 477
<210> 93
<211> 377
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (377)
<223> n = A,T,C or G
<400> 93gaacggctgg accttgcctc gcattgtgct gctggcagga ataccttggc aagcagctcc 60agtccgagca gccccagacc gctgccgccc gaagctaagc ctgcctctgg ccttcccctc 120cgcctcaatg cagaaccant agtgggagca ctgtgtttag agttaagagt gaacactgtn 180tgattttact tgggaatttc ctctgttata tagcttttcc caatgctaat ttccaaacaa 240caacaacaaa ataacatgtt tgcctgttna gttgtataaa agtangtgat tctgtatnta 300aagaaaatat tactgttaca tatactgctt gcaanttctg tatttattgg tnctctggaa 360ataaatatat tattaaa 377
<210> 94
<211> 495
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (495)
<223> n = A,T,C or G
<400> 94ccctttgagg ggttagggtc cagttcccag tggaagaaac aggccaggag aantgcgtgc 60cgagctgang cagatttccc acagtgaccc cagagccctg ggctatagtc tctgacccct 120ccaaggaaag accaccttct ggggacatgg gctggagggc aggacctaga ggcaccaagg 180gaaggcccca ttccggggct gttccccgag gaggaaggga aggggctctg tgtgcccccc 240acgaggaana ggccctgant cctgggatca nacacccctt cacgtgtatc cccacacaaa 300tgcaagctca ccaaggtccc ctctcagtcc cttccctaca ccctgaacgg ncactggccc 360acacccaccc agancancca cccgccatgg ggaatgtnct caaggaatcg cngggcaacg 420tggactctng tcccnnaagg gggcagaatc tccaatagan gganngaacc cttgctnana 480aaaaaaaana aaaaa 495
<210> 95
<211> 472
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(472)
<223> n = A,T,C or G
<400> 95ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt ttgtctgctc 60cctctggaag ccttgcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120tagctgtttt gagttgattc gcaccactgc accacaactc aatatgaaaa ctatttnact 180tatttattat cttgtgaaaa gtatacaatg aaaattttgt tcatactgta tttatcaagt 240atgatgaaaa gcaatagata tatattcttt tattatgttn aattatgatt gccattatta 300atcggcaaaa tgtggagtgt atgttctttt cacagtaata tatgcctttt gtaacttcac 360ttggttattt tattgtaaat gaattacaaa attcttaatt taagaaaatg gtangttata 420tttanttcan taatttcttt ccttgtttac gttaattttg aaaagaatgc at 472
<210> 96
<211> 476
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(476)
<223> n = A,T,C or G
<400> 96ctgaagcatt tcttcaaact tntctacttt tgtcattgat acctgtagta agttgacaat 60gtggtgaaat ttcaaaatta tatgtaactt ctactagttt tactttctcc cccaagtctt 120ttttaactca tgatttttac acacacaatc cagaacttat tatatagcct ctaagtcttt 180attcttcaca gtagatgatg aaagagtcct ccagtgtctt gngcanaatg ttctagntat 240agctggatac atacngtggg agttctataa actcatacct cagtgggact naaccaaaat 300tgtgttagtc tcaattccta ccacactgag ggagcctccc aaatcactat attcttatct 360gcaggtactc ctccagaaaa acngacaggg caggcttgca tgaaaaagtn acatctgcgt 420tacaaagtct atcttcctca nangtctgtn aaggaacaat ttaatcttct agcttt 476
<210> 97
<211> 479
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(479)
<223> n = A,T,C or G
<400> 97actctttcta atgctgatat gatcttgagt ataagaatgc atatgtcact agaatggata 60aaataatgct gcaaacttaa tgttcttatg caaaatggaa cgctaatgaa acacagctta 120caatcgcaaa tcaaaactca caagtgctca tctgttgtag atttagtgta ataagactta 180gattgtgctc cttcggatat gattgtttct canatcttgg gcaatnttcc ttagtcaaat 240caggctacta gaattctgtt attggatatn tgagagcatg aaatttttaa naatacactt 300gtgattatna aattaatcac aaatttcact tatacctgct atcagcagct agaaaaacat 360ntnnttttta natcaaagta ttttgtgttt ggaantgtnn aaatgaaatc tgaatgtggg 420ttcnatctta ttttttcccn gacnactant tnctttttta gggnctattc tganccatc 479
<210> 98
<211> 461
<212> DNA
<213> Homo sapien
<400> 98agtgacttgt cctccaacaa aaccccttga tcaagtttgt ggcactgaca atcagaccta 60tgctagttcc tgtcatctat tcgctactaa atgcagactg gaggggacca aaaaggggca 120tcaactccag ctggattatt ttggagcctg caaatctatt cctacttgta cggactttga 180agtgattcag tttcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 240tgaagccact ctgaacacgc tggttatcta gatgagaaca gagaaataaa gtcagaaaat 300ttacctggag aaaagaggct ttggccgggg accatcccat tgaaccttct cttaaggact 360ttaagaaaaa ctaccacatg ttgtgtatcc tggtgccggc cgtttatgaa ctgaccaccc 420tttggaataa tcttgacgct cctgaacttg ctcctctgcg a 461
<210> 99
<211> 171
<212> DNA
<213> Homo sapien
<400> 99gtggccgcgc gcaggtgttt cctcgtaccg cagggccccc tcccttcccc aggcgtccct 60cggcgcctct gcgggcccga ggaggagcgg ctggcgggtg gggggagtgt gacccaccct 120cggtgagaaa agccttctct agcgatctga gaggcgtgcc ttgggggtac c 171
<210> 100
<211> 269
<212> DNA
<213> Homo sapien
<400> 100cggccgcaag tgcaactcca gctggggccg tgcggacgaa gattctgcca gcagttggtc 60cgactgcgac gacggcggcg gcgacagtcg caggtgcagc gcgggcgcct ggggtcttgc 120aaggctgagc tgacgccgca gaggtcgtgt cacgtcccac gaccttgacg ccgtcgggga 180cagccggaac agagcccggt gaagcgggag gcctcgggga gcccctcggg aagggcggcc 240cgagagatac gcaggtgcag gtggccgcc 269
<210> 101
<211> 405
<212> DNA
<213> Homo sapien
<400> 101tttttttttt ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc tttgtcgtgg 120ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaacgaagca aataacatgg 180agtgggtgca ccctccctgt agaacctggt tacaaagctt ggggcagttc acctggtctg 240tgaccgtcat tttcttgaca tcaatgttat tagaagtcag gatatctttt agagagtcca 300ctgttctgga gggagattag ggtttcttgc caaatccaac aaaatccact gaaaaagttg 360gatgatcagt acgaataccg aggcatattc tcatatcggt ggcca 405
<210> 102
<211> 470
<212> DNA
<213> Homo sapien
<400> 102tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60ggcacttaat ccatttttat ttcaaaatgt ctacaaattt aatcccatta tacggtattt 120tcaaaatcta aattattcaa attagccaaa tccttaccaa ataataccca aaaatcaaaa 180atatacttct ttcagcaaac ttgttacata aattaaaaaa atatatacgg ctggtgtttt 240caaagtacaa ttatcttaac actgcaaaca ttttaaggaa ctaaaataaa aaaaaacact 300ccgcaaaggt taaagggaac aacaaattct tttacaacac cattataaaa atcatatctc 360aaatcttagg ggaatatata cttcacacgg gatcttaact tttactcact ttgtttattt 420ttttaaacca ttgtttgggc ccaacacaat ggaatccccc ctggactagt 470
<210> 103
<211> 581
<212> DNA
<213> Homo sapien
<400> 103tttttttttt ttttttttga cccccctctt ataaaaaaca agttaccatt ttattttact 60tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac 120taaatggaaa ctgccttaga tacataattc ttaggaatta gcttaaaatc tgcctaaagt 180gaaaatcttc tctagctctt ttgactgtaa atttttgact cttgtaaaac atccaaattc 240atttttcttg tctttaaaat tatctaatct ttccattttt tccctattcc aagtcaattt 300gcttctctag cctcatttcc tagctcttat ctactattag taagtggctt ttttcctaaa 360agggaaaaca ggaagagaaa tggcacacaa aacaaacatt ttatattcat atttctacct 420acgttaataa aatagcattt tgtgaagcca gctcaaaaga aggcttagat ccttttatgt 480ccattttagt cactaaacga tatcaaagtg ccagaatgca aaaggtttgt gaacatttat 540tcaaaagcta atataagata tttcacatac tcatctttct g 581
<210> 104
<211> 578
<212> DNA
<213> Homo sapien
<400> 104tttttttttt tttttttttt tttttctctt cttttttttt gaaatgagga tcgagttttt 60cactctctag atagggcatg aagaaaactc atctttccag ctttaaaata acaatcaaat 120ctcttatgct atatcatatt ttaagttaaa ctaatgagtc actggcttat cttctcctga 180aggaaatctg ttcattcttc tcattcatat agttatatca agtactacct tgcatattga 240gaggtttttc ttctctattt acacatatat ttccatgtga atttgtatca aacctttatt 300ttcatgcaaa ctagaaaata atgtttcttt tgcataagag aagagaacaa tatagcatta 360caaaactgct caaattgttt gttaagttat ccattataat tagttggcag gagctaatac 420aaatcacatt tacgacagca ataataaaac tgaagtacca gttaaatatc caaaataatt 480aaaggaacat ttttagcctg ggtataatta gctaattcac tttacaagca tttattagaa 540tgaattcaca tgttattatt cctagcccaa cacaatgg 578
<210> 105
<211> 538
<212> DNA
<213> Homo sapien
<400> 105tttttttttt tttttcagta ataatcagaa caatatttat ttttatattt aaaattcata 60gaaaagtgcc ttacatttaa taaaagtttg tttctcaaag tgatcagagg aattagatat 120gtcttgaaca ccaatattaa tttgaggaaa atacaccaaa atacattaag taaattattt 180aagatcatag agcttgtaag tgaaaagata aaatttgacc tcagaaactc tgagcattaa 240aaatccacta ttagcaaata aattactatg gacttcttgc tttaattttg tgatgaatat 300ggggtgtcac tggtaaacca acacattctg aaggatacat tacttagtga tagattctta 360tgtactttgc taatacgtgg atatgagttg acaagtttct ctttcttcaa tcttttaagg 420ggcgagaaat gaggaagaaa agaaaaggat tacgcatact gttctttcta tggaaggatt 480agatatgttt cctttgccaa tattaaaaaa ataataatgt ttactactag tgaaaccc 538
<210> 106
<211> 473
<212> DNA
<213> Homo sapien
<400> 106tttttttttt ttttttagtc aagtttctat ttttattata attaaagtct cggtcatttc 60atttattagc tctgcaactt acatatttaa attaaagaaa cgttttagac aactgtacaa 120tttataaatg taaggtgcca ttattgagta atatattcct ccaagagtgg atgtgtccct 180tctcccacca actaatgaac agcaacatta gtttaatttt attagtagat atacactgct 240gcaaacgcta attctcttct ccatccccat gtgatattgt gtatatgtgt gagttggtag 300aatgcatcac aatctacaat caacagcaag atgaagctag gctgggcttt cggtgaaaat 360agactgtgtc tgtctgaatc aaatgatctg acctatcctc ggtggcaaga actcttcgaa 420ccgcttcctc aaaggcgctg ccacatttgt ggctctttgc acttgtttca aaa 473
<210> 107
<211> 1621
<212> DNA
<213> Homo sapien
<400> 107cgccatggca ctgcagggca tctcggtcat ggagctgtcc ggcctggccc cgggcccgtt 60ctgtgctatg gtcctggctg acttcggggc gcgtgtggta cgcgtggacc ggcccggctc 120ccgctacgac gtgagccgct tgggccgggg caagcgctcg ctagtgctgg acctgaagca 180gccgcgggga gccgccgtgc tgcggcgtct gtgcaagcgg tcggatgtgc tgctggagcc 240cttccgccgc ggtgtcatgg agaaactcca gctgggccca gagattctgc agcgggaaaa 300tccaaggctt atttatgcca ggctgagtgg atttggccag tcaggaagct tctgccggtt 360agctggccac gatatcaact atttggcttt gtcaggtgtt ctctcaaaaa ttggcagaag 420tggtgagaat ccgtatgccc cgctgaatct cctggctgac tttgctggtg gtggccttat 480gtgtgcactg ggcattataa tggctctttt tgaccgcaca cgcactgaca agggtcaggt 540cattgatgca aatatggtgg aaggaacagc atatttaagt tcttttctgt ggaaaactca 600gaaatcgagt ctgtgggaag cacctcgagg acagaacatg ttggatggtg gagcaccttt 660ctatacgact tacaggacag cagatgggga attcatggct gttggagcaa tagaacccca 720gttctacgag ctgctgatca aaggacttgg actaaagtct gatgaacttc ccaatcagat 780gagcatggat gattggccag aaatgaagaa gaagtttgca gatgtatttg caaagaagac 840gaaggcagag tggtgtcaaa tctttgacgg cacagatgcc tgtgtgactc cggttctgac 900ttttgaggag gttgttcatc atgatcacaa caaggaacgg ggctcgttta tcaccagtga 960ggagcaggac gtgagccccc gccctgcacc tctgctgtta aacaccccag ccatcccttc 1020tttcaaaagg gatcctttca taggagaaca cactgaggag atacttgaag aatttggatt 1080cagccgcgaa gagatttatc agcttaactc agataaaatc attgaaagta ataaggtaaa 1140agctagtctc taacttccag gcccacggct caagtgaatt tgaatactgc atttacagtg 1200tagagtaaca cataacattg tatgcatgga aacatggagg aacagtatta cagtgtccta 1260ccactctaat caagaaaaga attacagact ctgattctac agtgatgatt gaattctaaa 1320aatggttatc attagggctt ttgatttata aaactttggg tacttatact aaattatggt 1380agttattctg ccttccagtt tgcttgatat atttgttgat attaagattc ttgacttata 1440ttttgaatgg gttctagtga aaaaggaatg atatattctt gaagacatcg atatacattt 1500atttacactc ttgattctac aatgtagaaa atgaggaaat gccacaaatt gtatggtgat 1560aaaagtcacg tgaaacaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1620a 1621
<210> 108
<211> 382
<212> PRT
<213> Homo sapien
<400> 108Met Ala Leu Gln Gly Ile Ser Val Met Glu Leu Ser Gly Leu Ala Pro1 5 10 15Gly Pro Phe Cys Ala Met Val Leu Ala Asp Phe Gly Ala Arg Val Val
20 25 30Arg Val Asp Arg Pro Gly Ser Arg Tyr Asp Val Ser Arg Leu Gly Arg35 40 45Gly Lys Arg Ser Leu Val Leu Asp Leu Lys Gln Pro Arg Gly Ala Ala
50 55 60Val Leu Arg Arg Leu Cys Lys Arg Set Asp Val Leu Leu Glu Pro Phe65 70 75 80Arg Arg Gly Val Met Glu Lys Leu Gln Leu Gly Pro Glu Ile Leu Gln
85 90 95Arg Glu Asn Pro Arg Leu Ile Tyr Ala Arg Leu Ser Gly Phe Gly Gln
100 105 110Ser Gly Ser Phe Cys Arg Leu Ala Gly His Asp Ile Asn Tyr Leu Ala
115 120 125Leu Ser Gly Val Leu Ser Lys Ile Gly Arg Set Gly Glu Asn Pro Tyr
130 135 140Ala Pro Leu Asn Leu Leu Ala Asp Phe Ala Gly Gly Gly Leu Met Cys145 150 155 160Ala Leu Gly Ile Ile Met Ala Leu Phe Asp Arg Thr Arg Thr Asp Lys
165 170 175Gly Gln Val Ile Asp Ala Asn Met Val Glu Gly Thr Ala Tyr Leu Ser
180 185 190Ser Phe Leu Trp Lys Thr Gln Lys Ser Ser Leu Trp Glu Ala Pro Arg
195 200 205Gly Gln Asn Met Leu Asp Gly Gly Ala Pro Phe Tyr Thr Thr Tyr Arg
210 215 220Thr Ala Asp Gly Glu Phe Met Ala Val Gly Ala Ile Glu Pro Gln Phe225 230 235 240Tyr Glu Leu Leu Ile Lys Gly Leu Gly Leu Lys Ser Asp Glu Leu Pro
245 250 255Asn Gln Met Ser Met Asp Asp Trp Pro Glu Met Lys Lys Lys Phe Ala
260 265 270Asp Val Phe Ala Lys Lys Thr Lys Ala Glu Trp Cys Gln Ile Phe Asp
275 280 285Gly Thr Asp Ala Cys Val Thr Pro Val Leu Thr Phe Glu Glu Val Val
290 295 300His His Asp His Asn Lys Glu Arg Gly Ser Phe Ile Thr Ser Glu Glu305 310 315 320Gln Asp Val Ser Pro Arg Pro Ala Pro Leu Leu Leu Asn Thr Pro Ala
325 330 335Ile Pro Set Phe Lys Arg Asp Pro Phe Ile Gly Glu His Thr Glu Glu
340 345 350Ile Leu Glu Glu Phe Gly Phe Set Arg Glu Glu Ile Tyr Gln Leu Asn
355 360 365Ser Asp Lys Ile Ile Glu Ser Asn Lys Val Lys Ala Ser Leu
370 375 380
<210> 109
<211> 1524
<212> DNA
<213> Homo sapien
<400> 109ggcacgaggc tgcgccaggg cctgagcgga ggcgggggca gcctcgccag cgggggcccc 60gggcctggcc atgcctcact gagccagcgc ctgcgcctct acctcgccga cagctggaac 120cagtgcgacc tagtggctct cacctgcttc ctcctgggcg tgggctgccg gctgaccccg 180ggtttgtacc acctgggccg cactgtcctc tgcatcgact tcatggtttt cacggtgcgg 240ctgcttcaca tcttcacggt caacaaacag ctggggccca agatcgtcat cgtgagcaag 300atgatgaagg acgtgttctt cttcctcttc ttcctcggcg tgtggctggt agcctatggc 360gtggccacgg aggggctcct gaggccacgg gacagtgact tcccaagtat cctgcgccgc 420gtcttctacc gtccctacct gcagatcttc gggcagattc cccaggagga catggacgtg 480gccctcatgg agcacagcaa ctgctcgtcg gagcccggct tctgggcaca ccctcctggg 540gcccaggcgg gcacctgcgt ctcccagtat gccaactggc tggtggtgct gctcctcgtc 600atcttcctgc tcgtggccaa catcctgctg gtcaacttgc tcattgccat gttcagttac 660acattcggca aagtacaggg caacagcgat ctctactgga aggcgcagcg ttaccgcctc 720atccgggaat tccactctcg gcccgcgctg gccccgccct ttatcgtcat ctcccacttg 780cgcctcctgc tcaggcaatt gtgcaggcga ccccggagcc cccagccgtc ctccccggcc 840ctcgagcatt tccgggttta cctttctaag gaagccgagc ggaagctgct aacgtgggaa 900tcggtgcata aggagaactt tctgctggca cgcgctaggg acaagcggga gagcgactcc 960gagcgtctga agcgcacgtc ccagaaggtg gacttggcac tgaaacagct gggacacatc 1020cgcgagtacg aacagcgcct gaaagtgctg gagcgggagg tccagcagtg tagccgcgtc 1080ctggggtggg tggccgaggc cctgagccgc tctgccttgc tgcccccagg tgggccgcca 1140ccccctgacc tgcctgggtc caaagactga gccctgctgg cggacttcaa ggagaagccc 1200ccacagggga ttttgctcct agagtaaggc tcatctgggc ctcggccccc gcacctggtg 1260gccttgtcct tgaggtgagc cccatgtcca tctgggccac tgtcaggacc acctttggga 1320gtgtcatcct tacaaaccac agcatgcccg gctcctccca gaaccagtcc cagcctggga 1380ggatcaaggc ctggatcccg ggccgttatc catctggagg ctgcagggtc cttggggtaa 1440cagggaccac agacccctca ccactcacag attcctcaca ctggggaaat aaagccattt 1500cagaggaaaa aaaaaaaaaa aaaa 1524
<210> 110
<211> 3410
<212> DNA
<213> Homo sapien
<400> 110gggaaccagc ctgcacgcgc tggctccggg tgacagccgc gcgcctcggc caggatctga 60gtgatgagac gtgtccccac tgaggtgccc cacagcagca ggtgttgagc atgggctgag 120aagctggacc ggcaccaaag ggctggcaga aatgggcgcc tggctgattc ctaggcagtt 180ggcggcagca aggaggagag gccgcagctt ctggagcaga gccgagacga agcagttctg 240gagtgcctga acggccccct gagccctacc cgcctggccc actatggtcc agaggctgtg 300ggtgagccgc ctgctgcggc accggaaagc ccagctcttg ctggtcaacc tgctaacctt 360tggcctggag gtgtgtttgg ccgcaggcat cacctatgtg ccgcctctgc tgctggaagt 420gggggtagag gagaagttca tgaccatggt gctgggcatt ggtccagtgc tgggcctggt 480ctgtgtcccg ctcctaggct cagccagtga ccactggcgt ggacgctatg gccgccgccg 540gcccttcatc tgggcactgt ccttgggcat cctgctgagc ctctttctca tcccaagggc 600cggctggcta gcagggctgc tgtgcccgga tcccaggccc ctggagctgg cactgctcat 660cctgggcgtg gggctgctgg acttctgtgg ccaggtgtgc ttcactccac tggaggccct 720gctctctgac ctcttccggg acccggacca ctgtcgccag gcctactctg tctatgcctt 780catgatcagt cttgggggct gcctgggcta cctcctgcct gccattgact gggacaccag 840tgccctggcc ccctacctgg gcacccagga ggagtgcctc tttggcctgc tcaccctcat 900cttcctcacc tgcgtagcag ccacactgct ggtggctgag gaggcagcgc tgggccccac 960cgagccagca gaagggctgt cggccccctc cttgtcgccc cactgctgtc catgccgggc 1020ccgcttggct ttccggaacc tgggcgccct gcttccccgg ctgcaccagc tgtgctgccg 1080catgccccgc accctgcgcc ggctcttcgt ggctgagctg tgcagctgga tggcactcat 1140gaccttcacg ctgttttaca cggatttcgt gggcgagggg ctgtaccagg gcgtgcccag 1200agctgagccg ggcaccgagg cccggagaca ctatgatgaa ggcgttcgga tgggcagcct 1260ggggctgttc ctgcagtgcg ccatctccct ggtcttctct ctggtcatgg accggctggt 1320gcagcgattc ggcactcgag cagtctattt ggccagtgtg gcagctttcc ctgtggctgc 1380cggtgccaca tgcctgtccc acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg 1440gttcaccttc tcagccctgc agatcctgcc ctacacactg gcctccctct accaccggga 1500gaagcaggtg ttcctgccca aataccgagg ggacactgga ggtgctagca gtgaggacag 1560cctgatgacc agcttcctgc caggccctaa gcctggagct cccttcccta atggacacgt 1620gggtgctgga ggcagtggcc tgctcccacc tccacccgcg ctctgcgggg cctctgcctg 1680tgatgtctcc gtacgtgtgg tggtgggtga gcccaccgag gccagggtgg ttccgggccg 1740gggcatctgc ctggacctcg ccatcctgga tagtgccttc ctgctgtccc aggtggcccc 1800atccctgttt atgggctcca ttgtccagct cagccagtct gtcactgcct atatggtgtc 1860tgccgcaggc ctgggtctgg tcgccattta ctttgctaca caggtagtat ttgacaagag 1920cgacttggcc aaatactcag cgtagaaaac ttccagcaca ttggggtgga gggcctgcct 1980cactgggtcc cagctccccg ctcctgttag ccccatgggg ctgccgggct ggccgccagt 2040ttctgttgct gccaaagtaa tgtggctctc tgctgccacc ctgtgctgct gaggtgcgta 2100gctgcacagc tgggggctgg ggcgtccctc tcctctctcc ccagtctcta gggctgcccg 2160actggaggcc ttccaagggg gcttcagtct ggacttatac agggaggcca gaagggctcc 2220atgcactgga atgcggggac tctgcaggtg gattacccag gctcagggtt aacagctagc 2280ctcctagttg agacacacct agagaagggt ttttgggagc tgaataaact cagtcacctg 2340gtttcccatc tctaagcccc ttaacctgca gcttcgttta atgtagctct tgcatgggag 2400tttctaggat gaaacactcc tccatgggat ttgaacatat gacttatttg taggggaaga 2460gtcctgaggg gcaacacaca agaaccaggt cccctcagcc cacagcactg tctttttgct 2520gatccacccc cctcttacct tttatcagga tgtggcctgt tggtccttct gttgccatca 2580cagagacaca ggcatttaaa tatttaactt atttatttaa caaagtagaa gggaatccat 2640tgctagcttt tctgtgttgg tgtctaatat ttgggtaggg tgggggatcc ccaacaatca 2700ggtcccctga gatagctggt cattgggctg atcattgcca gaatcttctt ctcctggggt 2760ctggcccccc aaaatgccta acccaggacc ttggaaattc tactcatccc aaatgataat 2820tccaaatgct gttacccaag gttagggtgt tgaaggaagg tagagggtgg ggcttcaggt 2880ctcaacggct tccctaacca cccctcttct cttggcccag cctggttccc cccacttcca 2940ctcccctcta ctctctctag gactgggctg atgaaggcac tgcccaaaat ttcccctacc 3000cccaactttc ccctaccccc aactttcccc accagctcca caaccctgtt tggagctact 3060gcaggaccag aagcacaaag tgcggtttcc caagcctttg tccatctcag cccccagagt 3120atatctgtgc ttggggaatc tcacacagaa actcaggagc accccctgcc tgagctaagg 3180gaggtcttat ctctcagggg gggtttaagt gccgtttgca ataatgtcgt cttatttatt 3240tagcggggtg aatattttat actgtaagtg agcaatcaga gtataatgtt tatggtgaca 3300aaattaaagg ctttcttata tgtttaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3360aaaaaaaara aaaaaaaaaa aaaaaaaaaa aaaaaaataa aaaaaaaaaa 3410
<210> 111
<211> 1289
<212> DNA
<213> Homo sapien
<400> 111agccaggcgt ccctctgcct gcccactcag tggcaacacc cgggagctgt tttgtccttt 60gtggagcctc agcagttccc tctttcagaa ctcactgcca agagccctga acaggagcca 120ccatgcagtg cttcagcttc attaagacca tgatgatcct cttcaatttg ctcatctttc 180tgtgtggtgc agccctgttg gcagtgggca tctgggtgtc aatcgatggg gcatcctttc 240tgaagatctt cgggccactg tcgtccagtg ccatgcagtt tgtcaacgtg ggctacttcc 300tcatcgcagc cggcgttgtg gtctttgctc ttggtttcct gggctgctat ggtgctaaga 360ctgagagcaa gtgtgccctc gtgacgttct tcttcatcct cctcctcatc ttcattgctg 420aggttgcagc tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt 480tgctggtagt gcctgccatc aagaaagatt atggttccca ggaagacttc actcaagtgt 540ggaacaccac catgaaaggg ctcaagtgct gtggcttcac caactatacg gattttgagg 600actcacccta cttcaaagag aacagtgcct ttcccccatt ctgttgcaat gacaacgtca 660ccaacacagc caatgaaacc tgcaccaagc aaaaggctca cgaccaaaaa gtagagggtt 720gcttcaatca gcttttgtat gacatccgaa ctaatgcagt caccgtgggt ggtgtggcag 780ctggaattgg gggcctcgag ctggctgcca tgattgtgtc catgtatctg tactgcaatc 840tacaataagt ccacttctgc ctctgccact actgctgcca catgggaact gtgaagaggc 900accctggcaa gcagcagtga ttgggggagg ggacaggatc taacaatgtc acttgggcca 960gaatggacct gccctttctg ctccagactt ggggctagat agggaccact ccttttagcg 1020atgcctgact ttccttccat tggtgggtgg atgggtgggg ggcattccag agcctctaag 1080gtagccagtt ctgttgccca ttcccccagt ctattaaacc cttgatatgc cccctaggcc 1140tagtggtgat cccagtgctc tactggggga tgagagaaag gcattttata gcctgggcat 1200aagtgaaatc agcagagcct ctgggtggat gtgtagaagg cacttcaaaa tgcataaacc 1260tgttacaatg ttaaaaaaaa aaaaaaaaa 1289
<210> 112
<211> 315
<212> PRT
<213> Homo sapien
<400> 112Met Val Phe Thr Val Arg Leu Leu His Ile PheThr Val Asn Lys Gln1 5 10 15Leu Gly Pro Lys Ile Val Ile Val Ser Lys Met Met Lys Asp Val Phe
20 25 30Phe Phe Leu Phe Phe Leu Gly Val Trp Leu Val Ala Tyr Gly Val Ala
35 40 45Thr Glu Gly Leu Leu Arg Pro Arg Asp Ser Asp Phe Pro Ser Ile Leu
50 55 60Arg Arg Val Phe Tyr Arg Pro Tyr Leu Gln Ile Phe Gly Gln Ile Pro65 70 75 80Gln Glu Asp Met Asp Val Ala Leu Met Glu His Ser Asn Cys Ser Ser
85 90 95Glu Pro Gly Phe Trp Ala His Pro Pro Gly Ala Gln Ala Gly Thr Cys
100 105 110Val Ser Gln Tyr Ala Asn Trp Leu Val Val Leu Leu Leu Val Ile Phe
115 120 125Leu Leu Val Ala Ash Ile Leu Leu Val Asn Leu Leu Ile Ala Met Phe
130 135 140Set Tyr Thr Phe Gly Lys Val Gln Gly Asn Ser Asp Leu Tyr Trp Lys145 150 155 160Ala Gln Arg Tyr Arg Leu Ile Arg Glu Phe His Ser Arg Pro Ala Leu
165 170 175Ala Pro Pro Phe Ile Val Ile Ser His Leu Arg Leu Leu Leu Arg Gln
180 185 190Leu Cys Arg Arg Pro Arg Ser Pro Gln Pro Ser Ser Pro Ala Leu Glu
195 200 205His Phe Arg Val Tyr Leu Ser Lys Glu Ala Glu Arg Lys Leu Leu Thr
210 215 220Trp Glu Ser Val His Lys Glu Asn Phe Leu Leu Ala Arg Ala Arg Asp225 230 235 240Lys Arg Glu Ser Asp Ser Glu Arg Leu Lys Arg Thr Ser Gln Lys Val
245 250 255Asp Leu Ala Leu Lys Gln Leu Gly His Ile Arg Glu Tyr Glu Gln Arg
260 265 270Leu Lys Val Leu Glu Arg Glu Val Gln Gln Cys Ser Arg Val Leu Gly
275 280 285Trp Val Ala Glu Ala Leu Ser Arg Ser Ala Leu Leu Pro Pro Gly Gly
290 295 300Pro Pro Pro Pro Asp Leu Pro Gly Ser Lys Asp305 310 315
<210> 113
<211> 553
<212> PRT
<213> Homo sapien
<400> 113Met Val Gln Arg Leu Trp Val Ser Arg Leu Leu Arg His Arg Lys Ala1 5 10 15Gln Leu Leu Leu Val Asn Leu Leu Thr Phe Gly Leu Glu Val Cys Leu
20 25 30Ala Ala Gly Ile Thr Tyr Val Pro Pro Leu Leu Leu Glu Val Gly Val
35 40 45Glu Glu Lys Phe Met Thr Met Val Leu Gly Ile Gly Pro Val Leu Gly
50 55 60Leu Val Cys Val Pro Leu Leu Gly Ser Ala Ser Asp His Trp Arg Gly65 70 75 80Arg Tyr Gly Arg Arg Arg Pro Phe Ile Trp Ala Leu Ser Leu Gly Ile
85 90 95Leu Leu Ser Leu Phe Leu Ile Pro Arg Ala Gly Trp Leu Ala Gly Leu
100 105 110Leu Cys Pro Asp Pro Arg Pro Leu Glu Leu Ala Leu Leu Ile Leu Gly
115 120 125Val Gly Leu Leu Asp Phe Cys Gly Gln Val Cys Phe Thr Pro Leu Glu
130 135 140Ala Leu Leu Ser Asp Leu Phe Arg Asp Pro Asp His Cys Arg Gln Ala145 150 155 160Tyr Ser Val Tyr Ala Phe Met Ile Ser Leu Gly Gly Cys Leu Gly Tyr
165 170 175Leu Leu Pro Ala Ile Asp Trp Asp Thr Ser Ala Leu Ala Pro Tyr Leu
180 185 190Gly Thr Gln Glu Glu Cys Leu Phe Gly Leu Leu Thr Leu Ile Phe Leu
195 200 205Thr Cys Val Ala Ala Thr Leu Leu Val Ala Glu Glu Ala Ala Leu Gly
210 215 220Pro Thr Glu Pro Ala Glu Gly Leu Ser Ala Pro Ser Leu Ser Pro His225 230 235 240Cys Cys Pro Cys Arg Ala Arg Leu Ala Phe Arg Asn Leu Gly Ata Leu
245 250 255Leu Pro Arg Leu His Gln Leu Cys Cys Arg Met Pro Arg Thr Leu Arg
260 265 270Arg Leu Phe Val Ala Glu Leu Cys Ser Trp Met Ala Leu Met Thr Phe
275 280 285Thr Leu Phe Tyr Thr Asp Phe Val Gly Glu Gly Leu Tyr Gln Gly Val
290 295 300Pro Arg Ala Glu Pro Gly Thr Glu Ala Arg Arg His Tyr Asp Glu Gly305 310 315 320Val Arg Met Gly Ser Leu Gly Leu Phe Leu Gln Cys Ala Ile Ser Leu
325 330 335Val Phe Ser Leu Val Met Asp Arg Leu Val Gln Arg Phe Gly Thr
340 345 350Ala Val Tyr Leu Ala Ser Val Ala Ala Phe Pro Val Ala Ala Gly Ala
355 360 365Thr Cys Leu Ser His Ser Val Ala Val Val Thr Ala Ser Ala Ala Leu
370 375 380Thr Gly Phe Thr Phe Ser Ala Leu Gln Ile Leu Pro Tyr Thr Leu Ala385 390 395 400Ser Leu Tyr His Arg Glu Lys Gln Val Phe Leu Pro Lys Tyr Arg Gly
405 410 415Asp Thr Gly Gly Ala Ser Ser Glu Asp Ser Leu Met Thr Ser Phe Leu
420 425 430Pro Gly Pro Lys Pro Gly Ala Pro Phe Pro Asn Gly His Val Gly Ala
435 440 445Gly Gly Ser Gly Leu Leu Pro Pro Pro Pro Ala Leu Cys Gly Ala Ser
450 455 460Ala Cys Asp Val Ser Val Arg Val Val Val Gly Glu Pro Thr Glu Ala465 470 475 480Arg Val Val Pro Gly Arg Gly Ile Cys Leu Asp Leu Ala Ile Leu Asp
485 490 495Ser Ala Phe Leu Leu Ser Gln Val Ala Pro Ser Leu Phe Met Gly Ser
500 505 510Ile Val Gln Leu Ser Gln Ser Val Thr Ala Tyr Met Val Ser Ala Ala
515 520 525Gly Leu Gly Leu Val Ala Ile Tyr Phe Ala Thr Gln Val Val Phe Asp
530 535 540Lys Set Asp Leu Ala Lys Tyr Ser Ala545 550
<210> 114
<211> 241
<212> PRT
<213> Homo sapien
<400> 114Met Gln Cys Phe Ser Phe Ile Lys Thr Met Met Ile Leu Phe Asn Leu1 5 10 15Leu Ile Phe Leu Cys Gly Ala Ala Leu Leu Ala Val Gly Ile Trp Val
20 25 30Ser Ile Asp Gly Ala Ser Phe Leu Lys Ile Phe Gly Pro Leu Ser Ser
35 40 45Ser Ala Met Gln Phe Val Asn Val Gly Tyr Phe Leu Ile Ala Ala Gly
50 55 60Val Val Val Phe Ala Leu Gly Phe Leu Gly Cys Tyr Gly Ala Lys Thr65 70 75 80Glu Ser Lys Cys Ala Leu Val Thr Phe Phe Phe Ile Leu Leu Leu Ile
85 90 95Phe Ile Ala Glu Val Ala Ala Ala Val Val Ala Leu Val Tyr Thr Thr
100 105 110Met Ala Glu His Phe Leu Thr Leu Leu Val Val Pro Ala Ile Lys Lys
115 120 125Asp Tyr Gly Ser Gln Glu Asp Phe Thr Gln Val Trp Asn Thr Thr Met
130 135 140Lys Gly Leu Lys Cys Cys Gly Phe Thr Asn Tyr Thr Asp Phe Glu Asp145 150 155 160Ser Pro Tyr Phe Lys Glu Asn Ser Ala Phe Pro Pro Phe Cys Cys Asn
165 170 175Asp Asn Val Thr Asn Thr Ala Asn Glu Thr Cys Thr Lys Gln Lys Ala
180 185 190His Asp Gln Lys Val Glu Gly Cys Phe Asn Gln Leu Leu Tyr Asp Ile
195 200 205Arg Thr Asn Ala Val Thr Val Gly Gly Val Ala Ala Gly Ile Gly Gly
210 215 220Leu Glu Leu Ala Ala Met Ile Val Ser Met Tyr Leu Tyr Cys Asn Leu225 230 235 240Gln
<210> 115
<211> 366
<212> DNA
<213> Homo sapien
<400> 115gctctttctc tcccctcctc tgaatttaat tctttcaact tgcaatttgc aaggattaca 60catttcactg tgatgtatat tgtgttgcaa aaaaaaaaaa gtgtctttgt ttaaaattac 120ttggtttgtg aatccatctt gctttttccc cattggaact agtcattaac ccatctctga 180actggtagaa aaacatctga agagctagtc tatcagcatc tgacaggtga attggatggt 240tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt 300tctctacatg cataacaaac cctgctccaa tctgtcacat aaaagtctgt gacttgaagt 360ttagtc 366
<210> 116
<211> 282
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (282)
<223> n = A,T,C or G
<400> 116acaaagatga accatttcct atattatagc aaaattaaaa tctacccgta ttctaatatt 60gagaaatgag atnaaacaca atnttataaa gtctacttag agaagatcaa gtgacctcaa 120agactttact attttcatat tttaagacac atgatttatc ctattttagt aacctggttc 180atacgttaaa caaaggataa tgtgaacagc agagaggatt tgttggcaga aaatctatgt 240tcaatctnga actatctana tcacagacat ttctattcct tt 282
<210> 117
<211> 305
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(305)
<223> n = A,T,C or G
<400> 117acacatgtcg cttcactgcc ttcttagatg cttctggtca acatanagga acagggacca 60tatttatcct ccctcctgaa acaattgcaa aataanacaa aatatatgaa acaattgcaa 120aataaggcaa aatatatgaa acaacaggtc tcgagatatt ggaaatcagt caatgaagga 180tactgatccc tgatcactgt cctaatgcag gatgtgggaa acagatgagg tcacctctgt 240gactgcccca gcttactgcc tgtagagagt ttctangctg cagttcagac agggagaaat 300tgggt 305
<210> 118
<211> 71
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(71)
<223> n = A,T,C or G
<400> 118accaaggtgt ntgaatctct gacgtgggga tctctgattc ccgcacaatc tgagtggaaa 60aantcctggg t 71
<210> 119
<211> 212
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(212)
<223> n = A,T,C or G
<400> 119actccggttg gtgtcagcag cacgtggcat tgaacatngc aatgtggagc ccaaaccaca 60gaaaatgggg tgaaattggc caactttcta tnaacttatg ttggcaantt tgccaccaac 120agtaagctgg cccttctaat aaaagaaaat tgaaaggttt ctcactaanc ggaattaant 180aatggantca aganactccc aggcctcagc gt 212
<210> 120
<211> 90
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(90)
<223> n = A,T,C or G
<400> 120actcgttgca natcaggggc cccccagagt caccgttgca ggagtccttc tggtcttgcc 60ctccgccggc gcagaacatg ctggggtggt
<210> 121
<211> 218
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(218)
<223> n = A,T,C or G
<400> 121tgtancgtga anacgacaga nagggttgtc aaaaatggag aanccttgaa gtcattttga 60gaataagatt tgctaaaaga tttggggcta aaacatggtt attgggagac atttctgaag 120atatncangt aaattangga atgaattcat ggttcttttg ggaattcctt tacgatngcc 180agcatanact tcatgtgggg atancagcta cccttgta 218
<210> 122
<211> 171
<212> DNA
<213> Homo sapien
<400> 122taggggtgta tgcaactgta aggacaaaaa ttgagactca actggcttaa ccaataaagg 60catttgttag ctcatggaac aggaagtcgg atggtggggc atcttcagtg ctgcatgagt 120caccaccccg gcggggtcat ctgtgccaca ggtccctgtt gacagtgcgg t 171
<210> 123
<211> 76
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(76)
<223> n = A,T,C or G
<400> 123tgtagcgtga agacnacaga atggtgtgtg ctgtgctatc caggaacaca tttattatca 60ttatcaanta ttgtgt 76
<210> 124
<211> 131
<212> DNA
<213> Homo sapien
<400> 124acctttcccc aaggccaatg tcctgtgtgc taactggccg gctgcaggac agctgcaatt 60caatgtgctg ggtcatatgg aggggaggag actctaaaat agccaatttt attctcttgg 120ttaagatttg t 131
<210> 125
<211> 432
<212> DNA
<213> Homo sapien
<400> 125actttatcta ctggctatga aatagatggt ggaaaattgc gttaccaact ataccactgg 60cttgaaaaag aggtgatagc tcttcagagg acttgtgact tttgctcaga tgctgaagaa 120ctacagtctg catttggcag aaatgaagat gaatttggat taaatgagga tgctgaagat 180ttgcctcacc aaacaaaagt gaaacaactg agagaaaatt ttcaggaaaa aagacagtgg 240ctcttgaagt atcagtcact tttgagaatg tttcttagtt actgcatact tcatggatcc 300catggtgggg gtcttgcatc tgtaagaatg gaattgattt tgcttttgca agaatctcag 360caggaaacat cagaaccact attttctagc cctctgtcag agcaaacctc agtgcctctc 420ctctttgctt gt 432
<210> 126
<211> 112
<212> DNA
<213> Homo sapien
<400> 126acacaacttg aatagtaaaa tagaaactga gctgaaattt ctaattcact ttctaaccat 60agtaagaatg atatttcccc ccagggatca ccaaatattt ataaaaattt gt 112
<210> 127
<211> 54
<212> DNA
<213> Homo sapien
<400> 127accacgaaac cacaaacaag atggaagcat caatccactt gccaagcaca gcag 54
<210> 128
<211> 323
<212> DNA
<213> Homo sapien
<400> 128acctcattag taattgtttt gttgtttcat ttttttctaa tgtctcccct ctaccagctc 60acctgagata acagaatgaa aatggaagga cagccagatt tctcctttgc tctctgctca 120ttctctctga agtctaggtt acccattttg gggacccatt ataggcaata aacacagttc 180ccaaagcatt tggacagttt cttgttgtgt tttagaatgg ttttcctttt tcttagcctt 240ttcctgcaaa aggctcactc agtcccttgc ttgctcagtg gactgggctc cccagggcct 300aggctgcctt cttttccatg tcc 323
<210> 129
<211> 192
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (192)
<223> n = A,T,C or G
<400> 129acatacatgt gtgtatattt ttaaatatca cttttgtatc actctgactt tttagcatac 60tgaaaacaca ctaacataat ttntgtgaac catgatcaga tacaacccaa atcattcatc 120tagcacattc atctgtgata naaagatagg tgagtttcat ttccttcacg ttggccaatg 180gataaacaaa gt 192
<210> 130
<211> 362
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(362)
<223> n = A,T,C or G
<400> 130ccctttttta tggaatgagt agactgtatg tttgaanatt tanccacaac ctctttgaca 60tataatgacg caacaaaaag gtgctgttta gtcctatggt tcagtttatg cccctgacaa 120gtttccattg tgttttgccg atcttctggc taatcgtggt atcctccatg ttattagtaa 180ttctgtattc cattttgtta acgcctggta gatgtaacct gctangaggc taactttata 240cttatttaaa agctcttatt ttgtggtcat taaaatggca atttatgtgc agcactttat 300tgcagcagga agcacgtgtg ggttggttgt aaagctcttt gctaatctta aaaagtaatg 360gg 362
<210> 131
<211> 332
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(332)
<223> n = A,T,C or G
<400> 131ctttttgaaa gatcgtgtcc actcctgtgg acatcttgtt ttaatggagt ttcccatgca 60gtangactgg tatggttgca gctgtccaga taaaaacatt tgaagagctc caaaatgaga 120gttctcccag gttcgccctg ctgctccaag tctcagcagc agcctctttt aggaggcatc 180ttctgaacta gattaaggca gcttgtaaat ctgatgtgat ttggtttatt atccaactaa 240cttccatctg ttatcactgg agaaagccca gactccccan gacnggtacg gattgtgggc 300atanaaggat tgggtgaagc tggcgttgtg gt 332
<210> 132
<211> 322
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(322)
<223> n = A,T,C or G
<400> 132acttttgcca ttttgtatat ataaacaatc ttgggacatt ctcctgaaaa ctaggtgtcc 60agtggctaag agaactcgat ttcaagcaat tctgaaagga aaaccagcat gacacagaat 120ctcaaattcc caaacagggg ctctgtggga aaaatgaggg aggacctttg tatctcgggt 180tttagcaagt taaaatgaan atgacaggaa aggcttattt atcaacaaag agaagagttg 240ggatgcttct aaaaaaaact ttggtagaga aaataggaat gctnaatcct agggaagcct 300gtaacaatct acaattggtc ca 322
<210> 133
<211> 278
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(278)
<223> n = A,T,C or G
<400> 133acaagccttc acaagtttaa ctaaattggg attaatcttt ctgtanttat ctgcataatt 60cttgtttttc tttccatctg gctcctgggt tgacaatttg tggaaacaac tctattgcta 120ctatttaaaa aaaatcacaa atctttccct ttaagctatg ttnaattcaa actattcctg 180ctattcctgt tttgtcaaag aaattatatt tttcaaaata tgtntatttg tttgatgggt 240cccacgaaac actaataaaa accacagaga ccagcctg 278
<210> 134
<211> 121
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(121)
<223> n = A,T,C or G
<400> 134gtttanaaaa cttgtttagc tccatagagg aaagaatgtt aaactttgta ttttaaaaca 60tgattctctg aggttaaact tggttttcaa atgttatttt tacttgtatt ttgcttttgg 120t 121
<210> 135
<211> 350
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(350)
<223> n = A,T,C or G
<400> 135acttanaacc atgcctagca catcagaatc cctcaaagaa catcagtata atcctatacc 60atancaagtg gtgactggtt aagcgtgcga caaaggtcag ctggcacatt acttgtgtgc 120aaacttgata cttttgttct aagtaggaac tagtatacag tncctaggan tggtactcca 180gggtgccccc caactcctgc agccgctcct ctgtgccagn ccctgnaagg aactttcgct 240ccacctcaat caagccctgg gccatgctac ctgcaattgg ctgaacaaac gtttgctgag 300ttcccaagga tgcaaagcct ggtgctcaac tcctggggcg tcaactcagt 350
<210> 136
<211> 399
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(399)
<223> n = A,T,C or G
<400> 136tgtaccgtga agacgacaga agttgcatgg cagggacagg gcagggccga ggccagggtt 60gctgtgattg tatccgaata ntcctcgtga gaaaagataa tgagatgacg tgagcagcct 120gcagacttgt gtctgccttc aanaagccag acaggaaggc cctgcctgcc ttggctctga 180cctggcggcc agccagccag ccacaggtgg gcttcttcct tttgtggtga caacnccaag 240aaaactgcag aggcccaggg tcaggtgtna gtgggtangt gaccataaaa caccaggtgc 300tcccaggaac ccgggcaaag gccatcccca cctacagcca gcatgcccac tggcgtgatg 360ggtgcagang gatgaagcag ccagntgttc tgctgtggt 399
<210> 137
<211> 165
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (I)...(165)
<223> n = A,T,C or G
<400> 137actggtgtgg tngggggtga tgctggtggt anaagttgan gtgacttcan gatggtgtgt 60ggaggaagtg tgtgaacgta gggatgtaga ngttttggcc gtgctaaatg agcttcggga 120ttggctggtc ccactggtgg tcactgtcat tggtggggtt cctgt 165
<210> 138
<211> 338
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(338)
<223> n = A,T,C or G
<400> 138actcactgga atgccacatt cacaacagaa tcagaggtct gtgaaaacat taatggctcc 60ttaacttctc cagtaagaat cagggacttg aaatggaaac gttaacagcc acatgcccaa 120tgctgggcag tctcccatgc cttccacagt gaaagggctt gagaaaaatc acatccaatg 180tcatgtgttt ccagccacac caaaaggtgc ttggggtgga gggctggggg catananggt 240cangcctcag gaagcctcaa gttccattca gctttgccac tgtacattcc ccatntttaa 300aaaaactgat gccttttttt tttttttttg taaaattc 338
<210> 139
<211> 382
<212> DNA
<213> Homo sapien
<400> 139gggaatcttg gtttttggca tctggtttgc ctatagccga ggccactttg acagaacaaa 60gaaagggact tcgagtaaga aggtgattta cagccagcct agtgcccgaa gtgaaggaga 120attcaaacag acctcgtcat tcctggtgtg agcctggtcg gctcaccgcc tatcatctgc 180atttgcctta ctcaggtgct accggactct ggcccctgat gtctgtagtt tcacaggatg 240ccttatttgt cttctacacc ccacagggcc ccctacttct tcggatgtgt ttttaataat 300gtcagctatg tgccccatcc tccttcatgc cctccctccc tttcctacca ctgctgagtg 360gcctggaact tgtttaaagt gt 382
<210> 140
<211> 200
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(200)
<223> n = A,T,C or G
<400> 140accaaanctt ctttctgttg tgttngattt tactataggg gtttngcttn ttctaaanat 60acttttcatt taacancttt tgttaagtgt caggctgcac tttgctccat anaattattg 120ttttcacatt tcaacttgta tgtgtttgtc tcttanagca ttggtgaaat cacatatttt 180atattcagca taaaggagaa 200
<210> 141
<211> 335
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(335)
<223> n = A,T,C or G
<400> 141actttatttt caaaacactc atatgttgca aaaaacacat agaaaaataa agtttggtgg 60gggtgctgac taaacttcaa gtcacagact tttatgtgac agattggagc agggtttgtt 120atgcatgtag agaacccaaa ctaatttatt aaacaggata gaaacaggct gtctgggtga 180aatggttctg agaaccatcc aattcacctg tcagatgctg atanactagc tcttcagatg 240tttttctacc agttcagaga tnggttaatg actanttcca atggggaaaa agcaagatgg 300attcacaaac caagtaattt taaacaaaga cactt 335
<210> 142
<211> 459
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(459)
<223> n = A,T,C or G
<400> 142accaggttaa tattgccaca tatatccttt ccaattgcgg gctaaacaga cgtgtattta 60gggttgttta aagacaaccc agcttaatat caagagaaat tgtgaccttt catggagtat 120ctgatggaga aaacactgag ttttgacaaa tcttatttta ttcagatagc agtctgatca 180cacatggtcc aacaacactc aaataataaa tcaaatatna tcagatgtta aagattggtc 240ttcaaacatc atagccaatg atgccccgct tgcctataat ctctccgaca taaaaccaca 300tcaacacctc agtggccacc aaaccattca gcacagcttc cttaactgtg agctgtttga 360agctaccagt ctgagcacta ttgactatnt ttttcangct ctgaatagct ctagggatct 420cagcangggt gggaggaacc agctcaacct tggcgtant 459
<210> 143
<211> 140
<212> DNA
<213> Homo sapien
<400> 143acatttcctt ccaccaagtc aggactcctg gcttctgtgg gagttcttat cacctgaggg 60aaatccaaac agtctctcct agaaaggaat agtgtcacca accccaccca tctccctgag 120accatccgac ttccctgtgt 140
<210> 144
<211> 164
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(164)
<223> n = A,T,C or G
<400> 144acttcagtaa caacatacaa taacaacatt aagtgtatat tgccatcttt gtcattttct 60atctatacca ctctcccttc tgaaaacaan aatcactanc caatcactta tacaaatttg 120aggcaattaa tccatatttg ttttcaataa ggaaaaaaag atgt 164
<210> 145
<211> 303
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(303)
<223> n = A,T,C or G
<400> 145acgtagacca tccaactttg tatttgtaat ggcaaacatc cagnagcaat tcctaaacaa 60actggagggt atttataccc aattatccca ttcattaaca tgccctcctc ctcaggctat 120gcaggacagc tatcataagt cggcccaggc atccagatac taccatttgt ataaacttca 180gtaggggagt ccatccaagt gacaggtcta atcaaaggag gaaatggaac ataagcccag 240tagtaaaatn ttgcttagct gaaacagcca caaaagactt accgccgtgg tgattaccat 300caa 303
<210> 146
<211> 327
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(327)
<223> n = A,T,C or G
<400> 146actgcagctc aattagaagt ggtctctgac tttcatcanc ttctccctgg gctccatgac 60actggcctgg agtgactcat tgctctggtt ggttgagaga gctcctttgc caacaggcct 120ccaagtcagg gctgggattt gtttcctttc cacattctag caacaatatg ctggccactt 180cctgaacagg gagggtggga ggagccagca tggaacaagc tgccactttc taaagtagcc 240agacttgccc ctgggcctgt cacacctact gatgaccttc tgtgcctgca ggatggaatg 300taggggtgag ctgtgtgact ctatggt 327
<210> 147
<211> 173
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(173)
<223> n = A,T,C or G
<400> 147acattgtttt tttgagataa agcattgana gagctctcct taacgtgaca caatggaagg 60actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120atattcaagc acatatgtta tatattattc agttccatgt ttatagccta gtt 173
<210> 148
<211> 477
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(477)
<223> n = A,T,C or G
<400> 148acaaccactt tatctcatcg aatttttaac ccaaactcac tcactgtgcc tttctatcct 60atgggatata ttatttgatg ctccatttca tcacacatat atgaataata cactcatact 120gccctactac ctgctgcaat aatcacattc ccttcctgtc ctgaccctga agccattggg 180gtggtcctag tggccatcag tccangcctg caccttgagc ccttgagctc cattgctcac 240nccancccac ctcaccgacc ccatcctctt acacagctac ctccttgctc tctaacccca 300tagattatnt ccaaattcag tcaattaagt tactattaac actctacccg acatgtccag 360caccactggt aagccttctc cagccaacac acacacacac acacncacac acacacatat 420ccaggcacag gctacctcat cttcacaatc acccctttaa ttaccatgct atggtgg 477
<210> 149
<211> 207
<212> DNA
<213> Homo sapien
<400> 149acagttgtat tataatatca agaaataaac ttgcaatgag agcatttaag agggaagaac 60taacgtattt tagagagcca aggaaggttt ctgtggggag tgggatgtaa ggtggggcct 120gatgataaat aagagtcagc caggtaagtg ggtggtgtgg tatgggcaca gtgaagaaca 180tttcaggcag agggaacagc agtgaaa 207
<210> 150
<211> 111
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(111)
<223> n = A,T,C or G
<400> 150accttgattt cattgctgct ctgatggaaa cccaactatc taatttagct aaaacatggg 60cacttaaatg tggtcagtgt ttggacttgt taactantgg catctttggg t 111
<210> 151
<211> 196
<212> DNA
<213> Homo sapien
<400> 151agcgcggcag gtcatattga acattccaga tacctatcat tactcgatgc tgttgataac 60agcaagatgg ctttgaactc agggtcacca ccagctattg gaccttacta tgaaaaccat 120ggataccaac cggaaaaccc ctatcccgca cagcccactg tggtccccac tgtctacgag 180gtgcatccgg ctcagt 196
<210> 152
<211> 132
<212> DNA
<213> Homo sapien
<400> 152acagcacttt cacatgtaag aagggagaaa ttcctaaatg taggagaaag ataacagaac 60cttccccttt tcatctagtg gtggaaacct gatgctttat gttgacagga atagaaccag 120gagggagttt gt 132
<210> 153
<211> 285
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(285)
<223> n = A,T,C or G
<400> 153acaanaccca nganaggcca ctggccgtgg tgtcatggcc tccaaacatg aaagtgtcag 60cttctgctct tatgtcctca tctgacaact ctttaccatt tttatcctcg ctcagcagga 120gcacatcaat aaagtccaaa gtcttggact tggccttggc ttggaggaag tcatcaacac 180cctggctagt gagggtgcgg cgccgctcct ggatgacggc atctgtgaag tcgtgcacca 240gtctgcaggc cctgtggaag cgccgtccac acggagtnag gaatt 285
<210> 154
<211> 333
<212> DNA
<213> Homo sapien
<400> 154accacagtcc tgttgggcca gggcttcatg accctttctg tgaaaagcca tattatcacc 60accccaaatt tttccttaaa tatctttaac tgaaggggtc agcctcttga ctgcaaagac 120cctaagccgg ttacacagct aactcccact ggccctgatt tgtgaaattg ctgctgcctg 180attggcacag gagtcgaagg tgttcagctc ccctcctccg tggaacgaga ctctgatttg 240agtttcacaa attctcgggc cacctcgtca ttgctcctct gaaataaaat ccggagaatg 300gtcaggcctg tctcatccat atggatcttc cgg 333
<210> 155
<211> 308
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(308)
<223> n = A,T,C or G
<400> 155actggaaata ataaaaccca catcacagtg ttgtgtcaaa gatcatcagg gcatggatgg 60gaaagtgctt tgggaactgt aaagtgccta acacatgatc gatgattttt gttataatat 120ttgaatcacg gtgcatacaa actctcctgc ctgctcctcc tgggccccag ccccagcccc 180atcacagctc actgctctgt tcatccaggc ccagcatgta gtggctgatt cttcttggct 240gcttttagcc tccanaagtt tctctgaagc caaccaaacc tctangtgta aggcatgctg 300gccctggt 308
<210> 156
<211> 295
<212> DNA
<213> Homo sapien
<400> 156accttgctcg gtgcttggaa catattagga actcaaaata tgagatgata acagtgccta 60ttattgatta ctgagagaac tgttagacat ttagttgaag attttctaca caggaactga 120gaataggaga ttatgtttgg ccctcatatt ctctcctatc ctccttgcct cattctatgt 180ctaatatatt ctcaatcaaa taaggttagc ataatcagga aatcgaccaa ataccaatat 240aaaaccagat gtctatcctt aagattttca aatagaaaac aaattaacag actat 295
<210> 157
<211> 126
<212> DNA
<213> Homo sapien
<400> 157acaagtttaa atagtgctgt cactgtgcat gtgctgaaat gtgaaatcca ccacatttct 60gaagagcaaa acaaattctg tcatgtaatc tctatcttgg gtcgtgggta tatctgtccc 120cttagt 126
<210> 158
<211> 442
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (442)
<223> n = A,T,C or G
<400> 158acccactggt cttggaaaca cccatcctta atacgatgat ttttctgtcg tgtgaaaatg 60aanccagcag gctgccccta gtcagtcctt ccttccagag aaaaagagat ttgagaaagt 120gcctgggtaa ttcaccatta atttcctccc ccaaactctc tgagtcttcc cttaatattt 180ctggtggttc tgaccaaagc aggtcatggt ttgttgagca tttgggatcc cagtgaagta 240natgtttgta gccttgcata cttagccctt cccacgcaca aacggagtgg cagagtggtg 300ccaaccctgt tttcccagtc cacgtagaca gattcacagt gcggaattct ggaagctgga 360nacagacggg ctctttgcag agccgggact ctgagangga catgagggcc tctgcctctg 420tgttcattct ctgatgtcct gt 442
<210> 159
<211> 498
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (498)
<223> n = A,T,C or G
<400> 159acttccaggt aacgttgttg tttccgttga gcctgaactg atgggtgacg ttgtaggttc 60tccaacaaga actgaggttg cagagcgggt agggaagagt gctgttccag ttgcacctgg 120gctgctgtgg actgttgttg attcctcact acggcccaag gttgtggaac tggcanaaag l80gtgtgttgtt gganttgagc tcgggcggct gtggtaggtt gtgggctctt caacaggggc 240tgctgtggtg ccgggangtg aangtgttgt gtcacttgag cttggccagc tctggaaagt 300antanattct tcctgaaggc cagcgcttgt ggagctggca ngggtcantg ttgtgtgtaa 360cgaaccagtg ctgctgtggg tgggtgtana tcctccacaa agcctgaagt tatggtgtcn 420tcaggtaana atgtggtttc agtgtccctg ggcngctgtg gaaggttgta nattgtcacc 480aagggaataa gctgtggt 498
<210> 160
<211> 380
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(380)
<223> n = A,T,C or G
<400> 160acctgcatcc agcttccctg ccaaactcac aaggagacat caacctctag acagggaaac 60agcttcagga tacttccagg agacagagcc accagcagca aaacaaatat tcccatgcct 120ggagcatggc atagaggaag ctganaaatg tggggtctga ggaagccatt tgagtctggc 180cactagacat ctcatcagcc acttgtgtga agagatgccc catgacccca gatgcctctc 240ccacccttac ctccatctca cacacttgag ctttccactc tgtataattc taacatcctg 300gagaaaaatg gcagtttgac cgaacctgtt cacaacggta gaggctgatt tctaacgaaa 360cttgtagaat gaagcctgga 380
<210> 161
<211> 114
<212> DNA
<213> Homo sapien
<400> 161actccacatc ccctctgagc aggcggttgt cgttcaaggt gtatttggcc ttgcctgtca 60cactgtccac tggcccctta tccacttggt gcttaatccc tcgaaagagc atgt 114
<210> 162
<211> 177
<212> DNA
<213> Homo sapien
<400> 162actttctgaa tcgaatcaaa tgatacttag tgtagtttta atatcctcat atatatcaaa 60gttttactac tctgataatt ttgtaaacca ggtaaccaga acatccagtc atacagcttt 120tggtgatata taacttggca ataacccagt ctggtgatac ataaaactac tcactgt 177
<210> 163
<211> 137
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(137)
<223> n = A,T,C or G
<400> 163catttataca gacaggcgtg aagacattca cgacaaaaac gcgaaattct atcccgtgac 60canagaaggc agctacggct actcctacat cctggcgtgg gtggccttcg cctgcacctt 120catcagcggc atgatgt 137
<210> 164
<211> 469
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(469)
<223> n = A,T,C or G
<400> 164cttatcacaa tgaatgttct cctgggcagc gttgtgatct ttgccacctt cgtgacttta 60tgcaatgcat catgctattt catacctaat gagggagttc caggagattc aaccaggaaa 120tgcatggatc tcaaaggaaa caaacaccca ataaactcgg agtggcagac tgacaactgt 180gagacatgca cttgctacga aacagaaatt tcatgttgca cccttgtttc tacacctgtg 240ggttatgaca aagacaactg ccaaagaatc ttcaagaagg aggactgcaa gtatatcgtg 300gtggagaaga aggacccaaa aaagacctgt tctgtcagtg aatggataat ctaatgtgct 360tctagtaggc acagggctcc caggccaggc ctcattctcc tctggcctct aatagtcaat 420gattgtgtag ccatgcctat cagtaaaaag atntttgagc aaacacttt 469
<210> 165
<211> 195
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(195)
<223> n = A,T,C or G
<400> 165acagtttttt atanatatcg acattgccgg cacttgtgtt cagtttcata aagctggtgg 60atccgctgtc atccactatt ccttggctag agtaaaaatt attcttatag cccatgtccc 120tgcaggccgc ccgcccgtag ttctcgttcc agtcgtcttg gcacacaggg tgccaggact 180tcctctgaga tgagt 195
<210> 166
<211> 383
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(383)
<223> n = A,T,C or G
<400> 166acatcttagt agtgtggcac atcagggggc catcagggtc acagtcactc atagcctcgc 60cgaggtcgga gtccacacca ccggtgtagg tgtgctcaat cttgggcttg gcgcccacct 120ttggagaagg gatatgctgc acacacatgt ccacaaagcc tgtgaactcg ccaaagaatt 180tttgcagacc agcctgagca aggggcggat gttcagcttc agctcctcct tcgtcaggtg 240gatgccaacc tcgtctangg tccgtgggaa gctggtgtcc acntcaccta caacctgggc 300gangatctta taaagaggct ccnagataaa ctccacgaaa cttctctggg agctgctagt 360nggggccttt ttggtgaact ttc 383
<210> 167
<211> 247
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(247)
<223> n = A,T,C or G
<400> 167acagagccag accttggcca taaatgaanc agagattaag actaaacccc aagtcganat 60tggagcagaa actggagcaa gaagtgggcc tggggctgaa gtagagacca aggccactgc 120tatanccata cacagagcca actctcaggc caaggcnatg gttggggcag anccagagac 180tcaatctgan tccaaagtgg tggctggaac actggtcatg acanaggcag tgactctgac 240tgangtc 247
<210> 168
<211> 273
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(273)
<223> n = A,T,C or G
<400> 168acttctaagt tttctagaag tggaaggatt gtantcatcc tgaaaatggg tttacttcaa 60aatccctcan ccttgttctt cacnactgtc tatactgana gtgtcatgtt tccacaaagg 120gctgacacct gagcctgnat tttcactcat ccctgagaag ccctttccag tagggtgggc 180aattcccaac ttccttgcca caagcttccc aggctttctc ccctggaaaa ctccagcttg 240agtcccagat acactcatgg gctgccctgg gca 273
<210> 169
<211> 431
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(431)
<223> n = A,T,C or G
<400> 169acagccttgg cttccccaaa ctccacagtc tcagtgcaga aagatcatct tccagcagtc 60agctcagacc agggtcaaag gatgtgacat caacagtttc tggtttcaga acaggttcta 120ctactgtcaa atgacccccc atacttccgc aaaggctgtg gtaagttttg cacaggtgag 180ggcagcagaa agggggtant tactgatgga caccatcttc tctgtatact ccacactgac 240cttgccatgg gcaaaggccc ctaccacaaa aacaatagga tcactgctgg gcaccagctc 300acgcacatca ctgacaaccg ggatggaaaa agaantgcca actttcatac atccaactgg 360aaagtgatct gatactggat tcttaattac cttcaaaagc ttctgggggc catcagctgc 420tcgaacactg a 431
<210> 170
<211> 266
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(266)
<223> n = A,T,C or G
<400> 170acctgtgggc tgggctgtta tgcctgtgcc ggctgctgaa agggagttca gaggtggagc 60tcaaggagct ctgcaggcat tttgccagnc ctctccanag canagggagc aacctacact 120ccccgctaga aagacaccag attggagtcc tgggaggggg agttggggtg ggcatttgat 180gtatacttgt cacctgaatg aangagccag agaggaanga gacgaanatg anattggcct 240tcaaagctag gggtctggca ggtgga 266
<210> 171
<211> 1248
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(1248)
<223> n = A,T,C or G
<400> 171ggcagccaaa tcataaacgg cgaggactgc agcccgcact cgcagccctg gcaggcggca 60ctggtcatgg aaaacgaatt gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg 120tcagccgcac actgtttcca gaagtgagtg cagagctcct acaccatcgg gctgggcctg 180cacagtcttg aggccgacca agagccaggg agccagatgg tggaggccag cctctccgta 240cggcacccag agtacaacag acccttgctc gctaacgacc tcatgctcat caagttggac 300gaatccgtgt ccgagtctga caccatccgg agcatcagca ttgcttcgca gtgccctacc 360gcggggaact cttgcctcgt ttctggctgg ggtctgctgg cgaacggcag aatgcctacc 420gtgctgcagt gcgtgaacgt gccggtggtg tctgaggagg tctgcagtaa gctctatgac 480ccgctgtacc accccagcat gttctgcgcc ggcggagggc aagaccagaa ggactcctgc 540aacggtgact ctggggggcc cctgatctgc aacgggtact tgcagggcct tgtgtctttc 600ggaaaagccc cgtgtggcca agttggcgtg ccaggtgtct acaccaacct ctgcaaattc 660actgagtgga tagagaaaac cgtccaggcc agttaactct ggggactggg aacccatgaa 720attgaccccc aaatacatcc tgcggaagga attcaggaat atctgttccc agcccctcct 780ccctcaggcc caggagtcca ggcccccagc ccctcctccc tcaaaccaag ggtacagatc 840cccagcccct cctccctcag acccaggagt ccagaccccc cagcccctcc tccctcagac 900ccaggagtcc agcccctcct ccctcagacc caggagtcca gaccccccag cccctcctcc 960ctcagaccca ggggtccagg cccccaaccc ctcctccctc agactcagag gtccaagccc 1020ccaacccntc attccccaga cccagaggtc caggtcccag cccctcntcc ctcagaccca 1080gcggtccaat gccacctaga ctntccctgt acacagtgcc cccttgtggc acgttgaccc 1140aaccttacca gttggttttt catttttngt ccctttcccc tagatccaga aataaagttt 1200aagagaagng caaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1248
<210> 172
<211> 159
<212> PRT
<213> Homo sapien
<220>
<221> VARIANT
<222> (1)...(159)
<223> Xaa = Any Amino Acid
<400> 172Met Val Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro1 5 10 15Leu Leu Ala Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Set
20 25 30Glu Ser Asp Thr Ile Arg Ser Ile Ser Ile Ala Ser Gln Cys Pro Thr
35 40 45Ala Gly Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly
50 55 60Arg Met Pro Thr Val Leu Gln Cys Val Asn Val Set Val Val Ser Glu65 70 75 80Glu Val Cys Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe
85 90 95Cys Ala Gly Gly Gly Gln Xaa Gln Xaa Asp Ser Cys Asn Gly Asp Ser
100 105 110Gly Gly Pro Leu Ile Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe
115 120 125Gly Lys Ala Pro Cys Gly Gln Val Gly Val Pro Gly Val Tyr Thr Asn
130 135 140Leu Cys Lys Phe Thr Glu Trp Ile Glu Lys Thr Val Gln Ala Ser145 150 155
<210> 173
<211> 1265
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(1265)
<223> n = A,T,C or G
<400> 173ggcagcccgc actcgcagcc ctggcaggcg gcactggtca tggaaaacga attgttctgc 60tcgggcgtcc tggtgcatcc gcagtgggtg ctgtcagccg cacactgttt ccagaactcc 120tacaccatcg ggctgggcct gcacagtctt gaggccgacc aagagccagg gagccagatg 180gtggaggcca gcctctccgt acggcaccca gagtacaaca gacccttgct cgctaacgac 240ctcatgctca tcaagttgga cgaatccgtg tccgagtctg acaccatccg gagcatcagc 300attgcttcgc agtgccctac cgcggggaac tcttgcctcg tttctggctg gggtctgctg 360gcgaacggtg agctcacggg tgtgtgtctg ccctcttcaa ggaggtcctc tgcccagtcg 420cgggggctga cccagagctc tgcgtcccag gcagaatgcc taccgtgctg cagtgcgtga 480acgtgtcggt ggtgtctgag gaggtctgca gtaagctcta tgacccgctg taccacccca 540gcatgttctg cgccggcgga gggcaagacc agaaggactc ctgcaacggt gactctgggg 600ggcccctgat ctgcaacggg tacttgcagg gccttgtgtc tttcggaaaa gccccgtgtg 660gccaagttgg cgtgccaggt gtctacacca acctctgcaa attcactgag tggatagaga 720aaaccgtcca ggccagttaa ctctggggac tgggaaccca tgaaattgac ccccaaatac 780atcctgcgga aggaattcag gaatatctgt tcccagcccc tcctccctca ggcccaggag 840tccaggcccc cagcccctcc tccctcaaac caagggtaca gatccccagc ccctcctccc 900tcagacccag gagtccagac cccccagccc ctcctccctc agacccagga gtccagcccc 960tcctccntca gacccaggag tccagacccc ccagcccctc ctccctcaga cccaggggtt 1020gaggccccca acccctcctc cttcagagtc agaggtccaa gcccccaacc cctcgttccc 1080cagacccaga ggtnnaggtc ccagcccctc ttccntcaga cccagnggtc caatgccacc 1140tagattttcc ctgnacacag tgcccccttg tggnangttg acccaacctt accagttggt 1200ttttcatttt tngtcccttt cccctagatc cagaaataaa gtttaagaga ngngcaaaaa 1260aaaaa 1265
<210> 174
<211> 1459
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(1459)
<223> n = A,T,C or G
<400> 174ggtcagccgc acactgtttc cagaagtgag tgcagagctc ctacaccatc gggctgggcc 60tgcacagtct tgaggccgac caagagccag ggagccagat ggtggaggcc agcctctccg 120tacggcaccc agagtacaac agacccttgc tcgctaacga cctcatgctc atcaagttgg 180acgaatccgt gtccgagtct gacaccatcc ggagcatcag cattgcttcg cagtgcccta 240ccgcggggaa ctcttgcctc gtttctggct ggggtctgct ggcgaacggt gagctcacgg 300gtgtgtgtct gccctcttca aggaggtcct ctgcccagtc gcgggggctg acccagagct 360ctgcgtccca ggcagaatgc ctaccgtgct gcagtgcgtg aacgtgtcgg tggtgtctga 420ngaggtctgc antaagctct atgacccgct gtaccacccc ancatgttct gcgccggcgg 480agggcaagac cagaaggact cctgcaacgt gagagagggg aaaggggagg gcaggcgact 540cagggaaggg tggagaaggg ggagacagag acacacaggg ccgcatggcg agatgcagag 600atggagagac acacagggag acagtgacaa ctagagagag aaactgagag aaacagagaa 660ataaacacag gaataaagag aagcaaagga agagagaaac agaaacagac atggggaggc 720agaaacacac acacatagaa atgcagttga ccttccaaca gcatggggcc tgagggcggt 780gacctccacc caatagaaaa tcctcttata acttttgact ccccaaaaac ctgactagaa 840atagcctact gttgacgggg agccttacca ataacataaa tagtcgattt atgcatacgt 900tttatgcatt catgatatac ctttgttgga attttttgat atttctaagc tacacagttc 960gtctgtgaat ttttttaaat tgttgcaact ctcctaaaat ttttctgatg tgtttattga 1020aaaaatccaa gtataagtgg acttgtgcat tcaaaccagg gttgttcaag ggtcaactgt 1080gtacccagag ggaaacagtg acacagattc atagaggtga aacacgaaga gaaacaggaa 1140aaatcaagac tctacaaaga ggctgggcag ggtggctcat gcctgtaatc ccagcacttt 1200gggaggcgag gcaggcagat cacttgaggt aaggagttca agaccagcct ggccaaaatg 1260gtgaaatcct gtctgtacta aaaatacaaa agttagctgg atatggtggc aggcgcctgt 1323aatcccagct acttgggagg ctgaggcagg agaattgctt gaatatggga ggcagaggtt 1380gaagtgagtt gagatcacac cactatactc cagctggggc aacagagtaa gactctgtct 1440caaaaaaaaa aaaaaaaaa 1459
<210> 175
<211> 1167
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (1167)
<223> n = A,T,C or G
<400> 175gcgcagccct ggcaggcggc actggtcatg gaaaacgaat tgttctgctc gggcgtcctg 60gtgcatccgc agtgggtgct gtcagccgca cactgtttcc agaactccta caccatcggg 120ctgggcctgc acagtcttga ggccgaccaa gagccaggga gccagatggt ggaggccagc 180ctctccgtac ggcacccaga gtacaacaga ctcttgctcg ctaacgacct catgctcatc 240aagttggacg aatccgtgtc cgagtctgac accatccgga gcatcagcat tgcttcgcag 300tgccctaccg cggggaactc ttgcctcgtn tctggctggg gtctgctggc gaacggcaga 360atgcctaccg tgctgcactg cgtgaacgtg tcggtggtgt ctgaggangt ctgcagtaag 420ctctatgacc cgctgtacca ccccagcatg ttctgcgccg gcggagggca agaccagaag 480gactcctgca acggtgactc tggggggccc ctgatctgca acgggtactt gcagggcctt 540gtgtctttcg gaaaagcccc gtgtggccaa cttggcgtgc caggtgtcta caccaacctc 600tgcaaattca ctgagtggat agagaaaacc gtccagncca gttaactctg gggactgga 660acccatgaaa ttgaccccca aatacatcct gcggaangaa ttcaggaata tctgttccca 720gcccctcctc cctcaggccc aggagtccag gcccccagcc cctcctccct caaaccaagg 780gtacagatcc ccagcccctc ctccctcaga cccaggagtc cagacccccc agcccctcnt 840ccntcagacc caggagtcca gcccctcctc cntcagacgc aggagtccag accccccagc 900ccntcntccg tcagacccag gggtgcaggc ccccaacccc tcntccntca gagtcagagg 960tccaagcccc caacccctcg ttccccagac ccagaggtnc aggtcccagc ccctcctccc 1020tcagacccag cggtccaatg ccacctagan tntccctgta cacagtgccc ccttgtggca 1080ngttgaccca accttaccag ttggtttttc attttttgtc cctttcccct agatccagaa 1140ataaagtnta agagaagcgc aaaaaaa 1167
<210> 176
<211> 205
<212> PRT
<213> Homo sapien
<220>
<221> VARIANT
<222> (1) ... (205)
<223> Xaa = Any Amino Acid
<400> 176Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp1 5 10 15Val Leu Set Ala Ala His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu
20 25 30Gly Leu His Ser Leu Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val
35 40 45Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Leu Leu Leu
50 55 60Ala Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Ser Glu Ser65 70 75 80Asp Thr Ile Arg Ser Ile Ser Ile Ala Set Gln Cys Pro Thr Ala Gly
85 90 95Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly Arg Met
100 105 110Pro Thr Val Leu His Cys Val Asn Val Set Val Val Ser Glu Xaa Val
115 120 125Cys Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Set Met Phe Cys Ala
130 135 140Gly Gly Gly Gln Asp Gln Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly145 150 155 160Pro Leu Ile Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe Gly Lys
165 170 175Ala Pro Cys Gly Gln Leu Gly Val Pro Gly Val Tyr Thr Asn Leu Cys
180 185 190Lys Phe Thr Glu Trp Ile Glu Lys Thr Val Gln Xaa Ser
195 200 205
<210> 177
<211> 1119
<212> DNA
<213> Homo sapien
<400> 177gcgcactcgc agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc 60gtcctggtgc atccgcagtg ggtgctgtca gccgcacact gtttccagaa ctcctacacc 120atcgggctgg gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag 180gccagcctct ccgtacggca cccagagtac aacagaccct tgctcgctaa cgacctcatg 240ctcatcaagt tggacgaatc cgtgtccgag tctgacacca tccggagcat cagcattgct 300tcgcagtgcc ctaccgcggg gaactcttgc ctcgtttctg gctggggtct gctggcgaac 360gatgctgtga ttgccatcca gtcccagact gtgggaggct gggagtgtga gaagctttcc 420caaccctggc agggttgtac catttcggca acttccagtg caaggacgtc ctgctgcatc 480ctcactgggt gctcactact gctcactgca tcacccggaa cactgtgatc aactagccag 540caccatagtt ctccgaagtc agactatcat gattactgtg ttgactgtgc tgtctattgt 600actaaccatg ccgatgttta ggtgaaatta gcgtcacttg gcctcaacca tcttggtatc 660cagttatcct cactgaattg agatttcctg cttcagtgtc agccattccc acataatttc 720tgacctacag aggtgaggga tcatatagct cttcaaggat gctggtactc ccctcacaaa 780ttcatttctc ctgttgtagt gaaaggtgcg ccctctggag cctcccaggg tgggtgtgca 840ggtcacaatg atgaatgtat gatcgtgttc ccattaccca aagcctttaa atccctcatg 900ctcagtacac cagggcaggt ctagcatttc ttcatttagt gtatgctgtc cattcatgca 960accacctcag gactcctgga ttctctgcct agttgagctc ctgcatgctg cctccttggg 1020gaggtgaggg agagggccca tggttcaatg ggatctgtgc agttgtaaca cattaggtgc 1080ttaataaaca gaagctgtga tgttaaaaaa aaaaaaaaa 1119
<210> 178
<211> 164
<212> PRT
<213> Homo sapien
<220>
<221> VARIANT
<222> (1)...(164)
<223> Xaa = Any Amino Acid
<400> 178Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp1 5 10 15val Leu Ser Ala Ala His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu
20 25 30Gly Leu His Ser Leu Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val
35 40 45Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro Leu Leu
50 55 60Ala Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Ser Glu Ser65 70 75 80Asp Thr Ile Arg Ser Ile Ser Ile Ala Ser Gln Cys Pro Thr Ala Gly
85 90 95Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Asp Ala Val
100 105 110Ile Ala Ile Gln Ser Xaa Thr Val Gly Gly Trp Glu Cys Glu Lys Leu
115 120 125Ser Gln Pro Trp Gln Gly Cys Thr Ile Ser Ala Thr Ser Ser Ala Arg
130 135 140Thr Ser Cys Cys Ile Leu Thr Gly Cys Ser Leu Leu Leu Thr Ala Ser145 150 155 160Pro Gly Thr Leu
<210> 179
<211> 250
<212> DNA
<213> Homo sapien
<400> 179ctggagtgcc ttggtgtttc aagcccctgc aggaagcaga atgcaccttc tgaggcacct 60ccagctgccc ccggccgggg gatgcgaggc tcggagcacc cttgcccggc tgtgattgct 120gccaggcact gttcatctca gcttttctgt ccctttgctc ccggcaagcg cttctgctga 180aagttcatat ctggagcctg atgtcttaac gaataaaggt cccatgctcc acccgaaaaa 240aaaaaaaaaa 250
<210> 180
<211> 202
<212> DNA
<213> Homo sapien
<400> 180actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca 60tcacccagac cccgcccctg cccgtgcccc acgctgctgc taacgacagt atgatgctta 120ctctgctact cggaaactat ttttatgtaa ttaatgtatg ctttcttgtt tataaatgcc 180tgatttaaaa aaaaaaaaaa aa 202
<210> 181
<211> 558
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(558)
<223> n = A,T,C or G
<400> 181tccytttgkt naggtttkkg agacamccck agacctwaan ctgtgtcaca gacttcyngg 60aatgtttagg cagtgctagt aatttcytcg taatgattct gttattactt tcctnattct 120ttattcctct ttcttctgaa gattaatgaa gttgaaaatt gaggtggata aatacaaaaa 180ggtagtgtga tagtataagt atctaagtgc agatgaaagt gtgttatata tatccattca 240aaattatgca agttagtaat tactcagggt taactaaatt actttaatat gctgttgaac 300ctactctgtt ccttggctag aaaaaattat aaacaggact ttgttagttt gggaagccaa 360attgataata ttctatgttc taaaagttgg gctatacata aattattaag aaatatggaw 420ttttattccc aggaatatgg kgttcatttt atgaatatta cscrggatag awgtwtgagt 480aaaaycagtt ttggtwaata ygtwaatatg tcmtaaataa acaakgcttt gacttatttc 540caaaaaaaaa aaaaaaaa 558
<210> 182
<211> 479
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(479)
<223> n = A,T,C or G
<400> 182acagggwttk grggatgcta agsccccrga rwtygtttga tccaaccctg gcttwttttc 60agaggggaaa atggggccta gaagttacag mscatytagy tggtgcgmtg gcacccctgg 120cstcacacag astcccgagt agctgggact acaggcacac agtcactgaa gcaggccctg 180ttwgcaattc acgttgccac ctccaactta aacattcttc atatgtgatg tccttagtca 240ctaaggttaa actttcccac ccagaaaagg caacttagat aaaatcttag agtactttca 300tactmttcta agtcctcttc cagcctcact kkgagtcctm cytgggggtt gataggaant 360ntctcttggc tttctcaata aartctctat ycatctcatg tttaatttgg tacgcatara 420awtgstgara aaattaaaat gttctggtty mactttaaaa araaaaaaaa aaaaaaaaa 479
<210> 183
<211> 384
<212> DNA
<213> Homo sapien
<400> 183aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60agtaccagta ccaataacag tgccagtgcc agtgccagca ccagtggtgg cttcagtgct 120ggtgccagcc tgaccgccac tctcacattt gggctcttcg ctggccttgg tggagctggt 180gccagcacca gtggcagctc tggtgcctgt ggtttctcct acaagtgaga ttttagatat 240tgttaatcct gccagtcttt ctcttcaagc cagggtgcat cctcagaaac ctactcaaca 300cagcactcta ggcagccact atcaatcaat tgaagttgac actctgcatt aratctattt 360gccatttcaa aaaaaaaaaa aaaa 384
<210> 184
<211> 496
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(496)
<223> n = A,T,C or G
<400> 184accgaattgg gaccgctggc ttataagcga tcatgtyynt ccrgtatkac ctcaacgagc 60agggagatcg agtctatacg ctgaagaaat ttgacccgat gggacaacag acctgctcag 120cccatcctgc tcggttctcc ccagatgaca aatactctsg acaccgaatc accatcaaga 180aacgcttcaa ggtgctcatg acccagcaac cgcgccctgt cctctgaggg tcccttaaac 240tgatgtcttt tctgccacct gttacccctc ggagactccg taaccaaact cttcggactg 300tgagccctga tgcctttttg ccagccatac tctttggcat ccagtctctc gtggcgattg 360attatgcttg tgtgaggcaa tcatggtggc atcacccata aagggaacac atttgacttt 420tttttctcat attttaaatt actacmagaw tattwmagaw waaatgawtt gaaaaactst 480taaaaaaaaa aaaaaa 496
<210> 185
<211> 384
<212> DNA
<213> Homo sapien
<400> 185gctggtagcc tatggcgkgg cccacggagg ggctcctgag gccacggrac agtgacttcc 60caagtatcyt gcgcsgcgtc ttctaccgtc cctacctgca gatcttcggg cagattcccc 120aggaggacat ggacgtggcc ctcatggagc acagcaactg ytcgtcggag cccggcttct 180gggcacaccc tcctggggcc caggcgggca cctgcgtctc ccagtatgcc aactggctgg 240tggtgctgct cctcgtcatc ttcctgctcg tggccaacat cctgctggtc aacttgctca 300ttgccatgtt cagttacaca ttcggcaaag tacagggcaa cagcgatctc tactgggaag 360gcgcagcgtt accgcctcat ccgg 384
<210> 186
<211> 577
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(577)
<223> n = A,T,C or G
<400> 186gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc 60tnccatcgtc atactgtagg tttgccacca cytcctggca tcttggggcg gcntaatatt 120ccaggaaact ctcaatcaag tcaccgtcga tgaaacctgt gggctggttc tgtcttccgc 180tcggtgtgaa aggatctccc agaaggagtg ctcgatcttc cccacacttt tgatgacttt 240attgagtcga ttctgcatgt ccagcaggag gttgtaccag ctctctgaca gtgaggtcac 300cagccctatc atgccgttga mcgtgccgaa garcaccgag ccttgtgtgg gggkkgaagt 360ctcacccaga ttctgcatta ccagagagcc gtggcaaaag acattgacaa actcgcccag 420gtggaaaaag amcamctcct ggargtgctn gccgctcctc gtcmgttggt ggcagcgctw 480tccttttgac acacaaacaa gttaaaggca ttttcagccc ccagaaantt gtcatcatcc 540aagatntcgc acagcactna tccagttggg attaaat 577
<210> 187
<211> 534
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(534)
<223> n = A,T,C or G
<400> 187aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgstg agaatycatw 60actkggaaaa gmaacattaa agcctggaca ctggtattaa aattcacaat atgcaacact 120ttaaacagtg tgtcaatctg ctcccyynac tttgtcatca ccagtctggg aakaagggta 180tgccctattc acacctgtta aaagggcgct aagcattttt gattcaacat cttttttttt 240gacacaagtc cgaaaaaagc aaaagtaaac agttatyaat ttgttagcca attcactttc 300ttcatgggac agagccatyt gatttaaaaa gcaaattgca taatattgag cttygggagc 360tgatatttga gcggaagagt agcctttcta cttcaccaga cacaactccc tttcatattg 420ggatgttnac naaagtwatg tctctwacag atgggatgct tttgtggcaa ttctgttctg 480aggatctccc agtttattta ccacttgcac aagaaggcgt tttcttcctc aggc 534
<210> 188
<211> 761
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(761)
<223> n = A,T,C or G
<400> 188agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg 60tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg 120cctctttggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180ttgtcttctg tgtaaatggt actagagaaa acacctatnt tatgagtcaa tctagttngt 240tttattcgac atgaaggaaa tttccagatn acaacactna caaactctcc ctkgackarg 300ggggacaaag aaaagcaaaa ctgamcataa raaacaatwa cctggtgaga arttgcataa 360acagaaatwr ggtagtatat tgaarnacag catcattaaa rmgttwtktt wttctccctt 420gcaaaaaaca tgtacngact tcccgttgag taatgccaag ttgttttttt tatnataaaa 480cttgcccttc attacatgtt tnaaagtggt gtggtgggcc aaaatattga aatgatggaa 540ctgactgata aagctgtaca aataagcagt gtgcctaaca agcaacacag taatgttgac 600atgcttaatt cacaaatgct aatttcatta taaatgtttg ctaaaataca ctttgaacta 660tttttctgtn ttcccagagc tgagatntta gattttatgt agtatnaagt gaaaaantac 720gaaaataata acattgaaga aaaananaaa aaanaaaaaa a 761
<210> 189
<211> 482
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(482)
<223> n = A,T,C or G
<400> 189tttttttttt tttgccgatn ctactatttt attgcaggan gtgggggtgt atgcaccgca 60caccggggct atnagaagca agaaggaagg agggagggca cagcccctcg ctgagcaaca 120aagccgcctg ctgccttctc tgtctgtctc ctggtgcagg cacatgggga gaccttcccc 180aaggcagggg ccaccagtcc aggggtggga atacaggggg tgggangtgt gcataagaag 240tgataggcac aggccacccg gtacagaccc ctcggctcct gacaggtnga tttcgaccag 300gtcattgtgc cctgcccagg cacagcgtan atctggaaaa gacagaatgc tttccttttc 360aaatttggct ngtcatngaa ngggcanttt tccaanttng gctnggtctt ggtacncttg 420gttcggccca gctccncgtc caaaaantat tcacccnnct ccnaattgct tgcnggnccc 480cc 482
<210> 190
<211> 471
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (471)
<223> n = A,T,C or G
<400> 190tttttttttt ttttaaaaca gtttttcaca acaaaattta ttagaagaat agtggttttg 60aaaactctcg catccagtga gaactaccat acaccacatt acagctngga atgtnctcca 120aatgtctggt caaatgatac aatggaacca ttcaatctta cacatgcacg aaagaacaag 180cgcttttgac atacaatgca caaaaaaaaa aggggggggg gaccacatgg attaaaattt 240taagtactca tcacatacat taagacacag ttctagtcca gtcnaaaatc agaactgcnt 300tgaaaaattt catgtatgca atccaaccaa agaacttnat tggtgatcat gantnctcta 360ctacatcnac cttgatcatt gccaggaacn aaaagttnaa ancacncngt acaaaaanaa 420tctgtaattn anttcaacct ccgtacngaa aaatnttnnt tatacactcc c 471
<210> 191
<211> 402
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(402)
<223> n = A,T,C or G
<400> 191gagggattga aggtctgttc tastgtcggm ctgttcagcc accaactcta acaagttgct 60gtcttccact cactgtctgt aagcttttta acccagacwg tatcttcata aatagaacaa 120attcttcacc agtcacatct tctaggacct ttttggattc agttagtata agctcttcca 180cttcctttgt taagacttca tctggtaaag tcttaagttt tgtagaaagg aattyaattg 240ctcgttctct aacaatgtcc tctccttgaa gtatttggct gaacaaccca cctaaagtcc 300ctttgtgcat ccattttaaa tatacttaat agggcattgk tncactaggt taaattctgc 360aagagtcatc tgtctgcaaa agttgcgtta gtatatctgc ca 402
<210> 192
<211> 601
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(601)
<223> n = A,T,C or G
<400> 192gagctcggat ccaataatct ttgtctgagg gcagcacaca tatncagtgc catggnaact 60ggtctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac 120atgcytyttt gaytaccgtg tgccaagtgc tggtgattct yaacacacyt ccatcccgyt 180cttttgtgga aaaactggca cttktctgga actagcarga catcacttac aaattcaccc 240acgagacact tgaaaggtgt aacaaagcga ytcttgcatt gctttttgtc cctccggcac 300cagttgtcaa tactaacccg ctggtttgcc tccatcacat ttgtgatctg tagctctgga 360tacatctcct gacagtactg aagaacttct tcttttgttt caaaagcarc tcttggtgcc 420tgttggatca ggttcccatt tcccagtcyg aatgttcaca tggcatattt wacttcccac 480aaaacattgc gatttgaggc tcagcaacag caaatcctgt tccggcattg gctgcaagag 540cctcgatgta gccggccagc gccaaggcag gcgccgtgag ccccaccagc agcagaagca 600g 601
<210> 193
<211> 608
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (608)
<223> n = A,T,C or G
<400> 193atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcytt 120cccaacgcag gcagmagcgg gsccggtcaa tgaactccay tcgtggcttg gggtkgacgg 180tkaagtgcag gaagaggctg accacctcgc ggtccaccag gatgcccgac tgtgcgggac 240ctgcagcgaa actcctcgat ggtcatgagc gggaagcgaa tgaggcccag ggccttgccc 300agaaccttcc gcctgttctc tggcgtcacc tgcagctgct gccgctgaca ctcggcctcg 360gaccagcgga caaacggcrt tgaacagccg cacctcacgg atgcccagtg tgtcgcgctc 420caggammgsc accagcgtgt ccaggtcaat gtcggtgaag ccctccgcgg gtratggcgt 480ctgcagtgtt tttgtcgatg ttctccaggc acaggctggc cagctgcggt tcatcgaaga 540gtcgcgcctg cgtgagcagc atgaaggcgt tgtcggctcg cagttcttct tcaggaactc 600cacgcaat 608
<210> 194
<211> 392
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(392)
<223> n = A,T,C or G
<400> 194gaacggctgg accttgcctc gcattgtgct tgctggcagg gaataccttg gcaagcagyt 60ccagtccgag cagccccaga ccgctgccgc ccgaagctaa gcctgcctct ggccttcccc 120tccgcctcaa tgcagaacca gtagtgggag cactgtgttt agagttaaga gtgaacactg 180tttgatttta cttgggaatt tcctctgtta tatagctttt cccaatgcta atttccaaac 240aacaacaaca aaataacatg tttgcctgtt aagttgtata aaagtaggtg attctgtatt 300taaagaaaat attactgtta catatactgc ttgcaatttc tgtatttatt gktnctstgg 360aaataaatat agttattaaa ggttgtcant cc 392
<210> 195
<211> 502
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(502)
<223> n = A,T,C or G
<400> 195ccsttkgagg ggtkaggkyc cagttyccga gtggaagaaa caggccagga gaagtgcgtg 60ccgagctgag gcagatgttc ccacagtgac ccccagagcc stgggstata gtytctgacc 120cctcncaagg aaagaccacs ttctggggac atgggctgga gggcaggacc tagaggcacc 180aagggaaggc cccattccgg ggstgttccc cgaggaggaa gggaaggggc tctgtgtgcc 240ccccasgagg aagaggccct gagtcctggg atcagacacc ccttcacgtg tatccccaca 300caaatgcaag ctcaccaagg tcccctctca gtccccttcc stacaccctg amcggccact 360gscscacacc cacccagagc acgccacccg ccatggggar tgtgctcaag gartcgcngg 420gcarcgtgga catctngtcc cagaaggggg cagaatctcc aatagangga ctgarcmstt 480gctnanaaaa aaaaanaaaa aa 502
<210> 196
<211> 665
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(665)
<223> n = A,T,C or G
<400> 196ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt ttgtctgctc 60cctctggaag ccttcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120wagctgtttk gagttgatts gcaccactgc acccacaact tcaatatgaa aacyawttga 180actwatttat tatcttgtga aaagtataac aatgaaaatt ttgttcatac tgtattkatc 240aagtatgatg aaaagcaawa gatatatatt cttttattat gttaaattat gattgccatt 300attaatcggc aaaatgtgga gtgtatgttc ttttcacagt aatatatgcc ttttgtaact 360tcacttggtt attttattgt aaatgartta caaaattctt aatttaagar aatggtatgt 420watatttatt tcattaattt ctttcctkgt ttacgtwaat tttgaaaaga wtgcatgatt 480tcttgacaga aatcgatctt gatgctgtgg aagtagtttg acccacatcc ctatgagttt 540ttcttagaat gtataaaggt tgtagcccat cnaacttcaa agaaaaaaat gaccacatac 600tttgcaatca ggctgaaatg tggcatgctn ttctaattcc aactttataa actagcaaan 660aagtg 665
<210> 197
<211> 492
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(492)
<223> n = A,T,C or G
<400> 197ttttnttttt ttttttttgc aggaaggatt ccatttattg tggatgcatt ttcacaatat 60atgtttattg gagcgatcca ttatcagtga aaagtatcaa gtgtttataa natttttagg 120aaggcagatt cacagaacat gctngtcngc ttgcagtttt acctcgtana gatnacagag 180aattatagtc naaccagtaa acnaggaatt tacttttcaa aagattaaat ccaaactgaa 240caaaattcta ccctgaaact tactccatcc aaatattgga ataanagtca gcagtgatac 300attctcttct gaactttaga ttttctagaa aaatatgtaa tagtgatcag gaagagctct 360tgttcaaaag tacaacnaag caatgttccc ttaccatagg ccttaattca aactttgatc 420catttcactc ccatcacggg agtcaatgct acctgggaca cttgtatttt gttcatnctg 480ancntggctt aa 492
<210> 198
<211> 478
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(478)
<223> n = A,T,C or G
<400> 198tttnttttgn atttcantct gtannaanta ttttcattat gtttattana aaaatatnaa 60tgtntccacn acaaatcatn ttacntnagt aagaggccan ctacattgta caacatacac 120tgagtatatt ttgaaaagga caagtttaaa gtanacncat attgccganc atancacatt 180tatacatggc ttgattgata tttagcacag canaaactga gtgagttacc agaaanaaat 240natatatgtc aatcngattt aagatacaaa acagatccta tggtacatan catcntgtag 300gagttgtggc tttatgttta ctgaaagtca atgcagttcc tgtacaaaga gatggccgta 360agcattctag tacctctact ccatggttaa gaatcgtaca cttatgttta catatgtnca 420gggtaagaat tgtgttaagt naanttatgg agaggtccan gagaaaaatt tgatncaa 478
<210> 199
<211> 482
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (482)
<223> n = A,T,C or G
<400> 199agtgacttgt cctccaacaa aaccccttga tcaagtttgt ggcactgaca atcagaccta 60tgctagttcc tgtcatctat tcgctactaa atgcagactg gaggggacca aaaaggggca 120tcaactccag ctggattatt ttggagcctg caaatctatt cctacttgta cggactttga 180agtgattcag tttcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 240tgaagccnac tctgaacacg ctggttatct nagatgagaa ncagagaaat aaagtcnaga 300aaatttacct ggangaaaag aggctttngg ctggggacca tcccattgaa ccttctctta 360anggacttta agaanaaact accacatgtn tgtngtatcc tggtgccngg ccgtttantg 420aacntngacn ncacccttnt ggaatanant cttgacngcn tcctgaactt gctcctctgc 480ga 482
<210> 200
<211> 270
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(270)
<223> n = A,T,C or G
<400> 200cggccgcaag tgcaactcca gctggggccg tgcggacgaa gattctgcca gcagttggtc 60cgactgcgac gacggcggcg gcgacagtcg caggtgcagc gcgggcgcct ggggtcttgc 120aaggctgagc tgacgccgca gaggtcgtgt cacgtcccac gaccttgacg ccgtcgggga 180cagccggaac agagcccggt gaangcggga ggcctcgggg agcccctcgg gaagggcggc 240ccgagagata cgcaggtgca ggtggccgcc 270
<210> 201
<211> 419
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(419)
<223> n = A,T,C or G
<400> 201tttttttttt ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc tttgtcgtgg 120ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaancgaagc anaantaaca 180tggagtgggt gcaccctccc tgtagaacct ggttacnaaa gcttggggca gttcacctgg 240tctgtgaccg tcattttctt gacatcaatg ttattagaag tcaggatatc ttttagagag 300tccactgtnt ctggagggag attagggttt cttgccaana tccaancaaa atccacntga 360aaaagttgga tgatncangt acngaatacc ganggcatan ttctcatant cggtggcca 419
<210> 202
<211> 509
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(509)
<223> n = A,T,C or G
<400> 202tttntttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60tggcacttaa tccattttta tttcaaaatg tctacaaant ttnaatncnc cattatacng 120gtnattttnc aaaatctaaa nnttattcaa atntnagcca aantccttac ncaaatnnaa 180tacncncaaa aatcaaaaat atacntntct ttcagcaaac ttngttacat aaattaaaaa 240aatatatacg gctggtgttt tcaaagtaca attatcttaa cactgcaaac atntttnnaa 300ggaactaaaa taaaaaaaaa cactnccgca aaggttaaag ggaacaacaa attcntttta 360caacancnnc nattataaaa atcatatctc aaatcttagg ggaatatata cttcacacng 420ggatcttaac ttttactnca ctttgtttat ttttttanaa ccattgtntt gggcccaaca 480caatggnaat nccnccncnc tggactagt 509
<210> 203
<211> 583
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(583)
<223> n = A,T,C or G
<400> 203tttttttttt ttttttttga cccccctctt ataaaaaaca agttaccatt ttattttact 60tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac 120taaatggaaa ctgccttaga tacataattc ttaggaatta gcttaaaatc tgcctaaagt 180gaaaatcttc tctagctctt ttgactgtaa atttttgact cttgtaaaac atccaaattc 240atttttcttg tctttaaaat tatctaatct ttccattttt tccctattcc aagtcaattt 300gcttctctag cctcatttcc tagctcttat ctactattag taagtggctt ttttcctaaa 360agggaaaaca ggaagagana atggcacaca aaacaaacat tttatattca tatttctacc 420tacgttaata aaatagcatt ttgtgaagcc agctcaaaag aaggcttaga tccttttatg 480tccattttag tcactaaacg atatcnaaag tgccagaatg caaaaggttt gtgaacattt 540attcaaaagc taatataaga tatttcacat actcatcttt ctg 583
<210> 204
<211> 589
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(589)
<223> n = A,T,C or G
<400> 204ttttttttnt tttttttttt ttttttnctc ttcttttttt ttganaatga ggatcgagtt 60tttcactctc tagatagggc atgaagaaaa ctcatctttc cagctttaaa ataacaatca 120aatctcttat gctatatcat attttaagtt aaactaatga gtcactggct tatcttctcc 180tgaaggaaat ctgttcattc ttctcattca tatagttata tcaagtacta ccttgcatat 240tgagaggttt ttcttctcta tttacacata tatttccatg tgaatttgta tcaaaccttt 300attttcatgc aaactagaaa ataatgtntt cttttgcata agagaagaga acaatatnag 360cattacaaaa ctgctcaaat tgtttgttaa gnttatccat tataattagt tnggcaggag 420ctaatacaaa tcacatttac ngacnagcaa taataaaact gaagtaccag ttaaatatcc 480aaaataatta aaggaacatt tttagcctgg gtataattag ctaattcact ttacaagcat 540ttattnagaa tgaattcaca tgttattatt ccntagccca acacaatgg 589
<210> 205
<211> 545
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(545)
<223> n = A,T,C or G
<400> 205tttttntttt ttttttcagt aataatcaga acaatattta tttttatatt taaaattcat 60agaaaagtgc cttacattta ataaaagttt gtttctcaaa gtgatcagag gaattagata 120tngtcttgaa caccaatatt aatttgagga aaatacacca aaatacatta agtaaattat 180ttaagatcat agagcttgta agtgaaaaga taaaatttga cctcagaaac tctgagcatt 240aaaaatccac tattagcaaa taaattacta tggacttctt gctttaattt tgtgatgaat 300atggggtgtc actggtaaac caacacattc tgaaggatac attacttagt gatagattct 360tatgtacttt gctanatnac gtggatatga gttgacaagt ttctctttct tcaatctttt 420aaggggcnga ngaaatgagg aagaaaagaa aaggattacg catactgttc tttctatngg 480aaggattaga tatgtttcct ttgccaatat taaaaaaata ataatgttta ctactagtga 540aaccc 545
<210> 206
<211> 487
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(487)
<223> n = A,T,C or G
<400> 206tttttttttt ttttttagtc aagtttctna tttttattat aattaaagtc ttggtcattt 60catttattag ctctgcaact tacatattta aattaaagaa acgttnttag acaactgtna 120caatttataa atgtaaggtg ccattattga gtanatatat tcctccaaga gtggatgtgt 180cccttctccc accaactaat gaancagcaa cattagttta attttattag tagatnatac 240actgctgcaa acgctaattc tcttctccat ccccatgtng atattgtgta tatgtgtgag 300ttggtnagaa tgcatcanca atctnacaat caacagcaag atgaagctag gcntgggctt 360tcggtgaaaa tagactgtgt ctgtctgaat caaatgatct gacctatcct cggtggcaag 420aactcttcga accgcttcct caaaggcngc tgccacattt gtggcntctn ttgcacttgt 480ttcaaaa 487
<210> 207
<211> 332
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(332)
<223> n = A,T,C or G
<400> 207tgaattggct aaaagactgc atttttanaa ctagcaactc ttatttcttt cctttaaaaa 60tacatagcat taaatcccaa atcctattta aagacctgac agcttgagaa ggtcactact 120gcatttatag gaccttctgg tggttctgct gttacntttg aantctgaca atccttgana 180atctttgcat gcagaggagg taaaaggtat tggattttca cagaggaana acacagcgca 240gaaatgaagg ggccaggctt actgagcttg tccactggag ggctcatggg tgggacatgg 300aaaagaaggc agcctaggcc ctggggagcc ca 332
<210> 208
<211> 524
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(524)
<223> n = A,T,C or G
<400> 208agggcgtggt gcggagggcg ttactgtttt gtctcagtaa caataaatac aaaaagactg 60gttgtgttcc ggccccatcc aaccacgaag ttgatttctc ttgtgtgcag agtgactgat 120tttaaaggac atggagcttg tcacaatgtc acaatgtcac agtgtgaagg gcacactcac 180tcccgcgtga ttcacattta gcaaccaaca atagctcatg agtccatact tgtaaatact 240tttggcagaa tacttnttga aacttgcaga tgataactaa gatccaagat atttcccaaa 300gtaaatagaa gtgggtcata atattaatta cctgttcaca tcagcttcca tttacaagtc 360atgagcccag acactgacat caaactaagc ccacttagac tcctcaccac cagtctgtcc 420tgtcatcaga caggaggctg tcaccttgac caaattctca ccagtcaatc atctatccaa 480aaaccattac ctgatccact tccggtaatg caccaccttg gtga 524
<210> 209
<211> 159
<212> DNA
<213> Homo sapien
<400> 209gggtgaggaa atccagagtt gccatggaga aaattccagt gtcagcattc ttgctccttg 60tggccctctc ctacactctg gccagagata ccacagtcaa acctggagcc aaaaaggaca 120caaaggactc tcgacccaaa ctgccccaga ccctctcca 159
<210> 210
<211> 256
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(256)
<223> n = A,T,C or G
<400> 210actccctggc agacaaaggc agaggagaga gctctgttag ttctgtgttg ttgaactgcc 60actgaatttc tttccacttg gactattaca tgccanttga gggactaatg gaaaaacgta 120tggggagatt ttanccaatt tangtntgta aatggggaga ctggggcagg cgggagagat 180ttgcagggtg naaatgggan ggctggtttg ttanatgaac agggacatag gaggtaggca 240ccaggatgct aaatca 256
<210> 211
<211> 264
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)... (264)
<223> n = A,T,C or G
<400> 211acattgtttt tttgagataa agcattgaga gagctctcct taacgtgaca caatggaagg 60actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120atattcaagc acatatgtta tatattattc agttccatgt ttatagccta gttaaggaga 180ggggagatac attcngaaag aggactgaaa gaaatactca agtnggaaaa cagaaaaaga 240aaaaaaggag caaatgagaa gcct 264
<210> 212
<211> 328
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(328)
<223> n = A,T,C or G
<400> 212acccaaaaat ccaatgctga atatttggct tcattattcc canattcttt gattgtcaaa 60ggatttaatg ttgtctcagc ttgggcactt cagttaggac ctaaggatgc cagccggcag 120gtttatatat gcagcaacaa tattcaagcg cgacaacagg ttattgaact tgcccgccag 180ttnaatttca ttcccattga cttgggatcc ttatcatcag ccagagagat tgaaaattta 240cccctacnac tctttactct ctgganaggg ccagtggtgg tagctataag cttggccaca 300tttttttttc ctttattcct ttgtcaga 328
<210> 213
<211> 250
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(250)
<223> n = A,T,C or G
<400> 213acttatgagc agagcgacat atccnagtgt agactgaata aaactgaatt ctctccagtt 60taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat tccaagagtt 180ttcaatattt gcatgaacct gctgataanc catgttaana aacaaatatc tctctnacct 240tctcatcggt 250
<210> 214
<211> 444
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(444)
<223> n = A,T,C or G
<400> 214acccagaatc caatgctgaa tatttggctt cattattccc agattctttg attgtcaaag 60gatttaatgt tgtctcagct tgggcacttc agttaggacc taaggatgcc agccggcagg 120tttatatatg cagcaacaat attcaagcgc gacaacaggt tattgaactt gcccgccagt 180tgaatttcat tcccattgac ttgggatcct tatcatcagc canagagatt gaaaatttac 240ccctacgact ctttactctc tggagagggc cagtggtggt agctataagc ttggccacat 300ttttttttcc tttattcctt tgtcagagat gcgattcatc catatgctan aaaccaacag 360agtgactttt acaaaattcc tataganatt gtgaataaaa ccttacctat agttgccatt 420actttgctct ccctaatata cctc 444
<210> 215
<211> 366
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(366)
<223> n = A,T,C or G
<400> 215acttatgagc agagcgacat atccaagtgt anactgaata aaactgaatt ctctccagtt 60taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat tccaagagtt 180ttcaatattt gcatgaacct gctgataagc catgttgaga aacaaatatc tctctgacct 240tctcatcggt aagcagaggc tgtaggcaac atggaccata gcgaanaaaa aacttagtaa 300tccaagctgt tttctacact gtaaccaggt ttccaaccaa ggtggaaatc tcctatactt 360ggtgcc 366
<210> 216
<211> 260
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(260)
<223> n = A,T,C or G
<400> 216ctgtataaac agaactccac tgcangaggg agggccgggc caggagaatc tccgcttgtc 60caagacaggg gcctaaggag ggtctccaca ctgctnntaa gggctnttnc atttttttat 120taataaaaag tnnaaaaggc ctcttctcaa cttttttccc ttnggctgga aaatttaaaa 180atcaaaaatt tcctnaagtt ntcaagctat catatatact ntatcctgaa aaagcaacat 240aattcttcct tccctccttt 260
<210> 217
<211> 262
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(262)
<223> n = A,T,C or G
<400> 217acctacgtgg gtaagtttan aaatgttata atttcaggaa naggaacgca tataattgta 60tcttgcctat aattttctat tttaataagg aaatagcaaa ttggggtggg gggaatgtag 120ggcattctac agtttgagca aaatgcaatt aaatgtggaa ggacagcact gaaaaatttt 180atgaataatc tgtatgatta tatgtctcta gagtagattt ataattagcc acttacccta 240atatccttca tgcttgtaaa gt 262
<210> 218
<211> 205
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(205)
<223> n = A,T,C or G
<400> 218accaaggtgg tgcattaccg gaantggatc aangacacca tcgtggccaa cccctgagca 60cccctatcaa ctcccttttg tagtaaactt ggaaccttgg aaatgaccag gccaagactc 120aggcctcccc agttctactg acctttgtcc ttangtntna ngtccagggt tgctaggaaa 180anaaatcagc agacacaggt gtaaa 205
<210> 219
<211> 114
<212> DNA
<213> Homo sapien
<400> 219tactgttttg tctcagtaac aataaataca aaaagactgg ttgtgttccg gccccatcca 60accacgaagt tgatttctct tgtgtgcaga gtgactgatt ttaaaggaca tgga 114
<210> 220
<211> 93
<212> DNA
<213> Homo sapien
<400> 220actagccagc acaaaaggca gggtagcctg aattgctttc tgctctttac atttctttta 60aaataagcat ttagtgctca gtccctactg agt 93
<210> 221
<211> 167
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(167)
<223> n = A,T,C or G
<400> 221actangtgca ggtgcgcaca aatatttgtc gatattccct tcatcttgga ttccatgagg 60tcttttgccc agcctgtggc tctactgtag taagtttctg ctgatgagga gccagnatgc 120cccccactac cttccctgac gctccccana aatcacccaa cctctgt 167
<210> 222
<211> 351
<212> DNA
<213> Homo sapien
<400> 222agggcgtggt gcggagggcg gtactgacct cattagtagg aggatgcatt ctggcacccc 60gttcttcacc tgtcccccaa tccttaaaag gccatactgc ataaagtcaa caacagataa 120atgtttgctg aattaaagga tggatgaaaa aaattaataa tgaatttttg cataatccaa 180ttttctcttt tatatttcta gaagaagttt ctttgagcct attagatccc gggaatcttt 240taggtgagca tgattagaga gcttgtaggt tgcttttaca tatatctggc atatttgagt 300ctcgtatcaa aacaatagat tggtaaaggt ggtattattg tattgataag t 351
<210> 223
<211> 383
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(383)
<223> n = A,T,C or G
<400> 223aaaacaaaca aacaaaaaaa acaattcttc attcagaaaa attatcttag ggactgatat 60tggtaattat ggtcaattta atwrtrttkt ggggcatttc cttacattgt cttgacaaga 120ttaaaatgtc tgtgccaaaa ttttgtattt tatttggaga cttcttatca aaagtaatgc 180tgccaaagga agtctaagga attagtagtg ttcccmtcac ttgtttggag tgtgctattc 240taaaagattt tgatttcctg gaatgacaat tatattttaa ctttggtggg ggaaanagtt 300ataggaccac agtcttcact tctgatactt gtaaattaat cttttattgc acttgttttg 360accattaagc tatatgttta aaa 383
<210> 224
<211> 320
<212> DNA
<213> Homo sapien
<400> 224cccctgaagg cttcttgtta gaaaatagta cagttacaac caataggaac aacaaaaaga 60aaaagtttgt gacattgtag tagggagtgt gtacccctta ctccccatca aaaaaaaaat 120ggatacatgg ttaaaggata raagggcaat attttatcat atgttctaaa agagaaggaa 180gagaaaatac tactttctcr aaatggaagc ccttaaaggt gctttgatac tgaaggacac 240aaatgtggcc gtccatcctc ctttaragtt gcatgacttg gacacggtaa ctgttgcagt 300tttaractcm gcattgtgac 320
<210> 225
<211> 1214
<212> DNA
<213> Homo sapien
<400> 225gaggactgca gcccgcactc gcagccctggcaggcggcac tggtcatgga aaacgaattg 60ttctgctcgg gcgtcctggt gcatccgcag tgggtgctgt cagccgcaca ctgtttccag 120aactcctaca ccatcgggct gggcctgcac agtcttgagg ccgaccaaga gccagggagc 180cagatggtgg aggccagcct ctccgtacgg cacccagagt acaacagacc cttgctcgct 240aacgacctca tgctcatcaa gttggacgaa tccgtgtccg agtctgacac catccggagc 300atcagcattg cttcgcagtg ccctaccgcg gggaactctt gcctcgtttc tggctggggt 360ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg tgaacgtgtc ggtggtgtct 420gaggaggtct gcagtaagct ctatgacccg ctgtaccacc ccagcatgtt ctgcgccggc 480ggagggcaag accagaagga ctcctgcaac ggtgactctg gggggcccct gatctgcaac 540gggtacttgc agggccttgt gtctttcgga aaagccccgt gtggccaagt tggcgtgcca 600ggtgtctaca ccaacctctg caaattcact gagtggatag agaaaaccgt ccaggccagt 660taactctggg gactgggaac ccatgaaatt gacccccaaa tacatcctgc ggaaggaatt 720caggaatatc tgttcccagc ccctcctccc tcaggcccag gagtccaggc ccccagcccc 780tcctccctca aaccaagggt acagatcccc agcccctcct ccctcagacc caggagtcca 840gaccccccag cccctcctcc ctcagaccca ggagtccagc ccctcctccc tcagacccag 900gagtccagac cccccagccc ctcctccctc agacccaggg gtccaggccc ccaacccctc 960ctccctcaga ctcagaggtc caagccccca acccctcctt ccccagaccc agaggtccag 1020gtcccagccc ctcctccctc agacccagcg gtccaatgcc acctagactc tccctgtaca 1080cagtgccccc ttgtggcacg ttgacccaac cttaccagtt ggtttttcat tttttgtccc 1140tttcccctag atccagaaat aaagtctaag agaagcgcaa aaaaaaaaaa aaaaaaaaaa 1200aaaaaaaaaa aaaa 1214
<210> 226
<211> 119
<212> DNA
<213> Homo sapien
<400> 226acccagtatg tgcagggaga cggaacccca tgtgacagcc cactccacca gggttcccaa 60agaacctggc ccagtcataa tcattcatcc tgacagtggc aataatcacg ataaccagt 119
<210> 227
<211> 818
<212> DNA
<213> Homo sapien
<400> 227acaattcata gggacgacca atgaggacag ggaatgaacc cggctctccc ccagccctga 60tttttgctac atatggggtc ccttttcatt ctttgcaaaa acactgggtt ttctgagaac 120acggacggtt cttagcacaa tttgtgaaat ctgtgtaraa ccgggctttg caggggagat 180aattttcctc ctctggagga aaggtggtga ttgacaggca gggagacagt gacaaggcta 240gagaaagcca cgctcggcct tctctgaacc aggatggaac ggcagacccc tgaaaacgaa 300gcttgtcccc ttccaatcag ccacttctga gaacccccat ctaacttcct actggaaaag 360agggcctcct caggagcagt ccaagagttt tcaaagataa cgtgacaact accatctaga 420ggaaagggtg caccctcagc agagaagccg agagcttaac tctggtcgtt tccagagaca 480acctgctggc tgtcttggga tgcgcccagc ctttgagagg ccactacccc atgaacttct 540gccatccact ggacatgaag ctgaggacac tgggcttcaa cactgagttg tcatgagagg 600gacaggctct gccctcaagc cggctgaggg cagcaaccac tctcctcccc tttctcacgc 660aaagccattc ccacaaatcc agaccatacc atgaagcaac gagacccaaa cagtttggct 720caagaggata tgaggactgt ctcagcctgg ctttgggctg acaccatgca cacacacaag 780gtccacttct aggttttcag cctagatggg agtcgtgt 818
<210> 228
<211> 744
<212> DNA
<213> Homo sapien
<400> 228actggagaca ctgttgaact tgatcaagac ccagaccacc ccaggtctcc ttcgtgggat 60gtcatgacgt ttgacatacc tttggaacga gcctcctcct tggaagatgg aagaccgtgt 120tcgtggccga cctggcctct cctggcctgt ttcttaagat gcggagtcac atttcaatgg 180taggaaaagt ggcttcgtaa aatagaagag cagtcactgt ggaactacca aatggcgaga 240tgctcggtgc acattggggt gctttgggat aaaagattta tgagccaact attctctggc 300accagattct aggccagttt gttccactga agcttttccc acagcagtcc acctctgcag 360gctggcagct gaatggcttg ccggtggctc tgtggcaaga tcacactgag atcgatgggt 420gagaaggcta ggatgcttgt ctagtgttct tagctgtcac gttggctcct tccaggttgg 480ccagacggtg ttggccactc ccttctaaaa cacaggcgcc ctcctggtga cagtgacccg 540ccgtggtatg ccttggccca ttccagcagt cccagttatg catttcaagt ttggggtttg 600ttcttttcgt taatgttcct ctgtgttgtc agctgtcttc atttcctggg ctaagcagca 660ttgggagatg tggaccagag atccactcct taagaaccag tggcgaaaga cactttcttt 720cttcactctg aagtagctgg tggt 744
<210> 229
<211> 300
<212> DNA
<213> Homo sapien
<400> 229cgagtctggg ttttgtctat aaagtttgat ccctcctttt ctcatccaaa tcatgtgaac 60cattacacat cgaaataaaa gaaaggtggc agacttgccc aacgccaggc tgacatgtgc 120tgcagggttg ttgtttttta attattattg ttagaaacgt cacccacagt ccctgttaat 180ttgtatgtga cagccaactc tgagaaggtc ctatttttcc acctgcagag gatccagtct 240cactaggctc ctccttgccc tcacactgga gtctccgcca gtgtgggtgc ccactgacat 300
<210> 230
<211> 301
<212> DNA
<213> Homo sapien
<400> 230cagcagaaca aatacaaata tgaagagtgc aaagatctca taaaatctat gctgaggaat 60gagcgacagt tcaaggagga gaagcttgca gagcagctca agcaagctga ggagctcagg 120caatataaag tcctggttca cactcaggaa cgagagctga cccagttaag ggagaagttg 180cgggaaggga gagatgcctc cctctcattg aatgagcatc tccaggccct cctcactccg 240gatgaaccgg acaagtccca ggggcaggac ctccaagaaa cagacctcgg ccgcgaccac 300g 301
<210> 231
<211> 301
<212> DNA
<213> Homo sapien
<400> 231gcaagcacgc tggcaaatct ctgtcaggtc agctccagag aagccattag tcattttagc 60caggaactcc aagtccacat ccttggcaac tggggacttg cgcaggttag ccttgaggat 120ggcaacacgg gacttctcat caggaagtgg gatgtagatg agctgatcaa gacggccagg l80tctgaggatg gcaggatcaa tgatgtcagg ccggttggta ccgccaatga tgaacacatt 240tttttttgtg gacatgccat ccatttctgt caggatctgg ttgatgactc ggtcagcagc 300c 301
<210> 232
<211> 301
<212> DNA
<213> Homo sapien
<400> 232agtaggtatt tcgtgagaag ttcaacacca aaactggaac atagttctcc ttcaagtgtt 60ggcgacagcg gggcttcctg attctggaat ataactttgt gtaaattaac agccacctat 120agaagagtcc atctgctgtg aaggagagac agagaactct gggttccgtc gtcctgtcca 180cgtgctgtac caagtgctgg tgccagcctg ttacctgttc ccactgaaaa tctggctaat 240gctcttgtgt atcacttctg attctgacaa tcaatcaatc aatggcctag agcactgact 300g 301
<210> 233
<211> 301
<212> DNA
<213> Homo sapien
<400> 233atgactgact tcccagtaag gctctctaag gggtaagtag gaggatccac aggatttgag 60atgctaaggc cccagagatc gtttgatcca accctcttat tttcagaggg gaaaatgggg 120cctagaagtt acagagcatc tagctggtgc gctggcaccc ctggcctcac acagactccc 180gagtagctgg gactacaggc acacagtcac tgaagcaggc cctgttagca attctatgcg 240tacaaattaa catgagatga gtagagactt tattgagaaa gcaagagaaa atcctatcaa 300c 301
<210> 234
<211> 301
<212> DNA
<213> Homo sapien
<400> 234aggtcctaca catcgagact catccatgat tgatatgaat ttaaaaatta caagcaaaga 60cattttattc atcatgatgc tttcttttgt ttcttctttt cgttttcttc tttttctttt 120tcaatttcag caacatactt ctcaatttct tcaggattta aaatcttgag ggattgatct 180cgcctcatga cagcaagttc aatgtttttg ccacctgact gaaccacttc caggagtgcc 240ttgatcacca gcttaatggt cagatcatct gcttcaatgg cttcgtcagt atagttcttc 300 301
<210> 235
<211> 283
<212> DNA
<213> Homo sapien
<400> 235tggggctgtg catcaggcgg gtttgagaaa tattcaattc tcagcagaag ccagaatttg 60aattccctca tcttttaggg aatcatttac caggtttgga gaggattcag acagctcagg 120tgctttcact aatgtctctg aacttctgtc cctctttgtt catggatagt ccaataaata 180atgttatctt tgaactgatg ctcataggag agaatataag aactctgagt gatatcaaca 240ttagggattc aaagaaatat tagatttaag ctcacactgg tca 283
<210> 236
<211> 301
<212> DNA
<213> Homo sapien
<400> 236aggtcctcca ccaactgcct gaagcacggt taaaattggg aagaagtata gtgcagcata 60aatactttta aatcgatcag atttccctaa cccacatgca atcttcttca ccagaagagg 120tcggagcagc atcattaata ccaagcagaa tgcgtaacag ataaatacaa tggtatatag 180tgggtagacg gcttcatgag tacagtgtac tgtggtatcg taatctggac ttgggttgta 240aagcatcgtg taccagtcag aaagcatcaa tactcgacat gaacgaatat aaagaacacc 300a 301
<210> 237
<211> 301
<212> DNA
<213> Homo sapien
<400> 237cagtggtagt ggtggtggac gtggcgttgg tcgtggtgcc ttttttggtg cccgtcacaa 60actcaatttt tgttcgctcc tttttggcct tttccaattt gtccatctca attttctggg 120ccttggctaa tgcctcatag taggagtcct cagaccagcc atggggatca aacatatcct 180ttgggtagtt ggtgccaagc tcgtcaatgg cacagaatgg atcagcttct cgtaaatcta 240gggttccgaa attctttctt cctttggata atgtagttca tatccattcc ctcctttatc 300t 301
<210> 238
<211> 301
<212> DNA
<213> Homo sapien
<400> 238gggcaggttt tttttttttt ttttttgatg gtgcagaccc ttgctttatt tgtctgactt 60gttcacagtt cagccccctg ctcagaaaac caacgggcca gctaaggaga ggaggaggca 120ccttgagact tccggagtcg aggctctcca gggttcccca gcccatcaat cattttctgc 180accccctgcc tgggaagcag ctccctgggg ggtgggaatg ggtgactaga agggatttca 240gtgtgggacc cagggtctgt tcttcacagt aggaggtgga agggatgact aatttcttta 300t 301
<210> 239
<211> 239
<212> DNA
<213> Homo sapien
<400> 239ataagcagct agggaattct ttatttagta atgtcctaac ataaaagttc acataactgc 60ttctgtcaaa ccatgatact gagctttgtg acaacccaga aataactaag agaaggcaaa 120cataatacct tagagatcaa gaaacattta cacagttcaa ctgtttaaaa atagctcaac 180attcagccag tgagtagagt gtgaatgcca gcatacacag tatacaggtc cttcaggga 239
<210> 240
<211> 300
<212> DNA
<213> Homo sapien
<400> 240ggtcctaatg aagcagcagc ttccacattt taacgcaggt ttacggtgat actgtccttt 60gggatctgcc ctccagtgga accttttaag gaagaagtgg gcccaagcta agttccacat 120gctgggtgag ccagatgact tctgttccct ggtcactttc ttcaatgggg cgaatggggg 180ctgccaggtt tttaaaatca tgcttcatct tgaagcacac ggtcacttca ccctcctcac 240gctgtgggtg tactttgatg aaaataccca ctttgttggc ctttctgaag ctataatgtc 300
<210> 241
<211> 301
<212> DNA
<213> Homo sapien
<400> 241gaggtctggt gctgaggtct ctgggctagg aagaggagtt ctgtggagct ggaagccaga 60cctctttgga ggaaactcca gcagctatgt tggtgtctct gagggaatgc aacaaggctg 120ctcctccatg tattggaaaa ctgcaaactg gactcaactg gaaggaagtg ctgctgccag 180tgtgaagaac cagcctgagg tgacagaaac ggaagcaaac aggaacagcc agtcttttct 240tcctcctcct gtcatacggt ctccctcaag catcctttgt tgtcaggggc ctaaaaggga 300g 301
<210> 242
<211> 301
<212> DNA
<213> Homo sapien
<400> 242ccgaggtcct gggatgcaac caatcactct gtttcacgtg acttttatca ccatacaatt 60tgtggcattt cctcattttc tacattgtag aatcaagagt gtaaataaat gtatatcgat 120gtcttcaaga atatatcatt cctttttcac tagaacccat tcaaaatata agtcaagaat 180cttaatatca acaaatatat caagcaaact ggaaggcaga ataactacca taatttagta 240taagtaccca aagttttata aatcaaaagc cctaatgata accattttta gaattcaatc 300a 301
<210> 243
<211> 301
<212> DNA
<213> Homo sapien
<400> 243aggtaagtcc cagtttgaag ctcaaaagat ctggtatgag cataggctca tcgacgacat 60ggtggcccaa gctatgaaat cagagggagg cttcatctgg gcctgtaaaa actatgatgg 120tgacgtgcag tcggactctg tggcccaagg gtatggctct ctcggcatga tgaccagcgt 180gctggtttgt ccagatggca agacagtaga agcagaggct gcccacggga ctgtaacccg 240tcactaccgc atgttccaga aaggacagga gacgtccacc aatcccattg cttccatttt 300t 301
<210> 244
<211> 300
<212> DNA
<213> Homo sapien
<400> 244gctggtttgc aagaatgaaa tgaatgattc tacagctagg acttaacctt gaaatggaaa 60gtcatgcaat cccatttgca ggatctgtct gtgcacatgc ctctgtagag agcagcattc 120ccagggacct tggaaacagt tgacactgta aggtgcttgc tccccaagac acatcctaaa 180aggtgttgta atggtgaaaa cgtcttcctt ctttattgcc ccttcttatt tatgtgaaca 240actgtttgtc ttttgtgtat cttttttaaa ctgtaaagtt caattgtgaa aatgaatatc 300
<210> 245
<211> 301
<212> DNA
<213> Homo sapien
<400> 245gtctgagtat ttaaaatgtt attgaaatta tccccaacca atgttagaaa agaaagaggt 60tatatactta gataaaaaat gaggtgaatt actatccatt gaaatcatgc tcttagaatt 120aaggccagga gatattgtca ttaatgtara cttcaggaca ctagagtata gcagccctat 180gttttcaaag agcagagatg caattaaata ttgtttagca tcaaaaaggc cactcaatac 240agctaataaa atgaaagacc taatttctaa agcaattctt tataatttac aaagttttaa 300g 301
<210> 246
<211> 301
<212> DNA
<213> Homo sapien
<400> 246ggtctgtcct acaatgcctg cttcttgaaa gaagtcggca ctttctagaa tagctaaata 60acctgggctt attttaaaga actatttgta gctcagattg gttttcctat ggctaaaata 120agtgcttctt gtgaaaatta aataaaacag ttaattcaaa gccttgatat atgttaccac 180taacaatcat actaaatata ttttgaagta caaagtttga catgctctaa agtgacaacc 240caaatgtgtc ttacaaaaca cgttcctaac aaggtatgct ttacactacc aatgcagaaa 300c 301
<210> 247
<211> 301
<212> DNA
<213> Homo sapien
<400> 247aggtcctttg gcagggctca tggatcagag ctcaaactgg agggaaaggc atttcgggta 60gcctaagagg gcgactggcg gcagcacaac caaggaaggc aaggttgttt cccccacgct 120gtgtcctgtg ttcaggtgcg acacacaatc ctcatgggaa caggatcacc catgcgctgc 180ccttgatgat caaggttggg gcttaagtgg attaagggag gcaagttctg ggttccttgc 240cttttcaaac catgaagtca ggctctgtat ccctcctttt cctaactgat attctaacta 300a 301
<210> 248
<211> 301
<212> DNA
<213> Homo sapien
<400> 248aggtccttgg agatgccatt tcagccgaag gactcttctw ttcggaagta caccctcact 60attaggaaga ttcttagggg taatttttct gaggaaggag aactagccaa cttaagaatt 120acaggaagaa agtggtttgg aagacagcca aagaaataaa agcagattaa attgtatcag 180gtacattcca gcctgttggc aactccataa aaacatttca gattttaatc ccgaatttag 240ctaatgagac tggatttttg ttttttatgt tgtgtgtcgc agagctaaaa actcagttcc 300c 301
<210> 249
<211> 301
<212> DNA
<213> Homo sapien
<400> 249gtccagagga agcacctggt gctgaactag gcttgccctg ctgtgaactt gcacttggag 60ccctgacgct gctgttctcc ccgaaaaacc cgaccgacct ccgcgatctc cgtcccgccc 120ccagggagac acagcagtga ctcagagctg gtcgcacact gtgcctccct cctcaccgcc 180catcgtaatg aattattttg aaaattaatt ccaccatcct ttcagattct ggatggaaag 240actgaatctt tgactcagaa ttgtttgctg aaaagaatga tgtgactttc ttagtcattt 300a 301
<210> 250
<211> 301
<212> DNA
<213> Homo sapien
<400> 250ggtctgtgac aaggacttgc aggctgtggg aggcaagtga cccttaacac tacacttctc 60cttatcttta ttggcttgat aaacataatt atttctaaca ctagcttatt tccagttgcc 120cataagcaca tcagtacttt tctctggctg gaatagtaaa ctaaagtatg gtacatctac 180ctaaaagact actatgtgga ataatacata ctaatgaagt attacatgat ttaaagacta 240caataaaacc aaacatgctt ataacattaa gaaaaacaat aaagatacat gattgaaacc 300a 301
<210> 251
<211> 301
<212> DNA
<213> Homo sapien
<400> 251gccgaggtcc tacatttggc ccagtttccc cctgcatcct ctccagggcc cctgcctcat 60agacaacctc atagagcata ggagaactgg ttgccctggg ggcaggggga ctgtctggat 120ggcaggggtc ctcaaaaatg ccactgtcac tgccaggaaa tgcttctgag cagtacacct l80cattgggatc aatgaaaagc ttcaagaaat cttcaggctc actctcttga aggcccggaa 240cctctggagg ggggcagtgg aatcccagct ccaggacgga tcctgtcgaa aagatatcct 300c 301
<210> 252
<211> 301
<212> DNA
<213> Homo sapien
<400> 252gcaaccaatc actctgtttc acgtgacttt tatcaccata caatttgtgg catttcctca 60ttttctacat tgtagaatca agagtgtaaa taaatgtata tcgatgtctt caagaatata 120tcattccttt ttcactagga acccattcaa aatataagtc aagaatctta atatcaacaa 180atatatcaag caaactggaa ggcagaataa ctaccataat ttagtataag tacccaaagt 240tttataaatc aaaagcccta atgataacca tttttagaat tcaatcatca ctgtagaatc 300a 301
<210> 253
<211> 301
<212> DNA
<213> Homo sapien
<400> 253ttccctaaga agatgttatt ttgttgggtt ttgttccccc tccatctcga ttctcgtacc 60caactaaaaa aaaaaaataa agaaaaaatg tgctgcgttc tgaaaaataa ctccttagct 120tggtctgatt gttttcagac cttaaaatat aaacttgttt cacaagcttt aatccatgtg 180gatttttttt cttagagaac cacaaaacat aaaaggagca agtcggactg aatacctgtt 240tccatagtgc ccacagggta ttcctcacat tttctccata ggaaaatgct ttttcccaag 300g 301
<210> 254
<211> 301
<212> DNA
<213> Homo sapien
<400> 254cgctgcgcct ttcccttggg ggaggggcaa ggccagaggg ggtccaagtg cagcacgagg 60aacttgacca attcccttga agcgggtggg ttaaaccctg taaatgggaa caaaatcccc 120ccaaatctct tcatcttacc ctggtggact cctgactgta gaattttttg gttgaaacaa 180gaaaaaaata aagctttgga cttttcaagg ttgcttaaca ggtactgaaa gactggcctc 240acttaaactg agccaggaaa agctgcagat ttattaatgg gtgtgttagt gtgcagtgcc 300t 301
<210> 255
<211> 302
<212> DNA
<213> Homo sapien
<400> 255agcttttttt tttttttttt tttttttttt ttcattaaaa aatagtgctc tttattataa 60attactgaaa tgtttctttt ctgaatataa atataaatat gtgcaaagtt tgacttggat 120tgggattttg ttgagttctt caagcatctc ctaataccct caagggcctg agtagggggg 180aggaaaaaggactggaggtg gaatctttat aaaaaacaag agtgattgag gcagattgta 240aacattatta aaaaacaaga aacaaacaaa aaaatagaga aaaaaaccac cccaacacac 300aa 302
<210> 256
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 256gttccagaaa acattgaagg tggcttccca aagtctaact agggataccc cctctagcct 60aggaccctcc tccccacacc tcaatccacc aaaccatcca taatgcaccc agataggccc 120acccccaaaa gcctggacac cttgagcaca cagttatgac caggacagac tcatctctat 180aggcaaatag ctgctggcaa actggcatta cctggtttgt ggggatgggg gggcaagtgt 240gtggcctctc ggcctggtta gcaagaacat tcagggtagg cctaagttan tcgtgttagt 300t 301
<210> 257
<211> 301
<212> DNA
<213> Homo sapien
<400> 257gttgtggagg aactctggct tgctcattaa gtcctactga ttttcactat cccctgaatt 60tccccactta tttttgtctt tcactatcgc aggccttaga agaggtctac ctgcctccag 120tcttacctag tccagtctac cccctggagt tagaatggcc atcctgaagt gaaaagtaat 180gtcacattac tcccttcagt gatttcttgt agaagtgcca atccctgaat gccaccaaga 240tcttaatctt cacatcttta atcttatctc tttgactcct ctttacaccg gagaaggctc 300c 301
<210> 258
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 258cagcagtagt agatgccgta tgccagcacg cccagcactc ccaggatcag caccagcacc 60aggggcccag ccaccaggcg cagaagcaag ataaacagta ggctcaagac cagagccacc 120cccagggcaa caagaatcca ataccaggac tgggcaaaat cttcaaagat cttaacactg 180atgtctcggg cattgaggct gtcaataana cgctgatccc ctgctgtatg gtggtgtcat 240tggtgatccc tgggagcgcc ggtggagtaa cgttggtcca tggaaagcag cgcccacaac 300t 301
<210> 259
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 259tcatatatgc aaacaaatgc agactangcc tcaggcagag actaaaggac atctcttggg 60gtgtcctgaa gtgatttgga cccctgaggg cagacaccta agtaggaatc ccagtgggaa 120gcaaagccat aaggaagccc aggattcctt gtgatcagga agtgggccag gaaggtctgt 180tccsgctcac atctcatctg catgcagcac ggaccggatg cgcccactgg gtcttggctt 240ccctcccatc ttctcaagca gtgtccttgt tgagccattt gcatccttgg ctccaggtgg 300c 301
<210> 260
<211> 301
<212> DNA
<213> Homo sapien
<400> 260ttttttttct ccctaaggaa aaagaaggaa caagtctcat aaaaccaaat aagcaatggt 60aaggtgtctt aacttgaaaa agattaggag tcactggttt acaagttata attgaatgaa 120agaactgtaa cagccacagt tggccatttc atgccaatgg cagcaaacaa caggattaac 180tagggcaaaa taaataagtg tgtggaagcc ctgataagtg cttaataaac agactgattc 240actgagacat cagtacctgc ccgggcggcc gctcgagccg aattctgcag atatccatca 300c 301
<210> 261
<211> 301
<212> DNA
<213> Homo sapien
<400> 261aaatattcga gcaaatcctg taactaatgt gtctccataa aaggctttga actcagtgaa 60tctgcttcca tccacgattc tagcaatgac ctctcggaca tcaaagctcc tcttaaggtt 120agcaccaact attccataca attcatcagc aggaaataaa ggctcttcag aaggttcaat 180ggtgacatcc aatttcttct gataatttag attcctcaca accttcctag ttaagtgaag 240ggcatgatga tcatccaaag cccagtggtc acttactcca gactttctgc aatgaagatc 300a 301
<210> 262
<211> 301
<212> DNA
<213> Homo sapien
<400> 262gaggagagcc tgttacagca tttgtaagca cagaatactc caggagtatt tgtaattgtc 60tgtgagcttc ttgccgcaag tctctcagaa atttaaaaag atgcaaatcc ctgagtcacc 120cctagacttc ctaaaccaga tcctctgggg ctggaacctg gcactctgca tttgtaatga 180gggctttctg gtgcacacct aattttgtgc atctttgccc taaatcctgg attagtgccc 240catcattacc cccacattat aatgggatag attcagagca gatactctcc agcaaagaat 300c 301
<210> 263
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 263tttagcttgt ggtaaatgac tcacaaaact gattttaaaa tcaagttaat gtgaattttg 60aaaattacta cttaatccta attcacaata acaatggcat taaggtttga cttgagttgg 120ttcttagtat tatttatggt aaataggctc ttaccacttg caaataactg gccacatcat 180taatgactga cttcccagta aggctctcta aggggtaagt angaggatcc acaggatttg 240agatgctaag gccccagaga tcgtttgatc caaccctctt attttcagag gggaaaatgg 300g 301
<210> 264
<211> 301
<212> DNA
<213> Homo sapien
<400> 264aaagacgtta aaccactcta ctaccacttg tggaactctc aaagggtaaa tgacaaascc 60aatgaatgac tctaaaaaca atatttacat ttaatggttt gtagacaata aaaaaacaag 120gtggatagat ctagaattgt aacattttaa gaaaaccata scatttgaca gatgagaaag 180ctcaattata gatgcaaagt tataactaaa ctactatagt agtaaagaaa tacatttcac 240acccttcata taaattcact atcttggctt gaggcactcc ataaaatgta tcacgtgcat 300a 301
<210> 265
<211> 301
<212> DNA
<213> Homo sapien
<400> 265tgcccaagtt atgtgtaagt gtatccgcac ccagaggtaa aactacactg tcatctttgt 60cttcttgtga cgcagtattt cttctctggg gagaagccgg gaagtcttct cctggctcta 120catattcttg gaagtctcta atcaactttt gttccatttg tttcatttct tcaggaggga 180ttttcagttt gtcaacatgt tctctaacaa cacttgccca tttctgtaaa gaatccaaag 240cagtccaagg ctttgacatg tcaacaacca gcataactag agtatccttc agagatacgg 300c 301
<210> 266
<211> 301
<212> DNA
<213> Homo sapien
<400> 266taccgtctgc ccttcctccc atccaggcca tctgcgaatc tacatgggtc ctcctattcg 60acaccagatc actctttcct ctacccacag gcttgctatg agcaagagac acaacctcct 120ctcttctgtg ttccagcttc ttttcctgtt cttcccaccc cttaagttct attcctgggg 180atagagacac caatacccat aacctctctc ctaagcctcc ttataaccca gggtgcacag 240cacagactcc tgacaactgg taaggccaat gaactgggag ctcacagctg gctgtgcctg 300a 301
<210> 267
<211> 301
<212> DNA
<213> Homo sapien
<400> 267aaagagcaca ggccagctca gcctgccctg gccatctaga ctcagcctgg ctccatgggg 60gttctcagtg ctgagtccat ccaggaaaag ctcacctaga ccttctgagg ctgaatcttc 120atcctcacag gcagcttctg agagcctgat attcctagcc ttgatggtct ggagtaaagc 180ctcattctga ttcctctcct tcttttcttt caagttggct ttcctcacat ccctctgttc 240aattcgcttc agcttgtctg ctttagccct catttccaga agcttcttct ctttggcatc 300t 301
<210> 268
<211> 301
<212> DNA
<213> Homo sapien
<400> 268aatgtctcac tcaactactt cccagcctac cgtggcctaa ttctgggagt tttcttctta 60gatcttggga gagccggttc ttctaaggag aaggaggaag gacagatgta actttggatc 120tcgaagagga agtctaatgg aagtaattag tcaacggtcc ttgtttagac tcttggaata 180tgctgggtgg ctcagtgagc ccttttggag aaagcaagta ttattcttaa ggagtaacca 240cttcccattg ttctactttc taccatcatc aattgtatat tatgtattct ttggagaact 300a 301
<210> 269
<211> 301
<212> DNA
<213> Homo sapien
<400> 269taacaatata cactagctat ctttttaact gtccatcatt agcaccaatg aagattcaat 60aaaattacct ttattcacac atctcaaaac aattctgcaa attcttagtg aagtttaact 120atagtcacag accttaaata ttcacattgt tttctatgtc tactgaaaat aagttcacta 180cttttctgga tattctttac aaaatcttat taaaattcct ggtattatca cccccaatta 240tacagtagca caaccacctt atgtagtttt tacatgatag ctctgtagaa gtttcacatc 300t 301
<210> 270
<211> 301
<212> DNA
<213> Homo sapien
<400> 270cattgaagag cttttgcgaa acatcagaac acaagtgctt ataaaattaa ttaagcctta 60cacaagaata catattcctt ttatttctaa ggagttaaac atagatgtag ctgatgtgga 120gagcttgctg gtgcagtgca tattggataa cactattcat ggccgaattg atcaagtcaa 180ccaactcctt gaactggatc atcagaagaa gggtggtgca cgatatactg cactagataa 240tggaccaacc aactaaattc tctcaccagg ctgtatcagt aaactggctt aacagaaaac 300a 301
<210> 271
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,c or G
<400> 271aaaaggttct cataagatta acaatttaaa taaatatttg atagaacatt ctttctcatt 60tttatagctc atctttaggg ttgatattca gttcatgctt cccttgctgt tcttgatcca 120gaattgcaat cacttcatca gcctgtattc gctccaattc tctataaagt gggtccaagg 180tgaaccacag agccacagca cacctctttc ccttggtgac tgccttcacc ccatganggt 240tctctcctcc agatganaac tgatcatgcg cccacatttt gggttttata gaagcagtca 300c 301
<210> 272
<211> 301
<212> DNA
<213> Homo sapien
<400> 272taaattgcta agccacagat aacaccaatc aaatggaaca aatcactgtc ttcaaatgtc 60ttatcagaaa accaaatgag cctggaatct tcataatacc taaacatgcc gtatttagga 120tccaataatt ccctcatgat gagcaagaaa aattctttgc gcacccctcc tgcatccaca 180gcatcttctc caacaaatat aaccttgagt ggcttcttgt aatctatgtt ctttgttttc 240ctaaggactt ccattgcatc tcctacaata ttttctctac gcaccactag aattaagcag 300g 301
<210> 273
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 273acatgtgtgt atgtgtatct ttgggaaaan aanaagacat cttgtttayt atttttttgg 60agagangctg ggacatggat aatcacwtaa tttgctayta tyactttaat ctgactygaa 120gaaccgtcta aaaataaaat ttaccatgtc dtatattcct tatagtatgc ttatttcacc 180ttytttctgt ccagagagag tatcagtgac ananatttma gggtgaamac atgmattggt 240gggacttnty tttacngagm accctgcccg sgcgccctcg makcngantt ccgcsananc 300t 301
<210> 274
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 274cttatatact ctttctcaga ggcaaaagag gagatgggta atgtagacaa ttctttgagg 60aacagtaaat gattattaga gagaangaat ggaccaagga gacagaaatt aacttgtaaa 120tgattctctt tggaatctga atgagatcaa gaggccagct ttagcttgtg gaaaagtcca 180tctaggtatg gttgcattct cgtcttcttt tctgcagtag ataatgaggt aaccgaaggc 240aattgtgctt cttttgataa gaagctttct tggtcatatc aggaaattcc aganaaagtc 300C 301
<210> 275
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 275tcggtgtcag cagcacgtgg cattgaacat tgcaatgtgg agcccaaacc acagaaaatg 60gggtgaaatt ggccaacttt ctattaactt atgttggcaa ttttgccacc aacagtaagc 120tggcccttct aataaaagaa aattgaaagg tttctcacta aacggaatta agtagtggag 180tcaagagact cccaggcctc agcgtacctg cccgggcggc cgctcgaagc cgaattctgc 240agatatccat cacactggcg gncgctcgan catgcatcta gaaggnccaa ttcgccctat 300a 301
<210> 276
<211> 301
<212> DNA
<213> Homo sapien
<400> 276tgtacacata ctcaataaat aaatgactgc attgtggtat tattactata ctgattatat 60ttatcatgtg acttctaatt agaaaatgta tccaaaagca aaacagcaga tatacaaaat 120taaagagaca gaagatagac attaacagat aaggcaactt atacattgag aatccaaatc 180caatacattt aaacatttgg gaaatgaggg ggacaaatgg aagccagatc aaatttgtgt 240aaaactattc agtatgtttc ccttgcttca tgtctgagaa ggctctcctt caatggggat 300g 301
<210> 277
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 277tttgttgatg tcagtatttt attacttgcg ttatgagtgc tcacctggga aattctaaag 60atacagagga cttggaggaa gcagagcaac tgaatttaat ttaaaagaag gaaaacattg 120gaatcatggc actcctgata ctttcccaaa tcaacactct caatgcccca ccctcgtcct 180caccatagtg gggagactaa agtggccacg gatttgcctt angtgtgcag tgcgttctga 240gttcnctgtc gattacatct gaccagtctc ctttttccga agtccntccg ttcaatcttg 300c 301
<210> 278
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 278taccactaca ctccagcctg ggcaacagag caagacctgt ctcaaagcat aaaatggaat 60aacatatcaa atgaaacagg gaaaatgaag ctgacaattt atggaagcca gggcttgtca 120cagtctctac tgttattatg cattacctgg gaatttatat aagcccttaa taataatgcc 180aatgaacatc tcatgtgtgc tcacaatgtt ctggcactat tataagtgct tcacaggttt 240tatgtgttct tcgtaacttt atggantagg tactcggccg cgaacacgct aagccgaatt 300c 301
<210> 279
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 279aaagcaggaa tgacaaagct tgcttttctg gtatgttcta ggtgtattgt gacttttact 60gttatattaa ttgccaatat aagtaaatat agattatata tgtatagtgt ttcacaaagc 120ttagaccttt accttccagc caccccacag tgcttgatat ttcagagtca gtcattggtt 180atacatgtgt agttccaaag cacataagct agaanaanaa atatttctag ggagcactac 240catctgtttt cacatgaaat gccacacaca tagaactcca acatcaattt cattgcacag 300a 301
<210> 280
<211> 301
<212> DNA
<213> Homo sapien
<400> 280ggtactggag ttttcctccc ctgtgaaaac gtaactactg ttgggagtga attgaggatg 60tagaaaggtg gtggaaccaa attgtggtca atggaaatag gagaatatgg ttctcactct 120tgagaaaaaa acctaagatt agcccaggta gttgcctgta acttcagttt ttctgcctgg 180gtttgatata gtttagggtt ggggttagat taagatctaa attacatcag gacaaagaga 240cagactatta actccacagt taattaagga ggtatgttcc atgtttattt gttaaagcag 300t 301
<210> 281
<211> 301
<212> DNA
<213> Homo sapien
<400> 281aggtacaaga aggggaatgg gaaagagctg ctgctgtggc attgttcaac ttggatattc 60gccgagcaat ccaaatcctg aatgaagggg catcttctga aaaaggagat ctgaatctca 120atgtggtagc aatggcttta tcgggttata cggatgagaa gaactccctt tggagagaaa 180tgtgtagcac actgcgatta cagctaaata acccgtattt gtgtgtcatg tttgcatttc 240tgacaagtga aacaggatct tacgatggag ttttgtatga aaacaaagtt gcagtacctc 300g 301
<2t0> 282
<211> 301
<212> DNA
<213> Homo sapien
<400> 282caggtactac agaattaaaa tactgacaag caagtagttt cttggcgtgc acgaattgca 60tccagaaccc aaaaattaag aaattcaaaa agacattttg tgggcacctg ctagcacaga 120agcgcagaag caaagcccag gcagaaccat gctaacctta cagctcagcc tgcacagaag 180cgcagaagca aagcccaggc agaaccatgctaaccttaca gctcagcctg cacagaagcg 240cagaagcaaa gcccaggcag aacatgctaa ccttacagct cagcctgcac agaagcacag 300a 301
<210> 283
<211> 301
<212> DNA
<213> Homo sapien
<400> 283atctgtatac ggcagacaaa ctttatarag tgtagagagg tgagcgaaag gatgcaaaag 60cactttgagg gctttataat aatatgctgc ttgaaaaaaa aaatgtgtag ttgatactca 120gtgcatctcc agacatagta aggggttgct ctgaccaatc aggtgatcat tttttctatc 180acttcccagg ttttatgcaa aaattttgtt aaattctata atggtgatat gcatctttta 240ggaaacatat acatttttaa aaatctattt tatgtaagaa ctgacagacg aatttgcttt 300g 301
<210> 284
<211> 301
<212> DNA
<213> Homo sapien
<400> 284caggtacaaa acgctattaa gtggcttaga atttgaacat ttgtggtctt tatttacttt 60gcttcgtgtg tgggcaaagc aacatcttcc ctaaatatat attaccaaga aaagcaagaa 120gcagattagg tttttgacaa aacaaacagg ccaaaagggg gctgacctgg agcagagcat 180ggtgagaggc aaggcatgag agggcaagtt tgttgtggac agatctgtgc ctactttatt 240actggagtaa aagaaaacaa agttcattga tgtcgaagga tatatacagt gttagaaatt 300a 301
<210> 285
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 285acatcaccat gatcggatcc cccacccatt atacgttgta tgcttacata aatactcttc 60aatgatcatt agtgttttaa aaaaaatact gaaaactcct tctgcatccc aacctctaac 120caggaaagca aatgctattt acagacctgc aagccctccc tcaaacnaaa ctatttctgg 180attaaatatg tctgacttct tttgaggtca cacgactagg caaatgctat ttacgatctg 240caaaagctgt ttgaagagtc aaagccccca tgtgaacacg atttctggac cctgtaacag 300t 301
<210> 286
<211> 301
<212> DNA
<213> Homo sapien
<400> 286taccactgca ttccagcctg ggtgacagag tgagactccg tctccaaaaa aaactttgct 60tgtatattat ttttgcctta cagtggatcattctagtagg aaaggacagt aagatttttt 120atcaaaatgt gtcatgccag taagagatgt tatattcttt tctcatttct tccccaccca 180aaaataagct accatatagc ttataagtct caaatttttg ccttttacta aaatgtgatt 240gtttctgttc attgtgtatg cttcatcacc tatattaggc aaattccatt ttttcccttg 300t 301
<210> 287
<211> 301
<212> DNA
<213> Homo sapien
<400> 287tacagatctg ggaactaaat attaaaaatg agtgtggctg gatatatgga gaatgttggg 60cccagaagga acgtagagat cagatattac aacagctttg ttttgagggt tagaaatatg 120aaatgatttg gttatgaacg cacagtttag gcagcagggc cagaatcctg accctctgcc 180ccgtggttat ctcctcccca gcttggctgc ctcatgttat cacagtattc cattttgttt 240gttgcatgtc ttgtgaagcc atcaagattt tctcgtctgt tttcctctca ttggtaatgc 300t 301
<210> 288
<211> 301
<212> DNA
<213> Homo sapien
<400> 288gtacacctaa ctgcaaggac agctgaggaa tgtaatgggc agccgctttt aaagaagtag 60agtcaatagg aagacaaatt ccagttccag ctcagtctgg gtatctgcaa agctgcaaaa 120gatctttaaa gacaatttca agagaatatt tccttaaagt tggcaatttg gagatcatac 180aaaagcatct gcttttgtga tttaatttag ctcatctggc cactggaaga atccaaacag 240tctgccttaa ttttggatga atgcatgatg gaaattcaat aatttagaaa gttaaaaaaa 300a 301
<210> 289
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 289ggtacactgt ttccatgtta tgtttctaca cattgctacc tcagtgctcc tggaaactta 60gcttttgatg tctccaagta gtccaccttc atttaactct ttgaaactgt atcatctttg 120ccaagtaaga gtggtggcct atttcagctg ctttgacaaa atgactggct cctgacttaa 180cgttctataa atgaatgtgc tgaagcaaag tgcccatggt ggcggcgaan aagagaaaga 240tgtgttttgt tttggactct ctgtggtccc ttccaatgct gtgggtttcc aaccagngga 300a 301
<210> 290
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 290acactgagct cttcttgata aatatacaga atgcttggca tatacaagat tctatactac 60tgactgatct gttcatttct ctcacagctc ttacccccaa aagcttttcc accctaagtg 120ttctgacctc cttttctaat cacagtaggg atagaggcag anccacctac aatgaacatg 180gagttctatc aagaggcaga aacagcacag aatcccagtt ttaccattcg ctagcagtgc 240tgccttgaac aaaaacattt ctccatgtct cattttcttc atgcctcaag taacagtgag 300a 301
<210> 291
<211> 301
<212> DNA
<213> Homo sapien
<400> 291caggtaccaa tttcttctat cctagaaaca tttcatttta tgttgttgaa acataacaac 60tatatcagct agattttttt tctatgcttt acctgctatg gaaaatttga cacattctgc 120tttactcttt tgtttatagg tgaatcacaa aatgtatttt tatgtattct gtagttcaat 180agccatggct gtttacttca tttaatttat ttagcataaa gacattatga aaaggcctaa 240acatgagctt cacttcccca ctaactaatt agcatctgtt atttcttaac cgtaatgcct 300a 301
<210> 292
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 292accttttagt agtaatgtct aataataaat aagaaatcaa ttttataagg tccatatagc 60tgtattaaat aatttttaag tttaaaagat aaaataccat cattttaaat gttggtattc 120aaaaccaaag natataaccg aaaggaaaaa cagatgagac ataaaatgat ttgcnagatg 180ggaaatatag tasttyatga atgttnatta aattccagtt ataatagtgg ctacacactc 240tcactacaca cacagacccc acagtcctat atgccacaaa cacatttcca taacttgaaa 300a 301
<210> 293
<211> 301
<212> DNA
<213> Homo sapien
<400> 293ggtaccaagt gctggtgcca gcctgttacc tgttctcact gaaaagtctg gctaatgctc 60ttgtgtagtc acttctgatt ctgacaatca atcaatcaat ggcctagagc actgactgtt 120aacacaaacg tcactagcaa agtagcaaca gctttaagtc taaatacaaa gctgttctgt 180gtgagaattt tttaaaaggc tacttgtata ataacccttg tcatttttaa tgtacctcgg 240ccgcgaccac gctaagccga attctgcaga tatccatcac actggcggcc gctcgagcat 300g 301
<210> 294
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 294tgacccataa caatatacac tagctatctt tttaactgtc catcattagc accaatgaag 60attcaataaa attaccttta ttcacacatc tcaaaacaat tctgcaaatt cttagtgaag 120tttaactata gtcacaganc ttaaatattc acattgtttt ctatgtctac tgaaaataag 180ttcactactt ttctgggata ttctttacaa aatcttatta aaattcctgg tattatcacc 240cccaattata cagtagcaca accaccttat gtagttttta catgatagct ctgtagaggt 300t 301
<210> 295
<211> 305
<212> DNA
<213> Homo sapien
<400> 295gtactctttc tctcccctcc tctgaattta attctttcaa cttgcaattt gcaaggatta 60cacatttcac tgtgatgtat attgtgttgc aaaaaaaaaa gtgtctttgt ttaaaattac 120ttggtttgtg aatccatctt gctttttccc cattggaact agtcattaac ccatctctga 180actggtagaa aaacrtctga agagctagtc tatcagcatc tgacaggtga attggatggt 240tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt 300tctct 305
<210> 296
<211> 301
<212> DNA
<213> Homo sapien
<400> 296aggtactatg ggaagctgct aaaataatat ttgatagtaa aagtatgtaa tgtgctatct 60cacctagtag taaactaaaa ataaactgaa actttatgga atctgaagtt attttccttg 120attaaataga attaataaac caatatgagg aaacatgaaa ccatgcaatc tactatcaac 180tttgaaaaag tgattgaacg aaccacttag ctttcagatg atgaacactg ataagtcatt 240tgtcattact ataaatttta aaatctgtta ataagatggc ctatagggag gaaaaagggg 300c 301
<210> 297
<211> 300
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(300)
<223> n = A,T,C or G
<400> 297actgagtttt aactggacgc caagcaggca aggctggaag gttttgctct ctttgtgcta 60aaggttttga aaaccttgaa ggagaatcat tttgacaaga agtacttaag agtctagaga 120acaaagangt gaaccagctg aaagctctcg ggggaanctt acatgtgttg ttaggcctgt 180tccatcattg ggagtgcact ggccatccct caaaatttgt ctgggctggc ctgagtggtc 240accgcacctc ggccgcgacc acgctaagcc gaattctgca gatatccatc acactggcgg 300
<210> 298
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 298tatggggttt gtcacccaaa agctgatgct gagaaaggcc tccctggggc ccctcccgcg 60ggcatctgag agacctggtg ttccagtgtt tctggaaatg ggtcccagtg ccgccggctg 120tgaagctctc agatcaatca cgggaagggc ctggcggtgg tggccacctg gaaccaccct 180gtcctgtctg tttacatttc actaycaggt tttctctggg cattacnatt tgttccccta 240caacagtgac ctgtgcattc tgctgtggcc tgctgtgtct gcaggtggct ctcagcgagg 300t 301
<210> 299
<211> 301
<212> DNA
<213> Homo sapien
<400> 299gttttgagac ggagtttcac tcttgttgcc cagactggac tgcaatggca gggtctctgc 60tcactgcacc ctctgcctcc caggttcgag caattctcct gcctcagcct cccaggtagc 120tgggattgca ggctcacgcc accataccca gctaattttt ttgtattttt agtagagacg 180gagtttcgcc atgttggcca gctggtctca aactcctgac ctcaagcgac ctgcctgcct 240cggcctccca aagtgctgga attataggca tgagtcaaca cgcccagcct aaagatattt 300t 301
<210> 300
<211> 301
<212> DNA
<213> Homo sapien
<400> 300attcagtttt atttgctgcc ccagtatctg taaccaggag tgccacaaaa tcttgccaga 60tatgtcccac acccactggg aaaggctccc acctggctac ttcctctatc agctgggtca 120gctgcattcc acaaggttct cagcctaatg agtttcacta cctgccagtc tcaaaactta 180gtaaagcaag accatgacat tcccccacgg aaatcagagt ttgccccacc gtcttgttac 240tataaagcct gcctctaaca gtccttgctt cttcacacca atcccgagcg catcccccat 300g 301
<210> 301
<211> 301
<212> DNA
<213> Homo sapien
<400> 301ttaaattttt gagaggataa aaaggacaaa taatctagaa atgtgtcttc ttcagtctgc 60agaggacccc aggtctccaa gcaaccacat ggtcaagggc atgaataatt aaaagttggt 120gggaactcac aaagaccctc agagctgaga cacccacaac agtgggagct cacaaagacc 180ctcagagctg agacacccac aacagtggga gctcacaaag accctcagag ctgagacacc 240cacaacagca cctcgttcag ctgccacatg tgtgaataag gatgcaatgt ccagaagtgt 300t 301
<210> 302
<211> 301
<212> DNA
<213> Homo sapien
<400> 302aggtacacat ttagcttgtg gtaaatgact cacaaaactg attttaaaat caagttaatg 60tgaattttga aaattactac ttaatcctaa ttcacaataa caatggcatt aaggtttgac 120ttgagttggt tcttagtatt atttatggta aataggctct taccacttgc aaataactgg 180ccacatcatt aatgactgac ttcccagtaa ggctctctaa ggggtaagta ggaggatcca 240caggatttga gatgctaagg ccccagagat cgtttgatcc aaccctctta ttttcagagg 300g 301
<210> 303
<211> 301
<212> DNA
<213> Homo sapien
<400> 303aggtaccaac tgtggaaata ggtagaggat cattttttct ttccatatca actaagttgt 60atattgtttt ttgacagttt aacacatctt cttctgtcag agattctttc acaatagcac 120tggctaatgg aactaccgct tgcatgttaa aaatggtggt ttgtgaaatg atcataggcc 180agtaacgggt atgtttttct aactgatctt ttgctcgttc caaagggacc tcaagacttc 240catcgatttt atatctgggg tctagaaaag gagttaatct gttttccctc ataaattcac 300c 301
<210> 304
<211> 301
<212> DNA
<213> Homo sapien
<400> 304acatggatgt tattttgcag actgtcaacc tgaatttgta tttgcttgac attgcctaat 60tattagtttc agtttcagct tacccacttt ttgtctgcaa catgcaraas agacagtgcc 120ctttttagtg tatcatatca ggaatcatct cacattggtt tgtgccatta ctggtgcagt 180gactttcagc cacttgggta aggtggagtt ggccatatgt ctccactgca aaattactga 240ttttcctttt gtaattaata agtgtgtgtg tgaagattct ttgagatgag gtatatatct 300c 301
<210> 305
<211> 301
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(301)
<223> n = A,T,C or G
<400> 305gangtacagc gtggtcaagg taacaagaag aaaaaaatgt gagtggcatc ctgggatgag 60cagggggaca gacctggaca gacacgttgt catttgctgc tgtgggtagg aaaatgggcg 120taaaggagga gaaacagata caaaatctcc aactcagtat taaggtattc tcatgcctag 180aatattggta gaaacaagaa tacattcata tggcaaataa ctaaccatgg tggaacaaaa 240ttctgggatt taagttggat accaangaaa ttgtattaaa agagctgttc atggaataag 300a 301
<210> 306
<211> 8
<212> PRT
<213> Homo sapien
<400> 306Val Leu Gly Trp Val Ala Glu Leu1 5
<210> 307
<211> 637
<212> DNA
<213> Homo sapien
<400> 307acagggratg aagggaaagg gagaggatga ggaagccccc ctggggattt ggtttggtcc 60ttgtgatcag gtggtctatg gggcttatcc ctacaaagaa gaatccagaa ataggggcac 120attgaggaat gatacttgag cccaaagagc attcaatcat tgttttattt gccttmtttt 180cacaccattg gtgagggagg gattaccacc ctggggttat gaagatggtt gaacacccca 240cacatagcac cggagatatg agatcaacag tttcttagcc atagagattc acagcccaga 300gcaggaggac gcttgcacac catgcaggat gacatggggg atgcgctcgg gattggtgtg 360aagaagcaag gactgttaga ggcaggcttt atagtaacaa gacggtgggg caaactctga 420tttccgtggg ggaatgtcat ggtcttgctt tactaagttt tgagactggc aggtagtgaa 480actcattagg ctgagaacct tgtggaatgc acttgaccca sctgatagag gaagtagcca 540ggtgggagcc tttcccagtg ggtgtgggac atatctggca agattttgtg gcactcctgg 600ttacagatac tggggcagca aataaaactg aatcttg 637
<210> 308
<211> 647
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(647)
<223> n = A,T,C or G
<400> 308acgattttca ttatcatgta aatcgggtca ctcaaggggc caaccacagc tgggagccac 60tgctcagggg aaggttcata tgggactttc tactgcccaa ggttctatac aggatataaa 120ggngcctcac agtatagatc tggtagcaaa gaagaagaaa caaacactga tctctttctg 180ccacccctct gaccctttgg aactcctctg accctttaga acaagcctac ctaatatctg 240ctagagaaaa gaccaacaac ggcctcaaag gatctcttac catgaaggtc tcagctaatt 300cttggctaag atgtgggttc cacattaggt tctgaatatg gggggaaggg tcaatttgct 360cattttgtgt gtggataaag tcaggatgcc caggggccag agcagggggc tgcttgcttt 420gggaacaatg gctgagcata taaccatagg ttatggggaa caaaacaaca tcaaagtcac 480tgtatcaatt gccatgaaga cttgagggac ctgaatctac cgattcatct taaggcagca 540ggaccagttt gagtggcaac aatgcagcag cagaatcaat ggaaacaaca gaatgattgc 600aatgtccttt tttttctcct gcttctgact tgataaaagg ggaccgt 647
<210> 309
<211> 460
<212> DNA
<213> Homo sapien
<400> 309actttatagt ttaggctgga cattggaaaa aaaaaaaagc cagaacaaca tgtgatagat 60aatatgattg gctgcacact tccagactga tgaatgatga acgtgatgga ctattgtatg 120gagcacatct tcagcaagag ggggaaatac tcatcatttt tggccagcag ttgtttgatc 180accaaacatc atgccagaat actcagcaaa ccttcttagc tcttgagaag tcaaagtccg 240ggggaattta ttcctggcaa ttttaattgg actccttatg tgagagcagc ggctacccag 300ctggggtggt ggagcgaacc cgtcactagt ggacatgcag tggcagagct cctggtaacc 360acctagagga atacacaggc acatgtgtga tgccaagcgt gacacctgta gcactcaaat 420ttgtcttgtt tttgtctttc ggtgtgtaag attcttaagt 460
<210> 310
<211> 539
<212> DNA
<213> Homo sapien
<400> 310acgggactta tcaaataaag ataggaaaag aagaaaactc aaatattata ggcagaaatg 60ctaaaggttt taaaatatgt caggattgga agaaggcatg gataaagaac aaagttcagt 120taggaaagag aaacacagaa ggaagagaca caataaaagt cattatgtat tctgtgagaa 180gtcagacagt aagatttgtg ggaaatgggt tggtttgttg tatggtatgt attttagcaa 240taatctttat ggcagagaaa gctaaaatcc tttagcttgc gtgaatgatc acttgctgaa 300ttcctcaagg taggcatgat gaaggagggt ttagaggaga cacagacaca atgaactgac 360ctagatagaa agccttagta tactcagcta ggaatagtga ttctgagggc acactgtgac 420atgattatgt cattacatgt atggtagtga tggggatgat aggaaggaag aacttatggc 480atattttcac ccccacaaaa gtcagttaaa tattgggaca ctaaccatcc aggtcaaga 539
<210> 311
<211> 526
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(526)
<223> n = A,T,C or G
<400> 311caaatttgag ccaatgacat agaattttac aaatcaagaa gcttatrctg gggccatttc 60ttttgacgtt ttctctaaac tactaaagag gcattaatga tccataaatt atattatcta 120catttacagc atttaaaatg tgttcagcat gaaatattag ctacagggga agctaaataa 180attaaacatg gaataaagat ttgtccttaa atataatcta caagaagact ttgatatttg 240tttttcacaa gtgaagcatt cttataaagt gtcataacct ttttggggaa actatgggaa 300aaaatgggga aactctgaag ggttttaagt atcttacctg aagctacaga ctccataacc 360tctctttaca gggagctcct gcagccccta cagaaatgag tggctgagat tcttgattgc 420acagcaagag cttctcatct aaaccctttc cctttttagt atctgtgtat caagtataaa 480agttctataa actgtagtnt acttatttta atccccaaag cacagt 526
<210> 312
<211> 500
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(500)
<223> n = A,T,C or G
<400> 312cctctctctc cccaccccct gactctagag aactgggttt tctcccagta ctccagcaat 60tcatttctga aagcagttga gccactttat tccaaagtac actgcagatg ttcaaactct 120ccatttctct ttcccttcca cctgccagtt ttgctgactc tcaacttgtc atgagtgtaa 180gcattaagga cattatgctt cttcgattct gaagacaggc cctgctcatg gatgactctg 240gcttcttagg aaaatatttt tcttccaaaa tcagtaggaa atctaaactt atcccctctt 300tgcagatgtc tagcagcttc agacatttgg ttaagaaccc atgggaaaaa aaaaaatcct 360tgctaatgtg gtttcctttg taaaccanga ttcttatttg nctggtatag aatatcagct 420ctgaacgtgt ggtaaagatt tttgtgtttg aatataggag aaatcagttt gctgaaaagt 480tagtcttaat tatctattgg 500
<210> 313
<211> 718
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)..,(718)
<223> n = A,T,C or G
<400> 313ggagatttgt gtggtttgca gccgagggag accaggaaga tctgcatggt gggaaggacc 60tgatgataca gaggtgagaa ataagaaagg ctgctgactt taccatctga ggccacacat 120ctgctgaaat ggagataatt aacatcacta gaaacagcaa gatgacaata taatgtctaa 180gtagtgacat gtttttgcac atttccagcc cttttaaata tccacacaca caggaagcac 240aaaaggaagc acagagatcc ctgggagaaa tgcccggccg ccatcttggg tcatcgatga 300gcctcgccct gtgcctgntc ccgcttgtga gggaaggaca ttagaaaatg aattgatgtg 360ttccttaaag gatggcagga aaacagatcc tgttgtggat atttatttga acgggattac 420agatttgaaa tgaagtcaca aagtgagcat taccaatgag aggaaaacag acgagaaaat 480cttgatggtt cacaagacat gcaacaaaca aaatggaata ctgtgatgac acgagcagcc 540aactggggag gagataccac ggggcagagg tcaggattct ggccctgctg cctaactgtg 600cgttatacca atcatttcta tttctaccct caaacaagct gtngaatatc tgacttacgg 660ttcttntggc ccacattttc atnatccacc ccntcntttt aannttantc caaantgt 718
<210> 314
<211> 358
<212> DNA
<213> Homo sapien
<400> 314gtttatttac attacagaaa aaacatcaag acaatgtata ctatttcaaa tatatccata 60cataatcaaa tatagctgta gtacatgttt tcattggtgt agattaccac aaatgcaagg 120caacatgtgt agatctcttg tcttattctt ttgtctataa tactgtattg tgtagtccaa 180gctctcggta gtccagccac tgtgaaacat gctcccttta gattaacctc gtggacgctc 240ttgttgtatt gctgaactgt agtgccctgt attttgcttc tgtctgtgaa ttctgttgct 300tctggggcat ttccttgtga tgcagaggac caccacacag atgacagcaa tctgaatt 358
<210> 315
<211> 341
<212> DNA
<213> Homo sapien
<400> 315taccacctcc ccgctggcac tgatgagccg catcaccatg gtcaccagca ccatgaaggc 60ataggtgatg atgaggacat ggaatgggcc cccaaggatg gtctgtccaa agaagcgagt 120gacccccatt ctgaagatgt ctggaacctc taccagcagg atgatgatag ccccaatgac 180agtcaccagc tccccgacca gccggatatc gtccttaggg gtcatgtagg cttcctgaag 240tagcttctgc tgtaagaggg tgttgtcccg ggggctcgtg cggttattgg tcctgggctt 300gagggggcgg tagatgcagc acatggtgaa gcagatgatg t 341
<210> 316
<211> 151
<212> DNA
<213> Homo sapien
<400> 316agactgggca agactcttac gccccacact gcaatttggt cttgttgccg tatccattta 60tgtgggcctt tctcgagttt ctgattataa acaccactgg agcgatgtgt tgactggact 120cattcaggga gctctggttg caatattagt t 151
<210> 317
<211> 151
<212> DNA
<213> Homo sapien
<400> 317agaactagtg gatcctaatg aaatacctga aacatatatt ggcatttatc aatggctcaa 60atcttcattt atctctggcc ttaaccctgg ctcctgaggc tgcggccagc agatcccagg 120ccagggctct gttcttgcca cacctgcttg a 151
<210> 318
<211> 151
<212> DNA
<213> Homo sapien
<400> 318actggtggga ggcgctgttt agttggctgt tttcagaggg gtctttcgga gggacctcct 60gctgcaggct ggagtgtctt tattcctggc gggagaccgc acattccact gctgaggctg 120tgggggcggt ttatcaggca gtgataaaca t 151
<210> 319
<211> 151
<212> DNA
<213> Homo sapien
<400> 319aactagtgga tccagagcta taggtacagt gtgatctcag ctttgcaaac acattttcta 60catagatagt actaggtatt aatagatatg taaagaaaga aatcacacca ttaataatgg 120taagattggg tttatgtgat tttagtgggt a 151
<210> 320
<211> 150
<212> DNA
<213> Homo sapien
<400> 320aactagtgga tccactagtc cagtgtggtg gaattccatt gtgttggggt tctagatcgc 60gagcggctgc cctttttttt tttttttttg ggggggaatt tttttttttt aatagttatt 120gagtgttcta cagcttacag taaataccat 150
<210> 321
<211> 151
<212> DNA
<213> Homo sapien
<400> 321agcaactttg tttttcatcc aggttatttt aggcttagga tttcctctca cactgcagtt 60tagggtggca ttgtaaccag ctatggcata ggtgttaacc aaaggctgag taaacatggg 120tgcctctgag aaatcaaagt cttcatacac t 151
<210> 322
<211> 151
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(151)
<223> n = A,T,C or G
<400> 322atccagcatc ttcctgtt tcttgccttc ctttttcttc ttcttasatt ctgcttgagg 60tttgggcttg gtcagtttgc cacagggctt ggagatggtg acagtcttct ggcattcggc 120attgtgcagg gctcgcttca nacttccagt t 151
<210> 323
<211> 151
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(151)
<223> n = A,T,C or G
<400> 323tgaggacttg tkttcttttt ctttattttt aatcctctta ckttgtaaat atattgccta 60nagactcant tactacccag tttgtggttt twtgggagaa atgtaactgg acagttagct 120gttcaatyaa aaagacactt ancccatgtg g 151
<210> 324
<211> 461
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(461)
<223> n = A,T,C or G
<400> 324acctgtgtgg aatttcagct ttcctcatgc aaaaggattt tgtatccccg gcctacttga 60agaagtggtc agctaaagga atccaggttg ttggttggac tgttaatacc tttgatgaaa 120agagttacta cgaatcccat cttggttcca gctatatcac tgacagcatg gtagaagact 180gcgaacctca cttctagact ttcacggtgg gacgaaacgg gttcagaaac tgccaggggc 240ctcatacagg gatatcaaaa taccctttgt gctacccagg ccctggggaa tcaggtgact 300cacacaaatg caatagttgg tcactgcatt tttacctgaa ccaaagctaa acccggtgtt 360gccaccatgc accatggcat gccagagttc aacactgttg ctcttgaaaa ttgggtctga 420aaaaacgcac aagagcccct gccctgccct agctgangca c 461
<210> 325
<211> 400
<212> DNA
<213> Homo sapien
<400> 325acactgtttc catgttatgt ttctacacat tgctacctca gtgctcctgg aaacttagct 60tttgatgtct ccaagtagtc caccttcatt taactctttg aaactgtatc atctttgcca 120agtaagagtg gtggcctatt tcagctgctt tgacaaaatg actggctcct gacttaacgt 180tctataaatg aatgtgctga agcaaagtgc ccatggtggc ggcgaagaag agaaagatgt 240gttttgtttt ggactctctg tggtcccttc caatgctgtg ggtttccaac caggggaagg 300gtcccttttg cattgccaag tgccataacc atgagcacta cgctaccatg gttctgcctc 360ctggccaagc aggctggttt gcaagaatga aatgaatgat 400
<210> 326
<211> 1215
<212> DNA
<213> Homo sapien
<400> 326ggaggactgc agcccgcact cgcagccctg gcaggcggca ctggtcatgg aaaacgaatt 60gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg tcagccgcac actgtttcca 120gaactcctac accatcgggc tgggcctgca cagtcttgag gccgaccaag agccagggag 180ccagatggtg gaggccagcc tctccgtacg gcacccagag tacaacagac ccttgctcgc 240taacgacctc atgctcatca agttggacga atccgtgtcc gagtctgaca ccatccggag 300catcagcatt gcttcgcagt gccctaccgc ggggaactct tgcctcgttt ctggctgggg 360tctgctggcg aacggcagaa tgcctaccgt gctgcagtgc gtgaacgtgt cggtggtgtc 420tgaggaggtc tgcagtaagc tctatgaccc gctgtaccac cccagcatgt tctgcgccgg 480cggagggcaa gaccagaagg actcctgcaa cggtgactct ggggggcccc tgatctgcaa 540cgggtacttg cagggccttg tgtctttcgg aaaagccccg tgtggccaag ttggcgtgcc 600aggtgtctac accaacctct gcaaattcac tgagtggata gagaaaaccg tccaggccag 660ttaactctgg ggactgggaa cccatgaaat tgacccccaa atacatcctg cggaaggaat 720tcaggaatat ctgttcccag cccctcctcc ctcaggccca ggagtccagg cccccagccc 780ctcctccctc aaaccaaggg tacagatccc cagcccctcc tccctcagac ccaggagtcc 840agacccccca gcccctcctc cctcagaccc aggagtccag cccctcctcc ctcagaccca 900ggagtccaga ccccccagcc cctcctccct cagacccagg ggtccaggcc cccaacccct 960cctccctcag actcagaggt ccaagccccc aacccctcct tccccagacc cagaggtcca 1020ggtcccagcc cctcctccct cagacccagc ggtccaatgc cacctagact ctccctgtac 1080acagtgcccc cttgtggcac gttgacccaa ccttaccagt tggtttttca ttttttgtcc 1140ctttccccta gatccagaaa taaagtctaa gagaagcgca aaaaaaaaaa aaaaaaaaaa 1200aaaaaaaaaa aaaaa 1215
<210> 327
<211> 220
<212> PRT
<213> Homo sapien
<400> 327Glu Asp Cys Ser Pro His Ser Gln Pro Trp Gln Ala Ala Leu Val Met1 5 10 15Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp Val
20 25 30Leu Ser Ala Ala His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu Gly
35 40 45Leu His Ser Leu Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val Glu
50 55 60Ala Ser Leu Ser Val Arg His Pro Glu Tyr Ash Arg Pro Leu Leu Ala65 70 75 80Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Ser Glu Ser Asp
85 90 95Thr Ile Arg Ser Ile Ser Ile Ala Ser Gln Cys Pro Thr Ala Gly Asn
100 105 110Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly Arg Met Pro
115 120 125Thr Val Leu Gln Cys Val Asn Val Ser Val Val Ser Glu Glu Val Cys
130 135 140Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe Cys Ala Gly145 150 155 160Gly Gly Gln Asp Gln Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly Pro
165 170 175Leu Ile Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe Gly Lys Ala
180 185 190Pro Cys Gly Gln Val Gly Val Pro Gly Val Tyr Thr Asn Leu Cys Lys
195 200 205Phe Thr Glu Trp Ile Glu Lys Thr Val Gln Ala Ser
210 215 220
<210> 328
<211> 234
<212> DNA
<213> Homo sapien
<400> 328cgctcgtctc tggtagctgc agccaaatca taaacggcga ggactgcagc ccgcactcgc 60agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc gtcctggtgc 120atccgcagtg ggtgctgtca gccacacact gtttccagaa ctcctacacc atcgggctgg 180gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag gcca 234
<210> 329
<211> 77
<212> PRT
<213> Homo sapien
<400> 329Leu Val Ser Gly Ser Cys Ser Gln Ile Ile Asn Gly Glu Asp Cys Ser1 5 10 15Pro His Ser Gln Pro Trp Gln Ala Ala Leu Val Met Glu Asn Glu Leu
20 25 30Phe Cys Ser Gly Val Leu Val His Pro Gln Trp Val Leu Ser Ala Thr
35 40 45His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu Gly Leu His Ser Leu
50 55 60Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val Glu Ala65 70 75
<210> 330
<211> 70
<212> DNA
<213> Homo sapien
<400> 330cccaacacaa tggcccgatc ccatccctga ctccgccctc aggatcgctc gtctctggta 60gctgcagcca 70
<210> 331
<211> 22
<212> PRT
<213> Homo sapien
<400> 331Gln His Asn Gly Pro Ile Pro Ser Leu Thr Pro Pro Ser Gly Ser Leu1 5 10 15Val Ser Gly Ser Cys Ser
20
<210> 332
<211> 2507
<212> DNA
<213> Homo sapien
<400> 332tggtgccgct gcagccggca gagatggttg agctcatgtt cccgctgttg ctcctccttc 60tgcccttcct tctgtatatg gctgcgcccc aaatcaggaa aatgctgtcc agtggggtgt 120gtacatcaac tgttcagctt cctgggaaag tagttgtggt cacaggagct aatacaggta 180tcgggaagga gacagccaaa gagctggctc agagaggagc tcgagtatat ttagcttgcc 240gggatgtgga aaagggggaa ttggtggcca aagagatcca gaccacgaca gggaaccagc 300aggtgttggt gcggaaactg gacctgtctg atactaagtc tattcgagct tttgctaagg 360gcttcttagc tgaggaaaag cacctccacg ttttgatcaa caatgcagga gtgatgatgt 420gtccgtactc gaagacagca gatggctttg agatgcacat aggagtcaac cacttgggtc 480acttcctcct aacccatctg ctgctagaga aactaaatga atcagcccca tcaaggatag 540taaatgtgtc ttccctcgca catcaccttg gaatgatcca cttccataac ctgcatggct 600agaaattcta caatgcaggc ctggcctact gtcacagcaa gctagccaac atcctcttca 660cccaggaact ggcccggaga ctaaaaggct ctggcgttac gacgtattct gtacaccctg 720gcacagtcca atctgaactg gttcggcact catctttcat gagatggatg tggtggcttt 780tctccttttt catcaagact cctcagcagg gagcccagac cagcctgcac tgtgccttaa 840cagaaggtct tgagattcta agtgggaatc atttcagtga ctgtcatgtg gcatgggtct 900ctgcccaagc tcgtaatgag actatagcaa ggcggctgtg ggacgtcagt tgtgacctgc 960tgggcctccc aatagactaa caggcagtgc cagttggacc caagagaaga ctgcagcaga 1020ctacacagta cttcttgtca aaatgattct ccttcaaggt tttcaaaacc tttagcacaa 1080agagagcaaa accttccagc cttgcctgct tggtgtccag ttaaaactca gtgtactgcc 1140agattcgtct aaatgtctgt catgtccaga tttactttgc ttctgttact gccagagtta 1200ctagagatat cataatagga taagaagacc ctcatatgac ctgcacagct cattttcctt 1260ctgaaagaaa ctactaccta ggagaatcta agctatagca gggatgattt atgcaaattt 1320gaactagctt ctttgttcac aattcagttc ctcccaacca accagtcttc acttcaagag 1380ggccacactg caacctcagc ttaacatgaa taacaaagac tggctcagga gcagggcttg 1440cccaggcatg gtggatcacc ggaggtcagt agttcaagac cagcctggcc aacatggtga 1500aaccccacct ctactaaaaa ttgtgtatat ctttgtgtgt cttcctgttt atgtgtgcca 1560agggagtatt ttcacaaagt tcaaaacagc cacaataatc agagatggag caaaccagtg 1620ccatccagtc tttatgcaaa tgaaatgctg caaagggaag cagattctgt atatgttggt 1680aactacccac caagagcaca tgggtagcag ggaagaagta aaaaaagaga aggagaatac 1740tggaagataa tgcacaaaat gaagggacta gttaaggatt aactagccct ttaaggatta 1800actagttaag gattaatagc aaaagayatt aaatatgcta acatagctat ggaggaattg 1860agggcaagca cccaggactg atgaggtctt aacaaaaacc agtgtggcaa aaaaaaaaaa 1920aaaaaaaaaa aaaaatccta aaaacaaaca aacaaaaaaa acaattcttc attcagaaaa 1980attatcttag ggactgatat tggtaattat ggtcaattta ataatatttt ggggcatttc 2040cttacattgt cttgacaaga ttaaaatgtc tghgccaaaa ttttgtattt tatttggaga 2100cttcttatca aaagtaatgc tgccaaagga agtctaagga attagtagtg ttcccatcac 2160ttgtttggag tgtgctattc taaaagattt tgatttcctg gaatgacaat tatattttaa 2220ctttggtggg ggaaagagtt ataggaccac agtcttcact tctgatactt gtaaattaat 2280cttttattgc acttgttttg accattaagc tatatgttta gaaatggtca ttttacggaa 2340aaattagaaa aattctgata atagtgcaga ataaatgaat taatgtttta cttaatttat 2400attgaactgt caatgacaaa taaaaattct ttttgattat tttttgtttt catttaccag 2460aataaaaacg taagaattaa aagtttgatt acaaaaaaaa aaaaaaa 2507
<210> 333
<211> 3030
<212> DNA
<213> Homo sapien
<400> 333gcaggcgact tgcgagctgg gagcgattta aaacgctttg gattcccccg gcctgggtgg 60ggagagcgag ctgggtgccc cctagattcc ccgcccccgc acctcatgag ccgaccctcg 120gctccatgga gcccggcaat tatgccacct tggatggagc caaggatatc gaaggcttgc 180tgggagcggg aggggggcgg aatctggtcg cccactcccc tctgaccagc cacccagcgg 240cgcctacgct gatgcctgct gtcaactatg cccccttgga tctgccaggc tcggcggagc 300cgccaaagca atgccaccca tgccctgggg tgccccaggg gacgtcccca gctcccgtgc 360cttatggtta ctttggaggc gggtactact cctgccgagt gtcccggagc tcgctgaaac 420cctgtgccca ggcagccacc ctggccgcgt accccgcgga gactcccacg gccggggaag 480agtaccccag ycgccccact gagtttgcct tctatccggg atatccggga acctaccagc 540ctatggccag ttacctggac gtgtctgtgg tgcagactct gggtgctcct ggagaaccgc 600gacatgactc cctgttgcct gtggacagtt accagtcttg ggctctcgct ggtggctgga 660acagccagat gtgttgccag ggagaacaga acccaccagg tcccttttgg aaggcagcat 720ttgcagactc cagcgggcag caccctcctg acgcctgcgc ctttcgtcgc ggccgcaaga 780aacgcattcc gtacagcaag gggcagttgc gggagctgga gcgggagtat gcggctaaca 840agttcatcac caaggacaag aggcgcaaga tctcggcagc caccagcctc tcggagcgcc 900agattaccat ctggtttcag aaccgccggg tcaaagagaa gaaggttctc gccaaggtga 960agaacagcgc taccccttaa gagatctcct tgcctgggtg ggaggagcga aagtgggggt 1020gtcctgggga gaccaggaac ctgccaagcc caggctgggg ccaaggactc tgctgagagg 1080cccctagaga caacaccctt cccaggccac tggctgctgg actgttcctc aggagcggcc 1140tgggtaccca gtatgtgcag ggagacggaa ccccatgtga cagcccactc caccagggtt 1200ccaaagaac ctggcccagt cataatcatt catcctgaca gtggcaataa tcacgataac 1260cagtactagc tgccatgatc gttagcctca tattttctat ctagagctct gtagagcact 1320ttagaaaccg ctttcatgaa ttgagctaat tatgaataaa tttggaaggc gatccctttg 1380cagggaagct ttctctcaga cccccttcca ttacacctct caccctggta acagcaggaa 1440gactgaggag aggggaacgg gcagattcgt tgtgtggctg tgatgtccgt ttagcatttt 1500tctcagctga cagctgggta ggtggacaat tgtagaggct gtctcttcct ccctccttgt 1560ccaccccata gggtgtaccc actggtcttg gaagcaccca tccttaatac gatgattttt 1620ctgtcgtgtg aaaatgaagc cagcaggctg cccctagtca gtccttcctt ccagagaaaa 1680agagatttga gaaagtgcct gggtaattca ccattaattt cctcccccaa actctctgag 1740tcttccctta atatttctgg tggttctgac caaagcaggt catggtttgt tgagcatttg 1800ggatcccagt gaagtagatg tttgtagcct tgcatactta gcccttccca ggcacaaacg 1820gagtggcaga gtggtgccaa ccctgttttc ccagtccacg tagacagatt cacagtgcgg 1920aattctggaa gctggagaca gacgggctct ttgcagagcc gggactctga gagggacatg 1980agggcctctg cctctgtgtt cattctctga tgtcctgtac ctgggctcag tgcccggtgg 2040gactcatctc ctggccgcgc agcaaagcca gcgggttcgt gctggtcctt cctgcacctt 2100aggctggggg tggggggcct gccggcgcat tctccacgat tgagcgcaca ggcctgaagt 2160ctggacaacc cgcagaaccg aagctccgag cagcgggtcg gtggcgagta gtggggtcgg 2220tggcgagcag ttggtggtgg gccgcggccg ccactacctc gaggacattt ccctcccgga 2280gccagctctc ctagaaaccc cgcggcggcc gccgcagcca agtgtttatg gcccgcggtc 2340gggtgggatc ctagccctgt ctcctctcct gggaaggagt gagggtggga cgtgacttag 2400acacctacaa atctatttac caaagaggag cccgggactg agggaaaagg ccaaagagtg 2460tgagtgcatg cggactgggg gttcagggga agaggacgag gaggaggaag atgaggtcga 2520tttcctgatt taaaaaatcg tccaagcccc gtggtccagc ttaaggtcct cggttacatg 2580cgccgctcag agcaggtcac tttctgcctt ccacgtcctc cttcaaggaa gccccatgtg 2640ggtagctttc aatatcgcag gttcttactc ctctgcctct ataagctcaa acccaccaac 2700gatcgggcaa gtaaaccccc tccctcgccg acttcggaac tggcgagagt tcagcgcaga 2760tgggcctgtg gggagggggc aagatagatg agggggagcg gcatggtgcg gggtgacccc 2820ttggagagag gaaaaaggcc acaagagggg ctgccaccgc cactaacgga gatggccctg 2880gtagagacct ttgggggtct ggaacctctg gactccccat gctctaactc ccacactctg 2940ctatcagaaa cttaaacttg aggattttct ctgtttttca ctcgcaataa aytcagagca 3000aacaaaaaaa aaaaaaaaaa aaaactcgag 3030
<210> 334
<211> 2417
<212> DNA
<213> Homo sapien
<400> 334ggcggccgct ctagagctag tgggatcccc cgggctgcac gaattcggca cgagtgagtt 60ggagttttac ctgtattgtt ttaatttcaa caagcctgag gactagccac aaatgtaccc 120agtttacaaa tgaggaaaca ggtgcaaaaa ggttgttacc tgtcaaaggt cgtatgtggc 180agagccaaga tttgagccca gttatgtctg atgaacttag cctatgctct ttaaacttct 240gaatgctgac cattgaggat atctaaactt agatcaattg cattttccct ccaagactat 300ttacttatca atacaataat accaccttta ccaatctatt gttttgatac gagactcaaa 360tatgccagat atatgtaaaa gcaacctaca agctctctaa tcatgctcac ctaaaagatt 420cccgggatct aataggctca aagaaacttc ttctagaaat ataaaagaga aaattggatt 480atgcaaaaat tcattattaa tttttttcat ccatccttta attcagcaaa catttatctg 540ttgttgactt tatgcagtat ggccttttaa ggattggggg acaggtgaag aacggggtgc 600cagaatgcat cctcctacta atgaggtcag tacacatttg cattttaaaa tgccctgtcc 660agctgggcat ggtggatcat gcctgtaatc tcaacattgg aaggccaagg caggaggatt 720gcttcagccc aggagttcaa gaccagcctg ggcaacatag aaagacccca tctctcaatc 780aatcaatcaa tgccctgtct ttgaaaataa aactctttaa gaaaggttta atgggcaggg 840tgtggtagct catgcctata atacagcact ttgggaggct gaggcaggag gatcacttta 900gcccagaagt tcaagaccag cctgggcaac aagtgacacc tcatctcaat tttttaataa 960aatgaataca tacataagga aagataaaaa gaaaagttta atgaaagaat acagtataaa 1020acaaatctct tggacctaaa agtatttttg ttcaagccaa atattgtgaa tcacctctct 1080gtgttgagga tacagaatat ctaagcccag gaaactgagc agaaagttca tgtactaact 1140aatcaacccg aggcaaggca aaaatgagac taactaatca atccgaggca aggggcaaat 1200tagacggaac ctgactctgg tctattaagc gacaactttc cctctgttgt atttttcttt 1260tattcaatgt aaaaggataa aaactctcta aaactaaaaa caatgtttgt caggagttac 1320aaaccatgac caactaatta tggggaatca taaaatatga ctgtatgaga tcttgatggt 1380ttacaaagtg tacccactgt taatcacttt aaacattaat gaacttaaaa atgaatttac 1440ggagattgga atgtttcttt cctgttgtat tagttggctc aggctgccat aacaaaatac 1500cacagactgg gaggcttaag taacagaaat tcatttctca cagttctggg ggctggaagt 1560ccacgatcaa ggtgcaggaa aggcaggctt cattctgagg cccctctctt ggctcacatg 1620tggccaccct cccactgcgt gctcacatga cctctttgtg ctcctggaaa gagggtgtgg 1680gggacagagg gaaagagaag gagagggaac tctctggtgt ctcgtctttc aaggacccta 1740acctgggcca ctttggccca ggcactgtgg ggtggggggt tgtggctgct ctgctctgag 1800tggccaagat aaagcaacag aaaaatgtcc aaagctgtgc agcaaagaca agccaccgaa 1860cagggatctg ctcatcagtg tggggacctc caagtcggcc accctggagg caagccccca 1920cagagcccat gcaaggtggc agcagcagaa gaagggaatt gtccctgtcc ttggcacatt 1980cctcaccgac ctggtgatgc tggacactgc gatgaatggt aatgtggatg agaatatgat 2040ggactcccag aaaaggagac ccagctgctc aggtggctgc aaatcattac agccttcatc 2100ctggggagga actgggggcc tggttctggg tcagagagca gcccagtgag ggtgagagct 2160acagcctgtc ctgccagctg gatccccagt cccggtcaac cagtaatcaa ggctgagcag 2220atcaggcttc ccggagctgg tcttgggaag ccagccctgg ggtgagttgg ctcctgctgt 2280ggtactgaga caatattgtc ataaattcaa tgcgcccttg tatccctttt tcttttttat 2340ctgtctacat ctataatcac tatgcatact agtctttgtt agtgtttcta ttcmacttaa 2400tagagatatg ttatact 2417
<210> 335
<211> 2984
<212> DNA
<213> Homo sapien
<400> 335atccctcctt ccccactctc ctttccagaa ggcacttggg gtcttatctg ttggactctg 60aaaacacttc aggcgccctt ccaaggcttc cccaaacccc taagcagccg cagaagcgct 120cccgagctgc cttctcccac actcaggtga tcgagttgga gaggaagttc agccatcaga 180agtacctgtc ggcccctgaa cgggcccacc tggccaagaa cctcaagctc acggagaccc 240aagtgaagat atggttccag aacagacgct ataagactaa gcgaaagcag ctctcctcgg 300agctgggaga cttggagaag cactcctctt tgccggccct gaaagaggag gccttctccc 360ggcctccct ggtctccgtg tataacagct atccttacta cccatacctg tactgcgtgg 420gcagctggag cccagctttt tggtaatgcc agctcaggtg acaaccatta tgatcaaaaa 480ctgccttccc cagggtgtct ctatgaaaag cacaaggggc caaggtcagg gagcaagagg 540tgtgcacacc aaagctattg gagatttgcg tggaaatctc asattcttca ctggtgagac 600aatgaaacaa cagagacagt gaaagtttta atacctaagt cattccccca gtgcatactg 660taggtcattt tttttgcttc tggctacctg tttgaagggg agagagggaa aatcaagtgg 720tattttccag cactttgtat gattttggat gagctgtaca cccaaggatt ctgttctgca 780actccatcct cctgtgtcac tgaatatcaa ctctgaaaga gcaaacctaa caggagaaag 840gacaaccagg atgaggatgt caccaactga attaaactta agtccagaag cctcctgttg 900gccttggaat atggccaagg ctctctctgt ccctgtaaaa gagaggggca aatagagagt 960ctccaagaga acgccctcat gctcagcaca tatttgcatg ggagggggag atgggtggga 1020ggagatgaaa atatcagctt ttcttattcc tttttattcc ttttaaaatg gtatgccaac 1080ttaagtattt acagggtggc ccaaatagaa caagatgcac tcgctgtgat tttaagacaa 1140gctgtataaa cagaactcca ctgcaagagg gggggccggg ccaggagaat ctccgcttgt 1200ccaagacagg ggcctaagga gggtctccac actgctgcta ggggctgttg cattttttta 1260ttagtagaaa gtggaaaggc ctcttctcaa cttttttccc ttgggctgga gaatttagaa 1320tcagaagttt cctggagttt tcaggctatc atatatactg tatcctgaaa ggcaacataa 1380ttcttccttc cctcctttta aaattttgtg ttcctttttg cagcaattac tcactaaagg 1440gcttcatttt agtccagatt tttagtctgg ctgcacctaa cttatgcctc gcttatttag 1500cccgagatct ggtctttttt tttttttttt tttttccgtc tccccaaagc tttatctgtc 1560ttgacttttt aaaaaagttt gggggcagat tctgaattgg ctaaaagaca tgcattttta 1620aaactagcaa ctcttatttc tttcctttaa aaatacatag cattaaatcc caaatcctat 1680ttaaagacct gacagcttga gaaggtcact actgcattta taggaccttc tggtggttct 1740gctgttacgt ttgaagtctg acaatccttg agaatctttg catgcagagg aggtaagagg 1800tattggattt tcacagagga agaacacagc gcagaatgaa gggccaggct tactgagctg 1860tccagtggag ggctcatggg tgggacatgg aaaagaaggc agcctaggcc ctggggagcc 1920cagtccactg agcaagcaag ggactgagtg agccttttgc aggaaaaggc taagaaaaag 1980gaaaaccatt ctaaaacaca acaagaaact gtccaaatgc tttgggaact gtgtttattg 2040cctataatgg gtccccaaaa thggtaacct agacttcaga gagaatgagc agagagcaaa 2100ggagaaatct ggctgtcctt ccattttcat tctgttatct caggtgagct ggtagagggg 2160agacattaga aaaaaatgaa acaacaaaac aattactaat gaggtacgct gaggcctggg 2220agtctcttga ctccactact taattccgtt tagtgagaaa cctttcaatt ttcttttatt 2280agaagggcca gcttactgtt ggtggcaaaattgccaacataagttaatag aaagttggcc 2340aatttcaccc cattttctgt ggtttgggct ccacattgca atgttcaatg ccacgtgctg 2400ctgacaccga ccggagtact agccagcaca aaaggcaggg tagcctgaat tgctttctgc 2460tctttacatt tcttttaaaa taagcattta gtgctcagtc cctactgagt actctttctc 2520tcccctcctc tgaatttaat tctttcaact tgcaatttgc aaggattaca catttcactg 2580tgatgtatat tgtgttgcaa aaaaaaaaaa aagtgtcttt gtttaaaatt acttggtttg 2640tgaatccatc ttgctttttc cccattggaa ctagtcatta acccatctct gaactggtag 2700aaaaacatct gaagagctag tctatcagca tctgacaggt gaattggatg gttctcagaa 2760ccatttcacc cagacagcct gtttctatcc tgtttaataa attagtttgg gttctctaca 2820tgcataacaa accctgctcc aatctgtcac ataaaagtct gtgacttgaa gtttagtcag 2880cacccccacc aaactttatt tttctatgtg ttttttgcaa catatgagtg ttttgaaaat 2940aaagtaccca tgtctttatt agaaaaaaaa aaaaaaaaaa aaaa 2984
<210> 336
<211> 147
<212> PRT
<213> Homo sapien
<400> 336Pro Ser Phe Pro Thr Leu Leu Ser Arg Arg His Leu Gly Ser Tyr Leu1 5 10 15Leu Asp Ser Glu Asn Thr Ser Gly Ala Leu Pro Arg Leu Pro Gln Thr
20 25 30Pro Lys Gln Pro Gln Lys Arg Ser Arg Ala Ala Phe Ser His Thr Gln
35 40 45val Ile Glu Leu Glu Arg Lys Phe Ser His Gln Lys Tyr Leu Ser Ala
50 55 60Pro Glu Arg Ala His Leu Ala Lys Asn Leu Lys Leu Thr Glu Thr Gln65 70 75 80 Val Lys Ile Trp Phe Gln Asn Arg Arg Tyr Lys Thr Lys Arg Lys Gln
85 90 95Leu Ser Ser Glu Leu Gly Asp Leu Glu Lys His Ser Ser Leu Pro Ala
100 105 110Leu Lys Glu Glu Ala Phe Ser Arg Ala Ser Leu Val Ser Val Tyr Asn
115 120 125Ser Tyr Pro Tyr Tyr Pro Tyr Leu Tyr Cys Val Gly Ser Trp Ser Pro
130 135 140Ala Phe Trp145
<210> 337
<211> 9
<212> PRT
<213> Homo sapien
<400> 337Ala Leu Thr Gly Phe Thr Phe Ser Ala1 5
<210> 338
<211> 9
<212> PRT
<213> Homo sapien
<400> 338Leu Leu Ala Asn Asp Leu Met Leu Ile1 5
<210> 339
<211> 318
<212> PRT
<213> Homo sapien
<400> 339Met Val Glu Leu Met Phe Pro Leu Leu Leu Leu Leu Leu Pro Phe Leu1 5 10 15Leu Tyr Met Ala Ala Pro Gln Ile Arg Lys Met Leu Ser Ser Gly Val
20 25 30Cys Thr Ser Thr Val Gln Leu Pro Gly Lys Val Val Val Val Thr Gly
35 40 45Ala Asn Thr Gly Ile Gly Lys Glu Thr Ala Lys Glu Leu Ala Gln Arg
50 55 60Gly Ala Arg Val Tyr Leu Ala Cys Arg Asp Val Glu Lys Gly Glu Leu65 70 75 80Val Ala Lys Glu Ile Gln Thr Thr Thr Gly Asn Gln Gln Val Leu Val
85 90 95Arg Lys Leu Asp Leu Ser Asp Thr Lys Ser Ile Arg Ala Phe Ala Lys
100 105 110Gly Phe Leu Ala Glu Glu Lys His Leu His Val Leu Ile Asn Asn Ala
115 120 125Gly Val Met Met Cys Pro Tyr Ser Lys Thr Ala Asp Gly Phe Glu Met
130 135 140His Ile Gly Val Asn His Leu Gly His Phe Leu Leu Thr His Leu Leu145 150 155 160Leu Glu Lys Leu Lys Glu Ser Ala Pro Ser Arg Ile Val Asn Val Ser
165 170 175Ser Leu Ala His His Leu Gly Arg Ile His Phe His Asn Leu Gln Gly
180 185 190Glu Lys Phe Tyr Asn Ala Gly Leu Ala Tyr Cys His Ser Lys Leu Ala
195 200 205Asn Ile Leu Phe Thr Gln Glu Leu Ala Arg Arg Leu Lys Gly Ser Gly
210 215 220Val Thr Thr Tyr Ser Val His Pro Gly Thr Val Gln Ser Glu Leu Val225 230 235 240Arg His Ser Ser Phe Met Arg Trp Met Trp Trp Leu Phe Ser Phe Phe
245 250 255Ile Lys Thr Pro Gln Gln Gly Ala Gln Thr Ser Leu His Cys Ala Leu
260 265 270Thr Glu Gly Leu Glu Ile Leu Ser Gly Asn His Phe Ser Asp Cys His
275 280 285Val Ala Trp Val Ser Ala Gln Ala Arg Asn Glu Thr Ile Ala Arg Arg
290 295 300Leu Trp Asp Val Ser Cys Asp Leu Leu Gly Leu Pro Ile Asp305 310 315
<210> 340
<211> 483
<212> DNA
<213> Homo sapien
<400> 340gccgaggtct gccttcacac ggaggacacg agactgcttc ctcaagggct cctgcctgcc 60tggacactgg tgggaggcgc tgtttagttg gctgttttca gaggggtctt tcggagggac 120ctcctgctgc aggctggagt gtctttattc ctggcgggag accgcacatt ccactgctga 180ggttgtgggg gcggtttatc aggcagtgat aaacataaga tgtcatttcc ttgactccgg 240ccttcaattt tctctttggc tgacgacgga gtccgtggtg tcccgatgta actgacccct 300gctccaaacg tgacatcact gatgctcttc tcgggggtgc tgatggcccg cttggtcacg 360tgctcaatct cgccattcga ctcttgctcc aaactgtatg aagacacctg actgcacgtt 420ttttctgggc ttccagaatt taaagtgaaa ggcagcactc ctaagctccg actccgatgc 480ctg 483
<210> 341
<211> 344
<212> DNA
<213> Homo sapien
<400> 341ctgctgctga gtcacagatt tcattataaa tagcctccct aaggaaaata cactgaatgc 60tatttttact aaccattcta tttttataga aatagctgag agtttctaaa ccaactctct 120gctgccttac aagtattaaa tattttactt ctttccataa agagtagctc aaaatatgca 180attaatttaa taatttctga tgatggtttt atctgcagta atatgtatat catctattag 240aatttactta atgaaaaact gaagagaaca aaatttgtaa ccactagcac ttaagtactc 300ctgattctta acattgtctt taatgaccac aagacaacca acag 344
<210> 342
<211> 592
<212> DNA
<213> Homo sapien
<400> 342acagcaaaaa agaaactgag aagcccaaty tgctttcttg ttaacatcca cttatccaac 60caatgtggaa acttcttata cttggttcca ttatgaagtt ggacaattgc tgctatcaca 120cctggcaggt aaaccaatgc caagagagtg atggaaacca ttggcaagac tttgttgatg 180accaggattg gaattttata aaaatattgt tgatgggaag ttgctaaagg gtgaattact 240tccctcagaa gagtgtaaag aaaagtcaga gatgctataa tagcagctat tttaattggc 300aagtgccact gtggaaagag ttcctgtgtg tgctgaagtt ctgaagggca gtcaaattca 360tcagcatggg ctgtttggtg caaatgcaaa agcacaggtc tttttagcat gctggtctct 420cccgtggcct tatgcaaata atcgtcttct tctaaatttc tcctaggctt cattttccaa 480agttcttctt ggtttgtgat gtcttttctg ctttccatta attctataaa atagtatggc 540ttcagccacc cactcttcgc cttagcttga ccgtgagtct cggctgccgc tg 592
<210> 343
<211> 382
<212> DNA
<213> Homo sapien
<400> 343ttcttgacct cctcctcctt caagctcaaa caccacctcc cttattcagg accggcactt 60cttaatgttt gtggctttct ctccagcctc tcttaggagg ggtaatggtg gagttggcat 120cttgtaactc tcctttctcc tttcttcccc tttctctgcc cgcctttccc atcctgctgt 180agacttcttg attgtcagtc tgtgtcacat ccagtgattg ttttggtttc tgttcccttt 240ctgactgccc aaggggctca gaaccccagc aatcccttcc tttcactacc ttcttttttg 300ggggtagttg gaagggactg aaattgtggg gggaaggtag gaggcacatc aataaagagg 360aaaccaccaa gctgaaaaaa aa 382
<210> 344
<211> 536
<212> DNA
<213> Homo sapien
<400> 344ctgggcctga agctgtaggg taaatcagag gcaggcttct gagtgatgag agtcctgaga 60caataggcca cataaacttg gctggatgga acctcacaat aaggtggtca cctcttgttt 120gtttaggggg atgccaagga taaggccagc tcagttatat gaagagaagc agaacaaaca 180agtctttcag agaaatggat gcaatcagag tgggatcccg gtcacatcaa ggtcacactc 240caccttcatg tgcctgaatg gttgccaggt cagaaaaatc caccccttac gagtgcggct 300tcgaccctat atcccccgcc cgcgtccctt tctccataaa attcttctta gtagctatta 360ccttcttatt atttgatcta gaaattgccc tccttttacc cctaccatga gccctacaaa 420caactaacct gccactaata gttatgtcat ccctcttatt aatcatcatc ctagccctaa 480gtctggccta tgagtgacta caaaaaggat tagactgagc cgaataacaa aaaaaa 536
<210> 345
<211> 251
<212> DNA
<213> Homo sapien
<400> 345accttttgag gtctctctca ccacctccac agccaccgtc accgtgggat gtgctggatg 60tgaatgaagc ccccatcttt gtgcctcctg aaaagagagt ggaagtgtcc gaggactttg 120gcgtgggcca ggaaatcaca tcctacactg cccaggagcc agacacattt atggaacaga 180aaataacata tcggatttgg agagacactg ccaactggct ggagattaat ccggacactg 240gtgccatttc c 251
<210> 346
<211> 282
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(282)
<223> n = A,T,C or G<400> 346cgcgtctctg acactgtgat catgacaggg gttcaaacag aaagtgcctg ggccctcctt 60ctaagtcttg ttaccaaaaa aaggaaaaag aaaagatctt ctcagttaca aattctggga 120agggagacta tacctggctc ttgccctaag tgagaggtct tccctcccgc accaaaaaat 180agaaaggctt tctatttcac tggcccaggt agggggaagg agagtaactt tgagtctgtg 240ggtctcattt cccaaggtgc cttcaatgct catnaaaacc aa 282
<210> 347
<211> 201
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1) ... (201)
<223> n = A,T,C or G
<400> 347acacacataa tattataaaa tgccatctaa ttggaaggag ctttctatca ttgcaagtca 60taaatataac ttttaaaana ntactancag cttttaccta ngctcctaaa tgcttgtaaa 120tctgagactg actggaccca cccagaccca gggcaaagat acatgttacc atatcatctt 180tataaagaat ttttttttgt c 201
<210> 348
<211> 251
<212> DNA
<213> Homo sapien
<400> 348ctgttaatca caacatttgt gcatcacttg tgccaagtga gaaaatgttc taaaatcaca 60agagagaaca gtgccagaat gaaactgacc ctaagtccca ggtgcccctg ggcaggcaga 120aggagacact cccagcatgg aggagggttt atcttttcat cctaggtcag gtctacaatg 180ggggaaggtt ttattataga actcccaaca gcccacctca ctcctgccac ccacccgatg 240gccctgcctc c 251
<210> 349
<211> 251
<212> DNA
<213> Homo sapien
<400> 349taaaaatcaa gccatttaat tgtatctttg aaggtaaaca atatatggga gctggatcac 60aacccctgag gatgccagag ctatgggtcc agaacatggt gtggtattat caacagagtt 120cagaagggtc tgaactctac gtgttaccag agaacataat gcaattcatg cattccactt 180agcaattttg taaaatacca gaaacagacc ccaagagtct ttcaagatga ggaaaattca 240actcctggtt t 251
<210> 350
<211> 908
<212> DNA
<213> Homo sapien
<400> 350ctggacactt tgcgagggct tttgctggct gctgctgctg cccgtcatgc tactcatcgt 60agcccgcccg gtgaagctcg ctgctttccc tacctcctta agtgactgcc aaacgcccac 120cggctggaat tgctctggtt atgatgacag agaaaatgat ctcttcctct gtgacaccaa 180cacctgtaaa tttgatgggg aatgtttaagaattggagac actgtgactt gcgtctgtca 240gttcaagtgc aacaatgact atgtgcctgt gtgtggctcc aatggggaga gctaccagaa 300tgagtgttac ctgcgacagg ctgcatgcaa acagcagagt gagatacttg tggtgtcaga 360aggatcatgt gccacagtcc atgaaggctc tggagaaact agtcaaaagg agacatccac 420ctgtgatatt tgccagtttg gtgcagaatg tgacgaagat gccgaggatg tctggtgtgt 480gtgtaatatt gactgttctc aaaccaactt caatcccctc tgcgcttctg atgggaaatc 540ttatgataat gcatgccaaa tcaaagaagc atcgtgtcag aaacaggaga aaattgaagt 600catgtctttg ggtcgatgtc aagataacac aactacaact actaagtctg aagatgggca 660ttatgcaaga acagattatg cagagaatgc taacaaatta gaagaaagtg ccagagaaca 720ccacatacct tgtccggaac attacaatgg cttctgcatg catgggaagt gtgagcattc 780tatcaatatg caggagccat cttgcaggtg tgatgctggt tatactggac aacactgtga 840aaaaaaggac tacagtgttc tatacgttgt tcccggtcct gtacgatttc agtatgtctt 900aatcgcag 908
<210> 351
<211> 472
<212> DNA
<213> Homo sapien
<400> 351ccagttattt gcaagtggta agagcctatt taccataaat aatactaaga accaactcaa 60gtcaaacctt aatgccattg ttattgtgaa ttaggattaa gtagtaattt tcaaaattca 120cattaacttg attttaaaat cagwtttgyg agtcatttac cacaagctaa atgtgtacac 180tatgataaaa acaaccattg tattcctgtt tttctaaaca gtcctaattt ctaacactgt 240atatatcctt cgacatcaat gaactttgtt ttcttttact ccagtaataa agtaggcaca 300gatctgtcca caacaaactt gccctctcat gccttgcctc tcaccatgct ctgctccagg 360tcagccccct tttggcctgt ttgttttgtc aaaaacctaa tctgcttctt gcttttcttg 420gtaatatata tttagggaag atgttgcttt gcccacacac gaagcaaagt aa 472
<210> 352
<211> 251
<212> DNA
<213> Homo sapien
<400> 352ctcaaagcta atctctcggg aatcaaacca gaaaagggca aggatcttag gcatggtgga 60tgtggataag gccaggtcaa tggctgcaag catgcagaga aagaggtaca tcggagcgtg 120caggctgcgt tccgtcctta cgatgaagac cacgatgcag tttccaaaca ttgccactac 180atacatggaa aggaggggga agccaaccca gaaatgggct ttctctaatc ctgggatacc 240aataagcaca a 251
<210> 353
<211> 436
<212> DNA
<213> Homo sapien
<400> 353tttttttttt tttttttttt ttttttacaa caatgcagtc atttatttat tgagtatgtg 60cacattatgg tattattact atactgatta tatttatcat gtgacttcta attaraaaat 120gtatccaaaa gcaaaacagc agatatacaa aattaaagag acagaagata gacattaaca 180gataaggcaa cttatacatt gacaatccaa atccaataca tttaaacatt tgggaaatga 240gggggacaaa tggaagccar atcaaatttg tgtaaaacta ttcagtatgt ttcccttgct 300tcatgtctga raaggctctc ccttcaatgg ggatgacaaa ctccaaatgc cacacaaatg 360ttaacagaat actagattca cactggaacg ggggtaaaga agaaattatt ttctataaaa 420gggctcctaa tgtagt 436
<210> 354
<211> 854
<212> DNA
<213> Homo sapien
<400> 354ccttttctag ttcaccagtt ttctgcaagg atgctggtta gggagtgtct gcaggaggag 60caagtctgaa accaaatcta ggaaacatag gaaacgagcc aggcacaggg ctggtgggcc 120atcagggacc accctttggg ttgatatttt gcttaatctg catcttttga gtaagatcat 180ctggcagtag aagctgttct ccaggtacat ttctctagct catgtacaaa aacatcctga 240aggactttgt caggtgcctt gctaaaagcc agatgcgttc ggcacttcct tggtctgagg 300ttaattgcac acctacaggc actgggctca tgctttcaag tattttgtcc tcactttagg 360gtgagtgaaa gatccccatt ataggagcac ttgggagaga tcatataaaa gctgactctt 420gagtacatgc agtaatgggg tagatgtgtg tggtgtgtct tcattcctgc aagggtgctt 480gttagggagt gtttccagga ggaacaagtc tgaaaccaat catgaaataa atggtaggtg 540tgaactggaa aactaattca aaagagagat cgtgatatca gtgtggttga tacaccttgg 600caatatggaa ggctctaatt tgcccatatt tgaaataata attcagcttt ttgtaataca 560aaataacaaa ggattgagaa tcatggtgtc taatgtataa aagacccagg aaacataaat 720atatcaactg cataaatgta aaatgcatgt gacccaagaa ggccccaaag tggcagacaa 780cattgtaccc attttccctt ccaaaatgtg agcggcgggc ctgctgcttt caaggctgtc 840acacgggatg tcag 854
<210> 355
<211> 676
<212> DNA
<213> Homo sapien
<400> 355gaaattaagt atgagctaaa ttccctgtta aaacctctag gggtgacaga tctcttcaac 60caggtcaaag ctgatctttc tggaatgtca ccaaccaagg gcctatattt atcaaaagcc 120atccacaagt catacctgga tgtcagcgaa gagggcacgg aggcagcagc agccactggg 180gacagcatcg ctgtaaaaag cctaccaatg agagctcagt tcaaggcgaa ccaccccttc 240ctgttcttta taaggcacac tcataccaac acgatcctat tctgtggcaa gcttgcctct 300ccctaatcag atggggttga gtaaggctca gagttgcaga tgaggtgcag agacaatcct 360gtgactttcc cacggccaaa aagctgttca cacctcacgc acctctgtgc ctcagtttgc 420tcatctgcaa aataggtcta ggatttcttc caaccatttc atgagttgtg aagctaaggc 480tttgttaatc atggaaaaag gtagacttat gcagaaagcc tttctggctt tcttatctgt 540ggtgtctcat ttgagtgctg tccagtgaca tgatcaagtc aatgagtaaa attttaaggg 600attagatttt cttgacttgt atgtatctgt gagatcttga ataagtgacc tgacatctct 660gcttaaagaa aaccag 676
<210> 356
<211> 574
<212> DNA
<213> Homo sapien
<400> 356tttttttttt tttttcagga aaacattctc ttactttatt tgcatctcag caaaggttct 60catgtggcac ctgactggca tcaaaccaaa gttcgtaggc caacaaagat gggccactca 120caagcttccc atttgtagat ctcagtgcct atgagtatct gacacctgtt cctctcttca 180gtctcttagg gaggcttaaa tctgtctcag gtgtgctaag agtgccagcc caaggkggtc 240aaaagtccac aaaactgcag tctttgctgg gatagtaagc caagcagtgc ctggacagca 300gagttctttt cttgggcaac agataaccag acaggactct aatcgtgctc ttattcaaca 360ttcttctgtc tctgcctaga ctggaataaa aagccaatct ctctcgtggc acagggaagg 420agatacaagc tcgtttacat gtgatagatc taacaaaggc atctaccgaa gtctggtctg 480gatagacggc acagggagct cttaggtcag cgctgctggt tggaggacat tcctgagtcc 540agctttgcag cctttgtgca acagtacttt ccca 574
<210> 357
<211> 393
<212> DNA
<213> Homo sapien
<400> 357tttttttttt tttttttttt tttttttttt tacagaatat aratgcttta tcactgkact 60taatatggkg kcttgttcac tatacttaaa aatgcaccac tcataaatat ttaattcagc 120aagccacaac caaracttga ttttatcaac aaaaacccct aaatataaac ggsaaaaaag 180atagatataa ttattccagt ttttttaaaa cttaaaarat attccattgc cgaattaara 240araarataag tgttatatgg aaagaagggc attcaagcac actaaaraaa cctgaggkaa 300gcataatctg tacaaaatta aactgtcctt tttggcattt taacaaattt gcaacgktct 360tttttttctt tttctgtttt tttttttttt tac 393
<210> 358
<211> 630
<212> DNA
<213> Homo sapien
<400> 358acagggtaaa caggaggatc cttgctctca cggagcttac attctagcag gaggacaata 60ttaatgttta taggaaaatg atgagtttat gacaaaggaa gtagatagtg ttttacaaga 120gcatagagta gggaagctaa tccagcacag ggaggtcaca gagacatccc taaggaagtg 180gagtttaaac tgagagaagc aagtgcttaa actgaaggat gtgttgaaga agaagggaga 240gtagaacaat ttgggcagag ggaaccttat agaccctaag gtgggaaggt tcaaagaact 300gaaagagagc tagaacagct ggagccgttc tccggtgtaa agaggagtca aagagataag 360attaaagatg tgaagattaa gatcttggtg gcattcaggg attggcactt ctacaagaaa 420tcactgaagg gagtaatgtg acattacttt tcacttcagg atggccattc taactccagg 480gggtagactg gactaggtaa gactggaggc aggtagacct cttctaaggc ctgcgatagt 540gaaagacaaa aataagtggg gaaattcagg ggatagtgaa aatcagtagg acttaatgag 600caagccagag gttcctccac aacaaccagt 630
<210> 359
<211> 620
<212> DNA
<213> Homo sapien
<400> 359acagcattcc aaaatataca tctagagact aarrgtaaat gctctatagt gaagaagtaa 60taattaaaaa atgctactaa tatagaaaat ttataatcag aaaaataaat attcagggag 120ctcaccagaa gaataaagth ctctgccagt tattaaagga ttactgctgg tgaattaaat 180atggcattcc ccaagggaaa tagagagatt cttctggatt atgttcaata tttatttcac 240aggattaact gttttaggaa cagatataaa gcttcgccac ggaagagatg gacaaagcac 300aaagacaaca tgatacctta ggaagcaaca ctaccctttc aggcataaaa tttggagaaa 360tgcaacatta tgcttcatga ataatatgta gaaagaaggt ctgatgaaaa tgacatcctt 420aatgtaagat aactttataa gaattctggg tcaaataaaa ttctttgaag aaaacatcca 480aatgtcattg acttatcaaa tactatcttg gcatataacc tatgaaggca aaactaaaca 540aacaaaaagc tcacaccaaa caaaaccatc aacttatttt gtattctata acatacgaga 600ctgtaaagat gtgacagtgt 620
<210> 360
<211> 431
<212> DNA
<213> Homo sapien
<400> 360aaaaaaaaaa agccagaaca acatgtgata gataatatga ttggctgcac acttccagac 60tgatgaatga tgaacgtgat ggactattgt atggagcaca tcttcagcaa gagggggaaa 120tactcatcat ttttggccag cagttgtttg atcaccaaac atcatgccag aatactcagc 180aaaccttctt agctcttgag aagtcaaagt ccgggggaat ttattcctgg caattttaat 240tggactcctt atgtgagagc agcggctacc cagctggggt ggtggagcga acccgtcact 300agtggacatg cagtggcaga gctcctggta accacctaga ggaatacaca ggcacatgtg 360tgatgccaag cgtgacacct gtagcactca aatttgtctt gtttttgtct ttcggtgtgt 420agattcttag t 431
<210> 361
<211> 351
<212> DNA
<213> Homo sapien
<400> 361acactgattt ccgatcaaaa gaatcatcat ctttaccttg acttttcagg gaattactga 60actttcttct cagaagatag ggcacagcca ttgccttggc ctcacttgaa gggtctgcat 120ttgggtcctc tggtctcttg ccaagtttcc cagccactcg agggagaaat atcgggaggt 180ttgacttcct ccggggcttt cccgagggct tcaccgtgag ccctgcggcc ctcagggctg 240caatcctgga ttcaatgtct gaaacctcgc tctctgcctg ctggacttct gaggccgtca 300ctgccactct gtcctccagc tctgacagct cctcatctgt ggtcctgttg t 351
<210> 362
<211> 463
<212> DNA
<213> Homo sapien
<400> 362acttcatcag gccataatgg gtgcctcccg tgagaatcca agcacctttg gactgcgcga 60tgtagatgag ccggctgaag atcttgcgca tgcgcggctt cagggcgaag ttcttggcgc 120ccccggtcac agaaatgacc aggttgggtg ttttcaggtg ccagtgctgg gtcagcagct 180cgtaaaggat ttccgcgtcc gtgtcgcagg acagacgtat atacttccct ttcttcccca 240gtgtctcaaa ctgaatatcc ccaaaggcgt cggtaggaaa ttccttggtg tgtttcttgt 300agttccattt ctcactttgg ttgatctggg tgccttccat gtgctggctc tgggcatagc 360cacacttgca cacattctcc ctgataagca cgatggtgtg gacaggaagg aaggatttca 420ttgagcctgc ttatggaaac tggtattgtt agcttaaata gac 463
<210> 363
<211> 653
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(653)
<223> n = A,T,C or G
<400> 363acccccgagt ncctgnctgg catactgnga acgaccaacg acacacccaa gctcggcctc 60ctcttggnga ttctgggtga catcttcatg aatggcaacc gtgccagwga ggctgtcctc 120tgggaggcac tacgcaagat gggactgcgtcctggggtga gacatcctct ccttggagat 180ctaacgaaac ttctcaccta tgagttgtaa agcagaaata cctgnactac agacgagtgc 240ccaacagcaa ccccccggaa gtatgagttc ctctrgggcc tccgttccta ccatgagasc 300tagcaagatg naagtgttga gantcattgc agaggttcag aaaagagacc cntcgtgact 360ggtctgcaca gttcatggag gctgcagatg aggccttgga tgctctggat gctgctgcag 420ctgaggccga agcccgggct gaagcaagaa cccgcatggg aattggagat gaggctgtgt 480ntgggccctg gagctgggat gacattgagt ttgagctgct gacctgggat gaggaaggag 540attttggaga tccntggtcc agaattccat ttaccttctg ggccagatac caccagaatg 600cccgctccag attccctcag acctttgccg gtcccattat tggtcstggt ggt 653
<210> 364
<211> 401
<212> DNA
<213> Homo sapien
<400> 364actagaggaa agacgttaaa ccactctact accacttgtg gaactctcaa agggtaaatg 60acaaagccaa tgaatgactc taaaaacaat atttacattt aatggtttgt agacaataaa 120aaaacaaggt ggatagatct agaattgtaa cattttaaga aaaccatagc atttgacaga 180tgagaaagct caattataga tgcaaagtta taactaaact actatagtag taaagaaata 240catttcacac ccttcatata aattcactat cttggcttga ggcactccat aaaatgtatc 300acgtgcatag taaatcttta tatttgctat ggcgttgcac tagaggactt ggactgcaac 360aagtggatgc gcggaaaatg aaatcttctt caatagccca g 401
<210> 365
<211> 356
<212> DNA
<213> Homo sapien
<400> 365ccagtgtcat atttgggctt aaaatttcaa gaagggcact tcaaatggct ttgcatttgc 60atgtttcagt gctagagcgt aggaatagac cctggcgtcc actgtgagat gttcttcagc 120taccagagca tcaagtctct gcagcaggtc attcttgggt aaagaaatga cttccacaaa 180ctctccatcc cctggctttg gcttcggcct tgcgttttcg gcatcatctc cgttaatggt 240gactgtcacg atgtgtatag tacagtttga caagcctggg tccatacaga ccgctggaga 300acattcggca atgtcccctt tgtagccagt ttcttcttcg agctcccgga gagcag 356
<210> 366
<211> 1851
<212> DNA
<213> Hcmo sapien
<400> 366tcatcaccat tgccagcagc ggcaccgtta gtcaggtttt ctgggaatcc cacatgagta 60cttccgtgtt cttcattctt cttcaatagc cataaatctt ctagctctgg ctggctgttt 120tcacttcctt taagcctttg tgactcttcc tctgatgtca gctttaagtc ttgttctgga 180ttgctgtttt cagaagagat ttttaacatc tgtttttctt tgtagtcaga aagtaactgg 240caaattacat gatgatgact agaaacagca tactctctgg ccgtctttcc agatcttgag 300aagatacatc aacattttgc tcaagtagag ggctgactat acttgctgat ccacaacata 360cagcaagtat gagagcagtt cttccatatc tatccagcgc atttaaattc gcttttttct 420tgattaaaaa tttcaccact tgctgttttt gctcatgtat accaagtagc agtggtgtga 480ggccatgctt gttttttgat tcgatatcag caccgtataa gagcagtgct tggccatta 540atttatcttc attgtagaca gcatagtgta gagtggtatt tccatactca tctggaatat 600ttggatcagt gccatgttcc agcaacatta acgcacattc atcttcctgg cattgtacgg 660cctttgtcag agctgtcctc tttttgttgt csaggacatt aagttgacat cgtctgtcca 720gcacgagttt tactacttct gaattcccat tggcagaggc cagatgtaga gcagtcctct 780tttgcttgtc cctcttgttc acatccgtgt ccctgagcat gacgatgaga tcctttctgg 840ggactttacc ccaccaggca gctctgtgga gcttgtccag atcttctcca tggacgtggt 900acctgggatc catgaaggcg ctgtcatcgt agtctcccca agcgaccacg ttgctcttgc 960cgctcccctg cagcagggga agcagtggca gcaccacttg cacctcttgc tcccaagcgt 1020cttcacagag gagtcgttgt ggtctccaga agtgcccacg ttgctcttgc cgctccccct 1080gtccatccag ggaggaagaa atgcaggaaa tgaaagatgc atgcacgatg gtatactcct 1140cagccatcaa acttctggac agcaggtcac ttccagcaag gtggagaaag ctgtccaccc 1200acagaggatg agatccagaa accacaatat ccattcacaa acaaacactt ttcagccaga 1260cacaggtact gaaatcatgt catctgcggc aacatggtgg aacctaccca atcacacatc 1320aagagatgaa gacactgcag tatatctgca caacgtaata ctcttcatcc ataacaaaat 1380aatataattt tcctctggag ccatatggat gaactatgaa ggaagaactc cccgaagaag 1440ccagtcgcag agaagccaca ctgaagctct gtcctcagcc atcagcgcca cggacaggar 1500tgtgtttctt ccccagtgat gcagcctcaa gttatcccga agctgccgca gcacacggtg 1560gctcctgaga aacaccccag ctcttccggt ctaacacagg caagtcaata aatgtgataa 1620tcacataaac agaattaaaa gcaaagtcac ataagcatct caacagacac agaaaaggca 1680tttgacaaaa tccagcatcc ttgtatttat tgttgcagtt ctcagaggaa atgcttctaa 1740cttttcccca tttagtatta tgttggctgt gggcttgtca taggtggttt ttattacttt 1800aaggtatgtc ccttctatgc ctgttttgct gagggtttta attctcgtgc c 1851
<210> 367
<211> 668
<212> DNA
<213> Homo sapien
<400> 367cttgagcttc caaataygga agactggccc ttacacasgt caatgttaaa atgaatgcat 60ttcagtattt tgaagataaa attrgtagat ctataccttg ttttttgatt cgatatcagc 120accrtataag agcagtgctt tggccattaa tttatctttc attrtagaca gcrtagtgya 180gagtggtatt tccatactca tctggaatat ttggatcagt gccatgttcc agcaacatta 240acgcacattc atcttcctgg cattgtacgg cctgtcagta ttagacccaa aaacaaatta 300catatcttag gaattcaaaa taacattcca cagctttcac caactagtta tatttaaagg 360agaaaactca tttttatgcc atgtattgaa atcaaaccca cctcatgctg atatagttgg 420ctactgcata cctttatcag agctgtcctc tttttgttgt caaggacatt aagttgacat 480cgtctgtcca gcaggagttt tactacttct gaattcccat tggcagaggc cagatgtaga 540gcagtcctat gagagtgaga agacttttta ggaaattgta gtgcactagc tacagccata 600gcaatgattc atgtaactgc aaacactgaa tagcctgcta ttactctgcc ttcaaaaaaa 660aaaaaaaa 668
<210> 368
<211> 1512
<212> DNA
<213> Homo sapien
<400> 368gggtcgccca gggggsgcgt gggctttcct cgggtgggtg tgggttttcc ctgggtgggg 60tgggctgggc trgaatcccc tgctggggtt ggcaggtttt ggctgggatt gacttttytc 120ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg 180atctgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggttgat 240tccatgccgg ctgcttcttc tgtgaagaag ccatttggtc tcaggagcaa gatgggcaag 300tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct 360ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc 420cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac 480gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagt 600gccttcatgg agcccaggta ccacgtccgtggagaagatc tggacaagct ccacagagct 660gcctggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cactgacgtg 720aacaagaagg acaagcaaaa gaggactgct ctacatctgg cctctgccaa tgggaattca 780gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtccttga caacaaaaag 840aggacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg 900gaacatggca ctgatccaaa tattccagat gagtatggaa ataccactct rcactaygct 960rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa 1020tcaaaaaaca aggtatagat ctactaattt tatcttcaaa atactgaaat gcattcattt 1080taacattgac gtgtgtaagg gccagtcttc cgtatttgga agctcaagca taacttgaat 1140gaaaatattt tgaaatgacc taattatctm agactttatt ttaaatattg ttattttcaa 1200agaagcatta gagggtacag tttttttttt ttaaatgcac ttctggtaaa tacttttgtt 1260gaaaacactg aatttgtaaa aggtaatact tactattttt caatttttcc ctcctaggat 1320ttttttcccc taatgaatgt aagatggcaa aatttgccct gaaataggtt ttacatgaaa 1380actccaagaa aagttaaaca tgtttcagtg aatagagatc ctgctccttt ggcaagttcc 1440taaaaaacag taatagatac gaggtgatgc gcctgtcagt ggcaaggttt aagatatttc 1500tgatctcgtg cc 1512
<210> 369
<211> 1853
<212> DNA
<213> Homo sapien
<400> 369gggtcgccca gggggsgcgt gggctttcct cgggtgggtg tgggttttcc ctgggtgggg 60tgggctgggc trgaatcccc tgctggggtt ggcaggtttt ggctgggatt gacttttytc 120ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg 180atctgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggttgat 240tccatgccgg ctgcttcttc tgtgaagaag ccatttggtc tcaggagcaa gstgggcaag 300tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct 360ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc 420cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac 480gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagy 600gccttcatgg akcccaggta ccacgtccrt ggagaagatc tggacaagct ccacagagct 660gcctggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cackgaygtg 720aacaagargg acaagcaaaa gaggactgct ctacatctgg cctctgccaa tgggaattca 780gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtccttga caacaaaaag 840aggacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg 900gaacatggca ctgatccaaa tattccagat gagtatggaa ataccactct rcactaygct 960rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa 1020tcaaaaaaca agcatggcct cacaccactg ytacttggtr tacatgagca aaaacagcaa 1080gtsgtgaaat ttttaatyaa gaaaaaagcg aatttaaaat gcrctggata gatatggaag 1140ractgctctc atacttgctg tatgttgtgg atcagcaagt atagtcagcc ytctacttga 1200gcaaaatrtt gatgtatctt ctcaagatct ggaaagacgg ccagagagta tgctgtttct 1260agtcatcatc atgtaatttg ccagttactt tctgactaca aagaaaaaca gatgttaaaa 1320atctcttctg aaaacagcaa tccagaacaa gacttaaagc tgacatcaga ggaagagtca 1380caaaggctta aaggaagtga aaacagccag ccagaggcat ggaaactttt aaatttaaac 1440ttttggttta atgttttttt tttttgcctt aataatatta gatagtccca aatgaaatwa 1500cctatgagac taggctttga gaatcaatag attctttttt taagaatctt ttggctagga 1560gcggtgtctc acgcctgtaa ttccagcacc ttgagaggct gaggtgggca gatcacgaga 1620tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact aaaaatacaa 1680aaacttagct gggtgtggtg gcgggtgcct gtagtcccag ctactcagga rgctgaggca 1740ggagaatggc atgaacccgg gaggtggagg ttgcagtgag ccgagatccg ccactacact 1800ccagcctggg tgacagagca agactctgtc tcaaaaaaaa aaaaaaaaaa aaa 1853
<210> 370
<211> 2184
<212> DNA
<213> Homo sapien
<400> 370ggcacgagaa ttaaaaccct cagcaaaaca ggcatagaag ggacatacct taaagtaata 60aaaaccacct atgacaagcc cacagccaac ataatactaa atggggaaaa gttagaagca 120tttcctctga gaacctcaac aataaataca aggatgctgg attttgtcaa atgccttttc 180tgtgtctgtt gagatgctta tgtgactttg cttttaattc tgtttatgtg attatcacat 240ttattgactt gcctgtgtta gaccggaaga gctggggtgt ttctcaggag ccaccgtgtg 300ctgcggcagc ttcgggataa cttgaggctg catcactggg gaagaaacac aytcctgtcc 360gtggcgctga tggctgagga cagagcttca gtgtggcttc tctgcgactg gcttcttcgg 420ggagttcttc cttcatagtt catccatatg gctccagagg aaaattatat tattttgtta 480tggatgaaga gtattacgtt gtgcagatat actgcagtgt cttcatctct tgatgtgtga 540ttgggtaggt tccaccatgt tgccgcagat gacatgattt cagtacctgt gtctggctga 600aaagtgtttg tttgtgaatg gatattgtgg tttctggatc tcatcctctg tgggtggaca 660gctttctcca ccttgctgga agtgacctgc tgtccagaag tttgatggct gaggagtata 720ccatcgtgca tgcatctttc atttcctgca tttcttcctc cctggatgga cagggggagc 780ggcaagagca acgtgggcac ttctggagac cacaacgact cctctgtgaa gacgcttggg 840agcaagaggt gcaagtggtg ctgccactgc ttcccctgct gcaggggagc ggcaagagca 900acgtggtcgc ttggggagac tacgatgaca gcgccttcat ggatcccagg taccacgtcc 960atggagaaga tctggacaag ctccacagag ctgcctggtg gggtaaagtc cccagaaagg 1020atctcatcgt catgctcagg gacacggatg tgaacaagag ggacaagcaa aagaggactg 1080ctctacatct ggcctctgcc aatgggaatt cagaagtagt aaaactcgtg ctggacagac 1140gatgtcaact taatgtcctt gacaacaaaa agaggacagc tctgacaaag gccgtacaat 1200gccaggaaga tgaatgtgcg ttaatgttgc tggaacatgg cactgatcca aatattccag 1260atgagtatgg aaataccact ctacactatg ctgtctacaa tgaagataaa ttaatggcca 1320aagcactgct cttatacggt gctgatatcg aatcaaaaaa caagcatggc ctcacaccac 1380tgctacttgg tatacatgag caaaaacagc aagtggtgaa atttttaatc aagaaaaaag 1440cgaatttaaa tgcgctggat agatatggaa gaactgctct catacttgct gtatgttgtg 1500gatcagcaag tatagtcagc cctctacttg agcaaaatgt tgatgtatct tctcaagatc 1560tggaaagacg gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact 1620ttctgactac aaagaaaaac agatgttaaa aatctcttct gaaaacagca atccagaaca 1680agacttaaag ctgacatcag aggaagagtc acaaaggctt aaaggaagtg aaaacagcca 1740gccagaggca tggaaacttt taaatttaaa cttttggttt aatgtttttt ttttttgcct 1800taataatatt agatagtccc aaatgaaatw acctatgaga ctaggctttg agaatcaata 1860gattcttttt ttaagaatct tttggctagg agcggtgtct cacgcctgta attccagcac 1920cttgagaggc tgaggtgggc agatcacgag atcaggagat cgagaccatc ctggctaaca 1980cggtgaaacc ccatctctac taaaaataca aaaacttagc tgggtgtggt ggcgggtgcc 2040tgtagtccca gctactcagg argctgaggc aggagaatgg catgaacccg ggaggtggag 2100gttgcagtga gccgagatcc gccactacac tccagcctgg gtgacagagc aagactctgt 2160ctcaaaaaaa aaaaaaaaaa aaaa 2184
<210> 371
<211> 1855
<212> DNA
<213> Homo sapien
<220>
<221> misc_feature
<222> (1)...(1855)
<223> n = A,T,C or G
<400> 371tgcacgcatc ggccagtgtc tgtgccacgt acactgacgc cccctgagat gtgcacgccg 60cacgcgcacg ttgcacgcgc ggcagcggct tggctggctt gtaacggctt gcacgcgcac 120gccgcccccg cataaccgtc agactggcct gtaacggctt gcaggcgcac gccgcacgcg 180cgtaacggct tggctgccct gtaacggctt gcacgtgcat gctgcacgcg cgttaacggc 240ttggctggca tgtagccgct tggcttggct ttgcattytt tgctkggctk ggcgttgkty 300tcttggattg acgcttcctc cttggatkga cgtttcctcc ttggatkgac gtttcytyty 360tcgcgttcct ttgctggact tgacctttty tctgctgggt ttggcattcc tttggggtgg 420gctgggtgtt ttctccgggg gggktkgccc ttcctggggt gggcgtgggk cgcccccagg 480gggcgtgggc tttccccggg tggggtggg ttttcctggg gtggggtggg ctgtgctggg 540atccccctgc tggggttggc agggattgac ttttttcttc aaacagattg gaaacccgga 600gtaacntgct agttggtgaa actggttggt agacgcgatc tgctggtact actgtttctc 660ctggctgtta aaagcagatg gtggctgagg ttgattcaat gccggctgct tcttctgtga 720agaagccatt tggtctcagg agcaagatgg gcaagtggtg cgccactgct tcccctgctg 780cagggggagc ggcaagagca acgtgggcac ttctggagac cacaacgact cctctgtgaa 840gacgcttggg agcaagaggt gcaagtggtg ctgcccactg cttcccctgc tgcaggggag 900cggcaagagc aacgtggkcg cttggggaga ctacgatgac agcgccttca tggakcccag 960gtaccacgtc crtggagaag atctggacaa gctccacaga gctgcctggt ggggtaaagt 1020ccccagaaag gatctcatcg tcatgctcag ggacactgay gtgaacaaga rggacaagca 1080aaagaggact gctctacatc tggcctctgc caatgggaat tcagaagtag taaaactcgt 1140gctggacaga cgatgtcaac ttaatgtcct tgacaacaaa aagaggacag ctctgacaaa 1200ggccgtacaa tgccaggaag atgaatgtgc gttaatgttg ctggaacatg gcactgatcc 1260aaatattcca gatgagtatg gaaataccac tctacactat gctgtctaca atgaagataa 1320attaatggcc aaagcactgc tcttatacgg tgctgatatc gaatcaaaaa acaaggtata 1380gatctactaa ttttatcttc aaaatactga aatgcattca ttttaacatt gacgtgtgta 1440agggccagtc ttccgtattt ggaagctcaa gcataacttg aatgaaaata ttttgaaatg 1500acctaattat ctaagacttt attttaaata ttgttatttt caaagaagca ttagagggta 1560cagttttttt tttttaaatg cacttctggt aaatactttt gttgaaaaca ctgaatttgt 1620aaaaggtaat acttactatt tttcaatttt tccctcctag gatttttttc ccctaatgaa 1680tgtaagatgg caaaatttgc cctgaaatag gttttacatg aaaactccaa gaaaagttaa 1740acatgtttca gtgaatagag atcctgctcc tttggcaagt tcctaaaaaa cagtaataga 1800tacgaggtga tgcgcctgtc agtggcaagg tttaagatat ttctgatctc gtgcc 1855
<210> 372
<211> 1059
<212> DNA
<213> Homo sapien
<400> 372gcaacgtggg cacttctgga gaccacaacg actcctctgt gaagacgctt gggagcaaga 60ggtgcaagtg gtgctgccca ctgcttcccc tgctgcaggg gagcggcaag agcaacgtgg 120gcgcttgrgg agactmcgat gacagygcct tcatggagcc caggtaccac gtccgtggag 180aagatctgga caagctccac agagctgccc tggtggggta aagtccccag aaaggatctc 240atcgtcatgc tcagggacac tgaygtgaac aagarggaca agcaaaagag gactgctcta 300catctggcct ctgccaatgg gaattcagaa gtagtaaaac tcstgctgga cagacgatgt 360caacttaatg tccttgacaa caaaaagagg acagctctga yaaaggccgt acaatgccag 420gaagatgaat gtgcgttaat gttgctggaa catggcactg atccaaatat tccagatgag 480tatggaaata ccactctrca ctaygctrtc tayaatgaag ataaattaat ggccaaagca 540ctgctcttat ayggtgctga tatcgaatca aaaaacaagg tatagatcta ctaattttat 600cttcaaaata ctgaaatgca ttcattttaa cattgacgtg tgtaagggcc agtcttccgt 660atttggaagc tcaagcataa cttgaatgaa aatattttga aatgacctaa ttatctaaga 720ctttatttta aatattgtta ttttcaaaga agcattagag ggtacagttt ttttttttta 780aatgcacttc tggtaaatac ttttgttgaa aacactgaat ttgtaaaagg taatacttac 840tatttttcaa tttttccctc ctaggatttt tttcccctaa tgaatgtaag atggcaaaat 900ttgccctgaa ataggtttta catgaaaact ccaagaaaag ttaaacatgt ttcagtgaat 960agagatcctg ctcctttggc aagttcctaa aaaacagtaa tagatacgag gtgatgcgcc 1020tgtcagtggc aaggtttaag atatttctga tctcgtgcc 1059
<210> 373
<211> 1155
<212> DNA
<213> Homo sapien
<400> 373atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatc2g 420gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 546tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660tgtgcgttaa tgttgccgga acatggcact gatccaaata ttccagatga gtatggaaat 720accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaaa tgtctcaaga 1140accagaaata aataa 1155
<210> 374
<211> 2000
<212> DNA
<213> Homo sapien
<400> 374atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660tgtgcgttaa tgttgctgga acatggcact gatccaaata ttccagatga gtatggaaat 720accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaca agacttaaag 1140ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa 1200atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag 1260aagcatgaaa gtaataatgt gggattacta gaaaacctga ctaatggtgt cactgctggc 1320aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt 1380cctgacaacg aaagtgaaga gtatcacaga atttgcgaat tagtttctga ctacaaagaa 1440aaacagatgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca 1500tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gctagaaaat 1560tttatggcta tcgaagaaat gaagaagcac ggaagtactc atgtcggatt cccagaaaac 1620ctgactaatg gtgccactgc tggcaatggt gatgatggat taattcctcc aaggaagagc 1680agaacacctg aaagccagca atttcctgac actgagaatg aagagtatca cagtgacgaa 1740caaaatgata ctcagaagca attttgtgaa gaacagaaca ctggaatatt acacgatgag 1800attctgattc atgaagaaaa gcagatagaa gtggttgaaa aaatgaattc tgagctttct 1860cttagttgta agaaagaaaa agacatcttg catgaaaata gtacgttgcg ggaagaaatt 1920gccatgctaa gactggagct agacacaatg aaacatcaga gccagctaaa aaaaaaaaaa 1980aaaaaaaaaa aaaaaaaaaa 2000
<210> 375
<211> 2040
<212> DNA
<213> Homo sapien
<400> 375atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660tgtgcgttaa tgttgctgga acatggcact gatccaaata ttccagatga gtatggaaat 720accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaca agacttaaag 1140ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa 1200atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag 1260aagcatgaaa gtaataatgt gggattacta gaaaacctga ctaatggtgt cactgctggc 1320aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt 1380cctgacaacg aaagtgaaga gtatcacaga atttgcgaat tagtttctga ctacaaagaa 1440aaacagatgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca 1500tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gaaaagatct 1560caagaaccag aaataaataa ggatggtgat agagagctag aaaattttat ggctatcgaa 1620gaaatgaaga agcacggaag tactcatgtc ggattcccag aaaacctgac taatggtgcc 1680actgctggca atggtgatga tggattaatt cctccaagga agagcagaac acctgaaagc 1740cagcaatttc ctgacactga gaatgaagag tatcacagtg acgaacaaaa tgatactcag 1800aagcaatttt gtgaagaaca gaacactgga atattacacg atgagattct gattcatgaa 1860gaaaagcaga tagaagtggt tgaaaaaatg aattctgagc tttctcttag ttgtaagaaa 1920gaaaaagaca tcttgcatga aaatagtacg ttgcgggaag aaattgccat gctaagactg 1980gagctagaca caatgaaaca tcagagccag ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2040
<210> 376
<211> 329
<212> PRT
<213> Homo sapien
<400> 376Met Asp Ile Val Val Ser Gly Ser His Pro Leu Trp Val Asp Ser Phe1 5 10 15Leu His Leu Ala Gly Ser Asp Leu Leu Ser Arg Ser Leu Met Ala Glu
20 25 30Glu Tyr Thr Ile Val His Ala Ser Phe Ile Ser Cys Ile Ser Ser Ser
35 40 45Leu Asp Gly Gln Gly Glu Arg Gln Glu Gln Arg Gly His Phe Trp Arg
50 55 60Pro Gln Arg Leu Leu Cys Glu Asp Ala Trp Glu Gln Glu Val Gln Val65 70 75 80Val Leu Pro Leu Leu Pro Leu Leu Gln Gly Ser Gly Lys Ser Asn Val
85 90 95Val Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe Met Asp Pro Arg Tyr
100 105 110His Val His Gly Glu Asp Leu Asp Lys Leu His Arg Ala Ala Trp Trp
115 120 125Gly Lys Val Pro Arg Lys Asp Leu Ile val Met Leu Arg Asp Thr Asp
130 135 140Val Asn Lys Arg Asp Lys Gln Lys Arg Thr Ala Leu His Leu Ala Ser145 150 155 160Ala Asn Gly Asn Ser Glu Val Val Lys Leu Val Leu Asp Arg Arg Cys
165 170 175Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr Ala Leu Thr Lys Ala
180 185 190Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly
195 200 205Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr
210 215 220Ala val Tyr Asn Glu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr225 230 235 240Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu
245 250 255Leu Gly Ile His Glu Gln Lys Gln Gln Val Val Lys Phe Leu Ile Lys
260 265 270Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu
275 280 285Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile Val Ser Pro Leu Leu
290 295 300Glu Gln Asn Val Asp Val Ser Ser Gln Asp Leu Glu Arg Arg Pro GLu305 310 315 320Ser Met Leu Phe Leu Val Ile Ile Met
325
<210> 377
<211> 148
<212> PRT
<213> Homo sapien
<220>
<221> VARIANT
<222> (1)...(148)
<223> Xaa = Any Amino Acid
<400> 377Met Thr Xaa Pro Ser Trp Ser Pro Gly Thr Thr Ser Val Glu Lys Ile1 5 10 15Trp Thr Ser Ser Thr Glu Leu Pro Trp Trp Gly Lys Val Pro Arg Lys
20 25 30Asp Leu Ile Val Met Leu Arg Asp Thr Asp Val Asn Lys Xaa Asp Lys
35 40 45Gln Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu
50 55 60Val Val Lys Leu Xaa Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp65 70 75 80Asn Lys Lys Arg Thr Ala Leu Xaa Lys Ala Val Gln Cys Gln Glu Asp
85 90 95Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro
100 105 110Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Xaa Tyr Asn Glu Asp
115 120 125Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser
130 135 140Lys Asn Lys Val145
<210> 378
<211> 1719
<212> PRT
<213> Homo sapien
<400> 378Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys1 5 10 15Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe
20 25 30Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp
35 40 45His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp
50 55 60Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val65 70 75 80Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn
85 90 95Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg G1y Ser
100 105 110Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe
115 120 125Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His
130 135 140Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met145 150 155 160Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Ala
165 170 175Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu
180 185 190Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr
195 200 205Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met
210 215 220Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn225 230 235 240Thr Thr Leu His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys
245 250 255Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly
260 265 270Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val
275 280 285Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr
290 295 300Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile305 310 315 320Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser Ser Gln Asp Leu
325 330 335Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val
340 345 350Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys Ile
355 360 365Ser Ser Glu Asn Ser Asn Pro Glu Asn Val Ser Arg Thr Arg Asn Lys
370 375 380Pro Arg Thr His Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser385 390 395 400Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys
405 410 415Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly
420 425 430Thr Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys
435 440 445Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly
450 455 460Lys Ser Asn Val Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys465 470 475 480Thr Leu Arg Asn Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys
485 490 495Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Ala Trp Giy Asp Tyr Asp
500 505 510Asp Ser Ala Phe Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu
515 520 525Asp Lys Leu His Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp
530 535 540Leu Ile Val Met Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln545 550 555 560Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val
565 570 575Val Lys Leu Leu Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn
580 585 590Lys Lys Arg Thr Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu
595 600 605Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp
610 615 620Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Ile Tyr Asn GluAsp Lys625 630 635 640Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp Ile Giu Ser Lys
645 650 655Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys
660 665 670Gln Gln Val Val Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala
675 680 685Leu Asp Arg Tyr Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly
690 695 700Ser Ala Ser Ile Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser705 710 715 720Ser Gln Asp Leu Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser
725 730 735His His His Val Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln
740 745 750Met Leu Lys Ile Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys
755 760 765Leu Thr Ser Glu Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser
770 775 780Gln Pro Glu Lys Met Ser Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp785 790 795 800Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly
805 810 815Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn
820 825 830Gly Leu Ile Pro Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe
835 840 845Pro Asp Asn Glu Ser Glu Glu Tyr His Arg Ile Cys Glu Leu Val Ser
850 855 860Asp Tyr Lys Glu Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn865 870 875 880Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu
885 890 895Glu Gly Ser Glu Asn Gly Gln Pro Glu Leu Glu Asn Phe Met Ala Ile
900 905 910Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe Pro Glu Asn
915 920 925Leu Thr Asn Gly Ala Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile Pro
930 935 940Pro Arg Lys Ser Arg Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu945 950 955 960Asn Glu Glu Tyr His Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe
965 970 975Cys Glu Glu Gln Asn Thr Gly Ile Leu His Asp Glu Ile Leu Ile His
980 985 990Glu Glu Lys Gln Ile Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser
995 1000 1005Leu Ser Cys Lys Lys Glu Lys Asp Ile Leu His Glu Asn Ser Thr Leu
1010 1015 1020Arg Glu Glu Ile Ala Met Leu Arg Leu Glu Leu Asp Thr Met Lys His1025 1030 1035 104Gln Ser Gln Leu Pro Arg Thr His Met Val Val Glu Val Asp Ser Met
1045 1050 1055Pro Ala Ala Ser Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met
1060 1065 1070Gly Lys Trp Cys Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys
1075 1080 1085Ser Asn Val Gly Thr Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr
1090 1095 1100Leu Arg Ser Lys Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys1105 1110 1115 112Arg Gly Ser Gly Lys Ser Asn Val Gly Ala Ser Gly Asp His Asp Asp
1125 1130 1135Ser Ala Met Lys Thr Leu Arg Asn Lys Met Gly Lys Trp Cys Cys His
1140 1145 1150Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Ala Trp
1155 1160 1165Gly Asp Tyr Asp Asp Ser Ala Phe Met Glu Pro Arg Tyr His Val Arg
1170 1175 1180Gly Glu Asp Leu Asp Lys Leu His Arg Ala Ala Trp Trp Gly Lys Val1185 1190 1195 120Pro Arg Lys Asp Leu Ile Val Met Leu Arg Asp Thr Asp Val Asn Lys
1205 1210 1215Lys Asp Lys Gln Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly
122 1225 1230Asn Ser Glu Val Val Lys Leu Leu Leu Asp Arg Arg Cys Gln Leu Asn
1235 1240 1245Val Leu Asp Asn Lys Lys Arg Thr Ala Leu Ile Lys Ala Val Gln Cys
1250 1255 1260Gln Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro1265 1270 1275 128Asn Ile Pro Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Ile Tyr
128 1290 1295Asn Glu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp
1300 1305 1310Ile Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val
1315 1320 1325His Glu Gln Lys Gln Gln Val Val Lys Phe Leu Ile Lys Lys Lys Ala
1330 1335 1340Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu Ile Leu Ala1345 1350 1355 136Val Cys Cys Gly Ser Ala Ser Ile Val Ser Leu Leu Leu Glu Gln Asn
1365 1370 1375Ile Asp Val Ser Ser Gln Asp Leu Ser Gly Gln Thr Ala Arg Glu Tyr
1380 1385 1390Ala Val Ser Ser His His His Val Ile Cys Gln Leu Leu Ser Asp Tyr
1395 1400 1405Lys Glu Lys Gln Met Leu Lys Ile Ser Ser Glu Asn Ser Asn Pro Glu1410 1415 1420Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Phe Lys Gly1425 1430 1435 144Ser Glu Asn Ser Gln Pro Glu Lys Met Ser Gln Glu Pro Glu Ile Asn
1445 1450 1455Lys Asp Gly Asp Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser
1460 1465 1470Asn Asn Val Gly Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Ala Gly
1475 1480 1485Asn Gly Asp Asn Gly Leu Ile Pro Gln Arg Lys Ser Arg Thr Pro Glu
1490 1495 1500Asn Gln Gln Phe Pro Asp Asn Glu Ser Glu Glu Tyr His Arg Ile Cys1505 1510 1515 152Glu Leu Val Ser Asp Tyr Lys Glu Lys Gln Met Pro Lys Tyr Ser Ser
1525 1530 1535Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu
1540 1545 1550Ser Gln Arg Leu Glu Gly Ser Glu Asn Gly Gln Pro Glu Lys Arg Ser
1555 1560 1565Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp Arg Glu Leu Glu Asn Phe
1570 1575 1580Met Ala Ile Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe1585 1590 1595 160Pro Glu Asn Leu Thr Asn Gly Ala Thr Ala Gly Asp Gly Asp Asp Gly
1605 1610 1615Leu Ile Pro Pro Arg Lys Ser Arg Thr Pro Glu Ser Gln Gln Phe Pro
1620 1625 1630Asp Thr Glu Asn Glu Glu Tyr His Ser Asp Glu Gln Asn Asp Thr Gln
1635 1640 1645Lys Gln Phe Cys Glu Glu Gln Asn Thr Gly Ile Leu His Asp Glu Ile
1650 1655 1660Leu Ile His Glu Glu Lys Gln Ile Glu Val Val Glu Lys Met Asn Ser1665 1670 1675 168Glu Leu Ser Leu Ser Cys Lys Lys Glu Lys Asp Ile Leu His Glu Asn
16 1690 1695Ser Thr Leu Arg Glu Glu Ile Ala Met Leu Arg Leu Glu Leu Asp Thr
1700 1705 1710Met Lys His Gln Ser Gln Leu
1715
<210> 379
<211> 656
<212> PRT
<213> Homo sapien
<400> 379Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys1 5 10 15Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe
20 25 30Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp
35 40 45His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp
50 55 60Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val65 70 75 80Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn
85 90 95Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser
100 105 110Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe
115 120 125Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His
130 135 140Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met145 150 155 160Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Ala
165 170 175Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu
180 185 190Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr
195 200 205Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met
210 215 220Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn225 230 235 240Thr Thr Leu His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys
245 250 255Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly
260 265 270Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val
275 280 285Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr
290 295 300Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile305 310 315 320Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser Ser Gln Asp Leu
325 330 335Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val
340 345 350Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys Ile
355 360 365Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu
370 375 380Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser Gln Pro Glu Lys385 390 395 400Met Ser Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp Arg Glu Val Glu
405 410 415Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn
420 425 430Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu Ile Pro
435 440 445Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe Pro Asp Asn Glu
450 455 460Ser Glu Glu Tyr His Arg Ile Cys Glu Leu Val Ser Asp Tyr Lys Glu465 470 475 480Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp
485 490 495Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu Glu Gly Ser Glu
500 505 510Asn Gly Gln Pro Glu Leu Glu Asn Phe Met Ala Ile Glu Glu Met Lys
515 520 525Lys His Gly Ser Thr His Val Gly Phe Pro Glu Asn Leu Thr Asn Gly
530 535 540Ala Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile Pro Pro Arg Lys Ser545 550 555 560Arg Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu Asn Glu Glu Tyr
565 570 575His Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe Cys Glu Glu Gln
580 585 590Asn Thr Gly Ile Leu His Asp Glu Ile Leu Ile His Glu Glu Lys Gln
595 600 605Ile Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser Leu Ser Cys Lys
610 615 620Lys Glu Lys Asp Ile Leu His Glu Asn Ser Thr Leu Arg Glu Glu Ile625 630 635 640Ala Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gln Ser Gln Leu
645 650 655
<210> 380
<211> 671
<212> PRT
<213> Homo sapien
<400> 380Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys1 5 10 15Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe
20 25 30Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp
35 40 45His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp
50 55 60Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val65 70 75 80Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn
85 90 95Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser
l00 105 110Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe
115 120 125Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His
130 135 140Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met145 150 155 160Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Ala
165 170 175Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu
180 185 190Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr
195 200 205Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met
210 215 220Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn
230 235 240
J His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys
245 250 255
Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly
260 265 270
Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val
275 280 285Jys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr
290 295 300Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile305 310 315 320Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser Ser Gln Asp Leu
325 330 335Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val
340 345 350Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys Ile
355 360 365Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu
370 375 380Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser Gln Pro Glu Lys385 390 395 400Met Ser Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp Arg Glu Val Glu
405 410 415Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn
420 425 430Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu Ile Pro
435 440 445Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe Pro Asp Asn Glu
450 455 460Ser Glu Glu Tyr His Arg Ile Cys Glu Leu Val Ser Asp Tyr Lys Glu465 470 475 480Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Agn Pro Glu Gln Asp
485 490 495Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu Glu Gly Ser Glu
500 505 510Asn Gly Gln Pro Glu Lys Arg Ser Gln Glu Pro Glu Ile Asn Lys Asp
515 520 525Gly Asp Arg Glu Leu Glu Asn Phe Met Ala Ile Glu Glu Met Lys Lys
530 535 540His Gly Ser Thr His Val Gly Phe Pro Glu Asn Leu Thr Asn Gly Ala545 550 555 560Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile Pro Pro Arg Lys Ser Arg
565 570 575Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu Asn Glu Glu Tyr His
580 585 590Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe Cys Glu Glu Gln Ash
595 600 605Thr Gly Ile Leu His Asp Glu Ile Leu Ile His Glu Glu Lys Gln Ile
610 615 620Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser Leu Ser Cys Lys Lys625 630 635 640Glu Lys Asp Ile Leu His Glu Asn Ser Thr Leu Arg Glu Glu Ile Ala
645 650 655Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gln Ser Gln Leu
660 665 670
<210> 381
<211> 251
<212> DNA
<213> Homo sapien
<400> 381ggagaagcgt ctgctggggc aggaaggggt ttccctgccc tctcacctgt ccctcaccaa 60ggtaacatgc ttcccctaag ggtatcccaa cccaggggcc tcaccatgac ctctgagggg 120ccaatatccc aggagaagca ttggggagtt gggggcaggt gaaggaccca ggactcacac 180atcctgggcc tccaaggcag aggagagggt cctcaagaag gtcaggagga aaatccgtaa 240caagcagtca g 251<210> 382<211> 3279<212> DNA<213> Homo sapiens<400> 382cttcctgcag cccccatgct ggtgaggggc acgggcagga acagtggacc caacatggaa 60atgctggagg gtgtcaggaa gtgatcgggc tctggggcag ggaggagggg tggggagtgt 120cactgggagg ggacatcctg cagaaggtag gagtgagcaa acacccgctg caggggaggg 180gagagccctg cggcacctgg gggagcagag ggagcagcac ctgcccaggc ctgggaggag 240gggcctggag ggcgtgagga ggagcgaggg ggctgcatggctggagtgag ggatcagggg 300cagggcgcga gatggcctca cacagggaag agagggcccc tcctgcaggg cctcacctgg 360gccacaggag gacactgctt ttcctctgag gagtcaggag ctgtggatgg tgctggacag 420aagaaggaca gggcctggct caggtgtcca gaggctgtcg ctggcttccc tttgggatca 480gactgcaggg agggagggcg gcagggttgt ggggggagtg acgatgagga tgacctgggg 540gtggctccag gccttgcccc tgcctgggcc ctcacccagc ctccctcaca gtctcctggc 600cctcagtctc tcccctccac tccatcctcc atctggcctc agtgggtcat tctgatcact 660gaactgacca tacccagccc tgcccacggc cctccatggc tccccaatgc cctggagagg 720ggacatctag tcagagagta gtcctgaaga ggtggcctct gcgatgtgcc tgtgggggca 780gcatcctgca gatggtcccg gccctcatcc tgctgacctg tctgcaggga ctgtcctcct 840ggaccttgcc ccttgtgcag gagctggacc ctgaagtccc ctccccatag gccaagactg 900gagccttgtt ccctctgttg gactccctgc ccatattctt gtgggagtgg gttctggaga 960catttctgtc tgttcctgag agctgggaat tgctctcagt catctgcctg cgcggttctg 1020agagatggag ttgcctaggc agttattggg gccaatcttt ctcactgtgt ctctcctcct 1080ttagccttag ggtgattctg ggggtccact tgtctgtaat ggtgtgcttc aaggtatcac 1140atcatggggc cctgagccat gtgccctgcc tgaaaagcct gctgtgtaca ccaaggtggt 1200gcattaccgg aagtggatca aggacaccat cgcagccaac ccctgagtgc ccctgtccca 1260cccctacctc tagtaaattt aagtccacct cacgttctgg catcacttgg cctttctgga 1320tgctggacac ctgaagcttg gaactcacct ggccgaagct cgagcctcct gagtcctact 1380gacctgtgct ttctggtgtg gagtccaggg ctgctaggaa aaggaatggg cagacacagg 1440tgtatgccaa tgtttctgaa atgggtataa tttcgtcctc tccttcggaa cactggctgt 1500ctctgaagac ttctcgctca gtttcagtga ggacacacac aaagacgtgg gtgaccatgt 1560tgtttgtggg gtgcagagat gggaggggtg gggcccaccc tggaagagtg gacagtgaca 1620caaggtggac actctctaca gatcactgag gataagctgg agccacaatg catgaggcac 1680acacacagca aggttgacgc tgtaaacata gcccacgctg tcctgggggc actgggaagc 1740ctagataagg ccgtgagcag aaagaagggg aggatcctcc tatgttgttg aaggagggac 1800tagggggaga aactgaaagc tgattaatta caggaggttt gttcaggtcc cccaaaccac 1860cgtcagattt gatgatttcc tagcaggact tacagaaata aagagctatc atgctgtggt 1920ttattatggt ttgttacatt gataggatac atactgaaat cagcaaacaa aacagatgta 1980tagattagag tgtggagaaa acagaggaaa acttgcagtt acgaagactg gcaacttggc 2040tttactaagt tttcagactg gcaggaagtc aaacctatta ggctgaggac cttgtggagt 2100gtagctgatc cagctgatag aggaactagc caggtggggg cctttccctt tggatggggg 2160gcatatccga cagttattct ctccaagtgg agacttacgg acagcatata attctccctg 2220caaggatgta tgataatatg tacaaagtaa ttccaactga ggaagctcac ctgatcctta 2280gtgtccaggg tttttactgg gggtctgtag gacgagtatg gagtacttga ataattgacc 2340tgaagtcctc agacctgagg ttccctagag ttcaaacaga tacagcatgg tccagagtcc 2400cagatgtaca aaaacaggga ttcatcacaa atcccatctt tagcatgaag ggtctggcat 2460ggcccaaggc cccaagtata tcaaggcact tgggcagaac atgccaagga atcaaatgtc 2520atctcccagg agttattcaa gggtgagccc tttacttggg atgtacaggc tttgagcagt 2580gcagggctgc tgagtcaacc ttttattgta Caggggatga gggaaaggga gaggatgagg 2640aagcccccct ggggatttgg tttggtcttg tgatcaggtg gtctatgggg ctatccctac 2700aaagaagaat ccagaaatag gggcacattg aggaatgata ctgagcccaa agagcattca 2760atcattgttt tatttgcctt cttttcacac cattggtgag ggagggatta ccaccctggg 2820gttatgaaga tggttgaaca ccccacacat agcaccggag atatgagatc aacagtttct 2880tagccataga gattcacagc ccagagcagg aggacgctgc acaccatgca ggatgacatg 2940ggggatgcgc tcgggattgg tgtgaagaag caaggactgt tagaggcagg ctttatagta 3000acaagacggt ggggcaaact ctgatttccg tgggggaatg tcatggtctt gctttactaa 3060gttttgagac tggcaggtag tgaaactcat taggctgaga accttgtgga atgcagctga 3120cccagctgat agaggaagta gccaggtggg agcctttccc agtgggtgtg ggacatatct 3180ggcaagattt tgtggcactc ctggttacag atactggggc agcaaataaa actgaatctt 3240gttttcagac cttaaaaaaa aaaaaaaaaa aaaagtttt 3279<210> 383<211> 155<212> PRT<213> Homo sapiens<400> 383Met Ala Gly Val Arg Asp Gln Gly Gln Gly Ala Arg Trp Pro His Thr
5 10 15Gly Lys Arg Gly Pro Leu Leu Gln Gly Leu Thr Trp Ala Thr Gly Gly
20 25 30His Cys Phe Ser Ser Glu Glu Ser Gly Ala Val Asp Gly Ala Gly Gln
35 40 45Lys Lys Asp Arg Ala Trp Leu Arg Cys Pro Glu Ala Val Ala Gly Phe
50 55 60Pro Leu Gly Ser Asp Cys Arg Glu Gly Gly Arg Gln Gly Cys Gly Gly65 70 75 80Ser Asp Asp Glu Asp Asp Leu Gly Val Ala Pro Gly Leu Ala Pro Ala
85 90 95Trp Ala Leu Thr Gln Pro Pro Ser Gln Ser Pro Gly Pro Gln Ser Leu
100 105 110Pro Ser Thr Pro Ser Ser Ile Trp Pro Gln Trp Val Ile Leu Ile Thr
115 120 125Glu Leu Thr Ile Pro Ser Pro Ala His Gly Pro Pro Trp Leu Pro Asn
130 135 140Ala Leu Glu Arg Gly His Leu Val Arg Glu145 150<210> 384<211> 557<212> DNA<213> Homo sapiens<400> 384ggatcctcta gagcggccgc ctactactac taaattcgcg gccgcgtcga cgaagaagag 60aaagatgtgt tttgttttgg actctctgtg gtcccttcca atgctgtggg tttccaacca 120ggggaagggt cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggt 180tctgcctcct ggccaagcag gctggtttgc aagaatgaaa tgaatgattc tacagctagg 240acttaacctt gaaatggaaa gtcttgcaat cccatttgca ggatccgtct gtgcacatgc 300ctctgtagag agcagcattc ccagggacct tggaaacagt tggcactgta aggtgcttgc 360tccccaagac acatcctaaa aggtgttgta atggtgaaaa cgtcttcctt ctttattgcc 420ccttcttatt tatgtgaaca actgtttgtc tttttttgta tcttttttaa actgtaaagt 480tcaattgtga aaatgaatat catgcaaata aattatgcga tttttttttc aaagtaaaaa 540aaaaaaaaaa aaaaaaa 557<210> 385<211> 337<212> DNA<213> Homo sapiens<400> 385ttcccaggtg atgtgcgagg gaagacacat ttactatcct tgatggggct gattccttta 60gtttctctag cagcagatgg gttaggagga agtgacccaa gtggttgact cctatgtgca 120tctcaaagcc atctgctgtc ttcgagtacg gacacatcat cactcctgca ttgttgatca 180aaacgtggag gtgcttttcc tcagctaaga agcccttagc aaaagctcga atagacttag 240tatcagacag gtccagtttc cgcaccaaca cctgctggtt ccctgtcgtg gtctggatct 300ctttggccac caattccccc ttttccacat cccggca 337<210> 386<211> 300<212> DNA<213> Homo sapiens<400> 386gggcccgcta ccggcccagg ccccgcctcg cgagtcctcc tccccgggtg cctgcccgca 60gcccgctcgg cccagagggt gggcgcgggg ctgcctctac cggctggcgg ctgtaactca 120gcgaccttgg cccgaaggct ctagcaagga cccaccgacc ccagccgcgg cggcggcggc 180gcggactttg cccggtgtgt ggggcggagc ggactgcgtg tccgcggacg ggcagcgaag 240atgttagcct tcgctgccag gaccgtggac cgatcccagg gctgtggtgt aacctcagcc 300<210> 387<211> 537<212> DNA<213> Homo sapiens<400> 387gggccgagtc gggcaccaag ggactctttg caggcttcct tcctcggatc atcaaggctg 60ccccctcctg tgccatcatg atcagcacct atgagttcgg caaaagcttc ttccagaggc 120tgaaccagga ccggcttctg ggcggctgaa aggggcaagg aggcaaggac cccgtctctc 180ccacggatgg ggagagggca ggaggagacc cagccaagtg ccttttcctc agcactgagg 240gagggggctt gtttcccttc cctcccggcg acaagctcca gggcagggct gtccctctgg 300gcggcccagc acttcctcag acacaacttc ttcctgctgc tccagtcgtg gggatcatca 360cttacccacc ccccaagttc aagaccaaat cttccagctg cccccttcgt gtttccctgt 420gtttgctgta gctgggcatg tctccaggaa ccaagaagcc ctcagcctgg tgtagtctcc 480ctgacccttg ttaattcctt aagtctaaag atgatgaact tcaaaaaaaa aaaaaaa 537<210> 388<211> 520<212> DNA<213> Homo sapiens<400> 388aggataattt ttaaaccaat caaatgaaaa aaacaaacaa acaaaaaagg aaatgtcatg 60tgaggttaaa ccagtttgca ttcccctaat gtggaaaaag taagaggact actcagcact 120gtttgaagat tgcctcttct acagcttctg agaattgtgt tatttcactt gccaagtgaa 180ggaccccctc cccaacatgc cccagcccac ccctaagcat ggtcccttgt caccaggcaa 240ccaggaaact gctacttgtg gacctcacca gagaccagga gggtttggtt agctcacagg 300acttccccca ccccagaaga ttagcatccc atactagact catactcaac tcaactaggc 360tcatactcaa ttgatggtta ttagacaatt ccatttcttt ctggttatta taaacagaaa 420atctttcctc ttctcattac cagtaaaggc tcttggtatc tttctgttgg aatgatttct 480atgaacttgt cttattttaa tggtgggttt tttttctggt 520<210> 389<211> 365<212> DNA<213> Homo sapiens<400> 389cgttgcccca gtttgacaga aggaaaggcg gagcttattc aaagtctaga gggagtggag 60gagttaaggc tggatttcag atctgcctgg ttccagccgc agtgtgccct ctgctccccc 120aacgactttc caaataatct caccagcgcc ttccagctca ggcgtcctag aagcgtcttg 180aagcctatgg ccagctgtct ttgtgttccc tctcacccgc ctgtcctcac agctgagact 240cccaggaaac cttcagacta ccttcctctg ccttcagcaa ggggcgttgc ccacattctc 300tgagggtcag tggaagaacc tagactccca ttgctagagg tagaaagggg aagggtgctg 360gggag 365<210> 390<211> 221<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(221)<223> n = A,T,C or G<400> 390tgcctctcca tcctggcccc gacttctctg tcaggaaagt ggggatggac cccatctgca 60tacacggntt ctcatgggtg tggaacatct ctgcttgcgg tttcaggaag gcctctggct 120gctctangag tctgancnga ntcgttgccc cantntgaca naaggaaagg cggagcttat 180tcaaagtcta gagggagtgg aggagttaag gctggatttc a 221<210> 391<211> 325<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1) ...(325)<223> n = A,T,C or G<400> 351tggagcaggt cccgaggcct ccctagagcc tggggccgac tctgtgncga tgcangcttt 60ctctcgcgcc cagcctggag ctgctcctgg catctaccaa caatcagncg aggcgagcag 120tagccagggc actgctgcca acagccagtc cnnataccat catgtnaccc ggtgngctct 180naanttngat ntccanagcc ctacccatcn tagttctgct ctcccaccgg ntaccagccc 240cactgcccag gaatcctaca gccagtaccc tgtcccgacg tctctaccta ccagtacgat 300gagacctccg gctactacta tgacc 325<210> 392<211> 277<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(277)<223> n = A,T,C or G<400> 392atattgttta actccttcct ttatatcttt taacattttc atggngaaag gttcacatct 60agtctcactt nggcnagngn ctcctacttg agtctcttcc ccggcctgnn ccagtngnaa 120antaccanga accgncatgn cttaanaacn ncctggtttn tgggttnntc aatgactgca 180tgcagtgcac caccctgtcc actacgtgat gctgtaggat taaagtctca cagtgggcgg 240ctgaggatac agcgccgcgt cctgtgttgc tggggaa 277<210> 393<211> 566<212> DNA<213> Homo sapiens<400> 393actagtccag tgtggtggaa ttcgcggccg cgtcgacgga caggtcagct gtctggctca 60gtgatctaca ttctgaagtt gtctgaaaat gtcttcatga ttaaattcag cctaaacgtt 120ttgccgggaa cactgcagag acaatgctgt gagtttccaa ccttagccca tctgcgggca 180gagaaggtct agtttgtcca tcagcattat catgatatca ggactggtta cttggttaag 240gaggggtcta ggagatctgt cccttttaga gacaccttac ttataatgaa gtatttggga 300gggtggtttt caaaagtaga aatgtcctgt attccgatga tcatcctgta aacattttat 360catttattaa tcatccctgc ctgtgtctat tattatattc atatctctac gctggaaact 420ttctgcctca atgtttactg tgcctttgtt tttgctagtt tgtgttgttg aaaaaaaaaa 480cattctctgc ctgagtttta atttttgtcc aaagttattt taatctatac aattaaaagc 540ttttgcctat caaaaaaaaa aaaaaa 566<210> 394<211> 384<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(384)<223> n = A,T,C or G<400> 394gaacatacat gtcccggcac ctgagctgca gtctgacatc atcgccatca cgggcctcgc 60tgcaaattng gaccgggcca aggctggact gctggagcgt gtgaaggagc tacaggccna 120gcaggaggac cgggctttaa ggagttttaa gctgagtgtc actgtagacc ccaaatacca 180tcccaagatt atcgggagaa agggggcagt aattacccaa atccggttgg agcatgacgt 240gaacatccag tttcctgata aggacgatgg gaaccagccc caggaccaaa ttaccatcac 300agggtacgaa aagaacacag aagctgccag ggatgctata ctgagaattg tgggtgaact 360tgagcagatg gtttctgagg acgt 384<210> 395<211> 399<212> DNA<213> Homo sapiens<400> 395ggcaaaactg tgtgacctca ataagacctc gcagatccaa ggtcaagtat cagaagtgac 60tctgaccttg gactccaaga cctacatcaa cagcctggct atattagatg atgagccagt 120tatcagaggt ttcatcattg cggaaattgt ggagtctaag gaaatcatgg cctctgaagt 180attcacgtct ttccagtacc ctgagttctc tatagagttg cctaacacag gcagaattgg 240ccagctactt gtctgcaatt gtatcttcaa gaataccctg gccatccctt tgactgacgt 300caagttctct ttggaaagcc tgggcatctc ctcactacag acctctgacc atgggacggt 360gcagcctggt gagaccatcc aatcccaaat aaaatgcac 399<210> 396<211> 403<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(403)<223> n = A,T,C or G<400> 396tggagttntc agtgcaaaca agccataaag cttcagtagc aaattactgt ctcacagaaa 60gacattttca acttctgctc cagctgctga taaaacaaat catgtgttta gcttgactcc 120agacaaggac aacctgttcc ttcataactc tctagagaaa aaaaggagtt gttagtagat 180actaaaaaaa gtggatgaat aatctggata tttttcctaa aaagattcct tgaaacacat 240taggaaaatg gagggcctta tgatcagaat gctagaatta gtccattgtg ctgaagcagg 300gtttagggga gggagtgagg gataaaagaa ggaaaaaaag aagagtgaga aaacctattt 360atcaaagcag gtgctatcac tcaatgttag gccctgctct ttt 403<210> 397<211> 100<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1) ...(100)<223> n = A,T,C or G<400> 397actagtncag tgtggtggaa ttcgcggccg cgtcgaccta naanccatct ctatagcaaa 60tccatccccg ctcctggttg gtnacagaat gactgacaaa 100<210> 398<211> 278<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (278)<223> n = A,T,C or G<400> 398gcggccgcgt cgacagcagt tccgccagcg ctcgcccctg ggtggggatg tgctgcacgc 60ccacctggac atctggaagt cagcggcctg gatgaaagag cggacttcac ctggggcgat 120tcactactgt gcctcgacca gtgaggagag ctggaccgac agcgaggtgg actcatcatg 180ctccgggcag cccatccacc tgtggcagtt cctcaaggag ttgctactca agccccacag 240ctatggccgc ttcattangt ggctcaacaa ggagaagg 278<210> 399<211> 298<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (298)<223> n = A,T,C or G<400> 399acggaggtgg aggaagcgnc cctgggatcg anaggatggg tcctgncatt gaccncctcn 60ggggtgccng catggagcgc atgggcgcgg gcctgggcca cggcatggat cgcgtgggct 120ccgagatcga gcgcatgggc ctggtcatgg accgcatggg ctccgtggag cgcatgggct 180ccggcattga gcgcatgggc ccgctgggcc tcgaccacat ggcctccanc attgancgca 240tgggccagac catggagcgc attggctctg gcgtggagcn catgggtgcc ggcatggg 298<210> 400<211> 548<212> DNA<213> Homo sapiens<400> 400acatcaacta cttcctcatt ttaaggtatg gcagttccct tcatcccctt ttcctgcctt 60gtacatgtac atgtatgaaa tttccttctc ttaccgaact ctctccacac atcacaaggt 120caaagaacca cacgcttaga agggtaagag ggcaccctat gaaatgaaat ggtgatttct 180tgagtctctt ttttccacgt ttaaggggcc atggcaggac ttagagttgc gagttaagac 240tgcagagggc tagagaatta tttcatacag gctttgaggc cacccatgtc acttatcccg 300tataccctct caccatcccc ttgtctactc tgatgccccc aagatgcaac tgggcagcta 360gttggcccca taattctggg cctttgttgt ttgttttaat tacttgggca tcccaggaag 420ctttccagtg atctcctacc atgggccccc ctcctgggat caagcccctc ccaggccctg 480tccccagccc ctcctgcccc agcccacccg cttgccttgg tgctcagccc tcccattggg 540agcaggtt 548<210> 401<211> 355<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(355)<223> n = A,T,C or G<400> 401actgtttcca tgttatgttt ctacacattg ctacctcagt gctcctggaa acttagcttt 60tgatgtctcc aagtagtcca ccttcattta actctttgaa actgtatcat ctttgccaag 120taagagtggt ggcctatttc agctgctttg acaaaatgac tggctcctga cttaacgttc 180tataaatgaa tgtgctgaag caaagtgccc atggtggcgg cgaagaagan aaagatgtgt 240tttgttttgg actctctgtg gtcccttcca atgctgnggg tttccaacca ggggaagggt 300cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggn tctgc 355<210> 402<211> 407<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (407)<223> n = A,T,C or G<400> 402atggggcaag ctggataaag aaccaagacc cactggagta tgctgtcttc aagaaaccca 60tctcacatgc ggtggcatac ataggctcaa aataaaggaa tggagaaaaa tatttcaagc 120aaatggaaaa cagaaaaaag caggtgttgc actcctactt tctgacaaaa cagactatgc 180gaataaagat aaaaaagaga aggacattac aaaggtggtc ctgacctttg ataaatctca 240ttgcttgata ccaacctggg ctgttttaat tgcccaaacc aaaaggataa tttgctgagg 300ttgtggagct tctcccctgc agagagtccc tgatctccca aaatttggtt gagatgtaag 360gntgattttg ctgacaactc cttttctgaa gttttactca tttccaa 407<210> 403<211> 303<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(303)<223> n = A,T,C or G<400> 403cagtatttat agccnaactg aaaagctagt agcaggcaag tctcaaatcc aggcaccaaa 60tcctaagcaa gagccatggc atggtgaaaa tgcaaaagga gagtctggcc aatctacaaa 120tagagaacaa gacctactca gtcatgaaca aaaaggcaga caccaacatg gatctcatgg 180gggattggat attgtaatta tagagcagga agatgacagt gatcgtcatt tggcacaaca 240tcttaacaac gaccgaaacc cattatttac ataaacctcc attcggtaac catgttgaaa 300gga 303<210> 404<211> 225<212> DNA<213> Homo sapiens<400> 404aagtgtaact tttaaaaatt tagtggattt tgaaaattct tagaggaaag taaaggaaaa 60attgttaatg cactcattta cctttacatg gtgaaagttc tctcttgatc ctacaaacag 120acattttcca ctcgtgtttc catagttgtt aagtgtatca gatgtgttgg gcatgtgaat 180ctccaagtgc ctgtgtaata aataaagtat ctttatttca ttcat 225<210> 405<211> 334<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(334)<223> n = A,T,C or G<400> 405gagctgttat actgtgagtt ctactaggaa atcatcaaat ctgagggttg tctggaggac 60ttcaatacac ctccccccat agtgaatcag cttccagggg gtccagtccc tctccttact 120tcatccccat cccatgccaa aggaagaccc tccctccttg gctcacagcc ttctctaggc 180ttcccagtgc ctccaggaca gagtgggtta tgttttcagc tccatccttg ctgtgagtgt 240ctggtgcggt tgtgcctcca gcttctgctc agtgcttcat ggacagtgtc cagcccatgt 300cactctccac tctctcanng tggatcccac ccct 334<210> 406<211> 216<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(216)<223> n = A,T,C or G<400> 406tttcatacct aatgagggag ttganatnac atnnaaccag gaaatgcatg gatctcaang 60gaaacaaaca cccaataaac tcggagtggc agactgacaa ctgtgagaca tgcacttgct 120acnaaacaca aatttnatgt tgcacccttg tttctacacc tgtgggttat gacaaagaca 180actgccaaag aatnttcaag aaggaggact gccant 216<210> 407<211> 413<212> DNA<213> Homo sapiens<400> 407gctgacttgc tagtatcatc tgcattcatt gaagcacaag aacttcatgc cttgactcat 60gtaaatgcaa taggattaaa aaataaattt gatatcacat ggaaacagac aaaaaatatt 120gtacaacatt gcacccagtg tcagattcta cacctggcca ctcaggaagc aagagttaat 180cccagaggtc tatgtcctaa tgtgttatgg caaatggatg tcatgcacgt accttcattt 240ggaaaattgt catttgtcca tgtgacagtt gatacttatt cacatttcat atgggcaacc 300tgccagacag gagaaagtct tcccatgtta aaagacattt attatcttgt tttcctgtca 360tgggagttcc agaaaaagtt aaaacagaca atgggccagg ttctgtagta aag 413<210> 408<211> 183<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(183)<223> n = A,T,C or G<400> 408ggagctngcc ctcaattcct ccatntctat gttancatat ttaatgtctt ttgnnattaa 60tncttaacta gttaatcctt aaagggctan ntaatcctta actagtccct ccattgtgag 120cattatcctt ccagtattcn ccttctnttt tatttactcc ttcctggcta cccatgtact 180ntt 183<210> 409<211> 250<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1) ... (250)<223> n = A,T,C or G<400> 409cccacgcatg ataagctctt tatttctgta agtcctgcta ggaaatcatc aaatctgacg 60gtggtttggg ggacctgaac aaacctcctg taattaatca gctttcagtt tctcccccta 120gtccctcctt caacaacata ggaggatcct ccccttcttt ctgctcacgg ccttatctag 180gcttcccagt gcccccagga cagcgtgggc tatgtttaca gcgcntcctt gctggggggg 240ggccntatgc 250<210> 410<211> 306<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(306)<223> n = A,T,C or G<400> 410ggctggtttg caagaatgaa atgaatgatt ctacagctag gacttaacct tgaaatggaa 60agtcttgcaa tcccatttgc aggatccgtc tgtgcacatg cctctgtaga gagcagcatt 120cccagggacc ttggaaacag ttggcactgt aaggtgcttg ctccccaaga cacatcctaa 180aaggtgttgt aatggtgaaa accgcttcct tctttattgc cccttcttat ttatgtgaac 240nactggttgg ctttttttgn atctttttta aactggaaag ttcaattgng aaaatgaata 300tcntgc 306<210> 411<211> 261<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(261)<223> n = A,T,C or G<400> 411agagatattn cttaggtnaa agttcataga gttcccatga actatatgac tggccacaca 60ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120tttaaatgtc tgaaatggaa cagatttcaa aaaaaaaccc cacaatctag ggtgggaaca 180aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc 240cttctctcaa ggngaggcaa a 261<210> 412<211> 241<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(241)<223> n = A,T,C or G<400> 412gttcaatgtt acctgacatt tctacaacac cccactcacc gatgtattcg ttgcccagtg 60ggaacatacc agcctgaatt tggaaaaaat aattgtgttt cttgcccagg aaatactacg 120actgactttg atggctccac aaacataacc cagtgtaaaa acagaagatg tggaggggag 180ctgggagatt tcactgggta cattgaattc ccaaactacc cangcaatta cccagccaac 240a 241<210> 413<211> 231<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(231)<223> n = A,T,C or G<400> 413aactcttaca atccaagtga ctcatctgtg tgcttgaatc ctttccactg tctcatctcc 60ctcatccaag tttctagtac cttctctttg ttgtgaagga taatcaaact gaacaacaaa 120aagtttactc tcctcatttg gaacctaaaa actctcttct tcctgggtct gagggctcca 180agaatccttg aatcanttct cagatcattg gggacaccan atcaggaacc t 231<210> 414<211> 234<212> DNA<213> Homo sapiens<400> 414actgtccatg aagcactgag cagaagctgg aggcacaacg caccagacac tcacagcaag 60gatggagctg aaaacataac ccactctgtc ctggaggcac tgggaagcct agagaaggct 120gtgagccaag gagggaggt cttcctttgg catgggatgg ggatgaagta aggagaggga 180ctggaccccc tggaagctga ttcactatgg ggggaggtgt attgaagtcc tcca 234<210> 415<211> 217<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(217)<223> n = A,T,C or G<400> 415gcataggatt aagactgagt atcttttcta cattctttta actttctaag gggcacttct 60caaaacacag accaggtagc aaatctccac tgctctaagg ntctcaccac cactttctca 120cacctagcaa tagtagaatt cagtcctact tctgaggcca gaagaatggt tcagaaaaat 180antggattat aaaaaataac aattaagaaa aataatc 217<210> 416<211> 213<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(213)<223> n = A,T,C or G<400> 416atgcatatnt aaagganact gcctcgcttt tagaagacat ctggnctgct ctctgcatga 60ggcacagcag taaagctctt tgattcccag aatcaagaac tctccccttc agactattac 120cgaatgcaag gtggttaatt gaaggccact aattgatgct caaatagaag gatattgact 180atattggaac agatggagtc tctactacaa aag 213<210> 417<211> 303<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(303)<223> n = A,T,C or G<400> 417nagtcttcag gcccatcagg gaagttcaca ctggagagaa gtcatacata tgtactgtat 60gtgggaaagg ctttactctg agttcaaatc ttcaagccca tcagagagtc cacactggag 120agaagccata caaatgcaat gagtgtggga agagcttcag gagggattcc cattatcaag 180ttcatctagt ggtccacaca ggagagaaac cctataaatg tgagatatgt gggaagggct 240tcantcaaag ttcgtatctt caaatccatc ngaaggncca cagtatanan aaacctttta 300agt 303<210> 418<211> 328<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(328)<223> n = A,T,C or G<400> 418tttttggcgg tggtggggca gggacgggac angagtctca ctctgttgcc caggctggag 60tgcacaggca tgatctcggc tcactacaac ccctgcctcc catgtccaag cgattcttgt 120gcctcagcct tccctgtagc tagaattaca ggcacatgcc accacaccca gctagttttt 180gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcaa actcctnacc 240tcagnggtca ggctggtctc aaactcctga cctcaagtga tctgcccacc tcagcctccc 300aaagtgctan gattacaggc cgtgagcc 328<210> 419<211> 389<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(389)<223> n = A,T,C or G<400> 419cctcctcaag acggcctgtg gtccgcctcc cggcaaccaa gaagcctgca gtgccatatg 60acccctgagc catggactgg agcctgaaag gcagcgtaca ccctgctcct gatcttgctg 120cttgtttcct ctctgtggct ccattcatag cacagttgtt gcactgaggc ttgtgcaggc 180cgagcaaggc caagctggct caaagagcaa ccagtcaact ctgccacggt gtgccaggca 240ccggttctcc agccaccaac ctcactcgct cccgcaaatg gcacatcagt tcttctaccc 300taaaggtagg accaaagggc atctgctttt ctgaagtcct ctgctctatc agccatcacg 360tggcagccac tcnggctgtg tcgacgcgg 389<210> 420<211> 408<212> DNA<213> Homo sapiens<400> 420gttcctccta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360acgttgaccg gactttgatg aagtgctatg acaaacctgg caagcccg 408<210> 421<211> 352<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(352)<223> n = A,T,C or G<400> 421gctcaaaaat ctttttactg atnggcatgg ctacacaatc attgactatt acggaggcca 60gaggagaatg aggcctggcc tgggagccct gtgcctacta naagcacatt agattatcca 120ttcactgaca gaacaggtct tttttgggtc cttcttctcc accacnatat acttgcagtc 180ctccttcttg aagattcttt ggcagttgtc tttgtcataa cccacaggtg tagaaacaag 240ggtgcaacat gaaatttctg tttcgtagca agtgcatgtc tcacaagttg gcangtctgc 300cactccgagt ttattgggtg tttgtttcct ttgagatcca tgcatttcct gg 352<210> 422<211> 337<212> DNA<213> Homo sapiens<400> 422atgccaccat gctggcaatg cagcgggcgg tcgaaggcct gcatatccag cccaagctgg 60cgatgatcga cggcaaccgt tgcccgaagt tgccgatgcc agccgaagcg gtggtcaagg 120gcgatagcaa ggtgccggcg atcgcggcgg cgtcaatcct ggccaaggtc agccgrgatc 180gtgaaatggc agctgtcgaa ttgatctacc cgggttatgg catcggcggg cataagggct 240atccgacacc ggtgcacctg gaagccttgc agcggctggg gccgacgccg attcaccgac 300gcttcttccg ccggtacggc tggcctatga aaattat 337<210> 423<211> 310<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (310)<223> n = A,T,C or G<400> 423gctcaaaaat ctttttactg atatggcatg gctacacaat cattgactat tagaggccag 60aggagaatga ggcctggcct gggagccctg tgcctactan aagcncatta gattatccat 120tcactgacag aacaggtctt ttttgggtcc ttcttctcca ccacgatata cttgcagtcc 180tccttcttga agattctttg gcagttgtct ttgtcataac ccacaggtgt anaaacaagg 240gtgcaacatg aaatttctgt ttcgtagcaa gtgcatgtct cacagttgtc aagtctgccc 300tccgagttta 310<210> 424<211> 370<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(370)<223> n = A,T,C or G<400> 424gctcaaaaat ctttttactg ataggcatgg ctacacaatc attgactatt agaggccaga 60ggagaatgag gcctggcctg ggagccctgt gcctactaga agcacattag attatccatt 120cactgacaga acaggtcttt tttgggtcct tcttctccac cacgatatac ttgcagtcct 180ccttcttgaa gattctttgg cagttgtctt tgtcataacc cacaggtgta gaaacatcct 240ggttgaatct cctggaactc cctcattagg tatgaaatag catgatgcat tgcataaagt 300cacgaaggtg gcaaagatca caacgctgcc cagganaaca ttcattgtga taagcaggac 360tccgtcgacg 370<210> 425<211> 216<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(216)<223> n = A,T,C or G<400> 425aattgctatn ntttattttg ccactcaaaa taattaccaa aaaaaaaaaa tnttaaatga 60taacaacnca acatcaaggn aaananaaca ggaatggntg accntgcata aatnggccga 120anattatcca ttatnttaag ggttgacttc aggntacagc acacagacaa acatgcccag 180gaggntntca ggaccgctcg atgtnttntg aggagg 216<210> 426<211> 596<212> DNA<213> Homo sapiens<400> 426cttccagtga ggataaccct gttgccccgg gccgaggttc tccattaggc tctgattgat 60tggcagtcag tgatggaagg gtgttctgat cattccgact gccccaaggg tcgctggcca 120gctctctgtt ttgctgagtt ggcagtagga cctaatttgt taattaagag tagatggtga 180gctgtccttg tattttgatt aacctaatgg ccttcccagc acgactcgga ttcagctgga 240gacatcacgg caacttttaa tgaaatgatt tgaagggcca ttaagaggca cttcccgtta 300ttaggcagtt catctgcact gataacttct tggcagctga gctggtcgga gctgtggccc 360aaacgcacac ttggcttttg gttttgagat acaactctta atcttttagt catgcttgag 420ggtggatggc cttttcagct ttaacccaat ttgcactgcc ttggaagtgt agccaggaga 480atacactcat atactcgtgg gcttagaggc cacagcagat gtcattggtc tactgcctga 540gtcccgctgg tcccatccca ggaccttcca tcggcgagta cctgggagcc cgtgct 596<210> 427<211> 107<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(107)<223> n = A,T,C or G<400> 427gaagaattca agttaggttt attcaaaggg cttacngaga atcctanacc caggncccag 60cccgggagca gccttanaga gctcctgttt gactgcccgg ctcagng 107<210> 428<211> 38<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(38)<223> n = A,T,C or G<400> 428gaacttccna anaangactt tattcactat tttacatt 38<210> 429<211> 544<212> DNA<213> Homo sapiens<400> 429ctttgctgga cggaataaaa gtggacgcaa gcatgacctc ctgatgaggg cgctgcattt 60attgaagagc ggctgcagcc ctgcggttca gattaaaatc cgagaattgt atagacgccg 120atatccacga actcttgaag gactttctga tttatccaca atcaaatcat cggttttcag 180tttggatggt ggctcatcac ctgtagaacc tgacttggcc gtggctggaa tccactcgtt 240gccttccact tcagttacac ctcactcacc atcctctcct gttggttctg tgctgcttca 300agatactaag cccacatttg agatgcagca gccatctccc ccaattcctc ctgtccatcc 360tgatgtgcag ttaaaaaatc tgccctttta tgatgtcctt gatgttctca tcaagcccac 420gagtttagtt caaagcagta ttcagcgatt tcaagagaag ttttttattt ttgctttgac 480acctcaacaa gttagagaga tatgcatatc cagggatttt ttgccaggtg gtaggagaga 540ttat 544<210> 430<211> 507<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(507)<223> n = A,T,C or G<400> 430cttatcncaa tggggctccc aaacttggct gtgcagtgga aactccgggg gaattttgaa 60gaacactgac acccatcttc caccccgaca ctctgattta attgggctgc agtgagaaca 120gagcatcaat ttaaaaagct gcccagaatg ttntcctggg cagcgttgtg atctttgccn 180ccttcgtgac tttatgcaat gcatcatgct atttcatacc taatgaggga gttccaggag 240attcaaccag gatgtttcta cncctgtggg ttatgacaaa gacaactgcc aaagaatntt 300caagaaggag gactgcaagt atatcgtggt ggagaagaag gacccaaaaa agacctgttc 360tgtcagtgaa tggataatct aatgtgcttc tagtaggcac agggctccca ggccaggcct 420cattctcctc tggcctctaa tagtcaatga ttgtgtagcc atgcctatca gtaaaaagat 480ttttgagcaa aaaaaaaaaa aaaaaaa 507<210> 431<211> 392<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(392)<223> n = A,T,C or G<400> 431gaaaattcag aatggataaa aacaaatgaa gtacaaaata tttcagattt acatagcgat 60aaacaagaaa gcacttatca ggaggactta caaatggaag tacactctan aaccatcatc 120tatcatggct aaatgtgaga ttagcacagc tgtattattt gtacattgca aacacctaga 180aagagatggg aaacaaaatc ccaggagttt tgtgtgtgga gtcctgggtt ttccaacaga 240catcattcca gcattctgag attagggnga ttggggatca ttctggagtt ggaatgttca 300acaaaagtga tgttgttagg taaaatgtac aacttctgga tctatgcaga cattgaaggt 360gcaatgagtc tggcttttac tctgctgttt ct 392<210> 432<211> 387<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(387)<223> n = A,T,C or G<400> 432ggtatccnta cataatcaaa tatagctgta gtacatgttt tcattggngt agattaccac 60aaatgcaagg caacatgtgt agatctcttg tcttattctt ttgtctataa tactgtattg 120ngtagtccaa gctctcggna gtccagccac tgngaaacat gctcccttta gattaacctc 180gtggacnctn ttgttgnatt gtctgaactg tagngccctg tattttgctt ctgtctgnga 240attctgttgc ttctggggca tttccttgng atgcagagga ccaccacaca gatgacagca 300atctgaattg ntccaatcac agctgcgatt aagacatact gaaatcgtac aggaccggga 360acaacgtata gaacactgga gtccttt 387<210> 433<211> 281<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (281)<223> n = A,T,C or G<400> 433ttcaactagc anagaanact gcttcagggn gtgtaaaatg aaaggcttcc acgcagttat 60ctgattaaag aacactaaga gagggacaag gctagaagcc gcaggatgtc tacactatag 120caggcnctat ttgggttggc tggaggagct gtggaaaaca tggagagatt ggcgctggag 180atcgccgtgg ctattcctcn ttgntattac accagngagg ntctctgtnt gcccactggt 240tnnaaaaccg ntatacaata atgatagaat aggacacaca t 281<210> 434<211> 484<212> DNA<213> Homo sapiens<400> 434ttttaaaata agcatttagt gctcagtccc tactgagtac tctttctctc ccctcctctg 60aatttaattc tttcaacttg caatttgcaa ggattacaca tttcactgtg atgtatattg 120tgttgcaaaa aaaaaaaagt gtctttgttt aaaattactt ggtttgtgaa tccatcttgc 180tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa acatctgaag 240agctagtcta tcagcatctg acaggtgaat tggatggttc tcagaaccat ttcacccaga 300cagcctgttt ctatcctgtt taataaatta gtttgggttc tctacatgca taacaaaccc 360tgctccaatc tgtcacataa aagtctgtga cttgaagttt agtcagcacc cccaccaaac 420tttatttttc tatgtgtttt ttgcaacata tgagtgtttt gaaaataaag tacccatgtc 480ttta 484<210> 435<211> 424<212> DNA<213> Homo sapiens<400> 435gcgccgctca gagcaggtca ctttctgcct tccacgtcct ccttcaagga agccccatgt 60gggtagcttt caatatcgca ggttcttact cctctgcctc tataagctca aacccaccaa 120cgatcgggca agtaaacccc ctccctcgcc gacttcggaa ctggcgagag ttcagcgcag 180atgggcctgt ggggaggggg caagatagat gagggggagc ggcatggtgc ggggtgaccc 240cttggagaga ggaaaaaggc cacaagaggg gctgccaccg ccactaacgg agatggccct 300ggtagagacc tttgggggtc tggaacctct ggactcccca tgctctaact cccacactct 360gctatcagaa acttaaactt gaggattttc tctgtttttc actcgcaata aattcagagc 420aaac 424<210> 436<211> 667<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(667)<223> n = A,T,C or G<400> 436accttgggaa nactctcaca atataaaggg tcgtagactt tactccaaat tccaaaaagg 60tctggccat gtaatcctga aagttttccc aaggtagcta taaaatcctt ataagggtgc 120agcctcttct ggaattcctc tgatttcaaa gtctcactct caagttcttg aaaacgaggg 180cagttcctga aaggcaggta tagcaactga tcttcagaaa gaggaactgt gtgcaccggg 240atgggctgcc agagtaggat aggattccag atgctgacac cttctggggg aaacagggct 300gcaggtttg tcatagcact catcaaagtc cggtcaacgt ctgtgcttcg aatataaacc 360tgttcatgtt tataggactc attcaagaat tttctatatc tctttcttat atactctcca 420agttcataat gctgctccat gcccagctgg gtgagttggc caaatccttg tggccatgag 480gattccttta tggggtcagt gggaaaggtg tcaatgggac ttcggtctcc atgccgaaac 540accaaagtca caaacttcaa ctccttggct agtacacttc ggtctagcca gaaaaaaagc 600agaaacaaga agccaaggct aaggcttgct gccctgccag gaggaggggt gcagctctca 660tgttgag 667<210> 437<211> 693<212> DNA<213> Homo sapiens<400> 437ctacgtctca accctcattt ttaggtaagg aatcttaagt ccaaagatat taagtgactc 60acacagccag gtaaggaaag ctggattggc acactaggac tctaccatac cgggttttgt 120taaagctcag gttaggaggc tgataagctt ggaaggaact tcagacaGct ttttcagatc 180ataaaagata attcttagcc catgttcttc tccagagcag acctgaaatg acagcacagc 240aggtactcct ctattttcac ccctcttgct tctactctct ggcagtcaga cctgtgggag 300gccatgggag aaagcagctc tctggatgtt tGtacagatc atggactatt ctctgtggac 360catttctcca gGttacccta ggtgtcacta ttggggggac agccagcatc tttagctttc 420atttgagttt ctgtctgtct tcagtagagg aaacttttgc tcttcacact tcacatctga 480acacctaact gctgttgctc ctgaggtggt Gaaagacaga tatagagctt acagtattta 540tcctatttct aggcactgag Ggctgtgggg taccttgtgg tgccaaaaca gatcctgttt 600taaggacatg ttgcttcaga gatgtctgta actatctggg ggctctgttg gctctttacc 660ctgcatcatg tgctctcttg gctgaaaatg acc 693<210> 438<211> 360<212> DNA<213> Homo sapiens<400> 438ctgcttatca caatgaatgt tctcctgggc agcgttgtga tctttgccac cttcgtgact 60ttatgcaatg catcatgcta tttcatacct aatgagggag ttccaggaga ttcaaccagg 120atgtttctac acctgtgggt tatgacaaag acaactgcca aagaatcttc aagaaggagg 180actgcaagta tatctggtgg agaagaagga cccaaaaaag acctgttctg tcagtgaatg 240gataatctaa tgtgcttcta gtaggcacag ggctcccagg ccaggcctca ttctcctctg 300gcctctaata gtcaataatt gtgtagccat gcctatcagt aaaaagattt ttgagcaaac 360<210> 439<211> 431<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(431)<223> n = A,T,C or G<400> 439gttcctnnta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360acgttgaccg gactttgatg agtgctatga caaacctggc agcccgtcga cgcggccgcg 420aatttagtag t 431<210> 440<211> 523<212> DNA<213> Homo sapiens<400> 440agagataaag cttaggtcaa agttcataga gttcccatga actatatgac tggccacaca 60ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120tttaaatgtc tgaaatggaa cagatttcaa aaaaaaaccc cacaatctag ggtgggaaca 180aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc 240cttctctcaa ggagaggcaa agaaaggaga tacagtggag acatctggaa agttttctcc 300actggaaaac tgctactatc tgtttttata tttctgttaa aatatatgag gctacagaac 360taaaaattaa aacctctttg tgtcccttgg tcctggaaca tttatgttcc ttttaaagaa 420acaaaaatca aactttacag aaagatttga tgtatgtaat acatatagca gctcttgaag 480tatatatatc atagcaaata agtcatctga tgagaacaag cta 523<210> 441<211> 430<212> DNA<213> Homo sapiens<400> 441gttcctccta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360acgttgacg gactttgatg agtgctatga caaacctggc agcccgtcga cgcggccgcg 420aatttagtag 430<210> 442<211> 362<212> DNA<213> Homo sapiens<400> 442ctaaggaatt agtagtgttc ccatcacttg tttggagtgt gctattctaa aagattttga 60tttcctggaa tgacaattat attttaactt tggtggggga aagagttata ggaccacagt 120cttcacttct gatacttgta aattaatctt ttattgcact tgttttgacc attaagctat 180atgtttagaa atggtcattt tacggaaaaa ttagaaaaat tctgataata gtgcagaata 240aatgaattaa tgttttactt aatttatatt gaactgtcaa tgacaaataa aaattctttt 300tgattatttt ttgttttcat ttaccagaat aaaaactaag aattaaaagt ttgattacag 360tc 362<210> 443<211> 624<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(624)<223> n = A,T,C or G<400> 443tttttttttt gcaacacaat atacatcaca gtgaaatgtg taatccttgc aaattgcaag 60ttgaaagaat taaattcaga ggaggggaga gaaagagtac tcagtaggga ctgagcacta 120aatgcttatt ttaaaagaaa tgtaaagagc agaaagcaat tcaggctacc ctgccttttg 180tgctggctag tactccggtc ggtgtcagca gcacgtggca ttgaacattg caatgtggag 240cccaaaccac agaaaatggg gtgaaattgg ccaactttct attaacttgg cttcctgttt 300tataaaatat tgtgaataat atcacctact tcaaagggca gttatgaggc ttaaatgaac 360taacgcctac aaaacactta aacatagata acataggtgc aagtactatg tatctggtac 420atggtaaaca tccttattat taaagtcaac gctaaaatga atgtgtgtgc atatgctaat 480agtacagaga gagggcactt aaaccaacta agggcctgga gggaaggttt cctggaaaga 540ngatgcttgt gctgggtcca aatcttggtc tactatgacc ttggccaaat tatttaaact 600ttgtccctat ctgctaaaca gatc 624<210> 444<211> 425<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(425)<223> n = A,T,C or G<400> 444gcacatcatt nntcttgcat tctttgagaa taagaagatc agtaaatagt tcagaagtgg 60gaagctttgt ccaggcctgt gtgtgaaccc aatgttttgc ttagaaatag aacaagtaag 120ttcattgcta tagcataaca caaaatttgc ataagtggtg gtcagcaaat ccttgaatgc 180tgcttaatgt gagaggttgg taaaatcctt tgtgcaacac tctaactccc tgaatgtttt 240gctgtgctgg gacctgtgca tgccagacaa ggccaagctg gctgaaagag caaccagcca 300cctctgcaat ctgccacctc ctgctggcag gatttgtttt tgcatcctgt gaagagccaa 360ggaggcacca gggcataagt gagtagactt atggtcgacg cggccgcgaa tttagtagta 420gtaga 425<210> 445<211> 414<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(414)<223> n = A,T,C or G<400> 445catgtttatg nttttggatt actttgggca cctagtgttt ctaaatcgtc tatcattctt 60ttctgttttt caaaagcaga gatggccaga gtctcaacaa actgtatctt caagtctttg 120tgaaattctt tgcatgtggc agattattgg atgtagtttc ctttaactag catataaatc 180tggtgtgttt cagataaatg aacagcaaaa tgtggtggaa ttaccatttg gaacattgtg 240aatgaaaaat tgtgtctcta gattatgtaa caaataacta tttcctaacc attgatcttt 300ggatttttat aatcctactc acaaatgact aggctctcc tcttgtattt tgaagcagtg 360tgggtgctgg attgataaaa aaaaaaaaag tcgacgcggc cgcgaattta gtag 414<210> 446<211> 631<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(631)<223> n = A,T,C or G<400> 446acaaattaga anaaagtgcc agagaacacc acataccttg tccggaacat tacaatggct 60tctgcatgca tgggaagtgt gagcattcta tcaatatgca ggagccatct tgcaggtgtg 120atgctggtta tactggacaa cactgtgaaa aaaaggacta cagtgttcta tacgttgttc 180ccggtcctgt acgatttcag tatgtcttaa tcgcagctgt gattggaaca attcagattg 240ctgtcatctg tgtggtggtc ctctgcatca caagggccaa actttaggta atagcattgg 300actgagattt gtaaactttc caaccttcca ggaaatgccc cagaagcaac agaattcaca 360gacagaagca aaatacaggg cactacagtt cagacaatac aacaagagcg tccacgaggt 420taatctaaag ggagcatgtt tcacagtggc tggactaccg agagcttgga ctacacaata 480cagtattata gacaaaagaa taagacaaga gatctacaca tgttgccttg catttgtggt 540aatctacacc aatgaaaaca tgtactacag ctatatttga ttatgtatgg atatatttga 600aatagtatac attgtcttga tgttttttct g 631<210> 447<211> 585<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(585)<223> n = A,T,C or G<400> 447ccttgggaaa antntcacaa tataaagggt cgtagacttt actccaaatt ccaaaaaggt 60cctggccatg taatcctgaa agttttccca aggtagctat aaaatcctta taagggtgca 120gcctcttctg gaattcctct gatttcaaag tctcactctc aagttcttga aaacgagggc 180agttcctgaa aggcaggtat agcaactgat cttcagaaag aggaactgtg tgcaccggga 240tgggctgcca gagtaggata ggattccaga tgctgacacc ttctgggga aacagggctg 300ccaggtttgt catagcactc atcaaagtcc ggtcaacgtc tgtgcttcga atataaacct 360gttcatgttt ataggactca ttcaagaatt ttctatatct ctttcttata tactctccaa 420gttcataatg ctgctccatg cccagctggg tgagttggcc aaatccttgt ggccatgagg 480attcctttat ggggtcagtg ggaaaggtgt caatgggact tcggtctcca tgccgaaaca 540ccaaagtcac aaacttcaac tccttggcta gtacacttcg gtcta 585<210> 448<211> 93<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(93)<223> n = A,T,C or G<400> 448tgctcgtggg tcattctgan nnccgaactg accntgccag ccctgccgan gggccnccat 60ggctccctag tgccctggag agganggggc tag 93<210> 449<211> 706<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(706)<223> n = A,T,C or G<400> 449ccaagttcat gctntgtgct ggacgctgga cagggggcaa aagcnnttgc tcgtgggtca 60ttctgancac cgaactgacc atgccagccc tgccgatggt cctccatggc tccctagtgc 120cctggagagg aggtgtctag tcagagagta gtcctggaag gtggcctctg ngaggagcca 180cggggacagc atcctgcaga tggtcgggcg cgtcccattc gccattcagg ctgcgcaact 240gttgggaagg gcgatcggtg cgggcctctt cgctattacg ccagctggcg aaaggggat 300gtgctgcaag gcgattaagt tgggtaacgc cagggttttc ccagtcncga cgttgtaaaa 360cgacggccag tgaattgaat ttaggtgacn ctatagaaga gctatgacgt cgcatgcacg 420cgtacgtaag cttggatcct ctagagcggc cgcctactac tactaaattc gcggccgcgt 480cgacgtggga tccncactga gagagtggag agtgacatgt gctggacnct gtccatgaag 540cactgagcag aagctggagg cacaacgcnc cagacactca cagctactca ggaggctgag 600aacaggttga acctgggagg tggaggttgc aatgagctga gatcaggccn ctgcncccca 660gcatggatga cagagtgaaa ctccatctta aaaaaaaaaa aaaaaa 706<210> 450<211> 493<212> DNA<213> Homo sapiens<400> 450gagacggagt gtcactctgt tgcccaggct ggagtgcagc aagacactgt ctaagaaaaa 60acagttttaa aaggtaaaac aacataaaaa gaaatatcct atagtggaaa taagagagtc 120aaatgaggct gagaacttta caaagggatc ttacagacat gtcgccaata tcactgcatg 180agcctaagta taagaacaac ctttggggag aaaccatcat ttgacagtga ggtacaattc 240caagtcaggt agtgaaatgg gtggaattaa actcaaatta atcctgccag ctgaaacgca 300agagacactg tcagagagtt aaaaagtgag ttctatccat gaggtgattc cacagtcttc 360tcaagtcaac acatctgtga actcacagac caagttctta aaccactgtt caaactctgc 420tacacatcag aatcacctgg agagctttac aaactcccat tgccgagggt cgacgcggcc 480gcgaatttag tag 493<210> 451<211> 501<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(501)<223> n = A,T,C or G<400> 451gggcgcgtcc cattcgccat tcaggctgcg caactgttgg gaagggcgat cggtgcgggc 60ctcttcgcta ttacgccagc tggcgaaagg gggatgtgct gcaaggcgat taagttgggt 120aacgccaggg ttttcccagt cncgacgttg taaaacgacg gccagtgaat tgaatttagg 180tgacnctata gaagagctat gacgtcgcat gcacgcgtac gtaagcttgg atcctctaga 240gcggccgcct actactacta aattcgcggc cgcgtcgacg tgggatccnc actgagagag 300tggagagtga catgtgctgg acnctgtcca tgaagcactg agcagaagct ggaggcacaa 360cgcnccagac actcacagct actcaggagg ctgagaacag gttgaacctg ggaggtggag 420gttgcaatga gctgagatca ggccnctgcn ccccagcatg gatgacagag tgaaactcca 480tcttaaaaaa aaaaaaaaaa a 501<210> 452<211> 51<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(51)<223> n = A,T,C or G<400> 452agacggtttc accnttacaa cnccttttag gatgggnntt ggggagcaag c 51<210> 453<211> 317<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(317)<223> n = A,T,C or G<400> 453tacatcttgc tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa 60acatctgaag agctagtcta tcagcatctg gcaagtgaat tggatggttc tcagaaccat 120ttcacccana cagcctgttt ctatcctgtt taataaatta gtttgggttc tctacatgca 180taacaaaccc tgctccaatc tgtcacataa aagtctgtga cttgaagttt antcagcacc 240cccaccaaac tttatttttc tatgtgtttt ttgcaacata tgagtgtttt gaaaataagg 300tacccatgtc tttatta 317<210> 454<211> 231<212> DNA<213> Homo sapiens<400> 454ttcgaggtac aatcaactct cagagtgtag tttccttcta tagatgagtc agcattaata 60taagccacgc cacgctcttg aaggagtctt gaattctcct ctgctcactc agtagaacca 120agaagaccaa attcttctgc atcccagctt gcaaacaaaa ttgttcttct aggtctccac 180ccttcctttt tcagtgttcc aaagctcctc acaatttcat gaacaacagc t 231<210> 455<211> 231<212> DNA<213> Homo sapiens<400> 455taccaaagag ggcataataa tcagtctcac agtagggttc accatcctcc aagtgaaaaa 60cattgttccg aatgggcttt ccacaggcta cacacacaaa acaggaaaca tgccaagttt 120gtttcaacgc attgatgact tctccaagga tcttcctttg gcatcgacca cattcagggg 180caaagaattt ctcatagcac agctcacaat acagggctcc tttctcctct a 231<210> 456<211> 231<212> DNA<213> Homo sapiens<400> 456ttggcaggta cccttacaaa gaagacacca taccttatgc gttattaggt ggaataatca 60ttccattcag tattatcgtt attattcttg gagaaaccct gtctgtttac tgtaaccttt 120tgcactcaaa ttcctttatc aggaataact acatagccac tatttacaaa gccattggaa 180cctttttatt tggtgcagct gctagtcagt ccctgactga cattgccaag t 231<210> 457<211> 231<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(231)<223> n = A,T,C or G<400> 457cgaggtaccc aggggtctga aaatctctnn tttantagtc gatagcaaaa ttgttcatca 60gcattcctta atatgatctt gctataatta gatttttctc cattagagtt catacagttt 120tatttgattt tattagcaat ctctttcaga agacccttga gatcattaag ctttgtatcc 180agttgtctaa atcgatgcct catttcctct gaggtgtcgc tggcttttgt g 231<210> 458<211> 231<212> DNA<213> Homo sapiens<400> 458aggtctggtt ccccccactt ccactcccct ctactctctc taggactggg ctgggccaag 60agaagagggg tggttaggga agccgttgag acctgaagcc ccaccctcta ccttccttca 120acaccctaac cttgggtaac agcatttgga attatcattt gggatgagta gaatttccaa 180ggtcctgggt taggcatttt ggggggccag accccaggag aagaagattc t 231<210> 459<211> 231<212> DNA<213> Homo sapiens<400> 459ggtaccgagg ctcgctgaca cagagaaacc ccaacgcgag gaaaggaatg gccagccaca 60ccttcgcgaa acctgtggtg gcccaccagt cctaacggga caggacagag agacagagca 120gccctgcact gttttccctc caccacagcc atcctgtccc tcattggctc tgtgctttcc 180actatacaca gtcaccgtcc caatgagaaa caagaaggag caccctccac a 231<210> 460<211> 231<212> DNA<213> Homo sapiens<400> 460gcaggtataa catgctgcaa caacagatgt gactaggaac ggccggtgac atggggaggg 60cctatcaccc tattcttgg ggctgcttct tcacagtgat catgaagcct agcagcaaat 120cccacctccc cacacgcaca cggccagcct ggagcccaca gaagggtcct cctgcagcca 180gtggagttg gtccagcctc cagtccaccc ctaccaggct taaggataga a 231<210> 461<211> 231<212> DNA<213> Homo sapiens<400> 461cgaggtttga gaagctctaa tgtgcagggg agccgagaag caggcggcct agggagggtc 60gcgtgtgctc cagaagagtg tgtgcatgcc agaggggaaa caggcgcctg tgtgtcctgg 120gtggggttca gtgaggagtg ggaaattggt tcagcagaac caagccgttg ggtgaataag 180agggggattc catggcactg atagagccct atagtttcag agctgggaat t 231<210> 462<211> 231<212> DNA<213> Homo sapiens<400> 462aggtaccctc attgtagcca tgggaaaatt gatgttcagt ggggatcagt gaattaaatg 60gggtcatgca agtataaaaa ttaaaaaaaa aagacttcat gcccaatctc atatgatgtg 120gaagaactgt tagagagacc aacagggtag tgggttagag atttccagag tcttacattt 180tctagaggag gtatttaatt tcttctcact catccagtgt tgtatttagg a 231<210> 463<211> 231<212> DNA<213> Homo sapiens<400> 463tactccagcc tggtgacaga gcgagaccct atcaccgccc cccaccccac caaaaaaaaa 60actgagtaga caggtgtcct cttggcatgg taagtcttaa gtcccctccc agatctgtga 120catttgacag gtgtcttttc ctctggacct cggtgtcccc atctgagtga gaaaaggcag 180tggggaggtg gatcttccag tcgaagcggt atagaagccc gtgtgaaaag c 231<210> 464<211> 231<212> DNA<213> Homo sapiens<400> 464gtactctaag attttatcta agttgccttt tctgggtggg aaagtttaac cttagtgact 60aaggacatca catatgaaga atgtttaagt tggaggtggc aacgtgaatt gcaaacaggg 120cctgcttcag tgactgtgtg cctgtagtcc cagctactcg ggagtctgtg tgaggccagg 180ggtgccagcg caccagctag atgctctgta acttctaggc cccattttcc c 231<210> 465<211> 231<212> DNA<213> Homo sapiens<400> 465catgttgttg tagctgtggt aatgctggct gcatctcaga cagggttaac ttcagctcct 60gtggcaaatt agcaacaaat tctgacatca tatttatggt ttctgtatct ttgttgatga 120aggatggcac aatttttgct tgtgttcata atatactcag attagttcag ctccatcaga 180taaactggag acatgcagga cattagggta gtgttgtagc tctggtaatg a 231<210> 466<211> 231<212> DNA<213> Homo sapiens<400> 466caggtacctc tttccattgg atactgtgct agcaagcatg ctctccgggg tttttttaat 60ggccttcgaa cagaacttgc cacataccca ggtataatag tttctaacat ttgcccagga 120cctgtgcaat caaatattgt ggagaattcc ctagctggag aagtcacaaa gactataggc 180aataatggag accagtccca caagatgaca accagtcgtt gtgtgcggct g 231<210> 467<211> 311<212> DNA<213> Homo sapiens<400> 467gtacaccctg gcacagtcca atctgaactg gttcggcact catctttcat gagatggatg 60tggtggcttt tctccttttt catcaagact cctcagcagg gagcccagac cagcctgcac 120tgtgccttaa cagaaggtct tgagattcta agtgggaatc atttcagtga ctgtcatgtg 180gcatgggtct ctgcccaagc tcgtaatgag actatagcaa ggcggctgtg ggacgtcagt 240tgtgacctgc tgggcctccc aatagactaa caggcagtgc cagttggacc caagagaaga 300ctgcagcaga c 311<210> 468<211> 3112<212> DNA<213> Homo sapiens<400> 468cattgtgttg ggagaaaaac agaggggaga tttgtgtggc tgcagccgag ggagaccagg 60aagatctgca tggtgggaag gacctgatga tacagagttt gataggagac aattaaaggc 120tggaaggcac tggatgcctg atgatgaagt ggactttcaa actggggcac tactgaaacg 180atgggatggc cagagacaca ggagatgagt tggagcaagc tcaataacaa agtggttcaa 240cgaggacttg gaattgcatg gagctggagc tgaagtttag cccaattgtt tactagttga 300gtgaatgtgg atgattggat gatcatttct catctctgag cctcaggttc cccatccata 360aaatgggata cacagtatga tctataaagt gggatatagt atgatctact tcactgggtt 420atttgaagga tgaattgaga taatttattt caggtgccta gaacaatgcc cagattagta 480catttggtgg aactgagaaa tggcataaca ccaaatttaa tatatgtcag atgttactat 540gattatcatt caatctcata gttttgtcat ggcccaattt atcctcactt gtgcctcaac 600aaattgaact gttaacaaag gaatctctgg tcctgggtaa tggctgagca ccactgagca 660tttccattcc agttggcttc ttgggtttgc tagctgcatc actagtcatc ttasataaat 720gaagttttaa catttctcca gtgatttttt tatctcacct ttgaagatac tatgttatgt 780gattaaataa agaacttgag aagaacaggt ttcattaaac ataaaatcaa tgtagacgca 840aattttctgg atgggcaata cttatgttca caggaaatgc tttaaaatat gcagaagata 900attaaatggc aatggacaaa gtgaaaaact tagacttttt tttttttttt ggaagtatct 960ggatgttcct tagtcactta aaggagaact gaaaaatagc agtgagttcc acataatcca 1020acctgtgaga ttaaggctct ttgtggggaa ggacaaagat ctgtaaattt acagtttcct 1080tccaaagcca acgtcgaatt ttgaaacata tcaaagctct tcttcaagac aaataatcta 1140tagtacatct ttcttatggg atgcacttat gaaaaatggt ggctgtcaac atctagtcac 1200tttagctctc aaaatggttc attttaagag aaagttttag aatctcatat ttattcctgt 1260ggaaggacag cattgtggct tggactttat aaggtcttta ttcaactaaa taggtgagaa 1320ataagaaagg ctgctgactt taccatctga ggccacacat ctgctgaaat ggagataatt 1380aacatcacta gaaacagcaa gatgacaata taatgtctaa gtagtgacat gtttttgcac 1440atttccagcc cctttaaata tccacacaca caggaagcac aaaaggaagc acagagatcc 1500ctgggagaaa tgcccggccg ccatcttggg tcatcgatga gcctcgccct gtgcctggtc 1560ccgcttgtga gggaaggaca ttagaaaatg aattgatgtg ttccttaaag gatgggcagg 1620aaaacagatc ctgttgtgga tatttatttg aacgggatta cagatttgaa atgaagtcac 1680aaagtgagca ttaccaatga gaggaaaaca gacgagaaaa tcttgatggc ttcacaagac 1740atgcaacaaa caaaatggaa tactgtgatg acatgaggca gccaagctgg ggaggagata 1800accacggggc agagggtcag gattctggcc ctgctgccta aactgtgcgt tcataaccaa 1860atcatttcat atttctaacc ctcaaaacaa agctgttgta atatctgatc tctacggttc 1920cttctgggcc caacattctc catatatcca gccacactca tttttaatat ttagttccca 1980gatctgtact gtgacctttc tacactgtag aataacatta ctcattttgt tcaaagaccc 2040ttcgtgttgc tgcctaatat gtagctgact gtttttccta aggagtgttc tggcccaggg 2100gatctgtgaa caggctggga agcatctcaa gatctttcca gggttatact tactagcaca 2160cagcatgatc attacggagt gaattatcta atcaacatca tcctcagtgt ctttgcccat 2220actgaaattc atttcccact tttgtgccca ttctcaagac ctcaaaatgt cattccatta 2280atatcacagg attaactttt ttttttaacc tggaagaatt caatgttaca tgcagctatg 2340ggaatttaat tacatatttt gttttccagt gcaaagatga ctaagtcctt tatccctccc 2400ctttgtttga ttttttttcc agtataaagt taaaatgctt agccttgtac tgaggctgta 2460tacagccaca gcctctcccc atccctccag ccttatctgt catcaccatc aacccctccc 2520atgcacctaa acaaaatcta acttgtaatt ccttgaacat gtcaggcata cattattcct 2580tctgcctgag aagctcttcc ttgtctctta aatctagaat gatgtaaagt tttgaataag 2640ttgactatct tacttcatgc aaagaaggga cacatatgag attcatcatc acatgagaca 2700gcaaatacta aaagtgtaat ttgattataa gagtttagat aaatatatga aatgcaagag 2760ccacagaggg aatgtttatg gggcacgttt gtaagcctgg gatgtgaagc aaaggcaggg 2820aacctcatag tatcttatat aatatacttc atttctctat ctctatcaca atatccaaca 2880agcttttcac agaattcatg cagtgcaaat ccccaaaggt aacctttatc catttcatgg 2940tgagtgcgct ttagaatttt ggcaaatcat actggtcact tatctcaact ttgagatgtg 3000tttgtccttg tagttaattg aaagaaatag ggcactcttg tgagccactt tagggttcac 3060tcctggcaat aaagaattta caaagagcaa aaaaaaaaaa aaaaaaaaaa aa 3112<210> 469<211> 2229<212> DNA<213> Homo sapiens<400> 469agctctttgt aaattcttta ttgccaggag tgaaccctaa agtggctcac aagagtgccc 60tatttctttc aattaactac aaggacaaac acatctcaaa gttgagataa gtgaccagta 120tgatttgcca aaattctaaa gcgcactcac catgaaatgg ataaaggtta cctttgggga 180tttgcactgc atgaattctg tgaaaagctt gttggatatt gtgatagaga tagagaaatg 240aagtatatta tataagatac tatgaggttc cctgcctttg cttcacatcc caggcttaca 300aacgtgcccc ataaacattc cctctgtggc tcttgcattt catatattta tctaaactct 360tataatcaaa tacactttta gtatttgctg tctcatgtga tgatgaatct catatgtgtc 420ccttctttgc atgaagtaag atagtcaact tattcaaaac tttacatcat tctagattta 480agagacaagg aagagcttct caggcagaag gaataatgta tgcctgacat gttcaaggaa 540ttacaagtta gattttgttt aggtgcatgg gaggggttga tggtgatgac agataaggct 600ggagggatgg ggagaggctg tggctgtata cagcctcagt acaaggctaa gcattttaac 660tttatactgg aaaaaaaatc aaacaaaggg gagggataaa ggacttagtc atctttgcac 720tggaaaacaa aatatgtaat taaattccca tagctgcatg taacattgaa ttcttccagg 780ttaaaaaaaa agttaatcct gtgatattaa tggaatgaca ttttgaggtc ttgagaatgg 840gcacaaaagt gggaaatgaa tttcagtatg ggcaaagaca ctgaggatga tgttgattag 900ataattcact ccgtaatgat catgctgtgt gctagtaagt ataaccctgg aaagatcttg 960agatgcttcc cagcctgttc acagatcccc tgggccagaa cactccttag gaaaaacagt 1020cagctacata ttaggcagca acacgaaggg tctttgaaca aaatgagtaa tgttattcta 1080cagtgtagaa aggtcacagt acagatctgg gaactaaata ttaaaaatga gtgtggctgg 1140atatatggag aatgttgggc ccagaaggaa ccgtagagat cagatattac aacagctttg 1200ttttgagggt tagaaatatg aaatgatttg gttatgaacg cacagtttag gcagcagggc 1260cagaatcctg accctctgcc ccgtggttat ctcctcccca gcttggctgc ctcatgtcat 1320cacagtattc cattttgttt gttgcatgtc ttgtgaagcc atcaagattt tctcgtctgt 1380tttcctctca ttggtaatgc tcactttgtg acttcatttc aaatctgtaa tcccgttcaa 1440ataaatatcc acaacaggat ctgttttcct gcccatcctt taaggaacac atcaattcat 1500tttctaatgt ccttccctca caagcgggac caggcacagg gcgaggctca tcgatgaccc 1560aagatggcgg ccgggcattt ctcccaggga tctctgtgct tccttttgtg cttcctgtgt 1620gtgtggatat ttaaaggggc tggaaatgtg caaaaacatg tcactactta gacattatat 1680tgtcatcttg ctgtttctag tgatgttaat tatctccatt tcagcagatg tgtggcctca 1740gatggtaaag tcagcagcct ttcttatttc tcacctggaa atacatacga ccatttgagg 1800agacaaatgg caaggtgtca gcataccctg aacttgagtt gagagctaca cacaatatta 1860ttggtttccg agcatcacaa acaccctctc tgtttcttca ctgggcacag aattttaata 1920cttatttcag tgggctgttg gcaggaacaa atgaagcaat ctacataaag tcactagtgc 1980agtgcctgac acacaccatt ctcttgaggt cccctctaga gatcccacag gtcatatgac 2040ttcttgggga gcagtggctc acacctgtaa tcccagcact ttgggaggct gaggcaggtg 2100ggtcacctga ggtcaggagt tcaagaccag cctggccaat atggtgaaac cccatctcta 2160ctaaaaatac aaaaattagc tgggcgtgct ggtgcatgcc tgtaatccca gccccaacac 2220aatggaatt 2229<210> 470<211> 2426<212> DNA<213> Homo sapiens<400> 470gtaaattctt tattgccagg agtgaaccct aaagtggctc acaagagtgc cctatttctt 60tcaattaact acaaggacaa acacatctca aagttgagat aagtgaccag tatgatttgc 120caaaattcta aagcgcactc accatgaaat ggataaaggt tacctttggg gatttgcact 180gcatgaattc tgtgaaaagc ttgttggata ttgtgataga gatagagaaa tgaagtatat 240tatataagat actatgaggt tccctgcctt tgcttcacat cccaggctta caaacgtgcc 300ccataaacat tccctctgtg gctcttgcat ttcatatatt tatctaaact cttataatca 360aattacactt ttagtatttg ctgtctcatg tgatgatgaa tctcatatgt gtcccttctt 420tgcatgaagt aagatagtca acttattcaa aactttacat cattctagat ttaagagaca 480aggaagagct tctcaggcag aaggaataat gtatgcctga catgttcaag gaattacaag 540ttagattttg tttaggtgca tgggaggggt tgatggtgat gacagataag gctggaggga 600tggggagagg ctgtggctgt atacagcctc agtacaaggc taagcatttt aactttatac 660tggaaaaaaa atcaaacaaa ggggagggat aaaggactta gtcatctttg cactggaaaa 720caaaatatgt aattaaattc ccatagctgc atgtaacatt gaattcttcc aggttaaaaa 780aaaaagttaa tcctgtgata ttaatggaat gacattttga ggtcttgaga atgggcacaa 840aagtgggaaa tgaatttcag tatgggcaaa gacactgagg atgatgttga ttagataatt 900cactccgtaa tgatcatgct gtgtgctagt aagtataacc ctggaaagat cttgagatgc 960ttcccagcct gttcacagat cccctgggcc agaacactcc ttaggaaaaa cagtcagcta 1020catattaggc agcaacacga agggtctttg aacaaaatga gtaatgttat tctacagtgt 1080agaaaggtca cagtacagat ctgggaacta aatattaaaa atgagtgtgg ctggatatat 1140ggagaatgtt gggcccagaa ggaaccgtag agatcagata ttacaacagc tttgttttga 1200gggttagaaa tatgaaatga tttggttatg aacgcacagt ttaggcagca gggccagaat 1260cctgaccctc tgccccgtgg ttatctcctc cccagcttgg ctgcctcatg tcatcacagt 1320attccatttt gtttgttgca tgtcttgtga agccatcaag attttctcgt ctgttttcct 1380ctcattggta atgctcactt tgtgacttca tttcaaatct gtaatcccgt tcaaataaat 1440atccacaaca ggatctgttt tcctgcccat cctttaagga acacatcaat tcattttcta 1500atgtccttcc ctcacaagcg ggaccaggca cagggcgagg ctcatcgatg acccaagatg 1560gcggccgggc atttctccca gggatctctg tgcttccttt tgtgcttcct gtgtgtgtgg 1620atatttaaag gggctggaaa tgtgcaaaaa catgtcacta cttagacatt atattgtcat 1680cttgctgttt ctagtgatgt taattatctc catttcagca gatgtgtggc ctcagatggt 1740aaagtcagca gcctttctta tttctcacct ggaaatacat acgaccattt gaggagacaa 1800atggcaaggt gtcagcatac cctgaacttg agttgagagc tacacacaat attattggtt 1860tccgagcatc acaaacaccc tctctgtttc ttcactgggc acagaatttt aatacttatt 1920tcagtgggct gttggcagga acaaatgaag caatctacat aaagtcacta gtgcagtgcc 1980tgacacacac cattctcttg aggtcccctc tagagatccc acaggtcata tgacttcttg 2040gggagcagtg gctcacacct gtaatcccag cactttggga ggctgaggca ggtgggtcac 2100ctgaggtcag gagttcaaga ccagcctggc caatatggtg aaaccccatc tctactaaaa 2160atacaaaaat tagctgggcg tgctggtgca tgcctgtaat cccagctact tgggaggctg 2220aggcaggaga attgctggaa catgggaggc ggaggttgca gtgagctgta attgtgccat 2280tgcactcgaa cctgggcgac agagtggaac tctgtttcca aaaaacaaac aaacaaaaaa 2340ggcatagtca gatacaacgt gggtgggatg tgtaaataga agcaggatat aaagggcatg 2400gggtgacggt tttgcccaac acaatg 2426<210> 471<211> 812<212> DNA<213> Homo sapiens<400> 471gaacaaaatg agtaatgtta ttctacagtg tagaaaggtc acagtacaga tctgggaact 60aaatattaaa aatgagtgtg gctggatata tggagaatgt tgggcccaga aggaaccgta 120gagatcagat attacaacag ctttgttttg agggttagaa atatgaaatg atttggttat 180gaacgcacag tttaggcagc agggccagaa tcctgaccct ctgccccgtg gttatctcct 240ccccagcttg gctgcctcat gtcatcacag tattccattt tgtttgttgc atgtcttgtg 300aagccatcaa gattttctcg tctgttttcc tctcattggt aatgctcact ttgtgacttc 360atttcaaatc tgtaatcccg ttcaaataaa tatccacaac aggatctgtt ttcctgccca 420tcctttaagg aacacatcaa ttcattttct aatgtccttc cctcacaagc gggaccaggc 480acagggcgag gctcatcgat gacccaagat ggcggccggg catttctccc agggatctct 540gtgcttcctt ttgtgcttcc tgtgtgtgtg gatatttaaa ggggctggaa atgtgcaaaa 600acatgtcact acttagacat tatattgtca tcttgctgtt tctagtgatg ttaattatct 660ccatttcagc agatgtgtgg cctcagatgg taaagtcagc agcctttctt atttctcacc 720tctgtatcat caggtccttc ccaccatgca gatcttcctg gtctccctcg gctgcagcca 780cacaaatctc ccctctgttt ttctgatgcc ag 812<210> 472<211> 515<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(515)<223> n = A,T,C or G<400> 472acggagactt attttctgat attgtctgca tatgtatgtt tttaagagtc tggaaatagt 60cttatgactt tcctatcatg cttattaata aataatacag cccagagaag atgaaaatgg 120gttccagaat tattggtcct tgcagcccgg tgaatctcag caagaggaac caccaactga 180caatcaggat attgaacctg gacaagagag agaaggaaca cctccgatcg aagaacgtaa 240agtagaaggt gattgccagg aaatggatct ggaaaagact cggagtgagc gtggagatgg 300ctctgatgta aaagagaaga ctccacctaa tcctaagcat gctaagacta aagaagcagg 360agatgggcag ccataagtta aaaagaagac aagctgaagc tacacacatg gctgatgtca 420cattgaaaat gtgactgaaa atttgaaaat tctctcaata aagtttgagt tttctctgaa 480gaaaaaaaaa naaaaaaaaa aaanaaaaan aaaaa 515
Claims (79)
1．至少包含前列腺肿瘤蛋白的免疫原性部分或其变体的分离多肽，其中所述肿瘤蛋白包含由选自下列的多核苷酸序列编码的氨基酸序列：
(a)SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472任一记录的序列；
(b)与任何上述序列在中等严谨条件下可杂交的序列；和
(c)(a)或(b)的任何序列的互补序列。
2．权利要求1的分离多肽，其中所述多肽包含由下列任一多核苷酸序列编码的氨基酸序列：SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472，或任何上述多核苷酸序列的互补序列。
3．包含SEQ ID NO:108、112、113、114、172、176、178、327、329、331、339和383任一记录的序列的分离多肽。
4．至少编码前列腺肿瘤蛋白的15个氨基酸残基或其因一个或多个取代、缺失、加入和/或插入而不同，但是与抗原特异的抗血清发生反应的能力没有实质性减小的变体的分离多核苷酸，其中所述肿瘤蛋白包含由含有下列任一序列的多核苷酸编码的氨基酸序列：SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472，或任何上述序列的互补序列。
5．编码前列腺肿瘤蛋白或其变体的分离多核苷酸，其中所述肿瘤蛋白包含由含有下列任一序列的多核苷酸编码的氨基酸序列：SEQ IDNO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472，或任何上述序列的互补序列。
6．包含下列任一记录的序列的分离多核苷酸：SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472。
7．包含与下列任一记录的序列在中等严谨条件下可杂交的序列的分离多核苷酸：SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472。
8．与权利要求4-7中任一项的多核苷酸互补的分离多核苷酸。
9．包含权利要求4-7中任一项的多核苷酸的表达载体。
10．用权利要求9的表达载体转化或转染的宿主细胞。
11．包含权利要求8的多核苷酸的表达载体。
12．用权利要求11的表达载体转化或转染的宿主细胞。
13．包含与生理学可接受的载体相组合的权利要求1的多肽的药物组合物。
14．包含与非特异免疫应答增强剂相组合的权利要求1的多肽的疫苗。
15．权利要求14的疫苗，其中非特异免疫应答增强剂是佐剂。
16．权利要求14的疫苗，其中非特异免疫应答增强剂诱导主要为Ⅰ类的应答。
17．包含与生理学可接受的载体相组合的权利要求4的多核苷酸的药物组合物。
18．包含与非特异免疫应答增强剂相组合的权利要求4的多核苷酸的疫苗。
19．权利要求18的疫苗，其中非特异免疫应答增强剂是佐剂。
20．权利要求18的疫苗，其中非特异免疫应答增强剂诱导主要为Ⅰ类的应答。
21．与包含由下列任一多核苷酸序列编码的氨基酸序列的前列腺肿瘤蛋白可特异结合的分离抗体或其抗原结合片段：SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472，或任何上述多核苷酸序列的互补序列。
22．包含与生理学可接受的载体相组合的权利要求18的抗体或其片段的药物组合物。
23．包含与药学可接受的载体或赋形剂相组合的表达权利要求1的多肽的抗原呈递细胞的药物组合物。
24．权利要求23的药物组合物，其中抗原呈递细胞是树突状细胞或巨噬细胞。
25．包含与非特异免疫应答增强剂相组合的表达权利要求1的多肽的抗原呈递细胞的疫苗。
26．权利要求25的疫苗，其中非特异免疫应答增强剂是佐剂。
27．权利要求25的疫苗，其中非特异免疫应答增强剂诱导主要为Ⅰ类的应答。
28．权利要求25的疫苗，其中抗原呈递细胞是树突状细胞。
29．抑制癌症在患者体内发展的方法，包括给患者施用有效量的权利要求1的多肽，并由此抑制患者体内癌症的发展。
30．抑制癌症在患者体内发展的方法，包括给患者施用有效量的权利要求4的多核苷酸，并由此抑制患者体内癌症的发展。
31．抑制癌症在患者体内发展的方法，包括给患者施用有效量的权利要求21的抗体或其抗原结合片段，并由此抑制患者体内癌症的发展。
32．抑制癌症在患者体内发展的方法，包括给患者施用有效量的表达权利要求1的多肽的抗原呈递细胞，并由此抑制患者体内癌症的发展。
33．权利要求32的方法，其中抗原呈递细胞是树突状细胞。
34．权利要求29-32任一项的方法，其中癌症是前列腺癌。
35．包含权利要求1的至少一种多肽的融合蛋白。
36．权利要求35的融合蛋白，其中该融合蛋白包含表达增强子，该增强子可增加其在用编码该融合蛋白的多核苷酸转染的宿主细胞中的表达。
37．权利要求35的融合蛋白，其中融合蛋白包含在权利要求1的多肽中不存在的T辅助表位。
38．权利要求35的融合蛋白，其中融合蛋白包含亲和标签。
39．编码权利要求35的融合蛋白的分离多核苷酸。
40．包含与生理学可接受的载体相组合的权利要求32的融合蛋白的药物组合物。
41．包含与非特异免疫应答增强剂相组合的权利要求35的融合蛋白的疫苗。
42．权利要求41的疫苗，其中非特异免疫应答增强剂是佐剂。
43．权利要求41的疫苗，其中非特异免疫应答增强剂诱导主要为Ⅰ类的应答。
44．包含与生理学可接受的载体相组合的权利要求40的多核苷酸的药物组合物。
45．包含与非特异免疫应答增强剂相组合的权利要求40的多核苷酸的疫苗。
46．权利要求45的疫苗，其中非特异免疫应答增强剂是佐剂。
47．权利要求45的疫苗，其中非特异免疫应答增强剂诱导主要为Ⅰ类的应答。
48．抑制癌症在患者体内发展的方法，包括给患者施用有效量的权利要求40或权利要求44的药物组合物。
49．抑制癌症在患者体内发展的方法，包括给患者施用有效量的权利要求41或权利要求45的疫苗。
50．从生物学样品中除去肿瘤细胞的方法，包括将生物学样品与能和前列腺肿瘤蛋白发生特异反应的T细胞在足以从样品中除去表达前列腺肿瘤蛋白的细胞的条件和时间下进行接触，其中所述肿瘤蛋白包含由选自下组的多核苷酸序列编码的氨基酸序列：
(ⅰ)SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472任一记录的多核苷酸；和
(ⅱ)上述多核苷酸的互补多核苷酸。
51．权利要求50的方法，其中生物学样品是血液或其级分。
52．抑制癌症在患者体内发展的方法，包括给患者施用经权利要求50的方法处理过的生物学样品。
53．用于刺激和/或扩增对前列腺肿瘤蛋白特异的T细胞的方法，包括将T细胞与下列一种或多种物质在足以刺激和/或扩增T细胞的条件和时间下进行接触：
(ⅰ)权利要求1的多肽；
(ⅱ)由包含SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472任一提供的序列的多核苷酸编码的多肽；
(ⅲ)编码(ⅰ)或(ⅱ)的多肽的多核苷酸；和/或
(ⅳ)表达(ⅰ)或(ⅱ)的多肽的抗原呈递细胞。
54．分离的T细胞群，其中包含经权利要求53的方法制备的T细胞。
55．抑制癌症在患者体内发展的方法，包括给患者施用有效量的权利要求54的T细胞群。
56．抑制癌症在患者体内发展的方法，包括下列步骤：
(a)将从患者分离得到的CD4+和/或CD8+T细胞与选自下组的至少一种组分一起温育：
(ⅰ)权利要求1的多肽；
(ⅱ)由包含SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472中任一序列的多核苷酸编码的多肽；
(ⅲ)编码(ⅰ)或(ⅱ)的多肽的多核苷酸；或
(ⅳ)表达(ⅰ)或(ⅱ)的多肽的抗原呈递细胞；
使得T细胞增殖；并
(b)给患者施用有效量的增殖T细胞，并由此抑制癌症在患者体内的发展。
57．抑制癌症在患者体内发展的方法，包括下列步骤：
(a)将从患者分离得到的CD4+和/或CD8+T细胞与选自下组的至少一种组分一起温育：
(ⅰ)权利要求1的多肽；
(ⅱ)由包含SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472中任一序列的多核苷酸编码的多肽；
(ⅱ)编码(ⅰ)或(ⅱ)的多肽的多核苷酸；或
(ⅵ)表达(ⅰ)或(ⅱ)的多肽的抗原呈递细胞；使得T细胞增殖；
(b)克隆至少一个增殖细胞；并
(c)给患者施用有效量的克隆T细胞，并由此抑制癌症在患者体内的发展。
58．测定患者体内是否存在癌症的方法，包括下列步骤：
(a)将从患者分离得到的生物学样品与能和前列腺肿瘤蛋白结合的结合剂接触，其中所述肿瘤蛋白包含由选自下组的多核苷酸序列编码的氨基酸序列：
(ⅰ)SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472任一记录的多核苷酸；和
(ⅱ)上述多核苷酸的互补多核苷酸；
(b)检测样品中与结合剂结合的多肽的量；并
(c)将多肽的量与预先测定的临界值进行比较，并由此测定患者体内是否存在癌症。
59．权利要求58的方法，其中结合剂是抗体。
60．权利要求59的方法，其中抗体是单克隆抗体。
61．权利要求58的方法，其中癌症是前列腺癌。
62．监控癌症在患者体内的进程的方法，包括下列步骤：
(a)将在第一时间点从患者得到的生物学样品与能和前列腺肿瘤蛋白结合的结合剂接触，其中所述肿瘤蛋白包含由下列任一多核苷酸序列编码的氨基酸序列：SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472记录的多核苷酸，或上述多核苷酸的互补多核苷酸；
(b)检测样品中与结合剂结合的多肽的量；
(c)使用随后第二时间点从患者得到的生物学样品，重复步骤(a)和(b)；并
(d)将步骤(c)检测到的多肽的量与步骤(b)检测到的量进行比较，并由此监控患者体内癌症的进程。
63．权利要求62的方法，其中结合剂是抗体。
64．权利要求63的方法，其中抗体是单克隆抗体。
65．权利要求62的方法，其中癌症是前列腺癌。
66．测定患者体内是否存在癌症的方法，包括下列步骤：
(a)将从患者得到的生物学样品与能和编码前列腺肿瘤蛋白的多核苷酸杂交的寡核苷酸接触，其中所述肿瘤蛋白包含由下列任一多核苷酸序列编码的氨基酸序列：SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472记录的多核苷酸序列，或上述任一多核苷酸的互补多核苷酸；
(b)检测样品中与寡核苷酸杂交的多核苷酸的量；并
(c)将与寡核苷酸杂交的多核苷酸的量与预先测定的临界值进行比较，并由此测定患者体内是否存在癌症。
67．权利要求66的方法，其中与寡核苷酸杂交的多核苷酸的量是使用聚合酶链式反应进行测定的。
68．权利要求66的方法，其中与寡核苷酸杂交的多核苷酸的量是使用杂交实验进行测定的。
69．监控癌症在患者体内的进程的方法，包括下列步骤：
(a)将从患者得到的生物学样品与能和编码前列腺肿瘤蛋白的多核苷酸杂交的寡核苷酸接触，其中所述肿瘤蛋白包含由下列任一多核苷酸序列编码的氨基酸序列：SEQ ID NO:1-111、115-171、173-175、177、179-305、307-315、326、328、330、332-335、340-375、381、382或384-472记录的多核苷酸序列，或上述任一多核苷酸的互补多核苷酸；
(b)检测样品中与寡核苷酸杂交的多核苷酸的量；
(c)使用随后第二时间点从患者得到的生物学样品，重复步骤(a)和(b)；并
(d)将步骤(c)检测到的多核苷酸的量与步骤(b)检测到的量进行比较，并由此监控患者体内癌症的进程。
70．权利要求69的方法，其中与寡核苷酸杂交的多核苷酸的量是使用聚合酶链式反应进行测定的。
71．权利要求69的方法，其中与寡核苷酸杂交的多核苷酸的量是使用杂交实验进行测定的。
72．一种诊断试剂盒，其中包括：
(a)权利要求21的一种或多种抗体；和
(b)包含报告基团的检测剂。
73．权利要求72的试剂盒，其中抗体是固定在固体支持物上的。
74．权利要求73的试剂盒，其中所述固体支持物包括硝酸纤维素、乳胶或塑料材料。
75．权利要求72的试剂盒，其中所述检测剂包括抗免疫球蛋白、蛋白G、蛋白A或凝集素。
76．权利要求72的试剂盒，其中报导基团选自：放射性同位素、荧光基团、发光基团、酶、生物素和染料颗粒。
77．包含与编码前列腺肿瘤蛋白的多核苷酸在中等严谨条件下可杂交的1O-40个核苷酸的寡核苷酸，其中所述肿瘤蛋白包含由下列任一多核苷酸序列编码的氨基酸序列：SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73-74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472记录的多核苷酸序列，或任何上述多核苷酸的互补序列。
78．权利要求77的寡核苷酸，其中所述寡核苷酸包含SEQ ID NO:2、3、8-29、41-45、47-52、54-65、70、73、74、79、81、87、90、92、93、97、103、104、107、109-111、115-160、171、173-175、177、181、188、191、193、194、198、203、204、207、209、220、222-225、227-305、307-315、326、328、330、332、334、350-365、381、382、384、386、389、390、392、393、396、401、402、407、408、410、413、415-419、422、426、427、432、434、435、442-444、446、450、452、453、459-461、468-471或472任一序列中的10-40个核苷酸。
79．一种诊断试剂盒，其中包括：
(a)权利要求77的寡核苷酸；和
(b)用于聚合酶链式反应或杂交实验的诊断剂。
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| US09/116,134 US7008772B1 (en) | 1997-02-25 | 1998-07-14 | Compounds for immunodiagnosis of prostate cancer and methods for their use |
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| US09/115,453 US6657056B2 (en) | 1997-02-25 | 1998-07-14 | Compounds for immunotherapy of prostate cancer and methods for their use |
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| US15982298A | 1998-09-23 | 1998-09-23 | |
| US09/159,812 US6613872B1 (en) | 1997-02-25 | 1998-09-23 | Compounds for immunotherapy of prostate cancer and methods for their use |
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| US09/232,880 US7270980B2 (en) | 1997-02-25 | 1999-01-15 | Compounds for immunodiagnosis of prostate cancer and methods for their use |
| US09/232,149 US6465611B1 (en) | 1997-02-25 | 1999-01-15 | Compounds for immunotherapy of prostate cancer and methods for their use |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1870466A2 (en) | 2007-12-26 |
| AU5314899A (en) | 2000-02-07 |
| BR9912007A (pt) | 2002-01-29 |
| CA2334038A1 (en) | 2000-01-27 |
| AU762812B2 (en) | 2003-07-03 |
| HUP0203035A2 (hu) | 2002-12-28 |
| AU2003248213A1 (en) | 2003-10-30 |
| NZ509178A (en) | 2004-04-30 |
| JP2002520054A (ja) | 2002-07-09 |
| NO20010196L (no) | 2001-03-12 |
| PL200772B1 (pl) | 2009-02-27 |
| TW200728465A (en) | 2007-08-01 |
| HUP0203035A3 (en) | 2007-12-28 |
| WO2000004149A3 (en) | 2000-07-20 |
| CN100419079C (zh) | 2008-09-17 |
| TR200100916T2 (zh) | 2002-06-21 |
| EP1097208A2 (en) | 2001-05-09 |
| CZ2001149A3 (cs) | 2002-02-13 |
| SA99200618B1 (ar) | 2007-01-20 |
| KR20010083111A (ko) | 2001-08-31 |
| PL346359A1 (en) | 2002-02-11 |
| TW200532020A (en) | 2005-10-01 |
| WO2000004149A2 (en) | 2000-01-27 |
| NO20010196D0 (no) | 2001-01-12 |
| EP1870466A3 (en) | 2008-03-19 |
| IL140845A0 (en) | 2002-02-10 |
| KR20070112860A (ko) | 2007-11-27 |
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