CN110382521A - 从氧化应激区分肿瘤抑制性foxo活性的方法 - Google Patents
从氧化应激区分肿瘤抑制性foxo活性的方法 Download PDFInfo
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Abstract
本发明涉及FOXO转录因子家族的某些靶基因,其是氧化应激状态的标志物并且可以用于推断医学受试者的机体的FOXO转录因子元件的氧化应激状态。本发明还涉及基于所述靶基因的表达水平推断FOXO转录元件的氧化应激状态的方法和推断FOXO/PI3K细胞信号传导通路的活性的方法以及用于实施所述方法的产品。
Description
发明领域
本发明一般涉及生物信息学、基因组/转录组处理、蛋白组处理及相关技术领域。更具体地,本发明涉及FOXO转录因子家族的某些靶基因,这些靶基因是氧化应激状态的标志物并且可以用于推断医学受试者中FOXO转录因子元件的氧化应激状态。本发明也涉及基于一或多个FOXO靶基因的表达水平推断医学受试者中FOXO转录因子元件的氧化应激状态的方法和基于在医学受试者的提取样品中所测量的FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平并基于医学受试者中FOXO转录因子元件的推断的氧化应激状态推断医学受试者中FOXO/PI3K细胞信号传导通路的活性的方法。本发明进一步涉及一种产品,其包括用于确定FOXO靶基因的表达水平的引物和/或探针。本发明进一步涉及一种装置,其包括配置成执行所述方法的数字处理器、存储可被执行这种方法的数字处理设备可执行的指令的非暂时性存储介质、和包括用于使数字处理设备执行这种方法的程序代码工具的计算机程序。
背景技术
基因组/转录组和蛋白组分析在诸如肿瘤学等医学领域中具有重要的、实际的和潜在的临床应用前景,其中已知多种癌症与基因组突变/变异的特定组合和/或特定基因的高或低表达水平是相关的,这些特定基因在癌症的生长和进化(例如细胞增殖和转移)中起作用。
例如,对于乳腺癌样品中细胞膜上HER2受体过表达的筛选目前是用于鉴定适合HER2抑制剂如曲妥珠单抗的患者所执行的标准测试。ERBB2基因的过表达(其导致细胞膜上HER2受体的过表达)发生在所有乳腺癌的大约25%至30%中并与增加的疾病复发和不良预后是相关的。然而,HER2受体的表达决不是驱动肿瘤生长的决策性指标,这是因为通过HER2受体所启动的信号传导可以例如由下游细胞信号传导通路来抑制。这也似乎反映在用曲妥珠单抗所治疗的HER2阳性乳腺癌患者中26%的初始响应率中(Charles L.Vogel等,“Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatmentof HER2-Overexpressing Metastatic Breast Cancer”,Journal of ClinicalOncology,Vol.20,No.3,February 2002,pages 719-726)。除此之外,HER2受体下游的细胞信号传导通路也可以由HER2受体下游蛋白中的突变/过表达来激活,导致(a)通过测量HER2表达水平将不会检测到的相对侵袭性肿瘤类型。
已经表明,表征患有肿瘤(例如乳腺癌)的患者的可能性可以通过研究在HER2受体下游的细胞信号传导通路中发生的效果来改善。因而,使用靶基因表达的数学建模推断PI3K细胞信号传导通路的活性的方法已经在公开的国际专利申请WO 2015/101635 A1(“Assessment of the PI3K cellular signaling pathway activity usingmathematical modelling of target gene expression”)中描述。
根据WO2015/101635 A1,使用靶基因表达的数学建模推断PI3K细胞信号传导通路的活性的方法包括:
至少基于医学受试者的提取样品中所测量的FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平推断医学受试者中FOXO/PI3K细胞信号传导通路的活性,其中该推断包括:
确定医学受试者的提取样品中FOXO转录因子元件的活性水平,FOXO转录因子元件控制PI3K细胞信号传导通路的一或多个靶基因的转录,该确定至少部分地基于评价将FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平与FOXO转录因子元件的活性水平相关联的数学模型;
基于医学受试者的提取样品中FOXO转录因子元件的所述确定的活性水平推断医学受试者中PI3K细胞信号传导通路的活性。
在本文中,已经认识到的是鉴定在HER2受体下游的细胞信号传导通路(诸如PI3K细胞信号传导通路)中发生效果的合适方式可以基于细胞信号传导通路的信号输出的测量,该细胞输出例如是通过转录因子(TF)(诸如FOXO转录因子元件,其被所述细胞信号传导通路控制)所控制的靶基因的转录。本文中所靶向的PI3K细胞信号传导通路不仅与乳腺癌相关,而且已知在许多类型的癌症中被不适当地激活(Jeffrey A.Engelman,“TargetingPI3K signalling in cancer:opportunities,challenges and limitations”,NatureReviews Cancer,No.9,August 2009,pages 550-562)。它被认为通过RTK受体家族来调控,RTK受体家族也包括HER家族。随后,PI3K细胞信号传导通路经通过多个过程传递其接收的信号,其中两个主要分支是mTOR复合物的激活和转录因子家族(通常称为FOXO)的失活(参见上面来自Jeffrey A.Engelman的文章中显示PI3K细胞信号传导通路的图)。该方法集中在PI3K细胞信号传导通路和FOXO TF家族上,FOXO TF家族的活性与PI3K细胞信号传导通路的活性实质上是负相关的,即FOXO的活性与PI3K细胞信号传导通路的无活性实质上是相关的,而FOXO的无活性与PI3K细胞信号传导通路的活性实质上是相关的。该方法通过(i)确定医学受试者的提取样品中FOXO转录因子元件的活性水平,其中该确定是至少部分地基于评价将PI3K细胞信号传导通路的一或多个靶基因(其转录通过FOXO转录因子元件来控制)的表达水平与FOXO转录因子元件的转录活性水平相关的数学模型,并且通过(ii)基于医学受试者的提取样品中FOXO转录因子元件的所述确定的活性水平推断医学受试者中PI3K细胞信号传导通路的活性,使得确定医学受试者中PI3K细胞信号传导通路的活性成为可能。这允许改善表征患有肿瘤(例如乳腺癌)的患者的可能性,肿瘤至少部分地通过丧失调控的PI3K细胞信号传导通路来驱动,因此可能应答PI3K细胞信号传导通路的抑制剂。
例如,细胞核FOXO3转录因子(FOXO转录因子家族的成员)可以在正常的细胞中而且也在细胞经历氧化应激的情况下(如在癌症细胞中)有活性。在两种情况下,FOXO都存在于细胞核中(参见图1)。当PI3K细胞信号传导通路变为有活性时,FOXO会从细胞核易位到细胞质,而这与FOXO的无活性是相关的。然而,当FOXO由于氧化应激而激活时,这是不可能的。
因此,在发现FOXO有活性且在细胞核中的情况下,这可能是正常的细胞,其中PI3K通路无活性且FOXO处于肿瘤抑制性状态,或者它可能处于细胞经历氧化应激并且PI3K通路有活性但防止了FOXO从细胞核的易位和无活性的情况。因此,希望找到一种从氧化应激中区分肿瘤抑制性FOXO活性的方法,以便使得PI3K通路有活性或无活性的推断更加可靠。推断PI3K活动的决策树显示在图2中。
发明内容
根据本发明的主要方面,上述问题通过一个FOXO靶基因或一组两个或更多个FOXO靶基因来解决,其用作医学受试者中FOXO转录因子元件的氧化应激状态的标志物,所述氧化应激状态基于医学受试者的提取样品中所述一个FOXO靶基因或所述组的两个或更多个FOXO靶基因的表达水平,其中所述靶基因选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT。
本发明基于以下认识:特异性FOXO靶基因在“正常的”(即肿瘤抑制性状态)与“氧化应激”状态之间是差异表达的,因此测量它们的表达水平允许区分这两种状态。
在本文中,FOXO转录因子(TF)元件定义成含有至少一个FOXO TF家族成员(即FOXO1、FOX03、FOXO4以及FOXO6)的蛋白复合物,其能够结合特异性DNA序列,从而控制靶基因的转录。
本文中FOXO转录因子元件的氧化应激状态是指其中FOXO有活性且在细胞核中但其中PI3K通路可以是有活性或无活性的状态。如果PI3K通路有活性,则由于细胞经历氧化应激而不会发生FOXO的失活。特别地,氧化应激状态是指细胞的癌症期或癌前期的状态。
相比之下,本文中FOXO转录因子元件的肿瘤抑制性状态是指其中FOXO在细胞核中有活性且PI3K通路无活性的状态。特别地,肿瘤抑制性状态是指细胞的正常健康状态。
本文中的“PI3K细胞信号传导通路”或“PI3K通路”优选地是指最终导致与该通路相关的转录因子(TF)复合物的转录活性的细胞信号传导通路。在本案下,这些由上述FOXOTF家族成员组成。因此,该通路在本发明的上下文中也可称为“FOXO/PI3K细胞信号传导通路”。
“靶基因”可以是“直接靶基因”和/或“间接靶基因”。
合适的靶基因在下文中描述。
SOD2(超氧化物歧化酶-2)是一种线粒体基质酶,其清除由线粒体中发生的广泛氧化还原和电子传递反应所产生的氧自由基。
BNIP3(BcL-2/腺病毒ElB-19-kDa蛋白相互作用蛋白3)通常表达为无活性的单体,但在毒性刺激后,它会形成稳定的同源二聚体,整合到线粒体外膜中,并且引起线粒体膜电位的丧失和细胞死亡(Sassone等,“BNIP3 has a key role in the mitochondrialdysfunction induced by mutant huntigtin”,Human Molecular Genetics,Vol.24,2015,pages 6530-6539)。
PCK1(磷酸烯醇丙酮酸羧激酶)是调控糖异生的主要靶点。PEPCK基因的转录由胰岛素、糖皮质激素、cAMP以及饮食来调控,以便将葡萄糖产生调节至生理要求。
MXI1基因编码基本的螺旋-环-螺旋亮氨酸拉链转录因子,其在体外结合MAX,形成相似于MYC-MAX异二聚体的序列特异性DNA结合复合物。MXI1拮抗MYC功能且是候选的肿瘤抑制基因(Delpuech O,Griffiths B,East P,Essafi A,Lam EW,Burgering B,DownwardJ,Schulze A,“Induction of Mxi1-SR alpha by FOXO3a contributes to repressionof Myc-dependent gene expression”,Molecular Cell Bio logy,Jul.2007;Vol.27(13),pages 4917-30)。
PPARGC1A是细胞核受体和调控代谢过程的其它转录因子的共激活物,所述代谢过程包括线粒体生物发生和呼吸、肝糖原异生和肌纤维型转换(Lin等,“Defects inadaptive energy metabolism with CNS-linked hyperactivity in PGC-1-alpha nullmice”,Cell,2004,Vol.119,pages 121-135)。
根据一优选的实施方案,本发明涉及至少四个FOXO靶基因、优选所有靶基因的组,其选自如上所述用作标志物的SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT。
根据一特别优选的实施方案,本发明涉及两或更多个FOXO靶基因、优选所有靶基因的组,其选自如上所述用作标志物的SOD2、BNIP3、MXI1和PCK1。
本发明的另一方面涉及一个FOXO靶基因或两或更多个FOXO靶基因的组作为标志物用于基于医学受试者的提取样品中所述一个FOXO靶基因或所述两或更多个FOXO靶基因的组的表达水平推断医学受试者中FOXO转录因子元件的氧化应激状态的用途,其中所述靶基因选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT。
术语“推断”在本发明的上下文中是指将创建的数学表达或模型应用于样品中所测量的数据集(诸如特定基因的表达水平)以获得与样品状态有关的信息的行为。例如,“推断”可以包括计算样品的评分(诸如氧化应激评分)和通过例如应用阈值推绎状态(诸如氧化应激状态),其中该评分根据样品状态高于或低于所述阈值。
“受试者”或“医学受试者”可以是人或动物。
提取样品可以是医学受试者的组织和/或细胞和/或体液的样品,或者可以来自细胞系和/或来源于医学受试者的组织培养物,并且如果适用的话,可以在实验室中进行体外培养(例如用于再生医学目的)。优选地经由活组织检查程序或其它样品提取程序,样品可以是例如从癌症病变、或从疑似癌症的病变、或从转移性肿瘤、或从存在被癌症细胞污染的液体的体腔(例如胸膜腔或腹腔或膀胱腔)、或从含有癌症细胞的其它体液等所获得的样品。提取样品的细胞也可以是来自血液恶性肿瘤(诸如白血病或淋巴瘤)的肿瘤细胞。在一些情况下,细胞样品也可以是循环肿瘤细胞(即已进入血流的肿瘤细胞)并可以使用合适的分离技术(例如单采血液成分术或常规静脉血液抽取)来提取。除了血液之外,提取样品的体液可以是尿液、胃肠道内容物或外渗液。如本文中所用,术语“提取样品”也包括以下情况,其中受试者的组织和/或细胞和/或体液已取自受试者并例如已放在显微镜载玻片上,和其中为了执行要求保护的方法,例如借助于激光捕获显微解剖(LCM)、或通过从载玻片上刮下感兴趣的细胞、或通过荧光激活细胞分选术来提取此样品的一部分。细胞或组织也可以来自正常的非恶性组织或来自除癌症之外的患病组织。
优选的是如上所述的用途,其中推断医学受试者中FOXO转录因子元件的氧化应激状态是基于在医学受试者的提取样品中选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT的至少四个FOXO靶基因、优选所有靶基因的表达水平。
进一步优选的是如上所述的用途,其中推断医学受试者中FOXO转录因子元件的氧化应激状态是基于医学受试者的提取样品中选自SOD2、BNIP3、MXl1和PCK1的两或更多个FOXO靶基因、优选所有靶基因的表达水平。
根据另一主要方面,本发明涉及一种用于推断医学受试者中FOXO转录因子元件的氧化应激状态的方法,其中该推断包括:
确定医学受试者的提取样品中一或多个FOXO靶基因的表达水平,其中所述靶基因选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT;并且
基于确定的医学受试者的提取样品中一或多个FOXO靶基因的表达水平推断医学受试者中FOXO转录因子元件的氧化应激状态。
用于确定如与肿瘤抑制性状态相对的FOXO转录因子元件的氧化应激状态的靶基因区分组通过将FOXO有活性的正常乳腺组织和正常结肠组织样品中的靶基因表达谱与分别来自乳腺癌和结肠癌的样品中的靶基因表达谱进行比较来发现。
优选的实施方案是如上所述的方法,其中所述推断是基于医学受试者的提取样品中选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT的至少四个、优选所有FOXO靶基因的表达水平。
进一步优选的实施方案是如上所述的方法,其中所述推断是基于医学受试者的提取样品中选自SOD2、BNIP3、MXI1以及PCK1的两或更多个、优选所有FOXO靶基因的表达水平。
已发现上面段落中所述的靶基因关于氧化应激状态可以特别提供有用的信息。
在另一实施方案中,本发明涉及如上所述的方法,其中当在医学受试者的提取样品中SOD2和/或BNIP3的表达水平与对照样品相比上调时和/或当在医学受试者的提取样品中选自MXI1、PCK1、PPARGC1A以及CAT的一或多个靶基因的表达水平与对照样品相比下调时,推断FOXO转录因子元件的氧化应激状态。
优选的实施方案是如上所述的方法,其中当在医学受试者的提取样品中SOD2和/或BNIP3的表达水平与对照样品相比上调时和/或当在医学受试者的提取样品中MXI1和/或PCK1的表达水平与对照样品相比下调时,推断FOXO转录因子元件的氧化应激状态。
如上所述,用于确定如与肿瘤抑制性状态相对的FOXO转录因子元件的氧化应激状态的靶基因区分组通过将FOXO有活性的正常乳腺组织和正常结肠组织样品中的靶基因表达谱与分别来自乳腺癌和结肠癌的样品中的靶基因表达谱进行比较来发现。
结果可以总结成这样,正常结肠中有活性的FOXO相对结肠癌中有活性的FOXO的比较显示:
结肠癌中SOD2和BNIP3的表达水平增加、和
正常结肠组织中MXI1、PCK1和PPARGC1A的表达水平增加。
上述结果在FOXO有活性的乳腺癌相对FOXO有活性的正常乳腺组织中是可重现的:
结肠癌中SOD2和BNIP3的表达水平增加、和
正常结肠组织中MXI1、PCK1、CAT和PPARGC1A的表达水平增加。
所述结果在FOXO有活性的食道癌相对FOXO有活性的正常食道组织中是可重现的:
食道癌中SOD2的表达水平增加、和
正常食道组织中MXI1和PPARGC1A的表达水平增加。
因此,本发明方法可以用于指示医学受试者中的癌症或癌症前状态,特别地它可以用于确定结肠癌、乳腺癌和食道癌的存在或不存在。
最显著区别的基因是SOD2、BNIP3(在癌症中两者均增加)和MXI1、PCK1(在癌症中两者均减少)。PPARGC1A在乳腺癌中提供较少的信息,因此是较少优选的。
对照样品可以是从健康医学受试者提取的“正常”组织、细胞或体液的样品,或者它可以指来自多个健康医学受试者的收集样品的平均表达数据。这种表达数据可以来源于公共数据库。
根据本发明方法也可以是至少基于受试者的氧化应激状态推断受试者中PI3K细胞信号传导通路的活性的方法,包括,
基于受试者中选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT的一或多个基因的表达水平推断受试者的氧化应激状态。
受试者的氧化应激状态优选是受试者中FOXO转录因子元件的氧化应激状态。
所述方法优选至少基于在受试者中所测量的PI3K细胞信号传导通路的一或多个靶基因的表达水平,受试者可以是医学受试者。优选地,所述方法使用受试者的提取样品来进行,即表达水平在受试者的提取样品中测量。
根据本发明的进一步方面,上述方法可以整合到如例如WO 2015/101635 A1中所述的用于推断FOXO/PI3K细胞信号传导通路活性的方法中,并且改善如上所述结果的可靠性。
优选地,推断受试者中PI3K细胞信号传导通路的活性因此是基于受试者的推断的氧化应激状态和受试者中FOXO转录因子元件的活性水平。
所述方法可以包括确定受试者中一或多个基因的表达水平。
所述一或多个基因的表达水平优选地在受试者的提取样品中确定。
优选地,推断受试者的氧化应激状态是基于受试者中选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT的至少四个、优选所有FOXO靶基因的表达水平。
进一步优选地,推断受试者的氧化应激状态是基于受试者中选自SOD2、BNIP3、MXI1以及PCK1的两或更多个、优选所有FOXO靶基因的表达水平。
进一步优选地,推断受试者的氧化应激状态是基于受试者中选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT的一个FOXO靶基因的表达水平。
另一优选实施方案是如上所述的方法,其进一步包括至少基于医学受试者的提取样品中所测量的FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平推断医学受试者中FOXO/PI3K细胞信号传导通路的活性,其中该推断包括:
确定医学受试者的提取样品中FOXO转录因子元件的活性水平,所述FOXO转录因子元件控制FOXO/PI3K细胞信号传导通路的一或多个靶基因的转录,该确定是至少部分地基于评价将FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平与FOXO转录因子元件的活性水平相关联的数学模型;
基于所述确定的医学受试者的提取样品中FOXO转录因子元件的活性水平和推断的医学受试者中FOXO转录因子元件的氧化应激状态推断医学受试者中FOXO/PI3K细胞信号传导通路的活性,
其中推断FOXO/PI3K细胞信号传导通路的活性通过使用所述数学模型的数字处理设备来进行。
本发明的进一步优选实施方案是至少基于医学受试者的提取样品中所测量的FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平推断医学受试者中FOXO/PI3K细胞信号传导通路的活性,其中该推断包括:
确定医学受试者的提取样品中FOXO转录因子元件的活性水平,所述FOXO转录因子元件控制FOXO/PI3K细胞信号传导通路的一或多个靶基因的转录,该确定是至少部分地基于评价将FOXO/PI3K细胞信号传导通路的一或多个靶基因的表达水平与FOXO转录因子元件的活性水平相关联的数学模型;
基于医学受试者的提取样品中选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT的一或多个FOXO靶基因的表达水平推断医学受试者中FOXO转录因子元件的氧化应激状态;
基于所述确定的医学受试者的提取样品中FOXO转录因子元件的活性水平和推断的医学受试者中FOXO转录因子元件的氧化应激状态推断医学受试者中FOXO/PI3K细胞信号传导通路的活性,
其中推断FOXO/PI3K细胞信号传导通路的活性通过使用所述数学模型的数字处理设备来进行。
通过不仅依赖于所述确定的FOXO转录因子元件的活性水平,而且包括推断的FOXO转录因子元件的氧化应激状态,推断的FOXO/PI3K细胞信号传导通路的活性如上所述会变得更加可靠。
如本领域技术人员将理解到,确定用于两种目的FOXO靶基因的表达水平、推断FOXO转录因子元件的氧化应激状态以及确定FOXO转录因子元件的活性水平,可以使用来自相同医学受试者的相同或不同样品和/或相同或不同探针来完成,并且可以基于如可适用靶基因的相同或不同或部分重叠的(组)。如果确定选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT的靶基因的一个、两个或更多个、或所有的表达水平,则结果可以用于两种目的。优选地,仅使用用于医学受试者的一个样品来确定上述方法所需的所有表达水平。
所述数学模型可以是概率模型、优选如WO 2015/101635 A1中所述的贝叶斯网络模型,其至少部分地基于与医学受试者的组织和/或细胞和/或体液的提取样品中所测量的FOXO转录因子元件和PI3K细胞信号传导通路的一或多个靶基因的表达水平相关的条件概率,或者所述数学模型可以至少部分地基于医学受试者的组织和/或细胞和/或体液的提取样品中所测量的PI3K细胞信号传导通路的一或多个靶基因的表达水平的一或多个线性组合。特别地,推断PI3K细胞信号传导通路的活性可以如公开的国际专利申请WO 2013/011479 A2(“Assessment of cellular signaling pathway activity usingprobabilistic modeling of target gene expression”)中所公开的那样或如公开的国际专利申请WO 2014/102668(“Assessment of cellular signaling pathway activityusing linear combination(s)of target gene expressions”)中所述的那样来进行。
根据本发明的一优选实施方案,当在医学受试者的提取样品中SOD2和/或BNIP3的表达水平与对照样品相比上调时和/或当在医学受试者的提取样品中选自MXI1、PCK1、PPARGC1A以及CAT的一或多个靶基因的表达水平与对照样品相比下调时,推断氧化应激状态。
根据本发明的一进一步优选实施方案,当在医学受试者的提取样品中SOD2和/或BNIP3的表达水平与对照样品相比上调时和/或当在医学受试者的提取样品中选自MXI1和/或PCK1的表达水平与对照样品相比下调时,推断氧化应激状态。
优选地,氧化应激状态是受试者中FOXO转录因子元件的氧化应激状态。
根据本发明的一优选实施方案,用于推断PI3K细胞信号传导通路活性的靶基因选自由下面靶基因组成的组中。
在如上所述的优选方法中,受试者中FOXO转录因子元件的活性水平至少基于受试者的提取样品中所测量的PI3K细胞信号传导通路的一或多个、优选至少三个靶基因的表达水平来确定,所述靶基因选自AGRP、BCL2L11、BCL6、BNIP3、BTG1、CAT、CAV1、CCND1、CCND2、CCNG2、CDKN1A、CDKN1B、ESR1、FASLG、FBXO32、GADD45A、INSR、MXI1、NOS3、PCK1、POMC、PPARGC1A、PRDX3、RBL2、SOD2以及TNFSF10。
在如上所述的进一步优选方法中,FOXO转录因子元件的活性水平至少基于受试者的提取样中所测量的PI3K细胞信号传导通路的一或多个、优选至少三个靶基因的表达水平来确定,所述靶基因选自ATP8A1、C10orf10、CBLB、DDB1、DYRK2、ERBB3、EREG、EXT1、FGFR2、IGF1R、IGFBP1、IGFBP3、LGMN、PPM1D、SEMA3C、SEPP1、SESN1、SLC5A3、SMAD4以及TLE4和/或选自ATG14、BIRC5、IGFBP1、KLF2、KLF4、MYOD1、PDK4、RAG1、RAG2、SESN1、SIRT1、STK11以及TXNIP。
FOXO转录因子元件的活性水平优选地基于在受试者的提取样品中所测量的上述靶基因的表达水平来推断。
特别优选的是一种方法,其中
推断医学受试者中FOXO/PI3K细胞信号传导通路的活性至少基于医学受试者的提取样品中所测量的FOXO/PI3K细胞信号传导通路的一或多个、优选至少三个靶基因的表达水平,所述靶基因选自AGRP、BCL2L11、BCL6、BNIP3、BTG1、CAT、CAV1、CCND1、CCND2、CCNG2、CDKN1A、CDKN1B、ESR1、FASLG、FBXO32、GADD45A、INSR、MXI1、NOS3、PCK1、POMC、PPARGC1A、PRDX3、RBL2、SOD2以及TNFSF10和/或其中推断FOXO转录因子元件的氧化应激状态是基于医学受试者的提取样品中所测量的FOXO转录因子SOD2、BNIP3、MXI1以及PCK1的一或多个、优选所有靶基因的表达水平。
进一步优选的是一实施方案,其中推断医学受试者中FOXO/PI3K细胞信号传导通路的活性是至少基于医学受试者的提取样品中所测量的FOXO/PI3K细胞信号传导通路的六或更多个、优选十或更多个、更优选所有靶基因的表达水平,所述靶基因选自AGRP、BCL2L11、BCL6、BNIP3、BTG1、CAT、CAV1、CCND1、CCND2、CCNG2、CDKN1A、CDKN1B、ESR1、FASLG、FBXO32、GADD45A、INSR、MXI1、NOS3、PCK1、POMC、PPARGC1A、PRDX3、RBL2、SOD2以及TNFSF10。
进一步优选的是一种方法,其中所述推断进一步基于医学受试者的组织和/或细胞和/或体液的提取样品中所测量的PI3K细胞信号传导通路的至少一个靶基因的表达水平,所述靶基因选自ATP8A1、C10orf10、CBLB、DDB1、DYRK2、ERBB3、EREG、EXT1、FGFR2、IGF1R、IGFBP1、IGFBP3、LGMN、PPM1D、SEMA3C、SEPP1、SESN1、SLC5A3、SMAD4以及TLE4。
进一步优选的是一种方法,其中所述推断进一步基于医学受试者的组织和/或细胞和/或体液的提取样品中所测量的PI3K细胞信号传导通路的至少一个靶基因的表达水平,所述靶基因选自ATG14、BIRC5、IGFBP1、KLF2、KLF4、MYOD1、PDK4、RAG1、RAG2、SESN1、SIRT1、STK11以及TXNIP。
如果所述推断是进一步基于选自前述段落中所指定组中的至少一个靶基因的表达水平和选自前述段落之前段落中所指定组中的至少一个靶基因的表达水平两者,则关于这两组,上述提及的靶基因IGFBP1可以仅含有在这些组的一个中。
本发明的另一方面涉及一种方法(如本文所述),其进一步包括:
基于推断的医学受试者的组织和/或细胞和/或体液中P13K细胞信号传导通路的活性确定PI3K细胞信号传导通路是否在医学受试者的组织和/或细胞和/或体液中正在异常运行。
在一优选的实施方案中,如上所述的方法因此进一步包括基于推断的受试者中PI3K细胞信号传导通路的活性确定在受试者中PI3K细胞信号传导通路是否正在异常运行。
短语“细胞信号传导通路正在异常运行”是指该通路的“活性”不如所预期的情况,其中术语“活性”可以指转录因子复合物驱动靶基因表达的活性。“正常”可以是当它在预期是无活性的组织中无活性并在预期是有活性的组织中有活性。再者,可能存在被认为是正常的某一活性水平,并且任何更高或更低的水平可被认为是异常的。
本发明也涉及一种方法(如本文所述),其进一步包括:
推荐为医学受试者处方校正PI3K细胞信号传导通路的异常运行的药物,
其中,只有当基于推断的PI3K细胞信号传导通路的活性将PI3K细胞信号传导通路确定为在医学受试者的组织和/或细胞和/或体液中正在异常运行时,才进行该推荐。
根据一优选实施方案,本发明方法因此进一步包括推荐为受试者处方校正PI3K细胞信号传导通路的异常运行的药物,其中如果基于推断的PI3K细胞信号传导通路的活性将PI3K细胞信号传导通路确定为正在受试者中异常运行,则进行该推荐。
有利地,上述方法可以用于指示医学受试者中的癌症或癌症前状态,特别地它可以用于确定结肠癌、乳腺癌和食道癌的存在或不存在。
本发明也涉及一种方法(如本文所述),其中所述推断包括:
至少基于在医学受试者的组织和/或细胞和/或体液的提取样品中所测量的PI3K细胞信号传导通路的靶基因的组的两个、三个或更多个靶基因的表达水平推断医学受试者中PI3K细胞信号传导通路的活性。
优选地,
PI3K细胞信号传导通路的靶基因的组包括选自AGRP、BCL2L11、BCL6、BNIP3、BTG1、CAT、CAV1、CCND1、CCND2、CCNG2、CDKN1A、CDKN1B、ESR1、FASLG、FBXO32、GADD45A、INSR、MXI1、NOS3、PCK1、POMC、PPARGC1A、PRDX3、RBL2、SOD2以及TNFSF10的至少九个、优选所有靶基因。
一种方法是特别优选的,其中PI3K细胞信号传导通路的靶基因的组进一步包括选自ATP8A1、C10orf10、CBLB、DDB1、DYRK2、ERBB3、EREG、EXT1、FGFR2、IGF1R、IGFBP1、IGFBP3、LGMN、PPM1D、SEMA3C、SEPP1、SESN1、SLC5A3、SMAD4以及TLE4的至少一个靶基因。
一种方法也是特别优选的,其中PI3K细胞信号传导通路的靶基因的组进一步包括选自ATG14、BIRC5、IGFBP1、KLF2、KLF4、MYOD1、PDK4、RAG1、RAG2、SESN1、SIRT1、STK11以及TXNIP的至少一个靶基因。
如果靶基因的组进一步包括选自前述段落中所指定组中的至少一个靶基因和选自前述段落之前段落中所指定组中的至少一个靶基因两者,则关于这两组,上述靶基因IGFBP1可以仅含有在这些组的一个中。
在进一步的方面中,本发明也涉及一种产品,其包括:
用于确定医学受试者的提取样品中一个FOXO靶基因或者两或更多个FOXO靶基因、优选至少四个FOXO靶基因的组的基因表达水平的引物和/或探针,其中所述靶基因选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A以及CAT、优选选自SOD2、BNIP3、MXI1以及PCK1;并且
任选地,进一步包括用于确定医学受试者的提取样品中除上述基因之外的基因、优选选自AGRP、BCL2L11、BCL6、BTG1、CAV1、CCND1、CCND2、CCNG2、CDKN1A、CDKN1B、ESR1、FASLG、FBXO32、GADD45A、INSR、NOS3、POMC、PRDX3、RBL2以及TNFSF1 0的FOXO/PI3K细胞信号传导通路的两或更多个靶基因的组的表达水平的引物和/或探针。
在一优选的实施方案中,上述产品是PCR试剂盒、RNA测序试剂盒或微阵列试剂盒。
用于本发明方法中的材料理想地合适于制备根据已知程序所产生的试剂盒。因此,本发明提供了一种试剂盒,其包括用于检测公开的基因和序列表达的物质。这种试剂盒任选地包括具有识别描述或标签的物质或与其在本发明方法中使用相关的说明书。这种试剂盒可以含有容器,每个容器具有在这些方法中所用的各种试剂(通常以浓缩形式)中的一种或多种,这些试剂包括例如预制的微阵列、缓冲剂、适当的三磷酸核苷酸(例如dATP、dCTP、dGTP以及dTTP;或者rATP、rCTP、RGTP以及UTP)、逆转录酶、DNA聚合酶、RNA聚合酶、以及一或多种引物。典型地,也将包括一指令集。
在本发明的上下文中,表达水平可以通过涉及检测由基因编码的mRNA的方法确定。
例如,标志物基因表达的核酸水平的测量可以通过纯化从样品中所获的核酸分子(例如RNA或cDNA),然后通过与如上文中所定义的特异性寡核苷酸探针杂交来评估。表达水平的比较可以通过目测或借助于适当的设备来完成。检测mRNA或表达产物的方法对本领域技术人员是已知的。
可替代地,标志物基因表达的核酸水平可以在DNA阵列或微阵列方法中检测。典型地,对来源于待测试患者的样品核酸进行处理并标记,优选地用荧光标记。随后,这种核酸分子可以用于用对应于本发明标志物基因的固定化捕获探针的杂交方法中。用于进行微阵列分析的合适装置对本领域技术人员是已知的。
在标准设置中,DNA阵列或微阵列包括检测许多基因的固定化高密度探针。阵列上的探针与标志物基因序列的一或多个部分是互补的。典型地,cDNA、PCR产物和寡核苷酸可用作探针。
基于DNA阵列或基于微阵列的检测方法典型地包括以下步骤:(1)从样品中分离mRNA并任选地将mRNA转化成cDNA,随后标记此RNA或cDNA。用于分离RNA、将其转化成cDNA和用于标记核酸的方法在微阵列技术手册中描述。(2)使来自步骤1的核酸与标志物基因的探针杂交。来自样品的核酸可以用诸如荧光染料Cy3(红色)或Cy5(蓝色)的染料标记。通常,对照样品用不同染料标记。(3)用探针检测来自样品的核酸的杂交,并且至少定性地(且更特别地定量地)确定样品中用于所研究标志物基因的mRNA的量。样品与对照之间的表达水平的差异可以基于信号强度的差异来估计。这些可以通过适当的软件(如但不限于例如由Affymetrix所提供的软件)来测量并分析。
对应于所用标志物基因的探针数量不存在限制,将其点在DNA阵列上。此外,标志物基因可以由两或更多种探针来表示,探针与基因的不同部分杂交。探针针对每个选择的标志物基因来设计。这种探针典型地是包括5至50个核苷酸残基的寡核苷酸。更长的DNA可以通过PCR或化学地来合成。合成这种寡核苷酸并将它们应用于基材上的方法在微阵列领域中是众所周知的。也可以将除了标志物基因之外的基因点在DNA阵列上。例如,可以将表达水平没有显著改变的基因的探针点在DNA阵列上以使测定结果标准化或比较多个阵列或不同测定的测定结果。
可替代地,标志物基因表达的核酸水平可以在逆转录感兴趣的转录物后以定量RT-PCR方法、优选实时PCR方法来检测。典型地,作为第一步,根据本领域技术人员已知的任何合适方法将转录物逆转录成cDNA分子。定量或实时PCR方法随后可以基于如上所述所获得的第一DNA链来进行。
优选地,作为主要的基于FRET的此类型探针,Taqman或Molecular Beacon探针可以用于定量PCR检测。在两种情况下,探针(用作与位于感兴趣的靶区域侧翼的一对相对引物结合使用的内部探针)优选地是如上文所定义的标志物基因特异性寡核苷酸组。在扩增靶区段后,探针可以在引物位位点之间的识别序列处选择性地结合产物,由此引起FRET信号传导相对于靶频率增加的增加。
优选地,根据本发明待用于定量PCR方法的Taqman探针可以包括如上所定义的约22至30个碱基的特异性寡核苷酸,其在两端上用FRET对来标记。典型地,5′末端将具有更短波长的荧光团,诸如荧光素(例如FAM),并且3′末端通常用更长波长的荧光猝灭剂(例如TAMRA)或非荧光猝灭剂化合物(例如黑洞猝灭剂)来标记。优选的是待用于定量PCR的探针(特别是如上文所定义的探针)在与报告染料相邻的5′末端处没有鸟嘌呤(G)以避免在探针被降解后猝灭报告荧光。
根据本发明待用于定量PCR方法的Molecular Beacon探针优选使用FRET相互作用来检测和定量PCR产物,其中每个探针具有5′荧光标记的末端和3′猝灭剂标记的末端。探针结构的此发夹或茎-环构型优选包括具有两个短自结合末端的茎和具有约20至30个碱基的长内部靶特异性区域的环。
也可以用于本发明上下文中的替代性检测机制针对仅用环结构制造并且没有短互补茎区域的探针。也可以用于本发明上下文中的用于定量PCR的替代的基于FRET的方法基于使用结合靶上相邻位点的两个杂交探针,其中第一探针在3′末端具有荧光供体标记且第二探针在其5′末端具有荧光受体标记。
根据另一公开的方面,一种装置包括数字处理器,其配置成如本文所述执行根据本发明的方法。
根据另一公开的方面,一种非暂时性存储介质存储指令,其可由数字处理设备执行以如本文所述执行根据本发明的方法。非暂时性存储介质可以是计算机可读存储介质,诸如硬盘驱动器或其它磁存储介质、光盘或其它光存储介质、随机存取存储器(RAM)、只读存储器(ROM)、闪存或其它电子存储介质、网络服务器等等。数字处理设备可以是手持设备(例如个人数据助理或智能电话)、笔记本计算机、台式计算机、平板计算机或设备、远程网络服务器等等。
根据另一公开的方面,一种计算机程序包括程序代码工具,其用于使得数字处理设备如本文所述执行根据本发明的方法。数字处理设备可以是手持设备(例如个人数据助理或智能电话)、笔记本计算机、台式计算机、平板计算机或设备、远程网络服务器等等。
例如,本文所述的本发明也可以有利地结合以下活动来使用:
基于在医学受试者的组织和/或细胞和/或体液中PI3K细胞信号传导通路的推断活性的诊断;
基于在医学受试者的组织和/或细胞和/或体液中PI3K细胞信号传导通路的推断活性的预后;
基于在医学受试者的组织和/或细胞和/或体液中PI3K细胞信号传导通路的推断活性的药物处方;
基于在医学受试者的组织和/或细胞和/或体液中PI3K细胞信号传导通路的推断活性的药物功效预测;
基于在医学受试者的组织和/或细胞和/或体液中PI3K细胞信号传导通路的推断活性的不良反应的预测;
监测药物功效;
药物开发;
测定开发;
通路研究;
癌症分期;
基于在医学受试者的组织和/或细胞和/或体液中PI3K细胞信号传导通路的推断活性的临床试验医学受试者的招募;
要进行的后续测试的选择;以及
伴随诊断测试的选择。
根据优选的实施方案,本发明的方法因此用于以下活动的至少一种:
基于受试者中PI3K细胞信号传导通路的推断活性的诊断;
基于受试者中PI3K细胞信号传导通路的推断活性的预后;
基于受试者中PI3K细胞信号传导通路的推断活性的药物处方;
基于受试者中PI3K细胞信号传导通路的推断活性的药物功效预测;
基于受试者中PI3K细胞信号传导通路的推断活性的不良反应预测;
监测药物功效;
药物开发;
测定开发;
通路研究;
癌症分期;
基于受试者中PI3K细胞信号传导通路的推断活性的临床试验受试者的招募;
要进行的后续测试的选择;以及
伴随诊断测试的选择。
在阅读和理解附图、以下说明书且特别是在阅读本文下面所提供的详细示例后,进一步的优点对本领域普通技术人员将是显而易见的。
应当理解的是本发明的方法、装置、非暂时性存储介质以及计算机程序具有相似和/或相同的优选实施方案,特别是如从属权利要求中所限定。
应当理解的是本发明的优选实施方案也可以是从属权利要求或上面实施方案与相应独立权利要求的任何组合。
参考下文所述的实施方案,本发明的这些和其它方面将显而易见并被阐明。
附图说明
图1示意性地显示了细胞中的FOXO/PI3K细胞信号传导通路,其中FOXO3位于细胞核中。
图2显示了用于推断PI3K细胞信号传导通路活性的示意性决策树。
图3显示了使用表1中所示的所有基因和探针,在数据集中指定的每个亚组的氧化应激评分。
图4显示了仅那些如由WO 2010/101635 A1中所述的FOXO活性模型所推断具有FOXO活性的样品的氧化应激评分。
图5显示了通过仅使用信息量最大的氧化应激诱导的FOXO靶基因SOD2、MXI1、PCK1以及BNIP3所获得的氧化应激评分。
图6显示了通过添加氧化应激节点而结合氧化应激的示意性FOXO模型结构。出于可读性目的,未显示表示探针集的节点。
图7显示了数据集GS20916上所测试的实施例2中所述和图6中所示的模型的结果。x轴显示了转录复合物(TC)节点有活性的概率,并且y轴显示了OXI(氧化应激状态)节点有活性的概率。黑色圆圈表示正常结肠样品,空心圆圈表示腺癌样品,并且十字表示结肠癌样品。
图8显示了预测FOXO活性的贝叶斯计算模型。A.用作建模方法基础的贝叶斯网络结构显示为细胞信号转导通路的转录程序的简化模型,其由三种类型的节点组成:转录因子、靶基因和对应于靶基因的微阵列探针组。B.在公共GEO数据集GSE16573上训练计算FOXO3模型,高数据集由来自HUVEC的Affymetrix微阵列2.0Plus表达数据组成,HUVEC含有4OHT可诱导的FOXO3.A3-ER表达构建体。每个条柱表示样品分析结果。纵轴表示FOXO“有活性”(水平轴上方的值)相对于“无活性”(在水平轴下方的值)的概率。
图9显示了乳腺癌症细胞系中正确预测的FOXO和PI3K活性。A.在不存在或存在多西环素(dox)培养16小时的MCF7-FOXO3.A3和MDA-MB-231细胞中FOXO3表达水平的Western印迹分析。更低的FOXO3印迹表示相同印迹的更长时间曝光。B.计算FOXO3模型的生物学验证使用了用20%FBS、PI3K抑制剂LY294002、多西环素或多西环素和LY294002的组合处理16小时的MCF7-FOXO3.A3细胞。每个条柱表示一个样品的分析结果。纵轴表示FOXO3“有活性”(水平轴上方的值)相对于“无活性”(在水平轴下方的值)的概率。C.计算FOXO3模型的生物学验证使用了用多西环素处理16小时的MCF7-FOXO3.A3和MDA-MB-231细胞。每个条柱表示一个样品的分析结果。纵轴表示FOXO3“有活性”(水平轴上方的值)相对于“无活性”(在水平轴下方的值)的概率。
图10显示了抑制PI3K通路并诱导FOXO活性的靶向药物。公共数据集来自用靶向生长因子通路的药物处理的样品。FOXO活性评分指示为log2odds。由Wilcoxon秩统计测验产生的p值指示在图中。A.GEO GSE51212.如所示(从左至右),肺癌细胞系HCC827用载体(DMSO)或者用埃罗替尼、AZD6244(司美替尼)或BEZ235处理。埃罗替尼抑制EGFR;司美替尼特异性抑制MEK1/MEK2;BEZ235是PI3K/mTOR的双重抑制剂。B.GEO GSE30516数据集.表示三阴性(BT20)、ER阳性(MCF7)、和HER2阳性乳腺癌(MDA-MB-453)的三种乳腺癌症细胞系用埃罗替尼处理(所示的时间段,从左到右)。
图11显示了结肠、结肠腺瘤和结肠癌中的FOXO活性和细胞定位。A.GSE8671数据集内相应正常结肠和结肠腺瘤患者样品中的计算FOXO模型的生物学验证。每个条柱表示一个样品的分析结果。纵轴表示FOXO3“有活性”(水平轴上方的值)相对于“无活性”(在水平轴下方的值)的概率。左侧的条柱表示正常组织,右侧的条柱表示腺瘤样品。B.计算FOXO3模型的生物学验证使用了具有正常结肠组织样品(“正常结肠,粘膜”:来自肿瘤组织的显微解剖正常的粘膜;“远端结肠,粘膜”:来自远端健康组织;“正常结肠,隐窝”:来自肿瘤组织的显微解剖正常的隐窝;“远端结肠,隐窝”:来自远端健康结肠的显微解剖隐窝;“结肠,手术”:来自正常的结肠的全厚度组织)、结肠腺瘤(在显微解剖粘膜、显微解剖隐窝和完整的手术样品中所分离的)和癌(在显微解剖粘膜、显微解剖隐窝和完整的手术样品中所分离的)患者样品的公共数据集(GSE20916)。每个条柱表示一个样品的分析结果。纵轴表示FOXO3“有活性”(水平轴上方的值)相对于“无活性”(在水平轴下方的值)的概率。左侧的条柱表示正常组织,中间的条柱表示腺瘤样品,并且右侧的条柱表示结肠癌样品。C.正常结肠、结肠腺瘤和两个癌症患者样品中FOXO3和苏木精的免疫组织化学染色。下面一组是通过黑方框所示区域的放大。
图12显示了预测的FOXO活性和FOXO活性的肿瘤抑制性模式与氧化应激模式之间的区分。为获得更大的用于分析的样品数量,编译并分析了来自GEO数据库的多个公共Affymetrix数据集(结肠:GSE14333、GSE20916、GSE2109、GSE37364、GSE39084、GSE40967、GSE4183、GSE8671;乳腺:EMTAB365、GSE10780、GSE12276、GSE18146、GSE21653、GSE26910、GSE42568、GSE45827、GSE6532、GSE7307、GSE20685、GSE9195、GSE17907;前列腺:GSE2109、GSE32982、GSE3325、GSE46602、GSE55945、GSE7307)。对于每个分析的样品,FOXO活性显示为Log2odds。虽然连续缩放,但是当FOXO活性评分高于0时,FOXO原则上被认为有活性。实心圆中的FOXO有活性样品具有高于FOXO有活性的正常健康组织样品中SOD表达的平均值±2SD的SOD2表达水平,指示氧化应激诱导的FOXO活性的高可能性。圆圈表示SOD2表达处于正常范围的FOXO有活性样品,指示FOXO可能在肿瘤抑制性模式中有活性。PI3K活性样品的数量表示FOXO无活性样品的数量加上FOXO有活性的高SOD2样品的数量。关于详细解释,参见正文。A.结肠癌B.乳腺癌。关于根据Perou的均匀乳腺癌亚分型的细节,参见实施例4中的方法。C.前列腺癌。
图13显示了PI3K-FOXO通路和FOXO活性的肿瘤抑制性模式与氧化应激模式之间的区分。A.PI3K-FOXO通路和与SOD2靶基因表达的关系。在健康正常组织中,FOXO诱导了控制细胞分裂的靶基因的转录。当PI3K通路被激活时,或通过基因组突变或通过来自微环境的刺激,FOXO活性被阻断,对细胞分裂的控制丧失并且细胞代谢增加,与氧化应激相关。氧化应激诱导了FOXO的激活,其现在具有可替代功能以防御细胞中的应激情况的后果。略微改变FOXO靶基因表达谱以便现在也包括SOD2。B.就组织样品中PI3K活性进行决策的决策树。此简化决策树是有效的,基于以下假设:(1)FOXO在癌症细胞中表达,和(2)被健康的FOXO有活性细胞的有限污染。
具体实施方式
以下实施例仅说明特别优选的方法和与其相关的选择的方面。其中所提供的教导可以用于构建几种测试和/或试剂盒,例如以检测、预测和/或诊断一或多个细胞信号传导通路的异常活性。再者,在使用如本文所述的方法时,可以有利地引导药物处方,可以进行药物预测和药物功效的监测(和/或不良反应),可以预测并监测药物抗性,例如以选择待进行的随后测试(如伴随诊断测试)。以下实施例不应解释为限制本发明的范围。
实施例1:使用线性评分推断FOXO转录因子元件的氧化应激状态的示例性实施方案
此处呈现了基于FOXO靶基因SOD2、BNIP3、PCK1、MXI1、PPARGC1A以及CAT的简单线性评分。对于与前述基因相关的每个探针组而言,在此实施例中,将每个靶基因的表达与其在健康样品中的表达进行比较,其中FOXO通路已知在其肿瘤抑制性形式中有活性而在其肿瘤促进形式中没有活性。
在此实施例中,阈值定义为健康组织样品中表达水平的平均值加上三倍标准偏差,可替代地如果基因由于FOXO通路的氧化应激诱导活性而上调(这是SOD2和BNIP3的情况),则可以使用两倍标准偏差或任何其它正数。如果基因在正常的FOXO活性中上调(这是PCK1、MXI1、PPARGC1A以及CAT的情况),则阈值设定为在健康样品中表达的平均值减去三倍标准偏差。然后对于每个样品,评分通过为每个表达(表达超过或低于对于分别通过氧化应激上调和通过肿瘤抑制性FOXO活性上调的基因的设定阈值)添加点来计算。
此处,使用公共可获得的结肠样品数据集GSE20916的此评分结果使用表1中所示的所有基因和探针组来显示,该结肠样品含有描绘为正常结肠样品的健康结肠样品、腺(癌)和结肠癌。
表1:氧化应激诱导的FOXO靶基因
GSE20916中指定的每个亚组的评分显示在图3中。如预期,癌样品的评分高于正常(健康)样品,这表明可以使用前述基因的表达水平检测结肠癌样品(第7组和第8组)中肿瘤促进FOXO活性,因为它们的FOXO氧化应激评分明显高于健康结肠样品(第1组至第4组)的评分。相比之下,如通过更高的FOXO氧化应激评分而显而易见的,许多腺瘤样品(第5组和第6组)与正常结肠组织相比也具有更高的FOXO氧化应激评分。
图4描绘了仅那些来自GSE20916具有FOXO活性的样品的FOXO氧化应激评分,FOXO活性使用WO 2010/101635 A1中所述的FOXO活性模型确定。而且在此情况下,结肠癌样品(第7组和第8组)与绝大多数正常或健康结肠样品(第1组至第4组)相比具有更高的FOXO氧化应激评分。而且此处,腺癌样品(第5组)似乎位于正常样品与结肠癌样品之间,然而发现仅三分之一的腺癌样品具有有活性的正常FOXO TF元件。
对于所有来自GSE20916的样品通过仅使用信息量最大的氧化应激诱导的FOXO靶基因SOD2、MXI1、PCK1以及BNIP3所获得的结果显示在图5中。观察到相似的行为。
作为基于连续缩放上实际测量的基因表达水平的此离散评分的替代,提出了表达值的可替代变换:
“z-评分”,即连续表达水平缩放,使得跨越所有样品的平均值是0且标准偏差是1,
“模糊的”,即使用以下格式的sigmoid函数将连续表达水平转换成0与1之间的值:1/(1+exp((thr-expr)/se)),其中expr是连续表达水平,thr是如前所述的阈值,并且se是影响0与1之间差异的软化参数。
实施例2:改善WO 2015/101635 A1中所述的贝叶斯网络的示例性实施方案
作为对FOXO通路中的氧化应激建模的可替代方法,将WO 2010/101635 A1中所述的贝叶斯网络改善成包括表示氧化应激诱导的FOXO活性的单独模块。除了包括定义氧化应激状态的额外节点的事实之外,贝叶斯网络的结构保持不变。此节点称为OXI且它具有两种状态:它或是有活性的或是无活性的。图6示意性地表示通过添加氧化应激节点而整合了氧化应激的FOXO模型结构。出于可读性目的,尚未显示表示探针组的节点。表1显示了与BNIP3、SOD2、MXI1以及PCK1相关的探针组。与仅连接到TC(转录复合物)节点的靶基因相关的探针组在此实施例实施方案中与WO 2015/101635 A1中所述的相同。如在图6中可见,在FOXO通路与氧化应激之间存在有向边。这允许整合不可能具有无活性FOXO通路并同时具有氧化应激的知识。
如先前所定义,存在四种基因(SOD2、BNIP3、PCK1以及MXI1),其对于氧化应激诱导的FOXO活性而言是信息量最大的指标。因此,可以在节点OXI与基因SOD2、BNIP3、PCK1以及MXI1之间找到有向边。基因SOD2和BNIP3在存在氧化应激的情况下具有更高的表达水平,而这就是为什么仅存在来自OXI而不是TC的有向边。基因PCK1和MXI1受氧化应激FOXO和‘正常’FOXO节点两者影响。因此,这些基因具有来自TC节点和OXI节点两者的有向边。此模型中其余的基因仅受FOXO通路影响,并且为此仅在TC状态与其余的靶基因之间存在有向边。此处显示了具有这四种FOXO氧化应激基因的贝叶斯网络,但本领域技术人员也可以容易地将此扩展到包括剩余的两个基因PPARGC1A和CAT。
如在WO 2015/101635 A1中可见,网络中的所有节点必须借助于条件概率表(CPT)来定量以允许定量推理。由于氧化应激节点的添加,因此需要稍微改变如表1中所示的基因CPT和探针组的校准。在WO 2015/101635 A1中,探针组与靶基因节点之间的边的CPT在通路活性为已知的样品上来校准,但现在也需要使用已知具有氧化应激诱导的FOXO活性的样品。对此的原因是需要对受氧化应激影响的基因的表达水平做出区分。因此,仅受氧化应激节点影响的基因的探针组使用所述通路被关闭作为无活性样品的样品以及具有氧化应激的样品作为活性样品的样品来校准。对于PCK1和MXI1的探针组而言,使用了它们仅在氧化应激不是FOXO活性的原因的情况下在FOXO有活性的样品中具有更高表达水平的信息。因此,选择已知具有氧化应激诱导的FOXO活性的样品作为这些探针组的无活性样品,而选择正常活性FOXO样品(无氧化应激)作为这些探针组的活性样品。对于属于受FOXO TC节点影响的基因的探针组而言,仅校准保持不变。TC与靶基因之间的CPT和仅具有来自OXI状态的边的基因与WO 2015/101635 A1中的相同。TC与OXI之间新定义的CPT显示在表2中。此表反映了在不存在TC的情况下氧化应激是不可能发生的知识,而没有在存在TC的情况下关于氧化应激的现有知识。需要为具有来自TC节点和OXI节点两者的有向边的基因定义另一CPT。由于TC和OXI两者都具有两种状态,它们组合为总共四种可能性,因此此表具有八个表项。此情况下为PCK1和MXI1定义的此表显示在表3中。
表2:P[OXI|TC]的条件概率。
P[OXI|TC] OXI=无活性 OXI=有活性
TC=不存在 0.95 0.05
TC=存在 0.5 0.5
表3:受TC和OXI两者影响的靶基因的条件概率:P[TG|TC,OXI]。
在下文中,来自数据集GSE20916的样品用于校准这种贝叶斯网络。此数据集包含正常、腺瘤、腺癌和结肠癌样品。这些样品允许校准网络,这是因为实验证据表明在正常结肠样品中FOXO通路有活性,但不存在氧化应激。我们选择样品GSM523290、GSM523314、GSM523289以及GSM523310,这是因为这些正常结肠样品通过WO 2015/101635 A1的FOXO模型预测为最有活性的。所选的氧化应激状态FOXO校准样品是通过WO 2015/101635 A1的FOXO模型预测为最有活性的癌结肠样品:GSM523331、GSM523303、GSM523344以及GSM523323。最后,需要具有无活性FOXO通路的样品。如通过WO 2015/101635 A1的FOXO模型所预测,这些样品选择为最无活性的癌:GSM523372、GSM523313、GSM523332以及GSM523283。
在图7中,描述的模型在数据集GSE20916上测试。对于此集中的每个样品,计算FOXO通路为有活性的概率、TC节点的概率和FOXO通路处于氧化应激状态中的概率,即OXI节点的概率。几乎所有如黑点所示的正常结肠样品都在没有氧化应激的情况下预测成具有活性FOXO通路,而这是符合预期的。腺癌且尤其是结肠癌样品与正常样品相比显示明显不同的FOXO活性和氧化应激诱导活性组合。这显示从氧化应激活性区分正常FOXO活性是可能的。
这些结果证实前述FOXO靶基因,PCK1、MXI1、SOD2以及BNIP3将会指示氧化应激诱导的活性(换言之FOXO通路的肿瘤抑制性或肿瘤促进活性),并可以以这种贝叶斯网络来解释,该贝叶斯网络能够更好地检测FOXO通路的肿瘤抑制性活性或氧化应激相关的活性,该活性可能是肿瘤促进的。这是一种新颖且富有创造性的技术实现,因为在现有技术中并没有提及或暗示添加依赖于FOXO靶基因亚组节点的OXI节点(其指示FOXO通路的氧化应激诱导的活性)以及‘正常’FOXO活性结果的节点。
本文所示的方法可以用于例如诊断PI3K细胞信号传导通路的(异常)活性、基于推断的PI3K细胞信号传导通路的活性的预后、基于推断的PI3K细胞信号传导通路的活性的临床试验中医学受试者的招募、选择待执行的后续测试、选择伴随诊断测试、临床决策支持系统等等。在此方面,参考公开的国际专利申请WO 2013/011479 A2(“Assessment ofcellular signaling pathway activity using probabilistic modeling of targetgene expression”)和公开的国际专利申请WO 2014/102668 A2(“Assessment ofcellular signaling pathway activity using linear combination(s)of target geneexpressions”),这些专利申请更详细地描述了这些应用。
实施例3:选择指示氧化应激的基因
对于不同的组织来源而言,确定了具有如通过FOXO3模型所评估的活性FOXO3评分的癌症组织与根据所述模型具有活性FOXO3评分的相应正常组织之间的氧化应激相关基因的差异mRNA表达。如通过Affymetrix微阵列(Human Genome U133 Plus 2.0阵列)上的基因特异性探针组所测量的基因表达水平从公共GEO数据集获得,并在来自这种数据集的大量组织样品上取平均值。随后,从来自同一组织来源的癌症组织样品或非癌症状况中所测量的相同mRNA的各自平均水平中减去来自非恶性正常组织的氧化应激相关基因BNIP3、MXI1、PCK1、PPARGGC1、SOD2的平均mRNA表达水平。例如,从几种不同肺癌亚型的平均表达水平中减去SOD2基因(两个探针组,215223_s和216841_s)的正常肺平均表达水平。对于各自基因的每个探针组而言,减去的组织样品类型在表4中左侧来指示,减去的平均mRNA表达水平在右侧每个基因符号下方来指示。方框中的数字指示差异表达的水平且正值指示减法导致阳性结果;负水平指示阴性结果。在非恶性状况结肠腺瘤(A)、巴雷特食管(C)和子宫内膜(E)中,氧化应激相关基因没有过表达。相比之下,在大多数癌症类型(A-D,F-H)中,与相应的正常组织相比,氧化应激相关基因过表达。对于FOXO3和ESR表达水平而言显示了相似的减法结果,以指示这些转录因子水平没有差异表达。含有来自正常结肠、结肠腺瘤和结肠癌(A)的样品的GEO数据集用于引导集以发现氧化应激相关基因。呈现了其它GEO数据集(B-H)以验证非结肠相关癌症类型和非恶性状况中的氧化应激基因组。
实施例4:SOD2在FOXO活性的两种功能状态之间进行区分的用途
PI3K信号转导通路通常在癌症中是过度激活的。肿瘤对PI3K通路抑制剂是潜在敏感的,但缺乏评估功能PI3K活性的可靠诊断测试。因为PI3K通路负调控FOXO转录因子,所以FOXO靶基因表达与PI3K活性是反向相关的。开发了基于知识的贝叶斯计算模型,使用FOXO靶基因mRNA水平推断癌症组织样品中的PI3K活性。在各种癌症细胞系中,用此模型观察到的是添加PI3K抑制剂引起FOXO活性的增加,证实PI3K通路活性的降低。在组织样品中,预测FOXO活性在具有不同侵袭性的多种癌症类型中有活性。细胞氧化应激与癌症和FOXO的可替代激活物相关,并时常与PI3K通路活性相关。发现SOD2在FOXO激活的两种模式之间差异表达。定义了健康组织SOD2表达的阈值水平,在该水平之上,FOXO活性被认为是氧化应激诱导的。在缓慢生长的Luminal A乳腺癌和低Gleason前列腺癌中,FOXO典型地以PI3K介导的方式有活性,指示无活性的PI3K通路。在更侵袭性的Luminal B中,发现HER2和基底样乳腺癌FOXO时常或无活性或通过氧化应激诱导而有活性,指示PI3K通路活性的高可能性。决策树有助于评估癌症样品中的PI3K通路活性。此基于mRNA的FOXO模型可用于ErbB-PI3K通路靶向药物的应答预测。
在过去十年中,癌症的系统治疗从常规化疗转向在个体患者基础上靶向所选肿瘤性状的药物的施用。此“精准医学”方法需要可靠地预测对靶向药物的应答的生物标志物(1)。癌症生长和转移通过大约10至12个细胞信号转导通路来驱动,这些细胞信号转导通路相对独立于来源的癌症细胞类型(2-4)。由于如受体酪氨酸激酶扩增、PTEN丧失、激活PIK3CA中突变的基因组变化或者受来自癌症细胞微环境的刺激,因此这些细胞信号转导通路之一,PI3K通路,主要的细胞生长因子信号传导通路之一,在癌症中时常被过度激活。PI3K通路抑制剂或单独地或与其它靶向策略或常规化疗组合用于癌症治疗中(5-7)。尽管基于PI3K通路突变分析选择了潜在应答患者,但是仅患者亚人群充分地应答药物(8,9)。为改善药物应答的预测并监测治疗效力或出现的耐药性,需要测量功能PI3K活性的测试。
先前,基于测量通路特异性转录因子的靶基因mRNA水平,描述了基于知识的计算方法用于评估癌症组织样品中的信号转导通路活性(10,11)。现在,基于FOXO与PI3K通路活性之间众所周知的反向关系,报道了用于定量评估PI3K通路活性的基于mRNA的诊断学开发,其使用Forkhead Box O(FOXO)转录因子诱导的转录作为读出(12-16)。使用用PI3K通路抑制剂处理的或携带多西环素可诱导的活性FOXO3构建体的乳腺癌症细胞系和肺癌细胞系对该模型进行生物学验证。
在癌症组织中,FOXO可以通过细胞氧化应激被可替代地激活,细胞氧化应激是癌症中的共同性状,其干扰与PI3K通路活性的反向关系。SOD2/MnSOD FOXO靶基因水平用于在FOXO活性的两种功能状态之间进行区分,导致评估个体患者癌症样品中PI3K通路活性的稳健方法。
方法
用于FOXO3活性的基于细胞培养的模型系统
将MCF7和MDA-MB-231乳腺癌症细胞系在含有10%FBS(Lonza)、100U/ml青霉素和100μg/ml链霉素(Lonza)的DMEM-F12中培养。使用聚乙烯亚胺将第三代包装载体转染到慢病毒颗粒生成的HEK293T细胞中(17)。用含有pINDUCER20-FOXO3.A3的慢病毒稳定地转导MCF7和MDA-MB-231细胞,允许组成型活性FOXO3(FOXO3.A3)的多西环素诱导的表达(13,18,19)。细胞用20%FBS或10M PI3K抑制剂LY294002(Selleckchem)处理16小时以分别激活和失活内源性PI3K通路。通过用10ng/ml多西环素处理16小时诱导FOXO3.A3表达。
RNA分离和Affymetrix微阵列杂交
处理的细胞在如所示各自孵育16小时后收获,使用RNeasy试剂盒(Qiagen)分离RNA,并通过ServiceXS(GenomeScan、Leiden、The Netherlands、http://www.genomescan.nl)和Eurofins AROS Denmark(http://arosab.com/)在Affymetrix HTHG-U133+PM阵列板上杂交。
Affymetrix的质量控制
在所有Affymetrix微阵列数据中,从对此研究进行的实验和来自公共GEO数据库的数据集,都进行了广泛的质量控制。所用的所有微阵列都来自Affymetrix HG-U133Plus2.0或Affymetrix HG-U133+PM微阵列,这些微阵列已经用具有‘随机效应’汇总的fRMA进行处理(23)。原则上,即使在一些少数重新选择的情况下,Affymetrix HG-U133+PM平台也含有HG-U133Plus2.0平台的所有完美匹配探针。为了使来自两种微阵列类型的处理数据是可比较的,使用了仅含有共享探针的芯片描述文件,并从HG-U133Plus2.0 frmavecs获取此子集的处理参数以处理来自这两个平台的数据。
已使用几个质量检查执行微阵列样品的质量控制。这些检查包括所有PM探针强度的平均值、阴性或极端(>16位)强度值、poly-A RNA(样品制备加标)和标记的cRNA(杂交加标)对照、ACTB和GAPDH 3’/5’比率、通过affyQCReport包确定的阳性和阴性边界对照的强度值和强度中心和通过来自affy包的AffyRNAdeg函数确定的RNA降解值。来自未通过质量准则的乳腺癌和结肠癌数据集的样品从进一步分析中除去。
表5显示了已使用的数据集和它们出现的图。
表5:
Westem印迹
Western印迹分析使用标准的6%-15%SDS-PAGE进行。蛋白用FOXO3的一抗兔抗体(1∶2000)(H144,Santa Cruz)检测。将印迹与HRP缀合的二抗在4℃下育16小时。使用ImageQuant LAS 4000扫描仪(GE healthcare),蛋白用增强的化学发光剂(Biorad)可视化。
免疫荧光和免疫组织化学
对于免疫荧光染色,细胞在玻璃盖玻片上生长,使用4%多聚甲醛固定并用含有2%牛血清白蛋白(BSA)(Invitrogen)和0.1%正常山羊血清(Invitrogen)的PBS封闭。将细胞与FOXO3抗体(Foxo3A Rabbit MAb,1∶500CST-75D8)、二抗Alexa563缀合的抗体和DAPI(Sigma)温育。载玻片在Zeiss LSM710共聚焦显微镜上成像。
对于FOXO3免疫组织化学染色,使4μm福尔马林固定石蜡包埋的(FFPE)组织样品的切片脱石蜡并再水合。在阻断内源性过氧化物酶活性后,用pH 9.0的TE缓冲液(Dako)在95℃至96℃的水浴中25分钟进行抗原恢复。在冷却至少15min并用PBS洗涤步骤后,样品用PBS中的1%BSA封闭15分钟。然后将切片与FOXO3抗体(1∶50,CST-75D8)在室温温育1小时。可视化使用Dako Envision+TM-System抗-兔-HRP(DAB)实现。作为复染剂,使用了Gill’s2Heamatoxilin。图像用3D Histech扫描仪生成。阴性对照由在不添加一抗的情况下经历相似染色程序的切片构成。作为阳性对照,使用了非恶性扁桃体组织。
用于预测FOXO活性的计算模型的开发
如先前所述,FOXO转录活性的计算模型的开发是基于概率贝叶斯网络推断(11)。
信号转导通路建模方法是基于使用概率贝叶斯网络推断从其靶基因的表达谱推断通路活性。先前,开发这种模型以确定Wnt和ER通路的功能活性。如早先所述,贝叶斯网络使用用于MATLAB的Bayes Net Toolbox来构建。用作建模方法基础的贝叶斯网络结构是细胞信号转导通路的转录程序的简化模型(图8A),其由三种类型的节点组成:(a)转录复合物、(b)靶基因和(c)对应于靶基因的微阵列探针组。该模型描述了(i)靶基因的表达如何依赖于转录复合物激活和(ii)探针组强度如何反过来依赖于各自靶基因的表达。
使用实验数据对贝叶斯网络模型中的概率关系进行定量,以便使定量推理能够在新实验样品上进行。描述靶基因与它们各自探针组(ii)之间关系的参数在具有FOXO3.A3.ER构建体稳定转染的HUVEC细胞系上进行训练,其中用4-OHT刺激12小时产生了活性FOXO转录程序,用作FOXO3有活性训练样品,并在没有刺激的情况下用作FOXO3无活性训练样品(公共数据可在GSE16573(20)获得)。在PI3K通路的情况下,通路有活性的活性评分与FOXO3转录因子处于活性转录状态的概率成反比。如别处(11)所述,手动设定加强转录复合物与靶基因(i)之间关系的参数以改善模型跨越不同组织类型的一般化行为。
一旦该模型已被校准,通过在底层中将探针组测量值作为观察结果输入,并通过在模型中倒推(inferring backwards)FOXO3转录因子的活性概率,它可以用于新肿瘤样品的微阵列(Affymetrix HG-U133Plus2.0)数据上。通过将探针组测量值作为观察结果输入该模型中,倒推FOXO转录因子活性评分为FOXO转录因子几率p/(1-p)的log-2值,将该模型固定(frozen)并应用于细胞系和组织样品的微阵列数据。如果通路活性超过高于0的活性评分(对应于高于1比1的通路为有活性的几率),则将样品分类为FOXO有活性,如果活性评分低于0,将样品分类为FOXO无活性。
手动设定加强FOXO转录复合物与靶基因之间关系的参数以改善跨越不同组织类型的模型的一般化行为(11)。描述靶基因与其各自探针组之间关系的参数在携带可诱导的组成型活性FOXO3.A3-ER的Human Umbilical Vein Endothelial Cells (HUVEC)的公共数据集上校准,设定FOXO活性的阈值(GSE16573)(20)。通过将探针组测量值作为观察结果输入该模型中,倒推FOXO转录因子活性评分为FOXO转录因子几率p/(1-p)的log-2值,将该模型固定并应用于细胞系和组织样品的微阵列数据。出于验证目的,FOXO活性分析总是在独立的fRMA(除非另有指示)预处理的来自描述实验和来自公共GEO数据集的Affymetrix HG-U133Plus2.0微阵列数据上进行。
FOXO3A的直接靶基因的鉴定
为了最佳性能,跨越多种不同组织类型,数学模型应该含有FOXO转录因子的直接靶基因。不幸地,如KEGG(www.genome.jp/kegg)和Biocarta(www.biocarta.com)的通路数据库在此方面是不完整和不一致的(23)。因此,基于每个个体基因为各自转录复合物的直接靶基因的广泛科学证据来手动选择靶基因,广泛科学证据包括启动子区域增强子基序分析、转录因子结合实验(EMSA和ChIP)、基因启动子荧光素酶报告基因实验以及差异mRNA表达分析。广泛评价了使用PubMed从MEDLINE数据库中所检索的关于FOXO靶基因的可获得文献。此外,通过仅选择具有多个可靠证据源表明被一或多个FOXO家族成员转录调控的基因从Thomson-Reuters的Metacore提取靶基因。最终,使用如早先所述的相似方法学(11),根据文献证据排序靶基因。也包括在通过van der Vos和Coffer(24)公开的列表中的仅排序最高的靶基因才被选为“真正的”靶基因。
与氧化应激相关的SOD2水平
为研究健康组织与肿瘤组织的FOXO活性样品之间个体FOXO靶基因表达水平的差异,使用了来自健康组织样品和相应的恶性前或恶性肿瘤组织样品的公共可获得的微阵列数据集(表7)。
在通过计算FOXO模型评分为FOXO有活性的样品中,表7显示了如通过Affymetrix微阵列上指示的探针组所测的两个FOXO3靶基因SOD2和BNIP3的平均表达水平(标准偏差以斜体显示)。GEO数据集编号在该表中指示。A.样品基于高于5.6(概率高于0.98)的FOXO3活性概率评分(根据FOXO模型)从GEO样品集中选择;B.样品基于高于0的FOXO3活性概率评分(根据FOXO模型)从GEO样品集中选择。
在微阵列上的不同基因特异性探针组上所测的log2-缩放的标准化强度反映了基因表达水平。FOXO靶基因表达水平在FOXO活性肿瘤与健康组织样品之间来比较。
为了在不存在氧化应激的情况下确定SOD2表达水平的变化,对于健康正常组织的不同类型确定了Affymetrix SOD2探针组值的平均值+2SD。在SOD2 mRNA水平超过这些阈值水平的FOXO有活性样品中,FOXO被认为是氧化应激诱导的。
根据Perou从公共数据集中对乳腺癌样品进行亚分型
根据通过Parker和同事们所述的方法,所有乳腺癌样品的内在乳腺癌亚型从微阵列数据来确定(21,22)。使用如通过Parker和同事们(21)以及Prosigna Packet Insert(technologies,nanoString.Package Insert Prosigna Breast Cancer PrognosticGene Signature Assay,s.l.:http://prosigna.com/docs/Prosigna_Packet_Insert_US.pdf,2015)所述的方法学,内在亚型从Affymetrix微阵列数据确定。PAM50中所包括的所有50个基因的fRMA标准化基因表达使用与PAM50基因相关的探针组从微阵列数据中提取。如果一个以上的探针组与单个基因相关,则选择具有最高方差的探针组。luminal A、luminal B、富集的HER2、基础样以及正常样的质心使用来自具有给定亚型的GSE21653的样品来计算。接下来,对于所有样品计算与这些质心的Pearson相关系数。将每个样品分配到具有最高相关性的亚型。
结果
用于PI3K-FOXO活性的计算模型的开发
创建了基于贝叶斯网络的FOXO活性的计算模型,其从组织样品中来自26个FOXO靶基因mRNA水平推断FOXO转录活性(图8A)。虽然从一个靶基因的mRNA水平推断转录因子活性不是充分特异的,但是从大量靶基因(典型地20-30个)的表达水平推断活性似乎是定量相关转录因子活性的高特异性方式。为了跨越多种不同组织类型的最佳性能,选择了直接靶基因。由于如KEGG(www.genome.jp/kegg)和Biocarta(www.biocarta.com)等的通路数据库在此方面是不一致的(23),因此基于文献(PubMed)和Thomson-Reuters的Metacore的科学证据来手动选择基因,并使用如早先所述的相似方法学排序(11)。选择排序最高的基因来构建计算FOXO通路模型(16,24)(表6)。具有可诱导的FOXO活性的HUVEC在未转化的环境中为FOXO活性状态提供“基础真相”证据,并在模型冻结前用于校准模型(图8B)。
贝叶斯模型的预测与包括独立样品数据的完整HUVEC数据集中的已知实验FOXO活性状态是一致的(图8B)。如在增殖细胞中所预期,HUVEC、用4OHT处理的HUVEC和HUVEC-FOXO3.A3-ER预测为具有低FOXO活性并因此具有活性PI3K信号传导。用4OHT处理的HUVEC-FOXO3.A3-ER预测为具有高活性FOXO,与组成型活性FOXO3.A3的诱导是一致的。在表达FOXO3.A3-ER-H212R(具有降低的DNA结合能力的FOXO3突变版本)的HUVEC中,该模型预测FOXO在未处理的细胞中无活性并在用4OHT处理的细胞中具有低FOXO3活性(20)。这些观察结果证实该模型特异性地检测通过FOXO诱导的转录变化,并对低水平FOXO活性敏感。
乳腺癌症细胞系中PI3K-FOXO模型的生物学验证
校准后,所述模型在独立的乳腺癌症细胞系中进行生物学验证。ER阳性、PIK3CAE545K突变体MCF7和三阴性MDA-MB-231细胞用多西环素可诱导的FOXO3.A3表达载体稳定转导,从而允许在用多西环素处理16小时后快速和受控诱导FOXO3蛋白表达和转录活性(图9A)。在未处理的细胞和20%FBS刺激的细胞中,FOXO3蛋白主要在细胞质中检测;在用多西环素、PI3K抑制剂LY294002、和多西环素组合LY294002所处理的细胞中转换成显性细胞核定位。这显示了FOXO3的细胞核易位在此实验细胞培养系统中以受控方式被诱导。在来自此细胞模型的Affymetrix mRNA表达数据上,FOXO模型分别预测了未处理的细胞中的低FOXO活性(PI3K通路有活性)、和多西环素处理的(PI3K通路无活性)MCF-FOXO3.A3细胞和MDA-MB-231-FOXO3.A3细胞中的高FOXO活性;20%FBS处理的MCF7细胞中的低FOXO活性(PI3K通路有活性),并且在多西环素、LY294002和组合的多西环素+LY294002处理的细胞中的高活性(所有PI3K通路无活性)(图9B/C)。这些结果一起证实了在独立的癌症细胞系样品中计算FOXO模型如所预期地预测了FOXO活性。
通路模型用于预测和监测对药物应答的用途
在FOXO活性与细胞系中PI3K活性成反向相关的前提下,研究的是FOXO模型是否在独立癌症细胞系数据集(GSE51212,GSE30516)中能够预测对靶向受体酪氨酸激酶活性的药物的应答。在用埃罗替尼(EGFR抑制剂)、司美替尼(MEK抑制剂)或BEZ235(PI3K/TOR双重抑制剂)处理的EGFR突变型HCC827肺癌细胞系中对FOXO3活性进行评分。FOXO在未处理的样品中评分为无活性,指示活性PI3K通路;在用所述三种药物的任一种处理后,FOXO评分为有活性,用EGFR抑制剂是最大的,证实所有三种药物在直接地和/或间接地阻断PI3K通路的活性中都是有效的(图10A)。在表示三阴性(BT20)、ER阳性(MCF7)和HER2阳性乳腺癌(MDA-MB-453)的三种乳腺癌细胞系中,当用埃罗替尼处理时,FOXO活性评分如预期增加(图10B)。
健康结肠和结肠直肠癌组织样品中的FOXO活性
为了在用于患者组织样品时模型的评估,使用了许多选择的公共数据集。首先,将FOXO活性模型应用于来源于32个正常结肠组织和32个腺瘤组织(GSE8671)的患者活组织检查的组织样品。在健康结肠与腺瘤组织之间观察到FOXO活性评分的明显差异,显示FOXO分别地有活性和无活性,表明结肠腺瘤中PI3K通路的预期激活(图11A)。
其次,将FOXO模型应用于含有正常结肠、良性结肠腺瘤和结肠癌组织(GSE20916)的患者组织集(图11B)。在正常结肠组织样品中,FOXO预测为有活性。在大多数腺瘤组织样品中,FOXO预测为无活性,与第一数据集中的发现一致,指示PI3K通路活性。然而,在一半的结肠癌组织样品中,FOXO预测为有活性。由于结肠癌被认为由结肠腺瘤产生,因此预期了至少相同频率的PI3K通路活性。
因而,在高达约三分之一的癌症组织样品中,高FOXO活性评分将预期指示无活性的PI3K通路。在其余的FOXO活性癌症样品中,可能存在高FOXO活性的另一原因,一个是FOXO通常为有活性的健康细胞的混合。为了对此进行研究,开发了FOXO3免疫组织化学(IHC)染色以确定组织样品中的细胞质和细胞核FOXO3定位。FOXO3发现主要在健康结肠隐窝细胞的细胞质中,但存在于健康粘膜细胞和其它非肿瘤健康细胞的细胞核中,与公共数据集GSE20916中所见的基于mRNA的FOXO活性评分一致(但不是相同的样品)(图11B/C)。这些结果表明正常细胞的混合可以导致假阳性FOXO评分。在结肠腺瘤细胞中,FOXO3显示了细胞质定位,而结肠癌症细胞明确显示了细胞核区域及具有细胞质染色的其它区域的异质的FOXO3定位。
FOXO活性可能存在于侵袭性癌症组织中的另一良好描述的原因是细胞氧化应激(12,25)。然而,正常组织中FOXO活性的功能明显不同于氧化应激期间的功能,并因此可能反映在转录靶基因的差异中。
为了确定使用的FOXO靶基因的组内哪些基因将最好区分正常样品与癌样品中的FOXO活性,在正常结肠与结肠癌组织样品之间比较靶基因表达水平,在这些样品中FOXO通过模型预测为有活性。与正常结肠组织相比,SOD2和BNIP3基因表达在FOXO有活性的癌症组织样品中强烈增加(表7)。两种基因都在应答氧化应激中起作用并在这些情况下通过FOXO被转录,使它们成为在FOXO活性的两种模式之间进行区分的主要候选物(26,27)。
实际上,比较各种FOXO活性正常组织与相应恶性前或恶性肿瘤组织样品(结肠癌、乳腺癌、巴雷特食管癌、食管癌、膀胱癌以及神经胶质瘤)之间的SOD2和BNIP基因表达水平证实了来自侵袭性癌症类型的FOXO活性样品中的SOD2和在较小程度上BNIP3的表达水平增加(表7)。与之形成鲜明对比的是,在两种良性过度增殖状况结肠腺瘤和巴雷特食管癌的FOXO活性样品中,FOXO活性与增加的SOD2和BNIP3表达不相关,指示在这些良性肿瘤中FOXO与健康组织同样以PI3K调控方式来激活。由于SOD2显示了FOXO活性正常组织样品与相应FOXO活性癌症类型之间最普遍和最深刻的差异表达,因此选择此基因作为在FOXO活性的两种模式之间进行区分的最可靠参数。PI3K调控的(非氧化应激)FOXO活性的SOD2上限阈值水平定义为高于正常组织中平均表达水平的两个标准偏差,并且计算健康结肠组织、乳腺组织和前列腺组织的SOD2上限阈值水平。
随后,将与SOD2表达阈值组合的FOXO模型应用于独立公共可获得数据集,其具有来自患有结肠癌、乳腺癌和前列腺癌的个体患者的数据。在具有升高的SOD2表达的FOXO有活性样品中,PI3K通路活性不能从FOXO活性来直接推断。另外,如果FOXO通过所述模型评分为无活性,则关于FOXO表达的知识对于关于PI3K活性的结论而言是需要的。FOXO3被认为是癌症中最相关的FOXO基因并在迄今为止分析的所有癌症类型的所有样品中始终表达,所述癌症类型包括乳腺癌、结肠癌、前列腺癌、脑癌、膀胱癌以及食道癌(表7)。
原发性结肠腺瘤和癌组织样品中的FOXO活性模式(经典或氧化应激)的预测
对大的健康结肠组织样品集(n=121)的分析允许设定FOXO活性样品中正常SOD2mRNA水平的阈值(图12A)。随后,汇编了患者结肠腺瘤和癌样品数据的扩展独立集并且确定了FOXO活性和SOD2表达水平。在正常结肠样品中,仅2.6%的FOXO活性样品具有超过阈值水平的SOD2表达。在FOXO有活性的少数腺瘤样品中(n=12,16%),SOD2水平升高(超过阈值)一半。在癌样品中,三分之一的样品评分为FOXO有活性,其中53.9%具有升高的SOD2表达。
原发性乳腺癌组织样品中FOXO活性模式(经典相对氧化应激)的预测
相似地,分析了来自乳腺癌患者的汇编数据集。在FOXO活性分析之前,所有癌症数据集中的乳腺癌肿瘤亚分型使用PAM50算法进行,以确保相似地确定所有数据集中的亚型(21)。与健康结肠组织中的发现一致,在正常乳腺组织中FOXO预测为一般是有活性的(85%)(图12B)。在luminal B、HER2和基底样亚型中,对于FOXO而言分别为37%、23%和20%评分为低,指示PI3K通路活性。随着癌症亚型侵袭性增加,观察到增加百分比的FOXO活性样品具有升高的SOD2(超过健康乳腺癌阈值):从luminal A中的4.7%到基底样乳腺癌中的71.4%。
原发性前列腺癌样品中FOXO活性模式(经典相对氧化应激)的预测
在来自汇编的公共患者数据集的正常前列腺组织和原发性前列腺癌样品中,FOXO活性分析显示了FOXO在91%的患有更低Gleason评分肿瘤(Gleason 4-7)的患者中有活性。具有较高Gleason评分(Gleason 8-9)的患者样品太少,不能得出任何比较性结论(图12C)。令人感兴趣地,在FOXO有活性的原发性前列腺癌样品中,SOD2表达都不会增加到超过为正常组织设定的阈值水平,指示对于前列腺癌而言,可以从FOXO活性评分安全地推断PI3K通路活性。在大多数原发性前列腺癌样品中,PI3K通路是无活性的。
鉴定具有活性PI3K通路的肿瘤
为了促进组织样品中功能PI3K通路活性的推断,基于以下前提创建简化决策树:(1)FOXO在来自样品的癌症细胞中表达和(2)测量的FOXO活性源自于癌症细胞(图13B)。假设PI3K通路在活性FOXO氧化应激的情况下有活性,那么对于每种研究的癌症类型而言这些样品可以添加(图12,FOXO有活性黑点)到具有无活性FOXO(指示活性PI3K通路)的大量样品中以计算可能患有具有活性PI3K通路的肿瘤的患者总数/百分比(图12,在带有星号的表中指示)。如此计算的PI3K通路活性样品的百分比在正常组织(结肠、乳腺、前列腺)中在8%与13%之间,并在Luminal A和正常样乳腺癌以及低Gleason评分的前列腺癌中是相当相似的(分别地13%、15%、15%);在Luminal B、HER2和基底样乳腺癌中,具有PI3K通路活性的样品的百分比高得多,分别为45%、45%和76%;而在结肠腺瘤和结肠癌中,几乎所有样品都评分为PI3K通路有活性(分别为样品的92%和85%)。
讨论
用于预测FOXO和PI3K活性的基于知识的贝叶斯模型
PI3K通路在癌症中是重要的增殖和存活通路并是ErbB生长因子信号转导机制的核心信号传导部分。许多靶向药物旨在阻断该通路中多个位置处的PI3K通路活性。改善对PI3K通路抑制剂的应答率需要可靠评估癌症样品中PI3K通路活性的测试。FOXO转录因子通过PI3K通路进行负调控,并原则上可以用作PI3K通路活性的反向读出(5、12、28)。为测量癌症组织样品中的PI3K通路活性,开发了基于计算知识的贝叶斯网络,从而从手边组织样品中待测量的已确立FOXO靶基因mRNA表达水平推断FOXO转录活性(11)。不同的FOXO成员是多余的,并且FOXO1、FOXO3和FOXO4诱导的基因调控的比较性分析指示每个FOXO成员的转录谱之间的较大重叠(16、24、29)。因此,所述FOXO活性模型,其整合了关于直接FOXO靶基因调控的知识,作为一般的FOXO活性预测机。
在FOXO可诱导的HUVEC上校准此贝叶斯模型产生了计算FOXO模型,其如所预期预测了具有组成型活性FOXO3或与PI3K通路靶向药物一起温育的乳腺癌症细胞系中的FOXO活性。MCF7细胞中的观察结果是FOXO与异位FOXO激活相比在用PI3K抑制剂药物LY294002处理的细胞中评分为较低活性,而这很容易通过异位表达所诱导的更高FOXO3蛋白水平和/或在用LY294002处理的情况下作为阳性生长因子信号传导反馈的结果来解释。PI3K通路的药理学抑制可以引发生长因子反馈应答,其可以重建构成癌症细胞中药物抗性开发的主要组分的生长因子信号传导(6、7、30)。与MCF7细胞相反,在未处理的MDA-MB-231细胞中检测到一些细胞核FOXO蛋白。然而,FOXO活性模型将此FOXO评分为转录上无活性-如在此快速分裂的细胞系中所预期的那样。因此,FOXO的细胞核存在不能总是用于推断转录活性。
在三种乳腺癌症细胞系中以及在具有突变的过度活性EGFR的肺癌细胞中,该模型鉴定出增加的FOXO活性,其与通过EGFR抑制剂埃罗替尼有效抑制PI3K通路活性相关。此外,用双重mTOR-P13K抑制剂(BEZ235)和MEK1/2抑制剂(司美替尼)处理肺癌细胞系相似地导致增加的FOXO活性,从而降低了推断的PI3K通路活性。通过生长因子受体的ErbB家族(EGFR、HER2、HER3、HER4)启动的信号转导导致经由PI3K-AKT和RAS-MEK-ERK-MDM2的FOXO失活(31)。
因此,所述贝叶斯模型在这些基于细胞培养的PI3K通路激活模型中稳健地预测了FOXO和PI3K活性,提供了所述模型的生物学验证。然而,肺癌细胞系对靶向EGFR下游信号传导通路的不同元件的三种药物的应答差异说明,为了做出关于靶向药物的最佳选择,可能需要进行额外分析(例如基因组突变分析)以确定PI3K通路活性的基础原因。
预测组织样品中FOXO活性的计算模型
将所述模型应用于组织材料以推断PI3K活性证明为更有挑战性。如所预期,在来自各种组织类型(结肠、乳腺、前列腺、食道、膀胱、脑)的健康组织样品中,FOXO评分为有活性。在结肠腺瘤样品中,FOXO活性时常丧失且将PI3K通路推断为有活性,再次强调FOXO在控制细胞分裂中的作用。在此情况下,生长因子诱导的PI3K通路激活启动促有丝分裂信号传导并阻断FOXO转录活性(12、32、33、34)。
在调控FOXO活性的不同机制之间进行区分
在癌症中,FOXO可以有活性的情况会变得更复杂。在PI3K通路时常被激活的结肠癌和luminal B、HER2和基底样乳腺癌亚型中,大多数样品预测为具有活性FOXO转录因子(2、35)。这表明在所有癌症组织样品中,简单地反转FOXO活性状态以推断PI3K通路活性是无效的。与控制细胞分裂相关的经典FOXO活性与生长因子/PI3K活性诱导的细胞增殖存在下的FOXO活性之间的区分子(differentiator)是必要的。
虽然被认为是肿瘤抑制物,但是FOXO也作为细胞稳态的调节物起作用并应答各种不利的细胞条件,包括DNA损伤、高水平的活性氧和低营养物可获得性(12、36、37)。实际上,在癌症样品中,活性PI3K通路可以与活性FOXO转录组合存在,因为FOXO可以经由氧化应激以可替代方式被激活以保护细胞对抗ROS(图13A)。在低氧和快速增殖的癌症组织中,这种氧化应激状态是时常发生的现象(12、38-40)。
对FOXO进行翻译后修饰以使其转录功能适应不同的细胞内条件(41)。假设FOXO的两种非常不同的功能作用将反映在FOXO靶mRNA表达谱的变化中。BNIP3和SOD2是所述计算模型所用的两个FOXO3靶基因并已知在细胞氧化应激存在时被诱导以保护细胞对抗此毒性状态的后果(26、27、42)。实际上,与FOXO有活性健康组织和良性过度增殖性结肠腺瘤相比,SOD2和BNIP3两者的高表达通过比较多个FOXO有活性的癌症样品与相应健康组织样品之间的FOXO靶基因表达水平来发现。这些结果支持以下概念:与生长因子信号传导平行的氧化应激可以在快速增殖的癌症组织中通过可替代通路诱导FOXO活性。这两种基因中的SOD2表达似乎在来自大量癌症类型的FOXO活性样品中与健康组织相比普遍升高。为了能够在经典FOXO活性与氧化应激相关的FOXO活性之间进行区分,定义了健康组织中SOD2表达的阈值水平。将此信息添加到FOXO模型中可提高在各种类型的癌症中推断PI3K通路活性的可靠性。
将此规则应用于乳腺癌亚型和前列腺癌亚型,其就初步临床验证所允许的侵袭性行为和预后方面是良好定义的。实际上,将SOD2表达水平的信息添加到FOXO活性评分,通常将luminal A乳腺癌和较低Gleason评分的前列腺癌中的FOXO活性分类为经典FOXO活性,具有推断的无活性PI3K通路。实际上,在不存在活性HER2-PI3K通路的情况下,这些癌症类型典型地更加可区分且缓慢地生长并通过ER通路来驱动。与之相反,在具有更侵袭性行为的乳腺癌亚型(即luminal B、HER2和基底样乳腺癌亚型)中,对FOXO无活性(指示活性PI3K通路)或FOXO活性的样品越来越多地分类为FOXO氧化应激活性。总之,在良好区分的缓慢生长的乳腺癌和前列腺癌中,FOXO通常在经典模式中有活性以控制细胞分裂,而在更侵袭性的癌症中FOXO通过PI3K通路激活来失活或在氧化应激模式中有活性。令人感兴趣地,氧化应激相关的FOXO活性实际上可以起作用以通过保护细胞免受通常导致细胞死亡的氧化应激损伤和刺激生长因子PI3K-AKT通路两者来支持肿瘤生长(43)。
计算FOXO模型鉴定个体癌症组织样品中PI3K通路活性的用途
计算模型的用途是评估个体癌症组织样品中的功能PI3K通路活性以支持选择针对ErbB生长因子信号传导通路(例如HER2-PI3K通路和EGFR通路)的靶向药物的决策和/或监测应答并检测对抗选定药物的出现的抗性。使用评估FOXO活性的FOXO计算模型组合指示FOXO活性模式的氧化应激SOD2基因标志物,PI3K通路有活性的可能性可以使用(略微简化的)决策树从高度特异的基因表达数据得出(图13B)。在FOXO评分为有活性的情况下,SOD2的表达水平解释成根据PI3K调控的相对于氧化应激诱导的FOXO活性做出决策。如果FOXO活性是通过氧化应激引起的,则隐藏PI3K通路活性的基础信息,并且不能就PI3K通路活性方面正式地做出决策。然而,细胞氧化应激相关的FOXO活性时常(如果不是总是)与高等级癌症中的生长因子通路活性同时发生(4、38)。因而,在活性FOXO/高SOD2存在时,存在PI3K通路为有活性的高可能性。将评分为FOXO无活性的或FOXO有活性的氧化应激的样品加起来提供了每个癌症亚型组内患者总数的指示,这些患者患有PI3K活性肿瘤并可能受益于PI3K通路抑制剂治疗。在低等级的Luminal A和较低Gleason评分的前列腺癌组中,由此计算的PI3K活性肿瘤的百分比接近于健康组织中所见的(粗略地约10%),而在更高等级的乳腺癌中,这在基底样乳腺癌组中增加到高达四分之三。实际上,PI3K通路可能是癌症中最时常激活的通路。
当在组织样品中FOXO预测为有活性并且SOD2的表达水平落在正常范围内时,互补的IHC染色可能对排除FOXO活性是通过癌症样品的健康组织细胞污染来引起的情况是必要的。考虑到此点,FOXO模型提供了一种用于确定肿瘤样品中功能PI3K通路活性的稳健方法。鉴定异常PI3K通路活性的突变原因的靶向基因组分析可以限制于推断出活性PI3K通路的患者。此方法期望改善旨在增加治疗功效的采用靶向ErbB PI3K-AKT-mTOR通路的药物的决策,并期望适用于许多不同的肿瘤类型。如药物开发期间药物应答的定量评估那样,监测治疗应答和耐药性例如在新佐剂或“机会窗口”设定中是另一种设想的应用。
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序列表:
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<110> 皇家飞利浦有限公司
<120> 从氧化应激区分肿瘤抑制性FOXO活性的方法
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cgtctggcaa atcttcgacg atcccatata ttagagctca cctctgtcat ttttccaatc 660
gaggaagtaa agacgggtgt gagagacccc gcagatgtgt cttcagagag tgacagtgcc 720
atgacctcca gcactgtgag caagcttgct gaagcccgga ggacaactta cctctcagga 780
cgatgggtct gtgacgatca caacggagac accagcatta gcattacagg gccttggatt 840
agcctcccta acaatgggga ctactctgcc tactacagct gggtggagga gaagaaaaca 900
acccaggggc ctgacatgga gcagagtaac cctgcctaca ccatcagtgc tgcgctgtgc 960
tatgcaactc agctggtcaa cattctgtct catatacttg atgtaaatct tcccaaaaag 1020
ctctgcaaca gtgaattttg tggcgaaaat ctaagcaagc agaaatttac tcgagcagtg 1080
aagaaactga atgcaaatat tctttacctt tgtttttctc agcatgtaaa tttagatcaa 1140
ttacaaccac tgcataccct caggaatcta atgtacctgg tcagtccaag ctctgaacac 1200
ctaggcaggt cagggccctt tgaagtacga gcagaccttg aggagtccat ggaatttgtg 1260
gatcccggag ttgctggaga atcagatgag agcggagatg agcgcgtcag cgatgaagaa 1320
accgacctgg gcacagactg ggagaacttg cctagtcccc ggttttgtga tatcccttcc 1380
cagtctgtgg aagtctccca gagtcagagc acccaggcgt ccccacccat cgcgagcagc 1440
agtgcaggtg ggatgatctc ctctgcagca gcctcggtga cctcctggtt taaagcttac 1500
actggacacc gttaacgagc atggaccaaa acataccaaa tctgcatcaa gaaagttctt 1560
ctcccactac actctagtaa acattttctg tttaagttaa gatagtgtct ggaacaaaga 1620
ggttaaagtg ttgttttgtt ttgtcttttt aagcagggag acaaacattt ctatttgcca 1680
agtggcctgt gatggtgacc aacatgctta tgataattaa gagaacaggg gtcgaaggtc 1740
tttctaccca gaccagtgct ggtggaagga ggacctgtgc gtgtggccag ttctgccaag 1800
gaagcagttg atttgggttc cctctgggcc cgggccaccg ggcccacaga tatgggtcag 1860
tgtgctggtc cttgcggtgc tgagactgtt cctgacactt taagttttag aggttggttg 1920
aatcacaaga ggtgattctt gattattagg acatgaaaga taaaagctct ttaataagag 1980
tttttctgcc attgtttttt gtatgagaac cagcaggcaa tttaaaattt ctaatttggt 2040
cctttgattt tgtttgggag gggtgagtta cacgtatttt attcatgctg ctctgtcgta 2100
gtttgtcaga cattcctgtt tttctttccc ccacacacca aagaaaatga aagtcttttt 2160
ctttaggacc cacatccata aatggaagaa atcctggctg caataatgtc tagagagttt 2220
ttaactattt tcttgtattc tgaggggaat taagcttatt cttacctagt tgaattcctg 2280
ccatccacac tatgagcatt ttgaaattga acttatattt tctgggtgaa aataagtcat 2340
gaaggtcatt cccttatgta agctcaatgc ctgcctgggc acaggggaaa agccacttag 2400
ttaagtggcc tctggtcatt cttgtggtgt ccactttctt tctatgggat tgagtaggtg 2460
gcaggtgttt tcaggggaaa ccatcctact tgtttccccg aactctttgt tgctctgagg 2520
acacagcttt gctcagaaat gcagcgcaga tccttacggc tgatgctact ctgctctgtt 2580
ctggggaaag cacaatataa agaaagaatt tcccagccag gcgcagtggc tcacgcctgt 2640
aatcccagca ctttaggagg ccgaggcagg cggatcactt gaggtcagga gtttgagagc 2700
agcctggcta acatggtgaa accctgtttc tactaaaaat acaaaaaatt accgggtgtg 2760
gtggcgcacg cctgtaatcc cagctactcg ggaggctgcg gcaggagaat cgcttgaacc 2820
gggaggcaga ggttgcagtg agccgagatt gtgccattgc actccagcct gggcaacaag 2880
agcgaaactc cgtctcaaaa aaaaaaagaa tttccctcag caggagatca ttttcagctc 2940
acgtgtcttg tcattctttt agtgacaatc ttacaagaaa actataatga gagaggcatt 3000
atgtacaaat atgtaagtag tttattttta ataactgcaa aaaaatccta tgtaacaact 3060
accaaaagaa atcctatgaa agagtcctaa caggcattat taccatatct tatgtgattg 3120
gcatgatagc acctctgata aatcattcag aggtttgcca tgccccagct tcttttctca 3180
tcataataat tgtagttgat actttgcctc caagtccgag gtgctatata gcttttgcta 3240
atggtatatt tggtgttttg tatagttttg ggtagagttg cagaacggag tttatttcta 3300
tccggtagtc acaaattcct tggctctatg aattttccat gaaaggagga agtaggcttt 3360
tctcgttgtg ggtggtcttt tttttttttg gagacggagt ctcactcagc tgcccaggct 3420
ggagtgtagt ggcaccatct ccgctcactg caaccaccat ctcctgggtt caagcaattc 3480
ttccatctca acctcccgag tagctgggat tataggcacc tgccatcatg cccagctaat 3540
ttttgtattt tagtaaagac gggggttttc accatgttgg ccaggctggt cttgaactcc 3600
tgacttcagg tgatccgctt gccttggcct cctaaagtgc taggattaca ggcctgagcc 3660
accgcgcccg gccccttatg ggttcttcta cactgctggg atctctgttt taagtgctca 3720
gcttcatgat tgattgctgg gcttccattt tcccatccag ttctggagtt cgtagagagt 3780
gaagatggta gacttgaaca gataaataaa cttaacgatc ttgtaagagt tgtctagcta 3840
cttaaaaccc tcagaagtaa gagcttagtc tcacgagttg taagagtggg atttggagct 3900
tggtggtgga gactgacttc agctgagaga tgcacaacag tcatggtttt cttaagcctc 3960
ttatgaaacc atgaatgaga gatgaagcta aagaatagaa tccagagatc acaaactcat 4020
ctagagtact tccacaaaat ttacaaagat gtgggaactt tatggatagg atatattttg 4080
tttgttgttg ttaatatcaa ctagaggcac tttacatagg gttaagtgat cgaacccttt 4140
tgtggttttg aacaccaaca tactggctta cactgctgaa atattttggg tttcattatt 4200
ttgcactgga tccaccctgt aaatactctt aagtatacat ttcaaccact gttttttcta 4260
ctctttttgc tgctcattaa aatctttcat gtaggtgcca gaaccatatg taaacagctt 4320
tttaaaaaat tgaagctggt attttgttta aacaaaaagc catagaactt ggtcatgttt 4380
tccattttaa aatgatttac tgaaacaaag taatactaat aaaaacccac aggcaccaaa 4440
caggctgctt aaaatggtct gttaaagaca ttttttggtt atggaatata agaaaagttt 4500
tgcacatctg taagggggaa aaacagtata tcaccattgg gtagagtgga cgggactcat 4560
gtaaggactc aatttgggga agagcattca gtggcatgct gttagaggac tagtgtccga 4620
gaatctcctc acagtatcat gttgcaggaa ttccccattg ctctgcaact tccaaaccag 4680
tttgagtcat acaaatgttt tctaaacttt tattgtatta ctgcaataaa tcttttaaca 4740
gtaaaaaaaa aaaaaaaaaa 4760
<210> 3
<211> 8270
<212> DNA
<213> Homo sapiens
<400> 3
aagagctcgc ccagctctgc gggcgccgcc accttcgccg ccaccgctgc ctttctcctc 60
ctcctgtcgg cgtgcggggg ccgcgcccgg cggcagctct gccctaggtg ggcggcggcg 120
cggcccaggc tgcagctgag cgctctgcgc ggcgcagccg ggtctcccgc gtgtaccacg 180
ccgtgacagg tgcagagtcc gggctgagga cccacctgca gccgccgccg cgatgcccac 240
catgcggagg accgtgtcgg agatccgctc gcgcgccgaa ggttatgaga agacagatga 300
tgtttcagag aagacctcac tggctgacca ggaggaagta aggactattt tcatcaacca 360
gccccagctg acaaaattct gcaataacca tgtcagcact gcaaaataca acataatcac 420
attccttcca agatttctct actctcagtt cagaagagct gctaattcat tttttctctt 480
tattgcactg ctgcagcaaa tacctgatgt gtcaccaaca ggtcgttata caacactggt 540
tcctctctta tttattttag ctgtggcagc tatcaaagag ataatagaag atattaaacg 600
acataaagct gataatgcag tgaacaagaa acaaacgcaa gttttgagaa atggtgcttg 660
ggaaattgtc cactgggaaa aggtggcagt aggggagata gtgaaagtga ccaatgggga 720
acatctccca gcagatctca tcagtctgtc ctcaagtgag ccccaagcca tgtgctacat 780
tgaaacatcc aacttagatg gtgaaacaaa cttgaaaatt agacagggct taccagcaac 840
atcagatatc aaagacgttg acagtttgat gaggatttct ggcagaattg agtgtgaaag 900
tccaaacaga catctctacg attttgttgg aaacataagg cttgatggac atggcaccgt 960
tccactggga gcagatcaga ttcttcttcg aggagctcag ttgagaaata cacagtgggt 1020
tcatggaata gttgtctaca ctggacatga caccaagctg atgcagaatt caacaagtcc 1080
accacttaag ctctcaaatg tggaacggat tacaaatgta caaattttga ttttattttg 1140
tatcttaatt gccatgtctc ttgtctgttc tgtgggctca gccatttgga atcgaaggca 1200
ttctggaaaa gactggtatc tcaatctaaa ctatggtggc gctagtaatt ttggactgaa 1260
tttcttgacc ttcatcatcc ttttcaacaa tctcattcct atcagcttat tggttacatt 1320
agaagttgtg aaatttaccc aggcatactt cataaattgg gatcttgaca tgcactatga 1380
acccacagac actgctgcta tggctcgaac atctaatctg aatgaggaac ttggccaggt 1440
taaatacata ttttctgaca aaactggtac tctgacatgc aatgtaatgc agtttaagaa 1500
gtgcaccata gcgggagttg cttatggcca tgtccctgaa cctgaggatt atggctgctc 1560
tcctgatgaa tggcagaact cacagtttgg agatgaaaaa acatttagtg attcatcatt 1620
gctggaaaat ctccaaaata atcatccaac tgcacctata atatgtgaat ttcttacaat 1680
gatggcagtc tgtcacacag cagtgccaga gcgagaaggt gacaagatta tttatcaagc 1740
agcatctcca gatgagggag cattggtcag agcagccaag caattgaatt ttgttttcac 1800
tggaagaaca cccgactcgg tgattataga ttcactgggg caggaagaaa gatatgaatt 1860
gctcaatgtc ttggagttta ccagtgctag gaaaagaatg tcagtgattg ttcgcactcc 1920
atctggaaag ttacgactct actgcaaagg agctgacact gtaatttatg atcgactggc 1980
agagacgtca aaatacaaag aaattaccct aaaacattta gagcagtttg ctacagaagg 2040
gttaagaact ttatgttttg ctgtggctga gatttcagag agcgactttc aggagtggcg 2100
agcagtctat cagcgagcat ctacatctgt gcagaacagg ctactcaaac tcgaagagag 2160
ttatgagttg attgaaaaga atcttcagct acttggagca acagccattg aggataaatt 2220
acaagatcaa gtgcctgaaa ccatagaaac gctaatgaaa gcagacatca aaatctggat 2280
ccttacaggg gacaagcaag aaactgccat taacatcgga cactcctgca aactgttgaa 2340
gaagaacatg ggaatgattg ttataaatga aggctctctt gatggaacaa gggaaactct 2400
cagtcgtcac tgtactaccc ttggtgatgc tctccggaaa gagaatgatt ttgctcttat 2460
aattgatggg aaaaccctca aatatgcctt aacctttgga gtacgacagt atttcctgga 2520
cttagctttg tcatgcaaag ctgtcatttg ctgtcgggtt tctcctcttc aaaaatctga 2580
agttgttgag atggttaaga aacaagtcaa agtcgtaacg cttgcaatcg gtgatggagc 2640
aaatgatgtc agcatgatac agacagcgca cgttggtgtt ggtatcagtg gcaatgaagg 2700
cctgcaggca gctaattcct ctgactactc catagctcag ttcaaatatt tgaagaattt 2760
actgatgatt catggtgcct ggaactataa cagagtctcc aagtgcatct tatactgctt 2820
ctacaagaat atagtgctct atattatcga gatctggttt gcctttgtta atggcttttc 2880
tggacagatc ctctttgaaa gatggtgtat aggtctctat aacgtgatgt ttacagcaat 2940
gcctccttta actcttggaa tatttgagag atcatgcaga aaagagaaca tgttgaagta 3000
ccctgaatta tacaaaacat ctcagaatgc cctggacttc aacaccaagg ttttctgggt 3060
tcattgttta aatggcctct tccactcagt tattctgttt tggtttccac taaaagccct 3120
tcagtatggt actgcatttg gaaatgggaa aacctcggat tatctgctac tgggaaactt 3180
tgtgtacact tttgtggtga taactgtgtg tttgaaagct ggattggaga catcatattg 3240
gacatggttc agccacatag cgatatgggg gagcatcgca ctctgggtgg tgttttttgg 3300
aatctactca tctctgtggc ctgccattcc gatggcccct gatatgtcag gagaggcagc 3360
catgttgttc agttctggag tcttttggat gggcttgtta ttcatccctg tggcatctct 3420
gctccttgat gtggtgtaca aggttatcaa gaggactgct tttaaaacat tggtcgatga 3480
agttcaggag ctggaggcaa aatctcaaga cccaggagca gttgtacttg gaaaaagcct 3540
gaccgagagg gcgcaactgc tcaagaacgt ctttaagaag aaccacgtga acttgtaccg 3600
ctctgaatcc ttgcaacaaa atctgctcca tgggtatgcg ttctctcaag atgaaaatgg 3660
aatcgtttca cagtctgaag tgataagagc atatgatacc acgaaacaga ggcccgacga 3720
atggtgatgg ggagagcctg aaaggcaggc tctgttacct ctctaaggag agctaccagg 3780
ttgtcaccgc agtctgctaa ccaattccag tctggtccat gaagaggaaa ggtagatctg 3840
agctcatctc gctgatggac attcagattc atgtatatta tagacataag cactgtgcaa 3900
ctgtactgta acaccatctc ttttggattt ttttaaggta tttgctaagt ctttgtaaac 3960
ggaaattgaa aatgacctgg tatcttgcca gagggctttc ttaaacggag aataagtcag 4020
tattcttatg ccattactgt ggggctgtaa ctgactgtca gtttattggc tgtaccacaa 4080
ggtaaccaac cattaaaaaa ctctaaatga tatttagtta aagggactct tggtatccag 4140
acttagattt caggatatgc tgaaacaaac cagcattctt aaggaactga ctcaccttcc 4200
tgagcaaaat ttctaaacaa gcatttgtgt ccaaaattgt cttgataaat gtttgccaaa 4260
gaggttcagt aagtgttttt ctagttcagt agtcatatgc ccagaaatgt aagagaaagt 4320
ttacttccag ttccgctgta agatctgcat gcctgacttt ccaaatgtaa gagtgattta 4380
caaaaatgaa tatttcaagg catttgctac taaaatcggt gatgttgcac ctttggcctt 4440
acaaatgctt ctttgttgtt tgtcgtgttt atttgttaga ggacacacgt gttaatgtga 4500
ctctgttgtt atgacactga tttttcaaac tatgtatgtt tcaggtattt ctgatgaagt 4560
ttcatcatca tttagatttt tctaaaaatc tggctaatgc agtagattga gtgatgtcat 4620
tttgtcttaa agtttttcct cttaagaaac atatgctacg tatttacgtg ggatttccaa 4680
agcttctgtt gcaatatttg gaataacatg tcagataaat gcatgggctt ttgtcctgtg 4740
ttccagttcc cactagagat gcctgtgtct tgtgtagcac acccagtgtt atggtgactg 4800
ccccctatac tgaagactga aaattatttc acagttcact catcaaatag ttcccaaaat 4860
tcgtcacatg ctgcttattg ggacaaatag gtagtacatt ttccccattt aaaaaatgcg 4920
gattttactc aggccggtaa ctttacagtc agaggacacg ttcatcatga gtagcttttg 4980
ttagtatgtt ttaaaatgta tcttcagttc aattattttc agcatttaca agacatctga 5040
aaatggctat tttgctacca acagtaaatg aaggggctgt ttaaaaacca caaccagttt 5100
tctacactat tttttaaata atactttcat ttgaaaaaaa ggaattagtt ttcagataca 5160
cttcagagat tgaagcaaac tatttgcctt ttactcaaaa gcctgcttgc ctttacatgg 5220
acttaccagc aaaataggta gaactttctc ttttaaaaaa agtcaactag aattgagaag 5280
aggtgatttt ttttcagatc gcttctcgag tttaatattt tcacattctt ttcacccttt 5340
ttctcaatct agatttaaaa ttaggatata tgtcatttcc ttgtctgtat ttgtagctcc 5400
ttagttacca gtatgcctct ccattttcta caaataagag gttataacac atatacataa 5460
ttctaacctt aagggaacac acgtttacat actttacttc ccaagccctt cctgtttggg 5520
gtacagattg agagagtcat gaatcaacac atctagcaag accacaggtg taagagtcta 5580
agatcgtctt caaaattctg aagtcccagt ctttacctgt ccagtgaatg aatattcaga 5640
gcagcttttc ctgggcttcc cagtggtgat agctgaggtc aaaccacaaa aaataagaaa 5700
gcaagagtga aatgcacccc tccagagaaa cactttgtag tgtttaattc tgttaataga 5760
gaagagctgc ttctgtttgc gctcacttca tcagtggcac ccttctgcag aattttaata 5820
taaaaacatt atggatataa tagaactgga ttttctgact taaaaatgta agttttattt 5880
taatcttgaa acgtggattg tttctgtgga gctcttaaac atgagaagaa tacttacggt 5940
tgataatgtg taacatgatc tgaaatgtga ctaatttgag cctctttgtc ccatcgtcct 6000
gtttttgaat tattgacatt gtcagtctct ttgcttcctg ggtgagactt ggggtttgag 6060
ggacagggaa tgaccttctt ggtgaaactt aaaatataac attgcaattg cagtgacttt 6120
acagtgttaa attagagaaa atagtctgat tttttaaacc ttccttaact ggaaaaaagt 6180
cacatggttt taccaggatt gaaataaaca gtcaatgtga cttttaacat gtgttttttt 6240
gaaataaagg gcacgtactc ttcaattaaa aagttcctta tagggactct ggcaaatgct 6300
aacacagttg ctttacaatg tttacaattc agacaatacg acttataata gaaaatcctc 6360
attcatttag cattgaaaag ctggaagttg cttctttaat gttgaatagt atacagtggt 6420
attgagcatg gactttctaa atgttttata tatacatata aaaatatatt ggtgtctcac 6480
acccagaaag atgttatatt gtagatatta ttaggaaaac agtgtttctc aggaacgttg 6540
taaattttaa atgatatatg tacttcccgt cctcccacct ccactctgtg ctctaatgtg 6600
agactgcttc agcagtgttg ctaagttaat ggaaaacttt ttctaatcaa gtcaggtgaa 6660
tgtgtattct gctaaataat gttagccatt tacatgaatt gtatggtcat taaatggaat 6720
cagtgattcc tctttaattt ccagagggga aatgaattat ggaaatcagt cagcattctg 6780
atcattaaat tttatacttt aattttgccg ttcagcattc taaatatcca atgtgaaagt 6840
cacatgataa tttgttttgc attgcgtgca ctgtacaaca cttacaactt gtcatttaaa 6900
atgttttctc gggaaatgaa tgctagtcag aaagtaatag attgtattat tcatagtttt 6960
aaaattatga caatgtcata attactacaa agctaaataa tcgtgtttat ttttgtgcag 7020
ttgccctttg atagttcctg gttttaaaac ctattaagtg tataatctta caaatagtca 7080
tctacaaaat ttatggagaa agtgcccagc ccattcacat cacatggacc aggaattctt 7140
ttgtaaatga cttaaggtaa catcatgcag ttcagtgcct aataaatgct ttttaatgat 7200
gaacatttct ataatgactc gtaagatacc atagtctgat ttttctcaca ttaaaataac 7260
tgaagtcact tgtgtaacgt agttatactt tgctgcattt taattaacct tcaacagcta 7320
ttaaagtgga atgtaagtta aattttgaag gaaaggaaat aaatgttttc catatttcgt 7380
cttgatttac tttctgtatg agaacagctg tgtttttgat aggtttatgg tttgcatgag 7440
ttcatattta aagtgatcca ggccaatgca tggctattgc tgtaaatctt gatgtttatt 7500
tctgccttgt aaagttctat cacggcctac ctggaattta aaattcagta gacaaattaa 7560
ttggtcctct gcacaacttt tttaataagt agattatttt acaaagaaat ttgaacaaat 7620
ttaattgaat cttttgttta gcttgcctct aagaactttt cttaataaag ctcccaaaac 7680
ttctcagcaa ataaatctcc cttaagtagg aaagctagat ttcatatttg cttactttga 7740
attaacagca actttccaca ggtaaatctg ttcttgcaaa gatgtgagca gaatagttaa 7800
aaataatatt tttatgtttc atggttctaa atggaagcca taaatgcagt aaatactatc 7860
tgttgtttaa ctactttaat cgtcattttt tacattttca agtttattag gttaagaaaa 7920
acagggcagc cttggaaggc agctactaca gaaaactgca gttttgcgtt aaagataaag 7980
tagtattttc agctccctga aaaaccattc ctgctgaaac tgctgtagaa attgtgaagc 8040
tgcatgagtg gagagtattg aatctgtggt tatagtagtt ttctcaggtt tgtttatctt 8100
gatgtttgat gcactgtgtt ttatagttat taaaattgag taatattatt tctatgcagt 8160
gttatgtgtc attggccttt tgtgaatgtg catgttttaa actgcaaatt ttaaacattt 8220
tgtcctctaa ttgttattaa aaatgaaata aactttacca ttacttaaaa 8270
<210> 4
<211> 417
<212> DNA
<213> Homo sapiens
<400> 4
atggcaaagc aaccttctga tgtaagttct gagtgtgacc gagaaggtag acaattgcag 60
cctgcggaga ggcctcccca gctcagacct ggggccccta cctccctaca gacagagcca 120
caagacagga gcccagcacc catgagttgt gacaaatcaa cacaaacccc aagtcctcct 180
tgccaggcct tcaaccacta tctcagtgca atggcttcca tgaggcaggc tgaacctgca 240
gatatgcgcc cagagatatg gatcgcccaa gagttgcggc gtatcggaga cgagtttaac 300
gcttactatg caaggagggt atttttgaat aattaccaag cagccgaaga ccacccacga 360
atggttatct tacgactgtt acgttacatt gtccgcctgg tgtggagaat gcattga 417
<210> 5
<211> 3575
<212> DNA
<213> Homo sapiens
<400> 5
accatcgtct tgggcccggg gagggagagc caccttcagg cccctcgagc ctcgaaccgg 60
aacctccaaa tccgagacgc tctgcttatg aggacctcga aatatgccgg ccagtgaaaa 120
aatcttgtgg ctttgagggc ttttggttgg ccaggggcag taaaaatctc ggagagctga 180
caccaagtcc tcccctgcca cgtagcagtg gtaaagtccg aagctcaaat tccgagaatt 240
gagctctgtt gattcttaga actggggttc ttagaagtgg tgatgcaaga agtttctagg 300
aaaggccgga caccaggttt tgagcaaaat tttggactgt gaagcaaggc attggtgaag 360
acaaaatggc ctcgccggct gacagctgta tccagttcac ccgccatgcc agtgatgttc 420
ttctcaacct taatcgtctc cggagtcgag acatcttgac tgatgttgtc attgttgtga 480
gccgtgagca gtttagagcc cataaaacgg tcctcatggc ctgcagtggc ctgttctata 540
gcatctttac agaccagttg aaatgcaacc ttagtgtgat caatctagat cctgagatca 600
accctgaggg attctgcatc ctcctggact tcatgtacac atctcggctc aatttgcggg 660
agggcaacat catggctgtg atggccacgg ctatgtacct gcagatggag catgttgtgg 720
acacttgccg gaagtttatt aaggccagtg aagcagagat ggtttctgcc atcaagcctc 780
ctcgtgaaga gttcctcaac agccggatgc tgatgcccca agacatcatg gcctatcggg 840
gtcgtgaggt ggtggagaac aacctgccac tgaggagcgc ccctgggtgt gagagcagag 900
cctttgcccc cagcctgtac agtggcctgt ccacaccgcc agcctcttat tccatgtaca 960
gccacctccc tgtcagcagc ctcctcttct ccgatgagga gtttcgggat gtccggatgc 1020
ctgtggccaa ccccttcccc aaggagcggg cactcccatg tgatagtgcc aggccagtcc 1080
ctggtgagta cagccggccg actttggagg tgtcccccaa tgtgtgccac agcaatatct 1140
attcacccaa ggaaacaatc ccagaagagg cacgaagtga tatgcactac agtgtggctg 1200
agggcctcaa acctgctgcc ccctcagccc gaaatgcccc ctacttccct tgtgacaagg 1260
ccagcaaaga agaagagaga ccctcctcgg aagatgagat tgccctgcat ttcgagcccc 1320
ccaatgcacc cctgaaccgg aagggtctgg ttagtccaca gagcccccag aaatctgact 1380
gccagcccaa ctcgcccaca gagtcctgca gcagtaagaa tgcctgcatc ctccaggctt 1440
ctggctcccc tccagccaag agccccactg accccaaagc ctgcaactgg aagaaataca 1500
agttcatcgt gctcaacagc ctcaaccaga atgccaaacc agaggggcct gagcaggctg 1560
agctgggccg cctttcccca cgagcctaca cggccccacc tgcctgccag ccacccatgg 1620
agcctgagaa ccttgacctc cagtccccaa ccaagctgag tgccagcggg gaggactcca 1680
ccatcccaca agccagccgg ctcaataaca tcgttaacag gtccatgacg ggctctcccc 1740
gcagcagcag cgagagccac tcaccactct acatgcaccc cccgaagtgc acgtcctgcg 1800
gctctcagtc cccacagcat gcagagatgt gcctccacac cgctggcccc acgttccctg 1860
aggagatggg agagacccag tctgagtact cagattctag ctgtgagaac ggggccttct 1920
tctgcaatga gtgtgactgc cgcttctctg aggaggcctc actcaagagg cacacgctgc 1980
agacccacag tgacaaaccc tacaagtgtg accgctgcca ggcctccttc cgctacaagg 2040
gcaacctcgc cagccacaag accgtccata ccggtgagaa accctatcgt tgcaacatct 2100
gtggggccca gttcaaccgg ccagccaacc tgaaaaccca cactcgaatt cactctggag 2160
agaagcccta caaatgcgaa acctgcggag ccagatttgt acaggtggcc cacctccgtg 2220
cccatgtgct tatccacact ggtgagaagc cctatccctg tgaaatctgt ggcacccgtt 2280
tccggcacct tcagactctg aagagccacc tgcgaatcca cacaggagag aaaccttacc 2340
attgtgagaa gtgtaacctg catttccgtc acaaaagcca gctgcgactt cacttgcgcc 2400
agaagcatgg cgccatcacc aacaccaagg tgcaataccg cgtgtcagcc actgacctgc 2460
ctccggagct ccccaaagcc tgctgaagca tggagtgttg atgctttcgt ctccagcccc 2520
ttctcagaat ctacccaaag gatactgtaa cactttacaa tgttcatccc atgatgtagt 2580
gcctctttca tccactagtg caaatcatag ctgggggttg ggggtggtgg gggtcggggc 2640
ctgggggact gggagccgca gcagctcccc ctcccccact gccataaaac attaagaaaa 2700
tcatattgct tcttctccta tgtgtaaggt gaaccatgtc agcaaaaagc aaaatcattt 2760
tatatgtcaa agcaggggag tatgcaaaag ttctgacttg actttagtct gcaaaatgag 2820
gaatgtatat gttttgtggg aacagatgtt tcttttgtat gtaaatgtgc attcttttaa 2880
aagacaagac ttcagtatgt tgtcaaagag agggctttaa tttttttaac caaaggtgaa 2940
ggaatatatg gcagagttgt aaatatataa atatatatat atataaaata aatatatata 3000
aacctaaaaa agatatatta aaaatataaa actgcgttaa aggctcgatt ttgtatctgc 3060
aggcagacac ggatctgaga atctttattg agaaagagca cttaagagaa tattttaagt 3120
attgcatctg tataagtaag aaaatatttt gtctaaaatg cctcagtgta tttgtatttt 3180
tttgcaagtg aaggtttaca atttacaaag tgtgtattaa aaaaaacaaa aagaacaaaa 3240
aaatctgcag aaggaaaaat gtgtaatttt gttctagttt tcagtttgta tatacccgta 3300
caacgtgtcc tcacggtgcc ttttttcacg gaagttttca atgatgggcg agcgtgcacc 3360
atcccttttt gaagtgtagg cagacacagg gacttgaagt tgttactaac taaactctct 3420
ttgggaatgt ttgtctcatc ccattctgcg tcatgcttgt gttataacta ctccggagac 3480
agggtttggc tgtgtctaaa ctgcattacc gcgttgtaaa atatagctgt acaaatataa 3540
gaataaaatg ttgaaaagtc aaactggaaa aaaaa 3575
<210> 6
<211> 2655
<212> DNA
<213> Homo sapiens
<400> 6
cccagaaggc cgcggggggt ggaccgccta agagggcgtg cgctcccgac atgccccgcg 60
gcgcgccatt aaccgccaga tttgaatcgc gggacccgtt ggcagaggtg gcggcggcgg 120
catgggtgcc ccgacgttgc cccctgcctg gcagcccttt ctcaaggacc accgcatctc 180
tacattcaag aactggccct tcttggaggg ctgcgcctgc accccggagc ggatggccga 240
ggctggcttc atccactgcc ccactgagaa cgagccagac ttggcccagt gtttcttctg 300
cttcaaggag ctggaaggct gggagccaga tgacgacccc atagaggaac ataaaaagca 360
ttcgtccggt tgcgctttcc tttctgtcaa gaagcagttt gaagaattaa cccttggtga 420
atttttgaaa ctggacagag aaagagccaa gaacaaaatt gcaaaggaaa ccaacaataa 480
gaagaaagaa tttgaggaaa ctgcggagaa agtgcgccgt gccatcgagc agctggctgc 540
catggattga ggcctctggc cggagctgcc tggtcccaga gtggctgcac cacttccagg 600
gtttattccc tggtgccacc agccttcctg tgggcccctt agcaatgtct taggaaagga 660
gatcaacatt ttcaaattag atgtttcaac tgtgctcttg ttttgtcttg aaagtggcac 720
cagaggtgct tctgcctgtg cagcgggtgc tgctggtaac agtggctgct tctctctctc 780
tctctctttt ttgggggctc atttttgctg ttttgattcc cgggcttacc aggtgagaag 840
tgagggagga agaaggcagt gtcccttttg ctagagctga cagctttgtt cgcgtgggca 900
gagccttcca cagtgaatgt gtctggacct catgttgttg aggctgtcac agtcctgagt 960
gtggacttgg caggtgcctg ttgaatctga gctgcaggtt ccttatctgt cacacctgtg 1020
cctcctcaga ggacagtttt tttgttgttg tgtttttttg tttttttttt tttggtagat 1080
gcatgacttg tgtgtgatga gagaatggag acagagtccc tggctcctct actgtttaac 1140
aacatggctt tcttattttg tttgaattgt taattcacag aatagcacaa actacaatta 1200
aaactaagca caaagccatt ctaagtcatt ggggaaacgg ggtgaacttc aggtggatga 1260
ggagacagaa tagagtgata ggaagcgtct ggcagatact ccttttgcca ctgctgtgtg 1320
attagacagg cccagtgagc cgcggggcac atgctggccg ctcctccctc agaaaaaggc 1380
agtggcctaa atccttttta aatgacttgg ctcgatgctg tgggggactg gctgggctgc 1440
tgcaggccgt gtgtctgtca gcccaacctt cacatctgtc acgttctcca cacgggggag 1500
agacgcagtc cgcccaggtc cccgctttct ttggaggcag cagctcccgc agggctgaag 1560
tctggcgtaa gatgatggat ttgattcgcc ctcctccctg tcatagagct gcagggtgga 1620
ttgttacagc ttcgctggaa acctctggag gtcatctcgg ctgttcctga gaaataaaaa 1680
gcctgtcatt tcaaacactg ctgtggaccc tactgggttt ttaaaatatt gtcagttttt 1740
catcgtcgtc cctagcctgc caacagccat ctgcccagac agccgcagtg aggatgagcg 1800
tcctggcaga gacgcagttg tctctgggcg cttgccagag ccacgaaccc cagacctgtt 1860
tgtatcatcc gggctccttc cgggcagaaa caactgaaaa tgcacttcag acccacttat 1920
ttctgccaca tctgagtcgg cctgagatag acttttccct ctaaactggg agaatatcac 1980
agtggttttt gttagcagaa aatgcactcc agcctctgta ctcatctaag ctgcttattt 2040
ttgatatttg tgtcagtctg taaatggata cttcacttta ataactgttg cttagtaatt 2100
ggctttgtag agaagctgga aaaaaatggt tttgtcttca actcctttgc atgccaggcg 2160
gtgatgtgga tctcggcttc tgtgagcctg tgctgtgggc agggctgagc tggagccgcc 2220
cctctcagcc cgcctgccac ggcctttcct taaaggccat ccttaaaacc agaccctcat 2280
ggctaccagc acctgaaagc ttcctcgaca tctgttaata aagccgtagg cccttgtcta 2340
agtgcaaccg cctagacttt ctttcagata catgtccaca tgtccatttt tcaggttctc 2400
taagttggag tggagtctgg gaagggttgt gaatgaggct tctgggctat gggtgaggtt 2460
ccaatggcag gttagagccc ctcgggccaa ctgccatcct ggaaagtaga gacagcagtg 2520
cccgctgccc agaagagacc agcaagccaa actggagccc ccattgcagg ctgtcgccat 2580
gtggaaagag taactcacaa ttgccaataa agtctcatgt ggttttatct aaaaaaaaaa 2640
aaaaaaaaaa aaaaa 2655
<210> 7
<211> 789
<212> DNA
<213> Homo sapiens
<400> 7
gccaccgccc gcagctgaag cacatccgca gcccggcgcg actccgatcg ccgcagttgc 60
cctctggcgc catgtccgag aacggagcgc ccgggatgca ggaggagagc ctgcagggct 120
cctgggtaga actgcacttc agcaataatg ggaacggggg cagcgttcca gcctcggttt 180
ctatttataa tggagacatg gaaaaaatac tgctggacgc acagcatgag tctggacgga 240
gtagctccaa gagctctcac tgtgacagcc cacctcgctc gcagacacca caagatacca 300
acagggcttc tgaaacagat acccatagca ttggagagaa aaacagctca cagtctgagg 360
aagatgatat tgaaagaagg aaagaagttg aaagcatctt gaagaaaaac tcagattgga 420
tatgggattg gtcaagtcgg ccggaaaata ttccccccaa ggagttcctc tttaaacacc 480
cgaagcgcac ggccaccctc agcatgagga acacgagcgt catgaagaaa gggggcatat 540
tctctgcaga atttctgaaa gttttccttc catctctgct gctctctcat ttgctggcca 600
tcggattggg gatctatatt ggaaggcgtc tgacaacctc caccagcacc ttttgatgaa 660
gaactggagt ctgacttggt tcgttagtgg attacttctg agcttgcaac atagctcact 720
gaagagctgt tagatcctgg gccttcgtgg ctcgagagac tagaatcgca gatacgaaaa 780
ccccgcagc 789
<210> 8
<211> 2251
<212> DNA
<213> Homo sapiens
<400> 8
ctgctgaagc gggaaggagg agctagggct gggggcggag ctttcacacg cgcaccctct 60
gttccctccc tccctccctc gacacaagca actgggtctc cagccgccac tccgggttta 120
tttgtttaca agcggattac gtcagctcct ccctctcttc cctatctctg gacccgcctc 180
ctgaactctt ttcccgcccc tttcggctcc gaaccggctt gcgtcacaat ggtgcgatat 240
tcggattggc tggagtcggc catcacgctc cagctacgcc acttcctttt cgtggcacta 300
taaagggtgc tgcacggcgc ttgcatctct tcgcctctcg gagctggaaa tgcagctatt 360
gagatcttcg aatgctgcgg agctggaggc ggaggcagct ggggaggtcc gagcgatgtg 420
accaggccgc catcgctcgt ctcttcctct ctcctgccgc ctcctgtctc gaaaataact 480
tttttagtct aaagaaagaa agacaaaagt agtcgtccgc ccctcacgcc ctctcttcct 540
ctcagccttc cgcccggtga ggaagcccgg ggtggctgct ccgccgtcgg ggccgcgccg 600
ccgagcccca gccgccccgg gccgcccccg cacgccgccc ccatgcatcc cttctacacc 660
cgggccgcca ccatgatagg cgagatcgcc gccgccgtgt ccttcatctc caagtttctc 720
cgcaccaagg ggctcacgag cgagcgacag ctgcagacct tcagccagag cctgcaggag 780
ctgctggcag gtgagcaggg gagtcctaag cgttgtttct ctgttcttct tttcttctat 840
agaacattat aaacatcact ggttcccaga aaagccatgc aagggatcgg gttaccgttg 900
tattcgcatc aaccataaaa tggatcctct gattggacag gcagcacagc ggattggact 960
gagcagtcag gagctgttca ggcttctccc aagtgaactc acactctggg ttgaccccta 1020
tgaagtgtcc tacagaattg gagaggatgg ctccatctgt gtgctgtatg aagcctcacc 1080
agcaggaggt agcactcaaa acagcaccaa cgtgcaaatg gtagacagcc gaatcagctg 1140
taaggaggaa cttctcttgg gcagaacgag cccttccaaa aactacaata tgatgactgt 1200
atcaggttaa gatatagtct gtggatggat catctgatga tgatggataa atttgatttt 1260
tgctttgggt gggctcctct tggggatgga ttatggaatt taaaccatgt cacagctgtg 1320
aagatctggc acaagataga atggtaaaaa aaaaaaaaaa ttttaagtga cagtgccata 1380
gtttggacag tacctttcaa tgattaattt taatagcctg tgagtccaag taaatgatca 1440
ctttatttgc tagggaggga agtcctaggg tggtttcagt ttctcccaga catacctaaa 1500
tttttacatc aatcctttta aagaaaatct gtatttcaaa gaatctttct ctgcagtaaa 1560
tctcgcaggg gaatttgcac tattacactt gaaagttgtt attgttaacc ttttcggcag 1620
cttttaatag gaaagttaaa cgttttaaac atggtagtac tggaaatttt acaagacttt 1680
tacctagcac ttaaatatgt ataaatgtac ataaagacaa actagtaagc atgacctggg 1740
gaaatggtca gaccttgtat tgtgtttttg gccttgaaag tagcaagtga ccagaatctg 1800
ccatggcaac aggctttaaa aaagaccctt aaaaagacac tgtctcaact gtggtgttag 1860
caccagccag ctctctgtac atttgctagc ttgtagtttt ctaagactga gtaaacttct 1920
tatttttaga aagtggaggt ctggtttgta actttccttg tacttaattg ggtaaaagtc 1980
ttttccacaa accaccatct attttgtgaa ctttgttagt catcttttat ttggtaaatt 2040
atgaactggt gtaaatttgt acagttcatg tatattgatt gtggcaaagt tgtacagatt 2100
tctatatttt ggatgagaaa tttttcttct ctctataata aatcgtttct tatcttggca 2160
ttttaatcaa tctctgtcat gatagaggtt gctaaagtat tttctagaga acggttctat 2220
aaactgaata tctgttgcac actggtcatg c 2251
<210> 9
<211> 2060
<212> DNA
<213> Homo sapiens
<400> 9
atttttggcc ctcgtgacag tgattgatag ctgctgggaa ggtataaaag cagcttgcct 60
gcgaaggttc ttcacactgc tcagggaaga gcctgctacg gtggactgtg agactcagtg 120
cactgtcctc ctcccagcga ccccacgctg gaccccctgc cggaccctcc acccttcggc 180
ccccaagctt cccaggggct tcctttggac tggactgtcc ctgctcatcc attctcctgc 240
cacccccaga cctcctcagc tccaggttgc cacctcctct cgccagagtg atgaggtccc 300
ggcttctgct ctccgtggcc catctgccca caattcggga gaccacggag gagatgctgc 360
ttgggggtcc tggacaggag cccccaccct ctcctagcct ggatgactac gtgaggtcta 420
tatctcgact ggcacagccc acctctgtgc tggacaaggc cacggcccag ggccaaccca 480
ggccacccca caggccagcc caggcctgcc ggaagggccg ccctgctgtg tccctgcgag 540
acatcaccgc acgtttcagt ggccagcagc ccacactgcc catggctgat actgtggacc 600
ccctggactg gctttttggg gagtcccagg aaaagcagcc aagccagagg gacctgccaa 660
ggaggactgg cccctctgct ggcctctggg gtccacatag acagatggac agcagcaagc 720
ccatgggggc ccccagaggg aggctctgtg aagccaggat gcctgggcat tccctggcaa 780
gaccaccgca ggatgggcag cagagctctg acctaagaag ctggactttt gggcagtctg 840
cccaagccat ggcctcccgc caccgccccc gccccagcag tgtcctcaga acactctact 900
cgcacctccc ggtgatccat gaactctgac ccctccccag taaaggcttc tgtagagagc 960
atgctgggtc tgcatctcct ctcgtctcct ccatggtggt cactgcccct ggcaggtctc 1020
tgaaagggaa atgcttttct gcagaggccc ctgcttgggc agttcacagt gagaccgacc 1080
ccctctgaat atgataacag cctgtttcac atgaggagat gttaccaatc ccgttcgctc 1140
tgacccttgc tggctgatca ccttgagcaa cttacttaac atctgtgttc ctcagtttct 1200
catgggtaat atagggataa ttactggcac ctgcctccca ggccattctg acgtgtaacc 1260
gcatatagga gcccactggc tgagtagcta ccatcatcgc tggtggggaa actggtggta 1320
ggggtgtgag ggtagtgggg gtgtcagccc cccaggtgtt tcagaacaag gcctcgggca 1380
ctcccaagtc tgcctcttgg ctcccaccct caaagcccat gttctgtgag gcccaagaga 1440
acacatggag tcttagcaaa tgcactaatg tattccgggg gactgtcacc tggcaccact 1500
ggggcactct gctggctaca actcatacgt cctgtggtgg cattgggaga gttcccccat 1560
gatgagggcc aagatagaat ctgtaccact cagtgctacc atccccaccc ctacaccact 1620
tccacacagg ggcctcatgg catggtcagg gtcccagctg tgggtgagag cagggcactg 1680
tccagctgtc cactggggaa gtcaagatgt cctaaggccc aggtcagggc atctggagtc 1740
tgaaggaccc tagttcctag aggcatctgg cagcaagaag gtgaggcatc agggaacggg 1800
aatcaggctg ggactgatca gaggtgaagg gacagagaga ggagaggagg aagattgagc 1860
tgggggcaac agccaagctc acctgggcag gtctctgcca cctccttgct ctgtgagctg 1920
tcagtctagg ttattctctt tttttgtggc tatttttaat tgctttggat ttgttaaatg 1980
ttttctgtct tctgttaagt gtgttttctc tggagataga atgtaaacca tattaaaagg 2040
aaaaagtttc agacaagcaa 2060
<210> 10
<211> 2300
<212> DNA
<213> Homo sapiens
<400> 10
actcggggca acaggcagat ttgcctgctg agggtggaga cccacgagcc gaggcctcct 60
gcagtgttct gcacagcaaa ccgcacgcta tggctgacag ccgggatccc gccagcgacc 120
agatgcagca ctggaaggag cagcgggccg cgcagaaagc tgatgtcctg accactggag 180
ctggtaaccc agtaggagac aaacttaatg ttattacagt agggccccgt gggccccttc 240
ttgttcagga tgtggttttc actgatgaaa tggctcattt tgaccgagag agaattcctg 300
agagagttgt gcatgctaaa ggagcagggg cctttggcta ctttgaggtc acacatgaca 360
ttaccaaata ctccaaggca aaggtatttg agcatattgg aaagaagact cccatcgcag 420
ttcggttctc cactgttgct ggagaatcgg gttcagctga cacagttcgg gaccctcgtg 480
ggtttgcagt gaaattttac acagaagatg gtaactggga tctcgttgga aataacaccc 540
ccattttctt catcagggat cccatattgt ttccatcttt tatccacagc caaaagagaa 600
atcctcagac acatctgaag gatccggaca tggtctggga cttctggagc ctacgtcctg 660
agtctctgca tcaggtttct ttcttgttca gtgatcgggg gattccagat ggacatcgcc 720
acatgaatgg atatggatca catactttca agctggttaa tgcaaatggg gaggcagttt 780
attgcaaatt ccattataag actgaccagg gcatcaaaaa cctttctgtt gaagatgcgg 840
cgagactttc ccaggaagat cctgactatg gcatccggga tctttttaac gccattgcca 900
caggaaagta cccctcctgg actttttaca tccaggtcat gacatttaat caggcagaaa 960
cttttccatt taatccattc gatctcacca aggtttggcc tcacaaggac taccctctca 1020
tcccagttgg taaactggtc ttaaaccgga atccagttaa ttactttgct gaggttgaac 1080
agatagcctt cgacccaagc aacatgccac ctggcattga ggccagtcct gacaaaatgc 1140
ttcagggccg cctttttgcc tatcctgaca ctcaccgcca tcgcctggga cccaattatc 1200
ttcatatacc tgtgaactgt ccctaccgtg ctcgagtggc caactaccag cgtgacggcc 1260
cgatgtgcat gcaggacaat cagggtggtg ctccaaatta ctaccccaac agctttggtg 1320
ctccggaaca acagccttct gccctggagc acagcatcca atattctgga gaagtgcgga 1380
gattcaacac tgccaatgat gataacgtta ctcaggtgcg ggcattctat gtgaacgtgc 1440
tgaatgagga acagaggaaa cgtctgtgtg agaacattgc cggccacctg aaggatgcac 1500
aaattttcat ccagaagaaa gcggtcaaga acttcactga ggtccaccct gactacggga 1560
gccacatcca ggctcttctg gacaagtaca atgctgagaa gcctaagaat gcgattcaca 1620
cctttgtgca gtccggatct cacttggcgg caagggagaa ggcaaatctg tgaggccggg 1680
gccctgcacc tgtgcagcga agcttagcgt tcatccgtgt aacccgctca tcactggatg 1740
aagattctcc tgtgctagat gtgcaaatgc aagctagtgg cttcaaaata gagaatccca 1800
ctttctatag cagattgtgt aacaatttta atgctatttc cccaggggaa aatgaaggtt 1860
aggatttaac agtcatttaa aaaaaaaatt tgttttgacg gatgattgga ttattcattt 1920
aaaatgatta gaaggcaagt ttctagctag aaatatgatt ttatttgaca aaatttgttg 1980
aaattatgta tgtttacata tcacctcatg gcctattata ttaaaatatg gctataaata 2040
tataaaaaga aaagataaag atgatctact cagaaatttt tatttttcta aggttctcat 2100
aggaaaagta catttaatac agcagtgtca tcagaagata acttgagcac cgtcatggct 2160
taatgtttat tcctgataat aattgatcaa attcattttt ttcactggag ttacattaat 2220
gttaattcag cactgatttc acaacagatc aatttgtaat tgcttacatt tttacaataa 2280
ataatctgta cgtaagaaca 2300
<210> 11
<211> 2723
<212> DNA
<213> Homo sapiens
<400> 11
gggagaaacg ttctcactcg ctctctgctc gctgcgggcg ctccccgccc tctgctgcca 60
gaaccttggg gatgtgccta gacccggcgc agcacacgtc cgggccaacc gcgagcagaa 120
caaacctttg gcgggcggcc aggaggctcc ctcccagcca ccgcccccct ccagcgcctt 180
tttttccccc catacaatac aagatcttcc ttcctcagtt cccttaaagc acagcccagg 240
gaaacctcct cacagttttc atccagccac gggccagcat gtctgggggc aaatacgtag 300
actcggaggg acatctctac accgttccca tccgggaaca gggcaacatc tacaagccca 360
acaacaaggc catggcagac gagctgagcg agaagcaagt gtacgacgcg cacaccaagg 420
agatcgacct ggtcaaccgc gaccctaaac acctcaacga tgacgtggtc aagattgact 480
ttgaagatgt gattgcagaa ccagaaggga cacacagttt tgacggcatt tggaaggcca 540
gcttcaccac cttcactgtg acgaaatact ggttttaccg cttgctgtct gccctctttg 600
gcatcccgat ggcactcatc tggggcattt acttcgccat tctctctttc ctgcacatct 660
gggcagttgt accatgcatt aagagcttcc tgattgagat tcagtgcatc agccgtgtct 720
attccatcta cgtccacacc gtctgtgacc cactctttga agctgttggg aaaatattca 780
gcaatgtccg catcaacttg cagaaagaaa tataaatgac atttcaagga tagaagtata 840
cctgattttt tttcctttta attttcctgg tgccaatttc aagttccaag ttgctaatac 900
agcaacaatt tatgaattga attatcttgg ttgaaaataa aaagatcact ttctcagttt 960
tcataagtat tatgtctctt ctgagctatt tcatctattt ttggcagtct gaatttttaa 1020
aacccattta aatttttttc cttacctttt tatttgcatg tggatcaacc atcgctttat 1080
tggctgagat atgaacatat tgttgaaagg taatttgaga gaaatatgaa gaactgagga 1140
ggaaaaaaaa aaaaaagaaa agaaccaaca acctcaactg cctactccaa aatgttggtc 1200
attttatgtt aagggaagaa ttccagggta tggccatgga gtgtacaagt atgtgggcag 1260
attttcagca aactcttttc ccactgttta aggagttagt ggattactgc cattcacttc 1320
ataatccagt aggatccagt gatccttaca agttagaaaa cataatcttc tgccttctca 1380
tgatccaact aatgccttac tcttcttgaa attttaacct atgatatttt ctgtgcctga 1440
atatttgtta tgtagataac aagacctcag tgccttcctg tttttcacat tttccttttc 1500
aaatagggtc taactcagca actcgcttta ggtcagcagc ctccctgaag accaaaatta 1560
gaatatccat gacctagttt tccatgcgtg tttctgactc tgagctacag agtctggtga 1620
agctcacttc tgggcttcat ctggcaacat ctttatccgt agtgggtatg gttgacacta 1680
gcccaatgaa atgaattaaa gtggaccaat agggctgagc tctctgtggg ctggcagtcc 1740
tggaagccag ctttccctgc ctctcatcaa ctgaatgagg tcagcatgtc tattcagctt 1800
cgtttatttt caagaataat cacgctttcc tgaatccaaa ctaatccatc accggggtgg 1860
tttagtggct caacattgtg ttcccatttc agctgatcag tgggcctcca aggaggggct 1920
gtaaaatgga ggccattgtg tgagcctatc agagttgctg caaacctgac ccctgctcag 1980
taaagcactt gcaaccgtct gttatgctgt gacacatggc ccctccccct gccaggagct 2040
ttggacctaa tccaagcatc cctttgccca gaaagaagat gggggaggag gcagtaataa 2100
aaagattgaa gtattttgct ggaataagtt caaattcttc tgaactcaaa ctgaggaatt 2160
tcacctgtaa acctgagtcg tacagaaagc tgcctggtat atccaaaagc tttttattcc 2220
tcctgctcat attgtgattc tgcctttggg gacttttctt aaaccttcag ttatgatttt 2280
tttttcatac acttattgga actctgcttg atttttgcct cttccagtct tcctgacact 2340
ttaattacca acctgttacc tactttgact ttttgcattt aaaacagaca ctggcatgga 2400
tatagtttta cttttaaact gtgtacataa ctgaaaatgt gctatactgc atacttttta 2460
aatgtaaaga tatttttatc tttatatgaa gaaaatcact taggaaatgg ctttgtgatt 2520
caatctgtaa actgtgtatt ccaagacatg tctgttctac atagatgctt agtccctcat 2580
gcaaatcaat tactggtcca aaagattgct gaaattttat atgcttactg atatatttta 2640
caatttttta tcatgcatgt cctgtaaagg ttacaagcct gcacaataaa aatgtttaac 2700
ggttaaacag tcaaaaaaaa aaa 2723
<210> 12
<211> 3976
<212> DNA
<213> Homo sapiens
<400> 12
ctgggtcctg tgtgtgccac aggggtgggg tgtccagcga gcggtctcct cctcctgcta 60
gtgctgctgc ggcgtcccgc ggcctccccg agtcgggcgg gaggggagag cgggtgtgga 120
tttgtcttga cggtaattgt tgcgtttcca cgtctcggag gcctgcgcgc tgggttgctc 180
cttcttcggg agcgagctgt tctcagcgat cccactccca gccggggctc cccacacaca 240
ctgggctgcg tgcgtgtgga gtgggacccg cgcacacgcg tgtctctgga cagctacggc 300
gccgaaagaa ctaaaattcc agatggcaaa ctcaatgaat ggcagaaacc ctggtggtcg 360
aggaggaaat ccccgaaaag gtcgaatttt gggtattatt gatgctattc aggatgcagt 420
tggaccccct aagcaagctg ccgcagatcg caggaccgtg gagaagactt ggaagctcat 480
ggacaaagtg gtaagactgt gccaaaatcc caaacttcag ttgaaaaata gcccaccata 540
tatacttgat attttgcctg atacatatca gcatttacga cttatattga gtaaatatga 600
tgacaaccag aaacttgccc aactcagtga gaatgagtac tttaaaatct acattgatag 660
ccttatgaaa aagtcaaaac gggcaataag actctttaaa gaaggcaagg agagaatgta 720
tgaagaacag tcacaggaca gacgaaatct cacaaaactg tcccttatct tcagtcacat 780
gctggcagaa atcaaagcaa tctttcccaa tggtcaattc cagggagata actttcgtat 840
cacaaaagca gatgctgctg aattctggag aaagtttttt ggagacaaaa ctatcgtacc 900
atggaaagta ttcagacagt gccttcatga ggtccaccag attagctctg gcctggaagc 960
aatggctcta aaatcaacaa ttgatttaac ttgcaatgat tacatttcag tttttgaatt 1020
tgatattttt accaggctgt ttcagccttg gggctctatt ttgcggaatt ggaatttctt 1080
agctgtgaca catccaggtt acatggcatt tctcacatat gatgaagtta aagcacgact 1140
acagaaatat agcaccaaac ccggaagcta tattttccgg ttaagttgca ctcgattggg 1200
acagtgggcc attggctatg tgactgggga tgggaatatc ttacagacca tacctcataa 1260
caagccctta tttcaagccc tgattgatgg cagcagggaa ggattttatc tttatcctga 1320
tgggaggagt tataatcctg atttaactgg attatgtgaa cctacacctc atgaccatat 1380
aaaagttaca caggaacaat atgaattata ttgtgaaatg ggctccactt ttcagctctg 1440
taagatttgt gcagagaatg acaaagatgt caagattgag ccttgtgggc atttgatgtg 1500
cacctcttgc cttacggcat ggcaggagtc ggatggtcag ggctgccctt tctgtcgttg 1560
tgaaataaaa ggaactgagc ccataatcgt ggaccccttt gatccaagag atgaaggctc 1620
caggtgttgc agcatcattg acccctttgg catgccgatg ctagacttgg acgacgatga 1680
tgatcgtgag gagtccttga tgatgaatcg gttggcaaac gtccgaaagt gcactgacag 1740
gcagaactca ccagtcacat caccaggatc ctctcccctt gcccagagaa gaaagccaca 1800
gcctgaccca ctccagatcc cacatctaag cctgccaccc gtgcctcctc gcctggatct 1860
aattcagaaa ggcatagtta gatctccctg tggcagccca acgggttcac caaagtcttc 1920
tccttgcatg gtgagaaaac aagataaacc actcccagca ccacctcctc ccttaagaga 1980
tcctcctcca ccgccacctg aaagacctcc accaatccca ccagacaata gactgagtag 2040
acacatccat catgtggaaa gcgtgccttc cagagacccg ccaatgcctc ttgaagcatg 2100
gtgccctcgg gatgtgtttg ggactaatca gcttgtggga tgtcgactcc taggggaggg 2160
ctctccaaaa cctggaatca cagcgagttc aaatgtcaat ggaaggcaca gtagagtggg 2220
ctctgaccca gtgcttatgc ggaaacacag acgccatgat ttgcctttag aaggagctaa 2280
ggtcttttcc aatggtcacc ttggaagtga agaatatgat gttcctcccc ggctttctcc 2340
tcctcctcca gttaccaccc tcctccctag cataaagtgt actggtccgt tagcaaattc 2400
tctttcagag aaaacaagag acccagtaga ggaagatgat gatgaataca agattccttc 2460
atcccaccct gtttccctga attcacaacc atctcattgt cataatgtaa aacctcctgt 2520
tcggtcttgt gataatggtc actgtatgct gaatggaaca catggtccat cttcagagaa 2580
gaaatcaaac atccctgact taagcatata tttaaaggga gatgtttttg attcagcctc 2640
tgatcccgtg ccattaccac ctgccaggcc tccaactcgg gacaatccaa agcatggttc 2700
ttcactcaac aggacgccct ctgattatga tcttctcatc cctccattag gtgaagatgc 2760
ttttgatgcc ctccctccat ctctcccacc tcccccacct cctgcaaggc atagtctcat 2820
tgaacattca aaacctcctg gctccagtag ccggccatcc tcaggacagg atctttttct 2880
tcttccttca gatccctttg ttgatctagc aagtggccaa gttcctttgc ctcctgctag 2940
aaggttacca ggtgaaaatg tcaaaactaa cagaacatca caggactatg atcagcttcc 3000
ttcatgttca gatggttcac aggcaccagc cagaccccct aaaccacgac cgcgcaggac 3060
tgcaccagaa attcaccaca gaaaacccca tgggcctgag gcggcattgg aaaatgtcga 3120
tgcaaaaatt gcaaaactca tgggagaggg ttatgccttt gaagaggtga agagagcctt 3180
agagatagcc cagaataatg tcgaagttgc ccggagcatc ctccgagaat ttgccttccc 3240
tcctccagta tccccacgtc taaatctata gcagccagaa ctgtagacac caaaatggaa 3300
agcaatcgat gtattccaag agtgtggaaa taaagagaac tgagatggaa ttcaagagag 3360
aagtgtctcc tcctcgtgta gcagcttgag aagaggcttg ggagtgcagc ttctcaaagg 3420
agaccgatgc ttgctcagga tgtcgacagc tgtggcttcc ttgtttttgc tagccatatt 3480
tttaaatcag ggttgaactg acaaaaataa tttaaagacg tttacttccc ttgaactttg 3540
aacctgtgaa atgctttacc ttgtttacag tttggcaaag ttgcagtttg ttcttgtttt 3600
tagtttagtt ttgttttggt gttttgatac ctgtactgtg ttcttcacag accctttgta 3660
gcgtggtcag gtctgctgta acatttccca ccaactctct tgctgtccac atcaacagct 3720
aaatcattta ttcatatgga tctctaccat ccccatgcct tgcccaggtc cagttccatt 3780
tctctcattc acaagatgct ttgaaggttc tgattttcaa ctgatcaaac taatgcaaaa 3840
aaaaaaaagt atgtattctt cactactgag tttcttcttt ggaaaccatc actattgaga 3900
gatgggaaaa acctgaatgt ataaagcatt tatttgtcaa taaactgcct tttgtaaggg 3960
gttttcacat aacata 3976
<210> 13
<211> 4304
<212> DNA
<213> Homo sapiens
<400> 13
cacacggact acaggggagt tttgttgaag ttgcaaagtc ctggagcctc cagagggctg 60
tcggcgcagt agcagcgagc agcagagtcc gcacgctccg gcgaggggca gaagagcgcg 120
agggagcgcg gggcagcaga agcgagagcc gagcgcggac ccagccagga cccacagccc 180
tccccagctg cccaggaaga gccccagcca tggaacacca gctcctgtgc tgcgaagtgg 240
aaaccatccg ccgcgcgtac cccgatgcca acctcctcaa cgaccgggtg ctgcgggcca 300
tgctgaaggc ggaggagacc tgcgcgccct cggtgtccta cttcaaatgt gtgcagaagg 360
aggtcctgcc gtccatgcgg aagatcgtcg ccacctggat gctggaggtc tgcgaggaac 420
agaagtgcga ggaggaggtc ttcccgctgg ccatgaacta cctggaccgc ttcctgtcgc 480
tggagcccgt gaaaaagagc cgcctgcagc tgctgggggc cacttgcatg ttcgtggcct 540
ctaagatgaa ggagaccatc cccctgacgg ccgagaagct gtgcatctac accgacaact 600
ccatccggcc cgaggagctg ctgcaaatgg agctgctcct ggtgaacaag ctcaagtgga 660
acctggccgc aatgaccccg cacgatttca ttgaacactt cctctccaaa atgccagagg 720
cggaggagaa caaacagatc atccgcaaac acgcgcagac cttcgttgcc ctctgtgcca 780
cagatgtgaa gttcatttcc aatccgccct ccatggtggc agcggggagc gtggtggccg 840
cagtgcaagg cctgaacctg aggagcccca acaacttcct gtcctactac cgcctcacac 900
gcttcctctc cagagtgatc aagtgtgacc cggactgcct ccgggcctgc caggagcaga 960
tcgaagccct gctggagtca agcctgcgcc aggcccagca gaacatggac cccaaggccg 1020
ccgaggagga ggaagaggag gaggaggagg tggacctggc ttgcacaccc accgacgtgc 1080
gggacgtgga catctgaggg cgccaggcag gcgggcgcca ccgccacccg cagcgagggc 1140
ggagccggcc ccaggtgctc ccctgacagt ccctcctctc cggagcattt tgataccaga 1200
agggaaagct tcattctcct tgttgttggt tgttttttcc tttgctcttt cccccttcca 1260
tctctgactt aagcaaaaga aaaagattac ccaaaaactg tctttaaaag agagagagag 1320
aaaaaaaaaa tagtatttgc ataaccctga gcggtggggg aggagggttg tgctacagat 1380
gatagaggat tttatacccc aataatcaac tcgtttttat attaatgtac ttgtttctct 1440
gttgtaagaa taggcattaa cacaaaggag gcgtctcggg agaggattag gttccatcct 1500
ttacgtgttt aaaaaaaagc ataaaaacat tttaaaaaca tagaaaaatt cagcaaacca 1560
tttttaaagt agaagagggt tttaggtaga aaaacatatt cttgtgcttt tcctgataaa 1620
gcacagctgt agtggggttc taggcatctc tgtactttgc ttgctcatat gcatgtagtc 1680
actttataag tcattgtatg ttattatatt ccgtaggtag atgtgtaacc tcttcacctt 1740
attcatggct gaagtcacct cttggttaca gtagcgtagc gtgcccgtgt gcatgtcctt 1800
tgcgcctgtg accaccaccc caacaaacca tccagtgaca aaccatccag tggaggtttg 1860
tcgggcacca gccagcgtag cagggtcggg aaaggccacc tgtcccactc ctacgatacg 1920
ctactataaa gagaagacga aatagtgaca taatatattc tatttttata ctcttcctat 1980
ttttgtagtg acctgtttat gagatgctgg ttttctaccc aacggccctg cagccagctc 2040
acgtccaggt tcaacccaca gctacttggt ttgtgttctt cttcatattc taaaaccatt 2100
ccatttccaa gcactttcag tccaataggt gtaggaaata gcgctgtttt tgttgtgtgt 2160
gcagggaggg cagttttcta atggaatggt ttgggaatat ccatgtactt gtttgcaagc 2220
aggactttga ggcaagtgtg ggccactgtg gtggcagtgg aggtggggtg tttgggaggc 2280
tgcgtgccag tcaagaagaa aaaggtttgc attctcacat tgccaggatg ataagttcct 2340
ttccttttct ttaaagaagt tgaagtttag gaatcctttg gtgccaactg gtgtttgaaa 2400
gtagggacct cagaggttta cctagagaac aggtggtttt taagggttat cttagatgtt 2460
tcacaccgga aggtttttaa acactaaaat atataattta tagttaaggc taaaaagtat 2520
atttattgca gaggatgttc ataaggccag tatgatttat aaatgcaatc tccccttgat 2580
ttaaacacac agatacacac acacacacac acacacacaa accttctgcc tttgatgtta 2640
cagatttaat acagtttatt tttaaagata gatcctttta taggtgagaa aaaaacaatc 2700
tggaagaaaa aaaccacaca aagacattga ttcagcctgt ttggcgtttc ccagagtcat 2760
ctgattggac aggcatgggt gcaaggaaaa ttagggtact caacctaagt tcggttccga 2820
tgaattctta tcccctgccc cttcctttaa aaaacttagt gacaaaatag acaatttgca 2880
catcttggct atgtaattct tgtaattttt atttaggaag tgttgaaggg aggtggcaag 2940
agtgtggagg ctgacgtgtg agggaggaca ggcgggagga ggtgtgagga ggaggctccc 3000
gaggggaagg ggcggtgccc acaccgggga caggccgcag ctccattttc ttattgcgct 3060
gctaccgttg acttccaggc acggtttgga aatattcaca tcgcttctgt gtatctcttt 3120
cacattgttt gctgctattg gaggatcagt tttttgtttt acaatgtcat atactgccat 3180
gtactagttt tagttttctc ttagaacatt gtattacaga tgcctttttt gtagtttttt 3240
ttttttttat gtgatcaatt ttgacttaat gtgattactg ctctattcca aaaaggttgc 3300
tgtttcacaa tacctcatgc ttcacttagc catggtggac ccagcgggca ggttctgcct 3360
gctttggcgg gcagacacgc gggcgcgatc ccacacaggc tggcgggggc cggccccgag 3420
gccgcgtgcg tgagaaccgc gccggtgtcc ccagagacca ggctgtgtcc ctcttctctt 3480
ccctgcgcct gtgatgctgg gcacttcatc tgatcggggg cgtagcatca tagtagtttt 3540
tacagctgtg ttattctttg cgtgtagcta tggaagttgc ataattatta ttattattat 3600
tataacaagt gtgtcttacg tgccaccacg gcgttgtacc tgtaggactc tcattcggga 3660
tgattggaat agcttctgga atttgttcaa gttttgggta tgtttaatct gttatgtact 3720
agtgttctgt ttgttattgt tttgttaatt acaccataat gctaatttaa agagactcca 3780
aatctcaatg aagccagctc acagtgctgt gtgccccggt cacctagcaa gctgccgaac 3840
caaaagaatt tgcaccccgc tgcgggccca cgtggttggg gccctgccct ggcagggtca 3900
tcctgtgctc ggaggccatc tcgggcacag gcccaccccg ccccacccct ccagaacacg 3960
gctcacgctt acctcaacca tcctggctgc ggcgtctgtc tgaaccacgc gggggccttg 4020
agggacgctt tgtctgtcgt gatggggcaa gggcacaagt cctggatgtt gtgtgtatcg 4080
agaggccaaa ggctggtggc aagtgcacgg ggcacagcgg agtctgtcct gtgacgcgca 4140
agtctgaggg tctgggcggc gggcggctgg gtctgtgcat ttctggttgc accgcggcgc 4200
ttcccagcac caacatgtaa ccggcatgtt tccagcagaa gacaaaaaga caaacatgaa 4260
agtctagaaa taaaactggt aaaaccccaa aaaaaaaaaa aaaa 4304
<210> 14
<211> 6531
<212> DNA
<213> Homo sapiens
<400> 14
gcccagccag cttgcgtcac cgcttcagag cggagaagag cgagcagggg agagcgagac 60
cagttttaag gggaggaccg gtgcgagtga ggcagccccg aggctctgct cgcccaccac 120
ccaatcctcg cctcccttct gctccacctt ctctctctgc cctcacctct cccccgaaaa 180
ccccctattt agccaaagga aggaggtcag gggaacgctc tcccctcccc ttccaaaaaa 240
caaaaacaga aaaacccttt tccaggccgg ggaaagcagg agggagaggg gccgccgggc 300
tggccatgga gctgctgtgc cacgaggtgg acccggtccg cagggccgtg cgggaccgca 360
acctgctccg agacgaccgc gtcctgcaga acctgctcac catcgaggag cgctaccttc 420
cgcagtgctc ctacttcaag tgcgtgcaga aggacatcca accctacatg cgcagaatgg 480
tggccacctg gatgctggag gtctgtgagg aacagaagtg cgaagaagag gtcttccctc 540
tggccatgaa ttacctggac cgtttcttgg ctggggtccc gactccgaag tcccatctgc 600
aactcctggg tgctgtctgc atgttcctgg cctccaaact caaagagacc agcccgctga 660
ccgcggagaa gctgtgcatt tacaccgaca actccatcaa gcctcaggag ctgctggagt 720
gggaactggt ggtgctgggg aagttgaagt ggaacctggc agctgtcact cctcatgact 780
tcattgagca catcttgcgc aagctgcccc agcagcggga gaagctgtct ctgatccgca 840
agcatgctca gaccttcatt gctctgtgtg ccaccgactt taagtttgcc atgtacccac 900
cgtcgatgat cgcaactgga agtgtgggag cagccatctg tgggctccag caggatgagg 960
aagtgagctc gctcacttgt gatgccctga ctgagctgct ggctaagatc accaacacag 1020
acgtggattg tctcaaagct tgccaggagc agattgaggc ggtgctcctc aatagcctgc 1080
agcagtaccg tcaggaccaa cgtgacggat ccaagtcgga ggatgaactg gaccaagcca 1140
gcacccctac agacgtgcgg gatatcgacc tgtgaggatg ccagttgggc cgaaagagag 1200
agacgcgtcc ataatctggt ctcttcttct ttctggttgt ttttgttctt tgtgttttag 1260
ggtgaaactt aaaaaaaaaa ttctgccccc acctagatca tatttaaaga tcttttagaa 1320
gtgagagaaa aaggtcctac gaaaacggaa taataaaaag catttggtgc ctatttgaag 1380
tacagcataa gggaatccct tgtatatgcg aacagttatt gtttgattat gtaaaagtaa 1440
tagtaaaatg cttacaggaa aacctgcaga gtagttagag aatatgtatg cctgcaatat 1500
gggaacaaat tagaggagac tttttttttt catgttatga gctagcacat acaccccctt 1560
gtagtataat ttcaaggaac tgtgtacgcc atttatggca tgattagatt gcaaagcaat 1620
gaactcaaga aggaattgaa ataaggaggg acatgatggg gaaggagtac aaaacaatct 1680
ctcaacatga ttgaaccatt tgggatggag aagcaccttt gctctcagcc acctgttact 1740
aagtcaggag tgtagttgga tctctacatt aatgtcctct tgctgtctac agtagctgct 1800
acctaaaaaa agatgtttta ttttgccagt tggacacagg tgattggctc ctgggtttca 1860
tgttctgtga catcctgctt cttcttccaa atgcagttca ttgcagacac caccatattg 1920
ctatctaatg gggaaatgta gctatgggcc ataaccaaaa ctcacatgaa acggaggcag 1980
atggagacca agggtgggat ccagaatgga gtcttttctg ttattgtatt taaaagggta 2040
atgtggcctt ggcatttctt cttagaaaaa aactaatttt tggtgctgat tggcatgtct 2100
ggttcacagt ttagcattgt tataaaccat tccattcgaa aagcactttg aaaaattgtt 2160
cccgagcgat agatgggatg gtttatgcaa gtcatgctga atactcctcc cctcttctct 2220
tttgccccct cccttcctgc ccccagtctg ggttactctt cgcttctggt atctggcgtt 2280
ctttggtaca cagttctggt gttcctacca ggactcaaga gacacccctt cctgctgaca 2340
ttcccatcac aacattcctc agacaagcct gtaaactaaa atctgttacc attctgatgg 2400
cacagaagga tcttaattcc catctctata cttctccttt ggacatggaa agaaaagtta 2460
ttgctggtgc aaagatagat ggctgaacat cagggtgtgg cattttgttc ccttttccgt 2520
tttttttttt ttattgttgt tgttaatttt attgcaaagt tgtattcagc gtacttgaat 2580
ttttcttcct ctccacttct tagaggcatt cagttagcaa agaggttgga gcaacaactt 2640
tttttttttt ttttgcacaa ttgtaattga caggtaatga agctatttgt taaaatattt 2700
gcctttttaa gtaaaaaaga aaaatcagaa cagggctatt tgaagaatta ttttatacac 2760
agattctgcc ttgtttcata gtatgagggt tgaagacgga aaacaatcta agggtctctc 2820
atttttttaa ttttgttttg ttcagtttgg tttttttttt tttttgcgct gctaagaagc 2880
taaagtcatc catccttatt cacgttgaca gtacctagct gtaatgtttc acagagtgtg 2940
ctgctatttt ataaacattt ttataatata ttattttact gcttaaattc caagtcctga 3000
agtagatggt tgagatatga gttcttcgta ctggaaaagc ccttccgtag tttgttttct 3060
tctggtagca tattcatggt tgtttttttt tttctttttt ggttttttgg tttttttttt 3120
ttcctctgat cacattcttc aaagacggag tattctttac ctcaggttta ctggacaaaa 3180
tcaataacta caaaaggcaa tgattcacgc ttttgttttc ataatacctc acaaccgtac 3240
agtttctgct tgggagccca ttcgcatgag gaatacagaa gcagtgtgag cagggctgac 3300
tccctctcag gtggaaggca gggcggtctc actcccaggg acctttttgg tcatggaggc 3360
catcgggctc ccagttagac cctggtatcc tcatcatgat ggaaaaaata cattgaacca 3420
agggatcctc cctccccttc aaggcagacg ttcagtacaa acatttatgc ggtaggctca 3480
gatgtcgtaa tttgcactta ggtaccaggt gtcaggaaac agactaaaaa gaattccacc 3540
aggctgtttg gagatcctca tcttggagct ttttcaaaag cggggcttca tctgcaaagg 3600
gccctttcat cttgaagttt ttcccctccg tctttcccct cccctggcat ggacaccttg 3660
tgtttaggat catctctgca ggtttcctag gtctgaatct gcgagtagat gaacctgcag 3720
caagcagcgt ttatggtgct tccttctccc tcctctgtct caaactgcgc aggcaagcac 3780
tatgcaagcc caggccctct gctgagcggt actaaacggt cgggttttca atcacactga 3840
attggcagga taagaaaaat aggtcagata agtatgggat gatagttgaa gggaggtgaa 3900
gaggctgctt ctctacagag gtgaaattcc agatgagtca gtctcttggg aagtgtgttt 3960
agaagggttc aggactttgt gagttagcat gaccctaaaa ttctagggga tttctggtgg 4020
gacaatgggt ggtgaattct gaagttttgg agagggaagt ggagcagcca gcaagtaagc 4080
tagccagagt tttctcaaga gccagctttg ctcagcacac tctcctgggc cccaaggagt 4140
cccacggaat ggggaaagcg ggaaccctgg agttcttggg aatcttggag cctaaagaga 4200
aaccgaggtg caaattcatt tcatggtgac tgacccttga gcttaaacag aagcagcaaa 4260
tgaaagaacc ggacaaataa ggaagggcac aagcctaccc gactctattt acagtctgta 4320
actttccact cttcctgtag tcccgaggcc cctgggtcct tctagctttt ctctttccca 4380
tccttggggc cttgtgtgat gatgggtgtg gggctgccga tgggaaagtc gggggttgtt 4440
aggcttttct gcctgctcct gcttaaacac aagaaggaat cctggatttt gccctctcct 4500
tagctcttag tctctttggt aggagttttg ttccagagga gctctccccc ttggatttga 4560
acttgctctt tttgttgttg ttgttctttc tcttcttttt cttacctccc actaaagggg 4620
ttccaaatta tcctggtctt tttctacctt gttgtgtttc tatctcgtct ttacttccat 4680
ctgtttgttt ttttctccat cagtgggggc cgagttgttc ccccagcctg ccaaattttg 4740
atccttcccc tcttttggcc aaatcctagg gggaagaaat cctagtatgc caaaaatata 4800
tgctaagcat aattaaactc catgcgggtc cataacagcc aagaagcctg caggagaaag 4860
ccaagggcag ttccctccgc agaacacccc atgcgtgctg agaggcgagc tccttgaaga 4920
aggggctgtt cttccaggag gccttatttt gaactgcctc aggaccccac tggagagcac 4980
agcatgcctt actactgggt catccttggt ctatgtgctc tgtactggag gctctgttct 5040
gcctcttatc agccaggtca ggggcacaca tggcttaagt gacaaagcca gaggagaaga 5100
caaccctgac agcatcacgc tgcatcccat tgctagcagg attggcaact cttcagacgg 5160
agctgcgctt ccctgcagtc tagcacctct agggcctctc cagactgtgc cctgggagct 5220
ctgggactga aaggttaaga acataaggca ggatcagatg actctctcca agagggcagg 5280
ggaattttct ctccatgggc cacaggggac agggctggga gaagaaatag acttgcacct 5340
tatgtcatgt aaataattga ttttctagtt caagaagata atattggtag tgtgggaatt 5400
ggaggtagga aggggaggaa gtctgagtaa gccagttggc ttctaagcca aaaggattcc 5460
tctttgttta tctctgagac agtccaacct tgagaatagc tttaaaaggg aaattaatgc 5520
tgagatgata aagtcccctt aagccaacaa accctctgta gctatagaat gagtgcaggt 5580
ttctattggt gtggactcag agcaatttac aagagctgtt catgcagcca tccatttgtg 5640
caaaataggg taagaagatt caagaggata tttattactt cctcatacca catggctttt 5700
gatgattctg gattctaaac aacccagaat ggtcatttca ggcacaacga tactacattc 5760
gtgtgtgtct gcttttaaac ttggctgggc tatcagaccc tattctcggc tcaggttttg 5820
agaagccatc agcaaatgtg tacgtgcatg ctgtagctgc agcctgcatc ccttcgcctg 5880
cagcctactt tggggaaata aagtgcctta ctgactgtag ccattacagt atccaatgtc 5940
ttttgacagg tgcctgtcct tgaaaaacaa agtttctatt tttattttta attggtttag 6000
ttcttaactg ctggccaact cttacatccc cagcaaatca tcgggccatt ggattttttc 6060
cattatgttc atcaccctta tatcatgtac ctcagatctc tctctctctc ctctctctca 6120
gttatgtagt ttcttgtctt ggactttttt ttttcttttc tttttctttt tttttttgct 6180
ttaaaacaag tgtgatgcca tatcaagtcc atgttattct ctcacagtgt actctataag 6240
aggtgtgggt gtctgtttgg tcaggatgtt agaaagtgct gataagtagc atgatcagtg 6300
tatgcgaaaa ggtttttagg aagtatggca aaaatgttgt attggctatg atggtgacat 6360
gatatagtca gctgcctttt aagaggtctt atctgttcag tgttaagtga tttaaaaaaa 6420
taataacctg ttttctgact agtttaaaga tggatttgaa aatggttttg aatgcaatta 6480
ggttatgcta tttggacaat aaactcacct tgacctaaat taaaaaaaaa a 6531
<210> 15
<211> 5489
<212> DNA
<213> Homo sapiens
<400> 15
gaaactctta acaaaaacaa ggggctcggg gaggtttccg ctgaggcggc gggggtgcgg 60
cggtgggctg gtcttccgcg gccggcgttg cgccgcggcg gagggtgggc gcgcggggag 120
cgggatggag ccggggctgt gaggccgagg cggcggtgcc tgggaggaag ggtcggatgc 180
cggaccgggg gcaccgctga ggcggtgggt ccccgacctg cgagacaggt ttggaagccc 240
ccgctgcgcc cagtccgtgc ggaccgcgag gccgcgggcg ggtggaggcg cgtctccggc 300
acgatgaagg atttgggggc agagcacttg gcaggtcatg aaggggtcca acttctcggg 360
ttgttgaacg tctacctgga acaagaagag agattccaac ctcgagaaaa agggctgagt 420
ttgattgagg ctaccccgga gaatgataac actttgtgtc caggattgag aaatgccaaa 480
gttgaagatt taaggagttt agccaacttt tttggatctt gcactgaaac ttttgtcctg 540
gctgtcaata ttttggacag gttcttggct cttatgaagg tgaaacctaa acatttgtct 600
tgcattggag tctgttcttt tttgctggct gctagaatag ttgaagaaga ctgcaatatt 660
ccatccactc atgatgtgat ccggattagt cagtgtaaat gtactgcttc tgacataaaa 720
cggatggaaa aaataatttc agaaaaattg cactatgaat tggaagctac tactgcctta 780
aactttttgc acttatacca tactattata ctttgtcata cttcagaaag gaaagaaata 840
ctgagccttg ataaactaga agctcagctg aaagcttgca actgccgact catcttttca 900
aaagcaaaac catctgtatt agccttgtgc cttctcaatt tggaagtgga aactttgaaa 960
tctgttgaat tactggaaat tctcttgcta gttaaaaaac attccaagat taatgacact 1020
gagttcttct actggagaga gttggtttct aaatgcctag ccgagtattc ttctcctgaa 1080
tgttgcaaac cagatcttaa gaagttggtt tggatcgttt caaggcgcac agcccagaac 1140
ctccacaaca gctactatag tgttcctgag ctgccaacga tacctgaggg gggttgtttt 1200
gatgaaagtg aaagtgagga ctcttgtgaa gatatgagtt gtggagagga gagtctcagc 1260
agctctcctc ccagtgatca agagtgcacc ttctttttca acttcaaagt ggcacaaaca 1320
ctgtgctttc catcttagaa atctgattgt tctgtcagaa tttatattta caggtttcaa 1380
agcaataaat gggggaatag gtagtttcct ggtttagccc ccatctagtc aggaattaat 1440
atactggaat acctaccttc tatttgttat tcagatcaga tctggcctat tttcatattt 1500
atcctaagcc atcaaatggg gtagtgcctc ttaaaccatt aacagtactt tagacattgg 1560
cactttattt ttctcgtaga tctttagcta ctttggggag gagggaaggt gctgatacct 1620
tcaatttgtt acttttcaag atttttaaaa ataactagtg tagcttatct taaacatttt 1680
ataaaacctt cagatgtctt taagcagatt ggaagtatgc aagtgcttcc ttagcaggga 1740
cagtggataa tccttaatgg tttatcatag atttcaccct ccccccttct cagaagagtg 1800
agtatgctct taaatgtcaa acacattttt gttgttttgt tttttaaatg atcagtgtct 1860
atttgatgtg atgcagatct tataaatttg ggaattataa tattgacatt tctgtgattt 1920
ttatatatgt aatgtcttaa ttgagatttc tgttaaggca gaaataatta ggctagggct 1980
cttagttttc attcctattg cccaagtatt gtcaaactat ggtattattt taatgttact 2040
ttaaaaatcc ataatctgct agttttgcat gtacttatat gaaaacagtg cagtaagttg 2100
aaaactcagt atctatggaa ttgataaatg ttgatctggt gtagtatatt ttatcgcatt 2160
ttcttatatt aaaaaatgtc tgcatgatta cattttattt cctttgtaat ttacatttca 2220
gaatagtgta ttgctatatg ggtgccaaga ttgaatatga agaacccgag tgtttgtagt 2280
attatagttt taagcaaatc tgtgtggtga tacagccata agaatggggc ttatataaac 2340
tctgtacatg taagattttg tacagagaat ttttaacttt ataaattgta tatgaacatg 2400
taaatctttt aaaatgtaca taaaatactg tattttttta ccttgtgtgt gatagtctag 2460
tcattgcatg taaatataat ttattatgta ttctgtagta taaatcatac attgatgact 2520
tacattttta ctggtaagtc aacatccgtt ggatgttttc tgaagtggct ctttttgaag 2580
tgataataga ttgtaattca aaataaaatt attaatgaat tctccttgtt tgggatcaca 2640
tcttaatttt taatctgtta aaagttcttg atgtatttta atgagaagac tttaggtgag 2700
gctacagtga ttccagagtg agccttctaa ctggctagca gaagttctct aggtttggca 2760
tctgtgcctt ggagatactg aaagagaatc tgtcatttga caattgacct ctttgtggga 2820
tggactcatt aagtatgctc tcagagactg gtatattacc agaatgccta ttaattttca 2880
gtgagaggca acaggtatta agtagaacag aatgctcagg ttggcagatt agaacgatct 2940
ttcaggagac aaagcaagtt ttaatcagtt gtttggttaa taagtatggg gtgttcgctg 3000
tgatagggcc ccgccagctt ctggctcttg tggacctcaa aagtatcagg tggttttgca 3060
agtggtggtc ctttcccctg ccccacccca ataggttccc catctgtcta gtttgatttt 3120
tgtagacctt tgttttctct agttagaaaa tcaggtacac tgaatatggt tttcatgtaa 3180
cacctcttct ctggagatag gggtatgttt tcctaccctt ctagtggaga atcctacttg 3240
aggatgacct ttcctctctt actaaataat attagtaaat agtgggcaat atattctgct 3300
ttcagatttt gatttgttga gatgtaaaag ttgtttgggg cttaccaaat ctcaagactc 3360
tctttagctc ctgcaggatt gtattgcttt tcttactgga tatttttcct gggtaagcat 3420
ctttgtggct tcatctcttc cccctgtggt tttcagtgta tttagtcgag acctctctgc 3480
tgagcttgca acctgtttat tcacatggcc tgccatgcca cttggaggtt tctgattact 3540
cccaaacctg ctggttcttt atgtctttct cagcgaataa ttccatctat tcatgttgga 3600
aacttaggtg atatgctcat ctccttttgc ctgtttatgg aggtcaccag cctctatcat 3660
ttgtatgatt tcgtttacac tgtttatatc tctctgtccc ccctttttct gccattggca 3720
tggtttagac ctgtactctt tatcagcaga ggtactgtaa tatatttgtg atccctcagc 3780
ttccaggctt actcctggtc tctgccttcc tatctacata tccttttaaa ataaaatttt 3840
aactatctcc tgaaaaattg ttgagtaggt cacgcacaat caggagaaaa atctattcat 3900
gacatacaag tctctgtcta atctgaacac tgcacctgtc tctggccttt ttttcttgtc 3960
atttcctaga ccttaaaaaa tgtgtattga gaaagaactc tgttagctat acagaagatg 4020
aactgggcaa tatagagtag cagcatggag accagtctga ctgaactaag gcagtggaag 4080
tgtggatgag gaagagaggt gaaaattgag aagcgctatc ctttctcttt gggcattatt 4140
aggaggctca cagacaagtc caggagcctg gttataccct cctgtgccat tcaaccaggt 4200
ggctttccca tgactgtgat gaataaaatt gagaagcccc tgcccttttc agagcagagg 4260
gtgaggagaa agctaccatt ttgtcctcat ccttaccccc gttgacttgg cgagagattt 4320
gacctttcag gttttgatcc tgtcattttc taggatgtgg tgcacgcact ttgctgttgc 4380
gcatggtgaa gtattgtgcc taggtcctgg gtcttcatct gtttggctct gctactgttt 4440
cctcctccca ggaagtgtgg ttagacaaat aatgtgtttt aattacctgt cacactcagg 4500
attaatacat actcaggtta actgtagaga ggcattggct tcagaacact cctcgtgaca 4560
attttaacca ttttctttgt ctagagtctg cctttttctt ttttacaatt tcttttattt 4620
caacactagg tttcaatatg gtgttcctgc tacctcccac ctccctcctc cctcatcaca 4680
catgcaaatt gtcagcttat tgagacaacc cacttagatt catatatgga caaggacaag 4740
gtattttgca tttgttactg gaattcagtt ttcctaacta tttactacca gaaatggtca 4800
ataacttact ttgtgtttag caaatcaaat tgtgtgatag atagtttccc agtatgatgg 4860
ccagtcagtc tttccatccc tgtgcctaca tgctgctctt cccgtccaca agtggagtct 4920
gtttctcttg agttttggct ggccttatga atggctttgc ttactgaagt gcagcagaag 4980
aaatttagta tatgtccaag cctaggcttt aagagactgg cagctttcct tttatccttt 5040
ttggaagcta gccaccatgc tgcaaagaag ctcagctgga ttactgaaag atgagaggcc 5100
atgtggagag agactcttga ggatgagaga ttatcttgga tgttccagcc ttaagctccc 5160
agctgaatgt gggtgtatcc tcagctacac cacagaaaac agaggaacta ctcagtcgat 5220
cccaatcaac ccacagactc actagaaata acaaattatt gttttaagcc acgaggtttt 5280
gggggagggt tgttaaacag taatagataa gtgagacaga ttgcttgtta tttatggtca 5340
aatggtgatt atctctggtg agattacagg tgatgttttt tttaagttat gcctatctgt 5400
agtttccttt ttttcctaaa attgatttga attattagtg tattaacaga ataaagaatg 5460
aactttaaaa cacaaaaaaa aaaaaaaaa 5489
<210> 16
<211> 2122
<212> DNA
<213> Homo sapiens
<400> 16
ggtggctatt ttgtccttgg gctgcctgtt ttcagctgct gcaaccacag ggatttcttc 60
tgttcaggcg ccatgtcaga accggctggg gatgtccgtc agaacccatg cggcagcaag 120
gcctgccgcc gcctcttcgg cccagtggac agcgagcagc tgagccgcga ctgtgatgcg 180
ctaatggcgg gctgcatcca ggaggcccgt gagcgatgga acttcgactt tgtcaccgag 240
acaccactgg agggtgactt cgcctgggag cgtgtgcggg gccttggcct gcccaagctc 300
taccttccca cggggccccg gcgaggccgg gatgagttgg gaggaggcag gcggcctggc 360
acctcacctg ctctgctgca ggggacagca gaggaagacc atgtggacct gtcactgtct 420
tgtacccttg tgcctcgctc aggggagcag gctgaagggt ccccaggtgg acctggagac 480
tctcagggtc gaaaacggcg gcagaccagc atgacagatt tctaccactc caaacgccgg 540
ctgatcttct ccaagaggaa gccctaatcc gcccacagga agcctgcagt cctggaagcg 600
cgagggcctc aaaggcccgc tctacatctt ctgccttagt ctcagtttgt gtgtcttaat 660
tattatttgt gttttaattt aaacacctcc tcatgtacat accctggccg ccccctgccc 720
cccagcctct ggcattagaa ttatttaaac aaaaactagg cggttgaatg agaggttcct 780
aagagtgctg ggcattttta ttttatgaaa tactatttaa agcctcctca tcccgtgttc 840
tccttttcct ctctcccgga ggttgggtgg gccggcttca tgccagctac ttcctcctcc 900
ccacttgtcc gctgggtggt accctctgga ggggtgtggc tccttcccat cgctgtcaca 960
ggcggttatg aaattcaccc cctttcctgg acactcagac ctgaattctt tttcatttga 1020
gaagtaaaca gatggcactt tgaaggggcc tcaccgagtg ggggcatcat caaaaacttt 1080
ggagtcccct cacctcctct aaggttgggc agggtgaccc tgaagtgagc acagcctagg 1140
gctgagctgg ggacctggta ccctcctggc tcttgatacc cccctctgtc ttgtgaaggc 1200
agggggaagg tggggtcctg gagcagacca ccccgcctgc cctcatggcc cctctgacct 1260
gcactgggga gcccgtctca gtgttgagcc ttttccctct ttggctcccc tgtacctttt 1320
gaggagcccc agctaccctt cttctccagc tgggctctgc aattcccctc tgctgctgtc 1380
cctccccctt gtcctttccc ttcagtaccc tctcagctcc aggtggctct gaggtgcctg 1440
tcccaccccc acccccagct caatggactg gaaggggaag ggacacacaa gaagaagggc 1500
accctagttc tacctcaggc agctcaagca gcgaccgccc cctcctctag ctgtgggggt 1560
gagggtccca tgtggtggca caggccccct tgagtggggt tatctctgtg ttaggggtat 1620
atgatggggg agtagatctt tctaggaggg agacactggc ccctcaaatc gtccagcgac 1680
cttcctcatc caccccatcc ctccccagtt cattgcactt tgattagcag cggaacaagg 1740
agtcagacat tttaagatgg tggcagtaga ggctatggac agggcatgcc acgtgggctc 1800
atatggggct gggagtagtt gtctttcctg gcactaacgt tgagcccctg gaggcactga 1860
agtgcttagt gtacttggag tattggggtc tgaccccaaa caccttccag ctcctgtaac 1920
atactggcct ggactgtttt ctctcggctc cccatgtgtc ctggttcccg tttctccacc 1980
tagactgtaa acctctcgag ggcagggacc acaccctgta ctgttctgtg tctttcacag 2040
ctcctcccac aatgctgaat atacagcagg tgctcaataa atgattctta gtgactttac 2100
ttgtaaaaaa aaaaaaaaaa aa 2122
<210> 17
<211> 2413
<212> DNA
<213> Homo sapiens
<400> 17
cttcttcgtc agcctccctt ccaccgccat attgggccac taaaaaaagg gggctcgtct 60
tttcggggtg tttttctccc cctcccctgt ccccgcttgc tcacggctct gcgactccga 120
cgccggcaag gtttggagag cggctgggtt cgcgggaccc gcgggcttgc acccgcccag 180
actcggacgg gctttgccac cctctccgct tgcctggtcc cctctcctct ccgccctccc 240
gctcgccagt ccatttgatc agcggagact cggcggccgg gccggggctt ccccgcagcc 300
cctgcgcgct cctagagctc gggccgtggc tcgtcggggt ctgtgtcttt tggctccgag 360
ggcagtcgct gggcttccga gaggggttcg ggctgcgtag gggcgctttg ttttgttcgg 420
ttttgttttt ttgagagtgc gagagaggcg gtcgtgcaga cccgggagaa agatgtcaaa 480
cgtgcgagtg tctaacggga gccctagcct ggagcggatg gacgccaggc aggcggagca 540
ccccaagccc tcggcctgca ggaacctctt cggcccggtg gaccacgaag agttaacccg 600
ggacttggag aagcactgca gagacatgga agaggcgagc cagcgcaagt ggaatttcga 660
ttttcagaat cacaaacccc tagagggcaa gtacgagtgg caagaggtgg agaagggcag 720
cttgcccgag ttctactaca gacccccgcg gccccccaaa ggtgcctgca aggtgccggc 780
gcaggagagc caggatgtca gcgggagccg cccggcggcg cctttaattg gggctccggc 840
taactctgag gacacgcatt tggtggaccc aaagactgat ccgtcggaca gccagacggg 900
gttagcggag caatgcgcag gaataaggaa gcgacctgca accgacgatt cttctactca 960
aaacaaaaga gccaacagaa cagaagaaaa tgtttcagac ggttccccaa atgccggttc 1020
tgtggagcag acgcccaaga agcctggcct cagaagacgt caaacgtaaa cagctcgaat 1080
taagaatatg tttccttgtt tatcagatac atcactgctt gatgaagcaa ggaagatata 1140
catgaaaatt ttaaaaatac atatcgctga cttcatggaa tggacatcct gtataagcac 1200
tgaaaaacaa caacacaata acactaaaat tttaggcact cttaaatgat ctgcctctaa 1260
aagcgttgga tgtagcatta tgcaattagg tttttcctta tttgcttcat tgtactacct 1320
gtgtatatag tttttacctt ttatgtagca cataaacttt ggggaaggga gggcagggtg 1380
gggctgagga actgacgtgg agcggggtat gaagagcttg ctttgattta cagcaagtag 1440
ataaatattt gacttgcatg aagagaagca attttgggga agggtttgaa ttgttttctt 1500
taaagatgta atgtcccttt cagagacagc tgatacttca tttaaaaaaa tcacaaaaat 1560
ttgaacactg gctaaagata attgctattt atttttacaa gaagtttatt ctcatttggg 1620
agatctggtg atctcccaag ctatctaaag tttgttagat agctgcatgt ggctttttta 1680
aaaaagcaac agaaacctat cctcactgcc ctccccagtc tctcttaaag ttggaattta 1740
ccagttaatt actcagcaga atggtgatca ctccaggtag tttggggcaa aaatccgagg 1800
tgcttgggag ttttgaatgt taagaattga ccatctgctt ttattaaatt tgttgacaaa 1860
attttctcat tttcttttca cttcgggctg tgtaaacaca gtcaaaataa ttctaaatcc 1920
ctcgatattt ttaaagatct gtaagtaact tcacattaaa aaatgaaata ttttttaatt 1980
taaagcttac tctgtccatt tatccacagg aaagtgttat ttttcaagga aggttcatgt 2040
agagaaaagc acacttgtag gataagtgaa atggatacta catctttaaa cagtatttca 2100
ttgcctgtgt atggaaaaac catttgaagt gtacctgtgt acataactct gtaaaaacac 2160
tgaaaaatta tactaactta tttatgttaa aagatttttt ttaatctaga caatatacaa 2220
gccaaagtgg catgttttgt gcatttgtaa atgctgtgtt gggtagaata ggttttcccc 2280
tcttttgtta aataatatgg ctatgcttaa aaggttgcat actgagccaa gtataatttt 2340
ttgtaatgtg tgaaaaagat gccaattatt gttacacatt aagtaatcaa taaagaaaac 2400
ttccatagct att 2413
<210> 18
<211> 4372
<212> DNA
<213> Homo sapiens
<400> 18
ggtgcctccg ggggcggggc ctccttcggt tggcggcctc gggcttcggg agtcctccaa 60
gaggccaggt gaggccgtcc cgtgatgccc cgcgccccgg ccgctctggc ctgcaacgtg 120
tctctggggc ggaggcagcg gcagtggagt tcgctgcgcg ctgttggggg ccacctgtct 180
tttcgcttgt gtccctcttt ctagtgtcgc gctcgagtcc cgacgggccg ctccaagcct 240
cgacatgtcg tacaactacg tggtaacggc ccagaagccc accgccgtga acggctgcgt 300
gaccggacac tttacttcgg ccgaagactt aaacctgttg attgccaaaa acacgagatt 360
agagatctat gtggtcaccg ccgaggggct tcggcccgtc aaagaggtgg gcatgtatgg 420
gaagattgcg gtcatggagc ttttcaggcc caagggggag agcaaggacc tgctgtttat 480
cttgacagcg aagtacaatg cctgcatcct ggagtataaa cagagtggcg agagcattga 540
catcattacg cgagcccatg gcaatgtcca ggaccgcatt ggccgcccct cagagaccgg 600
cattattggc atcattgacc ctgagtgccg gatgattggc ctgcgtctct atgatggcct 660
tttcaaggtt attccactag atcgcgataa taaagaactc aaggccttca acatccgcct 720
ggaggagctg catgtcattg atgtcaagtt cctatatggt tgccaagcac ctactatttg 780
ctttgtctac caggaccctc aggggcggca cgtaaaaacc tatgaggtgt ctctccgaga 840
aaaggaattc aataagggcc cttggaaaca ggaaaatgtc gaagctgaag cttccatggt 900
gatcgcagtc ccagagccct ttgggggggc catcatcatt ggacaggagt caatcaccta 960
tcacaatggt gacaaatacc tggctattgc ccctcctatc atcaagcaaa gcacgattgt 1020
gtgccacaat cgagtggacc ctaatggctc aagatacctg ctgggagaca tggaaggccg 1080
gctcttcatg ctgcttttgg agaaggagga acagatggat ggcaccgtca ctctcaagga 1140
tctccgtgta gaactccttg gagagacctc tattgctgag tgcttgacat accttgataa 1200
tggtgttgtg tttgtcgggt ctcgcctggg tgactcccag cttgtgaagc tcaacgttga 1260
cagtaatgaa caaggctcct atgtagtggc catggaaacc tttaccaact taggacccat 1320
tgtcgatatg tgcgtggtgg acctggagag gcaggggcag gggcagctgg tcacttgctc 1380
tggggctttc aaggaaggtt ctttgcggat catccggaat ggaattggaa tccacgagca 1440
tgccagcatt gacttaccag gcatcaaagg attatggcca ctgcggtctg accctaatcg 1500
tgagactgat gacactttgg tgctctcttt tgtgggccag acaagagttc tcatgttaaa 1560
tggagaggag gtagaagaaa ccgaactgat gggtttcgtg gatgatcagc agactttctt 1620
ctgtggcaac gtggctcatc agcagcttat ccagatcact tcagcatcgg tgaggttggt 1680
ctctcaagaa cccaaagctc tggtcagtga atggaaggag cctcaggcca agaacatcag 1740
tgtggcctcc tgcaatagca gccaggtggt ggtggctgta ggcagggccc tctactatct 1800
gcagatccat cctcaggagc tccggcagat cagccacaca gagatggaac atgaagtggc 1860
ttgcttggac atcaccccat taggagacag caatggactg tcccctcttt gtgccattgg 1920
cctctggacg gacatctcgg ctcgtatctt gaagttgccc tcttttgaac tactgcacaa 1980
ggagatgctg ggtggagaga tcattcctcg ctccatcctg atgaccacct ttgagagtag 2040
ccattacctc ctttgtgcct tgggagatgg agcgcttttc tactttgggc tcaacattga 2100
gacaggtctg ttgagcgacc gtaagaaggt gactttgggc acccagccca ccgtattgag 2160
gacttttcgt tctctttcta ccaccaacgt ctttgcttgt tctgaccgcc ccactgtcat 2220
ctatagcagc aaccacaaat tggtcttctc aaatgtcaac ctcaaggaag tgaactacat 2280
gtgtcccctc aattcagatg gctatcctga cagcctggcg ctggccaaca atagcaccct 2340
caccattggc accatcgatg agatccagaa gctgcacatt cgcacagttc ccctctatga 2400
gtctccaagg aagatctgct accaggaagt gtcccagtgt ttcggggtcc tctccagccg 2460
cattgaagtc caagacacga gtgggggcac gacagccttg aggcccagcg ctagcaccca 2520
ggctctgtcc agcagtgtaa gctccagcaa gctgttctcc agcagcactg ctcctcatga 2580
gacctccttt ggagaagagg tggaggtgca caacctactt atcattgacc aacacacctt 2640
tgaagtgctt catgcccacc agtttctgca gaatgaatat gccctcagtc tggtttcctg 2700
caagctgggc aaagacccca acacttactt cattgtgggc acagcaatgg tgtatcctga 2760
agaggcagag cccaagcagg gtcgcattgt ggtctttcag tattcggatg gaaaactaca 2820
gactgtggct gaaaaggaag tgaaaggggc cgtgtactct atggtggaat ttaacgggaa 2880
gctgttagcc agcatcaata gcacggtgcg gctctatgag tggacaacag agaaggagct 2940
gcgcactgag tgcaaccact acaacaacat catggccctc tacctgaaga ccaagggcga 3000
cttcatcctg gtgggcgacc ttatgcgctc agtgctgctg cttgcctaca agcccatgga 3060
aggaaacttt gaagagattg ctcgagactt taatcccaac tggatgagtg ctgtggaaat 3120
cttggatgat gacaattttc tgggggctga aaatgccttt aacttgtttg tgtgtcaaaa 3180
ggatagcgct gccaccactg acgaggagcg gcagcacctc caggaggttg gtcttttcca 3240
cctgggcgag tttgtcaatg tcttttgcca cggctctctg gtaatgcaga atctgggtga 3300
gacttccacc cccacacaag gctcggtgct cttcggcacg gtcaacggca tgatagggct 3360
ggtgacctca ctgtcagaga gctggtacaa cctcctgctg gacatgcaga atcgactcaa 3420
taaagtcatc aaaagtgtgg ggaagatcga gcactccttc tggagatcct ttcacaccga 3480
gcggaagaca gaaccagcca caggtttcat cgacggtgac ttgattgaga gtttcctgga 3540
tattagccgc cccaagatgc aggaggtggt ggcaaaccta cagtatgacg atggcagcgg 3600
tatgaagcga gaggccactg cagacgacct catcaaggtt gtggaggagc taactcggat 3660
ccattagcca agggcagggg gcccctttgc tgaccctccc caaaggcttt gccctgctgc 3720
cctccccctc ctctccacca tcgtcttctt ggccatggga ggcctttccc taagccagct 3780
gcccccagag ccacagttcc cctatgtgga agtggggcgg gcttcataga gacttgggaa 3840
tgagctgaag gtgaaacatt ttctccctgg atttttacca gtctcacatg attccagcca 3900
tcaccttaga ccaccaagcc ttgattggtg ttgccagttg tcctccttcc ggggaaggat 3960
tttgcagttc tttggctgaa aggaagctgt gcgtgtgtgt gtgtgtatgt gtgtgtgtgt 4020
atgtgtatct cacactcatg cattgtcctc tttttattta gattggcagt gtagggagtt 4080
gtgggtagtg gggaagaggg ttaggagggt ttcattgtct gtgaagtgag accttccttt 4140
tacttttctt ctattgcctc tgagagcatc aggcctagag gcctgactgc caagccatgg 4200
gtagcctggg tgtaaaacct ggagatggtg gatgatcccc acgccacagc ccttttgtct 4260
ctgcaaactg ccttcttcgg aaagaagaag gtgggaggat gtgaattgtt agtttctgag 4320
ttttaccaaa taaagtagaa tataagaaga aaggtaaaaa aaaaaaaaaa aa 4372
<210> 19
<211> 827
<212> DNA
<213> Homo sapiens
<400> 19
gtgatccttg gggccaggta tggcatgccc attgatatgt ggagcctggg ctgcatttta 60
gcagagctcc tgacgggtta ccccctcttg cctggggaag atgaagggga ccagctggcc 120
tgtatgattg aactgttggg catgccctca cagaaactgc tggatgcatc caaacgagcc 180
aaaaattttg tgagctccaa gggttatccc cgttactgca ctgtcacgac tctctcagat 240
ggctctgtgg tcctaaacgg aggccgttcc cggaggggga aactgagggg cccaccggag 300
agcagagagt gggggaacgc gctgaagggg tgtgatgatc cccttttcct tgacttctta 360
aaacagtgtt tagagtggga tcctgcagtg cgcatgaccc caggccaggc tttgcggcac 420
ccctggctga ggaggcggtt gccaaagcct cccaccgggg agaaaacgtc agtgaaaagg 480
ataactgaga gcaccggtgc tatcacatct atatccaagt tacctccacc ttctagctca 540
gcttccaaac tgaggactaa tttggcgcag atgacagatg ccaatgggaa tattcagcag 600
aggacagtgt tgccaaaact tgttagctga gctcacgtcc cctgatgctg gtaacctgaa 660
agatacgaca ttgctgagcc ttactgggtt gaaaaggagt agctcagacc tgtttttatt 720
tgctcaataa ctctactcat ttgtatcttt tcagcactta attttaatgt aagaaagttg 780
ttcattttgt ttttataaaa tacatgagga caatgaaaaa aaaaaaa 827
<210> 20
<211> 4975
<212> DNA
<213> Homo sapiens
<400> 20
ctctcacaca cacacacccc tcccctgcca tccctccccg gactccggct ccggctccga 60
ttgcaatttg caacctccgc tgccgtcgcc gcagcagcca ccaattcgcc agcggttcag 120
gtggctcttg cctcgatgtc ctagcctagg ggcccccggg ccggacttgg ctgggctccc 180
ttcaccctct gcggagtcat gagggcgaac gacgctctgc aggtgctggg cttgcttttc 240
agcctggccc ggggctccga ggtgggcaac tctcaggcag tgtgtcctgg gactctgaat 300
ggcctgagtg tgaccggcga tgctgagaac caataccaga cactgtacaa gctctacgag 360
aggtgtgagg tggtgatggg gaaccttgag attgtgctca cgggacacaa tgccgacctc 420
tccttcctgc agtggattcg agaagtgaca ggctatgtcc tcgtggccat gaatgaattc 480
tctactctac cattgcccaa cctccgcgtg gtgcgaggga cccaggtcta cgatgggaag 540
tttgccatct tcgtcatgtt gaactataac accaactcca gccacgctct gcgccagctc 600
cgcttgactc agctcaccga gattctgtca gggggtgttt atattgagaa gaacgataag 660
ctttgtcaca tggacacaat tgactggagg gacatcgtga gggaccgaga tgctgagata 720
gtggtgaagg acaatggcag aagctgtccc ccctgtcatg aggtttgcaa ggggcgatgc 780
tggggtcctg gatcagaaga ctgccagaca ttgaccaaga ccatctgtgc tcctcagtgt 840
aatggtcact gctttgggcc caaccccaac cagtgctgcc atgatgagtg tgccgggggc 900
tgctcaggcc ctcaggacac agactgcttt gcctgccggc acttcaatga cagtggagcc 960
tgtgtacctc gctgtccaca gcctcttgtc tacaacaagc taactttcca gctggaaccc 1020
aatccccaca ccaagtatca gtatggagga gtttgtgtag ccagctgtcc ccataacttt 1080
gtggtggatc aaacatcctg tgtcagggcc tgtcctcctg acaagatgga agtagataaa 1140
aatgggctca agatgtgtga gccttgtggg ggactatgtc ccaaagcctg tgagggaaca 1200
ggctctggga gccgcttcca gactgtggac tcgagcaaca ttgatggatt tgtgaactgc 1260
accaagatcc tgggcaacct ggactttctg atcaccggcc tcaatggaga cccctggcac 1320
aagatccctg ccctggaccc agagaagctc aatgtcttcc ggacagtacg ggagatcaca 1380
ggttacctga acatccagtc ctggccgccc cacatgcaca acttcagtgt tttttccaat 1440
ttgacaacca ttggaggcag aagcctctac aaccggggct tctcattgtt gatcatgaag 1500
aacttgaatg tcacatctct gggcttccga tccctgaagg aaattagtgc tgggcgtatc 1560
tatataagtg ccaataggca gctctgctac caccactctt tgaactggac caaggtgctt 1620
cgggggccta cggaagagcg actagacatc aagcataatc ggccgcgcag agactgcgtg 1680
gcagagggca aagtgtgtga cccactgtgc tcctctgggg gatgctgggg cccaggccct 1740
ggtcagtgct tgtcctgtcg aaattatagc cgaggaggtg tctgtgtgac ccactgcaac 1800
tttctgaatg gggagcctcg agaatttgcc catgaggccg aatgcttctc ctgccacccg 1860
gaatgccaac ccatgggggg cactgccaca tgcaatggct cgggctctga tacttgtgct 1920
caatgtgccc attttcgaga tgggccccac tgtgtgagca gctgccccca tggagtccta 1980
ggtgccaagg gcccaatcta caagtaccca gatgttcaga atgaatgtcg gccctgccat 2040
gagaactgca cccaggggtg taaaggacca gagcttcaag actgtttagg acaaacactg 2100
gtgctgatcg gcaaaaccca tctgacaatg gctttgacag tgatagcagg attggtagtg 2160
attttcatga tgctgggcgg cacttttctc tactggcgtg ggcgccggat tcagaataaa 2220
agggctatga ggcgatactt ggaacggggt gagagcatag agcctctgga ccccagtgag 2280
aaggctaaca aagtcttggc cagaatcttc aaagagacag agctaaggaa gcttaaagtg 2340
cttggctcgg gtgtctttgg aactgtgcac aaaggagtgt ggatccctga gggtgaatca 2400
atcaagattc cagtctgcat taaagtcatt gaggacaaga gtggacggca gagttttcaa 2460
gctgtgacag atcatatgct ggccattggc agcctggacc atgcccacat tgtaaggctg 2520
ctgggactat gcccagggtc atctctgcag cttgtcactc aatatttgcc tctgggttct 2580
ctgctggatc atgtgagaca acaccggggg gcactggggc cacagctgct gctcaactgg 2640
ggagtacaaa ttgccaaggg aatgtactac cttgaggaac atggtatggt gcatagaaac 2700
ctggctgccc gaaacgtgct actcaagtca cccagtcagg ttcaggtggc agattttggt 2760
gtggctgacc tgctgcctcc tgatgataag cagctgctat acagtgaggc caagactcca 2820
attaagtgga tggcccttga gagtatccac tttgggaaat acacacacca gagtgatgtc 2880
tggagctatg gtgtgacagt ttgggagttg atgaccttcg gggcagagcc ctatgcaggg 2940
ctacgattgg ctgaagtacc agacctgcta gagaaggggg agcggttggc acagccccag 3000
atctgcacaa ttgatgtcta catggtgatg gtcaagtgtt ggatgattga tgagaacatt 3060
cgcccaacct ttaaagaact agccaatgag ttcaccagga tggcccgaga cccaccacgg 3120
tatctggtca taaagagaga gagtgggcct ggaatagccc ctgggccaga gccccatggt 3180
ctgacaaaca agaagctaga ggaagtagag ctggagccag aactagacct agacctagac 3240
ttggaagcag aggaggacaa cctggcaacc accacactgg gctccgccct cagcctacca 3300
gttggaacac ttaatcggcc acgtgggagc cagagccttt taagtccatc atctggatac 3360
atgcccatga accagggtaa tcttgggggg tcttgccagg agtctgcagt ttctgggagc 3420
agtgaacggt gcccccgtcc agtctctcta cacccaatgc cacggggatg cctggcatca 3480
gagtcatcag aggggcatgt aacaggctct gaggctgagc tccaggagaa agtgtcaatg 3540
tgtagaagcc ggagcaggag ccggagccca cggccacgcg gagatagcgc ctaccattcc 3600
cagcgccaca gtctgctgac tcctgttacc ccactctccc cacccgggtt agaggaagag 3660
gatgtcaacg gttatgtcat gccagataca cacctcaaag gtactccctc ctcccgggaa 3720
ggcacccttt cttcagtggg tctcagttct gtcctgggta ctgaagaaga agatgaagat 3780
gaggagtatg aatacatgaa ccggaggaga aggcacagtc cacctcatcc ccctaggcca 3840
agttcccttg aggagctggg ttatgagtac atggatgtgg ggtcagacct cagtgcctct 3900
ctgggcagca cacagagttg cccactccac cctgtaccca tcatgcccac tgcaggcaca 3960
actccagatg aagactatga atatatgaat cggcaacgag atggaggtgg tcctgggggt 4020
gattatgcag ccatgggggc ctgcccagca tctgagcaag ggtatgaaga gatgagagct 4080
tttcaggggc ctggacatca ggccccccat gtccattatg cccgcctaaa aactctacgt 4140
agcttagagg ctacagactc tgcctttgat aaccctgatt actggcatag caggcttttc 4200
cccaaggcta atgcccagag aacgtaactc ctgctccctg tggcactcag ggagcattta 4260
atggcagcta gtgcctttag agggtaccgt cttctcccta ttccctctct ctcccaggtc 4320
ccagcccctt ttccccagtc ccagacaatt ccattcaatc tttggaggct tttaaacatt 4380
ttgacacaaa attcttatgg tatgtagcca gctgtgcact ttcttctctt tcccaacccc 4440
aggaaaggtt ttccttattt tgtgtgcttt cccagtccca ttcctcagct tcttcacagg 4500
cactcctgga gatatgaagg attactctcc atatcccttc ctctcaggct cttgactact 4560
tggaactagg ctcttatgtg tgcctttgtt tcccatcaga ctgtcaagaa gaggaaaggg 4620
aggaaaccta gcagaggaaa gtgtaatttt ggtttatgac tcttaacccc ctagaaagac 4680
agaagcttaa aatctgtgaa gaaagaggtt aggagtagat attgattact atcataattc 4740
agcacttaac tatgagccag gcatcatact aaacttcacc tacattatct cacttagtcc 4800
tttatcatcc ttaaaacaat tctgtgacat acatattatc tcattttaca caaagggaag 4860
tcgggcatgg tggctcatgc ctgtaatctc agcactttgg gaggctgagg cagaaggatt 4920
acctgaggca aggagtttga gaccagctta gccaacatag taagaccccc atctc 4975
<210> 21
<211> 4627
<212> DNA
<213> Homo sapiens
<400> 21
tcacttgcct gatatttcca gtgtcagagg gacacagcca acgtggggtc ccttctaggc 60
tgacagccgc tctccagcca ctgccgcgag cccgtctgct cccgccctgc ccgtgcactc 120
tccgcagccg ccctccgcca agccccagcg cccgctccca tcgccgatga ccgcggggag 180
gaggatggag atgctctgtg ccggcagggt ccctgcgctg ctgctctgcc tgggtttcca 240
tcttctacag gcagtcctca gtacaactgt gattccatca tgtatcccag gagagtccag 300
tgataactgc acagctttag ttcagacaga agacaatcca cgtgtggctc aagtgtcaat 360
aacaaagtgt agctctgaca tgaatggcta ttgtttgcat ggacagtgca tctatctggt 420
ggacatgagt caaaactact gcaggtgtga agtgggttat actggtgtcc gatgtgaaca 480
cttcttttta accgtccacc aacctttaag caaagagtat gtggctttga ccgtgattct 540
tattattttg tttcttatca cagtcgtcgg ttccacatat tatttctgca gatggtacag 600
aaatcgaaaa agtaaagaac caaagaagga atatgagaga gttacctcag gggatccaga 660
gttgccgcaa gtctgaatgg cgccatcaaa cttatgggca gggataacag tgtgcctggt 720
taatattaat attccatttt attaataata tttatgttgg gtcaagtgtt aggtcaataa 780
cactgtattt taatgtactt gaaaaatgtt tttatttttg ttttattttt gacagactat 840
ttgctaatgt ataatgtgca gaaaatattt aatatcaaaa gaaaattgat atttttatac 900
aagtaatttc ctgagctaaa tgcttcattg aaagcttcaa agtttatatg cctggtgcac 960
agtgcttaga agtaagcaat tcccaggtca tagctcaaga attgttagca aatgacagat 1020
ttctgtaagc ctatatatat agtcaaatcg atttagtaag tatgtttttt atgttcctca 1080
aatcagtgat aattggtttg actgtaccat ggtttgatat gtagttggca ccatggtatc 1140
atatattaaa acaataatgc aattagaatt tgggagaagc aaatataggt cctgtgttaa 1200
acactacaca tttgaaacaa gctaaccctg gggagtctat ggtctcttca ctcaggtctc 1260
agctataatt ctgttatatg aggggcagtg gacagttccc tatgccaact cacgactcct 1320
acaggtacta gtcactcatc taccagattc tgcctatgta aaatgaattg aaaaacaatt 1380
ttctgtaatc ttttatttaa gtagtgggca tttcatagct tcacaatgtt ccttttttgt 1440
atattacaac atttatgtga ggtaattatt gctcaacaga caattagaaa aaagtccaca 1500
cttgaagcct aaatttgtgc tttttaagaa tatttttaga ctatttcttt ttataggggc 1560
tttgctgaat tctaacatta aatcacagcc caaaatttga tggactaatt attattttaa 1620
aatatatgaa gacaataatt ctacatgttg tcttaagatg gaaatacagt tatttcatct 1680
tttattcaag gaagttttaa ctttaataca gctcagtaaa tggcttcttc tagaatgtaa 1740
agttatgtat ttaaagttgt atcttgacac aggaaatggg aaaaaactta aaaattaata 1800
tggtgtattt ttccaaatga aaaatctcaa ttgaaagctt ttaaaatgta gaaacttaaa 1860
cacaccttcc tgtggaggct gagatgaaaa ctagggctca ttttcctgac atttgtttat 1920
tttttggaag agacaaagat ttcttctgca ctctgagccc ataggtctca gagagttaat 1980
aggagtattt ttgggctatt gcataaggag ccactgctgc caccactttt ggattttatg 2040
ggaggctcct tcatcgaatg ctaaaccttt gagtagagtc tccctggatc acataccagg 2100
tcagggagga tctgttcttc ctctacgttt atcctggcat gtgctagggt aaacgaaggc 2160
ataataagcc atggctgacc tctggagcac caggtgccag gacttgtctc catgtgtatc 2220
catgcattat ataccctggt gcaatcacac gactgtcatc taaagtcctg gccctggccc 2280
ttactattag gaaaataaac agacaaaaac aagtaaatat atatggtcct atacatattg 2340
tatatatatt catatacaaa catgtatgta tacatgacct taatggatca tagaattgca 2400
gtcatttggt gctctgctaa ccatttatat aaaacttaaa aacaagagaa aagaaaaatc 2460
aattagatct aaacagttat ttctgtttcc tatttaatat agctgaagtc aaaatatgta 2520
agaacacatt ttaaatactc tacttacagt tggccctctg tggttagttc cacatctgtg 2580
gattcaacca accaaggacg gaaaatgctt aaaaaataat acaacaacaa caaaaaatac 2640
attataacaa ctatttactt tttttttttt ctttttgaga tggagtctcg ctctgttgcc 2700
caggttggag tgcagtggca cgatctcggc tcactgcaac ctcacctccc gggttcaaga 2760
gatcctcctg cctcagcctc ctgagcagct gggactacag gcgcatgcca ccatgcccag 2820
ctaatttttg tatttttagt agaggcgggg tttcaccatg ttggccagga tggtctcaat 2880
ctcctaacct tgagatccac cctccacagc ctcccaaact gctgggatta caggcgtgag 2940
ccaccgcacg tagcatttac attaggtatt acaagtaatg taaagatgat ttaagtatac 3000
aggaggatgt gaataggtta tatgcaagca ctatgccctt ttatataagt gacttgaaca 3060
tctgtgcccg attttagtat gtgcaggggg gcgatctggg aatcagtccc ctgtggatac 3120
caaggtacaa ctgtatttat taacgcttac tagatgtgag gagagtctga atattttcag 3180
tgatcttggc tgtttcaaaa aaatctattg acttttcaat aaatcagctg caatccattt 3240
atttcattta caaaagattt attgtaagcc tctcaatctt ggtttttcag ttgatcttaa 3300
gcatgtcaat tcataaaaac aagtcatttt tgtatttttc atctttaaga atgcttaaaa 3360
aagctaatcc ctaaaatagt tagatctttg taaatgcata ttaaataata aagtatgacc 3420
cacattactt tttatgggtg aaaataagac aaaaataata gttttagtga ggatggtgct 3480
gagtaaacat aaaaactgat ttgctctcag ctgatgtgtc ctgtacacag tgggaagatt 3540
ttagttcaca cttagtctaa ctcccccatt ttacagattt ctcactatat atatttctag 3600
aaggggctat gcatattcaa tgtattgaga accaaagcaa ccacaaatgc ataaatgcat 3660
aatttatggt cttcaaccaa ggccacataa taacccagtt aacttactct ttaaccagga 3720
atattaagtt ctataactag tactcaaggt ttaaccttaa aattaagatt tccttaacct 3780
taaccttaaa attgatatta tattaaacat acataataca atgtaactcc actgttctcc 3840
tgaatatttt ttgctctaat ctctctgccg aaagtcaaag tgatgggaga attggtatac 3900
tggtatgact acgtcttaag tcagattttt atttatgagt ctttgagact aaattcaatc 3960
accaccaggt atcaaatcaa cttttatgca gcaaatatat gattctagtg tctgactttt 4020
gttaaattca gtaatgcagt ttttaaaaac ctgtatctga cccactttgt aatttttgct 4080
ccaatatcca ttctgtagac ttttgaaaaa aaagttttta atttgatgcc caatatattc 4140
tgaccgttaa aaaattcttg ttcatatggg agaaggggga gtaatgactt gtacaaacag 4200
tatttctggt gtatatttta atgtttttaa aaagagtaat ttcatttaaa tatctgttat 4260
tcaaatttga tgatgttaaa tgtaatataa tgtattttct ttttattttg cactctgtaa 4320
ttgcactttt taagtttgaa gagccatttt ggtaaacggt ttttattaaa gatgctatgg 4380
aacataaagt tgtattgcat gcaatttaaa gtaacttatt tgactatgaa tattatcgga 4440
ttactgaatt gtatcaattt gtttgtgttc aatatcagct ttgataattg tgtaccttaa 4500
gatattgaag gagaaaatag ataatttaca agatattatt aatttttatt tatttttctt 4560
gggaattgaa aaaaattgaa ataaataaaa atgcattgaa catcttgcat tcaaaatctt 4620
cactgac 4627
<210> 22
<211> 6450
<212> DNA
<213> Homo sapiens
<400> 22
gagttgtgcc tggagtgatg tttaagccaa tgtcagggca aggcaacagt ccctggccgt 60
cctccagcac ctttgtaatg catatgagct cgggagacca gtacttaaag ttggaggccc 120
gggagcccag gagctggcgg agggcgttcg tcctgggagc tgcacttgct ccgtcgggtc 180
gccggcttca ccggaccgca ggctcccggg gcagggccgg ggccagagct cgcgtgtcgg 240
cgggacatgc gctgcgtcgc ctctaacctc gggctgtgct ctttttccag gtggcccgcc 300
ggtttctgag ccttctgccc tgcggggaca cggtctgcac cctgcccgcg gccacggacc 360
atgaccatga ccctccacac caaagcatct gggatggccc tactgcatca gatccaaggg 420
aacgagctgg agcccctgaa ccgtccgcag ctcaagatcc ccctggagcg gcccctgggc 480
gaggtgtacc tggacagcag caagcccgcc gtgtacaact accccgaggg cgccgcctac 540
gagttcaacg ccgcggccgc cgccaacgcg caggtctacg gtcagaccgg cctcccctac 600
ggccccgggt ctgaggctgc ggcgttcggc tccaacggcc tggggggttt ccccccactc 660
aacagcgtgt ctccgagccc gctgatgcta ctgcacccgc cgccgcagct gtcgcctttc 720
ctgcagcccc acggccagca ggtgccctac tacctggaga acgagcccag cggctacacg 780
gtgcgcgagg ccggcccgcc ggcattctac aggccaaatt cagataatcg acgccagggt 840
ggcagagaaa gattggccag taccaatgac aagggaagta tggctatgga atctgccaag 900
gagactcgct actgtgcagt gtgcaatgac tatgcttcag gctaccatta tggagtctgg 960
tcctgtgagg gctgcaaggc cttcttcaag agaagtattc aaggacataa cgactatatg 1020
tgtccagcca ccaaccagtg caccattgat aaaaacagga ggaagagctg ccaggcctgc 1080
cggctccgca aatgctacga agtgggaatg atgaaaggtg ggatacgaaa agaccgaaga 1140
ggagggagaa tgttgaaaca caagcgccag agagatgatg gggagggcag gggtgaagtg 1200
gggtctgctg gagacatgag agctgccaac ctttggccaa gcccgctcat gatcaaacgc 1260
tctaagaaga acagcctggc cttgtccctg acggccgacc agatggtcag tgccttgttg 1320
gatgctgagc cccccatact ctattccgag tatgatccta ccagaccctt cagtgaagct 1380
tcgatgatgg gcttactgac caacctggca gacagggagc tggttcacat gatcaactgg 1440
gcgaagaggg tgccaggctt tgtggatttg accctccatg atcaggtcca ccttctagaa 1500
tgtgcctggc tagagatcct gatgattggt ctcgtctggc gctccatgga gcacccagtg 1560
aagctactgt ttgctcctaa cttgctcttg gacaggaacc agggaaaatg tgtagagggc 1620
atggtggaga tcttcgacat gctgctggct acatcatctc ggttccgcat gatgaatctg 1680
cagggagagg agtttgtgtg cctcaaatct attattttgc ttaattctgg agtgtacaca 1740
tttctgtcca gcaccctgaa gtctctggaa gagaaggacc atatccaccg agtcctggac 1800
aagatcacag acactttgat ccacctgatg gccaaggcag gcctgaccct gcagcagcag 1860
caccagcggc tggcccagct cctcctcatc ctctcccaca tcaggcacat gagtaacaaa 1920
ggcatggagc atctgtacag catgaagtgc aagaacgtgg tgcccctcta tgacctgctg 1980
ctggagatgc tggacgccca ccgcctacat gcgcccacta gccgtggagg ggcatccgtg 2040
gaggagacgg accaaagcca cttggccact gcgggctcta cttcatcgca ttccttgcaa 2100
aagtattaca tcacggggga ggcagagggt ttccctgcca cagtctgaga gctccctggc 2160
tcccacacgg ttcagataat ccctgctgca ttttaccctc atcatgcacc actttagcca 2220
aattctgtct cctgcataca ctccggcatg catccaacac caatggcttt ctagatgagt 2280
ggccattcat ttgcttgctc agttcttagt ggcacatctt ctgtcttctg ttgggaacag 2340
ccaaagggat tccaaggcta aatctttgta acagctctct ttcccccttg ctatgttact 2400
aagcgtgagg attcccgtag ctcttcacag ctgaactcag tctatgggtt ggggctcaga 2460
taactctgtg catttaagct acttgtagag acccaggcct ggagagtaga cattttgcct 2520
ctgataagca ctttttaaat ggctctaaga ataagccaca gcaaagaatt taaagtggct 2580
cctttaattg gtgacttgga gaaagctagg tcaagggttt attatagcac cctcttgtat 2640
tcctatggca atgcatcctt ttatgaaagt ggtacacctt aaagctttta tatgactgta 2700
gcagagtatc tggtgattgt caattcactt ccccctatag gaatacaagg ggccacacag 2760
ggaaggcaga tcccctagtt ggccaagact tattttaact tgatacactg cagattcaga 2820
gtgtcctgaa gctctgcctc tggctttccg gtcatgggtt ccagttaatt catgcctccc 2880
atggacctat ggagagcaac aagttgatct tagttaagtc tccctatatg agggataagt 2940
tcctgatttt tgtttttatt tttgtgttac aaaagaaagc cctccctccc tgaacttgca 3000
gtaaggtcag cttcaggacc tgttccagtg ggcactgtac ttggatcttc ccggcgtgtg 3060
tgtgccttac acaggggtga actgttcact gtggtgatgc atgatgaggg taaatggtag 3120
ttgaaaggag caggggccct ggtgttgcat ttagccctgg ggcatggagc tgaacagtac 3180
ttgtgcagga ttgttgtggc tactagagaa caagagggaa agtagggcag aaactggata 3240
cagttctgag cacagccaga cttgctcagg tggccctgca caggctgcag ctacctagga 3300
acattccttg cagaccccgc attgcctttg ggggtgccct gggatccctg gggtagtcca 3360
gctcttattc atttcccagc gtggccctgg ttggaagaag cagctgtcaa gttgtagaca 3420
gctgtgttcc tacaattggc ccagcaccct ggggcacggg agaagggtgg ggaccgttgc 3480
tgtcactact caggctgact ggggcctggt cagattacgt atgcccttgg tggtttagag 3540
ataatccaaa atcagggttt ggtttgggga agaaaatcct cccccttcct cccccgcccc 3600
gttccctacc gcctccactc ctgccagctc atttccttca atttcctttg acctataggc 3660
taaaaaagaa aggctcattc cagccacagg gcagccttcc ctgggccttt gcttctctag 3720
cacaattatg ggttacttcc tttttcttaa caaaaaagaa tgtttgattt cctctgggtg 3780
accttattgt ctgtaattga aaccctattg agaggtgatg tctgtgttag ccaatgaccc 3840
aggtagctgc tcgggcttct cttggtatgt cttgtttgga aaagtggatt tcattcattt 3900
ctgattgtcc agttaagtga tcaccaaagg actgagaatc tgggagggca aaaaaaaaaa 3960
aaaaagtttt tatgtgcact taaatttggg gacaatttta tgtatctgtg ttaaggatat 4020
gcttaagaac ataattcttt tgttgctgtt tgtttaagaa gcaccttagt ttgtttaaga 4080
agcaccttat atagtataat atatattttt ttgaaattac attgcttgtt tatcagacaa 4140
ttgaatgtag taattctgtt ctggatttaa tttgactggg ttaacatgca aaaaccaagg 4200
aaaaatattt agtttttttt tttttttttg tatacttttc aagctacctt gtcatgtata 4260
cagtcattta tgcctaaagc ctggtgatta ttcatttaaa tgaagatcac atttcatatc 4320
aacttttgta tccacagtag acaaaatagc actaatccag atgcctattg ttggatattg 4380
aatgacagac aatcttatgt agcaaagatt atgcctgaaa aggaaaatta ttcagggcag 4440
ctaattttgc ttttaccaaa atatcagtag taatattttt ggacagtagc taatgggtca 4500
gtgggttctt tttaatgttt atacttagat tttcttttaa aaaaattaaa ataaaacaaa 4560
aaaaatttct aggactagac gatgtaatac cagctaaagc caaacaatta tacagtggaa 4620
ggttttacat tattcatcca atgtgtttct attcatgtta agatactact acatttgaag 4680
tgggcagaga acatcagatg attgaaatgt tcgcccaggg gtctccagca actttggaaa 4740
tctctttgta tttttacttg aagtgccact aatggacagc agatattttc tggctgatgt 4800
tggtattggg tgtaggaaca tgatttaaaa aaaaaactct tgcctctgct ttcccccact 4860
ctgaggcaag ttaaaatgta aaagatgtga tttatctggg gggctcaggt atggtgggga 4920
agtggattca ggaatctggg gaatggcaaa tatattaaga agagtattga aagtatttgg 4980
aggaaaatgg ttaattctgg gtgtgcacca aggttcagta gagtccactt ctgccctgga 5040
gaccacaaat caactagctc catttacagc catttctaaa atggcagctt cagttctaga 5100
gaagaaagaa caacatcagc agtaaagtcc atggaatagc tagtggtctg tgtttctttt 5160
cgccattgcc tagcttgccg taatgattct ataatgccat catgcagcaa ttatgagagg 5220
ctaggtcatc caaagagaag accctatcaa tgtaggttgc aaaatctaac ccctaaggaa 5280
gtgcagtctt tgatttgatt tccctagtaa ccttgcagat atgtttaacc aagccatagc 5340
ccatgccttt tgagggctga acaaataagg gacttactga taatttactt ttgatcacat 5400
taaggtgttc tcaccttgaa atcttataca ctgaaatggc cattgattta ggccactggc 5460
ttagagtact ccttcccctg catgacactg attacaaata ctttcctatt catactttcc 5520
aattatgaga tggactgtgg gtactgggag tgatcactaa caccatagta atgtctaata 5580
ttcacaggca gatctgcttg gggaagctag ttatgtgaaa ggcaaataaa gtcatacagt 5640
agctcaaaag gcaaccataa ttctctttgg tgcaagtctt gggagcgtga tctagattac 5700
actgcaccat tcccaagtta atcccctgaa aacttactct caactggagc aaatgaactt 5760
tggtcccaaa tatccatctt ttcagtagcg ttaattatgc tctgtttcca actgcatttc 5820
ctttccaatt gaattaaagt gtggcctcgt ttttagtcat ttaaaattgt tttctaagta 5880
attgctgcct ctattatggc acttcaattt tgcactgtct tttgagattc aagaaaaatt 5940
tctattcatt tttttgcatc caattgtgcc tgaactttta aaatatgtaa atgctgccat 6000
gttccaaacc catcgtcagt gtgtgtgttt agagctgtgc accctagaaa caacatactt 6060
gtcccatgag caggtgcctg agacacagac ccctttgcat tcacagagag gtcattggtt 6120
atagagactt gaattaataa gtgacattat gccagtttct gttctctcac aggtgataaa 6180
caatgctttt tgtgcactac atactcttca gtgtagagct cttgttttat gggaaaaggc 6240
tcaaatgcca aattgtgttt gatggattaa tatgcccttt tgccgatgca tactattact 6300
gatgtgactc ggttttgtcg cagctttgct ttgtttaatg aaacacactt gtaaacctct 6360
tttgcacttt gaaaaagaat ccagcgggat gctcgagcac ctgtaaacaa ttttctcaac 6420
ctatttgatg ttcaaataaa gaattaaact 6450
<210> 23
<211> 3376
<212> DNA
<213> Homo sapiens
<400> 23
ggcgaccgaa cgcggcggtc ggcagcgttc gcgcgggggc ctgcgaagcg ctgctcgggg 60
ccggcactgc ccgcggggag gacgcgccgc cgccgccacc cagcgccgcc gccgccgccg 120
cctccagccg ggccgccgcg cgtcccgggg gccggccccg cgagcgcagg agtaaacacc 180
gccggagtct tggagccgct gcagaaggga ataaagagag atgcagggat ttgtgaggtt 240
acggcgcccc agctgcaaga tgcactagcc ggctgaaccc gggatcggct gacttgttgg 300
aaccggagtg ctctgcacgg agagtggtgg atgagttgaa gttgccttcc cggggctcat 360
tttccacgct gccgagagga atccgagagg caaggcaatc acttcgtctt gccattgatt 420
gggtatcggg agcttttttt ttctcccctc tctctttctt ttcctccgtc ttgttgcatg 480
caagaaaatt acagtccgct gctcgcccgc cctgggtgcg agatattcag ccccgctctc 540
tcccgtgcat tgtgcaaccc aaagatgaaa gaccgaaggg gagaaagtta aagaaatcgc 600
ccacatgcgc tggatcagtc cacggcttgg ggaaaggcat ccagagaagg tgggagcgga 660
gagtttgaag tctttacagg cgggaagatg gcggactgga gctgaaagtg ttgattggga 720
aacttgggtg attcttgtgt ttatttacaa tcctcttgac ccaggcagga cacatgcagg 780
ccaaaaaacg ctatttcatc ctgctctcag ctggctcttg tctcgccctt ttgttttatt 840
tcggaggctt gcagtttagg gcatcgagga gccacagccg gagagaagaa cacagcggta 900
ggaatggctt gcaccacccc agtccggatc atttctggcc ccgcttcccg gacgctctgc 960
gccccttcgt tccttgggat caattggaaa acgaggattc cagcgtgcac atttcccccc 1020
ggcagaagcg agatgccaac tccagcatct acaaaggcaa gaagtgccgc atggagtcct 1080
gcttcgattt caccctttgc aagaaaaacg gcttcaaagt ctacgtatac ccacagcaaa 1140
aaggggagaa aatcgccgaa agttaccaaa acattctagc ggccatcgag ggctccaggt 1200
tctacacctc ggaccccagc caggcgtgcc tctttgtcct gagtctggat actttagaca 1260
gagaccagtt gtcacctcag tatgtgcaca atttgagatc caaagtgcag agtctccact 1320
tgtggaacaa tggtaggaat catttaattt ttaatttata ttccggcact tggcctgact 1380
acaccgagga cgtggggttt gacatcggcc aggcgatgct ggccaaagcc agcatcagta 1440
ctgaaaactt ccgacccaac tttgatgttt ctattcccct cttttctaag gatcatccca 1500
ggacaggagg ggagaggggg tttttgaagt tcaacaccat ccctcctctc aggaagtaca 1560
tgctggtatt caaggggaag aggtacctga cagggatagg atcagacacc aggaatgcct 1620
tatatcacgt ccataacggg gaggacgttg tgctcctcac cacctgcaag catggcaaag 1680
actggcaaaa gcacaaggat tctcgctgtg acagagacaa caccgagtat gagaagtatg 1740
attatcggga aatgctgcac aatgccactt tctgtctggt tcctcgtggt cgcaggcttg 1800
ggtccttcag attcctggag gctttgcagg ctgcctgcgt ccctgtgatg ctcagcaatg 1860
gatgggagtt gccattctct gaagtgatta attggaacca agctgccgtc ataggcgatg 1920
agagattgtt attacagatt ccttctacaa tcaggtctat tcatcaggat aaaatcctag 1980
cacttagaca gcagacacaa ttcttgtggg aggcttattt ttcttcagtt gagaagattg 2040
tattaactac actagagatt attcaggaca gaatattcaa gcacatatca cgtaacagtt 2100
taatatggaa caaacatcct ggaggattgt tcgtactacc acagtattca tcttatctgg 2160
gagattttcc ttactactat gctaatttag gtttaaagcc cccctccaaa ttcactgcag 2220
tcatccatgc ggtgaccccc ctggtctctc agtcccagcc agtgttgaag cttctcgtgg 2280
ctgcagccaa gtcccagtac tgtgcccaga tcatagttct atggaattgt gacaagcccc 2340
taccagccaa acaccgctgg cctgccactg ctgtgcctgt cgtcgtcatt gaaggagaga 2400
gcaaggttat gagcagccgt tttctgccct acgacaacat catcacagac gccgtgctca 2460
gccttgacga ggacacggtg ctttcaacaa cagaggtgga tttcgccttc acagtgtggc 2520
agagcttccc tgagaggatt gtggggtacc ccgcgcgcag ccacttctgg gataactcta 2580
aggagcggtg gggatacaca tcaaagtgga cgaacgacta ctccatggtg ttgacaggag 2640
ctgctattta ccacaaatat tatcactacc tatactccca ttacctgcca gccagcctga 2700
agaacatggt ggaccaattg gccaattgtg aggacattct catgaacttc ctggtgtctg 2760
ctgtgacaaa attgcctcca atcaaagtga cccagaagaa gcagtataag gagacaatga 2820
tgggacagac ttctcgggct tcccgttggg ctgaccctga ccactttgcc cagcgacaga 2880
gctgcatgaa tacgtttgcc agctggtttg gctacatgcc gctgatccac tctcagatga 2940
ggctcgaccc cgtcctcttt aaagaccagg tctctatttt gaggaagaaa taccgagaca 3000
ttgagcgact ttgaggaatc cggctgagtg ggggagggga agcaagaagg gatgggggtc 3060
aagctgctct ctcttcccag tgcagatcca ctcatcagca gagccagatt gtgccaacta 3120
tccaaaaact tagatgagca gaatgacaaa aaaaaaaagg ccaatgagaa ctcaactcct 3180
ggctcctggg actgcaccag actgctccaa actcacctca ctggcttctg tgtcccaaga 3240
ctaggttgtg tacagtttaa ttatggaaca ttaaataatt atttttgaaa tgattgctat 3300
gcaggtttaa acttttttaa tgatcaaaac tattaaaaac cagagttctt tgtttaatca 3360
aaaaaaaaaa aaaaaa 3376
<210> 24
<211> 972
<212> DNA
<213> Homo sapiens
<400> 24
tctagactca ggactgagaa gaagtaaaac cgtttgctgg ggctggcctg actcaccagc 60
tgccatgcag cagcccttca attacccata tccccagatc tactgggtgg acagcagtgc 120
cagctctccc tgggcccctc caggcacagt tcttccctgt ccaacctctg tgcccagaag 180
gcctggtcaa aggaggccac caccaccacc gccaccgcca ccactaccac ctccgccgcc 240
gccgccacca ctgcctccac taccgctgcc acccctgaag aagagaggga accacagcac 300
aggcctgtgt ctccttgtga tgtttttcat ggttctggtt gccttggtag gattgggcct 360
ggggatgttt cagctcttcc acctacagaa ggagctggca gaactccgag agtctaccag 420
ccagatgcac acagcatcat ctttggagaa gcaaataggc caccccagtc caccccctga 480
aaaaaaggag ctgaggaaag tggcccattt aacaggcaag tccaactcaa ggtccatgcc 540
tctggaatgg gaagacacct atggaattgt cctgctttct ggagtgaagt ataagaaggg 600
tggccttgtg atcaatgaaa ctgggctgta ctttgtatat tccaaagtat acttccgggg 660
tcaatcttgc aacaacctgc ccctgagcca caaggtctac atgaggaact ctaagtatcc 720
ccaggatctg gtgatgatgg aggggaagat gatgagctac tgcactactg ggcagatgtg 780
ggcccgcagc agctacctgg gggcagtgtt caatcttacc agtgctgatc atttatatgt 840
caacgtatct gagctctctc tggtcaattt tgaggaatct cagacgtttt tcggcttata 900
taagctctaa gagaagcact ttgggattct ttccattatg attctttgtt acaggcaccg 960
agatgttcta ga 972
<210> 25
<211> 1391
<212> DNA
<213> Homo sapiens
<400> 25
tgcaccccga gcatccgccc cgggtggcac gtccccgagc ccaccaggcc ggccccgtct 60
ccccatccgt ctagtccgct cgcggtgcca tgccattcct cgggcaggac tggcggtccc 120
ccgggcagaa ctgggtgaag acggccgacg gctggaagcg cttcctggat gagaagagcg 180
gcagtttcgt gagcgacctc agcagttact gcaacaagga ggtatacaat aaggagaatc 240
ttttcaacag cctgaactat gatgttgcag ccaagaagag aaagaaggac atgctgaata 300
gcaaaaccaa aactcagtat ttccaccaag aaaaatggat ctatgttcac aaaggaagta 360
ctaaagagcg ccatggatat tgcaccctgg gggaagcttt caacagactg gacttctcaa 420
ctgccattct ggattccaga agatttaact acgtggtccg gctgttggag ctgatagcaa 480
agtcacagct cacatccctg agtggcatcg cccaaaagaa cttcatgaat attttggaaa 540
aagtggtact gaaagtcctt gaagaccagc aaaacattag actaataagg gaactactcc 600
agaccctcta cacatcctta tgtacactgg tccaaagagt cggcaagtct gtgctggtcg 660
ggaacattaa catgtgggtg tatcggatgg agacgattct ccactggcag cagcagctga 720
acaacattca gatcaccagg cctgccttca aaggcctcac cttcactgac ctgcctttgt 780
gcctacaact gaacatcatg cagaggctga gcgacgggcg ggacctggtc agcctgggcc 840
aggctgcccc cgacctgcac gtgctcagcg aagaccggct gctgtggaag aaactctgcc 900
agtaccactt ctccgagcgg cagatccgca aacgattaat tctgtcagac aaagggcagc 960
tggattggaa gaagatgtat ttcaaacttg tccgatgtta cccaaggaaa gagcagtatg 1020
gagataccct tcagctctgc aaacactgtc acatcctttc ctggaagggc actgaccatc 1080
cgtgcactgc caataaccca gagagctgct ccgtttcact ttcaccccag gactttatca 1140
acttgttcaa gttctgaatc ccagcacatg acaacacttc agaagggtcc ccctgctgac 1200
tggagagctg ggaatatggc atttggacac ttcatttgta aatagtgtac attttaaaca 1260
ttggctcgaa acttcagaga taagtcatgg agaggacatt ggaggggaga aatgcagttg 1320
ctgactggga atttaagaat gtgaacttct cactagaatt ggtatggaaa agcaaaatac 1380
tgtaaataaa c 1391
<210> 26
<211> 4654
<212> DNA
<213> Homo sapiens
<400> 26
ggcggcggct ggaggagagc gcggtggaga gccgagcggg cgggcggcgg gtgcggagcg 60
ggcgagggag cgcgcgcggc cgccacaaag ctcgggcgcc gcggggctgc atgcggcgta 120
cctggcccgg cgcggcgact gctctccggg ctggcggggg ccggccgcga gccccggggg 180
ccccgaggcc gcagcttgcc tgcgcgctct gagccttcgc aactcgcgag caaagtttgg 240
tggaggcaac gccaagcctg agtcctttct tcctctcgtt ccccaaatcc gagggcagcc 300
cgcgggcgtc atgcccgcgc tcctccgcag cctggggtac gcgtgaagcc cgggaggctt 360
ggcgccggcg aagacccaag gaccactctt ctgcgtttgg agttgctccc cgcaaccccg 420
ggctcgtcgc tttctccatc ccgacccacg cggggcgcgg ggacaacaca ggtcgcggag 480
gagcgttgcc attcaagtga ctgcagcagc agcggcagcg cctcggttcc tgagcccacc 540
gcaggctgaa ggcattgcgc gtagtccatg cccgtagagg aagtgtgcag atgggattaa 600
cgtccacatg gagatatgga agaggaccgg ggattggtac cgtaaccatg gtcagctggg 660
gtcgtttcat ctgcctggtc gtggtcacca tggcaacctt gtccctggcc cggccctcct 720
tcagtttagt tgaggatacc acattagagc cagaagagcc accaaccaaa taccaaatct 780
ctcaaccaga agtgtacgtg gctgcgccag gggagtcgct agaggtgcgc tgcctgttga 840
aagatgccgc cgtgatcagt tggactaagg atggggtgca cttggggccc aacaatagga 900
cagtgcttat tggggagtac ttgcagataa agggcgccac gcctagagac tccggcctct 960
atgcttgtac tgccagtagg actgtagaca gtgaaacttg gtacttcatg gtgaatgtca 1020
cagatgccat ctcatccgga gatgatgagg atgacaccga tggtgcggaa gattttgtca 1080
gtgagaacag taacaacaag agagcaccat actggaccaa cacagaaaag atggaaaagc 1140
ggctccatgc tgtgcctgcg gccaacactg tcaagtttcg ctgcccagcc ggggggaacc 1200
caatgccaac catgcggtgg ctgaaaaacg ggaaggagtt taagcaggag catcgcattg 1260
gaggctacaa ggtacgaaac cagcactgga gcctcattat ggaaagtgtg gtcccatctg 1320
acaagggaaa ttatacctgt gtagtggaga atgaatacgg gtccatcaat cacacgtacc 1380
acctggatgt tgtggagcga tcgcctcacc ggcccatcct ccaagccgga ctgccggcaa 1440
atgcctccac agtggtcgga ggagacgtag agtttgtctg caaggtttac agtgatgccc 1500
agccccacat ccagtggatc aagcacgtgg aaaagaacgg cagtaaatac gggcccgacg 1560
ggctgcccta cctcaaggtt ctcaaggccg ccggtgttaa caccacggac aaagagattg 1620
aggttctcta tattcggaat gtaacttttg aggacgctgg ggaatatacg tgcttggcgg 1680
gtaattctat tgggatatcc tttcactctg catggttgac agttctgcca gcgcctggaa 1740
gagaaaagga gattacagct tccccagact acctggagat agccatttac tgcatagggg 1800
tcttcttaat cgcctgtatg gtggtaacag tcatcctgtg ccgaatgaag aacacgacca 1860
agaagccaga cttcagcagc cagccggctg tgcacaagct gaccaaacgt atccccctgc 1920
ggagacaggt aacagtttcg gctgagtcca gctcctccat gaactccaac accccgctgg 1980
tgaggataac aacacgcctc tcttcaacgg cagacacccc catgctggca ggggtctccg 2040
agtatgaact tccagaggac ccaaaatggg agtttccaag agataagctg acactgggca 2100
agcccctggg agaaggttgc tttgggcaag tggtcatggc ggaagcagtg ggaattgaca 2160
aagacaagcc caaggaggcg gtcaccgtgg ccgtgaagat gttgaaagat gatgccacag 2220
agaaagacct ttctgatctg gtgtcagaga tggagatgat gaagatgatt gggaaacaca 2280
agaatatcat aaatcttctt ggagcctgca cacaggatgg gcctctctat gtcatagttg 2340
agtatgcctc taaaggcaac ctccgagaat acctccgagc ccggaggcca cccgggatgg 2400
agtactccta tgacattaac cgtgttcctg aggagcagat gaccttcaag gacttggtgt 2460
catgcaccta ccagctggcc agaggcatgg agtacttggc ttcccaaaaa tgtattcatc 2520
gagatttagc agccagaaat gttttggtaa cagaaaacaa tgtgatgaaa atagcagact 2580
ttggactcgc cagagatatc aacaatatag actattacaa aaagaccacc aatgggcggc 2640
ttccagtcaa gtggatggct ccagaagccc tgtttgatag agtatacact catcagagtg 2700
atgtctggtc cttcggggtg ttaatgtggg agatcttcac tttagggggc tcgccctacc 2760
cagggattcc cgtggaggaa ctttttaagc tgctgaagga aggacacaga atggataagc 2820
cagccaactg caccaacgaa ctgtacatga tgatgaggga ctgttggcat gcagtgccct 2880
cccagagacc aacgttcaag cagttggtag aagacttgga tcgaattctc actctcacaa 2940
ccaatgagga atacttggac ctcagccaac ctctcgaaca gtattcacct agttaccctg 3000
acacaagaag ttcttgttct tcaggagatg attctgtttt ttctccagac cccatgcctt 3060
acgaaccatg ccttcctcag tatccacaca taaacggcag tgttaaaaca tgaatgactg 3120
tgtctgcctg tccccaaaca ggacagcact gggaacctag ctacactgag cagggagacc 3180
atgcctccca gagcttgttg tctccacttg tatatatgga tcagaggagt aaataattgg 3240
aaaagtaatc agcatatgtg taaagattta tacagttgaa aacttgtaat cttccccagg 3300
aggagaagaa ggtttctgga gcagtggact gccacaagcc accatgtaac ccctctcacc 3360
tgccgtgcgt actggctgtg gaccagtagg actcaaggtg gacgtgcgtt ctgccttcct 3420
tgttaatttt gtaataattg gagaagattt atgtcagcac acacttacag agcacaaatg 3480
cagtatatag gtgctggatg tatgtaaata tattcaaatt atgtataaat atatattata 3540
tatttacaag gagttatttt ttgtattgat tttaaatgga tgtcccaatg cacctagaaa 3600
attggtctct ctttttttaa tagctatttg ctaaatgctg ttcttacaca taatttctta 3660
attttcaccg agcagaggtg gaaaaatact tttgctttca gggaaaatgg tataacgtta 3720
atttattaat aaattggtaa tatacaaaac aattaatcat ttatagtttt ttttgtaatt 3780
taagtggcat ttctatgcag gcagcacagc agactagtta atctattgct tggacttaac 3840
tagttatcag atcctttgaa aagagaatat ttacaatata tgactaattt ggggaaaatg 3900
aagttttgat ttatttgtgt ttaaatgctg ctgtcagacg attgttctta gacctcctaa 3960
atgccccata ttaaaagaac tcattcatag gaaggtgttt cattttggtg tgcaaccctg 4020
tcattacgtc aacgcaacgt ctaactggac ttcccaagat aaatggtacc agcgtcctct 4080
taaaagatgc cttaatccat tccttgagga cagaccttag ttgaaatgat agcagaatgt 4140
gcttctctct ggcagctggc cttctgcttc tgagttgcac attaatcaga ttagcctgta 4200
ttctcttcag tgaattttga taatggcttc cagactcttt ggcgttggag acgcctgtta 4260
ggatcttcaa gtcccatcat agaaaattga aacacagagt tgttctgctg atagttttgg 4320
ggatacgtcc atctttttaa gggattgctt tcatctaatt ctggcaggac ctcaccaaaa 4380
gatccagcct catacctaca tcagacaaaa tatcgccgtt gttccttctg tactaaagta 4440
ttgtgttttg ctttggaaac acccactcac tttgcaatag ccgtgcaaga tgaatgcaga 4500
ttacactgat cttatgtgtt acaaaattgg agaaagtatt taataaaacc tgttaatttt 4560
tatactgaca ataaaaatgt ttctacagat attaatgtta acaagacaaa ataaatgtca 4620
cgcaacttat ttttttaata aaaaaaaaaa aaaa 4654
<210> 27
<211> 1398
<212> DNA
<213> Homo sapiens
<400> 27
ggagagcggg gccctttgtc ctccagtggc tggtaggcag tggctgggag gcagcggccc 60
aattagtgtc gtgcggcccg tggcgaggcg aggtccgggg agcgagcgag caagcaaggc 120
gggaggggtg gccggagctg cggcggctgg cacaggagga ggagcccggg cgggcgaggg 180
gcggccggag agcgccaggg cctgagctgc cggagcggcg cctgtgagtg agtgcagaaa 240
gcaggcgccc gcgcgctagc cgtggcagga gcagcccgca cgccgcgctc tctccctggg 300
cgacctgcag tttgcaatat gactttggag gaattctcgg ctggagagca gaagaccgaa 360
aggatggata aggtggggga tgccctggag gaagtgctca gcaaagccct gagtcagcgc 420
acgatcactg tcggggtgta cgaagcggcc aagctgctca acgtcgaccc cgataacgtg 480
gtgttgtgcc tgctggcggc ggacgaggac gacgacagag atgtggctct gcagatccac 540
ttcaccctga tccaggcgtt ttgctgcgag aacgacatca acatcctgcg cgtcagcaac 600
ccgggccggc tggcggagct cctgctcttg gagaccgacg ctggccccgc ggcgagcgag 660
ggcgccgagc agcccccgga cctgcactgc gtgctggtga cgaatccaca ttcatctcaa 720
tggaaggatc ctgccttaag tcaacttatt tgtttttgcc gggaaagtcg ctacatggat 780
caatgggttc cagtgattaa tctccctgaa cggtgatggc atctgaatga aaataactga 840
accaaattgc actgaagttt ttgaaatacc tttgtagtta ctcaagcagt tactccctac 900
actgatgcaa ggattacaga aactgatgcc aaggggctga gtgagttcaa ctacatgttc 960
tgggggcccg gagatagatg actttgcaga tggaaagagg tgaaaatgaa gaaggaagct 1020
gtgttgaaac agaaaaataa gtcaaaagga acaaaaatta caaagaacca tgcaggaagg 1080
aaaactatgt attaatttag aatggttgag ttacattaaa ataaaccaaa tatgttaaag 1140
tttaagtgtg cagccatagt ttgggtattt ttggtttata tgccctcaag taaaagaaaa 1200
gccgaaaggg ttaatcatat ttgaaaacca tattttattg tattttgatg agatattaaa 1260
ttctcaaagt tttattataa attctactaa gttattttat gacatgaaaa gttatttatg 1320
ctataaattt tttgaaacac aatacctaca ataaactggt atgaataatt gcatcatttc 1380
aaaaaaaaaa aaaaaaaa 1398
<210> 28
<211> 11242
<212> DNA
<213> Homo sapiens
<400> 28
tttttttttt ttttttttga gaaaggggaa tttcatccca aataaaagga atgaagtctg 60
gctccggagg agggtccccg acctcgctgt gggggctcct gtttctctcc gccgcgctct 120
cgctctggcc gacgagtgga gaaatctgcg ggccaggcat cgacatccgc aacgactatc 180
agcagctgaa gcgcctggag aactgcacgg tgatcgaggg ctacctccac atcctgctca 240
tctccaaggc cgaggactac cgcagctacc gcttccccaa gctcacggtc attaccgagt 300
acttgctgct gttccgagtg gctggcctcg agagcctcgg agacctcttc cccaacctca 360
cggtcatccg cggctggaaa ctcttctaca actacgccct ggtcatcttc gagatgacca 420
atctcaagga tattgggctt tacaacctga ggaacattac tcggggggcc atcaggattg 480
agaaaaatgc tgacctctgt tacctctcca ctgtggactg gtccctgatc ctggatgcgg 540
tgtccaataa ctacattgtg gggaataagc ccccaaagga atgtggggac ctgtgtccag 600
ggaccatgga ggagaagccg atgtgtgaga agaccaccat caacaatgag tacaactacc 660
gctgctggac cacaaaccgc tgccagaaaa tgtgcccaag cacgtgtggg aagcgggcgt 720
gcaccgagaa caatgagtgc tgccaccccg agtgcctggg cagctgcagc gcgcctgaca 780
acgacacggc ctgtgtagct tgccgccact actactatgc cggtgtctgt gtgcctgcct 840
gcccgcccaa cacctacagg tttgagggct ggcgctgtgt ggaccgtgac ttctgcgcca 900
acatcctcag cgccgagagc agcgactccg aggggtttgt gatccacgac ggcgagtgca 960
tgcaggagtg cccctcgggc ttcatccgca acggcagcca gagcatgtac tgcatccctt 1020
gtgaaggtcc ttgcccgaag gtctgtgagg aagaaaagaa aacaaagacc attgattctg 1080
ttacttctgc tcagatgctc caaggatgca ccatcttcaa gggcaatttg ctcattaaca 1140
tccgacgggg gaataacatt gcttcagagc tggagaactt catggggctc atcgaggtgg 1200
tgacgggcta cgtgaagatc cgccattctc atgccttggt ctccttgtcc ttcctaaaaa 1260
accttcgcct catcctagga gaggagcagc tagaagggaa ttactccttc tacgtcctcg 1320
acaaccagaa cttgcagcaa ctgtgggact gggaccaccg caacctgacc atcaaagcag 1380
ggaaaatgta ctttgctttc aatcccaaat tatgtgtttc cgaaatttac cgcatggagg 1440
aagtgacggg gactaaaggg cgccaaagca aaggggacat aaacaccagg aacaacgggg 1500
agagagcctc ctgtgaaagt gacgtcctgc atttcacctc caccaccacg tcgaagaatc 1560
gcatcatcat aacctggcac cggtaccggc cccctgacta cagggatctc atcagcttca 1620
ccgtttacta caaggaagca ccctttaaga atgtcacaga gtatgatggg caggatgcct 1680
gcggctccaa cagctggaac atggtggacg tggacctccc gcccaacaag gacgtggagc 1740
ccggcatctt actacatggg ctgaagccct ggactcagta cgccgtttac gtcaaggctg 1800
tgaccctcac catggtggag aacgaccata tccgtggggc caagagtgag atcttgtaca 1860
ttcgcaccaa tgcttcagtt ccttccattc ccttggacgt tctttcagca tcgaactcct 1920
cttctcagtt aatcgtgaag tggaaccctc cctctctgcc caacggcaac ctgagttact 1980
acattgtgcg ctggcagcgg cagcctcagg acggctacct ttaccggcac aattactgct 2040
ccaaagacaa aatccccatc aggaagtatg ccgacggcac catcgacatt gaggaggtca 2100
cagagaaccc caagactgag gtgtgtggtg gggagaaagg gccttgctgc gcctgcccca 2160
aaactgaagc cgagaagcag gccgagaagg aggaggctga ataccgcaaa gtctttgaga 2220
atttcctgca caactccatc ttcgtgccca gacctgaaag gaagcggaga gatgtcatgc 2280
aagtggccaa caccaccatg tccagccgaa gcaggaacac cacggccgca gacacctaca 2340
acatcaccga cccggaagag ctggagacag agtacccttt ctttgagagc agagtggata 2400
acaaggagag aactgtcatt tctaaccttc ggcctttcac attgtaccgc atcgatatcc 2460
acagctgcaa ccacgaggct gagaagctgg gctgcagcgc ctccaacttc gtctttgcaa 2520
ggactatgcc cgcagaagga gcagatgaca ttcctgggcc agtgacctgg gagccaaggc 2580
ctgaaaactc catcttttta aagtggccgg aacctgagaa tcccaatgga ttgattctaa 2640
tgtatgaaat aaaatacgga tcacaagttg aggatcagcg agaatgtgtg tccagacagg 2700
aatacaggaa gtatggaggg gccaagctaa accggctaaa cccggggaac tacacagccc 2760
ggattcaggc cacatctctc tctgggaatg ggtcgtggac agatcctgtg ttcttctatg 2820
tccaggccaa aacaggatat gaaaacttca tccatctgat catcgctctg cccgtcgctg 2880
tcctgttgat cgtgggaggg ttggtgatta tgctgtacgt cttccataga aagagaaata 2940
acagcaggct ggggaatgga gtgctgtatg cctctgtgaa cccggagtac ttcagcgctg 3000
ctgatgtgta cgttcctgat gagtgggagg tggctcggga gaagatcacc atgagccggg 3060
aacttgggca ggggtcgttt gggatggtct atgaaggagt tgccaagggt gtggtgaaag 3120
atgaacctga aaccagagtg gccattaaaa cagtgaacga ggccgcaagc atgcgtgaga 3180
ggattgagtt tctcaacgaa gcttctgtga tgaaggagtt caattgtcac catgtggtgc 3240
gattgctggg tgtggtgtcc caaggccagc caacactggt catcatggaa ctgatgacac 3300
ggggcgatct caaaagttat ctccggtctc tgaggccaga aatggagaat aatccagtcc 3360
tagcacctcc aagcctgagc aagatgattc agatggccgg agagattgca gacggcatgg 3420
catacctcaa cgccaataag ttcgtccaca gagaccttgc tgcccggaat tgcatggtag 3480
ccgaagattt cacagtcaaa atcggagatt ttggtatgac gcgagatatc tatgagacag 3540
actattaccg gaaaggaggg aaagggctgc tgcccgtgcg ctggatgtct cctgagtccc 3600
tcaaggatgg agtcttcacc acttactcgg acgtctggtc cttcggggtc gtcctctggg 3660
agatcgccac actggccgag cagccctacc agggcttgtc caacgagcaa gtccttcgct 3720
tcgtcatgga gggcggcctt ctggacaagc cagacaactg tcctgacatg ctgtttgaac 3780
tgatgcgcat gtgctggcag tataacccca agatgaggcc ttccttcctg gagatcatca 3840
gcagcatcaa agaggagatg gagcctggct tccgggaggt ctccttctac tacagcgagg 3900
agaacaagct gcccgagccg gaggagctgg acctggagcc agagaacatg gagagcgtcc 3960
ccctggaccc ctcggcctcc tcgtcctccc tgccactgcc cgacagacac tcaggacaca 4020
aggccgagaa cggccccggc cctggggtgc tggtcctccg cgccagcttc gacgagagac 4080
agccttacgc ccacatgaac gggggccgca agaacgagcg ggccttgccg ctgccccagt 4140
cttcgacctg ctgatccttg gatcctgaat ctgtgcaaac agtaacgtgt gcgcacgcgc 4200
agcggggtgg ggggggagag agagttttaa caatccattc acaagcctcc tgtacctcag 4260
tggatcttca gaactgccct tgctgcccgc gggagacagc ttctctgcag taaaacacat 4320
ttgggatgtt ccttttttca atatgcaagc agctttttat tccctgccca aacccttaac 4380
tgacatgggc ctttaagaac cttaatgaca acacttaata gcaacagagc acttgagaac 4440
cagtctcctc actctgtccc tgtccttccc tgttctccct ttctctctcc tctctgcttc 4500
ataacggaaa aataattgcc acaagtccag ctgggaagcc ctttttatca gtttgaggaa 4560
gtggctgtcc ctgtggcccc atccaaccac tgtacacacc cgcctgacac cgtgggtcat 4620
tacaaaaaaa cacgtggaga tggaaatttt tacctttatc tttcaccttt ctagggacat 4680
gaaatttaca aagggccatc gttcatccaa ggctgttacc attttaacgc tgcctaattt 4740
tgccaaaatc ctgaactttc tccctcatcg gcccggcgct gattcctcgt gtccggaggc 4800
atgggtgagc atggcagctg gttgctccat ttgagagaca cgctggcgac acactccgtc 4860
catccgactg cccctgctgt gctgctcaag gccacaggca cacaggtctc attgcttctg 4920
actagattat tatttggggg aactggacac aataggtctt tctctcagtg aaggtgggga 4980
gaagctgaac cggcttccct gccctgcctc cccagccccc tgcccaaccc ccaagaatct 5040
ggtggccatg ggccccgaag cagcctggcg gacaggcttg gagtcaaggg gccccatgcc 5100
tgcttctctc ccagccccag ctcccccgcc cgcccccaag gacacagatg ggaaggggtt 5160
tccagggact cagccccact gttgatgcag gtttgcaagg aaagaaattc aaacaccaca 5220
acagcagtaa gaagaaaagc agtcaatgga ttcaagcatt ctaagctttg ttgacatttt 5280
ctctgttcct aggacttctt catgggtctt acagttctat gttagaccat gaaacatttg 5340
catacacatc gtctttaatg tcacttttat aactttttta cggttcagat attcatctat 5400
acgtctgtac agaaaaaaaa aagctgctat tttttttgtt cttgatcttt gtggatttaa 5460
tctatgaaaa ccttcaggtc caccctctcc cctttctgct cactccaaga aacttcttat 5520
gctttgtact agagtgcgtg actttcttcc tcttttcccg gtaatggata cttctatcac 5580
ataatttgcc atgaactgtt ggatgccttt ttataaatac atcccccatc cctgctccca 5640
cctgcccctt tagttgtttt ctaacccgta ggctctctgg gcacgaggca gaaagcaggc 5700
cgggcaccca tcctgagagg gccgcgctcc tctccccagc ctgccctcac agcattggag 5760
cctgttacag tgcaagacat gatacaaact caggtcagaa aaacaaaggt taaatatttc 5820
acacgtcttt gttcagtgtt tccactcacc gtggttgaga agcctcaccc tctctttccc 5880
ttgcctttgc ttaggttgtg acacacatat atatatattt ttttaattct tgggtacaac 5940
agcagtgtta accgcagaca ctaggcattt ggattactat ttttcttaat ggctatttaa 6000
tccttccatc ccacgaaaaa cagctgctga gtccaaggga gcagcagagc gtggtccggc 6060
agggcctgtt gtggccctcg ccacccccct caccggaccg actgacctgt ctttggaacc 6120
agaacatccc aagggaactc cttcgcactg gcgttgagtg ggaccccggg atccaggctg 6180
gcccagggcg gcaccctcag ggctgtgccc gctggagtgc taggtggagg cagcacagac 6240
gccacggtgg cccaagagcc cctttgcttc ttgctggggg accagggctg tggtgctggc 6300
ccactttccc tcggccagga atccaggtcc ttggggccca ggggtcttgt cttgtttcat 6360
ttttagcact tctcaccaga gagatgacag cacaagagtt gcttctggga tagaaatgtt 6420
taggagtaag aacaaagctg ggatacggtg attgctagtt gtgactgaag attcaacaca 6480
gaaaagaaag tttatacggc ttttttgctg gtcagcagtt tgtcccactg ctttctctag 6540
tctctatccc atagcgtgtt ccctttaaaa aaaaaaaaaa ggtattatat gtaggagttt 6600
tcttttaatt tattttgtga taaattacca gtttcaatca ctgtagaaaa gccccattat 6660
gaatttaaat ttcaaggaaa gggtgtgtgt gtgtgtatgt gtggggtgtg tgtgtgtgag 6720
agtgatggga cagttcttga ttttttgggt tttttttccc ccaaacattt atctacctca 6780
ctcttatttt ttatatgtgt atatagacaa aagaatacat ctcacctttc tcagcacctg 6840
acaataggcc gttgatactg gtaacctcat ccacgccaca ggcgccacac ccaggtgatg 6900
cagggggaag ccaggctgta ttccggggtc aaagcaacac taactcacct ctctgctcat 6960
ttcagacagc ttgccttttt ctgagatgtc ctgttttgtg ttgctttttt tgttttgttt 7020
tctatcttgg tttccaccaa ggtgttagat ttctcctcct cctagccagg tggccctgtg 7080
aggccaacga gggcaccaga gcacacctgg gggagccacc aggctgtccc tggctggttg 7140
tctttggaac aaactgcttc tgtgcagatg gaatgaccaa cacatttcgt ccttaagaga 7200
gcagtggttc ctcaggttct gaggagagga aggtgtccag gcagcaccat ctctgtgcga 7260
atccccaggg taaaggcgtg gggcattggg tttgctcccc ttgctgctgc tccatccctg 7320
caggaggctc gcgctgaggc aggaccgtgc ggccatggct gctgcattca ttgagcacaa 7380
aggtgcagct gcagcagcag ctggagagca agagtcaccc agcctgtgcg ccagaatgca 7440
gaggctcctg acctcacagc cagtccctga tagaacacac gcaggagcag agtcccctcc 7500
ccctccaggc tgccctctca acttctccct cacctccttc cctaggggta gacagagatg 7560
taccaaacct tccggctgga aagcccagtg gccggcgccg aggctcgtgg cgtcacgccc 7620
cccccgccag ggctgtacct ccgtctccct ggtcctgctg ctcacaggac agacggctcg 7680
ctcccctctt ccagcagctg ctcttacagg cactgatgat ttcgctggga agtgtggcgg 7740
gcagctttgc ctaagcgtgg atggctcctc ggcaattcca gcctaagtga aggcgctcag 7800
gagcctcctg ctggaacgcg acccatctct cccaggaccc cggggatctt aaggtcattg 7860
agaaatactg ttggatcagg gttttgttct tccacactgt aggtgacccc ttggaataac 7920
ggcctctcct ctcgtgcaca tacctaccgg tttccacaac tggatttcta cagatcattc 7980
agctggttat aagggttttg tttaaactgt ccgagttact gatgtcattt tgtttttgtt 8040
ttatgtaggt agcttttaag tagaaaacac taacagtgta gtgcccatca tagcaaatgc 8100
ttcagaaaca cctcaataaa agagaaaact tggcttgtgt gatggtgcag tcactttact 8160
ggaccaaccc acccaccttg actataccaa ggcatcatct atccacagtt ctagcctaac 8220
ttcatgctga tttctctgcc tcttgatttt tctctgtgtg ttccaaataa tcttaagctg 8280
agttgtggca ttttccatgc aacctccttc tgccagcagc tcacactgct tgaagtcata 8340
tgaaccactg aggcacatca tggaattgat gtgagcatta agacgttctc ccacacagcc 8400
cttccctgag gcagcaggag ctggtgtgta ctggagacac tgttgaactt gatcaagacc 8460
cagaccaccc caggtctcct tcgtgggatg tcatgacgtt tgacatacct ttggaacgag 8520
cctcctcctt ggaagatgga agaccgtgtt cgtggccgac ctggcctctc ctggcctgtt 8580
tcttaagatg cggagtcaca tttcaatggt acgaaaagtg gcttcgtaaa atagaagagc 8640
agtcactgtg gaactaccaa atggcgagat gctcggtgca cattggggtg ctttgggata 8700
aaagatttat gagccaacta ttctctggca ccagattcta ggccagtttg ttccactgaa 8760
gcttttccca cagcagtcca cctctgcagg ctggcagccg aatggcttgc cagtggctct 8820
gtggcaagat cacactgaga tcgatgggtg agaaggctag gatgcttgtc tagtgttctt 8880
agctgtcacg ttggctcctt ccagggtggc cagacggtgt tggccactcc cttctaaaac 8940
acaggcgccc tcctggtgac agtgacccgc cgtggtatgc cttggcccat tccagcagtc 9000
ccagttatgc atttcaagtt tggggtttgt tcttttcgtt aatgttcctc tgtgttgtca 9060
gctgtcttca tttcctgggc taagcagcat tgggagatgt ggaccagaga tccactcctt 9120
aagaaccagt ggcgaaagac actttctttc ttcactctga agtagctggt ggtacaaatg 9180
agaacttcaa gagaggatgt tatttagact gaacctctgt tgccagagat gctgaagata 9240
cagaccttgg acaggtcaga gggtttcatt tttggccttc atcttagatg actggttgcg 9300
tcatttggag aagtgagtgc tccttgatgg tggaatgacc gggtggtggg tacagaacca 9360
ttgtcacagg gatcctggca cagagaagag ttacgagcag cagggtgcag ggcttggaag 9420
gaatgtgggc aaggttttga acttgattgt tcttgaagct atcagaccac atcgaggctc 9480
agcagtcatc cgtgggcatt tggtttcaac aaagaaacct aacatcctac tctggaaact 9540
gatctcggag ttaaggcgaa ttgttcaaga acacaaacta catcgcactc gtcagttgtc 9600
agttctgggg catgacttta gcgttttgtt tctgcgagaa cataacgatc actcattttt 9660
atgtcccacg tgtgtgtgtc cgcatctttc tggtcaacat tgttttaact agtcactcat 9720
tagcgttttc aatagggctc ttaagtccag tagattacgg gtagtcagtt gacgaagatc 9780
tggtttacaa gaactaatta aatgtttcat tgcatttttg taagaacaga ataattttat 9840
aaaatgtttg tagtttataa ttgccgaaaa taatttaaag acactttttt tttctctgtg 9900
tgtgcaaatg tgtgtttgtg atccattttt tttttttttt tttaggacac ctgtttacta 9960
gctagcttta caatatgcca aaaaaggatt tctccctgac cccatccgtg gttcaccctc 10020
ttttcccccc atgctttttg ccctagttta taacaaagga atgatgatga tttaaaaagt 10080
agttctgtat cttcagtatc ttggtcttcc agaaccctct ggttgggaag gggatcattt 10140
tttactggtc atttcccttt ggagtgtagc tactttaaca gatggaaaga acctcattgg 10200
ccatggaaac agccgaggtg ttggagccca gcagtgcatg gcaccgttcg gcatctggct 10260
tgattggtct ggctgccgtc attgtcagca cagtgccatg gacatgggaa gacttgactg 10320
cacagccaat ggttttcatg atgattacag catacacagt gatcacataa acgatgacag 10380
ctatggggca cacaggccat ttgcttacat gcctcgtatc atgactgatt actgctttgt 10440
tagaacacag aagagaccct attttattta aggcagaacc ccgaagatac gtatttccaa 10500
tacagaaaag aatttttaat aaaaactata acatacacaa aaattggttt taaagttgac 10560
tccacttcct ctaactccag tggattgttg gccatgtctc cccaactcca caatatctct 10620
atcatgggaa acacctgggg tttttgcgct acataggaga aagatctgga aactatttgg 10680
gttttgtttt caacttttca tttggatgtt tggcgttgca cacacacatc caccggtgga 10740
agagacgccc ggtgaaaaca cctgtctgct ttctaagcca gtgaggttga ggtgagaggt 10800
ttgccagagt ttgtctacct ctgggtatcc ctttgtctgg gataaaaaaa atcaaaccag 10860
aaggcgggat ggaatggatg caccgcaaat aatgcatttt ctgagttttc ttgttaaaaa 10920
aaaatttttt taagtaagaa aaaaaaaggt aataacatgg ccaatttgtt acataaaatg 10980
actttctgtg tataaattat tcctaaaaaa tcctgtttat ataaaaaatc agtagatgaa 11040
aaaaatttca aaatgttttt gtatattctg ttgtaagaat ttattcctgt tattgcgata 11100
tactctggat tctttacata atggaaaaaa gaaactgtct attttgaatg gctgaagcta 11160
aggcaacgtt agtttctctt actctgcttt tttctagtaa agtactacat ggtttaagtt 11220
aaataaaata attctgtatg ca 11242
<210> 29
<211> 1660
<212> DNA
<213> Homo sapiens
<400> 29
ggtgcactag caaaacaaac ttattttgaa cactcagctc ctagcgtgcg gcgctgccaa 60
tcattaacct cctggtgcaa gtggcgcggc ctgtgccctt tataaggtgc gcgctgtgtc 120
cagcgagcat cggccaccgc catcccatcc agcgagcatc tgccgccgcg ccgccgccac 180
cctcccagag agcactggcc accgctccac catcacttgc ccagagtttg ggccaccgcc 240
cgccgccacc agcccagaga gcatcggccc ctgtctgctg ctcgcgcctg gagatgtcag 300
aggtccccgt tgctcgcgtc tggctggtac tgctcctgct gactgtccag gtcggcgtga 360
cagccggcgc tccgtggcag tgcgcgccct gctccgccga gaagctcgcg ctctgcccgc 420
cggtgtccgc ctcgtgctcg gaggtcaccc ggtccgccgg ctgcggctgt tgcccgatgt 480
gcgccctgcc tctgggcgcc gcgtgcggcg tggcgactgc acgctgcgcc cggggactca 540
gttgccgcgc gctgccgggg gagcagcaac ctctgcacgc cctcacccgc ggccaaggcg 600
cctgcgtgca ggagtctgac gcctccgctc cccatgctgc agaggcaggg agccctgaaa 660
gcccagagag cacggagata actgaggagg agctcctgga taatttccat ctgatggccc 720
cttctgaaga ggatcattcc atcctttggg acgccatcag tacctatgat ggctcgaagg 780
ctctccatgt caccaacatc aaaaaatgga aggagccctg ccgaatagaa ctctacagag 840
tcgtagagag tttagccaag gcacaggaga catcaggaga agaaatttcc aaattttacc 900
tgccaaactg caacaagaat ggattttatc acagcagaca gtgtgagaca tccatggatg 960
gagaggcggg actctgctgg tgcgtctacc cttggaatgg gaagaggatc cctgggtctc 1020
cagagatcag gggagacccc aactgccaga tatattttaa tgtacaaaac tgaaaccaga 1080
tgaaataatg ttctgtcacg tgaaatattt aagtatatag tatatttata ctctagaaca 1140
tgcacattta tatatatatg tatatgtata tatatatagt aactactttt tatactccat 1200
acataacttg atatagaaag ctgtttattt attcactgta agtttatttt ttctacacag 1260
taaaaacttg tactatgtta ataacttgtc ctatgtcaat ttgtatatca tgaaacactt 1320
ctcatcatat tgtatgtaag taattgcatt tctgctcttc caaagctcct gcgtctgttt 1380
ttaaagagca tggaaaaata ctgcctagaa aatgcaaaat gaaataagag agagtagttt 1440
ttcagctagt ttgaaggagg acggttaact tgtatattcc accattcaca tttgatgtac 1500
atgtgtaggg aaagttaaaa gtgttgatta cataatcaaa gctacctgtg gtgatgttgc 1560
cacctgttaa aatgtacact ggatatgttg ttaaacacgt gtctataatg gaaacattta 1620
caataaatat tctgcatgga aatactgtta aaaaaaaaaa 1660
<210> 30
<211> 2638
<212> DNA
<213> Homo sapiens
<400> 30
agatgcgagc actgcggctg ggcgctgagg atcagccgct tcctgcctgg attccacagc 60
ttcgcgccgt gtactgtcgc cccatccctg cgcgcccagc ctgccaagca gcgtgccccg 120
gttgcaggcg tcatgcagcg ggcgcgaccc acgctctggg ccgctgcgct gactctgctg 180
gtgctgctcc gcgggccgcc ggtggcgcgg gctggcgcga gctcggcggg cttgggtccc 240
gtggtgcgct gcgagccgtg cgacgcgcgt gcactggccc agtgcgcgcc tccgcccgcc 300
gtgtgcgcgg agctggtgcg cgagccgggc tgcggctgct gcctgacgtg cgcactgagc 360
gagggccagc cgtgcggcat ctacaccgag cgctgtggct ccggccttcg ctgccagccg 420
tcgcccgacg aggcgcgacc gctgcaggcg ctgctggacg gccgcgggct ctgcgtcaac 480
gctagtgccg tcagccgcct gcgcgcctac ctgctgccag cgccgccagc tccaggtgag 540
ccgcccgcgc caggaaatgc tagtgagtcg gaggaagacc gcagcgccgg cagtgtggag 600
agcccgtccg tctccagcac gcaccgggtg tctgatccca agttccaccc cctccattca 660
aagataatca tcatcaagaa agggcatgct aaagacagcc agcgctacaa agttgactac 720
gagtctcaga gcacagatac ccagaacttc tcctccgagt ccaagcggga gacagaatat 780
ggtccctgcc gtagagaaat ggaagacaca ctgaatcacc tgaagttcct caatgtgctg 840
agtcccaggg gtgtacacat tcccaactgt gacaagaagg gattttataa gaaaaagcag 900
tgtcgccctt ccaaaggcag gaagcggggc ttctgctggt gtgtggataa gtatgggcag 960
cctctcccag gctacaccac caaggggaag gaggacgtgc actgctacag catgcagagc 1020
aagtagacgc ctgccgcaag gttaatgtgg agctcaaata tgccttattt tgcacaaaag 1080
actgccaagg acatgaccag cagctggcta cagcctcgat ttatatttct gtttgtggtg 1140
aactgatttt ttttaaacca aagtttagaa agaggttttt gaaatgccta tggtttcttt 1200
gaatggtaaa cttgagcatc ttttcacttt ccagtagtca gcaaagagca gtttgaattt 1260
tcttgtcgct tcctatcaaa atattcagag actcgagcac agcacccaga cttcatgcgc 1320
ccgtggaatg ctcaccacat gttggtcgaa gcggccgacc actgactttg tgacttaggc 1380
ggctgtgttg cctatgtaga gaacacgctt cacccccact ccccgtacag tgcgcacagg 1440
ctttatcgag aataggaaaa cctttaaacc ccggtcatcc ggacatccca acgcatgctc 1500
ctggagctca cagccttctg tggtgtcatt tctgaaacaa gggcgtggat ccctcaacca 1560
agaagaatgt ttatgtcttc aagtgacctg tactgcttgg ggactattgg agaaaataag 1620
gtggagtcct acttgtttaa aaaatatgta tctaagaatg ttctagggca ctctgggaac 1680
ctataaaggc aggtatttcg ggccctcctc ttcaggaatc ttcctgaaga catggcccag 1740
tcgaaggccc aggatggctt ttgctgcggc cccgtggggt aggagggaca gagagacagg 1800
gagagtcagc ctccacattc agaggcatca caagtaatgg cacaattctt cggatgactg 1860
cagaaaatag tgttttgtag ttcaacaact caagacgaag cttatttctg aggataagct 1920
ctttaaaggc aaagctttat tttcatctct catcttttgt cctccttagc acaatgtaaa 1980
aaagaatagt aatatcagaa caggaaggag gaatggcttg ctggggagcc catccaggac 2040
actgggagca catagagatt cacccatgtt tgttgaactt agagtcattc tcatgctttt 2100
ctttataatt cacacatata tgcagagaag atatgttctt gttaacattg tatacaacat 2160
agccccaaat atagtaagat ctatactaga taatcctaga tgaaatgtta gagatgctat 2220
atgatacaac tgtggccatg actgaggaaa ggagctcacg cccagagact gggctgctct 2280
cccggaggcc aaacccaaga aggtctggca aagtcaggct cagggagact ctgccctgct 2340
gcagacctcg gtgtggacac acgctgcata gagctctcct tgaaaacaga ggggtctcaa 2400
gacattctgc ctacctatta gcttttcttt atttttttaa ctttttgggg ggaaaagtat 2460
ttttgagaag tttgtcttgc aatgtattta taaatagtaa ataaagtttt taccattaaa 2520
aaaatatctt tccctttgtt attgaccatc tctgggcttt gtatcactaa ttattttatt 2580
ttattatata ataattattt tattataata aaatcctgaa aggggaaaat aaaaaaaa 2638
<210> 31
<211> 4723
<212> DNA
<213> Homo sapiens
<400> 31
ggggggctgc gcggccgggt cggtgcgcac acgagaagga cgcgcggccc ccagcgctct 60
tgggggccgc ctcggagcat gacccccgcg ggccagcgcc gcgcgcctga tccgaggaga 120
ccccgcgctc ccgcagccat gggcaccggg ggccggcggg gggcggcggc cgcgccgctg 180
ctggtggcgg tggccgcgct gctactgggc gccgcgggcc acctgtaccc cggagaggtg 240
tgtcccggca tggatatccg gaacaacctc actaggttgc atgagctgga gaattgctct 300
gtcatcgaag gacacttgca gatactcttg atgttcaaaa cgaggcccga agatttccga 360
gacctcagtt tccccaaact catcatgatc actgattact tgctgctctt ccgggtctat 420
gggctcgaga gcctgaagga cctgttcccc aacctcacgg tcatccgggg atcacgactg 480
ttctttaact acgcgctggt catcttcgag atggttcacc tcaaggaact cggcctctac 540
aacctgatga acatcacccg gggttctgtc cgcatcgaga agaacaatga gctctgttac 600
ttggccacta tcgactggtc ccgtatcctg gattccgtgg aggataatca catcgtgttg 660
aacaaagatg acaacgagga gtgtggagac atctgtccgg gtaccgcgaa gggcaagacc 720
aactgccccg ccaccgtcat caacgggcag tttgtcgaac gatgttggac tcatagtcac 780
tgccagaaag tttgcccgac catctgtaag tcacacggct gcaccgccga aggcctctgt 840
tgccacagcg agtgcctggg caactgttct cagcccgacg accccaccaa gtgcgtggcc 900
tgccgcaact tctacctgga cggcaggtgt gtggagacct gcccgccccc gtactaccac 960
ttccaggact ggcgctgtgt gaacttcagc ttctgccagg acctgcacca caaatgcaag 1020
aactcgcgga ggcagggctg ccaccaatac gtcattcaca acaacaagtg catccctgag 1080
tgtccctccg ggtacacgat gaattccagc aacttgctgt gcaccccatg cctgggtccc 1140
tgtcccaagg tgtgccacct cctagaaggc gagaagacca tcgactcggt gacgtctgcc 1200
caggagctcc gaggatgcac cgtcatcaac gggagtctga tcatcaacat tcgaggaggc 1260
aacaatctgg cagctgagct agaagccaac ctcggcctca ttgaagaaat ttcagggtat 1320
ctaaaaatcc gccgatccta cgctctggtg tcactttcct tcttccggaa gttacgtctg 1380
attcgaggag agaccttgga aattgggaac tactccttct atgccttgga caaccagaac 1440
ctaaggcagc tctgggactg gagcaaacac aacctcacca ccactcaggg gaaactcttc 1500
ttccactata accccaaact ctgcttgtca gaaatccaca agatggaaga agtttcagga 1560
accaaggggc gccaggagag aaacgacatt gccctgaaga ccaatgggga caaggcatcc 1620
tgtgaaaatg agttacttaa attttcttac attcggacat cttttgacaa gatcttgctg 1680
agatgggagc cgtactggcc ccccgacttc cgagacctct tggggttcat gctgttctac 1740
aaagaggccc cttatcagaa tgtgacggag ttcgatgggc aggatgcgtg tggttccaac 1800
agttggacgg tggtagacat tgacccaccc ctgaggtcca acgaccccaa atcacagaac 1860
cacccagggt ggctgatgcg gggtctcaag ccctggaccc agtatgccat ctttgtgaag 1920
accctggtca ccttttcgga tgaacgccgg acctatgggg ccaagagtga catcatttat 1980
gtccagacag atgccaccaa cccctctgtg cccctggatc caatctcagt gtctaactca 2040
tcatcccaga ttattctgaa gtggaaacca ccctccgacc ccaatggcaa catcacccac 2100
tacctggttt tctgggagag gcaggcggaa gacagtgagc tgttcgagct ggattattgc 2160
ctcaaagggc tgaagctgcc ctcgaggacc tggtctccac cattcgagtc tgaagattct 2220
cagaagcaca accagagtga gtatgaggat tcggccggcg aatgctgctc ctgtccaaag 2280
acagactctc agatcctgaa ggagctggag gagtcctcgt ttaggaagac gtttgaggat 2340
tacctgcaca acgtggtttt cgtccccaga aaaacctctt caggcactgg tgccgaggac 2400
cctaggccat ctcggaaacg caggtccctt ggcgatgttg ggaatgtgac ggtggccgtg 2460
cccacggtgg cagctttccc caacacttcc tcgaccagcg tgcccacgag tccggaggag 2520
cacaggcctt ttgagaaggt ggtgaacaag gagtcgctgg tcatctccgg cttgcgacac 2580
ttcacgggct atcgcatcga gctgcaggct tgcaaccagg acacccctga ggaacggtgc 2640
agtgtggcag cctacgtcag tgcgaggacc atgcctgaag ccaaggctga tgacattgtt 2700
ggccctgtga cgcatgaaat ctttgagaac aacgtcgtcc acttgatgtg gcaggagccg 2760
aaggagccca atggtctgat cgtgctgtat gaagtgagtt atcggcgata tggtgatgag 2820
gagctgcatc tctgcgtctc ccgcaagcac ttcgctctgg aacggggctg caggctgcgt 2880
gggctgtcac cggggaacta cagcgtgcga atccgggcca cctcccttgc gggcaacggc 2940
tcttggacgg aacccaccta tttctacgtg acagactatt tagacgtccc gtcaaatatt 3000
gcaaaaatta tcatcggccc cctcatcttt gtctttctct tcagtgttgt gattggaagt 3060
atttatctat tcctgagaaa gaggcagcca gatgggccgc tgggaccgct ttacgcttct 3120
tcaaaccctg agtatctcag tgccagtgat gtgtttccat gctctgtgta cgtgccggac 3180
gagtgggagg tgtctcgaga gaagatcacc ctccttcgag agctggggca gggctccttc 3240
ggcatggtgt atgagggcaa tgccagggac atcatcaagg gtgaggcaga gacccgcgtg 3300
gcggtgaaga cggtcaacga gtcagccagt ctccgagagc ggattgagtt cctcaatgag 3360
gcctcggtca tgaagggctt cacctgccat cacgtggtgc gcctcctggg agtggtgtcc 3420
aagggccagc ccacgctggt ggtgatggag ctgatggctc acggagacct gaagagctac 3480
ctccgttctc tgcggccaga ggctgagaat aatcctggcc gccctccccc tacccttcaa 3540
gagatgattc agatggcggc agagattgct gacgggatgg cctacctgaa cgccaagaag 3600
tttgtgcatc gggacctggc agcgagaaac tgcatggtcg cccatgattt tactgtcaaa 3660
attggagact ttggaatgac cagagacatc tatgaaacgg attactaccg gaaagggggc 3720
aagggtctgc tccctgtacg gtggatggca ccggagtccc tgaaggatgg ggtcttcacc 3780
acttcttctg acatgtggtc ctttggcgtg gtcctttggg aaatcaccag cttggcagaa 3840
cagccttacc aaggcctgtc taatgaacag gtgttgaaat ttgtcatgga tggagggtat 3900
ctggatcaac ccgacaactg tccagagaga gtcactgacc tcatgcgcat gtgctggcaa 3960
ttcaacccca agatgaggcc aaccttcctg gagattgtca acctgctcaa ggacgacctg 4020
caccccagct ttccagaggt gtcgttcttc cacagcgagg agaacaaggc tcccgagagt 4080
gaggagctgg agatggagtt tgaggacatg gagaatgtgc ccctggaccg ttcctcgcac 4140
tgtcagaggg aggaggcggg gggccgggat ggagggtcct cgctgggttt caagcggagc 4200
tacgaggaac acatccctta cacacacatg aacggaggca agaaaaacgg gcggattctg 4260
accttgcctc ggtccaatcc ttcctaacag tgcctaccgt ggcgggggcg ggcaggggtt 4320
cccattttcg ctttcctctg gtttgaaagc ctctggaaaa ctcaggattc tcacgactct 4380
accatgtcca gtggagttca gagatcgttc ctatacattt ctgttcatct taaggtggac 4440
tcgtttggtt accaatttaa ctagtcctgc agaggattta actgtgaacc tggagggcaa 4500
ggggtttcca cagttgctgc tcctttgggg caacgacggt ttcaaaccag gattttgtgt 4560
tttttcgttc cccccacccg cccccagcag atggaaagaa agcacctgtt tttacaaatt 4620
cttttttttt tttttttttt tttttttttg ctggtgtctg agcttcagta taaaagacaa 4680
aacttcctgt ttgtggaaca aaatttcgaa agaaaaaacc aaa 4723
<210> 32
<211> 3017
<212> DNA
<213> Homo sapiens
<400> 32
ggatccctga gcgtcacgcc gctgttgtgg agcgcgtgtt gacaacgtcg ccggggagac 60
gggcgggggc ggggcccggg agagggggag gcgcggccct ggcggcgcgc gaggggccgg 120
gctgtcagcg caaggcccag gccgccgcag tggccacggc cgctgccgcc cgccggctta 180
tataccgcgg ctaaatttag gctgcgcccg gagctcgtcc ccatccggga cgcgtttccg 240
ccgccgccgc tttggcccgg cccccgcgcg cgccgcgcct ataaggcttg ggcgggcccg 300
gccgcggccc acagagccgt ccccgcccgc ccgcgccccg accagcccgg cctcgggcag 360
ccactcaccg gtgtccccgt ccgcgtcctt cctccccggg tcccggccat ggcgctgagt 420
gaacccatcc tgccgtcctt ttccactttc gccagcccgt gccgcgagcg cggcctgcag 480
gaggtgaggg cggcggggac ggcggggcga ccgggaccgt gggcggcggg ctcggggtag 540
tagaacgtgg gctgcggggt gacaggacgc gaaggcgggg actgcagact caggagagga 600
ggatgcgggc cacggggatc gcggacttag ggtggtaaaa ggcaagcagc gccccccgag 660
ccccgccgcc cgctcacgcc cattgccctg tcgcccgcag cgctggccgc gcgccgaacc 720
cgagtccggc ggcaccgacg acgacctcaa cagcgtgctg gacttcatcc tgtccatggg 780
gctggatggc ctgggcgccg aggccgcccc ggagccgccg ccgccgcccc cgccgcctgc 840
gttctattac cccgaacccg gcgcgccccc gccctacagc gcccccgcgg gtggcctggt 900
gtctgagctg ctgcgacccg agctggatgc gccgccgggg cccgcactgc acggccgctt 960
tctgctggcg ccgcccggcc gcctggtcaa ggccgagccc cctgaagcgg acggcggcgg 1020
cggctacggc tgcgcccccg ggctgacccg tggaccgcgc ggcctcaagc gcgagggcgc 1080
cccaggcccg gcggcttcgt gcatgcgagg tcccgggggc cgccccccgc cgccgcccga 1140
cacaccgccg ctcagccccg acggccccgc gcgcctgccc gcgcccggtc cgcgcgcctc 1200
cttcccgccg cctttcggtg gccctggttt cggcgcgccc gggcccggcc tgcattacgc 1260
gccgcctgcg cccccagcct tcggtctttt cgacgacgcg gccgccgccg cggcagccct 1320
gggcctggcg ccccccgccg cccgcggtct cctcacgccg cctgcgtccc cgctggagct 1380
gctggaggcc aagccaaagc gcggccgccg ctcttggccc cgcaaacgca ccgccactca 1440
cacctgcagc tacgcgggct gcggcaagac ctacaccaag agttcgcatc tgaaggcgca 1500
tctgcgcacg cacacaggtg ggcggcacgc acgagccagg agcgcaggcg gggggacgcg 1560
ggaggagagg tcggattccc agcgcgcgcc agaaaatgaa tttaggacct cccttggggc 1620
gtggctcagg gggatctggc agtggtgcac gcttaggact ccccaggagc gtggctcggg 1680
aggttggttg ggggggcaca caggaacact ccctaaggaa gtgtgatccg agaggttggg 1740
gtgggggctt gcacgcttag gacgaggggg gcctccggag gttgggaaga gcacttagaa 1800
aacctcctgg aggcgtggct agggagacag tctcagaaag ttggggaggg ggagcaggtt 1860
taggagccgc tgggcacttg gctcagaatc cccggggctg aggctcaggt agttggggag 1920
taggtgcgcg tttaggaacc ccggggagat gctgcgtctc aggaagttgg ggagggcgct 1980
caggcttggg actcctctgg ggacaaggct caggaccttg gggagggagt gttcgctggg 2040
aaaccttgag agattccgtg tcttagaatg ctggagagag gtgcatgctt aggaccgtcg 2100
gggagcgtgg ctgacaacag tggggagtgg accttgcgct cctccgaccc cctgggggtg 2160
aggatccgga ttgtgggggg agttggggat gtagggcaag gatccctcag gggcgcaaca 2220
ctaccgcggg gagcgcgtca aggccctggt tagggatagg ttgcgctcgc cggggtagcc 2280
atacgtgccc tgtcctggga ggggaactga cgcttactct cgccccctcc ctgcaggtga 2340
gaagccctac cactgcaact gggacggctg cggctggaag tttgcgcgct cagacgagct 2400
cacgcgccac taccgaaagc acacgggcca ccggccattc cagtgccatc tgtgcgatcg 2460
tgccttctcg cgctccgatc acctggcgct gcacatgaaa cggcacatgt agccgggacg 2520
cccccgccca cctgcgcgcg gccgtggcgg gtcccacgcg ccgggcgcgg ccccctccca 2580
aactgtgact ggtatttatt ggacccagag aaccgggccg ggcacagcgt ggctacagag 2640
ggtctccctc gatgacgacg acgacgacgc caccacccca gcccccgtct gtgactgaag 2700
gcccggtggg aaaagaccac gatcctcctt gacgagtttt gtttttcaaa atggtgcaat 2760
aatttaagtg gcatcttctc tcccaccggg tctacactag aggatcgagg cttgtgatgc 2820
cttgtaagaa ataagggcct taatttgtac tgtctgcggc attttttata atattgtata 2880
tagtgactga caaatattgt attactgtac atagagagac aggtgggcat ttttgggcta 2940
cctggttcgt ttttataaga ttttgctggg ttggtttttt tttttattaa aaagttttgc 3000
atcttttaaa aaaaaaa 3017
<210> 33
<211> 2949
<212> DNA
<213> Homo sapiens
<400> 33
agtttcccga ccagagagaa cgaacgtgtc tgcgggcgcg cggggagcag aggcggtggc 60
gggcggcggc ggcaccggga gccgccgagt gaccctcccc cgcccctctg gccccccacc 120
ctcccacccg cccgtggccc gcgcccatgg ccgcgcgcgc tccacacaac tcaccggagt 180
ccgcgccttg cgccgccgac cagttcgcag ctccgcgcca cggcagccag tctcacctgg 240
cggcaccgcc cgcccaccgc cccggccaca gcccctgcgc ccacggcagc actcgaggcg 300
accgcgacag tggtggggga cgctgctgag tggaagagag cgcagcccgg ccaccggacc 360
tacttactcg ccttgctgat tgtctatttt tgcgtttaca acttttctaa gaacttttgt 420
atacaaagga actttttaaa aaagacgctt ccaagttata tttaatccaa agaagaagga 480
tctcggccaa tttggggttt tgggttttgg cttcgtttct tctcttcgtt gactttgggg 540
ttcaggtgcc ccagctgctt cgggctgccg aggaccttct gggcccccac attaatgagg 600
cagccacctg gcgagtctga catggctgtc agcgacgcgc tgctcccatc tttctccacg 660
ttcgcgtctg gcccggcggg aagggagaag acactgcgtc aagcaggtgc cccgaataac 720
cgctggcggg aggagctctc ccacatgaag cgacttcccc cagtgcttcc cggccgcccc 780
tatgacctgg cggcggcgac cgtggccaca gacctggaga gcggcggagc cggtgcggct 840
tgcggcggta gcaacctggc gcccctacct cggagagaga ccgaggagtt caacgatctc 900
ctggacctgg actttattct ctccaattcg ctgacccatc ctccggagtc agtggccgcc 960
accgtgtcct cgtcagcgtc agcctcctct tcgtcgtcgc cgtcgagcag cggccctgcc 1020
agcgcgccct ccacctgcag cttcacctat ccgatccggg ccgggaacga cccgggcgtg 1080
gcgccgggcg gcacgggcgg aggcctcctc tatggcaggg agtccgctcc ccctccgacg 1140
gctcccttca acctggcgga catcaacgac gtgagcccct cgggcggctt cgtggccgag 1200
ctcctgcggc cagaattgga cccggtgtac attccgccgc agcagccgca gccgccaggt 1260
ggcgggctga tgggcaagtt cgtgctgaag gcgtcgctga gcgcccctgg cagcgagtac 1320
ggcagcccgt cggtcatcag cgtcagcaaa ggcagccctg acggcagcca cccggtggtg 1380
gtggcgccct acaacggcgg gccgccgcgc acgtgcccca agatcaagca ggaggcggtc 1440
tcttcgtgca cccacttggg cgctggaccc cctctcagca atggccaccg gccggctgca 1500
cacgacttcc ccctggggcg gcagctcccc agcaggacta ccccgaccct gggtcttgag 1560
gaagtgctga gcagcaggga ctgtcaccct gccctgccgc ttcctcccgg cttccatccc 1620
cacccggggc ccaattaccc atccttcctg cccgatcaga tgcagccgca agtcccgccg 1680
ctccattacc aagagctcat gccacccggt tcctgcatgc cagaggagcc caagccaaag 1740
aggggaagac gatcgtggcc ccggaaaagg accgccaccc acacttgtga ttacgcgggc 1800
tgcggcaaaa cctacacaaa gagttcccat ctcaaggcac acctgcgaac ccacacaggt 1860
gagaaacctt accactgtga ctgggacggc tgtggatgga aattcgcccg ctcagatgaa 1920
ctgaccaggc actaccgtaa acacacgggg caccgcccgt tccagtgcca aaaatgcgac 1980
cgagcatttt ccaggtcgga ccacctcgcc ttacacatga agaggcattt ttaaatccca 2040
gacagtggat atgacccaca ctgccagaag agaattcagt attttttact tttcacactg 2100
tcttcccgat gagggaagga gcccagccag aaagcactac aatcatggtc aagttcccaa 2160
ctgagtcatc ttgtgagtgg ataatcagga aaaatgagga atccaaaaga caaaaatcaa 2220
agaacagatg gggtctgtga ctggatcttc tatcattcca attctaaatc cgacttgaat 2280
attcctggac ttacaaaatg ccaagggggt gactggaagt tgtggatatc agggtataaa 2340
ttatatccgt gagttggggg agggaagacc agaattccct tgaattgtgt attgatgcaa 2400
tataagcata aaagatcacc ttgtattctc tttaccttct aaaagccatt attatgatgt 2460
tagaagaaga ggaagaaatt caggtacaga aaacatgttt aaatagccta aatgatggtg 2520
cttggtgagt cttggttcta aaggtaccaa acaaggaagc caaagttttc aaactgctgc 2580
atactttgac aaggaaaatc tatatttgtc ttccgatcaa catttatgac ctaagtcagg 2640
taatatacct ggtttacttc tttagcattt ttatgcagac agtctgttat gcactgtggt 2700
ttcagatgtg caataatttg tacaatggtt tattcccaag tatgccttaa gcagaacaaa 2760
tgtgtttttc tatatagttc cttgccttaa taaatatgta atataaattt aagcaaacgt 2820
ctattttgta tatttgtaaa ctacaaagta aaatgaacat tttgtggagt ttgtattttg 2880
catactcaag gtgagaatta agttttaaat aaacctataa tattttatct gaaaaaaaaa 2940
aaaaaaaaa 2949
<210> 34
<211> 2073
<212> DNA
<213> Homo sapiens
<400> 34
agatgccacg ccccatagct ccaccagtca ccgcggcaca gtggccctta agcgaggagc 60
ggcggcgccc gcagcaatca cagcagtgcc gacgtcgtgg gtgtttggtg tgaggctgcg 120
agccgccgcg agttctcacg gtcccgccgg cgccaccacc gcggtcactc accgccgccg 180
ccgccaccac tgccaccacg gtcgcctgcc acaggtgtct gcaattgaac tccaaggtgc 240
agaatggttt ggaaagtagc tgtattcctc agtgtggccc tgggcattgg tgccgttcct 300
atagatgatc ctgaagatgg aggcaagcac tgggtggtga tcgtggcagg ttcaaatggc 360
tggtataatt ataggcacca ggcagacgcg tgccatgcct accagatcat tcaccgcaat 420
gggattcctg acgaacagat cgttgtgatg atgtacgatg acattgctta ctctgaagac 480
aatcccactc caggaattgt gatcaacagg cccaatggca cagatgtcta tcagggagtc 540
ccgaaggact acactggaga ggatgttacc ccacaaaatt tccttgctgt gttgagaggc 600
gatgcagaag cagtgaaggg cataggatcc ggcaaagtcc tgaagagtgg cccccaggat 660
cacgtgttca tttacttcac tgaccatgga tctactggaa tactggtttt tcccaatgaa 720
gatcttcatg taaaggacct gaatgagacc atccattaca tgtacaaaca caaaatgtac 780
cgaaagatgg tgttctacat tgaagcctgt gagtctgggt ccatgatgaa ccacctgccg 840
gataacatca atgtttatgc aactactgct gccaacccca gagagtcgtc ctacgcctgt 900
tactatgatg agaagaggtc cacgtacctg ggggactggt acagcgtcaa ctggatggaa 960
gattcggacg tggaagatct gactaaagag accctgcaca agcagtacca cctggtaaaa 1020
tcgcacacca acaccagcca cgtcatgcag tatggaaaca aaacaatctc caccatgaaa 1080
gtgatgcagt ttcagggtat gaaacgcaaa gccagttctc ccgtccccct acctccagtc 1140
acacaccttg acctcacccc cagccctgat gtgcctctca ccatcatgaa aaggaaactg 1200
atgaacacca atgatctgga ggagtccagg cagctcacgg aggagatcca gcggcatctg 1260
gatgccaggc acctcattga gaagtcagtg cgtaagatcg tctccttgct ggcagcgtcc 1320
gaggctgagg tggagcagct cctgtccgag agagccccgc tcacggggca cagctgctac 1380
ccagaggccc tgctgcactt ccggacccac tgcttcaact ggcactcccc cacgtacgag 1440
tatgcgttga gacatttgta cgtgctggtc aacctttgtg agaagccgta tccgcttcac 1500
aggataaaat tgtccatgga ccacgtgtgc cttggtcact actgaagagc tgcctcctgg 1560
aagcttttcc aagtgtgagc gccccaccga ctgtgtgctg atcagagact ggagaggtgg 1620
agtgagaagt ctccgctgct cgggccctcc tggggagccc ccgctccagg gctcgctcca 1680
ggaccttctt cacaagatga cttgctcgct gttacctgct tccccagtct tttctgaaaa 1740
actacaaatt agggtgggaa aagctctgta ttgagaaggg tcatatttgc tttctaggag 1800
gtttgttgtt ttgcctgtta gttttgagga gcaggaagct catgggggct tctgtagccc 1860
ctctcaaaag gagtctttat tctgagaatt tgaagctgaa acctctttaa atcttcagaa 1920
tgattttatt gaagagggcc gcaagcccca aatggaaaac tgtttttaga aaatatgatg 1980
atttttgatt gcttttgtat ttaattctgc aggtgttcaa gtcttaaaaa ataaagattt 2040
ataacagaac ccaaataaaa aaaaaaaaaa aaa 2073
<210> 35
<211> 3470
<212> DNA
<213> Homo sapiens
<400> 35
atacacacag actcacagcg agaccgacac acactcccat acactcacac acacaactgc 60
aggcagcgag gctcgggaag tcaggccggc ttttcgcccc ggcgccttct ctgctccagc 120
cggccgggtc tccctggggg cccggagctc ggccgggccg cgcagccccg ttagaggacg 180
agctcggcgg acccccgctc ctccatgggc aaacgcgggc ggccgcgcaa ggaggcgcgc 240
tgcgagggcg cggggctggc ccccgccgcg cccccggctg tgccccccgc cgtggccgcg 300
ccccagcccc cggccctgcc cgaggacccc gctggggcca agcccaggtg ccccttctca 360
gacattttca acaccagcga gaactcgatg gagaagcaca tcaacacttt tctgcagaac 420
gtgcagattc tgctcgaggc cgccagctac ctggagcaga tcgagaaaga aaacaaaaag 480
tgtgaacatg gctacgcctc ttcattcccg tccatgccga gcccccgact gcagcattca 540
aagcccccac ggaggttgag ccgggcacag aaacacagca gcgggagcag caacaccagc 600
actgccaaca gatctacaca caatgagctg gaaaagaatc gacgagctca tctgcgcctt 660
tgtttagaac gcttaaaagt tctgattcca ctaggaccag actgcacccg gcacacaaca 720
cttggtttgc tcaacaaagc caaagcacac atcaagaaac ttgaagaagc tgaaagaaaa 780
agccagcacc agctcgagaa tttggaacga gaacagagat ttttaaagtg gcgactggaa 840
cagctgcagg gtcctcagga gatggaacga atacgaatgg acagcattgg atcaactatt 900
tcttcagatc gttctgattc agagcgagag gagattgaag tggatgttga aagcacagag 960
ttctcccatg gagaagtgga caatataagt accaccagca tcagtgacat tgatgaccac 1020
agcagcctgc cgagtattgg gagtgacgag ggttactcca gtgccagtgt caaactttca 1080
ttcacttcat agaacccagc atgacataac agtgcagggc aaaatattca ctgggccaat 1140
tcaatacaaa caatctctta aattgggttc atgatgcagt ctcctcttta aaacaaaaca 1200
aaacaaaaca aaactatact tgaacaaaag ggtcagagga cctgtattta agcaaatact 1260
tagcaaaaag tggggcagag cctcccaagg agaacaaata ttcagaatat tcatattgga 1320
aaaatcacaa tttttaatgg cagcagaaaa cttgtgtgaa attttcttga tttgagttga 1380
ttgagaagag gacattggag atgccatcct ctttctcttt tctagtttgc tcatactaca 1440
ttgagtagac acatttaagg atggggttat gaacccttcc tgagctttat ggtcctaaaa 1500
gcaaaataaa aactattcga atgaaaagac aagaaaatca ggtattaatc ttggatagct 1560
aataatgagc tattaaaact cagcctggga cagtttatca tgaagcctgt ggatgatcaa 1620
tcctttatta ttattttttt tttttgaaaa aagctcattt catgctctgc aaaaggagag 1680
actcccatga agccttttga aagggatcat catgcagctc aactttctgt tggattccat 1740
gctaagcaag ctaaccttat cctgcattgt tagcactagg cacccagctg ccacctctcc 1800
atcctgctgc ccttaggcca catgggagca gtccatgcat gacagcctct atcctacaag 1860
gcctatgagt atggattggg ggggccaaaa ggaaaaagct ccatgtgcct ctttgtctgc 1920
gtgggtcaga agagttgtgc acgcagatta gcaggccaag gtctgagcca cagcagcatt 1980
tttatttcag attttgataa ctgtttatat gtgttgaaaa ccaaaatgac atctttttaa 2040
agcttatcca taaaaaaaaa tagatgtctt ttatagtgga aaaacacatg gggaaaaaaa 2100
tcatctattt tgatgcagca tttgataatg ataaaacacc tcacacctca ctctttatag 2160
tgcacaaaat gaatgaggtc tgggctaggt agaaaaaggg tcaatgctat ttttgttttt 2220
agaatcatta ccttttacca gcttttaacc atctgatatc tatagtagac acactatcat 2280
agttaacata gtaagttcag cacttgtctc attttaatgt aaagatttgc ttccattttc 2340
ctacaggcag tctctctctt cctcacagtc ccactgtgca ggtgctattg ttactcttac 2400
gaatattttc agtaatgtta ttttcttcta agtgaaattt ctagcctgca ctttgatgtc 2460
atgtgttccc tttgtctttc aaactccaag gttcccttgt ggccctctcc cttaccctgg 2520
gaaggcctct tggagacctt acccctggct gtttggactt tgtatacttt aaataattta 2580
actaccctta attacttaaa aaaaaaaaaa agctttatga ttttcataac ttattgctga 2640
ttttaatgga ttgttaattt cagtcctgta gttttatttt atgtttagat agggctgggc 2700
aaggaaaaag aaaataaaga caaccatatt tagcagtgca gttgagttgt gtgttaatgt 2760
tagactatcc ctttgtgagt gacactttaa cagcattcac tgcttctata tatagtgtac 2820
catcttggtc atacattacg cctcaacata tacttgtgct cttcctttgc ctccagaaga 2880
agtttttcct tgattgtgct atgtttcagt ggaagaaatt ctttgaagta gatgtgagtg 2940
aaaaactgca tgcctttaga agcccagtat cagaacttgc tacgtttcag gtgctaggga 3000
cttaatgaaa aacaggacaa aacaattcct ttttgtggcc caggtaaatt atttctggtt 3060
tcacttataa ttactaatgg ctgagtcaag atgttgtctc tgtgtttgct tactcttgat 3120
caagtgtgag acagtttgaa gactgtgcta ccatacaaag tgaatgaagc cagtgactaa 3180
gcttctgttt gttttgttat tctcatggcc ttcgcttgca ttatttgggc cttcattcag 3240
atgaacttga ggtgccattt tgttgcatat gtacaggatt atgggctgga aagcatttgt 3300
tataaaccta tagtgcacat tttaactgcc ccctaaatta cccttccctg ggtttgtttt 3360
ccttggggtg gtgtagattg tatgagtaag aagtattaat tttttaaaag acaaatcaac 3420
tttgaagaca caaaagttaa ttggaagaaa taaaaactgt gaacgaagaa 3470
<210> 36
<211> 1823
<212> DNA
<213> Homo sapiens
<400> 36
gagaagctag gggtgaggaa gccctggggc gctgccgccg ctttccttaa ccacaaatca 60
ggccggacag gagagggagg ggtgggggac agtgggtggg cattcagact gccagcactt 120
tgctatctac agccggggct cccgagcggc agaaagttcc ggccactctc tgccgcttgg 180
gttgggcgaa gccaggaccg tgccgcgcca ccgccaggat atggagctac tgtcgccacc 240
gctccgcgac gtagacctga cggcccccga cggctctctc tgctcctttg ccacaacgga 300
cgacttctat gacgacccgt gtttcgactc cccggacctg cgcttcttcg aagacctgga 360
cccgcgcctg atgcacgtgg gcgcgctcct gaaacccgaa gagcactcgc acttccccgc 420
ggcggtgcac ccggccccgg gcgcacgtga ggacgagcat gtgcgcgcgc ccagcgggca 480
ccaccaggcg ggccgctgcc tactgtgggc ctgcaaggcg tgcaagcgca agaccaccaa 540
cgccgaccgc cgcaaggccg ccaccatgcg cgagcggcgc cgcctgagca aagtaaatga 600
ggcctttgag acactcaagc gctgcacgtc gagcaatcca aaccagcggt tgcccaaggt 660
ggagatcctg cgcaacgcca tccgctatat cgagggcctg caggctctgc tgcgcgacca 720
ggacgccgcg ccccctggcg ccgcagccgc cttctatgcg ccgggcccgc tgcccccggg 780
ccgcggcggc gagcactaca gcggcgactc cgacgcgtcc agcccgcgct ccaactgctc 840
cgacggcatg atggactaca gcggcccccc gagcggcgcc cggcggcgga actgctacga 900
aggcgcctac tacaacgagg cgcccagcga acccaggccc gggaagagtg cggcggtgtc 960
gagcctagac tgcctgtcca gcatcgtgga gcgcatctcc accgagagcc ctgcggcgcc 1020
cgccctcctg ctggcggacg tgccttctga gtcgcctccg cgcaggcaag aggctgccgc 1080
ccccagcgag ggagagagca gcggcgaccc cacccagtca ccggacgccg ccccgcagtg 1140
ccctgcgggt gcgaacccca acccgatata ccaggtgctc tgaggggatg gtggccgccc 1200
acccgcccga gggatggtgc ccctagggtc cctcgcgccc aaaagattga acttaaatgc 1260
ccccctccca acagcgcttt aaaagcgacc tctcttgagg taggagaggc gggagaactg 1320
aagtttccgc ccccgcccca cagggcaagg acacagcgcg gttttttcca cgcagcaccc 1380
ttctcggaga cccattgcga tggccgctcc gtgttcctcg gtgggccaga gctgaacctt 1440
gaggggctag gttcagcttt ctcgcgccct cccccatggg ggtgagaccc tcgcagacct 1500
aagccctgcc ccgggatgca ccggttattt gggggggcgt gagacccagt gcactccggt 1560
cccaaatgta gcaggtgtaa ccgtaaccca cccccaaccc gtttcccggt tcaggaccac 1620
tttttgtaat acttttgtaa tctattcctg taaataagag ttgctttgcc agagcaggag 1680
cccctggggc tgtatttatc tctgaggcat ggtgtgtggt gctacaggga atttgtacgt 1740
ttataccgca ggcgggcgag ccgcgggcgc tcgctcaggt gatcaaaata aaggcgctaa 1800
tttataaaaa aaaaaaaaaa aaa 1823
<210> 37
<211> 4345
<212> DNA
<213> Homo sapiens
<400> 37
actgaaacta ggggcaagga gacgaagaga acatgaaagt taaactttaa gatgaagaac 60
aaagctgaac atactgatgc attggatctt tggagaggat ctcagaactc attgtactta 120
atttacaggc taaaacctta gaagaggaat ttattatatc ctacacaaga ctccagggaa 180
gcacatggcc ttggactgaa ggctggcatc tggaagctgt cagccaccag caccttctgc 240
agcaggaaaa ggccagggct ctgctggagc aggcagcaga gtggacgcac agtaacatgg 300
gcaacttgaa gagcgtggcc caggagcctg ggccaccctg cggcctgggg ctggggctgg 360
gccttgggct gtgcggcaag cagggcccag ccaccccggc ccctgagccc agccgggccc 420
cagcatccct actcccacca gcgccagaac acagcccccc gagctccccg ctaacccagc 480
ccccagaggg gcccaagttc cctcgtgtga agaactggga ggtggggagc atcacctatg 540
acaccctcag cgcccaggcg cagcaggatg ggccctgcac cccaagacgc tgcctgggct 600
ccctggtatt tccacggaaa ctacagggcc ggccctcccc cggccccccg gcccctgagc 660
agctgctgag tcaggcccgg gacttcatca accagtacta cagctccatt aagaggagcg 720
gctcccaggc ccacgaacag cggcttcaag aggtggaagc cgaggtggca gccacaggca 780
cctaccagct tagggagagc gagctggtgt tcggggctaa gcaggcctgg cgcaacgctc 840
cccgctgcgt gggccggatc cagtggggga agctgcaggt gttcgatgcc cgggactgca 900
ggtctgcaca ggaaatgttc acctacatct gcaaccacat caagtatgcc accaaccggg 960
gcaaccttcg ctcggccatc acagtgttcc cgcagcgctg ccctggccga ggagacttcc 1020
gaatctggaa cagccagctg gtgcgctacg cgggctaccg gcagcaggat ggctctgtgc 1080
ggggggaccc agccaacgtg gagatcaccg agctctgcat tcagcacggc tggaccccag 1140
gaaacggtcg cttcgacgtg ctgcccctgc tgctgcaggc cccagatgat cccccagaac 1200
tcttccttct gccccccgag ctggtccttg aggtgcccct ggagcacccc acgctggagt 1260
ggtttgcagc cctgggcctg cgctggtacg ccctcccggc agtgtccaac atgctgctgg 1320
aaattggggg cctggagttc cccgcagccc ccttcagtgg ctggtacatg agcactgaga 1380
tcggcacgag gaacctgtgt gaccctcacc gctacaacat cctggaggat gtggctgtct 1440
gcatggacct ggatacccgg accacctcgt ccctgtggaa agacaaggca gcagtggaaa 1500
tcaacgtggc cgtgctgcac agttaccagc tagccaaagt caccatcgtg gaccaccacg 1560
ccgccacggc ctctttcatg aagcacctgg agaatgagca gaaggccagg gggggctgcc 1620
ctgcagactg ggcctggatc gtgcccccca tctcgggcag cctcactcct gttttccatc 1680
aggagatggt caactatttc ctgtccccgg ccttccgcta ccagccagac ccctggaagg 1740
ggagtgccgc caagggcacc ggcatcacca ggaagaagac ctttaaagaa gtggccaacg 1800
ccgtgaagat ctccgcctcg ctcatgggca cggtgatggc gaagcgagtg aaggcgacaa 1860
tcctgtatgg ctccgagacc ggccgggccc agagctacgc acagcagctg gggagactct 1920
tccggaaggc ttttgatccc cgggtcctgt gtatggatga gtatgacgtg gtgtccctcg 1980
aacacgagac gctggtgctg gtggtaacca gcacatttgg gaatggggat cccccggaga 2040
atggagagag ctttgcagct gccctgatgg agatgtccgg cccctacaac agctcccctc 2100
ggccggaaca gcacaagagt tataagatcc gcttcaacag catctcctgc tcagacccac 2160
tggtgtcctc ttggcggcgg aagaggaagg agtccagtaa cacagacagt gcaggggccc 2220
tgggcaccct caggttctgt gtgttcgggc tcggctcccg ggcatacccc cacttctgcg 2280
cctttgctcg tgccgtggac acacggctgg aggaactggg cggggagcgg ctgctgcagc 2340
tgggccaggg cgacgagctg tgcggccagg aggaggcctt ccgaggctgg gcccaggctg 2400
ccttccaggc cgcctgtgag accttctgtg tgggagagga tgccaaggcc gccgcccgag 2460
acatcttcag ccccaaacgg agctggaagc gccagaggta ccggctgagc gcccaggccg 2520
agggcctgca gttgctgcca ggtctgatcc acgtgcacag gcggaagatg ttccaggcta 2580
caatccgctc agtggaaaac ctgcaaagca gcaagtccac gagggccacc atcctggtgc 2640
gcctggacac cggaggccag gaggggctgc agtaccagcc gggggaccac ataggtgtct 2700
gcccgcccaa ccggcccggc cttgtggagg cgctgctgag ccgcgtggag gacccgccgg 2760
cgcccactga gcccgtggca gtagagcagc tggagaaggg cagccctggt ggccctcccc 2820
ccggctgggt gcgggacccc cggctgcccc cgtgcacgct gcgccaggct ctcaccttct 2880
tcctggacat cacctcccca cccagccctc agctcttgcg gctgctcagc accttggcag 2940
aagagcccag ggaacagcag gagctggagg ccctcagcca ggatccccga cgctacgagg 3000
agtggaagtg gttccgctgc cccacgctgc tggaggtgct ggagcagttc ccgtcggtgg 3060
cgctgcctgc cccactgctc ctcacccagc tgcctctgct ccagccccgg tactactcag 3120
tcagctcggc acccagcacc cacccaggag agatccacct cactgtagct gtgctggcat 3180
acaggactca ggatgggctg ggccccctgc actatggagt ctgctccacg tggctaagcc 3240
agctcaagcc cggagaccct gtgccctgct tcatccgggg ggctccctcc ttccggctgc 3300
cacccgatcc cagcttgccc tgcatcctgg tgggtccagg cactggcatt gcccccttcc 3360
ggggattctg gcaggagcgg ctgcatgaca ttgagagcaa agggctgcag cccactccca 3420
tgactttggt gttcggctgc cgatgctccc aacttgacca tctctaccgc gacgaggtgc 3480
agaacgccca gcagcgcggg gtgtttggcc gagtcctcac cgccttctcc cgggaacctg 3540
acaaccccaa gacctacgtg caggacatcc tgaggacgga gctggctgcg gaggtgcacc 3600
gcgtgctgtg cctcgagcgg ggccacatgt ttgtctgcgg cgatgttacc atggcaacca 3660
acgtcctgca gaccgtgcag cgcatcctgg cgacggaggg cgacatggag ctggacgagg 3720
ccggcgacgt catcggcgtg ctgcgggatc agcaacgcta ccacgaagac attttcgggc 3780
tcacgctgcg cacccaggag gtgacaagcc gcatacgcac ccagagcttt tccttgcagg 3840
agcgtcagtt gcggggcgca gtgccctggg cgttcgaccc tcccggctca gacaccaaca 3900
gcccctgaga gccgcctggc tttcccttcc agttccggga gagcggctgc ccgactcagg 3960
tccgcccgac caggatcagc cccgctcctc ccctcttgag gtggtgcctt ctcacatctg 4020
tccagaggct gcaaggattc agcattattc ctccaggaag gagcaaaacg cctcttttcc 4080
ctctctaggc ctgttgcctc gggcctgggt ccgccttaat ctggaaggcc cctcccagca 4140
gcggtacccc agggcctact gccacccgct tcctgtttct tagtcgaatg ttagattcct 4200
cttgcctctc tcaggagtat cttacctgta aagtctaatc tctaaatcaa gtatttatta 4260
ttgaagattt accataaggg actgtgccag atgttaggag aactactaaa gtgcctaccc 4320
cagctcatgt ggattacaaa aaaaa 4345
<210> 38
<211> 2692
<212> DNA
<213> Homo sapiens
<400> 38
tttaaagctg ggaggttctg ccaccaagca cggccttccc actgggaaca caaacttgct 60
ggcgggaaga gcccggaaag aaacctgtgg atctcccttc gagatcatcc aaagagaaga 120
aaggtgacct cacattcgtg ccccttagca gcactctgca gaaatgcctc ctcagctgca 180
aaacggcctg aacctctcgg ccaaagttgt ccagggaagc ctggacagcc taccccaggc 240
agtgagggag tttctcgaga ataacgctga gctgtgtcag cctgatcaca tccacatctg 300
tgacggctct gaggaggaga atgggcggct tctgggccag atggaggaag agggcatcct 360
caggcggctg aagaagtatg acaactgctg gttggctctc actgacccca gggatgtggc 420
caggatcgaa agcaagacgg ttatcgtcac ccaagagcaa agagacacag tgcccatccc 480
caaaacaggc ctcagccagc tcggtcgctg gatgtcagag gaggattttg agaaagcgtt 540
caatgccagg ttcccagggt gcatgaaagg tcgcaccatg tacgtcatcc cattcagcat 600
ggggccgctg ggctcgcctc tgtcaaagat cggcatcgag ctgacggatt caccctacgt 660
ggtggccagc atgcggatca tgacgcggat gggcacgccc gtcctggaag cagtgggcga 720
tggggagttt gtcaaatgcc tccattctgt ggggtgccct ctgcctttac aaaagccttt 780
ggtcaacaac tggccctgca acccggagct gacgctcatc gcccacctgc ctgaccgcag 840
agagatcatc tcctttggca gtgggtacgg cgggaactcg ctgctcggga agaagtgctt 900
tgctctcagg atggccagcc ggctggccaa ggaggaaggg tggctggcag agcacatgct 960
gattctgggt ataaccaacc ctgagggtga gaagaagtac ctggcggccg catttcccag 1020
cgcctgcggg aagaccaacc tggccatgat gaaccccagc ctccccgggt ggaaggttga 1080
gtgcgtcggg gatgacattg cctggatgaa gtttgacgca caaggtcatt taagggccat 1140
caacccagaa aatggctttt tcggtgtcgc tcctgggact tcagtgaaga ccaaccccaa 1200
tgccatcaag accatccaga agaacacaat ctttaccaat gtggccgaga ccagcgacgg 1260
gggcgtttac tgggaaggca ttgatgagcc gctagcttca ggtgtcacca tcacgtcctg 1320
gaagaataag gagtggagct cagaggatgg ggaaccttgt gcccacccca actcgaggtt 1380
ctgcacccct gccagccagt gccccatcat tgatgctgcc tgggagtctc cggaaggtgt 1440
tcccattgaa ggcattatct ttggaggccg tagacctgct ggtgtccctc tagtctatga 1500
agctctcagc tggcaacatg gagtctttgt gggggcggcc atgagatcag aggccacagc 1560
ggctgcagaa cataaaggca aaatcatcat gcatgacccc tttgccatgc ggcccttctt 1620
tggctacaac ttcggcaaat acctggccca ctggcttagc atggcccagc acccagcagc 1680
caaactgccc aagatcttcc atgtcaactg gttccggaag gacaaggaag gcaaattcct 1740
ctggccaggc tttggagaga actccagggt gctggagtgg atgttcaacc ggatcgatgg 1800
aaaagccagc accaagctca cgcccatagg ctacatcccc aaggaggatg ccctgaacct 1860
gaaaggcctg gggcacatca acatgatgga gcttttcagc atctccaagg aattctggga 1920
gaaggaggtg gaagacatcg agaagtatct ggaggatcaa gtcaatgccg acctcccctg 1980
tgaaatcgag agagagatcc ttgccttgaa gcaaagaata agccagatgt aatcagggcc 2040
tgagtgcttt acctttaaaa tcattccctt tcccatccat aaggtgcagt aggagcaaga 2100
gagggcaagt gttcccaaat tgacgccacc ataataatca tcaccacacc gtgagcagat 2160
ctgaaaggca cactttgatt tttttaagga taagaaccac agaacactgg gtagtagcta 2220
atgaaattga gaagggaaat cttagcatgc ctccaaaaat tcacatccaa tgcatagttt 2280
gttcaaattt aaggttactc aggcattgat cttttcagtg ttttttcact ttagctatgt 2340
ggattagcta gaatgcacac caaaaaaata cttgagctgt atatatatat gtgtgtgtgt 2400
gtgtgtgtgt gtgtgtgtgt gtgtgcatgt atgtgcacat gtgtctgtgt ggtatatttg 2460
tgtatgtgta tttgtatgta ctgttattga aaatatattt aatacctttg gaaaaatctt 2520
gggcaagatg acctactagt tttccttgaa aaaaagttgc tttgttatta atattgtgct 2580
taaattattt ttatacacca ttgttcctta cctttacata attgcaatat ttccccctta 2640
ctacttcttg gaaaaaaatt acaaaatgaa gttttataga aaagaaaaaa aa 2692
<210> 39
<211> 3710
<212> DNA
<213> Homo sapiens
<400> 39
aggacgcgtt tccaagttcc agtgactcct cctgtttggg actcgggggg agagtgcggg 60
gagacaaata aaacctcggg cggcggcggc tggtgggaag acttgaactt gaatctcgaa 120
ccactgcatc tccgactctg cccagactct tcactccgcg gcaccctcaa accccagccc 180
aggccggggc gcacaagcca gccagcgcac ctgcagtcct cgcccggacg cgccgcgccc 240
cctcggaacc aggctctgct ccgagcagcc ttcgcccctc aagccagcca cagtccccgc 300
caggccgggt gggcgtcaag atgaaggcgg cccgcttcgt gctgcgcagc gctggctcgc 360
tcaacggcgc cggcctggtg ccccgagagg tggagcattt ctcgcgctac agcccgtccc 420
cgctgtccat gaagcagcta ctggactttg gttcagaaaa tgcatgtgaa agaacttctt 480
ttgcattttt gcgacaagaa ttgcctgtga gactcgccaa cattctgaag gaaattgata 540
tcctcccgac ccaattagta aatacctctt cagtgcaatt ggttaaaagc tggtatatac 600
agagcctgat ggatttggtg gaattccatg agaaaagccc agatgaccag aaagcattat 660
cagactttgt agatacactc atcaaagttc gaaatagaca ccataatgta gtccctacaa 720
tggcacaagg aatcatagag tataaagatg cctgtacagt tgacccagtc accaatcaaa 780
atcttcaata tttcttggat cgattttaca tgaaccgtat ttctactcgg atgctgatga 840
accagcacat tcttatattt agtgactcac agacaggaaa cccaagccac attggaagca 900
ttgatcctaa ctgtgatgtg gtagcagtgg tccaagatgc ctttgagtgt tcaaggatgc 960
tctgtgatca gtattattta tcatctccag aattaaagct tacacaagtg aatggaaaat 1020
ttccagacca accaattcac atcgtgtatg ttccttctca cctccatcat atgctctttg 1080
aactatttaa gaatgcaatg cgggcaacag ttgaacacca ggaaaatcag ccttccctta 1140
caccaataga ggttattgtt gtcttgggaa aagaagacct taccattaag atttcagaca 1200
gaggaggtgg tgttcccctg agaattattg accgcctctt tagttataca tactccactg 1260
caccaacgcc tgtgatggat aattcccgga atgctccttt ggctggtttt ggttacggct 1320
tgccaatttc tcgtctgtat gcaaagtact ttcaaggaga tctgaatctc tactctttat 1380
caggatatgg aacagatgct atcatctact taaaggcttt gtcttctgag tctatagaaa 1440
aacttccagt ttttaacaag tcagccttca aacattatca gatgagctct gaggctgatg 1500
actggtgtat cccaagcagg gaaccaaaga acctggcaaa agaagtggcc atgtgaagag 1560
ggacactcag gacactttac gggatcaaag tgggtctaca ccagtgctgc ttcctgaatg 1620
tttgtgtgtg aacccttgtt tcctccaaaa caaacgacag caacgaaaac tccttaatca 1680
gaacactgat ccaatgagga atggagcttg tttctgtgac ccaggagaac ttagtgcaag 1740
actacaggag ttaacagatg gccagctcct tattttttaa tgtagaataa ctcctgagtt 1800
tatatcaaat cctgaagaaa taagcctcag ttttccatct gtttttgata agaataagaa 1860
agggagtgag tgtgaagatg gtggttagca gtttcactaa gactgatatt ttaggcctct 1920
tgttcacatc aaaagatatt ggtgtcagaa taccagcatt ttcctgccat gcaaaggatt 1980
aaaacttagt ttacactatg tggttacaaa tatatgtcaa tgtacatttt gaacatattt 2040
atgtgctatg gaaggaaatg ctggtgacta aaataaggtt tactctgaaa gaggaggaat 2100
tttattcaaa gcattcaaac attttattca agtgtttcaa aattcaaagc attgtattca 2160
aagttgcagt gaaggcatca acttatgtaa aaactcagaa ggaaggctcc tctgataaaa 2220
acacagctcc tttattatgc tgcttttctt gttcacttta cacactaagt aaacacttat 2280
tgtcaggtgc ctagtcttga gtgaattgtt agatgtgcac tgaactcggg atgttgggga 2340
ttggagagag agaattgcca aagtaacagc aaaaatatct cttactttgc tttgtttata 2400
aataaattag tagattggaa aaactagtgt tagggaaaga aatcacatgt tcagagccta 2460
attcagtagg aagggctttt ctctaccctg aaatgaaggt aatccaaagg catccatttt 2520
ctaggcttaa aagatatatt tttgatatat ttaattatat tctctacact ccagcattaa 2580
tatgtctgtt taaaaattac taattctcaa atggctcaag aacattagaa tttaagtacc 2640
ttttagagta attattttaa gcaaatagcc tggacgtaag agattctcat gccagcatgc 2700
tttcatttgt cagttgttgt gactgagaga taatgaatga cacctgaaat gcatatggta 2760
tttttgggag agttaaggta taatttgaag gttggcagac cagttgcgct gattactctt 2820
agagaagaag aaatggaaaa atgaaagaag gcaggaagga aagaaaggat ataggaagag 2880
agggaagcag aaggcaggca tttttctatt ttccccacaa attatttcaa aaaaaatctg 2940
tattttctgg gatatgtcat tggcaagagg aagaactggt gttttgaaag cagtatggat 3000
tctttaaatg cctctcactc ttacaagata gtaggctttg agataataaa cttacccgtg 3060
tcaattaaca tttaaactgg catatagaaa aaaaggagga tttttctgca ttgtaaaata 3120
atcagtatgg tttatatgtt gaatttgaca tttgtgtgta atttcatggt ggcctagtgt 3180
tgtggtgctt ctggtaatgg taatagaagc tcaactattt ttttgtggat ttcagttttt 3240
atcatcagaa gtcctagaca gtgacatttc ttaatggtgg gagtccagct catgcatttc 3300
tgattataca aaacagtttg cagtaggtta tttgtcattt cagtttttta ctgaaatttg 3360
agctaaacat ttttacatgt aaatacttgt atttaccaaa gatttaaatc agttgattaa 3420
ttaattaact caaatactgt gaactatctc taaaacacta gaaaaaagaa atgttagtat 3480
ctcaattaca ccaactgtgc aaatgaactt tgataaaata gaaataatct acattggcct 3540
ttgtgaaatc tggggaagag ctttaggatt ctagtagatg gatactgaat actcaggccc 3600
acttaaatta ttaatgtata cattgtgttt ttgtctttat gctatgtaca gagaaatgtg 3660
ataatttttt ataataaata ttttttatga tgataaaaga aaaaaaaaaa 3710
<210> 40
<211> 1295
<212> DNA
<213> Homo sapiens
<400> 40
ccttcccctg gcccggggag ctgctccttg tgctgccggg aaggtcaaag tcccgcgccc 60
accaggagag ctcggcaagt atataaggac agaggagcgc gggaccaagc ggcggcgaag 120
gaggggaaga agagccgcga ccgagagagg ccgccgagcg tccccgccct cagagagcag 180
cctcccgaga caggcacttg ctggattctc caaaagtatc tgcagtggct gttccaccag 240
gagagcctca gcctgcctgg aagatgccga gatcgtgctg cagccgctcg ggggccctgt 300
tgctggcctt gctgcttcag gcctccatgg aagtgcgtgg ctggtgcctg gagagcagcc 360
agtgtcagga cctcaccacg gaaagcaacc tgctggagtg catccgggcc tgcaagcccg 420
acctctcggc cgagactccc atgttcccgg gaaatggcga cgagcagcct ctgaccgaga 480
acccccggaa gtacgtcatg ggccacttcc gctgggaccg attcggccgc cgcaacagca 540
gcagcagcgg cagcagcggc gcagggcaga agcgcgagga cgtctcagcg ggcgaagact 600
gcggcccgct gcctgagggc ggccccgagc cccgcagcga tggtgccaag ccgggcccgc 660
gcgagggcaa gcgctcctac tccatggagc acttccgctg gggcaagccg gtgggcaaga 720
agcggcgccc agtgaaggtg taccctaacg gcgccgagga cgagtcggcc gaggccttcc 780
ccctggagtt caagagggag ctgactggcc agcgactccg ggagggagat ggccccgacg 840
gccctgccga tgacggcgca ggggcccagg ccgacctgga gcacagcctg ctggtggcgg 900
ccgagaagaa ggacgagggc ccctacagga tggagcactt ccgctggggc agcccgccca 960
aggacaagcg ctacggcggt ttcatgacct ccgagaagag ccagacgccc ctggtgacgc 1020
tgttcaaaaa cgccatcatc aagaacgcct acaagaaggg cgagtgaggg cacagcgggg 1080
ccccagggct accctccccc aggaggtcga ccccaaagcc ccttgctctc ccctgccctg 1140
ctgccgcctc ccagcctggg gggtcgtggc agataatcag cctcttaaag ctgcctgtag 1200
ttaggaaata aaacctttca aatttcacat ccacctctga ctttgaatgt aaactgtgtg 1260
aataaagtaa aaatacgtag ccgtcaaata acagc 1295
<210> 41
<211> 6318
<212> DNA
<213> Homo sapiens
<400> 41
tagtaagaca ggtgccttca gttcactctc agtaaggggc tggttgcctg catgagtgtg 60
tgctctgtgt cactgtggat tggagttgaa aaagcttgac tggcgtcatt caggagctgg 120
atggcgtggg acatgtgcaa ccaggactct gagtctgtat ggagtgacat cgagtgtgct 180
gctctggttg gtgaagacca gcctctttgc ccagatcttc ctgaacttga tctttctgaa 240
ctagatgtga acgacttgga tacagacagc tttctgggtg gactcaagtg gtgcagtgac 300
caatcagaaa taatatccaa tcagtacaac aatgagcctt caaacatatt tgagaagata 360
gatgaagaga atgaggcaaa cttgctagca gtcctcacag agacactaga cagtctccct 420
gtggatgaag acggattgcc ctcatttgat gcgctgacag atggagacgt gaccactgac 480
aatgaggcta gtccttcctc catgcctgac ggcacccctc caccccagga ggcagaagag 540
ccgtctctac ttaagaagct cttactggca ccagccaaca ctcagctaag ttataatgaa 600
tgcagtggtc tcagtaccca gaaccatgca aatcacaatc acaggatcag aacaaaccct 660
gcaattgtta agactgagaa ttcatggagc aataaagcga agagtatttg tcaacagcaa 720
aagccacaaa gacgtccctg ctcggagctt ctcaaatatc tgaccacaaa cgatgaccct 780
cctcacacca aacccacaga gaacagaaac agcagcagag acaaatgcac ctccaaaaag 840
aagtcccaca cacagtcgca gtcacaacac ttacaagcca aaccaacaac tttatctctt 900
cctctgaccc cagagtcacc aaatgacccc aagggttccc catttgagaa caagactatt 960
gaacgcacct taagtgtgga actctctgga actgcaggcc taactccacc caccactcct 1020
cctcataaag ccaaccaaga taaccctttt agggcttctc caaagctgaa gtcctcttgc 1080
aagactgtgg tgccaccacc atcaaagaag cccaggtaca gtgagtcttc tggtacacaa 1140
ggcaataact ccaccaagaa agggccggag caatccgagt tgtatgcaca actcagcaag 1200
tcctcagtcc tcactggtgg acacgaggaa aggaagacca agcggcccag tctgcggctg 1260
tttggtgacc atgactattg ccagtcaatt aattccaaaa cagaaatact cattaatata 1320
tcacaggagc tccaagactc tagacaacta gaaaataaag atgtctcctc tgattggcag 1380
gggcagattt gttcttccac agattcagac cagtgctacc tgagagagac tttggaggca 1440
agcaagcagg tctctccttg cagcacaaga aaacagctcc aagaccagga aatccgagcc 1500
gagctgaaca agcacttcgg tcatcccagt caagctgttt ttgacgacga agcagacaag 1560
accggtgaac tgagggacag tgatttcagt aatgaacaat tctccaaact acctatgttt 1620
ataaattcag gactagccat ggatggcctg tttgatgaca gcgaagatga aagtgataaa 1680
ctgagctacc cttgggatgg cacgcaatcc tattcattgt tcaatgtgtc tccttcttgt 1740
tcttctttta actctccatg tagagattct gtgtcaccac ccaaatcctt attttctcaa 1800
agaccccaaa ggatgcgctc tcgttcaagg tccttttctc gacacaggtc gtgttcccga 1860
tcaccatatt ccaggtcaag atcaaggtct ccaggcagta gatcctcttc aagatcctgc 1920
tattactatg agtcaagcca ctacagacac cgcacgcacc gaaattctcc cttgtatgtg 1980
agatcacgtt caagatcgcc ctacagccgt cggcccaggt atgacagcta cgaggaatat 2040
cagcacgaga ggctgaagag ggaagaatat cgcagagagt atgagaagcg agagtctgag 2100
agggccaagc aaagggagag gcagaggcag aaggcaattg aagagcgccg tgtgatttat 2160
gtcggtaaaa tcagacctga cacaacacgg acagaactga gggaccgttt tgaagttttt 2220
ggtgaaattg aggagtgcac agtaaatctg cgggatgatg gagacagcta tggtttcatt 2280
acctaccgtt atacctgtga tgcttttgct gctcttgaaa atggatacac tttgcgcagg 2340
tcaaacgaaa ctgactttga gctgtacttt tgtggacgca agcaattttt caagtctaac 2400
tatgcagacc tagattcaaa ctcagatgac tttgaccctg cttccaccaa gagcaagtat 2460
gactctctgg attttgatag tttactgaaa gaagctcaga gaagcttgcg caggtaacat 2520
gttccctagc tgaggatgac agagggatgg cgaatacctc atgggacagc gcgtccttcc 2580
ctaaagacta ttgcaagtca tacttaggaa tttctcctac tttacactct ctgtacaaaa 2640
acaaaacaaa acaacaacaa tacaacaaga acaacaacaa caataacaac aatggtttac 2700
atgaacacag ctgctgaaga ggcaagagac agaatgatat ccagtaagca catgtttatt 2760
catgggtgtc agctttgctt ttcctggagt ctcttggtga tggagtgtgc gtgtgtgcat 2820
gtatgtgtgt gtgtatgtat gtgtgtggtg tgtgtgcttg gtttagggga agtatgtgtg 2880
ggtacatgtg aggactgggg gcacctgacc agaatgcgca agggcaaacc atttcaaatg 2940
gcagcagttc catgaagaca cgcttaaaac ctagaacttc aaaatgttcg tattctattc 3000
aaaaggaaat atatatatat atatatatat atatatatat atatataaat taaaaaggaa 3060
agaaaactaa caaccaacca accaaccaac caaccacaaa ccaccctaaa atgacagccg 3120
ctgatgtctg ggcatcagcc tttgtactct gtttttttaa gaaagtgcag aatcaacttg 3180
aagcaagctt tctctcataa cgtaatgatt atatgacaat cctgaagaaa ccacaggttc 3240
catagaacta atatcctgtc tctctctctc tctctctctc tctctttttt ttttcttttt 3300
ccttttgcca tggaatctgg gtgggagagg atactgcggg caccagaatg ctaaagtttc 3360
ctaacatttt gaagtttctg tagttcatcc ttaatcctga cacccatgta aatgtccaaa 3420
atgttgatct tccactgcaa atttcaaaag ccttgtcaat ggtcaagcgt gcagcttgtt 3480
cagcggttct ttctgaggag cggacaccgg gttacattac taatgagagt tgggtagaac 3540
tctctgagat gtgttcagat agtgtaattg ctacattctc tgatgtagtt aagtatttac 3600
agatgttaaa tggagtattt ttattttatg tatatactat acaacaatgt tcttttttgt 3660
tacagctatg cactgtaaat gcagccttct tttcaaaact gctaaatttt tcttaatcaa 3720
gaatattcaa atgtaattat gaggtgaaac aattattgta cactaacata tttagaagct 3780
gaacttactg cttatatata tttgattgta aaaacaaaaa gacagtgtgt gtgtctgttg 3840
agtgcaacaa gagcaaaatg atgctttccg cacatccatc ccttaggtga gcttcaatct 3900
aagcatcttg tcaagaaata tcctagtccc ctaaaggtat taaccacttc tgcgatattt 3960
ttccacattt tcttgtcgct tgtttttctt tgaagtttta tacactggat ttgttagggg 4020
aatgaaattt tctcatctaa aatttttcta gaagatatca tgattttatg taaagtctct 4080
caatgggtaa ccattaagaa atgtttttat tttctctatc aacagtagtt ttgaaactag 4140
aagtcaaaaa tctttttaaa atgctgtttt gttttaattt ttgtgatttt aatttgatac 4200
aaaatgctga ggtaataatt atagtatgat ttttacaata attaatgtgt gtctgaagac 4260
tatctttgaa gccagtattt ctttcccttg gcagagtatg acgatggtat ttatctgtat 4320
tttttacagt tatgcatcct gtataaatac tgatatttca ttcctttgtt tactaaagag 4380
acatatttat cagttgcaga tagcctattt attataaatt atgagatgat gaaaataata 4440
aagccagtgg aaattttcta cctaggatgc atgacaattg tcaggttgga gtgtaagtgc 4500
ttcatttggg aaattcagct tttgcagaag cagtgtttct acttgcacta gcatggcctc 4560
tgacgtgacc atggtgttgt tcttgatgac attgcttctg ctaaatttaa taaaaacttc 4620
agaaaaacct ccattttgat catcaggatt tcatctgagt gtggagtccc tggaatggaa 4680
ttcagtaaca tttggagtgt gtattcaagt ttctaaattg agattcgatt actgtttggc 4740
tgacatgact tttctggaag acatgataca cctactactc aattgttctt ttcctttctc 4800
tcgcccaaca cgatcttgta agatggattt cacccccagg ccaatgcagc taattttgat 4860
agctgcattc atttatcacc agcatattgt gttctgagtg aatccactgt ttgtcctgtc 4920
ggatgcttgc ttgatttttt ggcttcttat ttctaagtag atagaaagca ataaaaatac 4980
tatgaaatga aagaacttgt tcacaggttc tgcgttacaa cagtaacaca tctttaatcc 5040
gcctaattct tgttgttctg taggttaaat gcaggtattt taactgtgtg aacgccaaac 5100
taaagtttac agtctttctt tctgaatttt gagtatcttc tgttgtagaa taataataaa 5160
aagactatta agagcaataa attattttta agaaatcgag atttagtaaa tcctattatg 5220
tgttcaagga ccacatgtgt tctctatttt gcctttaaat ttttgtgaac caattttaaa 5280
tacattctcc tttttgccct ggattgttga catgagtgga atacttggtt tcttttctta 5340
cttatcaaaa gacagcacta cagatatcat attgaggatt aatttatccc ccctaccccc 5400
agcctgacaa atattgttac catgaagata gttttcctca atggacttca aattgcatct 5460
agaattagtg gagcttttgt atcttctgca gacactgtgg gtagcccatc aaaatgtaag 5520
ctgtgctcct ctcattttta tttttatttt tttgggagag aatatttcaa atgaacacgt 5580
gcaccccatc atcactggag gcaaatttca gcatagatct gtaggatttt tagaagaccg 5640
tgggccattg ccttcatgcc gtggtaagta ccacatctac aattttggta accgaactgg 5700
tgctttagta atgtggattt ttttcttttt taaaagagat gtagcagaat aattcttcca 5760
gtgcaacaaa atcaattttt tgctaaacga ctccgagaac aacagttggg ctgtcaacat 5820
tcaaagcagc agagagggaa ctttgcacta ttggggtatg atgtttgggt cagttgataa 5880
aaggaaacct tttcatgcct ttagatgtga gcttccagta ggtaatgatt atgtgtcctt 5940
tcttgatggc tgtaatgaga acttcaatca ctgtagtcta agacctgatc tatagatgac 6000
ctagaatagc catgtactat aatgtgatga ttctaaattt gtacctatgt gacagacatt 6060
ttcaataatg tgaactgctg atttgatgga gctactttaa gatttgtagg tgaaagtgta 6120
atactgttgg ttgaactatg ctgaagaggg aaagtgagcg attagttgag cccttgccgg 6180
gccttttttc cacctgccaa ttctacatgt attgttgtgg ttttattcat tgtatgaaaa 6240
ttcctgtgat tttttttaaa tgtgcagtac acatcagcct cactgagcta ataaagggaa 6300
acgaatgttt caaatcta 6318
<210> 42
<211> 4790
<212> DNA
<213> Homo sapiens
<400> 42
ggggaagcgc agtgcgcagg cgcaactgcc tggctctgct cgctccggcg ctccggccca 60
gctctcgcgg acaagtccag acatcgcgcg cccccccttc tccgggtccg ccccctcccc 120
cttctcggcg tcgtcgaaga taaacaatag ttggccggcg agcgcctagt gtgtctcccg 180
ccgccggatt cggcgggctg cgtgggaccg gcgggatccc ggccagccgg ccatggcggg 240
gctgtactcg ctgggagtga gcgtcttctc cgaccagggc gggaggaagt acatggagga 300
cgttactcaa atcgttgtgg agcccgaacc gacggctgaa gaaaagccct cgccgcggcg 360
gtcgctgtct cagccgttgc ctccgcggcc gtcgccggcc gcccttcccg gcggcgaagt 420
ctcggggaaa ggcccagcgg tggcagcccg agaggctcgc gaccctctcc cggacgccgg 480
ggcctcgccg gcacctagcc gctgctgccg ccgccgttcc tccgtggcct ttttcgccgt 540
gtgcgacggg cacggcgggc gggaggcggc acagtttgcc cgggagcact tgtggggttt 600
catcaagaag cagaagggtt tcacctcgtc cgagccggct aaggtttgcg ctgccatccg 660
caaaggcttt ctcgcttgtc accttgccat gtggaagaaa ctggcggaat ggccaaagac 720
tatgacgggt cttcctagca catcagggac aactgccagt gtggtcatca ttcggggcat 780
gaagatgtat gtagctcacg taggtgactc aggggtggtt cttggaattc aggatgaccc 840
gaaggatgac tttgtcagag ctgtggaggt gacacaggac cataagccag aacttcccaa 900
ggaaagagaa cgaatcgaag gacttggtgg gagtgtaatg aacaagtctg gggtgaatcg 960
tgtagtttgg aaacgacctc gactcactca caatggacct gttagaagga gcacagttat 1020
tgaccagatt ccttttctgg cagtagcaag agcacttggt gatttgtgga gctatgattt 1080
cttcagtggt gaatttgtgg tgtcacctga accagacaca agtgtccaca ctcttgaccc 1140
tcagaagcac aagtatatta tattggggag tgatggactt tggaatatga ttccaccaca 1200
agatgccatc tcaatgtgcc aggaccaaga ggagaaaaaa tacctgatgg gtgagcatgg 1260
acaatcttgt gccaaaatgc ttgtgaatcg agcattgggc cgctggaggc agcgtatgct 1320
ccgagcagat aacactagtg ccatagtaat ctgcatctct ccagaagtgg acaatcaggg 1380
aaactttacc aatgaagatg agttatacct gaacctgact gacagccctt cctataatag 1440
tcaagaaacc tgtgtgatga ctccttcccc atgttctaca ccaccagtca agtcactgga 1500
ggaggatcca tggccaaggg tgaattctaa ggaccatata cctgccctgg ttcgtagcaa 1560
tgccttctca gagaattttt tagaggtttc agctgagata gctcgagaga atgtccaagg 1620
tgtagtcata ccctcaaaag atccagaacc acttgaagaa aattgcgcta aagccctgac 1680
tttaaggata catgattctt tgaataatag ccttccaatt ggccttgtgc ctactaattc 1740
aacaaacact gtcatggacc aaaaaaattt gaagatgtca actcctggcc aaatgaaagc 1800
ccaagaaatt gaaagaaccc ctccaacaaa ctttaaaagg acattagaag agtccaattc 1860
tggccccctg atgaagaagc atagacgaaa tggcttaagt cgaagtagtg gtgctcagcc 1920
tgcaagtctc cccacaacct cacagcgaaa gaactctgtt aaactcacca tgcgacgcag 1980
acttaggggc cagaagaaaa ttggaaatcc tttacttcat caacacagga aaactgtttg 2040
tgtttgctga aatgcatctg ggaaatgagg tttttccaaa cttaggatat aagagggctt 2100
tttaaatttg gtgccgatgt tgaacttttt ttaaggggag aaaattaaaa gaaatataca 2160
gtttgacttt ttggaattca gcagttttat cctggccttg tacttgcttg tattgtaaat 2220
gtggattttg tagatgttag ggtataagtt gctgtaaaat ttgtgtaaat ttgtatccac 2280
acaaattcag tctctgaata cacagtattc agagtctctg atacacagta attgtgacaa 2340
tagggctaaa tgtttaaaga aatcaaaaga atctattaga ttttagaaaa acatttaaac 2400
tttttaaaat acttattaaa aaatttgtat aagccacttg tcttgaaaac tgtgcaactt 2460
tttaaagtaa attattaagc agactggaaa agtgatgtat tttcatagtg acctgtgttt 2520
cacttaatgt ttcttagagc caagtgtctt ttaaacatta ttttttattt ctgatttcat 2580
aattcagaac taaatttttc atagaagtgt tgagccatgc tacagttagt cttgtcccaa 2640
ttaaaatact atgcagtatc tcttacatca gtagcatttt tctaaaacct tagtcatcag 2700
atatgcttac taaatcttca gcatagaagg aagtgtgttt gcctaaaaca atctaaaaca 2760
attcccttct ttttcatccc agaccaatgg cattattagg tcttaaagta gttactccct 2820
tctcgtgttt gcttaaaata tgtgaagttt tccttgctat ttcaataaca gatggtgctg 2880
ctaattccca acatttctta aattatttta tatcatacag ttttcattga ttatatgggt 2940
atatattcat ctaataaatc agtgaactgt tcctcatgtt gctgaatttg tagttgttgg 3000
tttattttaa tggtatgtac aagttgagta tcccttatcc aaaatgcttg ggaccagaag 3060
tgtttcagat tttttaaaat tttggaatat ttgctttata ctgagctttt gagtgttccc 3120
aatctgaaat tcaaaatgct ctaatgagca tttcctttga gcatcatgcc tgctctgaaa 3180
aagtttctga ttctggagca ttttggattt tggattttca gattagggat gcttaacctg 3240
gattaacatt ctgttgtgcc atgatcatgc tttacagtga gtgtatttta tttatttatt 3300
attttgtttg tttgtttgag atggagtctc actctgtcat ccaggctaga gtgcagtggc 3360
gtgatctcgg ctgactgcaa cctctgcctc ccgggttcaa gtgattctcc tgcctcaatc 3420
tctctcccca gaagctggga ttacaggtgt gtgccaccac acccggctaa tttttttttt 3480
tttttttgag atggagtcta gctctgtcat ccaggctgga gtgcagtggt gtgatctcgg 3540
ctccctgcaa cctctgcctt ctgggttcct gcgattctcc tgcctcagcc tcctgagtag 3600
ctgagattac aggcacgcgc cactgtgccc agccaatttt tgtattttta gtagagatgg 3660
ggtttcacat gtcagtcatg ctggtcttga tctcctgacc tcgtgatcca cccgcctcga 3720
cctcccaaag tactgggatt acaggcgtga gccaccgcat ccggcctgag ttttatgctt 3780
tcaatgtatt tcttacattt cagttcaagt gattttcatg tctcagcctc ctgagtagct 3840
ggaactacag gtgcgtgcca ccatgcctgg ctaagttttg tatttttagt agagatgggt 3900
tttcatcatg ttggccaaga tggtcttgat ctcttgacct catgatccac cagcctaggc 3960
ctcccaaagt gctgggatta caggtgtgag ccaccgtgcc cagccaacta tgccattatt 4020
taaccatgtc cacacattct ggttattttc aatattttgc agaagataat tcttgatcgg 4080
tgtgtcttat gccacaagga ttaaaatatg tattcattgc tacaaaacaa tatctcgaaa 4140
tttagcagtt taaaacaaca aatattatct ccagtttctg agcctcagaa atctgagagt 4200
ggtttagctg ggtgatagtc tcgtggtttt ggtcaagcta ccaaccaggg ctacaatctt 4260
tcgaaggtgt cattggggct agaagatctg cttcccgcaa gactcacagc tgttggcagg 4320
agacctcagt ttgttgccac atgttcccct ccagagggcc tctcacaaca tggcagttat 4380
ttgtccccag agcaagcaac accggagggc aaggaagaag ccatgatgtt ttttgtaacc 4440
tagcctctga aagtgtcata ccaattctgt attttgttgg tcacacagac caagtcaact 4500
acaacgtggg agactcctac acaaggcatg aattctagga ggtgggcatt tttaagtgtc 4560
atctggaagg aggctgtcac aacctggaag ttaaaagcat tgatattctg aaatacagcg 4620
tgtataacat tgttttagta gggtgtgcaa tagttatgtt ttggtaatag cattaatgaa 4680
caatgttatt ttcatcttcc agacatctgg aagattgctc tagtggagta aaacatctta 4740
atgtattttg tccctaaata aactatctca ctaacaaaaa aaaaaaaaaa 4790
<210> 43
<211> 1637
<212> DNA
<213> homo sapiens
<400> 43
agagggcccg ctcaccaccc cgtaggcccc gcccctgcgt ctctgcccgc cccgtggcgc 60
ccgagtgcac tgaagatggc ggctgctgta ggacggttgc tccgagcgtc ggttgcccga 120
catgtgagtg ccattccttg gggcatttct gccactgcag ccctcaggcc tgctgcatgt 180
ggaagaacga gcttgacaaa tttattgtgt tctggttcca gtcaagcaaa attattcagc 240
accagttcct catgccatgc acctgctgtc acccagcatg caccctattt taagggtaca 300
gccgttgtca atggagagtt caaagaccta agccttgatg actttaaggg gaaatatttg 360
gtgcttttct tctatccttt ggatttcacc tttgtgtgtc ctacagaaat tgttgctttt 420
agtgacaaag ctaacgaatt tcacgacgtg aactgtgaag ttgtcgcagt ctcagtggat 480
tcccacttta gccatcttgc ctggataaat acaccaagaa agaatggtgg tttgggccac 540
atgaacatcg cactcttgtc agacttaact aagcagattt cccgagacta cggtgtgctg 600
ttagaaggtt ctggtcttgc actaagaggt ctcttcataa ttgaccccaa tggagtcatc 660
aagcatttga gcgtcaacga tctcccagtg ggccgaagcg tggaagaaac cctccgcttg 720
gtgaaggcgt tccagtatgt agaaacacat ggagaagtct gcccagcgaa ctggacaccg 780
gattctccta cgatcaagcc aagtccagct gcttccaaag agtactttca gaaggtaaat 840
cagtagatca cccatgtgta tctgcacctt ctcaactgag agaagaacca cagttgaaac 900
ctgcttttat cattttcaag atggttattt gtagaaggca aggaaccaat tatgcttgta 960
ttcataagta ttactctaaa tgttttgttt ttgtaattct ggctaagacc ttttaaacat 1020
ggttagttgc tagtacaagg aatcctttat tggtaacatc ttggtggctg gctagctagt 1080
ttctacagaa cataatttgc ctctatagaa ggctattctt agatcatgtc tcaatggaaa 1140
cactcttctt tcttagcctt acttgaatct tgcctataat aaagtagagc aacacacatt 1200
gaaagcttct gatcaacggt cctgaaattt tcatcttgaa tgtctttgta ttaaactgaa 1260
ttttctttta agctaacaaa gatcataatt ttcaatgatt agccgtgtaa ctcctgcaat 1320
gaatgtttat gtgattgaag caaatgtgaa tcgtattatt ttaaaaagtg gcagagtgac 1380
ttaactgatc atgcatgatc cctcatccct gaaattgagt ttatgtagtc attttactta 1440
ttttattcat tagctaactt tgtctatgta tatttctaga tattgattag tgtaatcgat 1500
tataaaggat atttatcaaa tccagggatt gcattttgaa attataatta ttttctttgc 1560
tgaagtattc attgtaaaac atacaaaata aacatatttt aaaacatttg cattttacca 1620
ccaaaaaaaa aaaaaaa 1637
<210> 44
<211> 6582
<212> DNA
<213> Homo sapiens
<400> 44
agagggcaag gagagagcag agaacacact ttgccttctc tttggtattg agtaatatca 60
accaaattgc agacatctca acactttggc caggcagcct gctgagcaag gtacctcagc 120
cagcatggca gcctctttcc cacccacctt gggactcagt tctgccccag atgaaattca 180
gcacccacat attaaatttt cagaatggaa atttaagctg ttccgggtga gatcctttga 240
aaagacacct gaagaagctc aaaaggaaaa gaaggattcc tttgagggga aaccctctct 300
ggagcaatct ccagcagtcc tggacaaggc tgatggtcag aagccagtcc caactcagcc 360
attgttaaaa gcccacccta agttttcaaa gaaatttcac gacaacgaga aagcaagagg 420
caaagcgatc catcaagcca accttcgaca tctctgccgc atctgtggga attcttttag 480
agctgatgag cacaacagga gatatccagt ccatggtcct gtggatggta aaaccctagg 540
ccttttacga aagaaggaaa agagagctac ttcctggccg gacctcattg ccaaggtttt 600
ccggatcgat gtgaaggcag atgttgactc gatccacccc actgagttct gccataactg 660
ctggagcatc atgcacagga agtttagcag tgccccatgt gaggtttact tcccgaggaa 720
cgtgaccatg gagtggcacc cccacacacc atcctgtgac atctgcaaca ctgcccgtcg 780
gggactcaag aggaagagtc ttcagccaaa cttgcagctc agcaaaaaac tcaaaactgt 840
gcttgaccaa gcaagacaag cccgtcagcg caagagaaga gctcaggcaa ggatcagcag 900
caaggatgtc atgaagaaga tcgccaactg cagtaagata catcttagta ccaagctcct 960
tgcagtggac ttcccagagc actttgtgaa atccatctcc tgccagatct gtgaacacat 1020
tctggctgac cctgtggaga ccaactgtaa gcatgtcttt tgccgggtct gcattctcag 1080
atgcctcaaa gtcatgggca gctattgtcc ctcttgccga tatccatgct tccctactga 1140
cctggagagt ccagtgaagt cctttctgag cgtcttgaat tccctgatgg tgaaatgtcc 1200
agcaaaagag tgcaatgagg aggtcagttt ggaaaaatat aatcaccaca tctcaagtca 1260
caaggaatca aaagagattt ttgtgcacat taataaaggg ggccggcccc gccaacatct 1320
tctgtcgctg actcggagag ctcagaagca ccggctgagg gagctcaagc tgcaagtcaa 1380
agcctttgct gacaaagaag aaggtggaga tgtgaagtcc gtgtgcatga ccttgttcct 1440
gctggctctg agggcgagga atgagcacag gcaagctgat gagctggagg ccatcatgca 1500
gggaaagggc tctggcctgc agccagctgt ttgcttggcc atccgtgtca acaccttcct 1560
cagctgcagt cagtaccaca agatgtacag gactgtgaaa gccatcacag ggagacagat 1620
ttttcagcct ttgcatgccc ttcggaatgc tgagaaggta cttctgccag gctaccacca 1680
ctttgagtgg cagccacctc tgaagaatgt gtcttccagc actgatgttg gcattattga 1740
tgggctgtct ggactatcat cctctgtgga tgattaccca gtggacacca ttgcaaagag 1800
gttccgctat gattcagctt tggtgtctgc tttgatggac atggaagaag acatcttgga 1860
aggcatgaga tcccaagacc ttgatgatta cctgaatggc cccttcactg tggtggtgaa 1920
ggagtcttgt gatggaatgg gagacgtgag tgagaagcat gggagtgggc ctgtagttcc 1980
agaaaaggca gtccgttttt cattcacaat catgaaaatt actattgccc acagctctca 2040
gaatgtgaaa gtatttgaag aagccaaacc taactctgaa ctgtgttgca agccattgtg 2100
ccttatgctg gcagatgagt ctgaccacga gacgctgact gccatcctga gtcctctcat 2160
tgctgagagg gaggccatga agagcagtga attaatgctt gagctgggag gcattctccg 2220
gactttcaag ttcatcttca ggggcaccgg ctatgatgaa aaacttgtgc gggaagtgga 2280
aggcctcgag gcttctggct cagtctacat ttgtactctt tgtgatgcca cccgtctgga 2340
agcctctcaa aatcttgtct tccactctat aaccagaagc catgctgaga acctggaacg 2400
ttatgaggtc tggcgttcca acccttacca tgagtctgtg gaagaactgc gggatcgggt 2460
gaaaggggtc tcagctaaac ctttcattga gacagtccct tccatagatg cactccactg 2520
tgacattggc aatgcagctg agttctacaa gatcttccag ctagagatag gggaagtgta 2580
taagaatccc aatgcttcca aagaggaaag gaaaaggtgg caggccacac tggacaagca 2640
tctccggaag aagatgaacc tcaaaccaat catgaggatg aatggcaact ttgccaggaa 2700
gctcatgacc aaagagactg tggatgcagt ttgtgagtta attccttccg aggagaggca 2760
cgaggctctg agggagctga tggatcttta cctgaagatg aaaccagtat ggcgatcatc 2820
atgccctgct aaagagtgcc cagaatccct ctgccagtac agtttcaatt cacagcgttt 2880
tgctgagctc ctttctacga agttcaagta taggtatgag ggaaaaatca ccaattattt 2940
tcacaaaacc ctggcccatg ttcctgaaat tattgagagg gatggctcca ttggggcatg 3000
ggcaagtgag ggaaatgagt ctggtaacaa actgtttagg cgcttccgga aaatgaatgc 3060
caggcagtcc aaatgctatg agatggaaga tgtcctgaaa caccactggt tgtacacctc 3120
caaatacctc cagaagttta tgaatgctca taatgcatta aaaacctctg ggtttaccat 3180
gaaccctcag gcaagcttag gggacccatt aggcatagag gactctctgg aaagccaaga 3240
ttcaatggaa ttttaagtag ggcaaccact tatgagttgg tttttgcaat tgagtttccc 3300
tctgggttgc attgagggct tctcctagca ccctttactg ctgtgtatgg ggcttcacca 3360
tccaagaggt ggtaggttgg agtaagatgc tacagatgct ctcaagtcag gaatagaaac 3420
tgatgagctg attgcttgag gcttttagtg agttccgaaa agcaacagga aaaatcagtt 3480
atctgaaagc tcagtaactc agaacaggag taactgcagg ggaccagaga tgagcaaaga 3540
tctgtgtgtg ttggggagct gtcatgtaaa tcaaagccaa ggttgtcaaa gaacagccag 3600
tgaggccagg aaagaaattg gtcttgtggt tttcattttt ttcccccttg attgattata 3660
ttttgtattg agatatgata agtgccttct atttcatttt tgaataattc ttcattttta 3720
taattttaca tatcttggct tgctatataa gattcaaaag agctttttaa atttttctaa 3780
taatatctta catttgtaca gcatgatgac ctttacaaag tgctctcaat gcatttaccc 3840
attcgttata taaatatgtt acatcaggac aactttgaga aaatcagtcc ttttttatgt 3900
ttaaattatg tatctattgt aaccttcaga gtttaggagg tcatctgctg tcatggattt 3960
ttcaataatg aatttagaat acacctgtta gctacagtta gttattaaat cttctgataa 4020
tatatgttta cttagctatc agaagccaag tatgattctt tatttttact ttttcatttc 4080
aagaaattta gagtttccaa atttagagct tctgcataca gtcttaaagc cacagaggct 4140
tgtaaaaata taggttagct tgatgtctaa aaatatattt catgtcttac tgaaacattt 4200
tgccagactt tctccaaatg aaacctgaat caatttttct aaatctaggt ttcatagagt 4260
cctctcctct gcaatgtgtt attctttcta taatgatcag tttactttca gtggattcag 4320
aattgtgtag caggataacc ttgtattttt ccatccgcta agtttagatg gagtccaaac 4380
gcagtacagc agaagagtta acatttacac agtgcttttt accactgtgg aatgttttca 4440
cactcatttt tccttacaac aattctgagg agtaggtgtt gttattatct ccatttgatg 4500
ggggtttaaa tgatttgctc aaagtcattt aggggtaata aatacttggc ttggaaattt 4560
aacacagtcc ttttgtctcc aaagcccttc ttctttccac cacaaattaa tcactatgtt 4620
tataaggtag tatcagaatt tttttaggat tcacaactaa tcactatagc acatgacctt 4680
gggattacat ttttatgggg caggggtaag caagttttta aatcatttgt gtgctctggc 4740
tcttttgata gaagaaagca acacaaaagc tccaaagggc cccctaaccc tcttgtggct 4800
ccagttattt ggaaactatg atctgcatcc ttaggaatct gggatttgcc agttgctggc 4860
aatgtagagc aggcatggaa ttttatatgc tagtgagtca taatgatatg ttagtgttaa 4920
ttagtttttt cttcctttga ttttattggc cataattgct actcttcata cacagtatat 4980
caaagagctt gataatttag ttgtcaaaag tgcatcggcg acattatctt taattgtatg 5040
tatttggtgc ttcttcaggg attgaactca gtatctttca ttaaaaaaca cagcagtttt 5100
ccttgctttt tatatgcaga atatcaaagt catttctaat ttagttgtca aaaacatata 5160
catattttaa cattagtttt tttgaaaact cttggttttg tttttttgga aatgagtggg 5220
ccactaagcc acactttccc ttcatcctgc ttaatccttc cagcatgtct ctgcactaat 5280
aaacagctaa attcacataa tcatcctatt tactgaagca tggtcatgct ggtttataga 5340
ttttttaccc atttctactc tttttctcta ttggtggcac tgtaaatact ttccagtatt 5400
aaattatcct tttctaacac tgtaggaact attttgaatg catgtgacta agagcatgat 5460
ttatagcaca acctttccaa taatccctta atcagatcac attttgataa accctgggaa 5520
catctggctg caggaatttc aatatgtaga aacgctgcct atggtttttt gcccttactg 5580
ttgagactgc aatatcctag accctagttt tatactagag ttttattttt agcaatgcct 5640
attgcaagtg caattatata ctccagggaa attcaccaca ctgaatcgag catttgtgtg 5700
tgtatgtgtg aagtatatac tgggacttca gaagtgcaat gtatttttct cctgtgaaac 5760
ctgaatctac aagttttcct gccaagccac tcaggtgcat tgcagggacc agtgataatg 5820
gctgatgaaa attgatgatt ggtcagtgag gtcaaaagga gccttgggat taataaacat 5880
gcactgagaa gcaagaggag gagaaaaaga tgtctttttc ttccaggtga actggaattt 5940
agttttgcct cagatttttt tcccacaaga tacagaagaa gataaagatt tttttggttg 6000
agagtgtggg tcttgcatta catcaaacag agttcaaatt ccacacagat aagaggcagg 6060
atatataagc gccagtggta gttgggagga ataaaccatt atttggatgc aggtggtttt 6120
tgattgcaaa tatgtgtgtg tcttcagtga ttgtatgaca gatgatgtat tcttttgatg 6180
ttaaaagatt ttaagtaaga gtagatacat tgtacccatt ttacattttc ttattttaac 6240
tacagtaatc tacataaata tacctcagaa atcatttttg gtgattattt tttgttttgt 6300
agaattgcac ttcagtttat tttcttacaa ataaccttac attttgttta atggcttcca 6360
agagcctttt ttttttttgt atttcagaga aaattcaggt accaggatgc aatggattta 6420
tttgattcag gggacctgtg tttccatgtc aaatgttttc aaataaaatg aaatatgagt 6480
ttcaatactt tttatatttt aatatttcca ttcattaata ttatggttat tgtcagcaat 6540
tttatgtttg aatatttgaa ataaaagttt aagatttgaa aa 6582
<210> 45
<211> 2457
<212> DNA
<213> Homo sapiens
<400> 45
attagatcag tgttcataag aacatctgta ggcacacata cacactctct ttacagtcag 60
ccttctgctt gccacagtca tagtgggcag tcagtgaatc ttccccaagt gctgacaatt 120
aatacctggt ttagcggcaa agattcagag aggcgtgagc agcccctctg gccttcagac 180
aaaaatctac gtaccatcag aaactatgtc tctgcagatg gtaacagtca gtaataacat 240
agccttaatt cagccaggct tctcactgat gaattttgat ggacaagttt tcttctttgg 300
acaaaaaggc tggcccaaaa gatcctgccc cactggagtt ttccatctgg atgtaaagca 360
taaccatgtc aaactgaagc ctacaatttt ctctaaggat tcctgctacc tccctcctct 420
tcgctaccca gccacttgca cattcaaagg cagcttggag tctgaaaagc atcaatacat 480
catccatgga gggaaaacac caaacaatga ggtttcagat aagatttatg tcatgtctat 540
tgtttgcaag aacaacaaaa aggttacttt tcgctgcaca gagaaagact tggtaggaga 600
tgttcctgaa gccagatatg gtcattccat taatgtggtg tacagccgag ggaaaagtat 660
gggtgttctc tttggaggac gctcatacat gccttctacc cacagaacca cagaaaaatg 720
gaatagtgta gctgactgcc tgccctgtgt tttcctggtg gattttgaat ttgggtgtgc 780
tacatcatac attcttccag aacttcagga tgggctatct tttcatgtct ctattgccaa 840
aaatgacacc atctatattt taggaggaca ttcacttgcc aataatatcc ggcctgccaa 900
cctgtacaga ataagggttg atcttcccct gggtagccca gctgtgaatt gcacagtctt 960
gccaggagga atctctgtct ccagtgcaat cctgactcaa actaacaatg atgaatttgt 1020
tattgttggt ggctatcagc ttgaaaatca aaaaagaatg atctgcaaca tcatctcttt 1080
agaggacaac aagatagaaa ttcgtgagat ggagacccca gattggaccc cagacattaa 1140
gcacagcaag atatggtttg gaagcaacat gggaaatgga actgtttttc ttggcatacc 1200
aggagacaat aaacaagttg tttcagaagg attctatttc tatatgttga aatgtgctga 1260
agatgatact aatgaagagc agacaacatt cacaaacagt caaacatcaa cagaagatcc 1320
aggggattcc actccctttg aagactctga agaattttgt ttcagtgcag aagcaaatag 1380
ttttgatggt gatgatgaat ttgacaccta taatgaagat gatgaagaag atgagtctga 1440
gacaggctac tggattacat gctgccctac ttgtgatgtg gatatcaaca cttgggtacc 1500
attctattca actgagctca acaaacccgc catgatctac tgctctcatg gggatgggca 1560
ctgggtccat gctcagtgca tggatctggc agaacgcaca ctcatccatc tgtcagcagg 1620
aagcaacaag tattactgca atgagcatgt ggagatagca agagctctac acactcccca 1680
aagagtccta cccttaaaaa agcctccaat gaaatccctc cgtaaaaaag gttctggaaa 1740
aatcttgact cctgccaaga aatcctttct tagaaggttg tttgattagt tttgcaaaag 1800
cctttcagat tcaggtgtat ggaatttttg aatctatttt taaaatcata acattgattt 1860
taaaaataca tttttgttta tttaaaatgc ctatgttttc ttttagttac atgaattaag 1920
ggccagaaaa aagtgtttat aatgcaatga taaataaagt cattctagac cctatacatt 1980
ttgaaaatat tttacccaaa tactcaattt actaatttat tcttcactga ggatttctga 2040
tctgattttt tattcaacaa accttaaaca cccagaagca gtaataatca tcgaggtatg 2100
tttatattta ttatataagt cttggtaaca aataacctat aaagtgttta tgacaaattt 2160
agccaataaa gaaattaaca cccaaaagaa ttaaattgat tattttgtgc aacataacaa 2220
ttcggcagtt ggccaaaact taaaagcaag atctactaca tcccacatta gtgttcttta 2280
tataccttca agcaaccctt tggattatgc ccatgaacaa gttagtttct catagcttta 2340
cagatgtaga tataaatata aatatatgta tacatataga tagataatgt tctccactga 2400
cacaaaagaa gaaataaata atctacatca aaaaaaaaaa aaaaaaaaaa aaaaaaa 2457
<210> 46
<211> 4903
<212> DNA
<213> Homo sapiens
<400> 46
gtcgtttgcg gcggcgcagg cgcggtgcgg gcggcggacg ggcgggcgct tcgccgtttg 60
aatggctgcg ggcccgggcc ctcacctcac ctgaggtccg gccgcccagg ggtgcgctat 120
gccgtcggga ggtgaccagt cgccaccgcc cccgcctccc cctccggcgg cggcagcctc 180
ggatgaggag gaggaggacg acggcgaggc ggaagacgcc gcgccgcctg ccgagtcgcc 240
cacccctcag atccagcagc ggttcgacga gctgtgcagc cgcctcaaca tggacgaggc 300
ggcgcgggcc gaggcctggg acagctaccg cagcatgagc gaaagctaca cgctggaggg 360
aaatgatctt cattggttag catgtgcctt atatgtggct tgcagaaaat ctgttccaac 420
tgtaagcaaa gggacagtgg aaggaaacta tgtatcttta actagaatcc tgaaatgttc 480
agagcagagc ttaatcgaat tttttaataa gatgaagaag tgggaagaca tggcaaatct 540
acccccacat ttcagagaac gtactgagag attagaaaga aacttcactg tttctgctgt 600
aatttttaag aaatatgaac ccatttttca ggacatcttt aaataccctc aagaggagca 660
acctcgtcag cagcgaggaa ggaaacagcg gcgacagccc tgtactgtgt ctgaaatttt 720
ccatttttgt tgggtgcttt ttatatatgc aaaaggtaat ttccccatga ttagtgatga 780
tttggtcaat tcttatcacc tgctgctgtg tgctttggac ttagtttatg gaaatgcact 840
tcagtgttct aatcgtaaag aacttgtgaa ccctaatttt aaaggcttat ctgaagattt 900
tcatgctaaa gattctaaac cttcctctga ccccccttgt atcattgaga aactgtgttc 960
cttacatgat ggcctagttt tggaagcaaa ggggataaag gaacatttct ggaaacccta 1020
tattaggaaa ctttatgaaa aaaagctcct taagggaaaa gaagaaaatc tcactgggtt 1080
tctagaacct gggaactttg gagagagttt taaagccatc aataaggcct atgaggagta 1140
tgttttatct gttgggaatt tagatgagcg gatatttctt ggagaggatg ctgaggagga 1200
aattgggact ctctcaaggt gtctgaacgc tggttcagga acagagactg ctgaaagggt 1260
gcagatgaaa aacatcttac agcagcattt tgacaagtcc aaagcactta gaatctccac 1320
accactaact ggtgttaggt acattaagga gaatagccct tgtgtgactc cagtttctac 1380
agctacgcat agcttgagtc gtcttcacac catgctgaca ggcctcagga atgcaccaag 1440
tgagaaactg gaacagattc tcaggacatg ttccagagat ccaacccagg ctattgctaa 1500
cagactgaaa gaaatgtttg aaatatattc tcagcatttc cagccagacg aggatttcag 1560
taattgtgct aaagaaattg ccagcaaaca ttttcgtttt gcggagatgc tttactataa 1620
agtattagaa tctgttattg agcaggaaca aaaaagacta ggagacatgg atttatctgg 1680
tattctggaa caagatgcgt tccacagatc tctcttggcc tgctgccttg aggtcgtcac 1740
tttttcttat aagcctcctg ggaattttcc atttattact gaaatatttg atgtgcctct 1800
ttatcatttt tataaggtga tagaagtatt cattagagca gaagatggcc tttgtagaga 1860
ggtggtaaaa caccttaatc agattgaaga acagatctta gatcatttgg catggaaacc 1920
agagtctcca ctctgggaaa aaattagaga caatgaaaac agagttccta catgtgaaga 1980
ggtcatgcca cctcagaacc tggaaagggc agatgaaatt tgcattgctg gctccccttt 2040
gactcccaga agggtgactg aagttcgtgc tgatactgga ggacttggaa ggagcataac 2100
atctccaacc acattatacg ataggtacag ctccccacca gccagcacta ccagaaggcg 2160
gctatttgtt gagaatgata gcccctctga tggagggacg cctgggcgca tgcccccaca 2220
gcccctagtc aatgctgtcc ctgtgcagaa tgtatctggg gagactgttt ctgtcacacc 2280
agttcctgga cagactttgg tcaccatggc aaccgccact gtcacagcca acaatgggca 2340
aacggtaacc attcctgtgc aaggtattgc caatgaaaat ggagggataa cattcttccc 2400
tgtccaagtc aatgttgggg ggcaggcaca agctgtgaca ggctccatcc agcccctcag 2460
tgctcaggcc ctggctggaa gtctgagctc tcaacaggtg acaggaacaa ctttgcaagt 2520
ccctggtcaa gtggccattc aacagatttc cccaggtggc caacagcaga agcaaggcca 2580
gtctgtaacc agcagtagta atagacccag gaagaccagc tctttatcgc ttttctttag 2640
aaaggtatac catttagcag ctgtccgcct tcgggatctc tgtgccaaac tagatatttc 2700
agatgaattg aggaaaaaaa tctggacctg ctttgaattc tccataattc agtgtcctga 2760
acttatgatg gacagacatc tggaccagtt attaatgtgt gccatttatg tgatggcaaa 2820
ggtcacaaaa gaagataagt ccttccagaa cattatgcgt tgttatagga ctcagccgca 2880
ggcccggagc caggtgtata gaagtgtttt gataaaaggg aaaagaaaaa gaagaaattc 2940
tggcagcagt gatagcagaa gccatcagaa ttctccaaca gaactaaaca aagatagaac 3000
cagtagagac tccagtccag ttatgaggtc aagcagcacc ttgccagttc cacagcccag 3060
cagtgctcct cccacaccta ctcgcctcac aggtgccaac agtgacatgg aagaagagga 3120
gaggggagac ctcattcagt tctacaacaa catctacatc aaacagatta agacatttgc 3180
catgaagtac tcacaggcaa atatggatgc tcctccactc tctccctatc catttgtaag 3240
aacaggctcc cctcgccgaa tacagttgtc tcaaaatcat cctgtctaca tttccccaca 3300
taaaaatgaa acaatgcttt ctcctcgaga aaagattttc tattacttca gcaacagtcc 3360
ttcaaagaga ctgagagaaa ttaatagtat gatacgcaca ggagaaactc ctactaaaaa 3420
gagaggaatt cttttggaag atggaagtga atcacctgca aaaagaattt gcccagaaaa 3480
tcattctgcc ttattacgcc gtctccaaga tgtagctaat gaccgtggtt cccactgagg 3540
ttagtctctt gtattaaact cttcacaaaa tctgtttagc agcagccttt aatgcatcta 3600
gattatggag cttttttcct taatccagct gatgagttac agcctgttag taacatgagg 3660
ggacattttg gtgagaaatg ggacttaact ccttccagtg tccttagaac attttaattc 3720
atcccaactg tctttttttc cctaccattc agtgattact gtcaaggctg cttagaatcc 3780
aaacttggat ttttgactct ggcaaagctt ttagaaatac tgcaagaaaa tgatgtgtac 3840
ccaaacgtga gcataggagg cttctgttga cgtactccaa cagaagaact gtgtttcaag 3900
ttcaatccta cctgttttgt ggtcagctgt agtcctcata aaaagcaaaa caaaaattag 3960
gtattttgtc ctaaaacacc tggtaggagt gtgtgatttt ttgcattcct gacaaaggag 4020
agcacaccca ggtttggagg tcctaggtca ttagccctcg tctcccgttc cctttgtgca 4080
catcttccct ctccccattc ggtgtggtgc agtgtgaaaa gtccttgatt gttcgggtgt 4140
gcaatgtctg agtgaacctg tataagtgga ggcactttag ggctgtaaaa tgcatgattt 4200
tgtaacccag attttgctgt atatttgtga tagcactttc tacaatgtga actttattaa 4260
atacaaaact tccaggctaa acatccaata ttttctttaa tgcttttata tttttttaaa 4320
atgttaaaac ccctatagcc accttttggg aatgttttaa attctccagt tttttgttat 4380
atagggatca accagctaag aaaagatttt aatcaagttg aattgagggg attaatatga 4440
aaacttatga cctcttcctt taggagggag ttatctaaaa gaaatgtcta ttaaggtgat 4500
atatttaaaa atatttttgg gtgttcctgg cagtttaaaa aaattggttg gagaatttag 4560
gtttttatta gtaccatagt accatttata caaattagaa aatgttattt aacagctgaa 4620
ttatctatac atatctttat taatcactat tgttccagca gttttcaagt caaattaata 4680
atcttattag ggagaaaatt caattgtaaa ttgaatcagt ataaacaaag ttactaggta 4740
acttcatatt gctgagagaa atatggaact tacattgttc aattagaata gtgttctgca 4800
aaaatattta taaaacttct caagatactg ctactgtaat tttatatgaa gataagtgta 4860
tttttcaata aagcatttat aaattaaaaa aaaaaaaaaa aaa 4903
<210> 47
<211> 5189
<212> DNA
<213> Homo sapiens
<400> 47
ggactgcgaa aggagcaggg ttgcggagct agggctccag cctgcggccg cgcattcttg 60
cgtctggcca gccgcgagct ctaagggtcg gccccgcccg gtccgccccc gcggctccct 120
gccaggctct cgcgggcgcg ctcggggtgg ggcctcgcgg ctggcggaga tgcggccggg 180
gctgcgcggt ggtgatgcga gcctgctggg cggcgcgccg gggcagccgg agccgcgcgc 240
cgcggcgctg taatcggaca ccaagagcgc tcgcccccgg cctccggcca ctttccattc 300
actccgaggt gcttgattga gcgacgcgga gaagagctcc gggtgccgcg gcactgcagc 360
gctgagattc ctttacaaag aaactcagag gaccgggaag aaagaatttc acctttgcga 420
cgtgctagaa aataaggtcg tctgggaaaa ggactggaga cacaagcgca tccaaccccg 480
gtagcaaact gatgactttt ccgtgctgat ttctttcaac ctcggtattt tcccttggat 540
attaacttgc atatctgaag aaatggcatt ccggacaatt tgcgtgttgg ttggagtatt 600
tatttgttct atctgtgtga aaggatcttc ccagccccaa gcaagagttt atttaacatt 660
tgatgaactt cgagaaacca agacctctga atacttcagc ctttcccacc atcctttaga 720
ctacaggatt ttattaatgg atgaagatca ggaccggata tatgtgggaa gcaaagatca 780
cattctttcc ctgaatatta acaatataag tcaagaagct ttgagtgttt tctggccagc 840
atctacaatc aaagttgaag aatgcaaaat ggctggcaaa gatcccacac acggctgtgg 900
gaactttgtc cgtgtaattc agactttcaa tcgcacacat ttgtatgtct gtgggagtgg 960
cgctttcagt cctgtctgta cttacttgaa cagagggagg agatcagagg accaagtttt 1020
catgattgac tccaagtgtg aatctggaaa aggacgctgc tctttcaacc ccaacgtgaa 1080
cacggtgtct gttatgatca atgaggagct tttctctgga atgtatatag atttcatggg 1140
gacagatgct gctatttttc gaagtttaac caagaggaat gcggtcagaa ctgatcaaca 1200
taattccaaa tggctaagtg aacctatgtt tgtagatgca catgtcatcc cagatggtac 1260
tgatccaaat gatgctaagg tgtacttctt cttcaaagaa aaactgactg acaataacag 1320
gagcacgaaa cagattcatt ccatgattgc tcgaatatgt cctaatgaca ctggtggact 1380
gcgtagcctt gtcaacaagt ggaccacttt cttaaaggcg aggctggtgt gctcggtaac 1440
agatgaagac ggcccagaaa cacactttga tgaattagag gatgtgtttc tgctggaaac 1500
tgataacccg aggacaacac tagtgtatgg catttttaca acatcaagct cagttttcaa 1560
aggatcagcc gtgtgtgtgt atcatttatc tgatatacag actgtgttta atgggccttt 1620
tgcccacaaa gaagggccca atcatcagct gatttcctat cagggcagaa ttccatatcc 1680
tcgccctgga acttgtccag gaggagcatt tacacccaat atgcgaacca ccaaggagtt 1740
cccagatgat gttgtcactt ttattcggaa ccatcctctc atgtacaatt ccatctaccc 1800
aatccacaaa aggcctttga ttgttcgtat tggcactgac tacaagtata caaagatagc 1860
tgtggatcga gtgaacgctg ctgatgggag ataccatgtc ctgtttctcg gaacagatcg 1920
gggtactgtg caaaaagtgg ttgttcttcc tactaacaac tctgtcagtg gcgagctcat 1980
tctggaggag ctggaagtct ttaagaatca tgctcctata acaacaatga aaatttcatc 2040
taaaaagcaa cagttgtatg tgagttccaa tgaaggggtt tcccaggtat ctctgcaccg 2100
ctgccacatc tatggtacag cctgtgctga ctgctgcctg gcgcgggacc cttattgcgc 2160
ctgggatggc cattcctgtt ccagattcta cccaactggg aaacggagga gccgaagaca 2220
agatgtgaga catggaaacc cactgactca atgcagagga tttaatctaa aagcatacag 2280
aaatgcagct gaaattgtcc agtatggagt aaaaaataac accacttttc tggagtgtgc 2340
ccccaagtct ccgcaggcat ctatcaagtg gctgttacag aaagacaaag acaggaggaa 2400
agaggttaag ctgaatgaac gaataatagc cacttcacag ggactcctga tccgctctgt 2460
tcagggttct gaccaaggac tttatcactg cattgctaca gaaaatagtt tcaagcagac 2520
catagccaag atcaacttca aagttttaga ttcagaaatg gtggctgttg tgacggacaa 2580
atggtcccca tggacctggg ccagctctgt gagggcttta cccttccacc cgaaggacat 2640
catgggggca ttcagccact cagaaatgca gatgattaac caatattgca aagacactcg 2700
gcagcaacat cagcagggag atgaatcaca gaaaatgaga ggggactatg gcaagttaaa 2760
ggccctcatc aatagtcgga aaagtagaaa caggaggaat cagttgccag agtcataata 2820
ttttcttatg tgggtcttat gcttccatta acaaatgctc tgtcttcaat gatcaaattt 2880
tgagcaaaga aacttgtgct ttaccaaggg gaattactga aaaaggtgat tactcctgaa 2940
gtgagtttta cacgaactga aatgagcatg cattttcttg tatgatagtg actagcacta 3000
gacatgtcat ggtcctcatg gtgcatataa atatatttaa cttaacccag attttattta 3060
tatctttatt caccttttct tcaaaatcga tatggtggct gcaaaactag aattgttgca 3120
tccctcaatt gaatgagggc catatccctg tggtattcct ttcctgcttt ggggctttag 3180
aattctaatt gtcagtgatt ttgtatatga aaacaagttc caaatccaca gcttttacgt 3240
agtaaaagtc ataaatgcat atgacagaat ggctatcaaa agaaatagaa aaggaagaca 3300
gcatttaaag ttgtataaaa acatgagtta ttcataaaga gaaaatgatg agtttttatg 3360
gttccaatga aatatgttgg ggttttttta agattgtaaa aataatcagt tactggtatc 3420
tgtcactgac ctttgtttcc ttattcagga agataaaaat cagtaaccta ccccatgaag 3480
atatttggtg ggagttatat cagtgaagca gtttggttta tattcttatg ttatcacctt 3540
ccaaacaaaa gcacttactt tttttggaag ttatttattt tagactcaaa gaatataatc 3600
tggcactact cagttattac tgtttgttct cttattccct agtctgtgtg gcaaattaaa 3660
caatataaga aggaaaaatt tgaagtatta gacttctaaa taaggtgtga aatcatcaaa 3720
aagaaaaatc aaagtagaaa ctactaattt tttaagagga atttataaca aatatggcta 3780
gttttcaact tcagtactca aattcaatga ttcttccttt tattaaaacc agtctcagat 3840
atcatactga tttttaagtc aacactatat attttatgat cttttcagtg tgatggcaag 3900
gtgcttgtta tgtctagaaa gtaagaaaac aatatgagga gacattctgt ctttcaaaag 3960
gtaatggtac atacgttcac tggtctctaa gtgtaaaagt agtaaatttt gtgatgaata 4020
aaataattat ctcctaattg tatgttagaa taattttatt agaataattt catactgaaa 4080
ttattttctc caaataaaaa ttagatggaa aaatgtgaaa aaaattattc atgctctcat 4140
atatatttta aaaacactac ttttgctttt ttatttacct tttaagacat tttcatgctt 4200
ccaggtaaaa acagatattg taccatgtac ctaatccaaa tatcatataa acattttatt 4260
tatagttaat aatctatgat gaaggtaatt aaagtagatt atggcctttt taagtattgc 4320
agtctaaaac ttcaaaaact aaaatcattg tcaaaattaa tatgattatt aatcagaata 4380
tcagaatatg attcactatt taaactatga taaattatga taatatatga ggaggcctcg 4440
ctatagcaaa aatagttaaa atgctgacat aacaccaaac ttcatttttt aaaaaatctg 4500
ttgttccaaa tgtgtataat tttaaagtaa tttctaaagc agtttattat aatggtttgc 4560
ctgcttaaaa ggtataatta aacttctttt ctcttctaca ttgacacaca gaaatgtgtc 4620
aatgtaaagc caaaaccatc ttctgtgttt atggccaatc tattctcaaa gttaaaagta 4680
aaattgtttc agagtcacag ttccctttat ttcacataag cccaaactga tagacagtaa 4740
cggtgtttag ttttatacta tatttgtgct atttaattct ttctattttc acaattatta 4800
aattgtgtac actttcatta cttttaaaaa tgtagaaatt cttcatgaac ataactctgc 4860
tgaatgtaaa agaaaatttt ttttcaaaaa tgctgttaat gtatactact ggtggttgat 4920
tggttttatt ttatgtagct tgacaattca gtgacttaat atctattcca tttgtattgt 4980
acataaaatt ttctagaaat acactttttt ccaaagtgta agtttgtgaa tagattttag 5040
catgatgaaa ctgtcataat ggtgaatgtt caatctgtgt aagaaaacaa actaaatgta 5100
gttgtcacac taaaatttaa ttggatattg atgaaatcat tggcctggca aaataaaaca 5160
tgttgaattc cccaaaaaaa aaaaaaaaa 5189
<210> 48
<211> 2164
<212> DNA
<213> Homo sapiens
<400> 48
ataaatatca gagtgtgctg ctgtggcttt gtggagctgc cagagtaaag caaagagaaa 60
ggaagcaggc ccgttggaag tggttgtgac aaccccagca atgtggagaa gcctggggct 120
tgccctggct ctctgtctcc tcccatcggg aggaacagag agccaggacc aaagctcctt 180
atgtaagcaa cccccagcct ggagcataag agatcaagat ccaatgctaa actccaatgg 240
ttcagtgact gtggttgctc ttcttcaagc cagctgatac ctgtgcatac tgcaggcatc 300
taaattagaa gacctgcgag taaaactgaa gaaagaagga tattctaata tttcttatat 360
tgttgttaat catcaaggaa tctcttctcg attaaaatac acacatctta agaataaggt 420
ttcagagcat attcctgttt atcaacaaga agaaaaccaa acagatgtct ggactctttt 480
aaatggaagc aaagatgact tcctcatata tgatagatgt ggccgtcttg tatatcatct 540
tggtttgcct ttttccttcc taactttccc atatgtagaa gaagccatta agattgctta 600
ctgtgaaaag aaatgtggaa actgctctct cacgactctc aaagatgaag acttttgtaa 660
acgtgtatct ttggctactg tggataaaac agttgaaact ccatcgcctc attaccatca 720
tgagcatcat cacaatcatg gacatcagca ccttggcagc agtgagcttt cagagaatca 780
gcaaccagga gcaccaaatg ctcctactca tcctgctcct ccaggccttc atcaccacca 840
taagcacaag ggtcagcata ggcagggtca cccagagaac cgagatatgc cagcaagtga 900
agatttacaa gatttacaaa agaagctctg tcgaaagaga tgtataaatc aattactctg 960
taaattgccc acagattcag agttggctcc taggagctga tgctgccatt gtcgacatct 1020
gatatttgaa aaaacagggt ctgcaatcac ctgacagtgt aaagaaaacc tcccatcttt 1080
atgtagctga cagggacttc gggcagagga gaacataact gaatcttgtc agtgacgttt 1140
gcctccagct gcctgacaaa taagtcagca gcttataccc acagaagcca gtgccagttg 1200
acgctgaaag aatcaggcaa aaaagtgaga atgaccttca aactaaatat ttaaaatagg 1260
acatactccc caatttagtc tagacacaat ttcatttcca gcatttttat aaactaccaa 1320
attagtgaac caaaaataga aattagattt gtgcaaacat ggagaaatct actgaattgg 1380
cttccagatt ttaaatttta tgtcatagaa atattgactc aaaccatatt ttttatgatg 1440
gagcaactga aaggtgattg cagcttttgg ttaatatgtc tttttttttc tttttccagt 1500
gttctatttg ctttaatgag aatagaaacg taaactatga cctaggggtt tctgttggat 1560
aattagcagt ttagaatgga ggaagaacaa caaagacatg ctttccattt ttttctttac 1620
ttatctctca aaacaatatt actttgtctt ttcaatcttc tacttttaac taataaaata 1680
agtggatttt gtattttaag atccagaaat acttaacacg tgaatatttt gctaaaaaag 1740
catatataac tattttaaat atccatttat cttttgtata tctaagactc atcctgattt 1800
ttactatcac acatgaataa agcctttgta tctttctttc tctaatgttg tatcatactc 1860
ttctaaaact tgagtggctg tcttaaaaga tataagggga aagataatat tgtctgtctc 1920
tatattgctt agtaagtatt tccatagtca atgatggttt aataggtaaa ccaaacccta 1980
taaacctgac ctcctttatg gttaatacta ttaagcaaga atgcagtaca gaattggata 2040
cagtacggat ttgtccaaat aaattcaata aaaaccttaa agctgaaaaa aaaaaaaaaa 2100
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2160
aaaa 2164
<210> 49
<211> 3212
<212> DNA
<213> Homo sapiens
<400> 49
gaacccggtg gctgcacaga caaaaaagcc ccgaatggct ggagggcgtt cagctgttaa 60
cagccttttg gggcagagca cggatttgac agctccacaa cgtgaggata tccactgacc 120
ccgcgagacg gaggagaacg cttccccgaa attctctgcc caccaaagcc agcgctgcaa 180
ggttgcaact ttcaaacttt gtttttccag aaagaagact gccctttcgt gtacaaggag 240
agggtgagag ggtgacctag cttgtagatc ggctgaaggc accagtggtt ccaaatgtca 300
cccagatgtg tgttttcatg acgatttgat ttctctgatt ttatttttac atttttcatt 360
ttaaaaatac aaagcaattt ttttggggca tgctgaaagg taactgaaga ccgcaaagga 420
aaaactattg tcatggctga aggagagaat gaagtgagat gggatggact ctgcagcaga 480
gattcaacta ctagggagac agcattggaa aacattaggc aaaccatttt gaggaaaacc 540
gagtatcttc gttcggtgaa agaaacacct catcgtccat cagacgggct ttcaaatacc 600
gagtcttcgg atgggttgaa taagctactt gctcatctgc ttatgctttc taagaggtgt 660
cccttcaaag atgtgagaga gaaaagtgag tttattctga agagcatcca ggaacttggc 720
attagaattc ctcgaccact aggacaggga ccaagcagat tcatcccaga aaaggagatc 780
ctccaagtgg ggagtgaaga cgcacagatg catgctttat ttgcagattc ttttgctgct 840
ttgggccgtt tggataacat tacgttagtg atggttttcc acccacaata tttagaaagt 900
ttcttaaaaa ctcagcacta tctactgcaa atggatgggc cgttacccct acattatcgt 960
cactacattg gaataatggc tgcggcaaga catcagtgct cctacttagt gaacctgcat 1020
gtaaatgatt tccttcatgt tggtggggac cccaagtggc tcaatggttt agagaatgct 1080
cctcaaaaac tacagaattt aggagaactt aacaaagtgt tagcccatag accttggctt 1140
attaccaaag aacacattga gggactttta aaagctgaag agcacagctg gtcccttgcg 1200
gaattggtac atgcagtagt tttactcaca cactatcatt ctcttgcctc attcacattc 1260
ggctgtggaa tcagtccaga aattcattgt gatggtggcc acacattcag acctccttct 1320
gttagcaact actgcatctg tgacattaca aatggcaatc acagtgtgga tgagatgccg 1380
gtcaactcag cagaaaatgt ttctgtaagt gattctttct ttgaggttga agccctcatg 1440
gaaaagatga ggcagttaca ggaatgtcga gatgaagaag aggcaagtca ggaagagatg 1500
gcttcacgtt ttgaaataga aaaaagagag agtatgtttg tcttctcttc agatgatgaa 1560
gaagttacac cagcaagagc tgtatctcgt cattttgagg atactagtta tggctataaa 1620
gatttctcta gacatgggat gcatgttcca acatttcgtg tccaggacta ttgctgggaa 1680
gatcatggtt attctttggt aaatcgcctt tatccagatg tgggacagtt gattgatgaa 1740
aaatttcaca ttgcttacaa tcttacttat aatacaatgg caatgcacaa agatgttgat 1800
acctcaatgc ttagacgggc aatttggaac tatattcact gcatgtttgg aataagatat 1860
gatgattatg actatggtga aattaaccag ctattggatc gtagctttaa agtttatatc 1920
aaaactgttg tttgcactcc tgaaaaggtt accaaaagaa tgtatgatag cttctggagg 1980
cagttcaagc actctgagaa ggttcatgtt aatctgcttc ttatagaagc taggatgcaa 2040
gcagaactcc tttatgctct gagagccatt acccgctata tgacctgatg cctttccttc 2100
attaaagatg attctggaat gatcagcaga tatagtctac aagggggaag gtactaagcc 2160
ccaggaccaa tggtagacaa aataattcag aaatccattg tgccatgatt cctttagttt 2220
ctgctatttt tctgtggaaa accactgctg gcacaagcag tgactgtttg gcagcttcaa 2280
gtttagagct gtgaagacag gctgccattc acagtatttt gctttttgac agtacaagat 2340
gctgtgtaac tgttttaata cagcaaatag taactctcca aatcctgttg cttttatgtt 2400
aaataagata acaagaattg gagcatgcaa agaatgggac ttggataatg acttaagctt 2460
tatatgtaaa gaattttaga agatcttggt gctgctattc ctgctggagg aatgaataga 2520
tggctgtttc agttaagcta ttagtaataa aagtgaacat tgctactatc tgagcctaca 2580
tacataactt gtgtgatttc aaattaaact tgcattatgt gttaattttc ttgcatctaa 2640
aaaagcatag aattcctact cacacagctc agcaacaacc attttgatgg taacagttaa 2700
tttctttcat tagtttttta aattcagggt tctggatatt aaattaaaat ggcattctta 2760
aagattttct tcaaaaagca atcctaaatg aaagtgtgta aattataaga agctggcgat 2820
cttttgatat gctgtttcac aggatcctga cactggaggg cagctgtctt gtgcattact 2880
tgtgtttcca gcaccaaagt tgtgggacat gttgctgtag actgctgcgc agtcctgggt 2940
gcattcagtc tctctgcctc tgcctgcctc ctggtcccca ctttaaaggc tgtgcagctc 3000
cttaaataat aaagctggaa aatattttta gtcgggttat caaatttgat ttacaaaaac 3060
gctaactttg tttgaaatgc aaacaggttt gaaaatatgt attaagtact ttgtattctg 3120
gaagcgtgaa ttgcttttga agtctgtcag tattactggt atttttaaat aaagaagaat 3180
ttttctccaa ttttaaaaaa aaaaaaaaaa aa 3212
<210> 50
<211> 4086
<212> DNA
<213> Homo sapiens
<400> 50
gtcgagcggg agcagaggag gcgagggagg agggccagag aggcagttgg aagatggcgg 60
acgaggcggc cctcgccctt cagcccggcg gctccccctc ggcggcgggg gccgacaggg 120
aggccgcgtc gtcccccgcc ggggagccgc tccgcaagag gccgcggaga gatggtcccg 180
gcctcgagcg gagcccgggc gagcccggtg gggcggcccc agagcgtgag gtgccggcgg 240
cggccagggg ctgcccgggt gcggcggcgg cggcgctgtg gcgggaggcg gaggcagagg 300
cggcggcggc aggcggggag caagaggccc aggcgactgc ggcggctggg gaaggagaca 360
atgggccggg cctgcagggc ccatctcggg agccaccgct ggccgacaac ttgtacgacg 420
aagacgacga cgacgagggc gaggaggagg aagaggcggc ggcggcggcg attgggtacc 480
gagataacct tctgttcggt gatgaaatta tcactaatgg ttttcattcc tgtgaaagtg 540
atgaggagga tagagcctca catgcaagct ctagtgactg gactccaagg ccacggatag 600
gtccatatac ttttgttcag caacatctta tgattggcac agatcctcga acaattctta 660
aagatttatt gccggaaaca atacctccac ctgagttgga tgatatgaca ctgtggcaga 720
ttgttattaa tatcctttca gaaccaccaa aaaggaaaaa aagaaaagat attaatacaa 780
ttgaagatgc tgtgaaatta ctgcaagagt gcaaaaaaat tatagttcta actggagctg 840
gggtgtctgt ttcatgtgga atacctgact tcaggtcaag ggatggtatt tatgctcgcc 900
ttgctgtaga cttcccagat cttccagatc ctcaagcgat gtttgatatt gaatatttca 960
gaaaagatcc aagaccattc ttcaagtttg caaaggaaat atatcctgga caattccagc 1020
catctctctg tcacaaattc atagccttgt cagataagga aggaaaacta cttcgcaact 1080
atacccagaa catagacacg ctggaacagg ttgcgggaat ccaaaggata attcagtgtc 1140
atggttcctt tgcaacagca tcttgcctga tttgtaaata caaagttgac tgtgaagctg 1200
tacgaggaga tatttttaat caggtagttc ctcgatgtcc taggtgccca gctgatgaac 1260
cgcttgctat catgaaacca gagattgtgt tttttggtga aaatttacca gaacagtttc 1320
atagagccat gaagtatgac aaagatgaag ttgacctcct cattgttatt gggtcttccc 1380
tcaaagtaag accagtagca ctaattccaa gttccatacc ccatgaagtg cctcagatat 1440
taattaatag agaacctttg cctcatctgc attttgatgt agagcttctt ggagactgtg 1500
atgtcataat taatgaattg tgtcataggt taggtggtga atatgccaaa ctttgctgta 1560
accctgtaaa gctttcagaa attactgaaa aacctccacg aacacaaaaa gaattggctt 1620
atttgtcaga gttgccaccc acacctcttc atgtttcaga agactcaagt tcaccagaaa 1680
gaacttcacc accagattct tcagtgattg tcacactttt agaccaagca gctaagagta 1740
atgatgattt agatgtgtct gaatcaaaag gttgtatgga agaaaaacca caggaagtac 1800
aaacttctag gaatgttgaa agtattgctg aacagatgga aaatccggat ttgaagaatg 1860
ttggttctag tactggggag aaaaatgaaa gaacttcagt ggctggaaca gtgagaaaat 1920
gctggcctaa tagagtggca aaggagcaga ttagtaggcg gcttgatggt aatcagtatc 1980
tgtttttgcc accaaatcgt tacattttcc atggcgctga ggtatattca gactctgaag 2040
atgacgtctt atcctctagt tcttgtggca gtaacagtga tagtgggaca tgccagagtc 2100
caagtttaga agaacccatg gaggatgaaa gtgaaattga agaattctac aatggcttag 2160
aagatgagcc tgatgttcca gagagagctg gaggagctgg atttgggact gatggagatg 2220
atcaagaggc aattaatgaa gctatatctg tgaaacagga agtaacagac atgaactatc 2280
catcaaacaa atcatagtgt aataattgtg caggtacagg aattgttcca ccagcattag 2340
gaactttagc atgtcaaaat gaatgtttac ttgtgaactc gatagagcaa ggaaaccaga 2400
aaggtgtaat atttataggt tggtaaaata gattgttttt catggataat ttttaacttc 2460
attatttctg tacttgtaca aactcaacac taactttttt ttttttaaaa aaaaaaaggt 2520
actaagtatc ttcaatcagc tgttgggtca agactaactt tcttttaaag gttcatttgt 2580
atgataaatt catatgtgta tatataattt tttttgtttt gtctagtgag tttcaacatt 2640
tttaaagttt tcaaaaagcc atcggaatgt taaattaatg taaagggaca gctaatctag 2700
accaaagaat ggtattttca cttttctttg taacattgaa tggtttgaag tactcaaaat 2760
ctgttacgct aaacttttga ttctttaaca caattatttt taaacactgg cattttccaa 2820
aactgtggca gctaactttt taaaatctca aatgacatgc agtgtgagta gaaggaagtc 2880
aacaatatgt ggggagagca ctcggttgtc tttactttta aaagtaatac ttggtgctaa 2940
gaatttcagg attattgtat ttacgttcaa atgaagatgg cttttgtact tcctgtggac 3000
atgtagtaat gtctatattg gctcataaaa ctaacctgaa aaacaaataa atgctttgga 3060
aatgtttcag ttgctttaga aacattagtg cctgcctgga tccccttagt tttgaaatat 3120
ttgccattgt tgtttaaata cctatcactg tggtagagct tgcattgatc ttttccacaa 3180
gtattaaact gccaaaatgt gaatatgcaa agcctttctg aatctataat aatggtactt 3240
ctactgggga gagtgtaata ttttggactg ctgttttcca ttaatgagga gagcaacagg 3300
cccctgatta tacagttcca aagtaataag atgttaattg taattcagcc agaaagtaca 3360
tgtctcccat tgggaggatt tggtgttaaa taccaaactg ctagccctag tattatggag 3420
atgaacatga tgatgtaact tgtaatagca gaatagttaa tgaatgaaac tagttcttat 3480
aatttatctt tatttaaaag cttagcctgc cttaaaacta gagatcaact ttctcagctg 3540
caaaagcttc tagtctttca agaagttcat actttatgaa attgcacagt aagcatttat 3600
ttttcagacc atttttgaac atcactccta aattaataaa gtattcctct gttgctttag 3660
tatttattac aataaaaagg gtttgaaata tagctgttct ttatgcataa aacacccagc 3720
taggaccatt actgccagag aaaaaaatcg tattgaatgg ccatttccct acttataaga 3780
tgtctcaatc tgaatttatt tggctacact aaagaatgca gtatatttag ttttccattt 3840
gcatgatgtt tgtgtgctat agatgatatt ttaaattgaa aagtttgttt taaattattt 3900
ttacagtgaa gactgttttc agctcttttt atattgtaca tagtctttta tgtaatttac 3960
tggcatatgt tttgtagact gtttaatgac tggatatctt ccttcaactt ttgaaataca 4020
aaaccagtgt tttttacttg tacactgttt taaagtctat taaaattgtc atttgacttt 4080
tttctg 4086
<210> 51
<211> 11579
<212> DNA
<213> Homo sapiens
<400> 51
cggaccgtgc tttcgccgcc tgggagccgt ccggcgcagc agtttctagg tccccactgt 60
ccccgccgtc ccgccccttc gcgtcccggg aaccggctgg cttccgagcc gcactcgccg 120
atcctccagg catgccccgc tacgagctgg ctttaatcct gaaagccatg cagcggggtt 180
ggtacagtag gcttcactag acttagctgc aactcagaat ttctcctcca gcacctgagt 240
aaatgctgat ggtcttgtgg agagtggatt aagagtacga gctaagttct caatcccaat 300
taagaagcgg aaaatttaaa ctgtcttctt caaagtttat cacaaccacc accatcaaga 360
cagcaaacca aaggacaaag actttgaccc tgctgtgttg ctctgtgtag tccagttcac 420
gtatggttta cagacttggc tggggttact aaaaataaat aaaaagttgg acacttctgt 480
cattggagcg ctattattca caagttacca gaatgagagc tgtactggac acagcagaca 540
ttgccatagt ggccctgtat tttatcctgg tcatgtgcat tggttttttt gccatgtgga 600
aatctaatag aagcaccgtg agtggatact tcctggcggg gcgctctatg acctgggtaa 660
caattggtgc ctctctgttt gtgagcaata ttgggagtga gcacttcatt gggctggcag 720
gatctggagc tgcaagtgga tttgcagtgg gcgcatggga attcaatgcc ttactgcttt 780
tacaacttct gggatgggtt ttcatcccaa tttacatccg gtcaggggta tataccatgc 840
ctgaatactt gtccaagcga tttggtggcc ataggattca ggtctatttt gcagccttgt 900
ctctgattct ctatattttc accaagctct cggtggatct gtattcgggt gcccttttta 960
tccaggagtc tttgggttgg aatctttatg tgtctgtcat cctgctcatt ggcatgactg 1020
ctttgctgac tgtcaccgga ggccttgttg cagtgatcta cacagacact ctgcaggctc 1080
tgctcatgat cattggggca cttacactta tgattattag cataatggag attggcgggt 1140
ttgaggaagt taagagaagg tacatgttgg cctcacccga tgtcacttcc atcttattga 1200
catacaacct ttccaacaca aattcttgta atgtctcccc taagaaagaa gccctgaaaa 1260
tgctgcggaa tccaacagat gaagatgttc cttggcctgg attcattctt gggcagaccc 1320
cagcttcagt atggtactgg tgtgctgacc aagtcatcgt gcagagggtc cttgcagcca 1380
aaaacattgc tcatgccaaa ggctctactc ttatggctgg cttcttaaag ctcctgccaa 1440
tgtttatcat agttgtccca ggaatgattt ccaggatact gtttactgat gatatagctt 1500
gcatcaaccc agagcactgc atgctggtgt gtggaagcag agctggttgc tccaatattg 1560
cttacccacg cctggtgatg aagctggttc ctgtgggcct tcggggttta atgatggcag 1620
tgatgattgc agctctgatg agtgacttag actctatctt taacagtgcc agtaccatat 1680
tcaccctcga tgtgtacaaa cttatccgca agagcgcaag ctcccgggag ttaatgattg 1740
tggggaggat atttgtggca tttatggtgg tgatcagcat agcatgggtg ccaatcatcg 1800
tggagatgca aggaggccag atgtaccttt acattcagga ggtagcagat tacctgacac 1860
ccccagtggc agccttgttc ctgctggcaa ttttctggaa gcgctgcaat gaacaagggg 1920
ctttctatgg tggaatggct ggctttgttc ttggagcagt ccgtttgata ctggcctttg 1980
cctaccgtgc cccagaatgt gaccaacctg ataataggcc gggcttcatc aaagacatcc 2040
attatatgta tgtggccaca ggattgtttt gggtcacggg actcattact gtaattgtga 2100
gccttctcac accacctccc acaaaggaac agattcgaac caccaccttt tggtctaaga 2160
agaacctggt ggtgaaggag aactgctccc caaaagagga accataccaa atgcaagaaa 2220
agagcattct gagatgcagt gagaataatg agaccatcaa ccacatcatt cccaacggga 2280
aatctgaaga cagcattaag ggccttcagc ctgaagatgt taatctgttg gtaacctgca 2340
gagaggaggg caacccagtg gcatccttag gtcattcaga ggcagaaaca ccagttgacg 2400
cttactccaa tgggcaagca gctctcatgg gtgagaaaga gagaaagaaa gaaacggatg 2460
atggaggtcg gtactggaag ttcatagact ggttttgtgg ctttaaaagt aagagcctca 2520
gcaagaggag tctcagagac ctgatggaag aggaggctgt ttgtttacag atgctagaag 2580
agactcggca agttaaagta atactaaata ttggactttt tgctgtgtgt tcacttggaa 2640
ttttcatgtt tgtttatttc tccttatgaa cttaaggata tggtgagaca ctaacttaag 2700
acaatactga ctggtctttg gggaaaaaag ttatgtaact gtgcatctct caggcattgt 2760
ttacgctgta ggttttagcc aaattttact tagcagaaaa tcatctaatt acaagacttt 2820
attttcccag agatggatta aagtaaatct tcaacttaag tgaagccaaa cctaacagac 2880
tgaattgtgc aaatgtggtt ttaaattttg cataccaaag taagaagaga ccaattattc 2940
tcacagagca cttagagcag aatatatgtt aagttaccat gaattaaggt atactgtctg 3000
cactgccaag tcttggcaga ccttaccctg aagtagaaga tttgctcatt tctaaagttt 3060
tttttctgtc tctgtaatcc ctcctaccat taagaaaaac ttatttctta gacattgtac 3120
aatcagttat gtactgaaaa tcgaatgtgc ttgtgtgata cttgtttcag gacaagttca 3180
tttgccaggt tcattttgtt agcatgagcc tacggattct gatttcccaa agaaagaatg 3240
ttttcctgta ggtatttttg taccaccagt atatggaatg ttagggaaaa actttgttcc 3300
agttcctttt tttttttctt tctactttca agtttaagtg aaccatactg aaatgaccaa 3360
caagtctgcc tgtaaagtta catgtcatga ttgtgttgtt aaatgattat gggggagaaa 3420
atgaagtaaa tgttgctgat gatccccata tttattgatc atattaaggt tgtttatata 3480
gtttggaaat gaccagcccc ctaagcagtg tttgattaac ttatgctaat cagatgatta 3540
ctcatatatt ctgctaattt tctagcttta ttcttgttat ttggaaaaat tattagccaa 3600
atgccttcct aggtggatcc agttggaaga tatgtccaga aacctgaaga aaaattgacg 3660
ctgcctttgt gtgctggatt gctctacttg attagatcat gatatatcaa ggttgaattt 3720
ttagagggaa aatttaattc tgatatctta ttgcatcctt gataagtttt tccctgattt 3780
tttttttcct caaaagactt tccatctgta cacagcctct acatttttgt tgtagtgact 3840
tagagcataa ggatgtttca gtgcaaactg gccgtcggta acagaaaact cagtgcatac 3900
tttgctgttg ttaggttgtc aatatagtct ttctgtagga tggatagcat gtttgagagg 3960
tgccaaacaa gaacttttgg ggttagtagt gtgtcttgtg gagggtatta caggactgtg 4020
taattatagg actctaactt gacatggctt ggcacccact tgcagctagt gggtacaggg 4080
tacaaaagat gttagagaaa agctctacag attacgtact tctgtgtctt cgtatgctca 4140
acactgtcct ttgtcctcca tgaaagatga aggaagcaaa ttatgtatgt actttctttg 4200
accttcttta atctctgata ctttttagat tgcatgattt tactaggctt gtatttaggg 4260
aaattacttt cataaatact tttgtagatt ttgaatcaaa actcagtctt tttaattttt 4320
ttgtagtcta taaactagtt tcattatgat ggacttgatt agtccaaagt taattttaga 4380
aattgtcagg tagcatagtg tcttcccatg atcaggaggc tttctgaagg actgagtctg 4440
taaatgaaaa aataatttat gtatgaatag catgtatttc tgaagagctt agagtgcctt 4500
gtagaatttt tttctcaatt ttattcttga ggtttataat ttgggggcca aatagataga 4560
gctcatcatt ttcttgtttg gaagttgagg ctgcgacatg tccaaggtta tgaagtctct 4620
tttgggaaga acagaaacca ggtctccaaa tctggactca tggtttgttc agatgtgtct 4680
ggacaaatgg ttgtcaatgt tttgtcctgt tttttcaaag gaactgttct tcctttggga 4740
caaccttttg gtgtttggga aagtaataag atcttggatt tttcaaatta acattaagtt 4800
gtaagaacta aaattttctt tgaaccacat tactgtgtaa ttcactgata attgacatat 4860
tggctgggca gcctatctct tccatatcca gcgtaaatga ataggaggtg tttgtgattt 4920
tttttttctc cctttattta acattgagtc ctagtagttt ggagaattag ggtccctcta 4980
ccttctttct gctcttgtct tagtaagata cataaggtac atcatcttgt gtctgtgtgt 5040
atatagcagt aggtcaagtt tagagtacta aagtctgtaa ataaggaatg actattagca 5100
tattcattag aattgtttat tcttgccagt ataaacatca ttttatttag actaaagtcc 5160
ctgaagcttg tctttcttat tgcttcccag taatagataa tgtgctcgag taagtttgtg 5220
aattgctgat tgcaacttaa ttcagggacc agtcttcaat ctatatttca ttagaatgat 5280
tgttcctgga atgatcatac atggactgtc ttaagctagc aaaatgttca tactttacac 5340
tgactaaatg ggtcctaaat gatgacattg gtctttagac attaacatgt gtatattttt 5400
atattagctc aagctaaggt tcagaattga agcttgatat tgactagaat agctaaaagt 5460
caaaatgagg tgaggacact ggtcttggaa ggtagagaaa aataaatgtc ttaccaggtg 5520
ttaatggtat ccccagttct tagacttttg tcttctcagg caattttcat ctcaagatct 5580
gatgagaagg gcatattaca ttggtatgca ggatgattat tgcatatttt gtgggacctc 5640
taatttccct ggtcatcttt cagaatattc tgttctgcca cccccagaga gtaaacactt 5700
gagccgattt cttcttcccc agctattctt tcctgggggt aattatgctt tgtctttaga 5760
ttagagaagc atcaagcaat agcaatggtg ctgtgtcctt cggcctaaat tcaatagatc 5820
tcatctccta gggcttcctt ttcacttggc tcaaaggatc cattgtattt tggcacaaag 5880
agcctggcca gggtcatgta gccatagctc ttagggatga tacctcaaga aattagctgg 5940
gacccatcac tctgtgaaac ttcacatttt aagaactgag ttgagggggt tgttatgcac 6000
ttctgtaact tgaggctaag caaggggtta actcttgtga gagccaatag agtgtgtctg 6060
tattcgcagt ccatggctca ttttctttat agtaggcata tggatcttcc cctctgactt 6120
tgaatatcat ttggtgtggc ctgtgggtta ttttcattct ttaccaccaa ataaagcggc 6180
ttattagcta ctcagttact tgctactcaa aggttaggtc ttccctgttc ctgcttggca 6240
gtgttaaagc ttacagggtt aacttatgat gattctcctg gctcattttc atcagaggca 6300
tgatgactgg aaagggatca catgggtcgt tggtggtgac acctcactgt ttcctaggtt 6360
tggatagaga gatgtataca agacctttcc tgttaaatta cgtgactaca gagacttgcc 6420
aggacaaaat tttcctaaga aatcagaaaa atgattaagt gagataagta cctgggtgac 6480
acagatatta gcccgttggt aaaagacaac aaatattagc ttaaaatctg catatgtaga 6540
atcattttca ttagatttag agcttgaagc accttggctc tcagctactt taaactcctc 6600
cccatataaa tcagggcacc aataaataag tttcagcttt ttaaaccctg gtttgatgtt 6660
aagcattata aagtacgaag tttgttacca cagtagagat aatttagtag aaaaatgctt 6720
tgaggcttca gtatttgtaa gattttgcat tagccagatg ctaggttgtt gaaggcattt 6780
cagtgttgat aatagcctga gcagacttct ttacaaatgg gatctgtttc tatatgtgta 6840
tatgcccact taccattcag agagactggt ctttctcttt gtcttccttc acattgctgt 6900
gtcagttcta cacctagtct tttcagcact tagcaaattc aaattttgat ttttttgtca 6960
gcttagttca ctttaaggca tattggcatg gtgtgtgaaa gtgatgtttt gccccagtat 7020
tgaggacttt tagatccaaa taatgactca ttaaatataa ttatgtttta agtatactga 7080
atttctgtta gcttaaaatg ttaattctca ggaatgattt tctcacactt tgtgttggct 7140
aataataaaa gcactgtttt attctcaaaa ctcctttttc aaaaattagg gagagagcag 7200
tagtgatcat ttatgtgagc ccctttgaaa tgatggtgtc agagtgcaga gaaacaatgg 7260
agttttgatg ccaaaaaggt ttttttgcag taaaagtaaa aatttggaat tagttggcat 7320
atagaggaac ccttttgtac tggaacgtat gaggctggat tgtgaaaagg taatctttcg 7380
attgctagac ttggttaact tagggctgca aatctttttc ttctgtcaag gtcacttaat 7440
atggaatgtt tttgtcagac tgtcctttgt tggaatactt tagctgttca gctactttga 7500
ctcctaggag agaatttagt taaggttcaa agtaattaac tggctttgcc agtggtgagt 7560
cccacaccat tattcactta gtagtcatat aaatgttttt atttaaactt ctctctcttc 7620
aatgctgaga ataaggcttt aaattactga ttcaccttta aaggaatgtt gtgagaattg 7680
atgtaatttc tgtttctgtt tccatctaaa cttctttata aaaagaggga ttagtttttt 7740
tgttttgggg taagcaccta atttatccag taaccaacaa ccctaaccat tggcatatat 7800
agtctttcac tcagaaataa acaaaaactg tttggtatat ctgtatcatt gctaatcttg 7860
tgcactttac tttttgggca gtaccataca tagtctgagg ctattgactt aaaccaataa 7920
ctgtacttta tgtaatgact cttaaatttg gttacctggg ttcacagctt gcttgaagag 7980
aaaggatgct agaataaagt aagcagctga agagcgagca aatcaagaca aaacacagtg 8040
gtctcagatt tttcgtagtg tgggaacagt ggttttgctc tataccactg aaaagcacta 8100
taacataatt gttgtccatg atactgaagc ttttcccctc acttctaggt tgtttacatt 8160
cagagctcta tcaataagag gaatacatat tacagtgaat tcgacaaccg cacaagttgg 8220
cagtaggtat ccccaaccta atttatcttg gtaaattcac cctgtttcct agtgctgctg 8280
gataaaagag tgtttacttt ttattgctct tagacagagt agtctagata agttttcaat 8340
ttatcaacat agcctagact tctgtaagtg gaatgttcat tagtaactca tctttttgtt 8400
gttataattg gaaacagaaa cgaggcttat tgctattgca gaaatcccaa actggcaaag 8460
gccagtatat atggtattcc ataatataac cagcttttga aatttatgtg tttggattag 8520
tgccttctgg ttaccagtat tgactctgct agtttgcacc tttccgttct taacagaaaa 8580
tttgtatttg ttattcctct taaattttgt cgtaactagt gaaggaagta aaaaaaaaaa 8640
aaaaacatgc attacattga catactttat gtgcagcctt tatttaggtt cagtgaaacc 8700
aggtagttct gtatttgtgt tgtagcctaa atgttgtttc ttttatatcc attaaaaact 8760
taaagttact tatgttctgt gatcttaatt ttgttgtgtt tccattgtag gttgataggt 8820
atatcgagaa caggtacgtg acaacagttt atattccatg atagaaagct aaagtccata 8880
gaaagcacaa aatcgtgttc acacattagt gtacccacac atagaaagca caagactaat 8940
agtattctct gtatcccaca agtgccagtc ataaaggcca ccaggtattt gtctcagagt 9000
tgctatgagc actacagtat tgataagccc aagacaatgc ggtatctaaa ctggtcctaa 9060
tggtaaggga cccaaaggaa taatctcaat aagtttgtac cacattgatg gagggagaga 9120
atataaatgt caagaatgcc aaaattatat ttgggggtta ctagctaaaa tggggtttga 9180
gggcttttta ctgcaacttg aaactggaga aatagggaca gatgtctagg tttttggtgg 9240
gtggaacagg tgacatattt ctgttttaag ctgtagtgtg attggggttt tttgtaaaaa 9300
atcttaaatc ttttaggaaa tattacctct taacagtgcc cccccaaaca tgcagaaagt 9360
catactttaa cagggcaaat actacttgtc tttgattttt tttgtgtacg tttgtatgtg 9420
agagatgaag ttacctttat ttttttccta tacttgactg tgcttcattt taataaagga 9480
taatttgatc tgagtgttct gagcatcaga ctaattctga agcatatttg ctagaggagc 9540
tactttgctt ttcacaatgg ggtggagagg attctttcac ttgtcccatt aaccctcttc 9600
tagtctagat gagatgaaat ctgttaatgt gtgtgtagaa gaaaacgtat gttcttctac 9660
tcagcattgc ccttttccac ctcctcactt cacctccgag tagcttgttt atcaagaatg 9720
aatgaatgtc tttgtcttaa attttgccca tgtgttaaaa gatgtaattc tcagaatggg 9780
agagaaatga ctacctttgt tcctactctt ttatataatt atccttttag ggaaagactt 9840
ggtcaactct aatatatcta gaaggaagac tatatctggt gtagactaat atgagatgtt 9900
ttagaagagt taacctgaac actttgaggg agagattatt cttgccagca aaaagctagc 9960
caggaatgag cctaccacat tatttgagaa tatcaaacct caggcctggg gggatgaggg 10020
gaagaagatt accagaagtg caggaaagag aagtttgagg aacacccttg gcttagcaac 10080
atgtgataat gcaaagctgt tataacctgt taatcctacg tactatgtgt tctgtacctt 10140
tacatgtttt taaatttaag atagtttgta agaactgtac aaaaaaatgc ttctggagat 10200
ttctttggca gaaatgcctt tcatctataa tttcatggag aactgcttta attagcctag 10260
gtgaaaagta gtcctagcag tgtaaatatg tataattaga gttttctaat ttcactgtga 10320
gatctctaac ttttgagtgg caaacagatc aagtcttttg ctcatagact tttctgtggg 10380
gttattaaaa tgcaaaagct ttattttttt taataatgcc atactccatt agtgtcagat 10440
gatggtatgg aatttgttcc cttgctttcc cccactgtta ctgcttcagt ttatagattg 10500
ccagcagagt tcagaaatag agcagggatt tacccgttct ttgcttggac atcccatttt 10560
cttttgtcca gacccatgtt ggcaatcatg tatgaactgt gttatacttc tcagtgcttt 10620
cttttttctt tttgataaga tggatatcaa aaatagttgc tgtgcaaaag ttagtagtct 10680
tcttcaagaa gaaaaccaat tctttttcta ataatatcct gtgaaattgc ttcattcatt 10740
catttatttt taagccaaat gtcagcagag tgctgctgct tttatctagt aattttgata 10800
tgtaagtatt aatgcatttt taaaagatgt ctacattgaa acatgttctt cccagtgtcc 10860
tgcttatgat gctttgttca gattttttgt aagagaccag ttagtacact gggggtgtat 10920
attgtgtaca tgtgtcattt tagttaggca ttgtaggcca aatgtgatta taaatgaagt 10980
tgatgaacat taattttgtt attagtgagt tttttgaatt gtaaatggat ttccagttta 11040
ccttctgttg tctacagctt ttttaatttt aaggtttgac taattgtatc catctcattg 11100
tacagtgttt tagttgcaag cagaaagtag aatttggtat aaagcaggtt atttctatat 11160
tgaaaggagt acagttgaaa ttgtagattt aagattgtta aaatcatgac aattctaact 11220
tgtctattct aacctattgt gtacaatctg attttttaaa attgtaaaca tgtatgatct 11280
tggtttcatg tgtttttgaa agtgttattg tttaaaaaat gaaaaaagca tatctgctaa 11340
agagctgtca gttttcatta ctgactctgt aaaatacact gttctttgtg tactgtgtgt 11400
tattttgcca gctgctgcat tagccttcaa aagtatttgg aaacttaaga tgaactacat 11460
ttcttgcaaa gtacattcct ttctgtggta ttttgtcctg taactgaagt atagtaatta 11520
ttttatggaa atgttagcaa ttctgtacca actttgaata aaatgaaaaa tttataaaa 11579
<210> 52
<211> 8789
<212> DNA
<213> Homo sapiens
<400> 52
atgctcagtg gcttctcgac aagttggcag caacaacacg gccctggtcg tcgtcgccgc 60
tgcggtaacg gagcggtttg ggtggcggag cctgcgttcg cgccttcccg ctctcctcgg 120
gaggcccttc ctgctctccc ctaggctccg cggccgccca gggggtggga gcgggtgagg 180
ggagccaggc gcccagcgag agaggccccc cgccgcaggg cggcccggga gctcgaggcg 240
gtccggcccg cgcgggcagc ggcgcggcgc tgaggagggg cggcctggcc gggacgcctc 300
ggggcggggg ccgaggagct ctccgggccg ccggggaaag ctacgggccc ggtgcgtccg 360
cggaccagca gcgcgggaga gcggactccc ctcgccaccg cccgagccca ggttatcctg 420
aatacatgtc taacaatttt ccttgcaacg ttagctgttg tttttcactg tttccaaagg 480
atcaaaattg cttcagaaat tggagacata tttgatttaa aaggaaaaac ttgaacaaat 540
ggacaatatg tctattacga atacaccaac aagtaatgat gcctgtctga gcattgtgca 600
tagtttgatg tgccatagac aaggtggaga gagtgaaaca tttgcaaaaa gagcaattga 660
aagtttggta aagaagctga aggagaaaaa agatgaattg gattctttaa taacagctat 720
aactacaaat ggagctcatc ctagtaaatg tgttaccata cagagaacat tggatgggag 780
gcttcaggtg gctggtcgga aaggatttcc tcatgtgatc tatgcccgtc tctggaggtg 840
gcctgatctt cacaaaaatg aactaaaaca tgttaaatat tgtcagtatg cgtttgactt 900
aaaatgtgat agtgtctgtg tgaatccata tcactacgaa cgagttgtat cacctggaat 960
tgatctctca ggattaacac tgcagagtaa tgctccatca agtatgatgg tgaaggatga 1020
atatgtgcat gactttgagg gacagccatc gttgtccact gaaggacatt caattcaaac 1080
catccagcat ccaccaagta atcgtgcatc gacagagaca tacagcaccc cagctctgtt 1140
agccccatct gagtctaatg ctaccagcac tgccaacttt cccaacattc ctgtggcttc 1200
cacaagtcag cctgccagta tactgggggg cagccatagt gaaggactgt tgcagatagc 1260
atcagggcct cagccaggac agcagcagaa tggatttact ggtcagccag ctacttacca 1320
tcataacagc actaccacct ggactggaag taggactgca ccatacacac ctaatttgcc 1380
tcaccaccaa aacggccatc ttcagcacca cccgcctatg ccgccccatc ccggacatta 1440
ctggcctgtt cacaatgagc ttgcattcca gcctcccatt tccaatcatc ctgctcctga 1500
gtattggtgt tccattgctt actttgaaat ggatgttcag gtaggagaga catttaaggt 1560
tccttcaagc tgccctattg ttactgttga tggatacgtg gacccttctg gaggagatcg 1620
cttttgtttg ggtcaactct ccaatgtcca caggacagaa gccattgaga gagcaaggtt 1680
gcacataggc aaaggtgtgc agttggaatg taaaggtgaa ggtgatgttt gggtcaggtg 1740
ccttagtgac cacgcggtct ttgtacagag ttactactta gacagagaag ctgggcgtgc 1800
acctggagat gctgttcata agatctaccc aagtgcatat ataaaggtct ttgatttgcg 1860
tcagtgtcat cgacagatgc agcagcaggc ggctactgca caagctgcag cagctgccca 1920
ggcagcagcc gtggcaggaa acatccctgg cccaggatca gtaggtggaa tagctccagc 1980
tatcagtctg tcagctgctg ctggaattgg tgttgatgac cttcgtcgct tatgcatact 2040
caggatgagt tttgtgaaag gctggggacc ggattaccca agacagagca tcaaagaaac 2100
accttgctgg attgaaattc acttacaccg ggccctccag ctcctagacg aagtacttca 2160
taccatgccg attgcagacc cacaaccttt agactgaggt cttttaccgt tggggccctt 2220
aaccttatca ggatggtgga ctacaaaata caatcctgtt tataatctga agatatattt 2280
cacttttgtt ctgctttatc ttttcataaa gggttgaaaa tgtgtttgct gccttgctcc 2340
tagcagacag aaactggatt aaaacaattt tttttttcct cttcagaact tgtcaggcat 2400
ggctcagagc ttgaagatta ggagaaacac attcttatta attcttcacc tgttatgtat 2460
gaaggaatca ttccagtgct agaaaattta gccctttaaa acgtcttaga gccttttatc 2520
tgcagaacat cgatatgtat atcattctac agaataatcc agtattgctg attttaaagg 2580
cagagaagtt ctcaaagtta attcacctat gttattttgt gtacaagttg ttattgttga 2640
acatacttca aaaataatgt gccatgtggg tgagttaatt ttaccaagag taactttact 2700
ctgtgtttaa aaagtaagtt aataatgtat tgtaatcttt catccaaaat attttttgca 2760
agttatatta gtgaagatgg tttcaattca gattgtcttg caacttcagt tttatttttg 2820
ccaaggcaaa aaactcttaa tctgtgtgta tattgagaat cccttaaaat taccagacaa 2880
aaaaatttaa aattacgttt gttattccta gtggatgact gttgatgaag tatacttttc 2940
ccctgttaaa cagtagttgt attcttctgt atttctaggc acaaggttgg ttgctaagaa 3000
gcctataaga ggaatttctt ttccttcatt catagggaaa ggttttgtat tttttaaaac 3060
actaaaagca gcgtcactct acctaatgtc tcactgttct gcaaaggtgg caatgcttaa 3120
actaaataat gaataaactg aatattttgg aaactgctaa attctatgtt aaatactgtg 3180
cagaataatg gaaacattac agttcataat aggtagtttg gatatttttg tacttgattt 3240
gatgtgactt tttttggtat aatgtttaaa tcatgtatgt tatgatattg tttaaaattc 3300
agtttttgta tcttggggca agactgcaaa cttttttata tcttttggtt attctaagcc 3360
ctttgccatc aatgatcata tcaattggca gtgactttgt atagagaatt taagtagaaa 3420
agttgcagat gtattgactg taccacagac acaatatgta tgctttttac ctagctggta 3480
gcataaataa aactgaatct caacatacaa agttgaattc taggtttgat ttttaagatt 3540
ttttttttct tttgcacttt tgagtccaat ctcagtgatg aggtaccttc tactaaatga 3600
caggcaacag ccagttctat tgggcagctt tgtttttttc cctcacactc taccgggact 3660
tccccatgga cattgtgtat catgtgtaga gttggttttt ttttttttta atttttattt 3720
tactatagca gaaatagacc tgattatcta caagatgata aatagattgt ctacaggata 3780
aatagtatga aataaaatca aggattatct ttcagatgtg tttacttttg cctggagaac 3840
ttttagctat agaaacactt gtgtgatgat agtcctcctt atatcacctg gaatgaacac 3900
agcttctact gccttgctca gaaggtcttt taaatagacc atcctagaaa ccactgagtt 3960
tgcttatttc tgtgatttaa acatagatct tgatccaagc tacatgactt ttgtctttaa 4020
ataacttatc taccacctca tttgtactct tgattactta caaattcttt cagtaaacac 4080
ctaattttct tctgtaaaag tttggtgatt taagttttat tggcagtttt ataaaaagac 4140
atcttctcta gaaattgcta actttaggtc cattttactg tgaatgagga ataggagtga 4200
gttttagaat aacagatttt taaaaatcca gatgatttga ttaaaacctt aatcatacat 4260
tgacataatt cattgcttct tttttttgag atatggagtc ttgctgtgtt gcccaggcag 4320
gagtgcagtg gtatgatctc agctcactgc aacctctgcc tcccgggttc aactgattct 4380
cctgcctcag cctccctggt agctaggatt acaggtgccc gccaccatgc ctggctaact 4440
tttgtagttt tagtagagac ggggttttgc ctgttggcca ggctggtctt gaactcctga 4500
cctcaagtga tccatccacc ttggcctccc aaagtgctgg gattacgggc gtgagccact 4560
gtccctggcc tcattgttcc cttttctact ttaaggaaag ttttcatgtt taatcatctg 4620
gggaaagtat gtgaaaaata tttgttaaga agtatctctt tggagccaag ccacctgtct 4680
tggtttcttt ctactaagag ccataaagta tagaaatact tctagttgtt aagtgcttat 4740
atttgtacct agatttagtc acacgctttt gagaaaacat ctagtatgtt atgatcagct 4800
attcctgaga gcttggttgt taatctatat ttctatttct tagtggtagt catctttgat 4860
gaataagact aaagattctc acaggtttaa aattttatgt ctactttaag ggtaaaatta 4920
tgaggttatg gttctgggtg ggttttctct agctaattca tatctcaaag agtctcaaaa 4980
tgttgaattt cagtgcaagc tgaatgagag atgagccatg tacacccacc gtaagacctc 5040
attccatgtt tgtccagtgc ctttcagtgc attatcaaag ggaatccttc atggtgttgc 5100
ctttattttc cggggagtag atcgtgggat atagtctatc tcatttttaa tagtttaccg 5160
cccctggtat acaaagataa tgacaataaa tcactgccat ataaccttgc tttttccaga 5220
aacatggctg ttttgtattg ctgtaaccac taaataggtt gcctatacca ttcctcctgt 5280
gaacagtgca gatttacagg ttgcatggtc tggcttaagg agagccatac ttgagacatg 5340
tgagtaaact gaactcatat tagctgtgct gcatttcaga cttaaaatcc atttttgtgg 5400
ggcagggtgt ggtgtgtaaa ggggggtgtt tgtaatacaa gttgaaggca aaataaaatg 5460
tcctgtctcc cagatgatat acatcttatt atttttaaag tttattgcta attgtaggaa 5520
ggtgagttgc aggtatcttt gactatggtc atctggggaa ggaaaatttt acattttact 5580
attaatgctc cttaagtgtc tatggaggtt aaagaataaa atggtaaatg tttctgtgcc 5640
tggtttgatg gtaactggtt aatagttact caccatttta tgcagagtca cattagttca 5700
caccctttct gagagccttt tgggagaagc agttttattc tctgagtgga acagagttct 5760
ttttgttgat aatttctagt ttgctccctt cgttattgcc aactttactg gcattttatt 5820
taatgatagc agattgggaa aatggcaaat ttaggttacg gaggtaaatg agtatatgaa 5880
agcaattacc tctaaagcca gttaacaatt attttgtagg tggggtacac tcagcttaaa 5940
gtaatgcatt tttttttccc gtaaaggcag aatccatctt gttgcagata gctatctaaa 6000
taatctcata tcctcttttg caaagactac agagaatagg ctatgacaat cttgttcaag 6060
cctttccatt tttttccctg ataactaagt aatttctttg aacataccaa gaagtatgta 6120
aaaagtccat ggccttattc atccacaaag tggcatccta ggcccagcct tatccctagc 6180
agttgtccca gtgctgctag gttgcttatc ttgtttatct ggaatcactg tggagtgaaa 6240
ttttccacat catccagaat tgccttattt aagaagtaaa acgttttaat ttttagcctt 6300
tttttggtgg agttatttaa tatgtatatc agaggatata ctagatggta acatttcttt 6360
ctgtgcttgg ctatctttgt ggacttcagg ggcttctaaa acagacagga ctgtgttgcc 6420
tttactaaat ggtctgagac agctatggtt ttgaattttt agtttttttt ttttaaccca 6480
cttcccctcc tggtctcttc cctctctgat aattaccatt catatgtgag tgttagtgtg 6540
cctcctttta gcattttctt cttctctttc tgattcttca tttctgactg cctaggcaag 6600
gaaaccagat aaccaaactt actagaacgt tctttaaaac acaagtacaa actctgggac 6660
aggacccaag acactttcct gtgaagtgct gaaaaagacc tcattgtatt ggcatttgat 6720
atcagtttga tgtagcttag agtgcttcct gattcttgct gagtttcagg tagttgagat 6780
agagagaagt gagtcatatt catattttcc cccttagaat aatattttga aaggtttcat 6840
tgcttccact tgaatgctgc tcttacaaaa actggggtta caagggttac taaattagca 6900
tcagtagcca gaggcaatac cgttgtctgg aggacaccag caaacaacac acaacaaagc 6960
aaaacaaacc ttgggaaact aaggccattt gttttgtttt ggtgtcccct ttgaagccct 7020
gccttctggc cttactcctg tacagatatt tttgacctat aggtgccttt atgagaattg 7080
agggtctgac atcctgcccc aaggagtagc taaagtaatt gctagtgttt tcagggattt 7140
taacatcaga ctggaatgaa tgaatgaaac tttttgtcct ttttttttct gttttttttt 7200
ttctaatgta gtaaggacta aggaaaacct ttggtgaaga caatcatttc tctctgttga 7260
tgtggatact tttcacaccg tttatttaaa tgctttctca ataggtccag agccagtgtt 7320
cttgttcaac ctgaaagtaa tggctctggg ttgggccaga cagttgcact ctctagtttg 7380
ccctctgcca caaatttgat gtgtgacctt tgggcaagtc atttatcttc tctgggcctt 7440
agttgcctca tctgtaaaat gagggagttg gagtagatta attattccag ctctgaaatt 7500
ctaagtgacc ttggctacct tgcagcagtt ttggatttct tccttatctt tgttctgctg 7560
tttgaggggg ctttttactt atttccatgt tattcaaagg agactaggct tgatatttta 7620
ttactgttct tttatggaca aaaggttaca tagtatgccc ttaagactta attttaacca 7680
aaggcctagc accaccttag gggctgcaat aaacacttaa cgcgcgtgcg cacgcgcgcg 7740
cgcacacaca cacacacaca cacacacaca cacaggtcag agtttaaggc tttcgagtca 7800
tgacattcta gcttttgaat tgcgtgcaca cacacacgca cgcacacact ctggtcagag 7860
tttattaagg ctttcgagtc atgacattat agcttttgag ttggtgtgtg tgacaccacc 7920
ctcctaagtg gtgtgtgctt gtaatttttt ttttcagtga aaatggattg aaaacctgtt 7980
gttaatgctt agtgatatta tgctcaaaac aaggaaattc ccttgaaccg tgtcaattaa 8040
actggtttat atgactcaag aaaacaatac cagtagatga ttattaactt tattcttggc 8100
tctttttagg tccattttga ttaagtgact tttggctgga tcattcagag ctctcttcta 8160
gcctaccctt ggatgagtac aattaatgaa attcatattt tcaaggacct gggagccttc 8220
cttggggctg ggttgagggt ggggggttgg ggagtcctgg tagaggccag ctttgtggta 8280
gctggagagg aagggatgaa accagctgct gttgcaaagg ctgcttgtca ttgatagaag 8340
gactcacggg cttggattga ttaagactaa acatggagtt ggcaaacttt cttcaagtat 8400
tgagttctgt tcaatgcatt ggacatgtga tttaagggaa aagtgtgaat gcttatagat 8460
gatgaaaacc tggtgggctg cagagcccag tttagaagaa gtgagttggg ggttggggac 8520
agatttggtg gtggtatttc ccaactgttt cctcccctaa attcagagga atgcagctat 8580
gccagaagcc agagaagagc cactcgtagc ttctgctttg gggacaactg gtcagttgaa 8640
agtcccagga gttcctttgt ggctttctgt atacttttgc ctggttaaag tctgtggcta 8700
aaaaatagtc gaacctttct tgagaactct gtaacaaagt atgtttttga ttaaaagaga 8760
aagccaacta aaaaaaaaaa aaaaaaaaa 8789
<210> 53
<211> 1593
<212> DNA
<213> Homo sapiens
<400> 53
gcggtgccct tgcggcgcag ctggggtcgc ggccctgctc cccgcgcttt cttaaggccc 60
gcgggcggcg caggagcggc actcgtggct gtggtggctt cggcagcggc ttcagcagat 120
cggcggcatc agcggtagca ccagcactag cagcatgttg agccgggcag tgtgcggcac 180
cagcaggcag ctggctccgg ttttggggta tctgggctcc aggcagaagc acagcctccc 240
cgacctgccc tacgactacg gcgccctgga acctcacatc aacgcgcaga tcatgcagct 300
gcaccacagc aagcaccacg cggcctacgt gaacaacctg aacgtcaccg aggagaagta 360
ccaggaggcg ttggccaagg gagatgttac agcccagata gctcttcagc ctgcactgaa 420
gttcaatggt ggtggtcata tcaatcatag cattttctgg acaaacctca gccctaacgg 480
tggtggagaa cccaaagggg agttgctgga agccatcaaa cgtgactttg gttcctttga 540
caagtttaag gagaagctga cggctgcatc tgttggtgtc caaggctcag gttggggttg 600
gcttggtttc aataaggaac ggggacactt acaaattgct gcttgtccaa atcaggatcc 660
actgcaagga acaacaggcc ttattccact gctggggatt gatgtgtggg agcacgctta 720
ctaccttcag tataaaaatg tcaggcctga ttatctaaaa gctatttgga atgtaatcaa 780
ctgggagaat gtaactgaaa gatacatggc ttgcaaaaag taaaccacga tcgttatgct 840
gagtatgtta agctctttat gactgttttt gtagtggtat agagtactgc agaatacagt 900
aagctgctct attgtagcat ttcttgatgt tgcttagtca cttatttcat aaacaactta 960
atgttctgaa taatttctta ctaaacattt tgttattggg caagtgattg aaaatagtaa 1020
atgctttgtg tgattgaatc tgattggaca ttttcttcag agagctaaat tacaattgtc 1080
atttataaaa ccatcaaaaa tattccatcc atatactttg gggacttgta gggatgcctt 1140
tctagtccta ttctattgca gttatagaaa atctagtctt ttgccccagt tacttaaaaa 1200
taaaatatta acactttccc aagggaaaca ctcggctttc tatagaaaat tgcacttttt 1260
gtcgagtaat cctctgcagt gatacttctg gtagatgtca cccagtggtt tttgttaggt 1320
caaatgttcc tgtatagttt ttgcaaatag agctgtatac tgtttaaatg tagcaggtga 1380
actgaactgg ggtttgctca cctgcacagt aaaggcaaac ttcaacagca aaactgcaaa 1440
aaggtggttt ttgcagtagg agaaaggagg atgtttattt gcagggcgcc aagcaaggag 1500
aattgggcag ctcatgcttg agacccaatc tccatgatga cctacaagct agagtattta 1560
aaggcagtgg taaatttcag gaaagcagaa gtt 1593
<210> 54
<211> 3286
<212> DNA
<213> Homo sapiens
<400> 54
gcgtgtcggg cgcggaaggg ggaggcggcc cggggcgccc gcgagtgagg cgcggggcgg 60
cgaagggagc gcgggtggcg gcacttgctg ccgcggcctt ggatgggctg ggcccccctc 120
gccgctccgc ctcctccaca cgcgcggcgg ccgcggcgag ggggacgcgc cgcccggggc 180
ccggcacctt cgggaacccc ccggcccgga gcctgcggcc tgcgccgcct cggccgccgg 240
gagccccgtg gagcccccgc cgccgcgccg ccccgcggac cggacgctga gggcactcgg 300
ggcggggcgc gcgctcgggc agacgtttgc ggggaggggg gcgcctgccg ggccccggcg 360
accaccttgg gggtcgcggg ccggctcggg gggcgcccag tgcgggccct cgcgggcgcc 420
gggcagcgac cagccctgag cggagctgtt ggccgcggcg ggaggcctcc cggacgcccc 480
cagccccccg aacgctcgcc cgggccggcg ggagtcggcg ccccccggga ggtccgctcg 540
gtcgtccgcg gcggagcgtt tgctcctggg acaggcggtg ggaccggggc gtcgccggag 600
acgcccccag cgaagttggg ctctccaggt gtgggggtcc cggggggtag cgacgtcgcg 660
gacccggcct gtgggatggg cggcccggag aagactgcgc tcggccgtgt tcatacttgt 720
ccgtgggcct gaggtccccg gaggatgacc tagcactgaa aagccccggc cggcctcccc 780
agggtccccg aggacgaagt tgaccctgac cgggccgtct cccagttctg aggcccgggt 840
cccactggaa ctcgcgtctg agccgccgtc ccggaccccc ggtgcccgcc ggtccgcaga 900
ccctgcaccg ggcttggact cgcagccggg actgacgtgt agaacaatcg tttctgttgg 960
aagaagggtt tttcccttcc ttttggggtt tttgttgcct tttttttttc ttttttcttt 1020
gtaaaatttt ggagaaggga agtcggaaca caaggaagga ccgctcaccc gcggactcag 1080
ggctggcggc gggactccag gaccctgggt ccagcatgga ggtggtggac ccgcagcagc 1140
tgggcatgtt cacggagggc gagctgatgt cggtgggtat ggacacgttc atccaccgca 1200
tcgactccac cgaggtcatc taccagccgc gccgcaagcg ggccaagctc atcggcaagt 1260
acctgatggg ggacctgctg ggggaaggct cttacggcaa ggtgaaggag gtgctggact 1320
cggagacgct gtgcaggagg gccgtcaaga tcctcaagaa gaagaagttg cgaaggatcc 1380
ccaacgggga ggccaacgtg aagaaggaaa ttcaactact gaggaggtta cggcacaaaa 1440
atgtcatcca gctggtggat gtgttataca acgaagagaa gcagaaaatg tatatggtga 1500
tggagtactg cgtgtgtggc atgcaggaaa tgctggacag cgtgccggag aagcgtttcc 1560
cagtgtgcca ggcccacggg tacttctgtc agctgattga cggcctggag tacctgcata 1620
gccagggcat tgtgcacaag gacatcaagc cggggaacct gctgctcacc accggtggca 1680
ccctcaaaat ctccgacctg ggcgtggccg aggcactgca cccgttcgcg gcggacgaca 1740
cctgccggac cagccagggc tccccggctt tccagccgcc cgagattgcc aacggcctgg 1800
acaccttctc cggcttcaag gtggacatct ggtcggctgg ggtcaccctc tacaacatca 1860
ccacgggtct gtaccccttc gaaggggaca acatctacaa gttgtttgag aacatcggga 1920
aggggagcta cgccatcccg ggcgactgtg gccccccgct ctctgacctg ctgaaaggga 1980
tgcttgagta cgaaccggcc aagaggttct ccatccggca gatccggcag cacagctggt 2040
tccggaagaa acatcctccg gctgaagcac cagtgcccat cccaccgagc ccagacacca 2100
aggaccggtg gcgcagcatg actgtggtgc cgtacttgga ggacctgcac ggcgcggacg 2160
aggacgagga cctcttcgac atcgaggatg acatcatcta cactcaggac ttcacggtgc 2220
ccggacaggt cccagaagag gaggccagtc acaatggaca gcgccggggc ctccccaagg 2280
ccgtgtgtat gaacggcaca gaggcggcgc agctgagcac caaatccagg gcggagggcc 2340
gggcccccaa ccctgcccgc aaggcctgct ccgccagcag caagatccgc cggctgtcgg 2400
cctgcaagca gcagtgaggc tggccgcctg cagcccgtgt ccaggagccc cgccaggtgc 2460
ccgcgccagg ccctcagtct tcctgccggt tccgcccgcc ctcccggaga ggtggccgcc 2520
atgcttctgt gccgaccacg ccccaggacc tccggagcgc cctgcagggc cgggcagggg 2580
gacagcaggg accgggcgca gccctccccc ctcggccgcc cggcagtgca cgcggcttgt 2640
tgacttcgca gccccgggcg gagccttccc gggcgggcgt gggaggaggg aggcggcctc 2700
catgcacttt atgtggagac tactggcccc gcccgtggcc tcgtgctccg cagggcgccc 2760
agcgccgtcc ggcggccccg ccgcagacca gctggcgggt gtggagacca ggctcctgac 2820
cccgccatgc atgcagcgcc acctggaagc cgcgcggccg ctttggtttt ttgtttggtt 2880
ggttccattt tctttttttc tttttttttt taagaaaaaa taaaaggtgg atttgagctg 2940
tggctgtgag gggtgtttgg gagctgctgg gtggcagggg ggctgtgggg tcgggctcac 3000
gtcgcggccg cctttgcgct ctcgggtcac cctgctttgg cggcccggcc ggagggcagg 3060
accctcacct ctcccccaag gccactgcgc tcttgggacc ccagagaaaa cccggagcaa 3120
gcaggagtgt gcggtcaata tttatatcat ccagaaaaga aaaacacgag aaacgccatc 3180
gcgggatggt gcagacgcgg cggggactcg gagggtgccg tgcgggcgag gccgcccaaa 3240
tttggcaata aataaagctt gggaagcttg gacctgaaaa aaaaaa 3286
<210> 55
<211> 5174
<212> DNA
<213> Homo sapiens
<400> 55
ggagagctcg ccagagcgct cgcatggcgg gccggtgatt gtagtcaatc tggccgtatt 60
ctcaggcagg gtcgcccggg gcggactaca tctcccggga tgctgcgcgg ccgccccgcg 120
gaagattgtg aatatgtatc agaatgttaa tgattagctg ctgctaaatt tggtcaaaga 180
agtcacctac acagagcgtg ttgttagagc tgtgctgagc gggtgtttgg gttgttggct 240
gctttcttcc ccctttctca cacacttgta tattattttg aggtggtgtt cgcagagttt 300
gaaaggagag agaattaaaa aaaaaagccg caagcgtttc actcttttat ttttataatc 360
cccttcaatt tggggttaaa aaaaagacaa gaaaacagga aggaagagaa ataaggaaat 420
gagatgtggt aaaagaagct aaaaggtgcc ttttaaaaga tcgttgctgt gaagtgaaaa 480
aaatctccag agaaaccaaa aagcaccgcc gagacctctt ccgaaccaaa ggagtttgtg 540
tttgctttta gggaagaaga aagatcattc attcggagga ataacaacca attaaaagac 600
aaataaaaaa agtttggagt gggacgcaga gcgagcgaga ggagctgccg gcgggcggtg 660
gggcgcggag cccgcacttt cccggccggg tgagcggcgg ccgcggcgcc gggctcggcg 720
ggtgcgcctc ggcggagcga acgtcggagc gttgccttgg gagacgcgcg ccggacaatg 780
cccgcggcgg gccagtgacg cccgcgggga atgcggagcg gcccggcagc cggcacccag 840
ccgccgccgc gcgttcctgc cgcccgtgtc acgcgagacc cggcgggggc cgggaccgcc 900
cgagccgccc ctcagaccga gccggccgcc tccgctgccg cggccgcctc ctcttcgggg 960
tcattaaagc caatgagccg cgcgcctctg ccgagcgcag ccaactaaat cggcttggat 1020
gattcgcgac ctgagcaaga tgtacccgca gaccagacac ccggcaccgc atcagcctgc 1080
tcaacccttt aaatttacaa tttccgaatc ctgtgatcgg attaaggaag agtttcagtt 1140
tttacaggct caataccaca gtctgaagct ggaatgtgag aaactcgcca gtgagaagac 1200
agagatgcag cggcattatg tcatgtatta tgaaatgtcc tatgggttga atatagaaat 1260
gcacaagcag gcagagattg tcaagaggct gaatgctatc tgtgcacaag tcattccttt 1320
cctgtcccaa gagcaccagc aacaagtggt gcaggctgtg gaacgggcca agcaggtgac 1380
catggcagaa ctgaacgcca tcattgggca acaactccag gcccagcatt tatcacatgg 1440
acatggtctc cccgtacctc tgactccaca cccttcaggg ctccagcccc ctgccattcc 1500
acccatcggt agcagtgccg ggcttctggc cctctccagt gctctaggag gtcagtccca 1560
tcttccaatt aaagatgaga agaagcacca tgacaatgat caccaaagag acagagactc 1620
catcaagagc tcttcagtat ccccatcagc cagtttccga ggtgctgaga agcacagaaa 1680
ctccgcagac tactcctcag agagcaaaaa gcagaaaact gaagaaaagg aaattgcagc 1740
tcgttatgac agcgatggtg agaaaagtga tgacaacttg gtggttgacg tttccaatga 1800
ggatccatct tcccctcgag ggagcccagc acattccccc agagagaatg gcctagacaa 1860
gacacgcctg ctcaagaaag atgccccgat tagtccagcc tctattgcat cttccagcag 1920
tactccctcc tccaaatcca aagaacttag ccttaagagg gatatgggga aattgagtga 1980
aacacgtctt agcgaagatg aacaatgcac attggggtta cagagatggt tttgtcgcct 2040
gtggtttatg aatgaaaaat ctactactcc cgtctcaaag tccaataccc ctactccacg 2100
aactgatgcg cccaccccag gcagtaactc tactcccgga ttgaggcctg tacctggaaa 2160
accaccagga gttgaccctt tggcctcaag cctaaggacc ccaatggcag taccttgtcc 2220
atatccaact ccatttggga ttgtgcccca tgctggaatg aacggagagc tgaccagccc 2280
cggagcggcc tacgctgggc tccacaacat ctcccctcag atgagcgcag ctgctgccgc 2340
cgccgctgct gctgctgcct atgggagatc accagtggtg ggatttgatc cacaccatca 2400
catgcgtgtg ccagcaatac ctccaaacct gacaggcatt ccaggaggaa aaccagcata 2460
ctccttccat gttagcgcag atggtcagat gcagcctgtc ccttttccac ccgacgccct 2520
catcggacct ggaatccccc ggcatgctcg ccagatcaac accctcaacc acggggaggt 2580
ggtgtgcgcg gtgaccatca gcaaccccac gagacacgtg tacacgggtg ggaagggctg 2640
cgtcaaggtc tgggacatca gccacccagg caataagagt cctgtctccc agctcgactg 2700
tctgaacagg gataactaca tccgttcctg cagattgctc cctgatggtc gcaccctaat 2760
tgttggaggg gaagccagta ctttgtccat ttgggacctg gcggctccaa ccccacgcat 2820
caaggcagag ctgacatcct cggcccccgc ctgctatgcc ctggccatca gccccgattc 2880
caaggtctgc ttctcatgct gcagcgacgg caacatcgct gtgtgggatc tgcacaacca 2940
gaccttggtg aggcaattcc agggccacac agatggagcc agctgtattg acatttctaa 3000
tgatggcacc aagctctgga caggtggttt ggacaacacg gtcaggtcct gggacctgcg 3060
cgaggggcgg cagctgcagc agcacgactt cacctcccag atcttttctc tgggctactg 3120
cccaactgga gagtggcttg cagtggggat ggagaacagc aatgtggaag ttttgcatgt 3180
caccaagcca gacaaatacc aactacatct tcatgagagc tgtgtgctgt cgctcaagtt 3240
tgcccattgt ggcaaatggt ttgtaagcac tggaaaggac aaccttctga atgcctggag 3300
aacaccttat ggggccagta tattccagtc caaagaatcc tcatcggtgc ttagctgtga 3360
catctccgtg gacgacaaat acattgtcac tggctctggg gataagaagg ccacagttta 3420
tgaagttatt tattaaagac aaatcttcat gcagactgga cttctcctcc tggtagcact 3480
ttgctctgtc atcctttttg ttcaccccca tccccgcatc taaaaccaag gatttcagat 3540
actcattgca gttgtggagt ttaatcccct ttcttaacct cacttcccac ttgctattga 3600
attgtgaata gtcattaaaa acctgtgata ccaaatcttc agctgtctac ttggaagaac 3660
atggaataag catacttaac agtgaaaaga atctttaatt atgtattata tctgtaatat 3720
atttattttg tttaaagaag gctttctaac aatgactgac taaataaagc tgtctgctcc 3780
tgcattgata atgaaggtgc gttgtatttg atacccctcc cccccttttt ttggcaaagg 3840
aggggaaagg aaggtttaaa ataattgatt taaaatgtca ctaagtgtag actgatgact 3900
gtatagagat gtgaaatgta taattacaca tggaagcaat atgttgctgt gttgttatta 3960
ggtttttttt gtttttgttt tctacatctt ttaaagactt ttggaaattt ggctgaacaa 4020
ttagaacaca acaggccaac tcatactcat ttggatctat ttagacaacg ttaaccaata 4080
tatctatagc tttagattat attcgataaa agtaattgga ctttttttct ttttttgact 4140
cgttgacaag tgtctttgta atatgttttt agttcccttt ttttgttgta ttataggcag 4200
atgaacaaat taaatttggc ctcaaagaga gaacttactc ccttctggat atttttgcca 4260
catttctttg caaaaggaga tatatatatc tttagtcagt tttgttgtta tgagaaatta 4320
tgggttattt tgtggcatgc tctttgggag ctgcacagtt atggggagga ctcccactgc 4380
tgtgcaagtt aagtctttta caaaacaagg acagcagagg agggtttgca gagacctccc 4440
tctgaaaaac acaaagaatg gactctctcc tgggatgagg acttgctttc tttacctccg 4500
gttctttcca tgtcttagtt ggatgtccct gaaatggaca caggctgtgc cattgtgcca 4560
gaaacattgt gttatctttt atgttgttgt tgttgctgtt aaactataat atgtgacttc 4620
tttttttatt attttttgtt tgaatgcttt aaaaatcttt taagtctgtg gatctgctga 4680
tgtacagtgc ctttgctgct atggatcaaa atcaaaagaa ccgtgtagat atactttatt 4740
gtataagtag aaaattactt aatttcatac tagaaatgga tggatgctgc aagttgaaat 4800
ggactgtcca ttgacgttcc taatgtggta gcagaaaaaa aaaaatggtg tcttaagtgc 4860
ttagtgtttg atgtcattaa cagtttcgta aaactctaca gtgtagaaag attttgatac 4920
taaactgtgc gttgtacata gttctaatgc attgtattga ccaccagtac ttctataatg 4980
gtagattgtt tgtgaattca gacttttaag cattaaacat aaataacttc tagtatgctt 5040
atttttctaa ttctttgtct tgatgacatt agtttatttt ttatctttgg ctgtgccact 5100
cctatatatt aaaaatgcct agttttttca agggagattg ttgttaaagt aaagtggttt 5160
tttttgttgt taaa 5174
<210> 56
<211> 1769
<212> DNA
<213> Homo sapiens
<400> 56
cctcactgac tataaaagaa tagagaagga agggcttcag tgaccggctg cctggctgac 60
ttacagcagt cagactctga caggatcatg gctatgatgg aggtccaggg gggacccagc 120
ctgggacaga cctgcgtgct gatcgtgatc ttcacagtgc tcctgcagtc tctctgtgtg 180
gctgtaactt acgtgtactt taccaacgag ctgaagcaga tgcaggacaa gtactccaaa 240
agtggcattg cttgtttctt aaaagaagat gacagttatt gggaccccaa tgacgaagag 300
agtatgaaca gcccctgctg gcaagtcaag tggcaactcc gtcagctcgt tagaaagatg 360
attttgagaa cctctgagga aaccatttct acagttcaag aaaagcaaca aaatatttct 420
cccctagtga gagaaagagg tcctcagaga gtagcagctc acataactgg gaccagagga 480
agaagcaaca cattgtcttc tccaaactcc aagaatgaaa aggctctggg ccgcaaaata 540
aactcctggg aatcatcaag gagtgggcat tcattcctga gcaacttgca cttgaggaat 600
ggtgaactgg tcatccatga aaaagggttt tactacatct attcccaaac atactttcga 660
tttcaggagg aaataaaaga aaacacaaag aacgacaaac aaatggtcca atatatttac 720
aaatacacaa gttatcctga ccctatattg ttgatgaaaa gtgctagaaa tagttgttgg 780
tctaaagatg cagaatatgg actctattcc atctatcaag ggggaatatt tgagcttaag 840
gaaaatgaca gaatttttgt ttctgtaaca aatgagcact tgatagacat ggaccatgaa 900
gccagttttt tcggggcctt tttagttggc taactgacct ggaaagaaaa agcaataacc 960
tcaaagtgac tattcagttt tcaggatgat acactatgaa gatgtttcaa aaaatctgac 1020
caaaacaaac aaacagaaaa cagaaaacaa aaaaacctct atgcaatctg agtagagcag 1080
ccacaaccaa aaaattctac aacacacact gttctgaaag tgactcactt atcccaagaa 1140
aatgaaattg ctgaaagatc tttcaggact ctacctcata tcagtttgct agcagaaatc 1200
tagaagactg tcagcttcca aacattaatg caatggttaa catcttctgt ctttataatc 1260
tactccttgt aaagactgta gaagaaagcg caacaatcca tctctcaagt agtgtatcac 1320
agtagtagcc tccaggtttc cttaagggac aacatcctta agtcaaaaga gagaagaggc 1380
accactaaaa gatcgcagtt tgcctggtgc agtggctcac acctgtaatc ccaacatttt 1440
gggaacccaa ggtgggtaga tcacgagatc aagagatcaa gaccatagtg accaacatag 1500
tgaaacccca tctctactga aagtgcaaaa attagctggg tgtgttggca catgcctgta 1560
gtcccagcta cttgagaggc tgaggcagga gaatcgtttg aacccgggag gcagaggttg 1620
cagtgtggtg agatcatgcc actacactcc agcctggcga cagagcgaga cttggtttca 1680
aaaaaaaaaa aaaaaaaaaa cttcagtaag tacgtgttat ttttttcaat aaaattctat 1740
tacagtatgt caaaaaaaaa aaaaaaaaa 1769
<210> 57
<211> 2979
<212> DNA
<213> Homo sapiens
<400> 57
gtggctcttc tggcccgggc tactatatag agacgtttcc gcctcctgct tgaaactaac 60
ccctcttttt ctccaaagga gtgcttgtgg agatcggatc ttttctccag caattggggg 120
aaagaaggct ttttctctga attagcttag tgtaaccagc ggcgtatatt ttttaggcgc 180
cttttcgaaa acctagtagt taatattcat ttgtttaaat cttattttat ttttaagctc 240
aaactgctta agaatacctt aattccttaa agtgaaataa ttttttgcaa aggggtttcc 300
tcgatttgga gctttttttt tcttccaccg tcatttctaa ctcttaaaac caactcagtt 360
ccatcatggt gatgttcaag aagatcaagt cttttgaggt ggtctttaac gaccctgaaa 420
aggtgtacgg cagtggcgag aaggtggctg gccgggtgat agtggaggtg tgtgaagtta 480
ctcgtgtcaa agccgttagg atcctggctt gcggagtggc taaagtgctt tggatgcagg 540
gatcccagca gtgcaaacag acttcggagt acctgcgcta tgaagacacg cttcttctgg 600
aagaccagcc aacaggtgag aatgagatgg tgatcatgag acctggaaac aaatatgagt 660
acaagttcgg ctttgagctt cctcaggggc ctctgggaac atccttcaaa ggaaaatatg 720
ggtgtgtaga ctactgggtg aaggcttttc ttgaccgccc gagccagcca actcaagaga 780
caaagaaaaa ctttgaagta gtggatctgg tggatgtcaa tacccctgat ttaatggcac 840
ctgtgtctgc taaaaaagaa aagaaagttt cctgcatgtt cattcctgat gggcgggtgt 900
ctgtctctgc tcgaattgac agaaaaggat tctgtgaagg tgatgagatt tccatccatg 960
ctgactttga gaatacatgt tcccgaattg tggtccccaa agctgccatt gtggcccgcc 1020
acacttacct tgccaatggc cagaccaagg tgctgactca gaagttgtca tcagtcagag 1080
gcaatcatat tatctcaggg acatgcgcat catggcgtgg caagagcctt cgggttcaga 1140
agatcaggcc ttctatcctg ggctgcaaca tccttcgagt tgaatattcc ttactgatct 1200
atgttagcgt tcctggatcc aagaaggtca tccttgacct gcccctggta attggcagca 1260
gatcaggtct aagcagcaga acatccagca tggccagccg aaccagctct gagatgagtt 1320
gggtagatct gaacatccct gataccccag aagctcctcc ctgctatatg gatgtcattc 1380
ctgaagatca ccgattggag agcccaacca ctcctctgct agatgacatg gatggctctc 1440
aagacagccc tatctttatg tatgcccctg agttcaagtt catgccacca ccgacttata 1500
ctgaggtgga tccctgcatc ctcaacaaca atgtgcagtg agcatgtgga agaaaagaag 1560
cagctttacc tacttgtttc tttttgtctc tcttcctgga cactcacttt ttcagagact 1620
caacagtctc tgcaatggag tgtgggtcca ccttagcctc tgacttccta atgtaggagg 1680
tggtcagcag gcaatctcct gggccttaaa ggatgcggac tcatcctcag ccagcgccca 1740
tgttgtgata caggggtgtt tgttggatgg gtttaaaaat aactagaaaa actcaggccc 1800
atccattttc tcagatctcc ttgaaaattg aggccttttc gatagtttcg ggtcaggtaa 1860
aaatggcctc ctggcgtaag cttttcaagg ttttttggag gctttttgta aattgtgata 1920
ggaactttgg accttgaact tacgtatcat gtggagaaga gccaatttaa caaactagga 1980
agatgaaaag ggaaattgtg gccaaaactt tgggaaaagg aggttcttaa aatcagtgtt 2040
tcccctttgt gcacttgtag aaaaaaaaga aaaaccttct agagctgatt tgatggacaa 2100
tggagagagc tttccctgtg attataaaaa aggaagctag ctgctctacg gtcatctttg 2160
cttagagtat actttaacct ggcttttaaa gcagtagtaa ctgccccacc aaaggtctta 2220
aaagccattt ttggagccta ttgcactgtg ttctcctact gcaaatattt tcatatggga 2280
ggatggtttt ctcttcatgt aagtccttgg aattgattct aaggtgatgt tcttagcact 2340
ttaattcctg tcaaattttt tgttctcccc ttctgccatc ttaaatgtaa gctgaaactg 2400
gtctactgtg tctctagggt taagccaaaa gacaaaaaaa attttactac ttttgagatt 2460
gccccaatgt acagaattat ataattctaa cgcttaaatc atgtgaaagg gttgctgctg 2520
tcagccttgc ccactgtgac ttcaaaccca aggaggaact cttgatcaag atgcccaacc 2580
ctgtgatcag aacctccaaa tactgccatg agaaactaga gggcaggtct tcataaaagc 2640
cctttgaacc cccttcctgc cctgtgttag gagataggga tattggcccc tcactgcagc 2700
tgccagcact tggtcagtca ctctcagcca tagcactttg ttcactgtcc tgtgtcagag 2760
cactgagctc cacccttttc tgagagttat tacagccaga aagtgtgggc tgaagatggt 2820
tggtttcatg tttttgtatt atgtatcttt ttgtatggta aagactatat tttgtactta 2880
accagatata tttttacccc agatggggat attctttgta aaaaatgaaa ataaagtttt 2940
tttaatggaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2979
Claims (14)
1.至少基于受试者的氧化应激状态、优选受试者的FOXO转录因子元件的氧化应激状态,推断受试者的PI3K细胞信号传导通路的活性的方法,包括:
基于受试者的选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT的一或多个基因的表达水平推断受试者的氧化应激状态,优选受试者的FOXO转录因子元件的氧化应激状态。
2.权利要求1的方法,其中所述推断受试者的PI3K细胞信号传导通路的活性基于推断的受试者的氧化应激状态和受试者的FOXO转录因子元件的活性水平。
3.权利要求1或2的方法,进一步包括确定受试者的所述一或多个基因的表达水平。
4.权利要求1-3任一项的方法,其中所述推断受试者的氧化应激状态基于受试者的选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT的至少4个、优选全部FOXO靶基因的表达水平。
5.权利要求1-3任一项的方法,其中所述推断受试者的氧化应激状态是基于选自受试者的SOD2、BNIP3、MXI1和PCK1的两个或更多个、优选全部FOXO靶基因的表达水平。
6.权利要求1-3任一项的方法,其中所述推断受试者的氧化应激状态基于受试者的选自SOD2、BNIP3、MXI1、PCK1、PPARGC1A和CAT的一个FOXO靶基因的表达水平。
7.权利要求4或5的方法,其中当受试者的提取样品中SOD2和/或BNIP3的表达水平与对照样品相比上调时和/或当受试者的提取样品中选自MXI1、PCK1、PPARGC1A和CAT的一或多个靶基因的表达水平与对照样品相比下调时,推断是氧化应激状态。
8.权利要求1-7任一项的方法,其中至少基于在受试者的提取样品中测量的选自如下一组中的一或多个、优选至少3个PI3K细胞信号传导通路的靶基因的表达水平确定受试者的FOXO转录因子元件的活性水平:AGRP、BCL2L11、BCL6、BNIP3、BTG1、CAT、CAVl、CCND1、CCND2、CCNG2、CDKN1A、CDKN1B、ESR1、FASLG、FBXO32、GADD45A、INSR、MXI1、NOS3、PCK1、POMC、PPARGC1A、PRDX3、RBL2、SOD2和TNFSF10。
9.权利要求1-8任一项的方法,其中进一步至少基于在受试者的提取样品中测量的选自ATP8A1、C10orf10、CBLB、DDB1、DYRK2、ERBB3、EREG、EXT1、FGFR2、IGF1R、IGFBP1、IGFBP3、LGMN、PPM1D、SEMA3C、SEPP1、SESN1、SLC5A3、SMAD4和TLE4和/或选自ATG14、BIRC5、IGFBP1、KLF2、KLF4、MYOD1、PDK4、RAG1、RAG2、SESN1、SIRT1、STK11和TXNIP的一或多个、优选至少3个PI3K细胞信号传导通路的靶基因的表达水平确定受试者的FOXO转录因子元件的活性水平。
10.权利要求1-9任一项的方法,进一步包括:
基于受试者的PI3K细胞信号传导通路的推断的活性确定受试者的PI3K细胞信号传导通路是否异常运行。
11.权利要求10的方法,进一步包括:
给受试者推荐处方纠正PI3K细胞信号传导通路的异常运行的药物,其中如果基于PI3K细胞信号传导通路的推断的活性确定受试者的PI3K细胞信号传导通路是异常运行的,进行所述推荐。
12.权利要求1-11任一项的方法,其中所述方法用于指示受试者的癌症状态或癌前状态。
13.权利要求1-12任一项的方法,其中所述方法用于如下活动的至少一种:
基于受试者的PI3K细胞信号传导通路的推断的活性的诊断;
基于受试者的PI3K细胞信号传导通路的推断的活性的预后;
基于受试者的PI3K细胞信号传导通路的推断的活性的药物处方;
基于受试者的PI3K细胞信号传导通路的推断的活性的药物功效预测;
基于受试者的PI3K细胞信号传导通路的推断的活性的副作用预测;
监测药物功效;
药物开发;
测定法开发;
通路研究;
癌症分期;
基于受试者的PI3K细胞信号传导通路的推断的活性的临床试验受试者的招募;
要进行的后续测试的选择;和
伴随诊断测试的选择。
14.一种计算机程序,其包含使得数字处理装置执行权利要求1-13任一项的方法的程序代码工具。
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PCT/EP2017/080298 WO2018096076A1 (en) | 2016-11-25 | 2017-11-24 | Method to distinguish tumor suppressive foxo activity from oxidative stress |
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CN116144667A (zh) * | 2022-12-29 | 2023-05-23 | 海南大学 | 卵形鲳鲹胰岛素样生长因子结合蛋白1基因、蛋白及应用 |
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US20230223108A1 (en) | 2020-04-16 | 2023-07-13 | Innosign B.V. | Prognostic pathways for viral infections |
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EP3965119A1 (en) | 2020-09-04 | 2022-03-09 | Koninklijke Philips N.V. | Methods for estimating heterogeneity of a tumour based on values for two or more genome mutation and/or gene expression related parameter, as well as corresponding devices |
EP3974540A1 (en) | 2020-09-25 | 2022-03-30 | Koninklijke Philips N.V. | Method for predicting immunotherapy resistance |
EP4015651A1 (en) | 2020-12-17 | 2022-06-22 | Koninklijke Philips N.V. | Treatment prediction and effectiveness of anti-tnf alpha treatment in ibd patients |
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