CN111712257B - 携带双特异性T细胞衔接器(BiTE)的腺病毒 - Google Patents

携带双特异性T细胞衔接器(BiTE)的腺病毒 Download PDF

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CN111712257B
CN111712257B CN201880055171.0A CN201880055171A CN111712257B CN 111712257 B CN111712257 B CN 111712257B CN 201880055171 A CN201880055171 A CN 201880055171A CN 111712257 B CN111712257 B CN 111712257B
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B·查皮尔
A·C·N·布罗姆利
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Abstract

一种包括式(I)的序列的腺病毒:5'ITR‑B1‑BA‑B2‑BX‑BB‑BY‑B3‑3'ITR (I)其中BY包括含有四个转基因的转基因盒,所述基因编码FAP‑BITE、CXL10、CXL9和IFN。本公开还扩展到包括所述病毒的药物组合物,以及使用所述病毒或调配物进行治疗。

Description

携带双特异性T细胞衔接器(BiTE)的腺病毒
本公开涉及一种修饰的腺病毒,具体地Enadenotucirev(EnAd),其具有FAP-BITE组合物,如包括腺病毒的药物调配物,病毒和病毒调配物的用途,特别是用于治疗的用途,尤其是用于治疗癌症的用途。本公开还扩展到用于制备病毒的方法和编码病毒的DNA。本公开还扩展到与本文的技术公开组合的序列表中提供的新序列,例如其中例证的病毒被例如序列表中提供的替代盒或替代病毒替代。
背景技术
就患者及其亲人的困难和痛苦,以及治疗、照顾和支持患者的高昂经济成本而言,癌症仍然是社会的巨大负担。
癌细胞周围的基质是物理保护,因为其可能具有诱捕免疫细胞以对抗肿瘤的功能。此外,基质屏蔽了肿瘤的缺氧微环境,这对于肿瘤的生长是允许的和最佳的。存在一些理论认为基质中的细胞是肿瘤中的能量来源。
肿瘤基质的一个大组分是成纤维细胞,所述成纤维细胞已经被破坏以起到引发癌症的作用。渗入基质的其它细胞是肿瘤相关巨噬细胞(TAM),其是2型(M2)巨噬细胞,所述巨噬细胞可以通过分泌如抑制免疫应答的IL-10等细胞因子和趋化因子来促进肿瘤生长。
因为产生环境的细胞是遍布全身的“天然的”免疫细胞或结缔组织细胞,所以靶向肿瘤基质特别困难。因此,用治疗剂靶向这些细胞可能导致严重的脱靶效应。
因此,需要一种将BiTE直接递送到肿瘤细胞的改进方法,其中它可以提供最大的治疗益处,具体地递送到由基质成纤维细胞包围的肿瘤细胞。
通过引用并入本文的WO2018/041838和WO2018/041827两者公开了编码BITE的某些腺病毒。然而,通过掺入活化的细胞因子来增强在病毒中包埋的BITE的活性将是有用的。与BITE共同定位的两种细胞因子的整合可以轻松完成。然而,当三种细胞因子与BITE共存时,基因的性质开始影响BITE的表达。本发明人制造了具有4个转基因的病毒NG-615,如图1所示。然而,BITE的表达减少了。令人惊讶地,(与NG-615相比),其中两种细胞因子被改变的病毒NG-641具有良好的活性,包含BITE的良好表达。因此,看来四种转基因一起与病毒共存是相容的。
当前要求保护的发明涉及容纳在纤维、L5和E4区之间共存的所述四个转基因的病毒。
发明内容
以下段落是本公开的概述:
1.一种包括式(I)的序列的腺病毒:
5'ITR-B1-BA-B2-BX-BB-BY-B3-3'ITR (I)
其中:
B1是键或包括:E1A、E1B或E1A到E1B;
BA包括-E2B-L1-L2-L3-E2A-L4;
B2是键或包括:E3;
BX是键或DNA序列,其包括:限制性位点、一个或多个转基因或两者;
BB包括L5;
BY包括含有四个转基因的转基因盒,所述基因编码FAP-BITE、CXL10、CXL9和IFN;
B3是键或包括:E4。
2.根据段落1所述的腺病毒,其中编码的FAB-BITE包括SEQ ID NO:5中所示的抗CD3或与其至少95%相同的序列,如SEQ ID NO:5。
3.根据段落1或2所述的腺病毒,其中所述FAP-BITE包括SEQ ID NO:9中所示的抗FAP或与其至少95%相同的序列,如SEQ ID NO:9
4.根据段落1所述的腺病毒,其中编码的FAB-BITE包括选自SEQ ID NO:75,SEQ IDNO:76的序列或与其任何一个至少95%相同的序列。
5.根据段落1到4中任一项所述的腺病毒,其中所述转基因盒编码SEQ ID NO:100中所示的CXL10或与其至少95%相同的序列,如SEQ ID NO:100。
6.根据段落1到5中任一项所述的腺病毒,其中所述转基因盒编码SEQ ID NO:99中所示的CXCL9或与其至少95%相同的序列,如SEQ ID NO:99。
7.根据段落1到6中任一项所述的腺病毒,其中所述转基因盒编码SEQ ID NO:98中所示的IFNα或与其至少95%相同的序列,如SEQ ID NO:98。
8.根据段落1到7中任一项所述的腺病毒,其中所述转基因被可操作地连接。
9.根据段落1到8中任一项所述的腺病毒,其中所述转基因被3种不同的高效自切割肽分开。
10.根据段落9所述的腺病毒,其中所述自切割肽独立地选自E2A、F2A、P2A和T2A。
11.根据段落1到10中任一项所述的腺病毒,其中从L5到E4的转基因的相对顺序是FAP-BITE、CXL10、CXL9和IFNα,例如如图1中的NG-641所示。
12.根据段落1到11中任一项所述的腺病毒,其中所述转基因盒具有SEQ ID NO:95中所示的多核苷酸序列或编码相同氨基酸序列的多核苷酸,具体地SEQ ID NO:95。
13.根据段落1到12中任一项所述的腺病毒,其中所述腺病毒包括SEQ ID NO:84。
14.根据段落1到13中任一项所述的腺病毒,其中所述腺病毒具有复制能力。
15.根据段落1到14中任一项所述的腺病毒,其中所述腺病毒是溶瘤的。
16.根据段落1到15中任一项所述的腺病毒,其中所述病毒具有六邻体和来自Ad11的纤维。
17.一种药物组合物,其包括根据段落1到16中任一项所述的腺病毒和赋形剂、稀释剂或载剂。
18.根据段落1到16中任一项所述的腺病毒或根据段落17所述的药物组合物,其用于治疗,例如用于治疗癌症。
19.一种治疗患者的方法,其包括施用根据段落1到16中任一项所述的腺病毒或根据段落17所述的药物组合物。
20.一种根据段落1到16中任一项所述的腺病毒或根据段落17所述的药物组合物用于制造用于癌症治疗的药物的用途。
在一个实施例中,根据本公开的一个或多个BiTE不包括跨膜结构域,并且因此不在癌细胞表面上表达,而是包括促进BiTE分子从通过病毒感染的癌细胞中释放的信号序列。
在一个实施例中,转基因盒处于内源启动子,例如主要的后启动子的控制之下。
有利地,诸位发明人已经发现,用BiTE分子携带腺病毒允许双特异性抗体片段分子“背负”腺病毒选择性感染癌细胞的能力,由此能够将BiTE靶向递送到肿瘤细胞。
有利地,BiTE很小并且可以在哺乳动物细胞中制备。因此,一旦被本公开的腺病毒感染,BiTE分子由肿瘤细胞合成、分泌并且可以局部起作用,从而扩散到病毒的直接足迹之外。因此,这允许BiTE扩散到感染的直接位点之外,但同时限制病毒的传播范围远远超过感染的肿瘤细胞位点。这最大限度地降低了不希望的脱靶效应的风险。
在一个实施例中,腺病毒是EnAd。与例如基于Ad5的其它腺病毒平台相比,EnAd已经显示具有增强的溶瘤活性。EnAd还已经示出了对人类上皮来源的癌细胞具有高选择性,如结肠癌、肺癌、膀胱癌和肾癌细胞。这使其成为BiTE分子的理想递送媒剂,因为T细胞可以被BiTE分子活化以攻击靶细胞,而EnAd同时感染和溶解癌细胞。这导致对肿瘤的双管齐下的攻击,其具有协同的溶瘤作用。
在一个实施例中,BITE的抗CD3组分对选自CD3ε、CD3γ和CD3δ,具体地CD3ε的抗原具有选择性。
FAP是一种肿瘤基质抗原。有利地,表达这些抗原的基质细胞(非转化细胞)不经历与转化细胞相同水平的突变抗性选择过程。因此,这些细胞更容易靶向癌症疗法,因为它们不是“移动靶”。此外,在基质细胞中发现的受体类型通常在不同类型的癌症中是常见的。因此,靶向FAP可能对多种癌症类型有效。
有利地,FAP在肿瘤相关成纤维细胞上被上调。成纤维细胞是固体癌的重要组分,支持干预的生长、侵袭和恢复。它们通常占晚期癌症中40%到60%的细胞。有利地,成纤维细胞是遗传上稳定的细胞,其比癌细胞更不可能逃避治疗。活化的成纤维细胞在各种肿瘤类型中也相对相似。因此,通过活化T细胞以靶向并且杀死表达FAP的肿瘤相关成纤维细胞,本公开的腺病毒可以帮助减少免疫抑制途径的谱,如由IL-10、TGFβ和IDO介导的途径。
在一个实施例中,BX不是键。
在一个实施例中,所述腺病毒是嵌合的。在一个实施例中,所述腺病毒是溶瘤的。在一个实施例中,所述腺病毒是嵌合的和溶瘤的。在一个实施例中,所述腺病毒能够进行复制。在一个实施例中,所述腺病毒是嵌合的、溶瘤的和能够进行复制的。在一个实施例中,所述腺病毒是复制型的。在另一个实施例中,所述腺病毒是嵌合的、溶瘤的和复制型的。在一个实施例中,所述腺病毒具有复制缺陷,即是载体。
在一个实施例中,BX包括转基因或转基因盒,具体地,编码BiTE的转基因盒。在一个实施例中,另外的转基因在外源启动子,如CMV启动子的控制下。
在一些实施例中采用外源启动子可能是有利的,因为所述外源启动子可以强烈地和组成性地表达抗体或片段,这在某些情况下可能特别有用,例如在患者具有严重弥漫性癌症的情况下。有利地,组成型外源启动子的使用导致转基因的连续转录,这在某些情况下可能是期望的。
在一个实施例中,转基因盒例如在编码序列的开始,具体地在转基因盒的L5末端包括Kozak序列。
在一个实施例中,转基因盒进一步包括多聚腺苷酸化序列,例如在序列的末端,具体地在转基因盒的E4区末端。
在一个实施例中,转基因盒具有图1所示的布置,如病毒NG-641。
在一个实施例中,BiTE分子具有短的半衰期,例如48小时或更短。
在一个实施例中,腺病毒仅含有一种BiTE。
在另一个实施例中,腺病毒含有两种BiTE。
在一个实施例中,FAP-BiTE包括VH结构域,所述VH结构域包括如SEQ ID NO:11中所阐述的氨基酸序列,或与其至少95%相同的氨基酸序列。
在一个实施例中,FAP-BiTE包括VL结构域,所述VL结构域包括SEQ ID NO:10中所阐述的氨基酸序列,或与其至少95%相同的氨基酸序列。
在一个实施例中,FAP-BiTE的抗CD3部分包括VH结构域,所述VH结构域包括SEQ IDNO:6中所阐述的氨基酸序列,或与其至少95%相同的氨基酸序列。
在一个实施例中,FAP-BiTE的抗CD3部分包括VL结构域,所述VL结构域包括SEQ IDNO:7中所阐述的氨基酸序列,或与其至少95%相同的氨基酸序列。
在一个实施例中,根据本公开的腺病毒包括SEQ ID NO:34或35中所阐述的序列或编码相同scFv氨基酸序列的多核苷酸,具体地SEQ ID NO:34。
在一个实施例中,根据本公开的腺病毒包括SEQ ID NO:68,SEQ ID NO:69中所阐述的序列或编码相同氨基酸序列的多核苷酸。
在一个实施例中,根据本公开的腺病毒包括SEQ ID NO:90中所阐述的序列或编码相同氨基酸序列的多核苷酸。
在一个实施例中,根据本公开的腺病毒包括SEQ ID NO:91中所阐述的序列或编码相同氨基酸序列的多核苷酸。
在一个实施例中,根据本公开的腺病毒包括SEQ ID NO:92中所阐述的序列或编码相同氨基酸序列的多核苷酸。
技术人员意识到DNA代码中存在冗余,因此本公开扩展到编码具有本文公开的氨基酸的BiTE的EnAd或Ad11。
C末端His亲和标签(如deca或hexa-his标签)可用于BiTE或腺病毒的纯化。但是,它是可选的,并且可以例如在最终产品中排除。技术人员意识到可以使用除deca-His之外的其它亲和标签,并且同样可以排除这些标签而不影响BiTE或腺病毒的生物学功能。
因此,在一个实施例中,BiTE包括如SEQ ID NO:1或2中所阐述的氨基酸序列,但是不包含序列的C末端端部的His亲和标签,如SEQ ID NO:61或62。
排除deca-His亲和标签进一步延伸到本文公开的包括deca-His亲和标签的所有其它序列,即本公开包含缺少C-末端His标签的相同氨基酸或DNA序列。
在一个方面,提供了包括如本文所描述的腺病毒和稀释剂或载剂的组合物。
在一个方面,提供了治疗患者的方法,包括施用治疗有效量的如本文所描述的腺病毒或组合物。
在一个实施例中,所述方法用于治疗癌症,例如上皮癌,具体地实体瘤。
在一个实施例中,提供了一种治疗方法,其包括将根据本公开的病毒与检查点抑制剂(如PD-1或PDL1抑制剂)组合施用,具体地其中检查点抑制剂在病毒中编码。
在一个实施例中,提供了一种治疗方法,其包括施用根据本公开的病毒,其不与检查点抑制剂(例如本文其它地方所列出的,如PD-1或PDL1抑制剂)组合,具体地其中检查点抑制剂不在病毒编码中。
根据本公开由病毒编码的BiTE具有增强病毒细胞毒性的能力。
令人惊讶的是,根据本公开的由病毒编码的BiTe可以活化CD4+细胞和/或CD8+细胞,例如甚至在肿瘤的抑制环境中的细胞,包含肿瘤的如腹水等液体环境中的T细胞。
有利地,根据本公开的由病毒编码的BiTe可以活化细胞毒性T细胞,例如甚至在肿瘤的抑制环境中的T细胞,包含肿瘤的如腹水等液体环境中的T细胞。
甚至更令人惊讶的是,根据本公开的由病毒编码的BiTE能够刺激(活化)T细胞增殖。
根据本公开的编码BiTE的病毒似乎能够绕过、克服或逆转肿瘤的免疫抑制微环境。
在一个实施例中,T细胞的活化导致T细胞标记物,例如CD25的上调。
具体实施方式
如本文所采用的免疫细胞是在免疫系统中具有功能作用的细胞,包含(但不限于)巨噬细胞、中性粒细胞、树突细胞、NK细胞、如T淋巴细胞(具体地T细胞和NKT细胞)等淋巴细胞。
如本文所采用的抗原结合位点是指分子的一部分,其包括一对可变区,具体地与靶抗原特异性相互作用的同源对。
具体地,如本文所采用的,旨在表示仅识别其特异性抗原的结合位点或与对抗原具有显著更高的结合亲和力的结合位点,与对其非特异性的抗原的亲和力相比具有特异性,例如结合亲和力高5倍、6倍、7倍、8倍、9倍、10倍。亲和力可以通过如BIAcore等技术进行测量。
如本文所采用的双特异性抗体分子是指具有两个抗原结合结构域的分子,其可以结合相同或不同的抗原。BiTE是双特异性抗体分子的亚类。
如本文所用的BITE是指双特异性T细胞衔接器,具体地包括抗CD3结合结构域和另外的结合结构域,在这种情况下是抗FAP结合结构域。通常,结合结构域呈scFv的形式。图12中显示了BiTE的示意图。
因此,如本文所使用的双特异性T细胞衔接器(BiTE)是指一类人工双特异性单克隆抗体,其包括2个scFv的不同抗体或来自约55KDa的单个肽链上的4个不同基因的氨基酸序列。其中一种scFv对免疫细胞具有特异性,如在T细胞表面表达的T细胞抗原,如CD3受体。在现有技术下,另一种scFv通常通过肿瘤特异性分子与肿瘤细胞结合。因此,BiTE能够通过其对T细胞上的抗原和肿瘤细胞上的抗原的特异性在T细胞与肿瘤细胞之间形成连接。这导致T细胞的活化并且触发T细胞对肿瘤细胞发挥其细胞毒性作用,而与MHC I或共刺激分子无关。
在一个实施例中,T细胞衔接器被布置为VL1-连接子1-VH1-连接子2-VH2-连接子3-VL2的形式,例如采用独立地选自本文公开的连接子序列的连接子。
在一个实施例中,BITE连接子的长度范围为10个到30个氨基酸,如10个、11个、12个、13个、14个、15个、16个、17个、18个、19个、20个、21个、22个、23个、24个、25个、26个、27个、28个、29个或30个,例如本文公开的连接子。
如本文所采用的基质或基质抗原是指基质中的抗原治疗靶,包含在基质基质的分子结构中表达,如结缔组织分子或与此基质相关的分子或与基质的细胞组分相关的抗原,例如已经渗入基质的成纤维细胞、肿瘤相关巨噬细胞、树突细胞、NK细胞和/或T细胞上表达。基质抗原的实例包含但不限于FAP、TGFβ、TREM1、IGFBP7、FSP-1、成纤维细胞相关的抗原、NG2、内皮唾液酸蛋白(CD248)、血小板衍生生长因子α受体(PDGFR-α)、血小板衍生生长因子-β受体(PDGFR-β)和波形蛋白。通常,基质抗原不在癌细胞上表达,即它们仅在基质细胞上表达。
成纤维细胞可以通过采用抗原成纤维细胞活化蛋白(FAP),具体地不结合CD26的FAP特异性抗体来靶向(参见US2012/0258119,通过引用并入本文)。
FAP最初被鉴定为反应性基质成纤维细胞上的丝氨酸蛋白酶。随后的分子克隆显示FAP与seprase相同,seprase是由黑素瘤细胞系表达的170kDa膜相关明胶酶。全长cDNA编码760个氨基酸(aa)的H型跨膜蛋白酶,其与二肽基肽酶IV(DPPIV)高度同源,在整个序列上具有52%的同一性,并且在催化结构域中具有几乎70%的同一性。通过引用并入本文的US5,587,299描述了编码FAP的核酸分子及其应用。
总之,FAP被认为是一种多功能蛋白质,所述多功能蛋白质通过其蛋白酶活性和其与其它细胞表面分子形成复合物的能力的组合,以细胞依赖性方式执行其生物学功能。上皮细胞和成纤维细胞系中FAP的过度表达促进恶性行为,指向临床情况,其中FAP的细胞表达水平与更差的临床结果相关。
通过旁分泌信号分子、癌细胞活化基质成纤维细胞并且诱导FAP的表达,这进而影响癌细胞的增殖、侵袭和迁移。最近的研究已经证明TGF-β是促进FAP蛋白表达的主要因素(Chen、H等人,(2009),《实验与分子病理学(Exp and Molec Pathology)》,doi:10.1016/j.yexmp。2009.09.001)。FAP在90%的人上皮癌中的反应性基质成纤维细胞中大量表达,包含乳腺癌、肺癌、结肠癌和卵巢癌(Garin-Chesa、P等人,(1990),《美国科学院院报(PNASUSA)》,87:7236-7239)。Chen等人最近表明FAPα影响HO-8910PM卵巢癌细胞的侵袭、增殖和迁移(Chen、H等人,(2009),《实验与分子病理学》,doi:10.1016/j.yexmp。2009.09.001)。
FAP可以通过结合所述抗原并且在空间上阻断其与生物相关分子的相互作用来靶向。可替代地,或另外使FAP分子与另一种FAP分子或不同分子交联,例如交联到T细胞。这种交联提高了携带FAP的细胞对免疫系统的可见性,然后所述免疫系统可以被活化到中性或破坏免疫系统。
本公开的腺病毒具有感染肿瘤细胞的能力,并且具体地选择优先感染肿瘤细胞。溶瘤病毒感染引起癌细胞的死亡和溶解,释放新生成的病毒颗粒。掺入的转基因,如BiTE和细胞因子在细胞中合成,并且在所述肿瘤细胞死亡之前由其主动分泌。细胞裂解后也会释放一些分子。
具有短半衰期的抗体分子,如BiTE可能特别适合用于本公开内容,因为这使脱靶效应最小化,因为如果分子变得全身可用,则身体会快速清除所述分子。
因此,根据本公开的腺病毒具有至少两种或三种攻击肿瘤的机制,包含破坏肿瘤基质的间接机制。
如本文所采用的转基因是指已经插入基因组序列的基因,所述基因组序列是对病毒不自然的基因(外源的)或通常不在病毒的特定位置发现的基因。转基因的实例是本领域已知的,并且在本文中讨论。如本文所采用的转基因还包含基因的功能片段,所述基因的功能片段是基因的一部分,其在插入时适合于执行全长基因的功能或大部分功能。
除非上下文另有指示,否则转基因和编码序列在插入病毒基因组的上下文中可互换使用。如本文所采用的编码序列意指例如编码功能性RNA、肽、多肽或蛋白质的DNA序列。通常,编码序列是用于编码目的功能性RNA、肽、多肽或蛋白质的转基因的cDNA。功能性RNA、肽、多肽和感兴趣的蛋白质描述如下。
显然,病毒基因组含有DNA的编码序列。在本说明书的上下文中,病毒的基因组序列中的内源(天然存在的基因)不被认为是转基因,除非之后通过重组技术修饰,使得它们在非天然位置或在非天然环境中。
在一个实施例中,如本文所采用的,转基因是指含有基因或cDNA序列的DNA区段,所述基因或cDNA序列已经从一种生物体中分离并且被引入不同的生物体,即本公开的病毒。在一个实施例中,此非天然DNA区段可以保留产生功能性RNA、肽、多肽或蛋白质的能力。
因此,在一个实施例中,插入的转基因编码人类或人源化蛋白质、多肽或肽。
如本文所用,可操作地连接是指转基因与必要的调控元件相关,以使基因具有功能性,即一旦病毒进入细胞内,就允许利用细胞机制表达基因。
在一个或多个实施例中,所述盒如图中或实例中的一个或多个所示布置。
如本文所采用的转基因盒是指编码以一个或多个编码序列和一个或多个调控元件形式的一个或多个转基因的DNA序列。
转基因盒可以编码一个或多个单顺反子和/或多顺反子mRNA序列。
在一个实施例中,转基因或转基因盒编码单顺反子或多顺反子mRNA,并且例如所述盒适于在内源启动子或外源启动子或其组合控制下的位置处插入腺病毒基因组。
如本文所采用的单顺反子mRNA是指编码单一功能性RNA、肽、多肽或蛋白质的mRNA分子。
在一个实施例中,转基因盒编码单顺反子mRNA。
在一个实施例中,在编码单顺反子mRNA的盒的上下文中,转基因盒意指任选地含有外源启动子的DNA区段(其是将确定转基因何时何地处于活跃状态的调节序列)或剪接位点(其是调节序列确定mRNA分子何时将被剪接体裂解)编码序列(即转基因),通常衍生自感兴趣的蛋白质的cDNA,任选地含有polyA信号序列和终止子序列。
在一个实施例中,转基因盒可以编码一个或多个多顺反子mRNA序列。
如本文所采用的多顺反子mRNA是指编码两种或更多种功能性RNA、肽或蛋白质或其组合的mRNA分子。在一个实施例中,转基因盒编码多顺反子mRNA。
在一个实施例中,在编码多顺反子mRNA的盒的上下文中,转基因盒包含任选地含有外源启动子的DNA区段(其是将确定转基因何时何地处于活跃状态的调节序列)或剪接位点(其是调节序列确定mRNA分子何时将被剪接体裂解)两个或多个编码序列(即转基因),通常衍生自感兴趣的蛋白质或肽的cDNA,例如其中每个编码序列被IRES或2A肽分开。在待转录的最后编码序列之后,所述盒可以任选地含有polyA序列和终止子序列。
在一个实施例中,转基因盒编码单顺反子mRNA,然后编码多顺反子mRNA。在另一个实施例中,转基因盒编码多顺反子mRNA,然后是单顺反子mRNA。
在一个实施例中,腺病毒是人类腺病毒。如本文所采用的“腺病毒”、“血清型”或“腺病毒血清型”是指任何可以指定为50多种目前已知的腺病毒血清型中的任何一种的腺病毒,其被分类为亚组A到F,并且进一步延伸到任何尚未鉴定或尚未分类的腺病毒血清型。参见例如Strauss,“腺病毒在人体内的感染(Adenovirus infections in humans)”,载于《腺病毒》,Ginsberg,ea.,美国纽约州纽约普莱南出版社,第451到596页,(1984)以及Shenk,“腺病毒科:病毒及其复制(Adenoviridae:The Viruses and TheirReplication)”,载于《病毒学领域》第2卷第四期,Knipe,35ea.,Lippincott Williams和Wilkins,第2265到2267页,(2001),如表1所示。
表1
在一个实施例中,本公开的腺病毒是亚组B病毒,即Ad11,具体地Ad11p(Slobitski菌株)及其衍生物,如EnAd。
腺病毒被指定为基于衣壳的其组/血清型,如六邻体和/或纤维。
在一个实施例中,本公开的腺病毒不是A组、C组、D组、E组或F组病毒。本公开的病毒不包括腺病毒死亡蛋白。
在一个实施例中,本公开的腺病毒是嵌合的。当腺病毒是嵌合的时,则将采用外衣壳的特性来确定血清型。如本文所采用的嵌合体是指包括来自至少两种不同病毒血清型的DNA的病毒,包含同一组内的不同血清型。
在一个实施例中,溶瘤病毒具有来自相同血清型的纤维、六邻体和五邻体蛋白,例如Ad11,具体地Ad11p,例如在后者的基因组序列的30812到31789、18254到21100和13682到15367位置发现,其中核苷酸位置是相对于genbank ID 217307399(登录号:GC689208)。
在一个实施例中,腺病毒是enadenotucirev(也称为EnAd,并且以前称为EnAd)。如本文所采用的Enadenotucirev是指SEQ ID NO:28的嵌合腺病毒。它是复制型溶瘤性嵌合腺病毒,其与野生型腺病毒相比具有增强的治疗性质(参见WO2005/118825)。EnAd具有嵌合E2B区,其具有来自Ad11p和Ad3的DNA,以及E3/E4中的缺失。enadenotucirev的结构变化导致基因组比Ad11p小约3.5kb,由此为转基因的插入提供了额外的“空间”。在EnAd中几乎所有E3区和E4区的一部分都缺失。因此,它在基因组中具有显著的空间以容纳额外的遗传物质,同时保持活力。此外,因为EnAd是亚组B腺病毒,所以人类预先存在的免疫力不如例如Ad5那么常见。具有Ad11纤维、五邻体和六邻体的嵌合溶瘤病毒的其它实例包含OvAd1和OvAd2(参见通过引用并入的WO2008/080003)。因此,在一个实施例中,所采用的腺病毒是OvAd1或OvAd2。
EnAd似乎优先感染肿瘤细胞,在这些细胞中快速复制并且导致细胞溶解。反过来,这可以生成炎症性免疫应答,由此刺激身体也来对抗癌症。EnAd的部分成功被假设与体内病毒的快速复制有关。
有利地,利用可以在癌细胞内表达的编码如BiTE等某些蛋白质的DNA来携带病毒,可以使身体自身的防御能够更有效地用于对抗肿瘤细胞,例如通过使细胞对于免疫系统更加可见或通过优先向靶肿瘤细胞递送治疗基因/蛋白质。
重要的是转基因的表达不会不利地影响病毒的复制或其它有利性质。因此,必须将一个或多个基因插入不损害病毒的复制能力和其它有利性质的位置。另外,腺病毒的基因组是紧密堆积的,并且因此很难找到合适的位置来插入转基因。这也限制了可以容纳的转基因的大小。
如本文所采用的溶瘤腺病毒意指与非癌细胞相比优先杀死癌细胞的腺病毒。在一个实施例中,溶瘤病毒是凋亡的。也就是说,其加速了程序性细胞死亡。
在一个实施例中,溶瘤病毒是溶细胞的。本公开的溶瘤腺病毒的溶细胞活性可以在代表性肿瘤细胞系中确定,并且数据转换为效力的测量,例如用如Ad5等属于亚组C的腺病毒来用作标准物(即,效力为1)。用于确定细胞溶解活性的合适方法是MTS测定(参见WO2005/118825的实例4,图2,其通过引用并入本文)。
在一个实施例中,溶瘤病毒是坏死性的。也就是说,其引起或加速细胞坏死或免疫原性细胞死亡。在一个实施例中,坏死性细胞死亡是有利的,因为其触发、诱导患者(宿主)免疫应答。
除非上下文另有指示,否则本文所采用的腺病毒是指能够进行复制的病毒(如复制型病毒)以及复制缺陷型病毒载体。
能够如本文所采用的复制是指复制型病毒或病毒,其复制依赖于癌细胞中的因子,例如上调因子,如p53或类似物。
在一个实施例中,病毒是复制型的。在本说明书的上下文中起作用的复制是指具有在体外和体内的细胞中复制的所有必需机制的病毒,即没有包装细胞系的辅助。例如在E1区缺失、能够在互补包装细胞系中复制的病毒载体在本文上下文中不是复制型病毒。
病毒载体是复制缺陷的,并且需要包装细胞提供互补基因以允许复制。
如本文所采用的腺病毒基因组意指编码与腺病毒的功能/生命周期相关的结构蛋白和元件的DNA序列。
迄今为止检查的所有人类腺病毒基因组具有相同的一般组织,即编码特定功能的基因位于病毒基因组中的相同位置(在本文中称为结构元件)。病毒基因组的每个末端都具有称为反向末端重复序列(或ITR)的短序列,这是病毒复制所必需的。病毒基因组含有五个早期转录单位(E1A、E1B、E2、E3和E4)、三个延迟早期单位(IX、IVa2和E2晚期)以及被处理以生成五个晚期mRNA家族(L1到L5)的一个晚期单位(主要晚期)。由早期基因编码的蛋白质主要参与宿主细胞对感染的应答的复制和调节,而晚期基因编码病毒结构蛋白。早期基因以字母E为前缀,并且晚期基因以字母L为前缀。
腺病毒的基因组紧密堆积,也就是说几乎不存在非编码序列,并且因此很难找到合适的位置来插入转基因。
在一个实施例中,根据本公开的溶瘤病毒或部分溶瘤病毒可以是E4和/或E3区中的缺失的结果,例如在E4区的一部分中缺失或在E3区中完全缺失,或者可替代地在E4区的一部分(如E4或f4)中缺失并且在E3区中完全缺失,例如在本文公开的序列中举例说明。
在一个实施例中,溶瘤病毒是EnAd或其活性衍生物,其保留病毒的基本有益性质。EnAd在WO2005/118825中公开(通过引用并入本文)并且本文提供了病毒的完整序列SEQ IDNO:28。嵌合E2B区在本文中公开为SEQ ID NO:60。
有利地,本公开的腺病毒在体外感染多种不同的结肠癌细胞系后展现出与EnAd相似的病毒活性,例如复制和/或感染性。
腺病毒的结构元素
由于腺病毒的结构通常类似于下文的元素是根据结构要素和参考的常用术语来讨论的,这些是本领域技术人员已知的。当在本文中提及元件时,我们指的是编码所述元件的DNA序列或编码腺病毒中所述元件的相同结构蛋白的DNA序列。因为DNA代码的冗余,所以后者是相关的。可能需要考虑病毒对密码子使用的偏好以获得优化结果。
来自本公开的病毒中采用的腺病毒的任何结构元件可以包括天然序列或由天然序列组成,或者可以在给定长度上具有至少95%的相似性,如96%、97%、98%、99%或100%。可以修改原始序列以省略遗传物质的10%、9%、8%、7%、6%、5%、4%、3%、2%或1%。技术人员知道,当进行改变时,必须不破坏病毒的阅读框,以便破坏结构蛋白的表达。
在一个实施例中,给定元件是全长序列,即全长基因。
在一个实施例中,给定元素小于全长并且保持与全长序列相同或对应的功能。
在一个实施例中,对于在本公开的构建体中任选的给定元件,DNA序列可以小于全长并且不具有功能性。
编码腺病毒的结构或功能蛋白的结构基因通常通过DNA的非编码区连接。因此,为了将转基因插入本公开的病毒中,在哪里“切割”感兴趣的结构元件的基因组序列(尤其是其非编码区)存在一些灵活性。因此,出于本说明书的目的,所述元件将被认为是参考的结构元件,其程度适合于目的并且不编码外来材料。因此,如果合适,所述基因将与合适的非编码区相关联,例如在病毒的天然结构中发现的。
因此,在一个实施例中,将插入物(如编码限制性位点和/或转基因的DNA)插入基因组病毒DNA的非编码区,如内含子或基因间序列。已经说过,腺病毒的一些非编码区可能具有功能,例如在可替代的剪接、转录调节或转译调节中,并且可能需要考虑这一点。
本文鉴定的与L5区相关的位点(例如L5与E4区之间)适合于容纳编码复杂实体的各种DNA序列,如RNAi、细胞因子、单链或多聚体蛋白质,如抗体,如BiTE。
如本文所采用的基因是指编码和任选地与其相关的任何非编码序列,例如内含子和相关的外显子。在一个实施例中,基因包括必需的结构组分或仅由必需的结构组分组成,例如编码区。
下文是关于腺病毒的特定结构元素的讨论。
反向末端重复(ITR)序列对于所有已知的腺病毒是共同的,并且由于其对称性而如此命名,并且是病毒染色体复制起点。这些序列的另一个性质是其形成发夹的能力。
如本文所采用的5'ITR是指来自腺病毒5'末端的部分或全部ITR,其在合适位置掺入腺病毒时保留ITR的功能。在一个实施例中,5'ITR包括SEQ ID NO:28的约1bp到138bp的序列或沿整个长度与其90%、95%、96%、97%、98或99%相同的序列或由其组成,具体地由SEQ ID NO:28的约1bp到138bp组成的序列。
如本文所采用的3'ITR是指腺病毒3'末端的部分或全部ITR,其在合适位置掺入腺病毒时保留ITR的功能。在一个实施例中,3'ITR包括SEQ ID NO:28的约32189bp到32326bp的序列或沿整个长度与其90%、95%、96%、97%、98或99%相同的序列或由其组成,具体地说由SEQ ID NO:28的约32189bp到32326bp组成的序列。
如本文所采用的B1是指编码以下的DNA序列:腺病毒的E1A的部分或全部、腺病毒的E1B区的部分或全部以及独立地腺病毒的E1A区和E1B区的部分或全部。
当B1是键时,则E1A和E1B序列将从病毒中省略。在一个实施例中,B1是键,并且因此病毒是载体。
在一个实施例中,B1进一步包括转基因。本领域已知E1区可以容纳转基因,所述转基因可以以破坏性的方式插入E1区(即在序列的“中间”)或者可以缺失部分或全部E1区以提供更多的空间以容纳遗传物质。
如本文所采用的E1A是指编码部分或全部腺病毒E1A区的DNA序列。后者在本文中是指多肽/蛋白质E1A。其可以被突变使得由E1A基因编码的蛋白质具有保守或非保守的氨基酸变化,使得其具有:与野生型相同的功能(即对应的非突变蛋白质);与野生型蛋白质相比功能增加;功能降低,如与野生型蛋白质相比无功能或者与野生型蛋白质或其组合相比具有新功能,视情况而定。
如本文所采用的E1B是指编码部分或全部腺病毒E1B区(即多肽或蛋白质)的DNA序列,其可以被突变使得由E1B基因/区域编码的蛋白质具有保守或非保守的氨基酸变化,使得其具有:与野生型相同的功能(即对应的非突变蛋白质);与野生型蛋白质相比功能增加;功能降低,如与野生型蛋白质相比无功能或者与野生型蛋白质或其组合相比具有新功能,视情况而定。
因此,相对于如野生型E1A和/或E1B等野生型E1区,B1可以被修饰或未修饰。技术人员可以容易地识别E1A和/或E1B是否存在或(部分)缺失或突变。
如本文所采用的野生型是指已知的腺病毒。已知的腺病毒是已经鉴定和命名的腺病毒,无论所述序列是否可用。
在一个实施例中,B1具有SEQ ID NO:28的139bp到3932bp的序列。
如本文所采用的,BA是指编码E2B-L1-L2-L3-E2A-L4区的DNA序列,包含任何非编码序列,视情况而定。通常,此序列将不包括转基因。在一个实施例中,所述序列与来自已知腺病毒的连续序列基本相似或相同,例如表1中所示的血清型,具体地B组病毒,例如Ad3、Ad7、Ad11、Ad14、Ad16、Ad21、Ad34、Ad35、Ad51或其组合,如Ad3、Ad11或其组合。在一个实施例中,E2B-L1-L2-L3-E2A-L4是指包括这些元件和与所述区相关的其它结构元件,例如BA将通常包含编码蛋白质IV2a的序列,例如如下:IV2A IV2a-E2B-L1-L2-L3-E2A-L4。
在一个实施例中,E2B区是嵌合的。也就是说,包括来自两种或更多种不同腺病毒血清型的DNA序列,例如来自Ad3和Ad11,如Ad11p。在一个实施例中,E2B区在整个长度上具有SEQ ID NO:28的5068bp到10355bp的序列或与其95%、96%、97%、98%或99%相同的序列。
在一个实施例中,组分BA中的E2B包括SEQ ID NO:60中所示的序列(其对应于WO2005/118825中公开的SEQ ID NO:3)。
在一个实施例中,BA具有SEQ ID NO:28的3933bp到27184bp的序列。
如本文所采用的E3是指编码部分或全部腺病毒E3区(即蛋白质或多肽)的DNA序列,其可以被突变使得由E3基因编码的蛋白质具有保守或非保守的氨基酸变化,使得其具有:与野生型相同的功能(对应的未突变蛋白质);与野生型蛋白质相比功能增加;功能降低,如与野生型蛋白质相比无功能或者与野生型蛋白质或其组合相比具有新功能,视情况而定。
在一个实施例中,E3区形成表1中给出的腺病毒血清型或其组合,具体地B组血清型,例如Ad3、Ad7、Ad11(具体地Ad11p)、Ad14、Ad16、Ad21、Ad34、Ad35、Ad51或其组合,如Ad3、Ad11(具体地Ad11p)或其组合。
在一个实施例中,E3区被部分缺失,例如95%、90%、85%、80%、75%、70%、65%、60%、55%、50%、45%、40%、35%、30%、25%、20%、15%、10%、5%缺失。
在一个实施例中,B2是键,其中不存在编码E3区的DNA。
在一个实施例中,编码E3区的DNA可以被转基因代替或中断。如本文所采用的,“用如本文所采用的转基因代替的E3区包含部分或全部E3区被转基因代替。
在一个实施例中,B2区包括SEQ ID NO:28的27185bp到28165bp的序列。
在一个实施例中,B2由SEQ ID NO:28的27185bp到28165bp的序列组成。
如本文所采用的BX是指BB中L5基因的5'末端附近的DNA序列。在如本文所采用的L5基因的5'末端附近或近端是指:邻近(邻接)L5基因的5'末端或与其固有相关的非编码区,即与L5基因的5'主要末端紧靠或邻接或与其固有相关的非编码区。可替代地,在附近或近端可以指闭合L5基因,使得在BX区与L5基因的5'末端之间不存在编码序列。
因此,在一个实施例中,BX直接连接到L5的碱基,其代表例如L5基因的编码序列的起始。
因此,在一个实施例中,BX直接连接到L5的碱基,其代表例如非编码序列的起点,或直接连接到与L5天然相关的非编码区。如本文所采用的,天然关联L5的非编码区是指所有非编码区的一部分,所述非编码区是L5基因的一部分或与其邻接但不是另一基因的一部分。
在一个实施例中,BX包括SEQ ID NO:29的序列。此序列是人工非编码序列,其中可以插入DNA序列,例如包括转基因(或转基因盒)、限制性位点或其组合。此序列是有利的,因为其充当缓冲液,由于允许转基因的确切位置具有一定的灵活性,同时最小化对病毒稳定性和活力的破坏性影响。
一个或多个插入物可以出现在SEQ ID NO:29的5'末端、3'末端或在bp 1到201之间的任何位置处的任何位置。在一个实施例中,BX包括SEQ ID NO:29,其中DNA序列插入bp27与bp28之间或对应于SEQ ID NO:28的位置28192bp与28193bp之间的地方。
在一个实施例中,插入物是限制性位点插入物。在一个实施例中,限制性位点插入物包括一个或两个限制性位点。在一个实施例中,限制性位点是包括2个限制性位点的19bp限制性位点插入物。在一个实施例中,限制性位点插入物是包括1个限制性位点的9bp限制性位点插入物。在一个实施例中,限制性位点插入物包括一个或两个限制性位点和至少一个转基因,例如一个或两个转基因。在一个实施例中,限制性位点是19bp限制性位点插入物,其包括2个限制性位点和至少一个转基因,例如一个或两个转基因。在一个实施例中,限制性位点插入物是9bp限制性位点插入物,其包括1个限制性位点和至少一个转基因,例如一个、两个或三个转基因,如一个或两个。在一个实施例中,两个限制性位点夹在一个或多个,如两个转基因中(例如在转基因盒中)。在一个实施例中,当BX包括两个限制性位点时,所述限制性位点彼此不同。在一个实施例中,BX中的所述一个或多个限制性位点在其已经插入的特定腺病毒基因组中是非天然发生的。在一个实施例中,BX中的所述一个或多个限制性位点不同于位于腺病毒基因组中其它位置的其它限制性位点,例如不同于引入基因组其它部分的天然发生的限制性位点和/或限制性位点,如引入BY的限制性位点。因此,在一个实施例中,一个或多个限制性位点允许区段中的DNA被特异性切割。
与如本文所采用的BY相关的DNA序列是指BB的L5基因的3'末端附近的DNA序列。在如本文所采用的L5基因的3'末端附近或近端是指:邻近(邻接)L5基因的3'末端或与其固有相关的非编码区,即与L5基因的3'主要末端紧靠或邻接或与其固有相关的非编码区(即L5内源的非编码序列的全部或部分)。可替代地,在附近或近端可以指闭合L5基因,使得在BY区与L5基因的3'末端之间不存在编码序列。
因此,在一个实施例中,BY直接连接到L5的碱基,其代表编码序列的“末端”。
因此,在一个实施例中,BY直接连接到L5的碱基,其代表非编码序列的“末端”,或直接连接到与L5天然相关的非编码区。
本文中可固有地和自然地互换使用。在一个实施例中,BY包括SEQ ID NO:30的序列。此序列是非编码序列,其中可以插入DNA序列,例如包括转基因(或转基因盒)、限制性位点或其组合。此序列是有利的,因为其起缓冲液的作用,由于允许转基因的确切位置具有一定的灵活性,同时最小化对病毒稳定性和活力的破坏性影响。
一个或多个插入物可以在SEQ ID NO:30中从5'末端、3'末端或在bp 1到bp 35之间的任何点发生,例如在碱基对1/2、2/3、3/4、4/5、5/6、6/7、7/8、8/9、9/10、10/11、11/12、12/13、13/14、14/15、15/16、16/17、17/18、18/19、19/20、20/21、21/22、22/23、23/24、24/25、25/26、26/27、27/28、28/29、29/30、30/31、31/32、32/33、33/34或34/35之间。
如本文所采用的E4是指编码部分或全部腺病毒E4区(即多肽或蛋白质区域)的DNA序列,其可以被突变使得由E4基因编码的蛋白质具有保守或非保守的氨基酸变化,并且具有:与野生型相同的功能(对应的非突变蛋白质);与野生型蛋白质相比功能增加;功能降低,如与野生型蛋白质相比无功能或者与野生型蛋白质或其组合相比具有新功能,视情况而定。在一个实施例中,E4区缺失E4或f4。
在一个实施例中,E4区被部分缺失,例如95%、90%、85%、80%、75%、70%、65%、60%、55%、50%、45%、40%、35%、30%、25%、20%、15%、10%或5%缺失。在一个实施例中,E4区具有SEQ ID NO:28的32188bp到29380bp的序列。
在一个实施例中,B3是键,即其中不存在E4。
在一个实施例中,B3具有由SEQ ID NO:28的32188bp到29380bp组成的序列。
如本文所采用的,数字范围包括端点。
技术人员将理解,本文式中的元素,如式(I)是连续的,并且可以包含非编码DNA序列以及本文提及的基因和编码DNA序列(结构特征)。在一个或多个实施例中,本公开的式试图描述腺病毒基因组中的天然发生的序列。在此上下文中,技术人员将清楚所述配方是指表征基因组相关区段的主要元件,并且并不旨在是DNA的基因组延伸的详尽描述。
如本文所采用的,E1A、E1B、E3和E4各自独立地指野生型及其等同物,如本文所描述的每个区的突变或部分缺失形式,具体地来自已知腺病毒的野生型序列。
如本文所采用的,“插入”是指在5'末端、3'末端或在给定DNA序列参考片段内掺入的DNA序列,使得其中断参考序列。后者是用作相对于插入物所在的参考点的参考序列。在本公开的上下文中,插入物通常出现在SEQ ID NO:29或SEQ ID NO:30内。插入物可以是限制性位点插入物、转基因盒或两者。当序列被中断时,病毒仍将包括原始序列,但通常其将两个片段夹在插入物中。
在一个实施例中,转基因或转基因盒不包括非偏向插入转座子,如TN7转座子或其部分。如本文所采用的,Tn7转座子是指如WO2006/060314中所描述的非偏向插入转座子。
在一个实施例中,BX和BY中的一个或多个限制性位点独立地选自对本文所描述的酶具有特异性的限制性位点,例如NotI、FseI、AsiSI、SgfI和SbfI,具体地插入的限制性位点都是不同的,如NotI特异性位点和位于BX中的FseI特异性位点和位于BY中的SgfI和SbfI。
如上文在一个实施例中所讨论的,区BX和/或BY不包括限制性位点。有利地,可以在不具有限制性位点的情况下制备本公开的病毒和构建体,例如使用合成技术。这些技术在创建病毒和构建体时具有很大的灵活性。此外,诸位发明人已经确定,当通过合成技术制备病毒和构建体时,其性质不会降低。
其它调节序列
如本文所采用的,“基因表达调节剂”(或调节/调控元件)是指遗传特征,如通常通过启动或增强转录或转译而在基因表达中起作用的启动子、增强子或剪接受体序列。
如本文所采用的,“剪接受体序列”、“剪接受体”或“剪接位点”是指确定何时mRNA分子将被剪接体复合物的小核核糖核蛋白识别的调节序列。一旦组装后,剪接体催化mRNA分子的剪接受体位点与上游剪接供体位点之间的剪接,从而产生可以被转译成产生单个多肽或蛋白质的成熟mRNA分子。
在本发明中可以采用不同大小的剪接受体序列,并且这些可以描述为短剪接受体(小)、剪接受体(中等)和分支剪接受体(大)。
如本文所采用的,SSA意指短剪接受体,通常仅包括剪接位点,例如4个碱基对。如本文所采用的,SA意指剪接受体,通常包括短剪接受体和多聚嘧啶束,例如16bp。如本文所采用的,bSA意指支链剪接受体,通常包括短剪接受体,多聚嘧啶束和分支点,例如26个碱基对。
在一个实施例中,在本公开的构建体中采用的剪接受体SA和bSA分别显示在SEQID NO:45和46中。在一个实施例中,SSA用于根据本公开的盒中,并且具有核苷酸序列CAGG。
在一个实施例中,SA用于盒中。在一个实施例中,bSA用于盒中。
在一个实施例中,剪接位点立即由共有Kozak序列进行(即,在5'到3'方向上进行)。在一个实施例中,剪接位点和Kozak序列由多达100个或更少的碱基对分开。在一个实施例中,Kozak序列具有SEQ ID NO:47的核苷酸序列。
通常,当在内源或外源启动子(如内源启动子)的控制下时,编码序列将立即由Kozak序列进行。编码区的起始是由起始密码子(AUG)指示的,例如在序列(gcc)gccRccAUGg[SEQ ID NO:48]的上下文中,编码序列的“开始”的开始由粗体的碱基指示。小写字母表示此位置的共同碱基(不过其可以变化)并且大写字母指示高度保守的碱基,即“AUGG”序列是恒定的或很少变化,如果有的话;“R”指示通常在此位置观察到嘌呤(腺嘌呤或鸟嘌呤),并且括号内的序列(gcc)具有不确定的意义。因此,在一个实施例中,将起始密码子AUG掺入Kozak序列中。
如本文所采用的,内部核糖体进入DNA序列是指编码内部核糖体进入序列(IRES)的DNA序列。如本文所采用的,IRES意指允许启动信使RNA(mRNA)序列转译的核苷酸序列,包含在mRNA序列内起始的开始。当盒编码多顺反子mRNA时,这是特别有用的。使用IRES产生多顺反子mRNA,其被转译成多个单独的蛋白质或肽。在一个实施例中,内部核糖体进入DNA序列具有SEQ ID NO:49的核苷酸序列。在一个实施例中,特定的IRES仅在基因组中使用一次。这可能对基因组的稳定性有益。
如本文所采用的,“高自切割效率2A肽”或“2A肽”是指在转译后有效切割的肽。合适的2A肽包含P2A、F2A、E2A和T2A。诸位发明人已经注意到,一旦使用编码给定2A肽的特异性DNA序列一次,就可能不能再次使用相同的特异性DNA序列。然而,DNA代码中的冗余可以用于生成转译成相同2A肽的DNA序列。当盒编码多顺反子mRNA时,使用2A肽特别有用。使用2A肽导致转译的单个多肽链在转译后被修饰以生成多个单独的蛋白质或肽。
在一个实施例中,所采用的编码的P2A肽具有SEQ ID NO:50的氨基酸序列。在一个实施例中,所采用的编码的F2A肽具有SEQ ID NO:51的氨基酸序列。在一个实施例中,所采用的编码的E2A肽具有SEQ ID NO:52的氨基酸序列。在一个实施例中,所采用的编码的T2A肽具有SEQ ID NO:53的氨基酸序列。
在一个实施例中,由一个或多个转基因编码的mRNA或每种mRNA包括多腺苷酸化信号序列,如通常在mRNA序列的末端处,例如如SEQ ID NO:54中所示。因此,转基因或转基因盒的一个实施例包括至少一个编码多腺苷酸化信号序列的序列。
如本文所采用的,“PolyA”、“多聚腺苷酸化信号”或“多聚腺苷酸化序列”意指通常含有AATAAA位点的DNA序列,其一旦转录就可以被多蛋白复合物识别,所述多蛋白复合物裂解并且多聚腺苷酸化新生的mRNA分子。
在一个实施例中,多腺苷酸化序列具有SEQ ID NO:54的核苷酸序列。
在一个实施例中,构建体不包含多腺苷酸化序列。在一个实施例中,基因表达的调节子是剪接受体序列。
有利地,本公开的腺病毒表达并且释放抗体形式(如BiTE)和如细胞因子等其它蛋白质由其中的转基因编码到体外培养上清液中或到体内肿瘤组织基质中。前导序列可以帮助编码的蛋白质/多肽或肽离开癌细胞。因此,在一个实施例中,编码的“蛋白质”包括前导序列。如本文所采用的,前导序列是指位于启动子序列与编码区之间的多核苷酸序列,其可以在转录或转译水平上调节基因表达。
在一个实施例中,根据本公开的腺病毒包括转基因,所述转基因是报告基因,所述报告基因编码例如包含生物发光的成像剂、荧光成像剂(包含可活化的荧光成像剂),如荧光素酶、GFP或eGFP或红色荧光蛋白。
如本文所采用的,报告基因或报告序列意指产生在真核细胞中容易检测的产物的基因或DNA序列,并且可以用作标记物以确定与其DNA紧密连接或组合的另一种基因的活性。报告基因赋予易于鉴定和测量的表达它们的细胞或生物体的特性或者是可选择的标记。报告基因通常用作指示某种基因是否已经被细胞或生物群体吸收或表达。常见报告基因的实例包含但不限于:LacZ、荧光素酶、GFP、eGFP、新霉素磷酸转移酶、氯霉素乙酰转移酶、碘化钠同向转运体(NIS)、硝基还原酶(例如NfsA、NfsB)细胞内金属蛋白、HSV1-tk或雌激素受体。
在一个实施例中,遗传物质(具体地转基因)不编码或表达如显像剂、荧光素酶、GFP或eGFP等报告基因。
通过检查一组肿瘤细胞中的溶解潜力,可以研究根据本公开的病毒对特异性肿瘤类型的偏好,例如结肠肿瘤细胞系包含HT-29、DLD-1、LS174T、LS1034、SW403、HCT116、SW48和Colo320DM。任何可用的结肠肿瘤细胞系对于这种评估同样有用。
前列腺细胞系包含DU145和PC-3细胞。胰腺细胞系包含Panc-1细胞。乳腺肿瘤细胞系包含MDA231细胞系,并且卵巢细胞系包含OVCAR-3细胞系。造血细胞系包含但不限于:Raji和Daudi B淋巴细胞、K562成红细胞样细胞、U937骨髓细胞和HSB2 T淋巴细胞。其它可用的肿瘤细胞系同样有用。
本公开还延伸到本公开的新序列。在一个实施例中,病毒以本文公开的任何一个序列显示。
调配物
本公开还涉及如本文所描述的病毒的药物调配物。
在一个实施例中,提供了液体胃肠外调配物,例如对于根据本公开的输注或注射能够溶瘤的复制物,其中所述调配物提供的剂量范围为每体积剂量1×1010到1×1014个病毒颗粒。
肠胃外调配物意指设计为不通过GI道递送的调配物。典型的肠胃外递送途径包含注射、植入或输注。在一个实施例中,调配物以推注递送的形式提供。
在一个实施例中,肠胃外调配物是以注射的形式。注射包含静脉内、皮下、肿瘤内或肌内注射。如本文所采用的,注射意指通过注射器将液体注入体内。在一个实施例中,本公开的方法不涉及肿瘤内注射。
在一个实施例中,肠胃外调配物是以输注形式。
如本文所采用的,输注意指通过滴注、输注泵、注射器驱动器或等效装置以较慢的速率施用流体。在一个实施例中,输注在1.5分钟到120分钟的范围内施用,如约3分钟、4分钟、5分钟、6分钟、7分钟、8分钟、9分钟、10分钟、11分钟、12分钟、13分钟、14分钟、15分钟、16分钟、17分钟、18分钟、19分钟、20分钟、25分钟、30分钟、35分钟、40分钟、45分钟、50分钟、55分钟、60分钟、65分钟、70分钟、65分钟、80分钟、85分钟、90分钟、95分钟、100分钟、105分钟、110分钟或115分钟。
在一个实施例中,一剂量的调配物小于100ml,例如30ml,如通过注射器驱动器施用。在一个实施例中,一剂量的调配物小于10ml,例如9ml、8ml、7ml、6ml、5ml、4ml、3ml、2ml或1ml。在一个实施例中,一剂量的调配物小于1ml,如0.9ml、0.8ml、0.7ml、0.6ml、0.5ml、0.4ml、0.3ml、0.2ml或0.1ml。
在一个实施例中,注射以缓慢注射施用,例如在1.5分钟到30分钟的时间内施用。
在一个实施例中,所述调配物用于静脉内(i.v.)施用。此途径对溶瘤病毒的传递特别有效,因为其可以快速进入大多数器官和组织,并且是特别适用于转移瘤的治疗,例如已建立的转移灶,尤其是位于如肝脏和肺部等高度血管化区的转移灶。
治疗调配物通常在制造和储存条件下是无菌和稳定的。所述组合物可以被配制成适合于施用于人类的溶液、微乳液、脂质体或其它肠胃外调配物,并且可以被配制成如注射器或小瓶等预填充装置,具体地作为单剂量。
调配物通常包括药学上可接受的稀释剂或载剂,例如与病毒相容的无毒等渗载剂,并且其中病毒在所需的一段时间内是稳定的。
载剂可以是溶剂或分散介质,其含有例如水、乙醇、多元醇(例如甘油、丙二醇和液体聚乙二醇等)及其合适的混合物。例如,通过使用分散剂或表面活性剂,如卵磷脂或如聚山梨醇酯80或40等非离子表面活性剂,可以保持适当的流动性。在分散体中,可以通过表面活性剂的存在来辅助维持所需的粒度。等渗剂的实例包含组合物中的糖、如甘露醇等多元醇、山梨糖醇或氯化钠。
在一个实施例中,所采用的肠胃外调配物可以包括例如下列缓冲液中的一个或多个:4-(2-羟乙基)-1-哌嗪乙磺酸、磷酸盐缓冲液和/或Tris缓冲液、糖,例如右旋糖、甘露糖、蔗糖或类似物、如氯化钠等盐、氯化镁或氯化钾、洗涤剂,如briji、PS-80、PS-40或类似物等非离子表面活性剂。调配物还可以包括如EDTA或乙醇或EDTA和乙醇的组合等防腐剂,所述防腐剂被认为可以防止一个或多个可能的降解途径。
在一个实施例中,调配物将包括根据本公开的纯化的溶瘤病毒,例如每剂量1×1010个到1×1014个病毒颗粒,如每剂量1×1010个到1×1012个病毒颗粒。在一个实施例中,调配物中病毒的浓度范围为2×108vp/mL到2×1014vp/mL,如2×1012vp/ml。
在一个实施例中,肠胃外调配物包括甘油。
在一个实施例中,调配物包括如本文所描述的溶瘤腺病毒、HEPES(N-2-羟乙基哌嗪-N'-2-乙磺酸)、甘油和缓冲液。
在一个实施例中,肠胃外调配物由本公开的病毒、例如5mM HEPES、例如5%到20%(v/v)甘油、盐酸组成,例如将pH调节到7到8的范围并且水用于注射。
在一个实施例中,将浓度为2×1012vp/mL的0.7mL的本公开的病毒配制在5mMHEPES、20%甘油中,最终pH为7.8。
在《雷明顿氏药物科学(Remington's Pharmaceutical Sciences)》(MackPublishing Company(马克出版公司),新泽西州,1991)中可获得药学上可接受的载剂的详尽讨论。
在一个实施例中,调配物作为包含吸入的局部施用的调配物提供。
合适的可吸入制剂包含可吸入粉末、含有推进剂气体的计量气溶胶或不含推进剂气体的可吸入溶液。根据本公开的可吸入粉末通常含有如本文所描述的病毒和生理学上可接受的赋形剂。
这些可吸入粉末可以包含单糖(例如葡萄糖或阿拉伯糖)、二糖(例如乳糖、蔗糖、麦芽糖)、低聚糖和多糖(例如葡聚糖)、多元醇(例如山梨糖醇、甘露醇、木糖醇)、盐(例如氯化钠、碳酸钙)或其彼此的混合物。适合使用单糖或二糖,使用乳糖或葡萄糖,具体地但不限于其水合物形式。
用于在肺中沉积的颗粒需要小于10微米的粒度,如1微米到9微米,例如0.1μm到5μm,具体地1μm到5μm。携带病毒的粒度是最重要的,并且因此在一个实施例中,根据本公开的病毒可以被吸附或吸收到颗粒上,如给定大小的乳糖颗粒。
可以用于制备可吸入气溶胶的推进剂气体在本领域中是已知的。合适的推进剂气体选自烃类,如正丙烷、正丁烷或异丁烷以及卤代烃,如甲烷、乙烷、丙烷、丁烷、环丙烷或环丁烷的氯化和/或氟化衍生物。上述推进剂气体可以单独使用或以其混合物使用。
特别合适的推进剂气体是选自TG 11、TG 12、TG 134a和TG227的卤代烷烃衍生物。在上述卤代烃中,TG134a(1,1,1,2-四氟乙烷)和TG227(1,1,1,2,3,3,3-七氟丙烷)及其混合物是特别合适的。
含有推进剂气体的可吸入气溶胶还可以含有其它成分,如助溶剂、稳定剂、表面活化剂(表面活性剂)、抗氧化剂、润滑剂和调节pH的方法。所有这些成分在本领域中是已知的。
根据本发明的含有推进剂气体的可吸入气溶胶可以含有最多5%重量的活性物质。根据本发明的气溶胶含有例如0.002重量%到5重量%、0.01重量%到3重量%、0.015重量%到2重量%、0.1重量%到2重量%、0.5重量%到2重量%或0.5重量%到1重量%的活性成分。
可替代地,肺部的局部施用还可以通过施用液体溶液或悬浮液调配物,例如采用如喷雾器等装置,例如,连接到压缩机的喷雾器(例如,连接到由弗吉尼亚州里士满的帕里呼吸设备公司(Pari Respiratory Equipment,Inc.)制造的Pari Master(R)压缩机的PariLC-Jet Plus(R)喷雾器)。
本发明的病毒可以分散在溶剂中递送,例如以溶液或悬浮液的形式递送,例如如上文所描述的用于肠胃外调配物。其可以悬浮在合适的生理溶液中,例如盐水或其它药理学上可接受的溶剂或缓冲溶液。本领域已知的缓冲溶液可以含有0.05mg到0.15mg的乙二胺四乙酸二钠、8.0mg到9.0mg NaCl、0.15mg到0.25mg聚山梨醇酯、0.25mg到0.30mg无水柠檬酸和0.45mg到0.55mg柠檬酸钠/1ml水,以便达到约4.0到5.0的pH。
治疗性悬浮液或溶液调配物还可以含有一个或多个赋形剂。赋形剂在本领域中是众所周知的并且包含缓冲液(例如,柠檬酸盐缓冲液、磷酸盐缓冲液、乙酸盐缓冲液和碳酸氢盐缓冲液)、氨基酸、尿素、醇、抗坏血酸、磷脂、蛋白质(例如血清白蛋白)、EDTA、氯化钠、脂质体、甘露醇、山梨糖醇和甘油。溶液或悬浮液可以包封在脂质体或可生物降解的微球中。调配物通常采用无菌制造方法以基本上无菌的形式提供。
这可以包含通过过滤用于调配物的缓冲溶剂/溶液的生产和灭菌、抗体在无菌缓冲溶剂溶液中的无菌悬浮以及通过本领域普通技术人员熟悉的方法将调配物分配到无菌容器中。
根据本公开的可雾化调配物可以例如作为包装在箔包封中的单剂量单位(例如,密封的塑料容器或小瓶)提供。每个小瓶含有体积中的单位剂量,例如2mL溶剂/溶液缓冲液。
治疗
在另外的方面,本公开涉及如本文所描述的用于治疗的病毒或其调配物,具体地用于治疗癌症。
在一个实施例中,治疗方法用于治疗肿瘤,具体地实体瘤。
如本文所采用的,肿瘤是指由过度细胞分裂引起的异常组织块,其是不受控制的和渐进的,也称为肿瘤。肿瘤可以是良性的(非癌性的)或恶性的。肿瘤涵盖所有形式的癌症和转移。
在一个实施例中,肿瘤是实体瘤。实体瘤可以定位或转移。
在一个实施例中,肿瘤是上皮来源的。
在一个实施例中,肿瘤是恶性肿瘤,如结肠直肠癌、肝癌、前列腺癌、胰腺癌、乳腺癌、卵巢癌、甲状腺癌、肾癌、膀胱癌、头颈癌或肺癌。
在一个实施例中,肿瘤是结肠直肠恶性肿瘤。
如本文所采用的,恶性肿瘤意指癌细胞。
在一个实施例中,溶瘤腺病毒用于治疗或预防转移。
在一个实施例中,本文的方法或调配物用于治疗耐药性癌症。
在一个实施例中,病毒与进一步的癌症治疗或疗法的施用组合施用。
在一个实施例中,提供了根据本公开的用来制造用于治疗癌症,例如上文所描述的癌症的药物的病毒或调配物。
在另外的方面,提供了一种治疗癌症的方法,其包括将治疗有效量的根据本公开的病毒或调配物施用给有需要的患者,例如人类患者。
在一个实施例中,本文的溶瘤病毒或调配物与另一种疗法组合施用。
如本文所采用的,“组合”旨在涵盖在癌症治疗或疗法之前,同时和/或之后施用溶瘤病毒的位置。
癌症疗法包含手术、放射疗法、靶向疗法和/或化学疗法。
如本文所采用的,癌症治疗是指用治疗化合物或生物制剂治疗,例如旨在治疗癌症和/或其维持疗法的抗体。
在一个实施例中,癌症治疗选自任何其它抗癌疗法,包含化学治疗剂、靶向抗癌剂、放射疗法、放射性同位素疗法或其任何组合。
在一个实施例中,本公开的如溶瘤腺病毒等病毒可以用作对于如手术(新辅助疗法)等疗法的预治疗,以缩小肿瘤、治疗转移和/或预防转移或进一步转移。可以在如手术(辅助疗法)等疗法后使用溶瘤腺病毒以治疗转移和/或预防转移或进一步转移。
如本文所采用的,同时地是与溶瘤腺病毒调配物同时或大致同时施用另外的癌症治疗。治疗可以包含在相同的调配物中或作为单独的调配物施用。
在一个实施例中,病毒与化学治疗剂的施用组合施用。
如本文所采用的,化学治疗剂是指特异性的抗肿瘤化学试剂或选择性破坏恶性细胞和组织的药物。例如,烷化剂、抗代谢物、蒽环霉素、植物生物碱、拓扑异构酶抑制剂以及其它抗肿瘤剂。化学疗法的其它实例包含多柔比星、5-氟尿嘧啶(5-FU)、紫杉醇、卡培他滨、伊立替康以及如顺铂和奥沙利铂等铂。优选的剂量可以由医师根据所治疗的癌症的性质来选择。
在一个实施例中,治疗剂是更昔洛韦,其可以帮助控制免疫应答和/或肿瘤血管形成。
在一个实施例中,本文方法中采用的一个或多个疗法是节拍法,即使用低剂量抗癌药物的连续或频繁治疗,通常伴随其它治疗方法。
亚组B溶瘤腺病毒,具体地Ad11和由其衍生的如EnAd等腺病毒可以与化学治疗剂特别协同,因为所述腺病毒似乎具有很大程度上不依赖于细胞凋亡的作用机制,从而通过主要的坏死性机制杀死癌细胞。而且,化学疗法期间发生的免疫抑制可以使溶瘤病毒更有效地发挥作用。
如本文所采用的,治疗剂量是指当在合适的治疗方案中采用时适合于实现预期治疗效果的如溶瘤腺病毒等病毒的量,所述合适的治疗方案例如改善疾病的症状或病症。当病毒颗粒的数量足以导致以下情况时,剂量可以被视为治疗癌症或转移的治疗剂量:肿瘤或转移性生长减慢或停止、或肿瘤或转移的大小缩小和/或延长患者的寿命。合适的治疗剂量通常是治疗效果与可耐受毒性之间的平衡,例如考虑到治疗所获得的益处,副作用和毒性是可耐受的。
在一个实施例中,每周施用根据本公开的病毒或治疗构建体(包含由其构成的调配物),例如一周1剂量在第1天、第3天、第5天施用,然后每个后续一周施用一剂量。
在一个实施例中,根据本公开的病毒或治疗构建体(包含由其构成的调配物)每两周或每三周施用,例如在第1周的第1天、第3天和第5天施用,并且在第2周或第3周也在第1天、第3天和第5天施用。此给药方案可以适当地重复多次。
在一个实施例中,每月施用根据本公开的病毒或治疗构建体(包含由其构成的调配物)。
在一个实施例中,通过重组技术制备本公开的病毒和构建体。技术人员将理解,携带腺病毒基因组可以通过其它技术手段制造,包含完全合成基因组或包括所有基因组的一部分的质粒。技术人员将理解,在合成基因组的情况下,插入区可以不包括限制性位点核苷酸,因为后者是使用克隆方法插入基因后的假象。
本公开进一步扩展到通过插入转基因或转基因盒获得或可获得的式(I)的腺病毒或其子公式。
如本文所采用的,“是”意指包括。
在本说明书的上下文中,“包括”应解释为“包含”。
包括某些特征/元件的本发明的实施例还旨在扩展到相关元件/特征的“由……组成”或“基本上由……组成”的可替代的实施例。
在技术上适当时,可以组合本发明的实施例。
如专利和申请等技术参考文献以引用的方式并入本文中。
本文具体和明确地叙述的任何实施例可以单独或与一个或多个另外的实施例组合形成免责声明的基础。
本申请要求通过引用并入本文的GB1713765.4、WO2018/041838和WO2018/041827的优先权。这些文件可以用于纠正本说明书中的错误,具体地序列表中的错误。
仅通过以下实例进一步描述本发明,所述实例参考附图,其中:
附图说明
图1 示出了NG-615、NG-640和NG-641转基因盒的示意图
图2:病毒基因组在肺癌、乳腺癌和膀胱癌细胞系中的复制。用NG-617、NG-615、NG-640、NG-641或enadenotucirev病毒颗粒处理A549(A)、MDA-MB-453(B)和RT4(C)细胞系长达7天。在处理后2天、3天、4天和7天评估通过qPCR检测到的病毒基因组的量。
图3:病毒介导的肺癌细胞溶瘤。用NG-617、NG-615、NG-640、NG-641或enadenotucirev病毒颗粒处理A549细胞长达4天。使用xCelligence系统(A)评估整个培养过程中的细胞活力。对于每种病毒处理(B),确定观察到50%杀死的时间(KT50)。
图4:肺癌和膀胱癌细胞中的NG-615转基因表达。用NG-615或enadenotucirev病毒颗粒处理A549(左图)和RT4细胞(右图),或使其不被感染长达7天。通过ELISA评估细胞上清液中Flt3配体(A)、MIP1α(B)和IFNα(C)的分泌。在经enadenotucirev处理或未处理的对照细胞中未检测到转基因表达(数据未显示)。
图5:肺癌和膀胱癌细胞中的NG-641转基因表达。用NG-641或enadenotucirev病毒颗粒处理A549(左图)和RT4细胞(右图),或使其不被感染长达7天。通过ELISA评估细胞上清液中CXCL9(A)、CXCL10(B)或IFNα(C)的分泌。在经enadenotucirev处理或未处理的对照细胞中未检测到转基因表达(数据未显示)。
图6:功能性转基因在肺癌细胞中的表达。用NG-615、NG-641或enadenotucirev病毒颗粒处理A549细胞长达4天。在处理后的第4天,使用基于细胞的报告基因测定评估产生的功能性IFNα(A)或MIP1α(B)转基因的水平。
图7:功能性FAP-BiTE在肺癌细胞中的表达。用NG-615、NG-641或enadenotucirev病毒颗粒处理A549细胞长达4天。在处理后2(A)天、3(B)天和4(C)天,通过测量与表达FAP的成纤维细胞系MRC-5共培养的Jurkat T细胞系的活化来评估细胞上清液中功能性FAP-BiTE的表达水平。
图8A:NG-641感染的A549细胞上清液中的转基因编码IFNα诱导Jurkat Dual报告基因细胞产生SEAP。用未感染(UIC)或被enadenotucirev(EnAd)或NG-641感染的A549癌细胞系上清液处理Jurkat-Dual报告基因细胞,并且测量分泌的胚胎碱性磷酸酶(SEAP)报告基因的水平。
图8B:NG-641感染的A549细胞上清液中的转基因编码CXCL9/10活化PathHunterβ-Arrestin细胞中的GPCR途径。用未感染(UIC)或被enadenotucirev(EnAd)或NG-641感染的A549癌细胞系的上清液处理PathHunterβ-Arrestin细胞,并且通过发光检测G蛋白偶联受体(GPCR)途径的CXCL9/10特异性诱导。
图9:NG-641感染的A549细胞的上清液中转基因编码CXCL9/10诱导CXCR3在活化的T细胞的表面上的下调。用未感染(UIC)或被enadenotucirev(EnAd)或NG-641感染的A549癌细胞系的上清液处理抗CD3/CD28活化的人T细胞,并且通过流式细胞术测量转基因CXCL9/10诱导的CXCR3下调。
图10:用EnAd、NG-615、NG-617、NG-640或NG-641,抗CD3/28或未感染的(UIC)接种的原代人肿瘤样本的离体培养物中内源性肿瘤浸润T细胞的活化病毒转基因产物IFNα和Flt3L的水平示出在A)中,并且IFNγ、TNFα、IL-17A、粒酶B和IL-13的水平示出在B)中。
图11:用EnAd、NG-617、NG-640或NG-641处理或未感染(UIC)的原代NSCLC肿瘤样品的体外培养物中内源性肿瘤浸润的T细胞的表面标记物表达和内细胞因子的活化。表达CD25、CD69和CD107a的CD4和CD8 T细胞的水平分别示出在A和B中。细胞内IFNγ和由CD4和CD8 T细胞表达的TNFα的水平分别示出在C和D中。
图12 本公开的包括或缺少任选的十八组氨酸(decahistidine)亲和标签的BiTE抗体的示意图。Ig SP:信号肽;10His:十八组氨酸亲和标签;L:GS连接子;VL:可变轻结构域;VH:可变重结构域。
图13 (A)斑点印迹示出了重组BiTE定量。(B)示出了显示FAP的ELISA结果的图。
图14 示出了在FAP BiTE和对照BiTE存在下使用流式细胞术测量的单独或与NHDF细胞共培养的T细胞的CD69(A)和CD25(B)的表达水平的图。图(C)示出了在FAP BiTE存在下单独或与NHDF细胞共培养的T细胞和通过细胞内细胞因子染色测量的对照BiTE的IFNγ表达的水平。
图15 (A)示出了显示已经与T细胞和FAP BiTE或对照BiTE共培养的NHDF细胞的细胞毒性的LDH测定的结果的图。(B)示出了显示已经与T细胞和FAP BiTE或对照BiTE共培养的BTC100细胞的细胞毒性的LDH测定结果的图。(C)与T细胞和FAP BiTE与对照BiTE共培养后的NHDF细胞的图。
图16 是示出了跨多个细胞和细胞系表达EpCAM和FAP的细胞百分比的图。
图17 (A)示出了随着BiTE浓度增加,FAP BiTE的NHDF剂量应答的图。图(B)和图(C)示出了显示已经与T细胞和EpCAM BiTE或对照BiTE共培养的DLD细胞的细胞毒性的LDH测定的结果。
图18 (A)示出了通过FAP或同位素对照抗体确定并且通过流式细胞术分析的CHO细胞中的FAP表达的图。(B)示出了显示已经与T细胞和FAP BiTE或对照BiTE共培养的CHO或CHO-FAP细胞的细胞毒性的LDH测定结果的图。
图19 示出了使用流式细胞术分析CHO对CHO-FAP细胞的T细胞活化(基于CD69和CD25表达水平)的图。
图20 (A)示出了FAP BiTE活化使用流式细胞术分析的CD4+或CD8+T细胞(基于CD69和CD25表达水平)的能力的图。(B)示出了显示已经与CD4+或CD8+T细胞和FAP BiTE或对照BiTE共培养的NHDF细胞的细胞毒性的LDH测定结果的图。
图21 (A)示出了用对照或FAP BiTE培养的腹水中CD3+T细胞的数量的图。(B)示出了用对照或FAP BiTE培养的腹水中T细胞的CD25表达水平的图。(C)示出了用对照或FAPBiTE培养的腹水的FAP+细胞数量的图。
图22 (A)示出了NG-601、NG-602、NG-603、NG-604、NG-605、NG-606和EnAd的每个细胞检测到的病毒基因组数量的定量的图。(B)示出了通过感染A549细胞评估的NG-601、NG-602、NG-603、NG-604、NG-605、NG-606或EnAd的溶瘤活性的图。
图23 示出了使用流式细胞术分析,通过NG-601、NG-602、NG-605和NG-606在与CHO-FAP共培养时T细胞活化(基于CD69和CD25表达水平)的图。
图24 示出了显示确定从NG-605和NG-606产生的FAP BiTE的量的实验结果的图。
图25 示出了用NG-607、NG-608、NG-609和NG-610感染的Ad293细胞的显微镜图像。
图26 (A)指示使用XCELLigence进行分析,NG-603、NG-604、NG-605、NG-606和EnAd杀死NHDF细胞的能力的图。(B)指示使用LDH测定法进行分析,NG-603、NG-604、NG-605、NG-606和EnAd杀死NHDF细胞的能力的图。
图27 示出了显示使用流式细胞术分析,通过NG-603、NG-604、NG-605、NG-606与NHDF细胞、SKOV和T细胞共培养的T细胞活化(基于CD69和CD25表达水平)的图。
图28 (A)示出了使用流式细胞术分析,通过NG-603、NG-604、NG-605、NG-606与NHDF和多个SKOV细胞对单个SKOV共培养的T细胞活化(基于CD69和CD25表达水平)的图。(B)指示使用LDH测定法分析,用NG-605和NG-606感染的NHDF细胞的细胞毒性的图。
图29 示出了通过重组FAP BiTE、EnAd、NG-603或NG-605,来自NHDF细胞溶解的间隔拍摄视频的静止帧图像。
图30 示出了通过NG-607、NG-608、NG-609或NG-610,来自NHDF细胞溶解的间隔拍摄视频的静止帧图像。
图31 示出了指示使用LDH测定法进行分析,在存在T细胞或不存在T细胞的情况下,用EnAd、NG-601、NG-602、NG-603和NG-604感染的DLD细胞的细胞毒性的图。
图32 (A)指示在用本公开的病毒感染的腹水样品中CD3+T细胞上CD25的表达水平的图。(B)指示用本公开的病毒感染的腹水样品中FAP+细胞的数量的图。
图33 示出了指示从癌症患者获得并且用本公开的病毒感染的腹水样品中CD3+T细胞的数量的图。
图34 示出了指示从癌症患者获得并且用本公开的病毒感染的腹水样品中CD3+T细胞上的CD25表达水平的图。
图35 示出了指示从癌症患者获得并且用本公开的病毒感染的腹水样品中的FAP+细胞数量的图。
图36 示出了在人类成纤维细胞存在下通过重组FAP BiTE蛋白活化T细胞细胞因子产生和用抗CD3/CD28珠进行多克隆活化的比较。(A)通过ELISA测量的IFNγ水平。(B)通过细胞因子珠阵列测量的细胞因子水平。
图37 FAP靶向BiTE诱导T细胞脱粒和FAP+细胞的特异性细胞毒性
(A)用NHDF细胞(5:1)和(B)含有BiTE的上清液对培养物中的T细胞进行脱粒。通过用CD107a特异性抗体培养6小时后CD107a的外化来评估脱粒,并且通过流式细胞术测量。CD3/CD28磁珠用作阳性对照。(C)与T细胞(1:5)和10倍连续稀释的含有BiTE的上清液共培养24小时后NHDF细胞的细胞毒性。通过将LDH释放到培养上清液中来评估细胞毒性。(D)在与来自六个健康供体和含有BiTE的上清液的PBMC衍生的T细胞(1:5)共培养24小时后,评估LDH释放(左)和T细胞上CD25诱导(右)对NHDF的溶解。
图38 表达FAP BiTE的EnAd选择性杀死FAP+成纤维细胞,并且降低腹膜腹水样品中的TGFb
(A,B)用PBMC衍生的T细胞和EnAd或重组病毒培养72小时后FAP+成纤维细胞(A)和EpCAM+肿瘤细胞(B)的数目。首先从三名患者腹水中分离腹水细胞并且离体扩增。通过流式细胞术在感染后72小时测量细胞数量。(C)在感染后72小时测量来自(A)的PBMC衍生的CD3细胞上的活化标记物CD25的诱导。(D)使用从(A)采集的上清液通过ELISA测量TGFb的水平。
图39 示出了FAP BiTE蛋白和EnAd-FAPBiTE病毒对患者恶性腹水活检样品中内源性肿瘤相关T细胞的活化和相关的FAP+细胞杀伤。(A)通过CD25表达测量的T细胞活化。(B)通过流式细胞术测量的残留数量的FAP+细胞。
图40 PD-L1阻断抗体对患者样品中BiTE介导的T细胞活化的影响
(A)通过流式细胞术评估在从腹膜腹水初始分离后FAP+细胞上内源性T细胞和PD-L1对PD1的表达。(B)在存在游离BiTE、EnAd或重组病毒的情况下,在存在或不存在抗PD-L1阻断抗体的情况下,将来自腹膜腹水的未纯化的总细胞在来自相同渗出物的50%液体中孵育。2天后,采集总细胞群,并且通过流式细胞术定量CD25+T细胞的数量。(C)通过ELISA测量的来自(B,D)的培养上清液中的干扰素γ的量。(D)使用流式细胞术测量(B)中残留的FAP+细胞的数量。
图41 表达BiTE的EnAd活化并且重定向来自患者活组织检查样品的T细胞以溶解NHDF成纤维细胞
(A)从健康供体或恶性渗出癌活组织检查样品中分离后内源性T细胞的PD-1表达。通过流式细胞术测量PD-1表达。(B)通过流式细胞术测量的PBMC和癌症活组织检查样品的未纯化细胞群中CD3+细胞的比例。(C)在处理后120小时从(B)采集的培养上清液中通过ELISA测量的干扰素γ水平。(D)通过与PBMC或总癌症活检细胞(1:5)和含有BiTE的上清液共培养的xCELLigence细胞毒性测定,在130小时内实时监测NHDF成纤维细胞的活力。
图42 示出了免疫抑制性腹水液样品对FAP BiTE介导的和抗CD3/CD28珠介导的PBMC T细胞活化的影响。(A)用抗CD3/Cd28磁珠活化的PBMC T细胞。(B)在NHDF细胞存在下用对照或FAP BITE活化的PBMC T细胞。NS:正常血清,A:腹膜腹水。
图43 表达EnAd的FAP BiTE使患者腹水中的CD11b+巨噬细胞极化为更炎性的表型
(A)在存在游离BiTE或表达病毒的BiTE的情况下,将来自腹水样品的未纯化的总细胞在50%腹水液中孵育。干扰素γ治疗用作阳性对照。3天后,采集总细胞群并且通过流式细胞术测量CD3+细胞上活化标记物CD25的诱导。(B)通过ELISA测量来自(A)的培养上清液中的干扰素γ的水平。(C)在第3天,通过流式细胞术测量来自(A)的CD11b+细胞上的CD68、CD86、CD206和CD163的表达水平。来自一式三份的代表性流式细胞术光谱与完整数据集一起显示。
图44 实体前列腺肿瘤的结构和细胞组成的表征
示出了通过ELISA测量的组织切片培养基中IFNg的水平。在指定的时间点从恶性和良性组织的切片培养物中采集上清液;和通过ELISA测量的恶性和良性组织的组织培养基中IL-2的水平。
图45 示出了转基因盒的示意图。
图46 示出了指示NG-611、NG-612和NG-617处理的肿瘤细胞中经每个细胞检测病毒基因组的数目的图。
图47 示出了与NG-612、enadenotucirev或未处理的对照上清液相比,在用NG-611病毒颗粒处理后24小时、48小时或72小时与表达SKOV细胞的EpCam和从A549细胞采集的上清液共培养后表达CD69(a)、CD25(b)、HLA-DR(c)、CD40L(d)或细胞表面CD107a(e)的T细胞的百分比。
图48 示出了与NG-611、enadenotucirev或未处理的对照上清液相比,在用NG-612病毒颗粒处理后24小时、48小时或72小时与表达MRC-5细胞的FAP和从A549细胞采集的上清液共培养后表达CD69(a)、CD25(b)、HLA-DR(c)、CD40L(d)或细胞表面CD107a(e)的T细胞的百分比。
图49 示出了表达EpCAM和FAP的MRC-5细胞的百分比
图50 示出了在用NG-611、NG-612或enadenotucirev病毒颗粒或未处理的对照上清液处理后24小时、48小时或72小时与SKOV细胞(A)或MRC-5细胞(B)的T细胞共培养物的上清液中的IFNγ表达,其与从A549细胞采集的上清液一起孵育。
图51 示出了体内表达病毒的BiTE的抗肿瘤功效和免疫活化。(a)用盐水、enadenotucirev或NG-611治疗的小鼠的肿瘤体积。(b)与enadenotucirev治疗或未治疗的对照相比,NG-611治疗的肿瘤中CD8与CD4 T细胞的比例。
图52 示出了指示NG-612和NG-615处理的肿瘤细胞中经每个细胞检测病毒基因组的数目的图。
图53 示出了IFNα、MIP1α和Flt3 L在NG-615的细胞上清液中与enadenotucirev与未处理的对照肿瘤细胞的上清液的表达。
图54 示出了与NG-612、enadenotucirev或未处理的对照上清液相比,在用NG-615病毒颗粒处理后24小时、48小时或72小时与表达MRC-5细胞的FAP和从A549细胞采集的上清液共培养后表达CD69(a)、CD25(b)、HLA-DR(c)、CD40L(d)或细胞表面CD107a(e)的T细胞的数量。
图55 示出了在用NG-612、NG-615或enadenotucirev病毒颗粒或未处理的对照上清液处理后24小时、48小时或72小时与MRC-5细胞的T细胞共培养物的上清液中的IFNγ表达,其与从A549细胞采集的上清液一起孵育。
序列
SEQ ID NO:1 抗FAP BiTE DNA编码序列,具有N末端信号序列和C末端deca-His亲和标签
SEQ ID NO:2 抗FAP BiTE氨基酸序列,具有N末端信号序列和C末端deca-His亲和标签
SEQ ID NO:3: 对照(抗FHA)BiTE DNA编码序列,具有N末端信号序列和C末端deca-His亲和标签
SEQ ID NO:4: 对照(抗FHA)BiTE氨基酸序列,具有N末端信号序列和C末端deca-His亲和标签
SEQ ID NO:5: 抗CD3 ScFv氨基酸序列
SEQ ID NO:6: 抗CD3 VH
SEQ ID NO:7: 抗CD3 VL
SEQ ID NO:8: 抗CD3 ScFv连接子序列
SEQ ID NO:9: 抗FAP ScFv
SEQ ID NO:10: 抗FAP VL结构域
SEQ ID NO:11: 抗FAP VH结构域
SEQ ID NO:12: 抗FAP和抗EpCAM连接子序列
SEQ ID NO:13: BiTE前导序列
SEQ ID NO:14: 对照BiTE(抗FHA)
SEQ ID NO:15: 对照(抗FHA)ScFv
SEQ ID NO:16: 对照(抗FHA)VL
SEQ ID NO:17: 对照(抗FHA)VH
SEQ ID NO:18: 对照(抗FHA)ScFv连接子序列
SEQ ID NO:19: Deca-His标签序列
SEQ ID NO:20: FAP BiTE-P2A-RFP(ITALICS=前导,BOLD=弗林蛋白酶切割位点,UNDERLINE=P2A序列,小写=RFP)
SEQ ID NO:21: 对照(抗FHA)BiTE-P2A-RFP(ITALICS=前导,BOLD=弗林蛋白酶切割位点,UNDERLINE=P2A序列,小写=RFP)
SEQ ID NO:22: 人类FAP DNA编码序列
SEQ ID NO:23: 人类FAP氨基酸序列
SEQ ID NO:24: CMV启动子序列
SEQ ID NO:25: SV40晚期多腺苷酸化序列
SEQ ID NO:26: NG-605(EnAd-CMV-FAPBiTE)
SEQ ID NO:27: NG-606(EnAd-SA-FAPBiTE)
SEQ ID NO:28 EnAd基因组
SEQ ID NO:29 BXDNA序列对应于并且包含EnAd基因组的bp 28166到bp 28366
SEQ ID NO:30 BYDNA序列对应于并且包含EnAd基因组的bp 29345到bp 29379
SEQ ID NO:31 HIS-Tag
SEQ ID NO:32 剪接受体序列
SEQ ID NO:33 SV40多腺苷酸化序列
SEQ ID NO:34 FAP BiTE核酸序列(OKT3)
SEQ ID NO:35 FAP BiTE核酸序列(aCD3)
SEQ ID NO:36 NG-611转基因盒
SEQ ID NO:37 NG-612转基因盒
SEQ ID NO:38 NG-613转基因盒
SEQ ID NO:39 限制性位点插入(BX)
SEQ ID NO:40 限制性位点插入(BY)
SEQ ID NO:41 CMV启动子序列
SEQ ID NO:42 PGK启动子序列
SEQ ID NO:43 CBA启动子序列
SEQ ID NO:44 短剪接受体(SSA)DNA序列
SEQ ID NO:45 剪接受体(SA)DNA序列
SEQ ID NO:46 分支剪接受体(bSA)DNA序列
SEQ ID NO:47 Kozak序列(零序列)
SEQ ID NO:48 起始密码子的实例
SEQ ID NO:49 内部核糖体进入序列(IRES)
SEQ ID NO:50 P2A肽
SEQ ID NO:51 F2A肽
SEQ ID NO:52 E2A肽
SEQ ID NO:53 T2A肽
SEQ ID NO:54 多聚腺苷酸化(polyA)序列
SEQ ID NO:55 前导序列
SEQ ID NO:56 前导序列
SEQ ID NO:57 IFNγ氨基酸序列
SEQ ID NO:58 IFNα氨基酸序列
SEQ ID NO:59 TNFα氨基酸序列
SEQ ID NO:60 对应于EnAd基因组的E2B区的DNA序列(bp 10355到bp 5068)
SEQ ID NO:61: 抗FAP BiTE DNA编码序列,具有N末端信号序列,不具有C末端deca-His亲和标签
SEQ ID NO:62: 抗FAP BiTE氨基酸序列,具有N末端信号序列,不具有C末端deca-His亲和标签
SEQ ID NO:63: 对照(抗FHA)BiTE DNA编码序列,具有N末端信号序列,不具有C末端deca-His亲和标签
SEQ ID NO:64: 对照(抗FHA)BiTE氨基酸序列,具有N末端信号序列,不具有C末端deca-His亲和标签
SEQ ID NO:65: 对照BiTe(抗FHA),不具有C末端deca-His亲和标签的
Q ID NO:66: NG-605(EnAd-CMV-FAPBiTE),不具有deca-His亲和标签
SEQ ID NO:67: NG-606(EnAd-SA-FAPBiTE),不具有deca-His亲和标签
SEQ ID NO:68: FAP BiTE核酸序列(OKT3)
SEQ ID NO:69: FAP BiTE核酸序列(aCD3)
SEQ ID NO:70: NG-611转基因盒
SEQ ID NO:71: NG-612转基因盒
SEQ ID NO:72: NG-613转基因盒
SEQ ID NO:73: NG-614转基因盒
SEQ ID NO:74: NG-617转基因盒
SEQ ID NO:75: FAP BiTE氨基酸序列(OKT3)
SEQ ID NO:76: FAP BiTE氨基酸序列(aCD3)
SEQ ID NO:77: NG-611基因组
SEQ ID NO:78: NG-612基因组
SEQ ID NO:79: NG-613基因组
SEQ ID NO:80: NG-614基因组
SEQ ID NO:81: NG-617基因组
SEQ ID NO:82: NG-615基因组
SEQ ID NO:83: NG-640基因组
SEQ ID NO:84: NG-641基因组
SEQ ID NO:85: 零序列
SEQ ID NO:86: Flt3L核酸序列
SEQ ID NO:87: 零序列
SEQ ID NO:88: MIP1α核酸序列
SEQ ID NO:89: 柔性连接子序列
SEQ ID NO:90: IFNα核酸序列
SEQ ID NO:91: CXCL10核酸序列
SEQ ID NO:92: CXCL9核酸序列
SEQ ID NO:93: NG-615转基因盒
SEQ ID NO:94: NG-640转基因盒
SEQ ID NO:95: NG-641转基因盒
SEQ ID NO:96: FLT3L氨基酸序列
SEQ ID NO:97: MIP1α氨基酸序列
SEQ ID NO:98: IFNα氨基酸序列
SEQ ID NO:99: CXCL9氨基酸序列
SEQ ID NO:100: CXCL10氨基酸序列
SEQ ID NO:101: NG-618基因组
SEQ ID NO:102: NG-618 FAP BiTE核酸序列
SEQ ID NO:103: NG-618转基因盒
SEQ ID NO:104到277是连接子序列
SEQ ID NO:278 NG-616基因组
SEQ ID NO:279到281是引物
实例
实例1
设计重组BiTE并且如本实例中所描述制备蛋白质。
1.1BiTE工程化
通过将具有不同特异性的两个单链抗体片段(ScFv)与柔性Gly4Ser连接子连接来生成BiTE。ScFv是通过连接子从亲本单克隆抗体连接VH和VL结构域而创建的。每个BiTE设计有用于哺乳动物分泌的N-末端信号序列和用于检测和纯化的C-末端十八组氨酸亲和标签。通过标准DNA克隆技术工程化BiTE并且将其插入蛋白质表达载体中(图1)。
使用来自专利WO2010037835A2的抗FAP ScFv和来自2005040220(其中的SEQ ID63)的抗CD3 ScFv从头创建抗FAP BiTE,其中添加了信号序列和亲和标签。
对照BiTE使用来自Hussein等人,2007的抗FHA(来自百日咳博德特氏菌的丝状血细胞凝集素)ScFv(Hussein AH等人(2007)“针对百日咳博德特氏菌表面粘附素丝状血凝素和百日咳杆菌素的单链可变片段抗体的构建和表征”。感染免疫75,5476-5482),以及来自专利WO 2005040220(其中SEQ ID NO:63)的抗CD3 ScFv,其中添加了信号序列和亲和标签。
1.2重组BiTE生产
通过使用CMV启动子(SEQ ID NO:24)将各序列克隆到pSF-CMV载体中以驱动蛋白质表达来产生重组BiTE蛋白质(图1)。通过NanoDrop测量质粒、pSF-CMV-FAPBiTE和pSF-CMV-ControlBiTE(表2)的质粒DNA浓度。包含空pSF-CMV载体作为阴性对照。用4mL OptiMEM稀释各54.7μg。将109.2ug PEI(线性,MW 25000,美国Polysciences公司)在4mL OptiMEM培养基中稀释,并且与4ml稀释的DNA混合以生成DNA-PEI复合物(DNA:PEI比为1:2(w/w))。在室温下孵育20分钟后,用OptiMEM将复合物混合物补足到18mL,并且将此转染混合物添加到含有90%汇合的Ad293细胞的T175烧瓶中。将细胞与转染混合物在37℃、5%CO2孵育4小时后,将30mL细胞培养基(补充有谷氨酰胺的DMEM高葡萄糖,无酚红)添加到细胞中,并且将烧瓶在37℃、5%CO2下孵育48小时。将另一个细胞烧瓶与pSF-CMV-GFP平行转染以确保有效的转染效率。为了采集分泌的蛋白质,收集转染细胞的上清液,并且在4℃下以350g离心5分钟以去除细胞组分(Allegra X-15R,贝克曼库尔特有限公司(Beckman Coulter))。将上清液转移到10k MWCO Amicon Ultra-15离心过滤装置(密理博公司(Millipore))中。在4750rpm和4℃下旋转后,用流过物调节渗余物的体积以获得高50倍的浓度。将等分的浓缩蛋白质储存在-80℃。
表2
在命名构建体中用作前缀的“p”指示构建体是质粒。
质粒ID [质粒DNA]ng/ml
pSF-CMV-FAPBiTE 6700
pSF-CMV-ControlBiTE 5300
pSF-Lenti-FAP 659.6
1.3与免疫调节蛋白结合表达FAP-BiTE的病毒的产生
产生了三种病毒(NG-640、NG-641和NG-615),它们编码靶向FAP的BiTE分子和2种或3种免疫调节蛋白(表1)。NG-640编码三种转基因蛋白、FAP-BiTE分子和趋化因子CXCL9和CXCL10。NG-641和NG-615两者都编码四种转基因蛋白。NG-641编码FAP-BiTE、趋化因子CXCL9和CXCL10和细胞因子IFNα,而NG-615编码FAP-BiTE、趋化因子MIP1α和细胞因子FLT3配体和IFNα。还产生了仅编码FAP-BiTE分子的病毒(NG-617)
表1
在每个转基因盒中,用短剪接受体序列(SSA,CAGG)将编码BiTE和其它免疫调节蛋白的cDNA侧接在5'末端,并且用SV40晚期poly(A)序列(PA,SEQUENCE ID NO:25)侧接在3'末端。使用2A高效可自切肽序列(P2A,T2A,E2A,SEQUENCE ID NO:50、53和52)分离每个转基因的cDNA序列。
病毒生产
质粒pEnAd2.4用于通过直接插入合成的转基因盒(分别为SEQ ID NO:93、94和95)使质粒pNG-615、pNG-640和pNG-641生成。NG-615含有四种编码FAP靶向BiTE(SEQ ID NO:102)、Flt3L(SEQ ID NO.86)、MIP1α(SEQ ID NO.88)和IFNα(SEQ ID NO.90)的转基因。NG-640和NG-641编码靶向BiTe的FAP(SEQ ID NO.102)、CXCL9(SEQ ID NO.92)和CXCL10(SEQID NO.91),NG-641还含有编码IFNα的第四转基因(SEQ ID NO.90)。在图1中示出了转基因盒的示意图。通过限制性分析和DNA测序确认质粒DNA的构建。
质粒、pNG-615、pNG-640和pNG-641通过用酶AscI限制性消化进行线性化以产生病毒基因组。根据下文给出的方法扩增和纯化病毒。
通过苯酚/氯仿提取纯化消化的DNA,并且在300μl>95%分子生物级乙醇和10μl3M乙酸钠中于-20℃沉淀16小时。通过在14000rpm离心5分钟沉淀析出的DNA,并且在500μl70%乙醇中洗涤,然后再次以14000rpm离心5分钟。将干净的DNA团粒空气干燥,重悬浮于含有15μl脂质体转染试剂的500μl OptiMEM中,并且在室温下孵育30分钟。然后将转染混合物逐滴添加到含有生长到70%汇合的293细胞的T-25烧瓶中。将细胞与转染混合物在37℃孵育2小时后,向细胞中添加5%CO2 4ml的细胞培养基(DMEM高葡萄糖和谷氨酰胺补充有2%FBS),并且将烧瓶在37℃,5%CO2孵育。
每24小时监测转染的293细胞,并且每48小时到72小时补充额外的培养基。通过观察细胞单层中的显著细胞病变效应(CPE)来监测病毒的产生。一旦观察到广泛的CPE,通过三次冻融循环从293细胞采集病毒。采集的病毒用于再感染293细胞以便扩增病毒原种。通过观察细胞单层中的显著CPE证实扩增期间活病毒的产生。一旦观察到CPE,通过三次冻融循环从293细胞采集病毒。在通过双氯化铯条带纯化病毒以产生纯化的病毒原种之前,将扩增的病毒原种用于进一步扩增。
实例2:病毒复制和溶瘤活性的分析
病毒复制
用1ppc NG-615、NG-640、NG-641、NG-617、enadenotucirev(EnAd)接种72小时或未感染的肺(A549)、乳腺(MDA-MB-453)或膀胱(RT4)癌细胞系用于通过qPCR定量病毒DNA。收集细胞上清液并且通过以1200rpm离心5分钟来澄清。50μL上清液用于DNA分析。
根据制造商的方案,使用Qiagen DNeasy试剂盒从上清液样品中提取DNA。还使用DNeasy试剂盒制备并且提取使用EnAd病毒颗粒(2.5e10到2.5e5vp)的标准曲线。使用针对早期基因E3的病毒基因特异性引物-探针,通过qPCR分析每个提取的样品或标准品。每个细胞中检测到的病毒基因组的数量的定量表明,对于所有测试的病毒(NG-617、NG-615、NG-640和NG-641),A549、MDA-MB-453和RT4中都有病毒复制(图2)。所有病毒的病毒复制都类似,并且与亲本EnAd病毒相同。在未感染的细胞中未检测到病毒基因组。
溶瘤活性
使用xCELLigence实时细胞分析仪(RTCA)监测接种了100ppc NG-615、NG-640、NG-641、NG-617、EnAd或未感染的肺(A549)癌细胞。每60分钟监测一次细胞增殖,持续96小时。通过计算杀死时间50(KT50),达到50%裂解的时间点来评估细胞的溶瘤作用(图3)。这些数据示出了所有测试病毒,包含亲本EnAd病毒的等效KT50。在未处理的细胞上未观察到溶瘤作用。
这些数据共同表明,包含BiTE和两个或三个免疫调节转基因不会显著影响EnAd病毒的复制或溶瘤活性。
实例3:病毒介导的转基因表达重组BiTE检测的分析
为了检测BiTE,可以使用蛋白质印迹技术用抗His抗体探测C-末端的十八组氨酸亲和标签。用溶解缓冲液调节蛋白质样品到终体积15μL,包含含有β-巯基乙醇和SDS的2.5μL 6x Laemmli SDS样品缓冲液。将样品在95℃孵育5分钟以使蛋白质变性并且加载到15孔10%预制聚丙烯酰胺凝胶(Mini-PROTEAN TGX预制凝胶,英国生命科学公司(BioRad))上。在Mini-PROTEAN Tetra系统(英国生命科学公司)内的1x运行缓冲液中,凝胶在180V下运行45分钟。将来自SDS凝胶的蛋白质通过在300mA和4℃下90分钟内在微型反式印迹细胞(MiniTrans-Blot Cell)(英国生命科学公司)内的1x转移缓冲液中湿电印迹转移到硝酸纤维素膜上。在冰袋存在下执行转移以限制热量。然后将硝酸纤维素膜用PBS-T中的5%牛奶在摇床上在室温下封闭1小时,并且用抗His(C-末端)抗体(小鼠α-6xHis,克隆3D5,英国英杰公司(Invitrogen),#46-0693)探测,在PBS/5%牛奶中1:5000稀释。在摇床上于4℃孵育过夜后,洗涤膜并且用HRP标记的多克隆次级α-小鼠免疫球蛋白抗体(在PBS/5%牛奶中1:10.000,Dako公司,#P0161)在室温下探测1小时。为了可视化,按照制造商的说明应用SuperSignal West Dura延长持续时间基板(英国赛默飞世尔科技公司)并且暴露于X射线胶片并在自动胶片处理器中显影。结果证明了用BiTE表达质粒转染的Ad293细胞中BiTE蛋白的表达和分泌,但不是亲本载体。
重组BiTE定量
为了测量重组BiTE蛋白的量,使用斑点印迹技术将BiTE信号与His标记的(C-末端10His)蛋白标准品(10x His标记的人类组织蛋白酶D,Biolegend公司,#556704)进行比较。制备两倍系列稀释的BiTE样品和蛋白质标准品,并且将1.5μL各自直接施加到硝酸纤维素膜上并且空气干燥20分钟。然后执行上文所描述的用于蛋白质印迹的阻断和染色方案。调节蛋白质标准品的摩尔浓度以表示BiTE浓度为250μg/mL。结果(图13A)证明了用BiTE表达质粒转染的Ad293细胞中BiTE蛋白的表达和分泌。
FAP结合ELISA
通过酶联免疫吸附测定(ELISA)评估从用pSF-CMV-FAPBiTE或pSF-CMV-对照BiTE转染的细胞分泌的FAP BiTE和对照(抗FHA)BiTE(SEQ ID NO:2和4)的FAP结合活性。包含空pSF-CMV载体上清液作为阴性对照。通过在4℃下用PBS缓冲液中的人类FAP/seprase蛋白(100ng/孔,义翘神州科技有限公司(Sino Biological Inc),10464-H07H-10)涂覆过夜来制备ELISA板(Nunc Immuno MaxiSorp 96孔微孔板)。用PBS 0.05%吐温20在所有后续结合步骤之间洗涤板。将板在室温下用5%BSA的PBS 0.05%吐温20封闭1小时。将等分的BiTE蛋白或从空pSF-CMV载体转染的孔采集的蛋白质稀释10倍到PBS/5%BSA/0.05%吐温20中。将所有样品添加到FAP涂覆的板中并且在室温下孵育2小时。将检测抗体,抗His(C末端)抗体(小鼠抗6xHis,克隆3D5,英杰公司,英国,#46-0693)以1:1000稀释,并且在室温下施加1小时。然后在室温下施加HRP缀合的抗小鼠Fc(在PBS/5%牛奶中1:1000,Dako公司)1小时,接着用HRP底物溶液3.3.5.5'-四甲基乙二胺(TMB,赛默飞世尔科技公司)执行HRP检测。使用终止溶液终止反应,并且在读板器上在450nm处测量显色。针对FAP BiTE、对照BiTE和空载体上清液绘制450nm处的吸光度,证明FAP BiTE与FAP蛋白的特异性结合。结果(图13B)示出了FAP BiTE而非对照BiTE与重组FAP蛋白的特异性结合。
通过ELISA评估转基因表达
使用ELISA评估趋化因子或细胞因子转基因IFNα、MIP1α、FLT3L、CXCL10和CXCL9的表达。A549和RT4癌细胞系接种了1ppc NG-615、NG-640、NG-641、NG-617、EnAd或未感染长达7天。在接种后4天和7天,澄清细胞上清液,并且通过ELISA评估转基因表达。
使用Verikine人类IFNα试剂盒(Pbl assay science)进行IFNαELISA,使用人类CCL3 Quantikine ELISA试剂盒(R&D systems)进行MIP1αELISA,使用Flt3L人类ELISA试剂盒(Abcam)进行Flt3L ELISA,使用CXCL9人类ELISA试剂盒(Abcam)进行CXCL9 ELISA,并且使用CXCL10人类ELISA试剂盒(Abcam)进行CXCL10 ELISA。所有测定均根据制造商的方案进行。
通过从标准曲线内插确定分泌的IFNα、MIPα、FLt3L、CXCL9和CXCL10的浓度。在NG-615处理过的细胞的细胞上清液中可以检测到IFNα、MIP1α和Flt3L表达,在NG-641处理过的细胞的上清液中可以检测到IFNα、CXCL9和CXCL10,并且在NG-640处理过的细胞的上清液中可以检测到CXCL9和CXCL10(图4和5)。在EnAd处理或未处理的对照细胞中未检测到趋化因子或细胞因子转基因表达。
通过基于细胞的报告基因测定评估功能性转基因表达
在使用Jurkat-Dual报告基因细胞系(Invivogen)的测定中评估了功能性FAP-BiTE和IFNα转基因的表达。这是一种通过两个诱导型报告基因构建体的稳定整合而转化的人类永生化的T淋巴细胞细胞系(Jurkat)。可诱导的报告基因构建体中的一个能够通过分泌的胚胎碱性磷酸酶(SEAP)的分泌和活性来研究干扰素调节因子(IRF)途径的IFN活化,而第二个是通过T细胞受体的信号传导而活化的NF-kB响应性分泌型荧光素酶报告基因。SEAP的活性与上清液中存在的IFN-的水平成正比,并且可以通过检测基片Quanti-BlueTM的SEAP诱导的降解来测量。使用CCR5报告基因细胞系(CHO-K1 CCR5β-arrestin,Invivogen)评估功能性MIP1α的表达。A549癌细胞系接种了1ppc NG-615、NG-640、NG-641、NG-617、EnAd或未感染。接种后2天、3天或4天,收集细胞上清液,并且澄清以进行分析。
为了评估IFNα功能,将20μL在培养基中按1:10、1:50或1:250稀释的每种上清液添加到Jurkat Dual细胞(2×105个细胞/孔)中,并且孵育16-20小时。然后从板上收集上清液,并且用200μL Quanti-BlueTM试剂处理1小时。使用酶标仪在640nm下测量吸光度(Abs)来分析板。可以在NG-615和NG-641处理的癌细胞,而不是NG-640、NG-617、EnAd处理或未感染的对照的上清液中检测到表明功能性IFNα的存在的反应(图6A)。在NG-615和NG-641处理的上清液中检测到的功能性IFNα的水平类似。
为了评估MIP1α功能,将CCR5报告基因细胞接种(5×103个细胞/孔)并且孵育20-24小时。然后将来自经处理的肿瘤细胞的5μL上清液加入每个孔中,并且孵育90分钟。然后使用检测溶液检测荧光素酶报告基因的活性,并且在发光读板器上进行定量。在NG-615处理的癌细胞的上清液和用已知表达MIP1a NG-347的阳性对照病毒处理的细胞的上清液中检测到表明存在功能性MIP1α的反应(图6B)。
为了评估FAP-BiTE功能,将MRC-5肺成纤维细胞(在其细胞膜上表达FAP)接种(2×104个细胞/孔)并且孵育4小时,以使细胞粘附到板上。然后将Jurkat-Dual细胞(2×105个细胞/孔)与来自处理过的肿瘤细胞的20μL上清液一起添加到孔中。将板孵育16-20小时。然后收获上清液,并且用50μL Quanti-Luc试剂处理,然后立即在读板器上读取板以检测荧光素酶活性。在NG-617、NG-615、NG-640和NG-641处理的癌细胞的上清液,而不是EnAd处理或未经处理的对照上清液中检测到表明功能性FAP-BiTE的存在的反应(图7)。出人意料的是,考虑到通过NG-615和NG-641产生的IFNα的水平类似,当与表达测试的病毒的所有其它BiTE相比时,包含其它含有4个转基因的病毒NG-641,NG-615处理的细胞的上清液具有显著较低水平的功能性FAP-BiTE表达。
实例2
在构建携带BiTE转基因的EnAd病毒之前,在许多不同的测定中评估重组BiTE蛋白的功能活性。
人类外周血单个核细胞(PBMC)的分离
通过密度梯度离心从健康供体的新鲜人类血液样品或从牛津的英国国家医疗服务系统血液与移植管理处(NHS Blood和Transplant UK)获得的全血白细胞锥体分离人类PBMC。在任一种情况下,将样品用PBS 1:2稀释,并且将25mL此混合物在50mL离心管中分层到13mL Ficoll(1.079g/mL,淋巴细胞分离液(Ficoll-Paque Plus),GE Healthcare公司)上。将样品在22℃下以1600rpm离心30分钟(Allegra X-15R,Beckman Coulter),用最低减速设置以保持相分离。离心后,可以观察到4层,其中包含在顶端的等离子体层,下面是含有PBMC的界面,底部是一个Ficoll层和一层红细胞和粒细胞。使用巴斯德吸管收集PBMC,并且用PBS(1200rpm,室温下10分钟)洗涤两次,并且重悬于补充有10%FBS的RPMI培养基中。
分离CD3阳性T细胞
根据制造商的方案,使用Pan T细胞分离试剂盒(美天旎生物技术公司(MiltenyiBiotec),#130-096-535)通过耗尽非CD3细胞从PBMC中提取CD3阳性(CD3+)T细胞。
处理原发性腹水样品
从丘吉尔医院(牛津大学医院)的肿瘤病房接收来自多种适应症的患者的原发性人类腹水样品,包含但不限于卵巢癌、胰腺癌、乳腺癌和胃癌。在收到样品后,将细胞和流体部分分离,将等分试样的流体冷冻在-20℃下以便储存和将来的分析。按照制造商的说明,用红细胞溶解缓冲液(罗氏公司(Roche),#11814389001)处理细胞级分以去除红细胞。通过对EpCAM、EGFR、FAP、CD45、CD11b、CD56、CD3、CD4、CD8、PD1和CTLA4的染色确定每个样品中存在的细胞类型,并且通过流式细胞术分析。然后将新鲜细胞用于离体T细胞活化和靶细胞溶解实验。在一些情况下,将细胞在补充有10%FBS的DMEM中传代以用于后续实验。
细胞系维护
将所有细胞系维持在表3中指定的DMEM(西格玛奥德里奇公司(Sigma-Aldrich),英国)或RPMI培养基(西格玛奥德里奇公司,英国)中,在潮湿的培养箱(MCO-17AIC,三洋公司(Sanyo))中于37℃和5%CO2下补充有10%(v/v)胎牛血清(FBS,GibcoTM)和1%(v/v)青霉素/链霉素(10mg/mL,西格玛奥德里奇公司,英国),除非另有说明。通过用胰蛋白酶/EDTA(0.05%胰蛋白酶0.02%EDTA,西格玛奥德里奇公司,英国)酶促解离,每2天到3天将细胞分开,然后达到汇合。在此过程中,抽吸培养基,并且用15ml PBS洗涤细胞,并且随后用2mL胰蛋白酶/EDTA在37℃处理细胞2分钟到10分钟。用10mL含有10%FBS的DMEM中和胰蛋白酶,并且将一部分细胞转移到含有新鲜培养基的新烧瓶中。对于常规细胞培养,培养基补充有10%FBS,用于2%FBS的感染和病毒质粒转染以及用于没有FBS补充的重组BiTE质粒转染。
表3
统计
在比较两个条件的情况下,使用t检验执行统计分析。在所有其它情况下,通过使用单向ANOVA执行统计分析。
通过重组FAP BiTE表征人类T细胞活化
比较了FAP BiTE在存在或不存在正常人类皮肤成纤维细胞(NHDF)细胞的情况下诱导T细胞活化的能力。在单独的培养基或300ng/mL FAP或对照BiTE的存在下,将人类CD3+T细胞(96孔U-底板中每孔70,000个细胞)单独或与NHDF细胞(10:1T:NHDF)共培养。将细胞在37℃共培养24小时,并且随后用无酶细胞解离缓冲液(赛默飞世尔科技公司,#13151014)采集。然后通过抗体染色和流式细胞术分析CD45+T细胞上CD69(图14A)和CD25(图14B)的表达水平,并且表示为几何平均荧光(gMFI)值。将板固定的抗CD3抗体(7.5μg/mL)用作T细胞活化的阳性对照。FAP BiTE选择性诱导T细胞上活化标记物CD69和CD25的表达,指示其能够活化T细胞。
在第二个类似的实验中,在与NHDF细胞(200,000个CD3+细胞加上96孔板的孔中的40,000个NHDF)和300ng/mL FAP或对照BiTE共培养6小时后,通过细胞内细胞因子染色评估T细胞。对CD45+T细胞进行细胞内染色以进行IFNγ表达,在采集前5小时将布雷菲德菌素A添加到培养基中。作为阳性对照,用可溶性PMA(10ng/mL)和离子霉素(1μg/mL)刺激T细胞。图14C中示出的结果指示,与对照BiTE相比,在NHDF存在下的FAP BiTE导致显著更高数量的表达IFNγ的T细胞。
实例4:
为了进一步评估从NG-641的转基因产生的IFNα的功能,用未感染或用每个细胞10个颗粒(ppc)的enadenotucirev(EnAd)或NG-641感染3天的A549肿瘤细胞的上清液处理Jurkat-DualTM细胞。为了证明SEAP的分泌是IFNα特异性的,α通过在Jurkat-Dual报告基因细胞系–包含同种型对照抗体作为阴性对照的处理之前,将IFNα特异性抗体与A549上清液一起孵育30分钟来阻断IFN。数据(图8A)示出,Jurkat Dual报告基因测定中NG-641处理的肿瘤细胞上清液的活性通过抗IFNα抗体,而不是同种型对照抑制,并且因此通过IFNα介导。使用不同的报告基因测定系统评估NG-641中CXCL9和CXL10趋化因子转基因的功能。此测定使用表达两种趋化因子的受体的CXCR3的PathHunterβ-arrestin报告基因细胞系(Eurofins)。CXCL9/10结合通过这些细胞表达的CXCR3后,GPCR活化导致β-arrestin募集到受体,这是使用基于酶片段互补(EFC)技术的信号增益测定测量的。用未感染或用每个细胞10个颗粒(ppc)的EnAd或NG-641感染3天的A549肿瘤细胞的上清液处理PathHunterβ-arrestin CXCR3报告基因细胞。上清液中CXCL9/10的浓度与测定中的发光成正比。为了证明GPCR活化是CXCL9/10特异性的,通过在PathHunterβ-arrestin细胞的处理之前,将CXCL9/10特异性抗体与A549上清液一起孵育30分钟来阻断CXCL9和CXCL10。图8B中所示的数据显示,与EnAd或未感染的对照相比,在NG-641处理的肿瘤细胞的上清液的存在下,CXCR3报告基因细胞的活性增加,并且这种增加被CXCL9/10的抗体阻断。
作为趋化因子功能性的替代性方法,趋化因子下调其特定受体的细胞表面表达的能力被用作测定的基础,评估了抗CD3/CD28活化的人类T细胞上CXCR3受体的水平。A549肿瘤细胞未感染或用每个细胞1个病毒颗粒(ppc)的enadenotucirev(EnAd)或NG-641感染7天,并且收集上清液。然后将活化的T细胞用上清液处理30分钟,并且通过流式细胞术测量CXCR3的水平,将数据绘制为平均荧光强度(MFI)。为了证明细胞表面CXCR3的下调是CXCL9/10特异性的,通过在活化的T细胞的处理之前,将CXCL9/10特异性抗体与A549肿瘤细胞上清液一起孵育30分钟来阻断CXCL9和CXCL10。图9中所示的数据示出由NG-641感染的A549肿瘤细胞的上清液诱导的CD4和CD8 T细胞上CXCR3表达的选择性下调,并且通过用抗CXCL9/10抗体预处理来消除这种作用。
实例5:表达FAP-BiTE的病毒在离体人肿瘤细胞培养物中的功能活性
首先,将通过生物库在伦理学完全批准下提供的来自计划外科手术切除的新鲜切除人肿瘤的样本用剪刀和手术刀切碎,并且然后使用GentleMAC组织分离器(MiltenyiBiotec)产生单细胞悬浮液。发现这些未分离的细胞制剂包括肿瘤细胞、成纤维细胞和不同的免疫细胞,包含T细胞,并且用于评估病毒感染原代肿瘤细胞,产生其编码的转基因并活化也存在于培养物中的肿瘤浸润T细胞的能力。将细胞重悬于由以下组成的培养基中:Ham's F-12营养混合物、GlutaMAXTM补充剂(Gibco)、1x胰岛素-转铁蛋白-硒-乙醇胺(ITS-X)(Gibco)、两性霉素B 2.5mg/mL(GibcoTM)、青霉素100单位/mL、链霉素100mg/mL、丙酮酸钠和10%FBS,并且以~1×106个细胞/ml接种在96孔板(最终体积0.25ml)或24孔板(最终体积0.5ml)中。它们以1000ppc接种了EnAd、NG-615、NG-617、NG-640或NG-641,或未经处理(UIC)。作为阳性T细胞活化对照,还分别用2μg/ml的抗CD3和抗CD28抗体刺激一些孔。将细胞在重复孔中培养72小时,然后收集上清液,并且使用基于多细胞因子荧光珠的试剂盒(LEGENDplexTM)和流式细胞仪测量产生的不同细胞因子的水平。对三非小细胞肺癌(NSCLC)样品(T016、T017、T024)、一个肾细胞癌(RCC)和一个大肠癌(CRC)肝转移样品进行了测试。与图4-6中的转基因表达数据一致,在用NG-615和NG-641处理的培养物中选择性地产生IFNα(图10A)。Flt3配体(FLT3L)在NG-615处理后很容易被检测到,但是其它病毒仅检测到非常低的水平,并且这些水平与通过用抗CD3/28活化T细胞诱导的那些水平类似,表明NG-615培养物中的Flt3L是转基因产物。其它细胞因子的结果表明,与实例3中所述的肿瘤细胞系接种研究一样(图7),与编码病毒NG-617、NG-640和其它带有4个转基因的病毒NG-641的其它FAP-BiTE相比,NG-615接种导致T细胞活化水平低得多,如图10B中针对IFNγ、TNFα、IL-17、粒酶B和IL-13所示。
还通过流式细胞术测量内源性肿瘤T细胞在切除的NSCLC肿瘤细胞培养物中的活化,评估培养3天之后,通过CD4和CD8 T细胞两者的T细胞活化标记CD25、CD69和CD107a以及细胞内细胞因子(IFNγ和TNFα)表达的水平。如图11A-D所示,EnAd对活化标记或细胞因子表达几乎没有影响,而NG-617、NG-640和NG-641处理均导致所有这些对T细胞活化的测量上调。带有FAP-BiTE的病毒的类似的活化水平与上述细胞因子数据一致(图10B)
实例6
在此实例中,评估了重组FAP BiTE活化的T细胞诱导成纤维细胞靶细胞死亡的能力。
FAP BiTE诱导T细胞介导的FAP阳性细胞系和原发细胞的溶解
在单独培养基或300ng/mL对照或FAP BiTE存在下,将NHDF(7,000个细胞)与70,000个T细胞在U形底96孔板的孔中共培养。共培养24小时后,采集上清液,并且按照制造商的说明通过LDH测定法确定细胞毒性。图15A中的结果示出了FAP BiTE显著增加NHDF细胞的溶解。
在类似的实验中,在具有或不具有300ng/mL对照或FAP BiTE下,将7,000个原代肺成纤维细胞(BTC100)与70,000个CD3+T细胞共培养。共培养24小时后,采集上清液,并且通过LDH测定法确定细胞毒性。图15B和图C中的结果示出了FAP BiTE显著增加原发性人类癌症相关成纤维细胞(CAF)细胞的溶解。这些和其它患者来源的细胞系的FAP表达如图16所示。
通过将8,000个NHDF细胞与40,000个T细胞共培养并且BiTE浓度范围为2×103到2×10-2ng/mL来评估FAP BiTE介导的细胞溶解的剂量-应答关系。在37℃共培养24小时后,对上清液执行LDH测定以确定靶细胞的细胞毒性。使用集成到GraphPad Prism中的四参数非线性拟合模型拟合剂量应答曲线,从而生成FAP BiTE的EC50值为3.2ng/mL。结果(图17A)示出了通过LDH测定法测量的FAP BiTE浓度与细胞毒性之间的剂量依赖性关系(显示为Abs490)。
实例7
生成稳定的表达FAP的CHO和Ad293细胞系,作为通过与亲本未转染细胞比较证明FAP BiTE的FAP抗原特异性的手段。
表达FAP的稳定转染的细胞系的生成
从NCBI数据库(SEQ ID 23)获得FAP基因的蛋白质序列,逆转录以生成由牛津遗传学有限公司(Oxford Genetics Ltd)(英国牛津)合成的DNA编码序列。通过标准克隆技术将FAP基因克隆到pSF-Lenti载体中,产生pSF-Lenti-FAP载体。用慢病毒FAP表达载体与pSF-CMV-HIV-Gag-Pol、pSF-CMV-VSV-G、pSF-CMV-HIV-Rev一起转染HEK293T细胞。脂质体2000用作转染试剂,并且以DNA:脂质体比例为1:2添加到载体DNA中,并且与细胞在37℃下孵育。48小时后采集含有慢病毒的上清液并且与聚凝胺混合(终浓度,8μg/mL)。将慢病毒/聚凝胺混合物添加到接种的Ad293或CHO细胞中并且在37℃下孵育。在第4天,将上清液更换为含有嘌呤霉素的培养基(Ad293为2μg/mL,并且CHO为7.5μg/mL)。然后克隆选择稳定的变体,并且通过用FAP或同位素对照抗体染色确定亲本细胞系或稳定转染的变体的FAP表达,并且通过流式细胞术分析(图18A)。
FAP BiTE介导的靶细胞溶解对表达FAP的细胞是特异性的
在单独培养基或2μg/mL对照或FAP BiTE存在于U形底96孔板的孔中,单独或与人类T细胞(70,000个)共培养CHO或CHO-FAP细胞(7,000个细胞)。孵育24小时后,采集上清液,并且如实例4中所描述的通过LDH细胞毒性测定法测量靶细胞细胞毒性(图18B)。还通过流式细胞术分析CD69和CD25的表达水平来确定T细胞活化(图19)。仅当CHO-FAP细胞与T细胞和FAP BiTE一起培养时才观察到细胞毒性。这指示FAP BiTE介导的T细胞活化和靶细胞溶解是高度特异性的并且限于FAP表达细胞,而不是FAP阴性亲本细胞系。
实例8
在进一步的实验中,评估了重组FAP BiTE蛋白活化CD4或CD8 T细胞的能力以及这些T细胞亚群中的每一种溶解NHDF细胞的能力。在300ng/mL对照或FAP BiTE存在下,在U形底96孔板的孔中将CD3+T细胞(35,000个)与7,000个NHDF细胞共培养,并且在37℃下孵育24小时。采集细胞并且用针对CD4或CD8和CD69和CD25的抗体染色,并且通过流式细胞术分析。结果(图20A)证明FAP BiTE诱导CD4+和CD8+T细胞中活化标记物CD69和CD25的增加。
在类似的实验中,评估了每个T细胞亚群(CD4和CD8)杀死靶细胞的能力。根据制造商的方案,通过使用CD4T细胞分离试剂盒(美天旎生物技术公司,#130-045-101)的阳性选择从CD3纯化的细胞中提取CD4+T细胞,其中CD8细胞在非分离的流过物中。在U形底96孔板的孔中,将7,000个NHDF与35,000个CD4+或CD8+T细胞一起与300ng/mL对照或FAP BiTE共培养,并且在37℃孵育。24小时后,采集上清液,并且通过LDH细胞毒性测定法测量靶细胞细胞毒性。结果(图20B)示出了FAP BiTE诱导CD4+和CD8+T细胞以杀死NHDF细胞。
实例9
表征FAP BiTE介导的原发性恶性腹水自体肿瘤相关淋巴细胞的活化
为了使用癌症患者衍生细胞评估BiTE蛋白的活性,获得含有CD3+T细胞和FAP+细胞的原发性恶性腹水液样品用于测试。在500ng/mL对照或FAP BiTE存在下,在100%腹水液或补充有1%人类血清的培养基中,将未纯化的腹水细胞(因此从接收时保持不变)以每孔250,000个细胞接种于U形底96孔板中。未处理的孔用作阴性对照。在37℃孵育5天后,采集总细胞群并且确定CD3+T细胞的数量(图21A)和CD3+T细胞上CD25的表达水平(图21B)。使用精密计数珠确定每孔的总细胞数。结果证明,FAP BiTE导致癌症患者的肿瘤相关T细胞的T细胞活化显著增加。
作为上述实验的延伸,采集重复孔并且通过流式细胞术确定FAP+细胞的数量(图21C)。使用精密计数珠确定每孔的总细胞数。结果示出了FAP BiTE导致腹水样品中自体FAP表达细胞数量的显著减少。
实例10
使用下文所描述的方法工程化、产生和纯化表达重组BiTE的EnAd病毒。
表达BiTE的Enadenotucirev的生成
EnAd是能够进行复制的嵌合B组腺病毒,在E2B区含有Ad3对Ad11p的频繁非同源核苷酸取代,几乎完整的E3缺失和较小的E4缺失定位于E4或f4(Kuhn等人,定向进化生成用于治疗结肠癌的新型溶瘤病毒,《公共科学图书馆期刊(PLoS One)》,2008年6月18日;3(6):e2409)。
通过直接插入编码FAP BiTE(SEQ ID NO:1)或对照BiTE(SEQ ID NO:3)的盒,质粒pEnAd2.4用于生成质粒ppEnAd2.4-CMV-FAPBiTE、pEnAd2.4-SA-FAPBiTE、pEnAd2.4-CMV-ControlBiTE、pEnAd2.4-SA-ControlBiTE(表4)。转基因盒含有5'短剪接受体序列CAGG或外源CMV启动子(SEQ ID NO:24)、EpCAM、FAP或对照BiTE cDNA序列和3'多聚腺苷酸化序列(SEQ ID NO:25)。通过DNA测序确认质粒的构建。外源CMV启动子具有组成型活性,并且因此导致转基因的早期表达。剪接受体序列在病毒主要晚期启动子的控制下驱动表达,并且在病毒基因组复制开始后导致后来的转基因表达。
表4
质粒ID [质粒DNA]ng/ml
pEnAd2.4-CMV-FAPBiTE 1322.8
pEnAd2.4-SA-FAPBiTE 3918.3
pEnAd2.4-CMV-ControlBiTE 189.1
pEnAd2.4-SA-ControlBiTE 236.2
pEnAd2.4-CMV-FAPBiTE-RFP 1599
pEnAd2.4-SA-FAPBiTE-RFP 1872
pEnAd2.4-CMV-ControlBiTE-RFP 1294
pEnAd2.4-SA-ControlBiTE-RFP 2082
病毒生产和表征
质粒EnAd2.4-CMV-EpCAMBiTE、pEnAd2.4-SA-EpCAMBiTE、pEnAd2.4-CMV-FAPBiTE、pEnAd2.4-SA-FAPBiTE、pEnAd2.4-CMV-ControlBiTE、pEnAd2.4-SA-ControlBiTE为通过用酶AscI限制性消化来线性化以产生线性病毒基因组。通过异丙醇提取纯化消化的DNA,并且在300μl>95%分子生物级乙醇和10μl 3M乙酸钠中于-20℃沉淀16小时。通过在14000rpm离心5分钟沉淀析出的DNA,并且在500μl 70%乙醇中洗涤,然后再次以14000rpm离心5分钟。将干净的DNA沉淀空气干燥并且重悬于100μL水中。将6.25μg DNA与15.6μL脂质体转染试剂在OptiMEM中混合,并且在室温下孵育20分钟。然后将转染混合物添加到含有生长到80%汇合的Ad293细胞的T-25烧瓶中。将细胞与转染混合物在37℃孵育4小时后,向细胞中添加5%CO2 4ml的细胞培养基(DMEM高葡萄糖和谷氨酰胺补充有10%FBS),并且将烧瓶在37℃,5%CO2孵育。每24小时监测转染的Ad293细胞,并且每48小时到72小时补充额外的培养基。通过观察细胞单层中的显著细胞病变效应(CPE)来监测病毒的产生。一旦观察到广泛的CPE,通过三次冻融循环从Ad293细胞采集病毒。通过连续稀释采集的溶解物并且重新感染Ad293细胞,并且采集含有单个噬菌斑的孔来选择单个病毒克隆。一旦感染达到完全CPE,就进行Ad293细胞的连续感染,以便扩增病毒原种。通过观察细胞单层中的显著CPE证实扩增期间活病毒的产生。
病毒纯化
一旦扩增有效的病毒原种,通过双氯化铯密度梯度离心(条带化)纯化病毒以产生NG-603、NG-604、NG-605和NG-606病毒原种。按照制造商的说明,通过micoBCA测定(生命技术公司(Life Technologies))滴定这些原种(表5)。
表5
实例11
使用下文所描述的方法表征NG-601、NG-602、NG-603、NG-604、NG-605和NG-606病毒的活性。
在癌细胞系中与EnAd相比编码EnAd活性的BiTE的表征
通过感染A549肺癌细胞分析NG-601、NG-602、NG-603、NG-604、NG-605、NG-606或EnAd复制的能力,并且通过qPCR评估。将A549细胞以2×105个细胞/孔的细胞密度接种在24孔板的孔中。将板在37℃、5%CO2下孵育18小时,然后将细胞用每个细胞100个病毒颗粒(ppc)感染或保持未感染。感染后24小时、48小时或72小时采集孔,并且使用PureLink基因组DNA微型试剂盒(英杰公司)根据制造商的方案纯化DNA。使用表6中详述的反应混合物中的EnAd六邻体基因特异性引物-探针组,通过qPCR对每种提取的样品或标准物定量总病毒基因组。按照表7中的程序执行qPCR。
表6
试剂 体积/孔(μl)
2×qPCRBIO探针混合物(PCRBiosystems) 10
EnAd正向引物 0.08
EnAd反向引物 0.08
EnAd探针 0.8
NFW 4.04
样品 5
孔体积 20
表7
对每个细胞检测到的病毒基因组数量的定量证明NG-601、NG-602、NG-603、NG-604、NG-605、NG-606和EnAd病毒复制在A549细胞系中具有可比性(图22A)。
通过感染A549评估NG-601、NG-602、NG-603、NG-604、NG-605、NG-606或EnAd的溶瘤活性(图22B)。将A549细胞以1.5×104个细胞/孔的细胞密度接种在96孔板中。将板在37℃、5%CO2下孵育18小时,然后用增加的ppc病毒(5倍连续稀释,4.1×10-7到5000病毒ppc)感染细胞或者保持未感染。在第5天通过CellTiterAQueous单溶液细胞增殖测定(CellTiter/>AQueous One Solution Cell Proliferation Assay)(MTS)(普洛麦格公司(Promega),#G3582)测量A549细胞毒性。使用集成到GraphPad Prism中的四参数非线性拟合模型拟合剂量应答曲线。为每种病毒生成的IC 50值证明NG-601、NG-602、NG-603、NG-604、NG-605、NG-606和EnAd的溶瘤活性对于每种病毒具有可比性。
从NG-603、NG-604、NG-605、NG-606确认功能性BiTE转基因表达
为了确定病毒NG-601、NG-602、NG-605、NG-606是否产生功能性BiTE,使用CHO、CHO-EpCAM和CHO-FAP细胞系作为靶细胞执行T细胞活化测定。将10,000个靶细胞与50,000个CD3+T细胞在U-底96孔板的孔中共培养,其中Ad293病毒上清液在培养基中稀释100倍并且在37℃、5%CO2下孵育24小时。采集T细胞并且用对CD25和CD69具有特异性的抗体染色,并且通过流式细胞术分析。结果(图23A和图23B)指示病毒NG-601和NG-602表达功能性BiTE转基因,当与CHO-EpCAM细胞共培养时,所述功能性BiTE转基因活化T细胞,并且NG-605和NG-606表达功能性BiTE转基因,当与CHO-FAP细胞共培养时活化T细胞,但与CHO细胞共培养时不活化T细胞。
结肠癌细胞系中BiTE表达的定量
评估了NG-601、NG-602、NG-605、NG-606感染人类结肠癌细胞系DLD的BiTE表达的量。将DLD细胞以每孔1.2×106个细胞的密度接种在6孔培养板中。接种后18小时,用100ppc的EnAd、NG-601、NG-602、NG-603、NG-604、NG-605、NG-606感染DLD细胞。将细胞培养72小时,然后从孔中收集上清液并且以1200rpm离心5分钟以去除细胞碎片。然后将澄清的上清液用于杀伤测定,与用已知浓度的重组BiTE生成的标准曲线相比具有细胞毒性,从而能够确定病毒上清液中BiTE的量。
为了确定从NG-605和NG-606产生的FAP BiTE的量,执行了细胞毒性测定法,其中8,000个NHDF与40,000个CD3+T细胞共培养,并且DLD病毒上清液以1/103、1/104和1/105稀释。通过将NHDF和CD3+T细胞与FAP或对照BiTE以10倍连续稀释度从3333到3.33x10-4ng/μL孵育来生成标准曲线。处理后24小时采集上清液,并且通过LDH测定法测量细胞毒性。通过比较病毒上清液的细胞毒性与重组BiTE标准曲线的细胞毒性来确定表达的BiTE的量。结果(图24)指示病毒NG-605和NG-606分别产生每百万DLD细胞9.8μg和49.2μg FAP BiTE。
实例12
除编码FAP或对照BiTE外,NG-607、NG-608、NG-609、NG-610病毒还携带用于使用荧光显微镜方法观察感染细胞(SEQ ID NO:20和21,表4)的红色荧光蛋白(RFP)转基因。使用下文所描述的方法表征这些病毒的功能活性。
确认来自NG-607、NG-608、NG-609、NG-610的转基因表达
通过感染Ad293细胞评估病毒NG-607、NG-608、NG-609和NG-610产生其BiTE转基因的能力。将Ad293细胞以1×106个细胞/孔接种在6孔板中。将板在37℃、5%CO2下孵育24小时,然后将细胞用100ppc的病毒感染或保持未感染。在感染后48小时,用荧光汞灯照射噬菌斑并且拍照(图18)。结果表明病毒NG-607、NG-608、NG-609和NG-610表达RFP转基因。
实例13
在接下来的一系列实验中,评估了EnAd和FAP或对照BiTE病毒NG-603、NG-604、NG-605、NG-606、NG-607、NG-608、NG-609、NG-610杀死包含肿瘤细胞和成纤维细胞的靶细胞的能力。
在第一项研究中,使用xCELLigence技术评估EnAd杀死DLD细胞的能力。将DLD细胞以1.2×104个细胞/孔接种在48孔E-板中,并且在37℃、5%CO2下孵育18小时,然后用100EnAd ppc感染细胞或保持未感染。XCELLigence用于在8天的孵育期间每15分钟测量靶细胞的细胞毒性。
在类似的实验中,使用xCELLigence在与SKOV肿瘤细胞和CD3+T细胞的共培养中评估NG-603、NG-604、NG-605、NG-606和EnAd杀死NHDF细胞的能力。将NHDF细胞和SKOV细胞分别以4×103和1×103个细胞/孔接种在48孔E板中。将板在37℃、5%CO2下孵育18小时,然后用100ppc的NG-603、NG-604、NG-605或NG-606的EnAd感染细胞或保持未感染。孵育2小时后,向每个孔中添加37,500个CD3+T细胞。xCELLigence用于每15分钟测量靶细胞的细胞毒性。结果(图26A)证明表达FAP BiTE的病毒NG-605和NG606,但不是EnAd或表达对照BiTE的病毒NG-603和NG-604,能够诱导NHDF细胞的溶解,其中动力学依赖于用于BiTE表达的启动子(CMV启动子更快)。
在类似的实验中,使用LDH细胞毒性测定法在与SKOV和CD3+T细胞的共培养中评估NG-603、NG-604、NG-605、NG-606和EnAd杀死NHDF细胞的能力。将NHDF细胞和SKOV细胞分别以8×103和2×103个细胞/孔接种于96孔U形底板中,并且用100ppc的NG-603、NG-604、NG-605或NG-606的EnAd感染细胞或保持未感染。孵育2小时后,向每个孔中添加75,000个CD3+T细胞,并且将板在37℃、5%CO2下孵育。在处理后0小时、24小时、48小时和96小时采集上清液,并且通过LDH细胞毒性测定法测量细胞毒性。结果(图26B)证明表达FAP BiTE的病毒NG-605和NG606,但不是EnAd或表达对照BiTE的病毒NG-603和NG-604,能够诱导NHDF细胞的溶解,其中动力学依赖于用于BiTE表达的启动子。
作为上述LDH实验的延伸,还在处理后0小时、24小时、48小时和96小时采集细胞,用CD45、CD69和CD25的抗体染色并且通过流式细胞术分析。结果(图27)证明表达FAP BiTE的病毒NG-605和NG-606,但不是EnAd或表达对照BiTE的病毒NG-603和NG-604,能够诱导T细胞活化,其中动力学依赖于用于BiTE表达的启动子。
在类似的实验中,评估了对FAP诱导FAP BiTE介导的T细胞活化的依赖性。在96孔U型底的板中,SKOV细胞以2×103个细胞/孔单独地或与NHDF细胞组合在8×103个细胞/孔接种。将病毒颗粒以100ppc添加到每个孔中,并且将板在37℃、5%CO2下孵育。两小时后,添加75,000个CD3+T细胞,并且进一步孵育板。在感染后96小时,采集细胞并且染色CD45和CD25并且通过流式细胞术分析(图28A)。结果证明,表达FAP BiTE的病毒NG-605和NG-606仅在FAP阳性NHDF细胞存在下诱导T细胞活化。
在类似的实验中,进一步研究了NG-605和NG-606中启动子(CMV或病毒MLP/SA)驱动的BiTE表达的特异性。在96孔U形底板中,以4×103个细胞/孔接种NHDF细胞。每孔添加100个病毒颗粒,并且将板在37℃、5%CO2下孵育。两小时后,添加40,000个CD3细胞并且进一步孵育板。在感染后72小时,采集上清液并且通过LDH细胞毒性测定法测量细胞毒性。结果(图28B)证明CMV驱动的病毒NG-605,但不是SA驱动的NG-606,能够在单独感染NHDF细胞时介导NHDF细胞的杀伤。
结果指示NG-605和NG-606均能够诱导T细胞活化和靶细胞溶解,尽管动力学特征根据所使用的启动子略有不同。
获得间隔拍摄视频以通过重组FAP BiTE、EnAd、NG-603或NG-605观察病毒或T细胞介导的靶细胞溶解。用CellTracker Orange CMTMR Dye(生命技术公司,#C2927)染色NHDF细胞,并且按照制造商的方案用CellTrace紫细胞增殖试剂盒(CellTrace Violet CellProliferation Kit)(生命技术公司,#C34557)染色CD3+T细胞。将染色的NHDF以7.5×103个细胞/孔接种在24孔板中,与1.35×104DLD或SKOV肿瘤细胞共培养。将板在37℃、5%CO2下孵育18小时。然后用300ng/mL FAP BiTE处理细胞或用100ppc的EnAd、NG-603和NG-605感染细胞或保持不处理。孵育两小时后,除了1.5μM CellEventCaspase3到7试剂(生命技术公司,#C10423)之外,将100,000个染色的CD3+T细胞添加到必要的孔中。在Nikon TE 2000-EEclipse倒置显微镜上获得视频,每15分钟捕获图像,持续96小时。在图29中示出了视频中的帧。结果示出了重组FAP BiTE和NG-605,但不是EnAd或NG-603,能够诱导NHDF细胞的快速溶解。
在类似的实验中,用CellTracker Green CMFDA Dye(生命技术公司,#C2925)染色NHDF细胞,并且按照制造商的方案用CellTrace紫细胞增殖试剂盒(CellTrace VioletCell Proliferation Kit)(生命技术公司,#C34557)染色CD3+T细胞。将染色的NHDF以7.5×103个细胞/孔接种在24孔板中,与1.35×104DLD或SKOV肿瘤细胞共培养。将板在37℃、5%CO2下孵育18小时。然后用100ppc的NG-607、NG-608、NG-609或NG-610感染细胞或保持未感染。孵育两小时后,将100,000个染色的CD3+T细胞添加到必要的孔中。在Nikon TE 2000-EEclipse倒置显微镜上获得视频,每15分钟捕获图像,持续96小时。在图30中示出了视频中的帧。结果示出了所有病毒都导致肿瘤细胞感染(RFP,红色荧光,阳性),但只有NG-609和NG-610能够诱导共培养的NHDF细胞快速溶解。
实例14
在此实例中,评估了EnAd、NG-603、NG-604、NG-605和NG-606对来自癌症患者的FAP+原发性恶性腹水的自体肿瘤相关淋巴细胞的活化。被认为适合进一步分析的患者样品是含有CD3+T细胞和FAP+细胞的样品。
在第一个实验中,将来自患者的未纯化(因此从接收时保持不变)腹水细胞以每孔250,000个细胞接种于100%腹水液中的U形底96孔板中。用100ppc的病毒感染细胞,未处理的孔用作阴性对照。EnAd-CMV-GFP和EnAd-SA-GFP还作为报告基因包含在实验中,并且分别用显微照片来确定感染和晚期病毒基因表达。在37℃孵育5天后,采集总细胞群并且确定CD3+T细胞上CD25的表达水平(图32A)。使用精密计数珠确定每孔的总细胞数。结果证明FAPBiTE病毒NG-605和NG-606导致肿瘤相关淋巴细胞的T细胞活化显著增加。
作为上述实验的延伸,采集重复孔并且通过流式细胞术确定内源性FAP+细胞的数量。使用精密计数珠确定每孔的总细胞数。结果(图40B)示出了NG-605和NG-606导致腹水样品中表达自体FAP细胞数量的显著减少,表明一些FAP+细胞已经被活化的T细胞杀死。
在第二个实验中,在100%腹水液或补充有1%人类血清的培养基中,将来自癌症患者的未纯化(因此从接收时保持不变)腹水细胞以每孔250,000个细胞接种于U形底96孔板中。用100ppc的病毒感染细胞,未处理的孔用作阴性对照。还包含EnAd-CMV-GFP和EnAd-SA-GFP作为报告基因以分别用显微照片来确定感染和晚期病毒基因表达。在37℃下孵育5天后,采集总细胞群并且确定CD3+T细胞的数量(图33)和CD3+T细胞上CD25的表达水平(图34)。使用精密计数珠确定每孔的总细胞数。结果证明,对于此患者,重组FAP BiTE和NG-605而非NG-606导致培养基中肿瘤相关淋巴细胞的T细胞活化显著增加。这两种病毒都没有导致腹水液中的活化。
作为上述实验的延伸,采集重复孔并且通过流式细胞术确定FAP+细胞的数量(图35)。使用精密计数珠确定每孔的总细胞数。结果证明,重组FAP BiTE和NG-605而非NG-606导致培养基中表达自体FAP细胞数量的显著减少。两种病毒均未导致腹水液中FAP+细胞减少。
实例15-讨论
溶瘤病毒提供了一种有趣的新策略,将多种治疗方式结合在一个有针对性的自我放大剂中(Keller和Bell,2016;Seymour&Fisher,2016)。由于它们在癌细胞内选择性复制并且在细胞间传播,因此一些溶瘤病毒被认为通过非凋亡性死亡途径介导细胞死亡(Ingemarsdotter等人,2010;Li等人,2013),这是允许病毒颗粒从垂死细胞中逃逸的过程的一部分。特别地,EnAd通过称为肿瘤或缺血性细胞死亡的促炎过程杀死细胞(Dyer,2017)。这种非凋亡性死亡机制导致几种促炎细胞组分的释放,如ATP、HMGB1和钙网蛋白的暴露(称为损伤相关分子模式,
DAMP)(Weerasinghe和Buja,2012),并且可能是病毒促进有效抗癌免疫应答的能力的关键。然而,除了直接溶解的后果之外,病毒还提供编码和表达其它抗癌生物制剂的潜力,从而避免了递送挑战并且确保生物制剂在肿瘤微环境中达到其最高浓度。Imlygic编码GM-CSF,然而携带病毒的可能性实际上是无限的,并且提供了许多令人兴奋的机会来设计具有添加的或协同的抗癌作用的多模式治疗策略(de Gruijl等人,2015;Hermiston&Kuhn,2002)。
在溶瘤病毒中编码BiTE提供了活化肿瘤浸润淋巴细胞变成细胞毒性和溶解抗原阳性靶细胞的有力手段,从而提供了与直接病毒溶解的效果完全分开的治疗方式。在此研究中,我们已经示出了
BiTE靶向的细胞毒性是完全抗原特异性的,可以由CD4和CD8T细胞介导
(Brischwein等人,2006),并且可以掺入溶瘤腺病毒中并且仅在允许病毒复制的细胞中表达。此外,目前的研究首次示出了液体癌活组织检查中的内源性T细胞可以被BiTE和病毒编码的BiTE活化,并且可以杀死内源性肿瘤细胞而无需任何额外的刺激或逆转免疫抑制。重要的是,这甚至可以在包括腹膜腹水或胸腔积液的微环境的初级流体中发生,作为实体瘤的免疫抑制微环境的替代物。
携带溶瘤病毒以表达BiTE结合了两种截然不同的治疗机制,前者提供允许病毒感染的肿瘤细胞的溶解性死亡,并且后者通过特异性的选择的抗原靶向T细胞细胞毒性。这在治疗方法的设计中提供了相当大的灵活性,可能使用BiTE向肿瘤相关细胞递送细胞毒性,所述细胞对病毒的直接杀伤具有相对抗性。例如,虽然我们已经使用识别癌相关抗原(EpCAM)的BiTE示例了这里的技术,但也可以使用BiTE方法靶向肿瘤相关成纤维细胞或其它基质细胞的细胞毒性。实际上,即使当BiTE识别的靶不限于在肿瘤微环境中表达时,通过将BiTE产生与病毒复制相关联,允许BiTE的表达在空间上限于肿瘤,从而使全身毒性最小化。这很重要,因为静脉内施用的BiTE示出了相对短的循环动力学(Klinger等人,2012),并且通常与相当大的靶向肿瘤外毒性相关(Teachey等人,2013)。
先前已经使用具有靶向Ephrin A2的BiTE的溶瘤痘苗病毒探索了在溶瘤病毒内编码BiTE的可能性。此试剂示出了Ephrin BiTE可以在体外和体内介导PBMC的活化和抗原靶向的肿瘤细胞杀伤。有趣的是,虽然BiTE可以活化T细胞,但是如果不添加外源性IL-2,其就不会导致T细胞增殖,而目前研究中使用的BiTE导致体外PBMC的广泛增殖和使用离体临床活检样品的肿瘤相关淋巴细胞的广泛增殖。
我们认为观察到的差异可能反映了不同的BiTE设计,所使用的不同溶瘤病毒或可能取决于抗原密度,从而在T细胞上产生足够的CD3交联。
溶瘤病毒治疗的一个中心目标是创建识别患者特异性新抗原以及“公共”肿瘤相关抗原的抗癌T细胞应答。溶解病毒可以通过在DAMP背景下溶解肿瘤细胞以及病毒相关病原体相关分子模式(PAMP)来刺激改善的抗原呈递来实现这一点。在静脉内递送EnAd后,切除的结肠肿瘤的免疫组织化学染色表明所述病毒促进CD8+T细胞大量流入肿瘤组织(Garcia-Carbonero,2017)。然而,尽管这可能是非常有效的方法,但是适应性T细胞应答最终依赖于肿瘤细胞对MHC I类抗原的表达,以允许靶向杀伤。MHC表达缺失是充分证明的肿瘤免疫逃避策略(Garrido等人,2016)。
值得注意的是,由BiTE携带的溶瘤病毒立即参与的细胞毒性策略由肿瘤细胞独立于MHC I类来发挥作用,并且因此即使当肿瘤细胞丧失MHC表达时也可以用于杀死癌细胞。
因此,本研究证明在EnAd内编码BiTE提供了一种特别有前景的策略,以在扩散的肿瘤中实现靶向表达,利用已知的血液稳定性和病毒的全身生物利用度,这现已经在几个早期临床试验中进行了研究。值得注意的是,在一项在原发性结肠癌切除前几天静脉注射病毒的研究中,随后对肿瘤切片的免疫组织学评估示出了病毒已经通过肿瘤到达区,并且产生强烈的核内六邻体信号,从而指示感染成功并且病毒在肿瘤细胞中选择性复制。这证实了临床前数据(Di等人,2014;Illingworth,2017),所述数据指示此病毒在100%人类血液中是稳定的,并且应该能够对人类患者的播散性和转移性恶性肿瘤进行肿瘤靶向感染。
BiAd可以由EnAd编码而没有任何溶瘤毒力的损失,反映了病毒的相当大的转基因包装能力。转基因的存在不会影响病毒颗粒的物理化学性质,因此修饰的病毒应该展现出与亲本试剂完全相同的临床药代动力学,并且应该能够在整个身体的肿瘤内选择性地表达编码的BiTE。这为系统靶向的癌症免疫疗法提供了一种令人兴奋且可能非常有效的新方法,所述癌症免疫疗法现在应优先用于临床评估。
实例16
患者恶性渗出液对人类T细胞活化和靶细胞细胞毒性的免疫抑制
恶性渗出物代表具有潜在免疫耐受性的环境,其具有通常在晚期转移性癌症患者中观察到的抑制的免疫应答。使用人类IL-10ELISA MAX试剂盒(Biolegend,430604)在正常血清或患者恶性渗出液(A,腹膜腹水;P,胸腔积液)中测量被认为是抗炎细胞因子的IL-10的量。渗出液中的IL-10水平(88.1pg/mL到633.4pg/mL)远远超过在正常血清中测量的水平(7.2pg/mL到10pg/mL)。
研究了CD3/CD28珠(Gibco,11161D)在正常血清、腹水或胸膜液存在下活化PBMC T细胞的能力。在正常血清或患者渗出液(50%)中用CD3/CD28珠(遵循制造商说明书)处理人类PBMC T细胞(96孔板中每孔100,000个细胞)。在每种液体中不处理的T细胞作为阴性对照。培养24小时后,采集细胞并且然后通过抗体染色分析CD3+T细胞上CD69和CD25的表达水平,并且将流式细胞术表示为双阳性(CD69+CD25+细胞)的百分比。在正常血清中,抗CD3/CD28珠产生CD25和CD69双重阳性的约60%的T细胞,而腹水液的存在减弱了6/12液体中的T细胞活化。
在类似的实验中,在正常血清、腹水或胸膜液(50%)存在下用CD3/CD28珠处理100,000个T细胞。将抗CD107a或同种型对照抗体直接添加到培养基中。1小时后,根据制造商的说明添加莫能菌素(BD Golgistop,BD Biosciences)。再过5小时后,采集细胞并且通过流式细胞术分析以确定脱粒。在正常血清中,抗CD3/CD28珠产生约22.5%的T细胞脱粒,而腹水液的存在减弱了10/12液体中的T细胞活化。脱粒水平与每种液体中IL-10的量显著相关(Pearson系数,r=-0.7645;p=0.0038)。
在类似的实验中,在正常血清、腹水或胸膜液(50%)存在下,将75,000个T细胞与15,000个SKOV3和EpCAM共培养。用每种液体中的对照BiTE处理的T细胞作为阴性对照。培养24小时后,采集细胞并且然后通过抗体染色分析CD3+T细胞上CD69和CD25的表达水平,并且将流式细胞术表示为双阳性(CD69+CD25+细胞)的百分比。在正常血清中,EpCAM BiTE给予约67.6%的CD25和CD69双重阳性的T细胞,而腹水液的存在减弱了0/12液体中的T细胞活化,并且在4/10液体中略微诱导活化。
在类似的实验中,在正常血清、腹水或胸膜液(50%)存在下,将75,000个T细胞与15,000个SKOV3和EpCAM共培养。用每种液体中的对照BiTE处理的T细胞作为阴性对照。将抗CD107a或同种型对照抗体直接添加到培养基中。1小时后,根据制造商的说明添加莫能菌素(BD Golgistop,BD Biosciences)。再过5小时后,采集细胞并且通过流式细胞术分析以确定脱粒。在正常血清中,EpCAM BiTE珠给予约41.4%的T细胞脱粒,而腹水液的存在减弱了2/12液体中的T细胞活化。
使用xCELLigence技术评估EnAd-SA-EpCAMBiTE和EnAd-SA-ControlBiTE诱导恶性渗出液中T细胞介导的靶细胞溶解的能力。将SKOV细胞分别以1e4细胞/孔接种在48孔E板中。将板在37℃、5%CO2下孵育18小时,然后将细胞用每个细胞100个病毒颗粒(ppc)感染或保持未感染。两小时后,添加正常血清或患者渗出液(最终,50%)中的PBMC T细胞(5:1)。xCELLigence用于每10分钟测量靶细胞的细胞毒性。结果表明,T细胞的BiTE介导的SKOV3溶解与所使用的液体无关。
将未纯化的腹水细胞(因此从接收时保持不变)以每孔100,000个细胞接种于RPMI培养基或腹水液中的平底96孔板中。用EpCAM或对照BiTE处理细胞,未处理的孔用作阴性对照。在37℃孵育24小时后,采集细胞并且确定CD3细胞上CD25和CD69的表达水平。结果证明EpCAM BiTE导致肿瘤相关淋巴细胞的T细胞活化(CD69/CD25双阳性)显著增加,腹水液略微增加。
在类似的实验中,将未纯化的腹水细胞(因此从接收时保持不变)以每孔100,000个细胞接种在RPMI培养基或腹水液中的平底96孔板中。用EpCAM、对照BiTE或重组BiTE病毒(100vp/细胞)处理细胞,未处理的孔用作阴性对照。在37℃孵育5天后,采集总细胞群,并且确定CD3+细胞的数量和CD3细胞上CD25的表达水平和通过流式细胞术确定的内源性EpCaM+细胞的数量。使用精密计数珠确定每孔的总细胞数。结果证明EpCAM BiTE和EnAd表达EpCAMBiTE导致肿瘤相关淋巴细胞的T细胞活化(CD3数,CD25)和RPMI培养基和腹水液中EpCAM+细胞的细胞毒性显著增加。
作为上述实验的延伸,在腹水液中相同地处理另外六个患者的渗出物样品(总共7个),并且通过流式细胞术确定CD3+的数量、T细胞的CD25表达和EpCAM+细胞的数量。结果示出了EpCAM BiTE和表达EpCAM BiTE的EnAd导致肿瘤相关淋巴细胞的T细胞活化(CD3数,CD25)和EpCAM+细胞的细胞毒性在一系列渗出活检样品中可重复地显著增加。
实例17
FAP BiTE通过不同的供体T细胞介导T细胞的活化和FAP+细胞的杀伤
在其它实验中,与使用抗CD3/CD28磁珠的对照BiTE和多克隆T细胞活化相比较,使用实例2中描述的方法进一步评估在NHDF和T细胞的共培养物中测试的重组FAP BiTE蛋白的T细胞活化性质。
培养24小时后取出的上清液通过ELISA测试IFNγ(图36A),并且通过细胞因子珠阵列(LEGENDplex人类T辅助细胞因子组,BioLegend#74001)测试一组细胞因子(图36B)。对照BiTE诱导任何细胞因子没有显著变化,然而,FAP-BiTE导致γ干扰素、IL-2、TNFα、IL-17和IL-10的强烈增加,与刺激的T细胞的不同亚群一致,并且IFNγ的产生远远大于由抗CD3/CD28引发的。
在存在NHDF细胞的情况下用FAP BiTE但不用对照BiTE刺激还诱导T细胞(CD4+和CD8+亚群)的快速脱粒(在6小时内),如通过T细胞表面上CD107a/LAMP1的外化(通过流式细胞术评估)所确定的,这与它们杀死靶细胞的能力密切相关(图36A和B)。通过FAP BiTE进行的此脱粒诱导转化为有效的成纤维细胞溶解(图69C),通过与PBMC T细胞(EC50为约2.5ng/mL)共培养24小时后的LDH释放所测量的,其中使用6/6供体T细胞观察到诱导的T细胞活化和细胞毒性(图69D)。对照BiTE没有诱导细胞毒性,与保持在灭活状态的T细胞一致。
实例18
FAP BiTE和EnAd-FAP BiTE病毒对不同癌症患者原发性恶性腹水样品细胞的影响
作为实例16中所描述的研究的后续,获得来自另外的癌症患者的新鲜原发性恶性腹膜腹水用于研究EnAd FAP BiTE病毒活性。将含有EpCAM+肿瘤细胞和FAP+成纤维细胞的三个患者样品离体扩增,并且将混合(贴壁)细胞群与PBMC衍生的T细胞和未修饰的或表达BiTE的EnAd病毒一起培养。72小时后,采集总细胞并且通过流式细胞术确定FAP+(图38A)和EpCAM+细胞(图38B)的数量。另外,测量T细胞的活化状态(通过CD25表达)(图38C)。用EnAd-CMV-FAPBiTE和EnAd-SA-FAPBiTE感染诱导所有患者样品中的T细胞活化和FAP+细胞消耗,而EpCAM+肿瘤细胞的水平没有显著变化。亲本EnAd或对照病毒均未诱导可观察到的T细胞活化,FAP+细胞数量与未感染对照相似。
重要的是,FAP+成纤维细胞的这种消耗一致地导致在上清液中检测到的免疫抑制细胞因子TGFβ水平的强烈降低(图38D)。
在第二系列实验中,评估来自五个患者活组织检查样品的总(和未纯化)细胞以评估样品中内源性肿瘤相关T细胞的活性。将细胞接种在50%腹水液中,并且用重组对照或FAP BiTE蛋白或100vp/细胞的EnAd或EnAd-BiTE病毒处理。孵育5天后,通过流式细胞术测量T细胞活化(通过CD25表达)和残留数量的FAP+细胞(图39A和B)。在所有3个患者样品中,重组FAP-BiTE和EnAd-CMV-FAP BiTE诱导强烈的T细胞活化,高达约80%的患者来源的T细胞被活化,这导致FAP+成纤维细胞显著消耗。有趣的是,EnAd-SA-FAP-BiTE在2/3样品中诱导CD25表达,在患者1中没有可观察到的活化或FAP+细胞消耗。这可能是由于病毒感染的肿瘤细胞不足以及BiTE蛋白的产生(通过流式细胞术在此样品中未检测到EpCAM+肿瘤细胞),这与肿瘤细胞对MLP(SA)驱动的转基因表达的需求一致(这还可能解释了EnAd-SA-FAP-BiTE病毒缺乏T细胞活化和FAP+细胞消耗,患者腹水样品如图42到图44所示)。总的来说,数据示出了在肿瘤细胞感染后,表达FAP-BiTE的EnAd可重复地导致肿瘤相关T细胞的活化以杀死内源性成纤维细胞。
另一项实验研究了是否可以通过使用患者活组织检查样品阻断PD-1检查点来改善FAP-BiTE活性,其中T细胞为73.6%PD-1阳性并且FAP+细胞为62.9%PDL1阳性(图40A)。在存在或不存在针对人类PDL1的纯化的阻断小鼠IgG2b抗体(BioLegend,克隆29E.2A3)的情况下建立与上文所描述的那些类似的共培养物,终浓度为2.5μg/mL。培养2天后,采集总细胞并且测量残留的FAP+细胞和T细胞活化。包含阻断性抗PDL1抗体导致CD25诱导适度增加(图40B)和IFNγ产生高两倍(图40C),而在第2天在任一情况下均没有改变FAP+细胞的消耗,几乎完全溶解(图40D)。
据报道,从卵巢癌患者腹水中分离的肿瘤相关淋巴细胞(TAL)富集了PD-1的表达并且影响了效应子功能-包含细胞毒性和IFNg产生。与此一致,来自六个癌症患者腹水活组织检查的CD3+细胞的PD-1表达比来自三个健康供体的外周血单核细胞(PBMC)的所述表达高2倍(图41A)。为了评估这些癌症活组织检查样品中T细胞的功能,将NHDF细胞和未纯化的PBMC或腹水细胞(在图41B中示出了样品中的每一个的%CD3+细胞)与对照或含有FAP BiTE的上清液共培养,并且5天后采集上清液,并且通过ELISA测试IFNγ(图41C)。对照BiTE未诱导IFNγ。三个腹水细胞样品以与PBMC样品相似的水平产生IFNγ,而其它三个样品对FAPBiTE具有减弱的应答。我们接下来研究这些T细胞诱导BiTE介导的NHDF细胞溶解的能力。将NHDF铺板,并且将PBMC或腹水细胞与含有BiTE的上清液一起添加,并且使用xCELLigence细胞毒性测定系统实时监测培养物中细胞的活力。尽管IFNγ产生的可变性,当添加FAP BiTE时,所有腹水样品都诱导NHDF细胞的完全细胞毒性,总体相似的BiTE介导的NHDF溶解速率与PBMC受影响时的速率相似(图41D)。
为了研究FAP BiTE是否可以在存在患者恶性渗出物样品(全部为50%)的情况下介导T细胞活化,在NHDF细胞存在下用对照或FAP BiTE活化PBMC T细胞,或用50%正常人类血清(NS)或不同(无细胞)恶性渗出物样品中的抗CD3/CD28磁珠活化。然而在正常血清中,74%的T细胞在用抗CD3/CD28珠刺激后24小时被活化(CD25和CD69均为双阳性),与NS中的应答相比,3/5测试的腹水液显著减弱了T细胞活化(图42A)。然而,当PBMC与NHDF一起培养并且用FAP BiTE刺激时,在任何渗出液存在下都没有观察到T细胞活化的抑制(图42B),这证明FAP BiTE可以克服免疫抑制机制以活化T细胞。
实例19
EnAd-FAPBiTE介导的溶瘤和T细胞刺激将患者腹水中的CD11b+TAM极化为更活化的表型
调查是否通过FAP BiTE介导的T细胞活化产生Th1细胞因子,包含IFNγ、TNFα和IL-2,以及随后消除FAP+成纤维细胞(以及相关的TGFβ1减少与肿瘤的其它变化相关)从免疫抑制和促致癌基因到抗肿瘤活性的微环境评估了未分离的腹水细胞样品中对肿瘤相关巨噬细胞(TAM)的作用。将未纯化的患者腹水细胞全部置于50%腹水液中,用游离对照或FAP BiTE处理或用EnAd-SA-对照BiTE或EnAd-SA-FAPBiTE病毒(100vp/细胞)感染。平行地,用IFNγ处理一些细胞以诱导活化的CD11b骨髓细胞表型。孵育3天后,首先测量T细胞的活化状态;通过流式细胞术测量CD25+细胞并且通过ELISA测量IFNγ分泌。
用FAP BiTE和EnAd-SA-FAPBiTE处理导致约60%的CD3+T细胞变为CD25+(图43A)和培养上清液中的大量IFNγ(图43B)。对于CD25表达或IFNγ,未观察到对照BiTE或对照病毒增加超过背景。为了评估TAM极化,通过流式细胞术在CD11b+细胞上测量CD64和CD86(M1或“活化的”巨噬细胞标记物)和CD206和CD163(M2或TAM标记物)的表达水平(图43C)。用游离FAP BiTE或表达FAP BiTE的EnAd处理诱导更活化的表型,表现为CD64表达的显著增加,以及CD206和CD163的强烈降低-类似于将IFNγ掺入培养物中时观察到的。
虽然在此实验中用游离FAP BiTE或对照病毒处理在背景上没有引起CD86的明显变化,但是表达FAP BiTE的EnAd诱导CD86表达的大量增加,指示EnAd病毒感染和FAP BiTE活性可以协同活化如此处测试的恶性腹水样品等抑制性肿瘤微环境中的原发性骨髓细胞。在此研究中,IFNγ处理诱导CD86的适度降低,指示由EnAd-SA-FAPBiTE观察到的CD86的强烈增加可能是通过IFNγ非依赖性机制。
实例20
EnAd-FAPBiTE活化肿瘤浸润淋巴细胞并且在离体固体前列腺肿瘤活检中诱导细胞毒性
组织切片培养提供了各种组织、器官和肿瘤的最现实的临床前模型之一。为了评估在这种高度临床相关的环境中表达FAP BiTE的病毒的活性,研究了来自切除的人类前列腺的恶性和良性前列腺组织的几个成对穿孔活组织检查。在初始筛选时,前体组织可再现地显示具有散布在含有分散的CD8 T细胞(图44B)的基质的大区之间的EpCAM+肿瘤细胞的环状环(图44A)。在邻近肿瘤区的成纤维细胞上发现FAP染色(图44C)。
通过振动切片机将核心切成300μm厚度,并且在病毒存在下(1.5e9 vp/切片)建立切片培养物或保持未感染。7天后,固定切片、石蜡包埋、切片并且通过免疫组织化学(IHC)通过染色CD25表达评估T细胞活化状态(图44D)。仅接受EnAd-CMV-FAPBiTE或EnAd-SA-FAPBiTE的样品示出了肿瘤浸润性T细胞的活化,通过强CD25染色显示。未经处理或对照病毒处理均未检测到CD25阳性细胞。通过ELISA测试感染后第4天和第7天从这些切片培养物中取出的上清液的IFNγ和IL-2,在用EnAd-SA-FAPBiTE病毒培养物中检测到的用FAP BiTE病毒(图44E)和IL-2感染的恶性但非良性的前列腺切片培养物中检测到IFNγ的增加(图44F)。与CMV驱动的FAPBiTE病毒相比,EnAd-SA-FAPBiTE诱导更高量的IFNγ,其可以更早检测到。
实例21–另外的表达FAP BiTE的EnAd病毒
生成编码单个BiTE的五种病毒(NG-611、NG-612、NG-613、NG-614、NG-617)(表8)。
表8
病毒ID 转基因盒
NG-612(SEQ ID NO:78 SSA1-FAPBiTE5-His3-PA4
NG-613(SEQ ID NO:79) SA6-FAPBiTE5-His3-PA4
NG-614(SEQ ID NO:73) SA6-FAPBiTE7-His3-PA4
NG-617(SEQ ID NO:81) SSA1-FAPBiTE5-PA4
在每个转基因盒中,编码BiTE的cDNA在5'末端处侧接短剪接受体序列(SSA,CAGG)或更长的剪接受体序列(SA,SEQUENCE ID NO:45)。在BiTE的3'末端处,编码SV40晚期poly(A)序列(PA,SEQUENCE ID NO:54),之后是组氨酸标签(HIS)或无标签。在病毒NG-611、NG-612、NG-613和NG-617中,BiTE分子的抗CD3部分使用小鼠抗人类CD3单克隆抗体OKT3的单链变体。
病毒生产
质粒pEnAd2.4用于通过直接插入合成的转基因盒(分别为SEQ ID NO:70到74)使质粒pNG-611、pNG-612、pNG-613、pNG-614和pNG-617生成。pNG-612、pNG-613和pNG-617转基因盒编码靶向SEQID NO.75的BiTE的FAP,并且pNG-614转基因盒编码靶向SEQ ID NO.76的BiTE的FAP。在图45A到C中示出了转基因盒的示意图。通过限制性分析和DNA测序确认质粒DNA的构建。
质粒、pNG-611、pNG-612、pNG-613、pNG-614和pNG-617通过用酶AscI限制性消化进行线性化以产生病毒基因组。根据下文给出的方法扩增和纯化病毒。
通过苯酚/氯仿提取纯化消化的DNA,并且在300μl>95%分子生物级乙醇和10μl3M乙酸钠中于-20℃沉淀16小时。通过在14000rpm离心5分钟沉淀析出的DNA,并且在500μl70%乙醇中洗涤,然后再次以14000rpm离心5分钟。将干净的DNA团粒空气干燥,重悬浮于含有15μl脂质体转染试剂的500μl OptiMEM中,并且在室温下孵育30分钟。然后将转染混合物逐滴添加到含有生长到70%汇合的293细胞的T-25烧瓶中。将细胞与转染混合物在37℃孵育2小时后,向细胞中添加5%CO2 4ml的细胞培养基(DMEM高葡萄糖和谷氨酰胺补充有2%FBS),并且将烧瓶在37℃,5%CO2孵育。
每24小时监测转染的293细胞,并且每48小时到72小时补充额外的培养基。通过观察细胞单层中的显著细胞病变效应(CPE)来监测病毒的产生。一旦观察到广泛的CPE,通过三次冻融循环从293细胞采集病毒。采集的病毒用于再感染293细胞以便扩增病毒原种。通过观察细胞单层中的显著CPE证实扩增期间活病毒的产生。一旦观察到CPE,通过三次冻融循环从293细胞采集病毒。在通过双氯化铯条带纯化病毒以产生纯化的病毒原种之前,将扩增的病毒原种用于进一步扩增。
通过qPCR评估病毒活性
用1ppc NG-611、NG-612、NG-617、enadenotucirev或保持未感染的A549细胞感染72小时,用于通过qPCR定量病毒DNA。收集细胞上清液并且通过以1200rpm离心5分钟来澄清。根据制造商的方案,使用Qiagen Dneasy试剂盒从45μL上清液中提取DNA。还使用DNeasy试剂盒制备并且提取使用enadenotucirev病毒颗粒(2.5e10到2.5e5vp)的标准曲线。使用针对早期基因E3的病毒基因特异性引物-探针,通过qPCR分析每个提取的样品或标准品。
每个细胞检测到的病毒基因组数量的定量证明NG-611、NG-612和NG-617在A549细胞系中示出了显著的基因组复制(图45D)。对于包含亲本病毒enadenotucirev的所有测试的病毒,这是类似的,指示包含BiTE转基因不影响病毒复制活性。在未感染的细胞中未检测到病毒基因组(数据未显示)。
由表达BiTE的病毒介导的T细胞活化和脱粒。
癌细胞感染
将A549细胞以2.5e5细胞/孔的密度接种到24孔板中。将板在37℃、5%CO2下孵育4小时,然后用1ppc的NG-611、NG-612、enadenotucirev感染细胞或保持未感染。在感染后24小时、48小时或72小时,从细胞中采集上清液,通过以1200rpm离心5分钟来澄清并且快速冷冻。
T细胞测定
将表达肺成纤维细胞系MRC-5或表达EpCam的卵巢癌细胞SKOV3的FAP分别以5.7e4细胞/孔和1.2e5细胞/孔的密度接种到48孔板中。将板在37℃、5%CO2下孵育4小时,然后用150μL/孔从A549板采集的解冻上清液替换培养基。然后还将从人类PBMC供体分离的纯化的CD3 T细胞添加到板中,得到T细胞与MRC-5或SKOV3的比例为2比1。将共培养物在37℃、5%CO2下孵育16小时,然后收集细胞上清液用于ELISA分析,并且采集T细胞用于流式细胞术分析。从共培养孔中去除含有非贴壁细胞的培养基并且离心(300xg)。小心去除上清液,用PBS5%BSA稀释1倍,并且储存用于ELISA分析。用PBS洗涤贴壁细胞单层一次,并且然后用胰蛋白酶分离。使用10%FBS RPMI培养基灭活胰蛋白酶,并且将细胞添加到已经从培养上清液中收集的细胞团粒中。将细胞离心(300xg),弃去上清液,并且将细胞团粒在200μL的PBS中洗涤。将细胞再次离心,然后在室温下重悬于50μL含有Live/Dead Aqua(生命技术公司)的PBS中15分钟。将细胞在FAC缓冲液中洗涤一次,然后用直接缀合的抗体组进行染色:与AF700缀合的抗CD3;与BV421缀合的抗CD25;与PE/CY5缀合的抗HLA-DR;与BV605缀合的抗CD40L;与PE缀合的抗CD69和与FITC缀合的抗CD107a。来自每种共培养条件的细胞样品也用相关的同种型对照抗体染色。所有染色都在FAC缓冲液中以50μL/孔的总体积在4℃下进行15分钟。然后用FAC缓冲液(200μL)洗涤细胞两次,然后再悬浮于200μL的FAC缓冲液中并且通过流式细胞术(Attune)分析。
上调T细胞活化标记物
通过在活的单细胞上表达T细胞活化标记物CD25、CD69、HLA-DR和CD40L或T细胞脱粒标记物CD107a来评估T细胞活化的流式细胞术分析。这些数据示出了当与EpCam+SKOV3细胞共培养时,与NG-612、enadenotucirev或未处理的对照上清液相比,当向细胞中添加NG-611上清液时,表达CD25、CD69、HLA-DR、CD40L或细胞表面CD107a的T细胞的数量显著增加(图47)。对于所有这些标记物,来自感染24小时的A549细胞的上清液刺激很少的T细胞活化,然而,在感染后48小时,上清液刺激所有标记物上的显著T细胞活化。在感染后72小时也是这种情况。
当与FAP+MRC-5细胞共培养时,与NG-611、enadenotucirev或未处理的对照上清液相比,当向细胞中添加NG-612上清液时,表达CD25、CD69、HLA-DR、CD40L或细胞表面CD107a的T细胞的数量显著增加(图48)。使用NG-611病毒还可以观察到一些T细胞活化,这可能是由于与由NG-611病毒表达的EpCam BiTE接合的MRC-5细胞系中EpCam(约5%)的低表达但可检测到的表达(图49)。对于所有这些标记物,来自感染24小时的A549细胞的上清液刺激很少的T细胞活化,然而,在感染后48小时,上清液刺激所有标记物上的显著T细胞活化。在与感染后72小时采集的上清液孵育后,CD25和CD69标记物也被上调,然而,在感染后72小时和感染后48小时采集上清液,检测到较低水平的活化标记物HLA-DR、CD40L和CD107a。这可能是由于在感染的后期存在高水平的BiTE导致快速和有效的T细胞活化,这意味着效应子功能需要在早于产生上清液的16小时的时间点测量。
为了检测IFNγ表达,将共培养上清液稀释到5%BSA/PBS测定缓冲液(范围为1:10到1:1000)中,并且使用人类IFNγQingtikine ELISA试剂盒(R&D systems)根据制造商的方案进行ELISA。通过从标准曲线内插确定分泌的IFNγ的浓度。IFNγ的表达只能在使用SKOV3细胞(图50A)上的NG-611或MRC-5细胞(图50B)上的NG-611、NG-612的共培养物的上清液中检测到。
实例22体内表达BiTE的病毒的免疫活化和抗肿瘤功效
在移植后18周,将NSG小鼠人源化CD34+造血干细胞(来自杰克森实验室(JacksonLabs))在两侧腹侧皮下植入HCT116肿瘤细胞。一旦肿瘤达到80mm3到400mm3,将3只小鼠分组,使得每个治疗组具有相等的肿瘤体积分布,每组7只小鼠。用盐水、enadenotucirev或NG-611瘤内注射小鼠,每次注射5×109个颗粒,每个肿瘤注射2次。对两侧的肿瘤进行治疗。每周测量3到4次肿瘤体积并且证明与enadenotucirev或未治疗的对照相比,NG-611治疗在给药后20天导致显著的抗肿瘤应答(图51a)。在给药后20天后,处理来自每组中4只小鼠的一个肿瘤用于流式细胞术,同时将剩余的肿瘤在干冰上冷冻。
流式细胞术
在小体积的RPMI培养基中切除后立即对肿瘤样品进行机械解聚。然后使解聚的肿瘤通过70μm细胞滤网并且以300g离心10分钟。将细胞团粒重悬于100μL含有Live/DeadAqua(生命技术公司)的PBS中,在冰上保持15分钟。将细胞在FAC缓冲液(5%BSA PBS)中洗涤一次,然后用一组直接缀合的抗体染色:抗CD8(RPA-T8,AF700);抗CD4(RPA-T4,PE);抗CD45(2D1,APC-Fire 750);抗CD3(OKT3,PerCP-Cy5.5);抗CD25(M-A251,PE-Dazzle594);抗CD69(FN50,APC);抗HLA-DR(L243,BV605);抗CD107a(H4A3,FITC)。还用相关的同种型对照抗体染色肿瘤细胞悬浮液库。所有染色都在FAC缓冲液中以50μL/孔的总体积在4℃下进行20分钟。用FAC缓冲液(200μL)洗涤细胞三次,然后再悬浮于200μL的FAC缓冲液中并且通过流式细胞术(Attune)分析。FAC分析证明与enadenotucirev处理或未处理的对照相比,在NG-611处理的肿瘤中肿瘤中CD8与CD4 T细胞的比例显著增加(图51b)。
实例23-EnAd病毒共表达FAP BiTE和免疫调节细胞因子和趋化因子
生成编码FAP BiTE和免疫调节蛋白的三种病毒(NG-615、NG-640和NG-641)(表9)。
表9
病毒生产
质粒pEnAd2.4用于通过直接插入合成的转基因盒(分别为SEQ ID NO:93到95)使质粒pNG-615、pNG-616、pNG-640和pNG-641生成。NG-615和NG-616含有四种编码FAP靶向BiTE(SEQ ID NO:75)、Flt3L(SEQ ID NO.96)、MIP1α(SEQ ID NO.97)和IFNα(SEQ IDNO.98)的转基因。NG-640和NG-641编码靶向BiTe的FAP(SEQ ID NO.75)、CXCL9(SEQ IDNO.99)和CXCL10(SEQ ID NO.100),NG-641还含有编码IFNα的第四转基因(SEQ ID NO.98)。通过限制性分析和DNA测序确认质粒DNA的构建。
质粒、pNG-615、pNG-616、pNG-640和pNG-641通过用酶AscI限制性消化进行线性化以产生病毒基因组。根据实例33中详述的方法扩增和纯化病毒。
通过qPCR和转基因ELISA评估病毒活性
癌细胞感染
用1ppc NG-615、enadenotucirev或保持未感染的A549细胞感染72小时,用于通过qPCR定量病毒DNA并且通过ELISA分析转基因表达。收集细胞上清液并且通过以1200rpm离心5分钟来澄清。将45μL上清液用于DNA分析,并且剩余的上清液用于ELISA。
qPCR
根据制造商的方案,使用Qiagen DNeasy试剂盒从上清液样品中提取DNA。还使用DNeasy试剂盒制备并且提取使用enadenotucirev病毒颗粒(2.5e10到2.5e5vp)的标准曲线。使用针对早期基因E3的病毒基因特异性引物-探针,通过qPCR分析每个提取的样品或标准品。对每个细胞检测到的病毒基因组数量的定量证明,NG-615在A549细胞系中示出了与亲本病毒enadenotucirev相似水平的显著基因组复制(图52)。这些数据指示包含BiTE和三种免疫调节转基因不会显著影响病毒复制活性。在未感染的细胞中未检测到病毒基因组。
ELISA
使用Verikine人类IFNα试剂盒(Pbl assay science)进行IFNαELISA,使用人类CCL3 Quantikine ELISA试剂盒(R&D systems)进行MIP1αELISA并且使用Flt3L人类ELISA试剂盒(Abcam)进行Flt3L ELISA。所有测定均根据制造商的方案进行。
通过从标准曲线内插确定分泌的IFNα、MIPα或FLt3L的浓度。IFNα、MIP1α和Flt3 L表达可以在NG-615的细胞上清液中检测到,但不能在enadenotucirev或未处理的对照细胞中检测到(图53)。
由表达BiTE的病毒介导的T细胞活化和脱粒。
癌细胞感染
将A549细胞以2.5e5细胞/孔的密度接种到24孔板中。将板在37℃、5%CO2下孵育4小时,然后用1ppc的NG-612、NG-615、enadenotucirev感染细胞或保持未感染。在感染后24小时、48小时或72小时,从细胞中采集上清液,通过以1200rpm离心5分钟来澄清并且快速冷冻。
T细胞测定
将表达肺成纤维细胞系MRC-5的FAP以5.7e4细胞/孔的密度接种到48孔板中。将板在37℃、5%CO2下孵育4小时,然后用150μL/孔从A549板采集的解冻上清液替换培养基。然后还将从人类PBMC供体分离的纯化的CD3 T细胞添加到板中,得到T细胞与MRC-5的比例为2比1。将共培养物在37℃、5%CO2下孵育16小时,然后收集细胞上清液用于ELISA分析,并且根据实例29中详述的方法采集T细胞用于流式细胞术分析。
上调T细胞活化标记物
通过在活的CD3+单细胞上表达T细胞活化标记物CD25、CD69、HLA-DR和CD40L或T细胞脱粒标记物CD107a来评估T细胞活化的流式细胞术分析。这些数据示出了当与FAP+MRC-5细胞共培养时,与enadenotucirev或未处理的对照上清液相比,当向细胞中添加NG-615或612上清液时,表达CD25、CD69、HLA-DR、CD40L或CD107a的T细胞的数量显著增加(图54)。
分泌刺激性细胞因子IFNγ
为了检测IFNγ表达,将共培养上清液稀释到5%BSA/PBS测定缓冲液(范围为1:10到1:1000)中,并且使用人类IFNγQingtikine试剂盒(RandD Systems)根据制造商的方案进行ELISA。通过从标准曲线内插确定分泌的IFNγ的浓度。IFNγ的表达只能在使用NG-612或NG-615感染的A549上清液的共培养物的上清液中检测到(图55)。
NG-641的SEQ ID NO:95转基因盒
CAGGCCCACCATGGGCTGGAGCTGCATCATCTTGTTCCTGGTCGCAACTGCTACCGGAGTCCATTCGGACATCGTCATGACCCAAAGCCCTGACTCGCTCGCTGTGTCACTGGGAGAGCGGGCGACTATCAACTGCAAATCATCCCAGAGCCTGCTGTATTCACGCAATCAGAAAAACTACCTGGCCTGGTATCAGCAGAAGCCGGGCCAGCCTCCCAAGCTGCTGATCTTCTGGGCCTCCACCCGCGAAAGCGGCGTGCCGGACCGCTTCAGCGGAAGCGGATTCGGAACTGACTTTACTCTGACCATTAGCTCCTTGCAGGCGGAGGACGTGGCCGTCTACTACTGCCAGCAGTATTTCTCCTATCCGCTCACCTTTGGGCAAGGCACCAAGGTGGAGATTAAGGGAGGGGGCGGCAGCGGGGGAGGCGGCAGCGGCGGCGGGGGATCGCAGGTCCAGCTCGTCCAATCCGGAGCCGAAGTCAAGAAGCCGGGAGCGTCGGTCAAGGTCAGCTGCAAAACTTCGCGCTACACCTTCACTGAGTACACGATCCACTGGGTCCGCCAGGCGCCCGGCCAGCGGCTGGAGTGGATCGGCGGGATCAACCCAAACAACGGAATCCCAAATTACAATCAGAAATTTAAAGGGCGGGTGACTATCACCGTGGATACCTCGGCCTCCACGGCGTACATGGAGCTCTCATCACTCAGATCGGAGGACACCGCGGTCTATTACTGCGCCCGCCGCCGGATCGCTTATGGATACGATGAAGGACATGCGATGGATTACTGGGGCCAGGGCACCCTCGTCACGGTGTCGTCAGGAGGCGGCGGTTCACAGGTGCAGCTGCAGCAGTCTGGGGCTGAACTGGCAAGACCTGGGGCCTCAGTGAAGATGTCCTGCAAGGCTTCTGGCTACACCTTTACTAGGTACACGATGCACTGGGTAAAACAGAGGCCTGGACAGGGTCTGGAATGGATTGGATACATTAATCCTAGCCGTGGTTATACTAATTACAATCAGAAGTTCAAGGACAAGGCCACATTGACTACAGACAAATCCTCCAGCACAGCCTACATGCAACTGAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGATATTATGATGATCATTACTGCCTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCAGGTGGCGGTGGCTCGGGCGGTGGTGGATCTGGTGGCGGCGGATCTGATATCGTGCTCACTCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGGAGAAGGTCACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTTACATGAACTGGTACCAGCAGAAGTCAGGCACCTCCCCCAAAAGATGGATTTATGACACATCCAAACTGGCTTCTGGAGTCCCTGCTCACTTCAGGGGCAGTGGGTCTGGGACCTCTTACTCTCTCACAATCAGCGGCATGGAGGCTGAAGATGCTGCCACTTATTACTGCCAGCAGTGGAGTAGTAACCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAACCGGGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTAATCAAACTGCCATTCTGATTTGCTGCCTTATCTTTCTGACTCTAAGTGGCATTCAAGGAGTACCTCTCTCTAGAACTGTACGCTGTACCTGCATCAGCATTAGTAATCAACCTGTTAATCCAAGGTCTTTAGAAAAACTTGAAATTATTCCTGCAAGCCAATTTTGTCCACGTGTTGAGATCATTGCTACAATGAAAAAGAAGGGTGAGAAGAGATGTCTGAATCCAGAATCGAAGGCCATCAAGAATTTACTGAAAGCAGTTAGCAAGGAAAGGTCTAAAAGATCTCCTGGAAGCGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTGGACCTAAGAAAAGTGGTGTTCTTTTCCTCTTGGGCATCATCTTGCTGGTTCTGATTGGAGTGCAAGGAACCCCAGTAGTGAGAAAGGGTCGCTGTTCCTGCATCAGCACCAACCAAGGGACTATCCACCTACAATCCTTGAAAGACCTTAAACAATTTGCCCCAAGCCCTTCCTGCGAGAAAATTGAAATCATTGCTACACTGAAGAATGGAGTTCAAACATGTCTAAACCCAGATTCAGCAGATGTGAAGGAACTGATTAAAAAGTGGGAGAAACAGGTCAGCCAAAAGAAAAAGCAAAAGAATGGGAAAAAACATCAAAAAAAGAAAGTTCTGAAAGTTCGAAAATCTCAACGTTCTCGTCAAAAGAAGACTACAGGAAGCGGACAGTGTACTAATTATGCTCTCTTGAAATTGGCTGGAGATGTTGAGAGCAACCCTGGACCTGCCTTGACCTTTGCTTTACTGGTGGCCCTCCTGGTGCTCAGCTGCAAGTCAAGCTGCTCTGTGGGCTGTGATCTGCCTCAAACCCACAGCCTGGGTAGCAGGAGGACCTTGATGCTCCTGGCACAGATGAGGAGAATCTCTCTTTTCTCCTGCTTGAAGGACAGACATGACTTTGGATTTCCCCAGGAGGAGTTTGGCAACCAGTTCCAAAAGGCTGAAACCATCCCTGTCCTCCATGAGATGATCCAGCAGATCTTCAATCTCTTCAGCACAAAGGACTCATCTGCTGCTTGGGATGAGACCCTCCTAGACAAATTCTACACTGAACTCTACCAGCAGCTGAATGACCTGGAAGCCTGTGTGATACAGGGGGTGGGGGTGACAGAGACTCCCCTGATGAAGGAGGACTCCATTCTGGCTGTGAGGAAATACTTCCAAAGAATCACTCTCTATCTGAAAGAGAAGAAATACAGCCCTTGTGCCTGGGAGGTTGTCAGAGCAGAAATCATGAGATCTTTTTCTTTGTCAACAAACTTGCAAGAAAGTTTAAGAAGTAAGGAATAAGCTAGCTTGACTGACTGAGATACAGCGTACCTTCAGCTCACAGACATGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGTTAACAACAACAATTGCATTCATTTTATGTTTCAGGTTCAGGGGGAGGTGTGGGAGGTTTTTTAAAGCAAGTAAAACCTCTACAAATGTGGTAGTCGTCAGCTAT
序列表
<110> 皮斯奥克斯治疗公司
<120> 携带双特异性T细胞衔接器(BiTE)的腺病毒
<130> P000260_WO
<150> GB1713765.4
<151> 2017-08-28
<150> PCT/EP2017/071674
<151> 2017-08-29
<150> PCT/EP2017/071655
<151> 2017-08-29
<160> 281
<170> PatentIn版本3.5
<210> 1
<211> 1551
<212> DNA
<213> 人工序列
<220>
<223> FAP BiTE核酸序列
<400> 1
atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt ccattcggac 60
atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg ggcgactatc 120
aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta cctggcctgg 180
tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc cacccgcgaa 240
agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac tctgaccatt 300
agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt ctcctatccg 360
ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag cgggggaggc 420
ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga agtcaagaag 480
ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac tgagtacacg 540
atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg gatcaaccca 600
aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat caccgtggat 660
acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga caccgcggtc 720
tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc gatggattac 780
tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca ggtgcagctg 840
cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc ctgcaaggct 900
tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc tggacagggt 960
ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa tcagaagttc 1020
aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat gcaactgagc 1080
agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga tgatcattac 1140
tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg cggtggctcg 1200
ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc tccagcaatc 1260
atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc aagtgtaagt 1320
tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat ttatgacaca 1380
tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg gacctcttac 1440
tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg ccagcagtgg 1500
agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg g 1551
<210> 2
<211> 517
<212> PRT
<213> 人工序列
<220>
<223> FAP-BiTE氨基酸序列
<400> 2
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val
20 25 30
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu
35 40 45
Leu Tyr Ser Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu
65 70 75 80
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe
85 90 95
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
100 105 110
Cys Gln Gln Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
145 150 155 160
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe
165 170 175
Thr Glu Tyr Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
180 185 190
Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn
195 200 205
Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser
210 215 220
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
225 230 235 240
Tyr Tyr Cys Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His
245 250 255
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
260 265 270
Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala
275 280 285
Arg Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr
290 295 300
Phe Thr Arg Tyr Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly
305 310 315 320
Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr
325 330 335
Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser
340 345 350
Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala
355 360 365
Val Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr
370 375 380
Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser
385 390 395 400
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln
405 410 415
Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr
420 425 430
Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
435 440 445
Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala
450 455 460
Ser Gly Val Pro Ala His Phe Arg Gly Ser Gly Ser Gly Thr Ser Tyr
465 470 475 480
Ser Leu Thr Ile Ser Gly Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
485 490 495
Cys Gln Gln Trp Ser Ser Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys
500 505 510
Leu Glu Ile Asn Arg
515
<210> 3
<211> 1629
<212> DNA
<213> 人工序列
<220>
<223> 对照(抗FHA)BiTE DNA编码序列,具有N末端信号序列和C末端
deca-His亲和标签
<400> 3
atgggttggt catgcatcat cctgtttctc gtcgcaactg cgaccggcgt gcattcggaa 60
ctggacatcg tgatgaccca ggcacctgca tcactggcag tgagcctggg acagagagcc 120
accatttcat gccgggccag caagagcgtg tcgtcatccg gatacaatta tctgcactgg 180
tatcagcaga aaccaggaca acctccaaag ctactcatct acctggcgtc gaacctcgaa 240
tcgggcgtcc cagctagatt ctcagggagc ggttcgggaa ccgatttcac cctgaacatc 300
caccctgtgg aggaggaaga cgcggcaacg tactattgcc agcattcccg cgagttccct 360
ctcactttcg gtgcgggaac taagctggag atcaagtcca gcggcggcgg aggtagcggt 420
ggaggtggcg gaggaagctc ccggtcgtcg ctggaggtgc agctgcaaca atccggcccg 480
gaactggtca agccaggcgc atccgtcaag atttcatgca agacctcggg gtacaccttc 540
accgggtaca cgatgcattg ggtcaggcag agccacggca agtccctgga atggatcgga 600
ggaatcaacc ccaaaaacgg cggcatcatc tacaaccaaa agttccaggg aaaagccact 660
ctgaccgtgg acaagtcgtc gagcacggcc agcatggagc tgcggtccct cacttccgac 720
gactcagccg tgtattactg cgcgagacgg gtctacgatg actacccata ctactacgct 780
atggactact ggggacaagg aaccagcgtg accgtctcat cggcgaaaac tactccgccg 840
tcggtgacgt cgggaggtgg tggaagcgac gtgcagctcg tccagtcggg tgccgaggtg 900
aagaagccag gagcctccgt gaaggtctcg tgcaaagcca gcggctacac ttttactagg 960
tacactatgc actgggtgcg gcaagcgccg ggacaaggtc tggagtggat cggatacatc 1020
aatccgtcgc ggggatacac taattacgcg gactccgtca agggacggtt tactatcact 1080
acggataagt ccactagcac cgcctacatg gaactgtcct cgctgcggtc ggaagacact 1140
gcgacctact actgcgctag atattacgat gaccactact gcctcgacta ttgggggcag 1200
ggcactacgg tcaccgtctc gtcgggagaa ggaacctcaa ctggatcggg cggatcggga 1260
ggctccggag gagccgacga catcgtgctt acccagtcgc ctgcgaccct gtccctgtcc 1320
ccaggagaga gagcgactct ttcatgcagg gcttcccaat cagtctccta catgaattgg 1380
tatcaacaaa aacccggcaa ggccccgaaa cgctggatct acgatacttc aaaggtggcc 1440
agcggtgtgc ctgcccgctt ctccgggtcg gggtccggca ccgattactc gttgactatc 1500
aatagcctgg aggccgagga cgctgcaact tactactgcc agcagtggtc ctccaaccct 1560
ctcaccttcg gaggcgggac caaggtggaa atcaaacatc accatcacca tcaccaccat 1620
caccattag 1629
<210> 4
<211> 542
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗-FHA)BiTE氨基酸序列,具有N末端信号序列和C末端
deca-His亲和标签
<400> 4
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu
20 25 30
Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys
35 40 45
Ser Val Ser Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu
65 70 75 80
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
85 90 95
Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr
100 105 110
Cys Gln His Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys
115 120 125
Leu Glu Ile Lys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly
130 135 140
Gly Ser Ser Arg Ser Ser Leu Glu Val Gln Leu Gln Gln Ser Gly Pro
145 150 155 160
Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser
165 170 175
Gly Tyr Thr Phe Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His
180 185 190
Gly Lys Ser Leu Glu Trp Ile Gly Gly Ile Asn Pro Lys Asn Gly Gly
195 200 205
Ile Ile Tyr Asn Gln Lys Phe Gln Gly Lys Ala Thr Leu Thr Val Asp
210 215 220
Lys Ser Ser Ser Thr Ala Ser Met Glu Leu Arg Ser Leu Thr Ser Asp
225 230 235 240
Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Val Tyr Asp Asp Tyr Pro
245 250 255
Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val
260 265 270
Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Thr Ser Gly Gly Gly Gly
275 280 285
Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
290 295 300
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg
305 310 315 320
Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
325 330 335
Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser
340 345 350
Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala
355 360 365
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr
370 375 380
Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln
385 390 395 400
Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser Thr Gly Ser
405 410 415
Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val Leu Thr Gln
420 425 430
Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser
435 440 445
Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
450 455 460
Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala
465 470 475 480
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
485 490 495
Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
500 505 510
Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys
515 520 525
Val Glu Ile Lys His His His His His His His His His His
530 535 540
<210> 5
<211> 243
<212> PRT
<213> 人工序列
<220>
<223> SEQ ID NO: 7
<400> 5
Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr
20 25 30
Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser Thr Gly Ser Gly
115 120 125
Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val Leu Thr Gln Ser
130 135 140
Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys
145 150 155 160
Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro
165 170 175
Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala Ser
180 185 190
Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser
195 200 205
Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys
210 215 220
Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys Val
225 230 235 240
Glu Ile Lys
<210> 6
<211> 119
<212> PRT
<213> 人工序列
<220>
<223> 抗CD3 VH
<400> 6
Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr
20 25 30
Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Thr Val Thr Val Ser Ser
115
<210> 7
<211> 106
<212> PRT
<213> 人工序列
<220>
<223> 抗CD3 VL
<400> 7
Asp Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Tyr Met
20 25 30
Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr
35 40 45
Asp Thr Ser Lys Val Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 8
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 抗CD3 ScFv连接子序列
<400> 8
Gly Glu Gly Thr Ser Thr Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly
1 5 10 15
Ala Asp
<210> 9
<211> 252
<212> PRT
<213> 人工序列
<220>
<223> 抗FAP ScFv
<400> 9
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile
100 105 110
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
130 135 140
Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe Thr Glu Tyr
145 150 155 160
Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile
165 170 175
Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn Gln Lys Phe
180 185 190
Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr
195 200 205
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
210 215 220
Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His Ala Met Asp
225 230 235 240
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 10
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 抗FAP VL结构域
<400> 10
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 11
<211> 124
<212> PRT
<213> 人工序列
<220>
<223> 抗FAP VH结构域
<400> 11
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe Thr Glu Tyr
20 25 30
Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His Ala Met Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 12
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 抗FAP和抗EpCAM连接子序列
<400> 12
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 13
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> BiTe前导序列
<400> 13
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser
<210> 14
<211> 542
<212> PRT
<213> 人工序列
<220>
<223> 对照BiTe(抗FHA)
<400> 14
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu
20 25 30
Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys
35 40 45
Ser Val Ser Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu
65 70 75 80
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
85 90 95
Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr
100 105 110
Cys Gln His Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys
115 120 125
Leu Glu Ile Lys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly
130 135 140
Gly Ser Ser Arg Ser Ser Leu Glu Val Gln Leu Gln Gln Ser Gly Pro
145 150 155 160
Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser
165 170 175
Gly Tyr Thr Phe Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His
180 185 190
Gly Lys Ser Leu Glu Trp Ile Gly Gly Ile Asn Pro Lys Asn Gly Gly
195 200 205
Ile Ile Tyr Asn Gln Lys Phe Gln Gly Lys Ala Thr Leu Thr Val Asp
210 215 220
Lys Ser Ser Ser Thr Ala Ser Met Glu Leu Arg Ser Leu Thr Ser Asp
225 230 235 240
Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Val Tyr Asp Asp Tyr Pro
245 250 255
Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val
260 265 270
Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Thr Ser Gly Gly Gly Gly
275 280 285
Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
290 295 300
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg
305 310 315 320
Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
325 330 335
Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser
340 345 350
Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala
355 360 365
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr
370 375 380
Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln
385 390 395 400
Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser Thr Gly Ser
405 410 415
Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val Leu Thr Gln
420 425 430
Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser
435 440 445
Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
450 455 460
Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala
465 470 475 480
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
485 490 495
Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
500 505 510
Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys
515 520 525
Val Glu Ile Lys His His His His His His His His His His
530 535 540
<210> 15
<211> 265
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗FHA)ScFv
<400> 15
Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu Ala Val Ser
1 5 10 15
Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser
20 25 30
Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Ser Gly Val
50 55 60
Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn
65 70 75 80
Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His
85 90 95
Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Ile
100 105 110
Lys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser
115 120 125
Arg Ser Ser Leu Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val
130 135 140
Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr
145 150 155 160
Phe Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His Gly Lys Ser
165 170 175
Leu Glu Trp Ile Gly Gly Ile Asn Pro Lys Asn Gly Gly Ile Ile Tyr
180 185 190
Asn Gln Lys Phe Gln Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser
195 200 205
Ser Thr Ala Ser Met Glu Leu Arg Ser Leu Thr Ser Asp Asp Ser Ala
210 215 220
Val Tyr Tyr Cys Ala Arg Arg Val Tyr Asp Asp Tyr Pro Tyr Tyr Tyr
225 230 235 240
Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala
245 250 255
Lys Thr Thr Pro Pro Ser Val Thr Ser
260 265
<210> 16
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗FHA)VL
<400> 16
Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu Ala Val Ser
1 5 10 15
Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser
20 25 30
Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Ser Gly Val
50 55 60
Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn
65 70 75 80
Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His
85 90 95
Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Ile
100 105 110
Lys
<210> 17
<211> 133
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗FHA)VH
<400> 17
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Thr Met His Trp Val Arg Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asn Pro Lys Asn Gly Gly Ile Ile Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Ser
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Val Tyr Asp Asp Tyr Pro Tyr Tyr Tyr Ala Met Asp Tyr
100 105 110
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Thr Ser
130
<210> 18
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗FHA)ScFv连接子序列
<400> 18
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser Arg
1 5 10 15
Ser Ser Leu
<210> 19
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> Deca-His标签序列
<400> 19
His His His His His His His His His His
1 5 10
<210> 20
<211> 786
<212> PRT
<213> 人工序列
<220>
<223> FAP BiTE-P2A-RFP
<400> 20
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val
20 25 30
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu
35 40 45
Leu Tyr Ser Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu
65 70 75 80
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe
85 90 95
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
100 105 110
Cys Gln Gln Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
145 150 155 160
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe
165 170 175
Thr Glu Tyr Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
180 185 190
Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn
195 200 205
Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser
210 215 220
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
225 230 235 240
Tyr Tyr Cys Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His
245 250 255
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
260 265 270
Gly Gly Gly Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
275 280 285
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr
290 295 300
Phe Thr Arg Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly
305 310 315 320
Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr
325 330 335
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr
340 345 350
Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala
355 360 365
Thr Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr
370 375 380
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser
385 390 395 400
Thr Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val
405 410 415
Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
420 425 430
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr
435 440 445
Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser
450 455 460
Lys Val Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly
465 470 475 480
Thr Asp Tyr Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala
485 490 495
Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly
500 505 510
Gly Thr Lys Val Glu Ile Lys His His His His His His His His His
515 520 525
His Arg Arg Lys Arg Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
530 535 540
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Ser Glu Leu Ile
545 550 555 560
Lys Glu Asn Met His Met Lys Leu Tyr Met Glu Gly Thr Val Asn Asn
565 570 575
His His Phe Lys Cys Thr Ser Glu Gly Glu Gly Lys Pro Tyr Glu Gly
580 585 590
Thr Gln Thr Met Lys Ile Lys Val Val Glu Gly Gly Pro Leu Pro Phe
595 600 605
Ala Phe Asp Ile Leu Ala Thr Ser Phe Met Tyr Gly Ser Lys Ala Phe
610 615 620
Ile Asn His Thr Gln Gly Ile Pro Asp Phe Phe Lys Gln Ser Phe Pro
625 630 635 640
Glu Gly Phe Thr Trp Glu Arg Ile Thr Thr Tyr Glu Asp Gly Gly Val
645 650 655
Leu Thr Ala Thr Gln Asp Thr Ser Phe Gln Asn Gly Cys Ile Ile Tyr
660 665 670
Asn Val Lys Ile Asn Gly Val Asn Phe Pro Ser Asn Gly Pro Val Met
675 680 685
Gln Lys Lys Thr Arg Gly Trp Glu Ala Asn Thr Glu Met Leu Tyr Pro
690 695 700
Ala Asp Gly Gly Leu Arg Gly His Ser Gln Met Ala Leu Lys Leu Val
705 710 715 720
Gly Gly Gly Tyr Leu His Cys Ser Phe Lys Thr Thr Tyr Arg Ser Lys
725 730 735
Lys Pro Ala Lys Asn Leu Lys Met Pro Gly Phe His Phe Val Asp His
740 745 750
Arg Leu Glu Arg Ile Lys Glu Ala Asp Lys Glu Thr Tyr Val Glu Gln
755 760 765
His Glu Met Ala Val Ala Lys Tyr Cys Asp Leu Pro Ser Lys Leu Gly
770 775 780
His Arg
785
<210> 21
<211> 799
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗FHA)BiTE-P2A-RFP
<400> 21
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu
20 25 30
Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys
35 40 45
Ser Val Ser Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu
65 70 75 80
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
85 90 95
Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr
100 105 110
Cys Gln His Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys
115 120 125
Leu Glu Ile Lys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly
130 135 140
Gly Ser Ser Arg Ser Ser Leu Glu Val Gln Leu Gln Gln Ser Gly Pro
145 150 155 160
Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser
165 170 175
Gly Tyr Thr Phe Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His
180 185 190
Gly Lys Ser Leu Glu Trp Ile Gly Gly Ile Asn Pro Lys Asn Gly Gly
195 200 205
Ile Ile Tyr Asn Gln Lys Phe Gln Gly Lys Ala Thr Leu Thr Val Asp
210 215 220
Lys Ser Ser Ser Thr Ala Ser Met Glu Leu Arg Ser Leu Thr Ser Asp
225 230 235 240
Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Val Tyr Asp Asp Tyr Pro
245 250 255
Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val
260 265 270
Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Thr Ser Gly Gly Gly Gly
275 280 285
Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
290 295 300
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg
305 310 315 320
Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
325 330 335
Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser
340 345 350
Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala
355 360 365
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr
370 375 380
Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln
385 390 395 400
Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser Thr Gly Ser
405 410 415
Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val Leu Thr Gln
420 425 430
Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser
435 440 445
Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
450 455 460
Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala
465 470 475 480
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
485 490 495
Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
500 505 510
Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys
515 520 525
Val Glu Ile Lys His His His His His His His His His His Arg Arg
530 535 540
Lys Arg Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly
545 550 555 560
Asp Val Glu Glu Asn Pro Gly Pro Met Ser Glu Leu Ile Lys Glu Asn
565 570 575
Met His Met Lys Leu Tyr Met Glu Gly Thr Val Asn Asn His His Phe
580 585 590
Lys Cys Thr Ser Glu Gly Glu Gly Lys Pro Tyr Glu Gly Thr Gln Thr
595 600 605
Met Lys Ile Lys Val Val Glu Gly Gly Pro Leu Pro Phe Ala Phe Asp
610 615 620
Ile Leu Ala Thr Ser Phe Met Tyr Gly Ser Lys Ala Phe Ile Asn His
625 630 635 640
Thr Gln Gly Ile Pro Asp Phe Phe Lys Gln Ser Phe Pro Glu Gly Phe
645 650 655
Thr Trp Glu Arg Ile Thr Thr Tyr Glu Asp Gly Gly Val Leu Thr Ala
660 665 670
Thr Gln Asp Thr Ser Phe Gln Asn Gly Cys Ile Ile Tyr Asn Val Lys
675 680 685
Ile Asn Gly Val Asn Phe Pro Ser Asn Gly Pro Val Met Gln Lys Lys
690 695 700
Thr Arg Gly Trp Glu Ala Asn Thr Glu Met Leu Tyr Pro Ala Asp Gly
705 710 715 720
Gly Leu Arg Gly His Ser Gln Met Ala Leu Lys Leu Val Gly Gly Gly
725 730 735
Tyr Leu His Cys Ser Phe Lys Thr Thr Tyr Arg Ser Lys Lys Pro Ala
740 745 750
Lys Asn Leu Lys Met Pro Gly Phe His Phe Val Asp His Arg Leu Glu
755 760 765
Arg Ile Lys Glu Ala Asp Lys Glu Thr Tyr Val Glu Gln His Glu Met
770 775 780
Ala Val Ala Lys Tyr Cys Asp Leu Pro Ser Lys Leu Gly His Arg
785 790 795
<210> 22
<211> 2283
<212> DNA
<213> 人工序列
<220>
<223> 人类FAP DNA编码序列
<400> 22
atgaagacct gggtgaaaat cgtgtttgga gtcgcaacca gcgccgtgct ggccctgttg 60
gtgatgtgca tcgtgctgcg cccgtcacgc gtgcataaca gcgaagaaaa caccatgaga 120
gctctgacgc taaaggacat cctgaatggc actttttcct ataagacttt cttcccgaat 180
tggattagcg ggcaggagta cctgcaccaa tcggcggata acaatatcgt gctctacaac 240
atcgaaactg gccagagcta caccatcctg tcgaatagaa ctatgaaatc ggtgaatgcg 300
tcgaactacg gacttagccc ggaccgccag ttcgtgtacc tagaatcgga ctacagcaag 360
ctgtggcggt acagctacac tgctacgtac tacatctacg acctgtcgaa tggcgagttc 420
gtgagaggaa acgaactccc ccgcccgatc caatacctgt gctggagccc tgtgggaagc 480
aagctggcgt acgtgtatca gaacaacatc tacctcaagc agaggccggg cgacccacct 540
ttccagatca cttttaacgg tcgggagaac aagattttca atggaatccc ggattgggtg 600
tacgaagaag agatgctggc gaccaaatat gcgctctggt ggtcgccaaa cggaaaattt 660
ctagcatacg ccgagttcaa tgacaccgac atccccgtca tcgcctacag ctactacgga 720
gatgagcaat acccacgcac tattaatatc ccgtacccga aagccggcgc taaaaatccg 780
gtcgtgcgga tcttcatcat cgacactacc tatccagctt acgtgggacc gcaagaggtc 840
cctgtgccag ccatgatcgc cagcagcgat tactacttct cctggctgac ttgggtcact 900
gacgagaggg tgtgcctcca atggctcaag cgcgtgcaga acgtgagcgt gctgtccatc 960
tgcgacttca gagaagattg gcaaacgtgg gactgtccga aaactcaaga gcatatcgag 1020
gagagcagaa ccggatgggc aggggggttc ttcgtgtcca ccccggtgtt cagctacgat 1080
gcgatctcgt actacaagat tttctccgat aaggacgggt acaaacatat ccactacatc 1140
aaggacaccg tggagaatgc gatccaaatc actagcggaa aatgggaagc gattaacatt 1200
ttccgggtga cgcaagactc attgttctat tcatccaatg aatttgaaga gtaccctggc 1260
cggaggaaca tctaccgcat ctccatcgga tcatacccac catcaaagaa gtgcgtgacc 1320
tgccatctcc gcaaggagcg ctgccaatac tacaccgcgt ccttctccga ttacgcgaag 1380
tactacgccc tggtgtgcta cggcccggga atcccaatct cgaccctaca tgatgggcgc 1440
accgaccagg agatcaaaat cctggaggaa aacaaggagc tcgaaaatgc tctgaaaaat 1500
attcaactac cgaaggagga aatcaagaag ctggaggtgg atgaaattac tctgtggtac 1560
aaaatgatcc tgccgccaca gttcgaccgc tccaagaagt acccgctgct gatccaggtg 1620
tacggaggac cctgctcaca gtcggtgcgc tcagtgtttg ctgtgaattg gatcagctac 1680
ctcgcatcaa aggaggggat ggtcatcgcg cttgtggacg gaagaggtac tgcattccag 1740
ggggacaaac tgctctacgc ggtgtaccgc aagctgggcg tctacgaggt ggaggaccaa 1800
atcacggcgg tcagaaagtt catcgagatg ggtttcatcg acgagaagag gatcgccatc 1860
tggggctggt cgtacggagg ttacgtgtcg tcactcgctc tggcgagcgg gactggattg 1920
ttcaaatgcg gtatcgcagt cgcccccgtg tcgtcatggg aatactacgc ctcggtgtat 1980
accgaacgct ttatgggact ccctactaaa gacgataacc tagagcacta caaaaactcg 2040
acggtgatgg cacgcgcaga gtactttcgc aatgtggatt acctcctgat ccacggaacc 2100
gccgatgata atgtccactt ccagaactca gcccaaatcg cgaaagccct ggtgaacgct 2160
caagtggact ttcaagcaat gtggtattca gaccagaacc acggactatc cggcctatcg 2220
actaatcacc tgtacaccca tatgacccat ttccttaaac agtgtttcag cctgtccgat 2280
tag 2283
<210> 23
<211> 760
<212> PRT
<213> 人工序列
<220>
<223> 人类FAP氨基酸序列
<400> 23
Met Lys Thr Trp Val Lys Ile Val Phe Gly Val Ala Thr Ser Ala Val
1 5 10 15
Leu Ala Leu Leu Val Met Cys Ile Val Leu Arg Pro Ser Arg Val His
20 25 30
Asn Ser Glu Glu Asn Thr Met Arg Ala Leu Thr Leu Lys Asp Ile Leu
35 40 45
Asn Gly Thr Phe Ser Tyr Lys Thr Phe Phe Pro Asn Trp Ile Ser Gly
50 55 60
Gln Glu Tyr Leu His Gln Ser Ala Asp Asn Asn Ile Val Leu Tyr Asn
65 70 75 80
Ile Glu Thr Gly Gln Ser Tyr Thr Ile Leu Ser Asn Arg Thr Met Lys
85 90 95
Ser Val Asn Ala Ser Asn Tyr Gly Leu Ser Pro Asp Arg Gln Phe Val
100 105 110
Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp Arg Tyr Ser Tyr Thr Ala
115 120 125
Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn Gly Glu Phe Val Arg Gly Asn
130 135 140
Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys Trp Ser Pro Val Gly Ser
145 150 155 160
Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile Tyr Leu Lys Gln Arg Pro
165 170 175
Gly Asp Pro Pro Phe Gln Ile Thr Phe Asn Gly Arg Glu Asn Lys Ile
180 185 190
Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu Glu Glu Met Leu Ala Thr
195 200 205
Lys Tyr Ala Leu Trp Trp Ser Pro Asn Gly Lys Phe Leu Ala Tyr Ala
210 215 220
Glu Phe Asn Asp Thr Asp Ile Pro Val Ile Ala Tyr Ser Tyr Tyr Gly
225 230 235 240
Asp Glu Gln Tyr Pro Arg Thr Ile Asn Ile Pro Tyr Pro Lys Ala Gly
245 250 255
Ala Lys Asn Pro Val Val Arg Ile Phe Ile Ile Asp Thr Thr Tyr Pro
260 265 270
Ala Tyr Val Gly Pro Gln Glu Val Pro Val Pro Ala Met Ile Ala Ser
275 280 285
Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp Val Thr Asp Glu Arg Val
290 295 300
Cys Leu Gln Trp Leu Lys Arg Val Gln Asn Val Ser Val Leu Ser Ile
305 310 315 320
Cys Asp Phe Arg Glu Asp Trp Gln Thr Trp Asp Cys Pro Lys Thr Gln
325 330 335
Glu His Ile Glu Glu Ser Arg Thr Gly Trp Ala Gly Gly Phe Phe Val
340 345 350
Ser Thr Pro Val Phe Ser Tyr Asp Ala Ile Ser Tyr Tyr Lys Ile Phe
355 360 365
Ser Asp Lys Asp Gly Tyr Lys His Ile His Tyr Ile Lys Asp Thr Val
370 375 380
Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys Trp Glu Ala Ile Asn Ile
385 390 395 400
Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr Ser Ser Asn Glu Phe Glu
405 410 415
Glu Tyr Pro Gly Arg Arg Asn Ile Tyr Arg Ile Ser Ile Gly Ser Tyr
420 425 430
Pro Pro Ser Lys Lys Cys Val Thr Cys His Leu Arg Lys Glu Arg Cys
435 440 445
Gln Tyr Tyr Thr Ala Ser Phe Ser Asp Tyr Ala Lys Tyr Tyr Ala Leu
450 455 460
Val Cys Tyr Gly Pro Gly Ile Pro Ile Ser Thr Leu His Asp Gly Arg
465 470 475 480
Thr Asp Gln Glu Ile Lys Ile Leu Glu Glu Asn Lys Glu Leu Glu Asn
485 490 495
Ala Leu Lys Asn Ile Gln Leu Pro Lys Glu Glu Ile Lys Lys Leu Glu
500 505 510
Val Asp Glu Ile Thr Leu Trp Tyr Lys Met Ile Leu Pro Pro Gln Phe
515 520 525
Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile Gln Val Tyr Gly Gly Pro
530 535 540
Cys Ser Gln Ser Val Arg Ser Val Phe Ala Val Asn Trp Ile Ser Tyr
545 550 555 560
Leu Ala Ser Lys Glu Gly Met Val Ile Ala Leu Val Asp Gly Arg Gly
565 570 575
Thr Ala Phe Gln Gly Asp Lys Leu Leu Tyr Ala Val Tyr Arg Lys Leu
580 585 590
Gly Val Tyr Glu Val Glu Asp Gln Ile Thr Ala Val Arg Lys Phe Ile
595 600 605
Glu Met Gly Phe Ile Asp Glu Lys Arg Ile Ala Ile Trp Gly Trp Ser
610 615 620
Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu Ala Ser Gly Thr Gly Leu
625 630 635 640
Phe Lys Cys Gly Ile Ala Val Ala Pro Val Ser Ser Trp Glu Tyr Tyr
645 650 655
Ala Ser Val Tyr Thr Glu Arg Phe Met Gly Leu Pro Thr Lys Asp Asp
660 665 670
Asn Leu Glu His Tyr Lys Asn Ser Thr Val Met Ala Arg Ala Glu Tyr
675 680 685
Phe Arg Asn Val Asp Tyr Leu Leu Ile His Gly Thr Ala Asp Asp Asn
690 695 700
Val His Phe Gln Asn Ser Ala Gln Ile Ala Lys Ala Leu Val Asn Ala
705 710 715 720
Gln Val Asp Phe Gln Ala Met Trp Tyr Ser Asp Gln Asn His Gly Leu
725 730 735
Ser Gly Leu Ser Thr Asn His Leu Tyr Thr His Met Thr His Phe Leu
740 745 750
Lys Gln Cys Phe Ser Leu Ser Asp
755 760
<210> 24
<211> 571
<212> DNA
<213> 人工序列
<220>
<223> CMV启动子序列
<400> 24
agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac 60
ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa 120
tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt 180
atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc 240
ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat 300
gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atgctgatgc 360
ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc 420
tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa 480
aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg 540
tctatataag cagagctggt ttagtgaacc g 571
<210> 25
<211> 192
<212> DNA
<213> 人工序列
<220>
<223> SV40晚期多腺苷酸化序列
<400> 25
cagacatgat aagatacatt gatgagtttg gacaaaccac aactagaatg cagtgaaaaa 60
aatgctttat ttgtgaaatt tgtgatgcta ttgctttatt tgtaaccatt ataagctgca 120
ataaacaagt taacaacaac aattgcattc attttatgtt tcaggttcag ggggaggtgt 180
gggaggtttt tt 192
<210> 26
<211> 34895
<212> DNA
<213> 人工序列
<220>
<223> NG-605 (EnAd-CMV-FAPBiTE)
<400> 26
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccagggg ctcccgccag atctagtaat caattacggg 29400
gtcattagtt catagcccat atatggagtt ccgcgttaca taacttacgg taaatggccc 29460
gcctggctga ccgcccaacg acccccgccc attgacgtca ataatgacgt atgttcccat 29520
agtaacgcca atagggactt tccattgacg tcaatgggtg gagtatttac ggtaaactgc 29580
ccacttggca gtacatcaag tgtatcatat gccaagtacg ccccctattg acgtcaatga 29640
cggtaaatgg cccgcctggc attatgccca gtacatgacc ttatgggact ttcctacttg 29700
gcagtacatc tacgtattag tcatcgctat taccatgctg atgcggtttt ggcagtacat 29760
caatgggcgt ggatagcggt ttgactcacg gggatttcca agtctccacc ccattgacgt 29820
caatgggagt ttgttttggc accaaaatca acgggacttt ccaaaatgtc gtaacaactc 29880
cgccccattg acgcaaatgg gcggtaggcg tgtacggtgg gaggtctata taagcagagc 29940
tggtttagtg aaccgtcaga tcagatcttt gtcgatccta ccatccactc gacacacccg 30000
ccagcggccg ctgccaagct tccgagctct cgaattcaaa ggaggtaccc accatgggct 30060
ggagctgcat catcttgttc ctggtcgcaa ctgctaccgg agtccattcg gacatcgtca 30120
tgacccaaag ccctgactcg ctcgctgtgt cactgggaga gcgggcgact atcaactgca 30180
aatcatccca gagcctgctg tattcacgca atcagaaaaa ctacctggcc tggtatcagc 30240
agaagccggg ccagcctccc aagctgctga tcttctgggc ctccacccgc gaaagcggcg 30300
tgccggaccg cttcagcgga agcggattcg gaactgactt tactctgacc attagctcct 30360
tgcaggcgga ggacgtggcc gtctactact gccagcagta tttctcctat ccgctcacct 30420
ttgggcaagg caccaaggtg gagattaagg gagggggcgg cagcggggga ggcggcagcg 30480
gcggcggggg atcgcaggtc cagctcgtcc aatccggagc cgaagtcaag aagccgggag 30540
cgtcggtcaa ggtcagctgc aaaacttcgc gctacacctt cactgagtac acgatccact 30600
gggtccgcca ggcgcccggc cagcggctgg agtggatcgg cgggatcaac ccaaacaacg 30660
gaatcccaaa ttacaatcag aaatttaaag ggcgggtgac tatcaccgtg gatacctcgg 30720
cctccacggc gtacatggag ctctcatcac tcagatcgga ggacaccgcg gtctattact 30780
gcgcccgccg ccggatcgct tatggatacg atgaaggaca tgcgatggat tactggggcc 30840
agggcaccct cgtcacggtg tcgtcaggag gcggcggttc agatgtgcaa ctcgtgcagt 30900
ccggtgcgga agtgaaaaag ccgggcgcga gcgtcaaagt gtcatgcaag gcgtcaggat 30960
atacgtttac tagatacact atgcactggg tgcgccaggc acctggtcag ggccttgaat 31020
ggatcggcta catcaatccg tcgagaggct acactaatta cgcggactca gtcaaagggc 31080
gcttcacgat tacgaccgac aagtccacct cgactgcata catggaactg tcctcgctga 31140
gaagcgagga caccgctact tactactgcg ctagatacta cgatgatcac tactgcctcg 31200
attactgggg ccagggaacc actgtcacgg tgtcatcggg agagggcacc tcaaccggat 31260
cagggggatc gggaggctcg ggcggcgcag acgacatcgt cctgacccag tcgcccgcca 31320
ccttgtcgct gtccccagga gaaagagcga ccctgtcatg ccgggcgtcg caaagcgtga 31380
gctatatgaa ttggtatcag cagaagccag gaaaggcgcc gaagagatgg atctacgaca 31440
cctccaaggt cgcttcaggt gtcccggcta gattctcagg atcgggatca ggaacggact 31500
actccctgac catcaattca ctggaagcag aagatgcggc cacctactac tgtcagcagt 31560
ggtcctccaa cccgctgact ttcggaggcg gaactaaggt cgagatcaag catcaccatc 31620
accatcacca ccatcaccat taggctagct tgactgactg agatacagcg taccttcagc 31680
tcacagacat gataagatac attgatgagt ttggacaaac cacaactaga atgcagtgaa 31740
aaaaatgctt tatttgtgaa atttgtgatg ctattgcttt atttgtaacc attataagct 31800
gcaataaaca agttaacaac aacaattgca ttcattttat gtttcaggtt cagggggagg 31860
tgtgggaggt tttttaaagc aagtaaaacc tctacaaatg tggtagtcgt cagctatcct 31920
gcaggaactt gtttatttga aaatcaattc acaaaatccg agtagttatt ttgcctcccc 31980
cttcccattt aacagaatac accaatctct ccccacgcac agctttaaac atttggatac 32040
cattagatat agacatggtt ttagattcca cattccaaac agtttcagag cgagccaatc 32100
tggggtcagt gatagataaa aatccatcgg gatagtcttt taaagcgctt tcacagtcca 32160
actgctgcgg atgcgactcc ggagtctgga tcacggtcat ctggaagaag aacgatggga 32220
atcataatcc gaaaacggta tcggacgatt gtgtctcatc aaacccacaa gcagccgctg 32280
tctgcgtcgc tccgtgcgac tgctgtttat gggatcaggg tccacagtgt cctgaagcat 32340
gattttaata gcccttaaca tcaactttct ggtgcgatgc gcgcagcaac gcattctgat 32400
ttcactcaaa tctttgcagt aggtacaaca cattattaca atattgttta ataaaccata 32460
attaaaagcg ctccagccaa aactcatatc tgatataatc gcccctgcat gaccatcata 32520
ccaaagttta atataaatta aatgacgttc cctcaaaaac acactaccca catacatgat 32580
ctcttttggc atgtgcatat taacaatctg tctgtaccat ggacaacgtt ggttaatcat 32640
gcaacccaat ataaccttcc ggaaccacac tgccaacacc gctcccccag ccatgcattg 32700
aagtgaaccc tgctgattac aatgacaatg aagaacccaa ttctctcgac cgtgaatcac 32760
ttgagaatga aaaatatcta tagtggcaca acatagacat aaatgcatgc atcttctcat 32820
aatttttaac tcctcaggat ttagaaacat atcccaggga ataggaagct cttgcagaac 32880
agtaaagctg gcagaacaag gaagaccacg aacacaactt acactatgca tagtcatagt 32940
atcacaatct ggcaacagcg ggtggtcttc agtcatagaa gctcgggttt cattttcctc 33000
acaacgtggt aactgggctc tggtgtaagg gtgatgtctg gcgcatgatg tcgagcgtgc 33060
gcgcaacctt gtcataatgg agttgcttcc tgacattctc gtattttgta tagcaaaacg 33120
cggccctggc agaacacact cttcttcgcc ttctatcctg ccgcttagcg tgttccgtgt 33180
gatagttcaa gtacaaccac actcttaagt tggtcaaaag aatgctggct tcagttgtaa 33240
tcaaaactcc atcgcatcta atcgttctga ggaaatcatc caagcaatgc aactggattg 33300
tgtttcaagc aggagaggag agggaagaga cggaagaacc atgttaattt ttattccaaa 33360
cgatctcgca gtacttcaaa ttgtagatcg cgcagatggc atctctcgcc cccactgtgt 33420
tggtgaaaaa gcacagctag atcaaaagaa atgcgatttt caaggtgctc aacggtggct 33480
tccagcaaag cctccacgcg cacatccaag aacaaaagaa taccaaaaga aggagcattt 33540
tctaactcct caatcatcat attacattcc tgcaccattc ccagataatt ttcagctttc 33600
cagccttgaa ttattcgtgt cagttcttgt ggtaaatcca atccacacat tacaaacagg 33660
tcccggaggg cgccctccac caccattctt aaacacaccc tcataatgac aaaatatctt 33720
gctcctgtgt cacctgtagc gaattgagaa tggcaacatc aattgacatg cccttggctc 33780
taagttcttc tttaagttct agttgtaaaa actctctcat attatcacca aactgcttag 33840
ccagaagccc cccgggaaca agagcagggg acgctacagt gcagtacaag cgcagacctc 33900
cccaattggc tccagcaaaa acaagattgg aataagcata ttgggaaccg ccagtaatat 33960
catcgaagtt gctggaaata taatcaggca gagtttcttg taaaaattga ataaaagaaa 34020
aatttgccaa aaaaacattc aaaacctctg ggatgcaaat gcaataggtt accgcgctgc 34080
gctccaacat tgttagtttt gaattagtct gcaaaaataa aaaaaaaaac aagcgtcata 34140
tcatagtagc ctgacgaaca gatggataaa tcagtctttc catcacaaga caagccacag 34200
ggtctccagc tcgaccctcg taaaacctgt catcatgatt aaacaacagc accgaaagtt 34260
cctcgcggtg accagcatga ataattcttg atgaagcata caatccagac atgttagcat 34320
cagttaacga gaaaaaacag ccaacatagc ctttgggtat aattatgctt aatcgtaagt 34380
atagcaaagc cacccctcgc ggatacaaag taaaaggcac aggagaataa aaaatataat 34440
tatttctctg ctgctgttca ggcaacgtcg cccccggtcc ctctaaatac acatacaaag 34500
cctcatcagc catggcttac cagacaaagt acagcgggca cacaaagcac aagctctaaa 34560
gtgactctcc aacctctcca caatatatat atacacaagc cctaaactga cgtaatggga 34620
gtaaagtgta aaaaatcccg ccaaacccaa cacacacccc gaaactgcgt caccagggaa 34680
aagtacagtt tcacttccgc aatcccaaca ggcgtaactt cctctttctc acggtacgtg 34740
atatcccact aacttgcaac gtcattttcc cacggtcgca ccgccccttt tagccgttaa 34800
ccccacagcc aatcaccaca cgatccacac tttttaaaat cacctcattt acatattggc 34860
accattccat ctataaggta tattatatag ataga 34895
<210> 27
<211> 34216
<212> DNA
<213> 人工序列
<220>
<223> NG-606 (EnAd-SA-FAPBiTE)
<400> 27
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cagatgtgca actcgtgcag tccggtgcgg aagtgaaaaa 30240
gccgggcgcg agcgtcaaag tgtcatgcaa ggcgtcagga tatacgttta ctagatacac 30300
tatgcactgg gtgcgccagg cacctggtca gggccttgaa tggatcggct acatcaatcc 30360
gtcgagaggc tacactaatt acgcggactc agtcaaaggg cgcttcacga ttacgaccga 30420
caagtccacc tcgactgcat acatggaact gtcctcgctg agaagcgagg acaccgctac 30480
ttactactgc gctagatact acgatgatca ctactgcctc gattactggg gccagggaac 30540
cactgtcacg gtgtcatcgg gagagggcac ctcaaccgga tcagggggat cgggaggctc 30600
gggcggcgca gacgacatcg tcctgaccca gtcgcccgcc accttgtcgc tgtccccagg 30660
agaaagagcg accctgtcat gccgggcgtc gcaaagcgtg agctatatga attggtatca 30720
gcagaagcca ggaaaggcgc cgaagagatg gatctacgac acctccaagg tcgcttcagg 30780
tgtcccggct agattctcag gatcgggatc aggaacggac tactccctga ccatcaattc 30840
actggaagca gaagatgcgg ccacctacta ctgtcagcag tggtcctcca acccgctgac 30900
tttcggaggc ggaactaagg tcgagatcaa gcatcaccat caccatcacc accatcacca 30960
ttaggctagc ttgactgact gagatacagc gtaccttcag ctcacagaca tgataagata 31020
cattgatgag tttggacaaa ccacaactag aatgcagtga aaaaaatgct ttatttgtga 31080
aatttgtgat gctattgctt tatttgtaac cattataagc tgcaataaac aagttaacaa 31140
caacaattgc attcatttta tgtttcaggt tcagggggag gtgtgggagg ttttttaaag 31200
caagtaaaac ctctacaaat gtggtagtcg tcagctatcc tgcaggaact tgtttatttg 31260
aaaatcaatt cacaaaatcc gagtagttat tttgcctccc ccttcccatt taacagaata 31320
caccaatctc tccccacgca cagctttaaa catttggata ccattagata tagacatggt 31380
tttagattcc acattccaaa cagtttcaga gcgagccaat ctggggtcag tgatagataa 31440
aaatccatcg ggatagtctt ttaaagcgct ttcacagtcc aactgctgcg gatgcgactc 31500
cggagtctgg atcacggtca tctggaagaa gaacgatggg aatcataatc cgaaaacggt 31560
atcggacgat tgtgtctcat caaacccaca agcagccgct gtctgcgtcg ctccgtgcga 31620
ctgctgttta tgggatcagg gtccacagtg tcctgaagca tgattttaat agcccttaac 31680
atcaactttc tggtgcgatg cgcgcagcaa cgcattctga tttcactcaa atctttgcag 31740
taggtacaac acattattac aatattgttt aataaaccat aattaaaagc gctccagcca 31800
aaactcatat ctgatataat cgcccctgca tgaccatcat accaaagttt aatataaatt 31860
aaatgacgtt ccctcaaaaa cacactaccc acatacatga tctcttttgg catgtgcata 31920
ttaacaatct gtctgtacca tggacaacgt tggttaatca tgcaacccaa tataaccttc 31980
cggaaccaca ctgccaacac cgctccccca gccatgcatt gaagtgaacc ctgctgatta 32040
caatgacaat gaagaaccca attctctcga ccgtgaatca cttgagaatg aaaaatatct 32100
atagtggcac aacatagaca taaatgcatg catcttctca taatttttaa ctcctcagga 32160
tttagaaaca tatcccaggg aataggaagc tcttgcagaa cagtaaagct ggcagaacaa 32220
ggaagaccac gaacacaact tacactatgc atagtcatag tatcacaatc tggcaacagc 32280
gggtggtctt cagtcataga agctcgggtt tcattttcct cacaacgtgg taactgggct 32340
ctggtgtaag ggtgatgtct ggcgcatgat gtcgagcgtg cgcgcaacct tgtcataatg 32400
gagttgcttc ctgacattct cgtattttgt atagcaaaac gcggccctgg cagaacacac 32460
tcttcttcgc cttctatcct gccgcttagc gtgttccgtg tgatagttca agtacaacca 32520
cactcttaag ttggtcaaaa gaatgctggc ttcagttgta atcaaaactc catcgcatct 32580
aatcgttctg aggaaatcat ccaagcaatg caactggatt gtgtttcaag caggagagga 32640
gagggaagag acggaagaac catgttaatt tttattccaa acgatctcgc agtacttcaa 32700
attgtagatc gcgcagatgg catctctcgc ccccactgtg ttggtgaaaa agcacagcta 32760
gatcaaaaga aatgcgattt tcaaggtgct caacggtggc ttccagcaaa gcctccacgc 32820
gcacatccaa gaacaaaaga ataccaaaag aaggagcatt ttctaactcc tcaatcatca 32880
tattacattc ctgcaccatt cccagataat tttcagcttt ccagccttga attattcgtg 32940
tcagttcttg tggtaaatcc aatccacaca ttacaaacag gtcccggagg gcgccctcca 33000
ccaccattct taaacacacc ctcataatga caaaatatct tgctcctgtg tcacctgtag 33060
cgaattgaga atggcaacat caattgacat gcccttggct ctaagttctt ctttaagttc 33120
tagttgtaaa aactctctca tattatcacc aaactgctta gccagaagcc ccccgggaac 33180
aagagcaggg gacgctacag tgcagtacaa gcgcagacct ccccaattgg ctccagcaaa 33240
aacaagattg gaataagcat attgggaacc gccagtaata tcatcgaagt tgctggaaat 33300
ataatcaggc agagtttctt gtaaaaattg aataaaagaa aaatttgcca aaaaaacatt 33360
caaaacctct gggatgcaaa tgcaataggt taccgcgctg cgctccaaca ttgttagttt 33420
tgaattagtc tgcaaaaata aaaaaaaaaa caagcgtcat atcatagtag cctgacgaac 33480
agatggataa atcagtcttt ccatcacaag acaagccaca gggtctccag ctcgaccctc 33540
gtaaaacctg tcatcatgat taaacaacag caccgaaagt tcctcgcggt gaccagcatg 33600
aataattctt gatgaagcat acaatccaga catgttagca tcagttaacg agaaaaaaca 33660
gccaacatag cctttgggta taattatgct taatcgtaag tatagcaaag ccacccctcg 33720
cggatacaaa gtaaaaggca caggagaata aaaaatataa ttatttctct gctgctgttc 33780
aggcaacgtc gcccccggtc cctctaaata cacatacaaa gcctcatcag ccatggctta 33840
ccagacaaag tacagcgggc acacaaagca caagctctaa agtgactctc caacctctcc 33900
acaatatata tatacacaag ccctaaactg acgtaatggg agtaaagtgt aaaaaatccc 33960
gccaaaccca acacacaccc cgaaactgcg tcaccaggga aaagtacagt ttcacttccg 34020
caatcccaac aggcgtaact tcctctttct cacggtacgt gatatcccac taacttgcaa 34080
cgtcattttc ccacggtcgc accgcccctt ttagccgtta accccacagc caatcaccac 34140
acgatccaca ctttttaaaa tcacctcatt tacatattgg caccattcca tctataaggt 34200
atattatata gataga 34216
<210> 28
<211> 32326
<212> DNA
<213> 人工序列
<220>
<223> EnAd基因组
<400> 28
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttaact tgtttatttg aaaatcaatt cacaaaatcc gagtagttat 29400
tttgcctccc ccttcccatt taacagaata caccaatctc tccccacgca cagctttaaa 29460
catttggata ccattagata tagacatggt tttagattcc acattccaaa cagtttcaga 29520
gcgagccaat ctggggtcag tgatagataa aaatccatcg ggatagtctt ttaaagcgct 29580
ttcacagtcc aactgctgcg gatgcgactc cggagtctgg atcacggtca tctggaagaa 29640
gaacgatggg aatcataatc cgaaaacggt atcggacgat tgtgtctcat caaacccaca 29700
agcagccgct gtctgcgtcg ctccgtgcga ctgctgttta tgggatcagg gtccacagtg 29760
tcctgaagca tgattttaat agcccttaac atcaactttc tggtgcgatg cgcgcagcaa 29820
cgcattctga tttcactcaa atctttgcag taggtacaac acattattac aatattgttt 29880
aataaaccat aattaaaagc gctccagcca aaactcatat ctgatataat cgcccctgca 29940
tgaccatcat accaaagttt aatataaatt aaatgacgtt ccctcaaaaa cacactaccc 30000
acatacatga tctcttttgg catgtgcata ttaacaatct gtctgtacca tggacaacgt 30060
tggttaatca tgcaacccaa tataaccttc cggaaccaca ctgccaacac cgctccccca 30120
gccatgcatt gaagtgaacc ctgctgatta caatgacaat gaagaaccca attctctcga 30180
ccgtgaatca cttgagaatg aaaaatatct atagtggcac aacatagaca taaatgcatg 30240
catcttctca taatttttaa ctcctcagga tttagaaaca tatcccaggg aataggaagc 30300
tcttgcagaa cagtaaagct ggcagaacaa ggaagaccac gaacacaact tacactatgc 30360
atagtcatag tatcacaatc tggcaacagc gggtggtctt cagtcataga agctcgggtt 30420
tcattttcct cacaacgtgg taactgggct ctggtgtaag ggtgatgtct ggcgcatgat 30480
gtcgagcgtg cgcgcaacct tgtcataatg gagttgcttc ctgacattct cgtattttgt 30540
atagcaaaac gcggccctgg cagaacacac tcttcttcgc cttctatcct gccgcttagc 30600
gtgttccgtg tgatagttca agtacaacca cactcttaag ttggtcaaaa gaatgctggc 30660
ttcagttgta atcaaaactc catcgcatct aatcgttctg aggaaatcat ccaagcaatg 30720
caactggatt gtgtttcaag caggagagga gagggaagag acggaagaac catgttaatt 30780
tttattccaa acgatctcgc agtacttcaa attgtagatc gcgcagatgg catctctcgc 30840
ccccactgtg ttggtgaaaa agcacagcta gatcaaaaga aatgcgattt tcaaggtgct 30900
caacggtggc ttccagcaaa gcctccacgc gcacatccaa gaacaaaaga ataccaaaag 30960
aaggagcatt ttctaactcc tcaatcatca tattacattc ctgcaccatt cccagataat 31020
tttcagcttt ccagccttga attattcgtg tcagttcttg tggtaaatcc aatccacaca 31080
ttacaaacag gtcccggagg gcgccctcca ccaccattct taaacacacc ctcataatga 31140
caaaatatct tgctcctgtg tcacctgtag cgaattgaga atggcaacat caattgacat 31200
gcccttggct ctaagttctt ctttaagttc tagttgtaaa aactctctca tattatcacc 31260
aaactgctta gccagaagcc ccccgggaac aagagcaggg gacgctacag tgcagtacaa 31320
gcgcagacct ccccaattgg ctccagcaaa aacaagattg gaataagcat attgggaacc 31380
gccagtaata tcatcgaagt tgctggaaat ataatcaggc agagtttctt gtaaaaattg 31440
aataaaagaa aaatttgcca aaaaaacatt caaaacctct gggatgcaaa tgcaataggt 31500
taccgcgctg cgctccaaca ttgttagttt tgaattagtc tgcaaaaata aaaaaaaaaa 31560
caagcgtcat atcatagtag cctgacgaac agatggataa atcagtcttt ccatcacaag 31620
acaagccaca gggtctccag ctcgaccctc gtaaaacctg tcatcatgat taaacaacag 31680
caccgaaagt tcctcgcggt gaccagcatg aataattctt gatgaagcat acaatccaga 31740
catgttagca tcagttaacg agaaaaaaca gccaacatag cctttgggta taattatgct 31800
taatcgtaag tatagcaaag ccacccctcg cggatacaaa gtaaaaggca caggagaata 31860
aaaaatataa ttatttctct gctgctgttc aggcaacgtc gcccccggtc cctctaaata 31920
cacatacaaa gcctcatcag ccatggctta ccagacaaag tacagcgggc acacaaagca 31980
caagctctaa agtgactctc caacctctcc acaatatata tatacacaag ccctaaactg 32040
acgtaatggg agtaaagtgt aaaaaatccc gccaaaccca acacacaccc cgaaactgcg 32100
tcaccaggga aaagtacagt ttcacttccg caatcccaac aggcgtaact tcctctttct 32160
cacggtacgt gatatcccac taacttgcaa cgtcattttc ccacggtcgc accgcccctt 32220
ttagccgtta accccacagc caatcaccac acgatccaca ctttttaaaa tcacctcatt 32280
tacatattgg caccattcca tctataaggt atattatata gataga 32326
<210> 29
<211> 200
<212> DNA
<213> 人工序列
<220>
<223> 对应于并且包含EnAd基因组的bp 28166-28366的B chi DNA序列
<400> 29
aaatgattaa taaaaaatca cttacttgaa atcagcaata aggtctctgt tgaaattttc 60
tcccagcagc acctcacttc cctcttccca actctggtat tctaaacccc gttcagcggc 120
atactttctc catactttaa aggggatgtc aaattttagc tcctctcctg tacccacaat 180
cttcatgtct ttcttcccag 200
<210> 30
<211> 35
<212> DNA
<213> 人工序列
<220>
<223> 对应于并且包含EnAd基因组的bp 29345-29379的B γDNA序列
<400> 30
caaataaagt ttaacttgtt tatttgaaaa tcaat 35
<210> 31
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> His标签
<400> 31
His His His His His His
1 5
<210> 32
<211> 14
<212> DNA
<213> 人工序列
<220>
<223> 剪接受体
<400> 32
tttctctctt cagg 14
<210> 33
<211> 192
<212> DNA
<213> 人工序列
<220>
<223> SV40聚腺苷酸化序列
<400> 33
cagacatgat aagatacatt gatgagtttg gacaaaccac aactagaatg cagtgaaaaa 60
aatgctttat ttgtgaaatt tgtgatgcta ttgctttatt tgtaaccatt ataagctgca 120
ataaacaagt taacaacaac aattgcattc attttatgtt tcaggttcag ggggaggtgt 180
gggaggtttt tt 192
<210> 34
<211> 1551
<212> DNA
<213> 人工序列
<220>
<223> FAP BiTE核酸序列(OKT3)
<400> 34
atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt ccattcggac 60
atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg ggcgactatc 120
aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta cctggcctgg 180
tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc cacccgcgaa 240
agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac tctgaccatt 300
agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt ctcctatccg 360
ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag cgggggaggc 420
ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga agtcaagaag 480
ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac tgagtacacg 540
atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg gatcaaccca 600
aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat caccgtggat 660
acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga caccgcggtc 720
tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc gatggattac 780
tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca ggtgcagctg 840
cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc ctgcaaggct 900
tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc tggacagggt 960
ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa tcagaagttc 1020
aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat gcaactgagc 1080
agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga tgatcattac 1140
tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg cggtggctcg 1200
ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc tccagcaatc 1260
atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc aagtgtaagt 1320
tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat ttatgacaca 1380
tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg gacctcttac 1440
tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg ccagcagtgg 1500
agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg g 1551
<210> 35
<211> 1557
<212> DNA
<213> 人工序列
<220>
<223> FAP BiTE核酸序列(aCD3)
<400> 35
atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt ccattcggac 60
atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg ggcgactatc 120
aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta cctggcctgg 180
tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc cacccgcgaa 240
agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac tctgaccatt 300
agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt ctcctatccg 360
ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag cgggggaggc 420
ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga agtcaagaag 480
ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac tgagtacacg 540
atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg gatcaaccca 600
aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat caccgtggat 660
acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga caccgcggtc 720
tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc gatggattac 780
tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaga tgtgcaactc 840
gtgcagtccg gtgcggaagt gaaaaagccg ggcgcgagcg tcaaagtgtc atgcaaggcg 900
tcaggatata cgtttactag atacactatg cactgggtgc gccaggcacc tggtcagggc 960
cttgaatgga tcggctacat caatccgtcg agaggctaca ctaattacgc ggactcagtc 1020
aaagggcgct tcacgattac gaccgacaag tccacctcga ctgcatacat ggaactgtcc 1080
tcgctgagaa gcgaggacac cgctacttac tactgcgcta gatactacga tgatcactac 1140
tgcctcgatt actggggcca gggaaccact gtcacggtgt catcgggaga gggcacctca 1200
accggatcag ggggatcggg aggctcgggc ggcgcagacg acatcgtcct gacccagtcg 1260
cccgccacct tgtcgctgtc cccaggagaa agagcgaccc tgtcatgccg ggcgtcgcaa 1320
agcgtgagct atatgaattg gtatcagcag aagccaggaa aggcgccgaa gagatggatc 1380
tacgacacct ccaaggtcgc ttcaggtgtc ccggctagat tctcaggatc gggatcagga 1440
acggactact ccctgaccat caattcactg gaagcagaag atgcggccac ctactactgt 1500
cagcagtggt cctccaaccc gctgactttc ggaggcggaa ctaaggtcga gatcaag 1557
<210> 36
<211> 1856
<212> DNA
<213> 人工序列
<220>
<223> NG-611转基因盒
<400> 36
caggcccacc atgggatgga gctgcatcat cctattcctc gtggcgacgg ccactggagt 60
gcatagcgaa ctggtgatga ctcagtcccc gtcatccctg acggtgaccg ccggcgagaa 120
ggtcaccatg tcgtgcaagt cctcgcaaag cctgcttaac agcggcaacc agaaaaacta 180
cctcacgtgg tatcagcaaa agccaggtca acccccaaaa ctgctcatct actgggcgag 240
cacccgcgag tcgggggtgc cagaccggtt caccggctcc gggtcaggaa ctgatttcac 300
cctaaccatc agctcggtgc aagcggagga cctggccgtg tactactgcc aaaatgatta 360
ctcgtaccct ctgacctttg gagcgggcac caagctcgaa atcaagggcg gtggaggaag 420
cggcggggga ggctcaggtg ggggaggatc agaagtccaa ctgctggagc agtcaggagc 480
cgaactggtc cgcccgggaa cctccgtcaa gatttcctgt aaggcttccg gctacgcttt 540
taccaattac tggctgggct gggtcaagca aagaccgggg catggcctgg agtggatcgg 600
cgacatcttc ccagggagcg gcaacatcca ctacaacgag aagttcaagg ggaaagcgac 660
tctgactgcc gacaaatcat ccagcaccgc ctacatgcag ctgtcgtcgc tcactttcga 720
agacagcgcg gtgtactttt gtgctcggct ccggaactgg gatgaaccaa tggactactg 780
gggacaagga actaccgtga ccgtctcctc cggcggcggt ggaagccagg tgcagctgca 840
gcagtctggg gctgaactgg caagacctgg ggcctcagtg aagatgtcct gcaaggcttc 900
tggctacacc tttactaggt acacgatgca ctgggtaaaa cagaggcctg gacagggtct 960
ggaatggatt ggatacatta atcctagccg tggttatact aattacaatc agaagttcaa 1020
ggacaaggcc acattgacta cagacaaatc ctccagcaca gcctacatgc aactgagcag 1080
cctgacatct gaggactctg cagtctatta ctgtgcaaga tattatgatg atcattactg 1140
ccttgactac tggggccaag gcaccactct cacagtctcc tcaggtggcg gtggctcggg 1200
cggtggtgga tctggtggcg gcggatctga tatcgtgctc actcagtctc cagcaatcat 1260
gtctgcatct ccaggggaga aggtcaccat gacctgcagt gccagctcaa gtgtaagtta 1320
catgaactgg taccagcaga agtcaggcac ctcccccaaa agatggattt atgacacatc 1380
caaactggct tctggagtcc ctgctcactt caggggcagt gggtctggga cctcttactc 1440
tctcacaatc agcggcatgg aggctgaaga tgctgccact tattactgcc agcagtggag 1500
tagtaaccca ttcacgttcg gctcggggac aaagttggaa ataaaccggc atcaccatca 1560
ccatcaccac catcaccatt aggctagctt gactgactga gatacagcgt accttcagct 1620
cacagacatg ataagataca ttgatgagtt tggacaaacc acaactagaa tgcagtgaaa 1680
aaaatgcttt atttgtgaaa tttgtgatgc tattgcttta tttgtaacca ttataagctg 1740
caataaacaa gttaacaaca acaattgcat tcattttatg tttcaggttc agggggaggt 1800
gtgggaggtt ttttaaagca agtaaaacct ctacaaatgt ggtagtcgtc agctat 1856
<210> 37
<211> 1868
<212> DNA
<213> 人工序列
<220>
<223> NG-612转基因盒
<400> 37
caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt 60
ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg 120
ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta 180
cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc 240
cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac 300
tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt 360
ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag 420
cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga 480
agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac 540
tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg 600
gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat 660
caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga 720
caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc 780
gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca 840
ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc 900
ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc 960
tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa 1020
tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat 1080
gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga 1140
tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg 1200
cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc 1260
tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc 1320
aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat 1380
ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg 1440
gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg 1500
ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg 1560
gcatcaccat caccatcacc accatcacca ttaggctagc ttgactgact gagatacagc 1620
gtaccttcag ctcacagaca tgataagata cattgatgag tttggacaaa ccacaactag 1680
aatgcagtga aaaaaatgct ttatttgtga aatttgtgat gctattgctt tatttgtaac 1740
cattataagc tgcaataaac aagttaacaa caacaattgc attcatttta tgtttcaggt 1800
tcagggggag gtgtgggagg ttttttaaag caagtaaaac ctctacaaat gtggtagtcg 1860
tcagctat 1868
<210> 38
<211> 1878
<212> DNA
<213> 人工序列
<220>
<223> NG-613转基因盒
<400> 38
tttctctctt caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg 60
ctaccggagt ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac 120
tgggagagcg ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc 180
agaaaaacta cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct 240
tctgggcctc cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa 300
ctgactttac tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc 360
agcagtattt ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag 420
ggggcggcag cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat 480
ccggagccga agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct 540
acaccttcac tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt 600
ggatcggcgg gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc 660
gggtgactat caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca 720
gatcggagga caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg 780
aaggacatgc gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg 840
gcggttcaca ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag 900
tgaagatgtc ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa 960
aacagaggcc tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata 1020
ctaattacaa tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca 1080
cagcctacat gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa 1140
gatattatga tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct 1200
cctcaggtgg cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc 1260
tcactcagtc tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca 1320
gtgccagctc aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca 1380
aaagatggat ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca 1440
gtgggtctgg gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca 1500
cttattactg ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg 1560
aaataaaccg gcatcaccat caccatcacc accatcacca ttaggctagc ttgactgact 1620
gagatacagc gtaccttcag ctcacagaca tgataagata cattgatgag tttggacaaa 1680
ccacaactag aatgcagtga aaaaaatgct ttatttgtga aatttgtgat gctattgctt 1740
tatttgtaac cattataagc tgcaataaac aagttaacaa caacaattgc attcatttta 1800
tgtttcaggt tcagggggag gtgtgggagg ttttttaaag caagtaaaac ctctacaaat 1860
gtggtagtcg tcagctat 1878
<210> 39
<211> 19
<212> DNA
<213> 人工序列
<220>
<223> 限制性位点插入(B chi)
<400> 39
gcggccgcta tggccggcc 19
<210> 40
<211> 19
<212> DNA
<213> 人工序列
<220>
<223> 限制性位点插入(Bγ)
<400> 40
gcgatcgcta ccctgcagg 19
<210> 41
<211> 572
<212> DNA
<213> 人工序列
<220>
<223> CMV启动子序列
<400> 41
agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac 60
ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa 120
tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt 180
atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc 240
ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat 300
gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atgctgatgc 360
ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc 420
tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa 480
aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg 540
tctatataag cagagctggt ttagtgaacc gt 572
<210> 42
<211> 505
<212> DNA
<213> 人工序列
<220>
<223> PGK启动子序列
<400> 42
ctaccgggta ggggaggcgc ttttcccaag gcagtctgga gcatgcgctt tagcagcccc 60
gctgggcact tggcgctaca caagtggcct ctggcctcgc acacattcca catccaccgg 120
taggcgccaa ccggctccgt tctttggtgg ccccttcgcg ccaccttcta cccctcccct 180
agtcaggaag ttcccccccg ccccgcagct cgcgtcatgc aggacgtgac aaatggaagt 240
agcacgtctc actagtctcg tgcaaatgga cagcaccgct gagcaatgga agcgggtagg 300
cccttggggc agcggccaat agcagctttg ctccttcgct ttctgggctc agaggctggg 360
aaggggtggg tccgggggcg ggctcagggg cgggctcagg ggcggggcgg gcgcccgaag 420
gtcctccgga ggcccggcat tccgcacgct tcaaaagcgc acgtctgccg cgctgttctc 480
ttcttcctca tctccgggcc tttcg 505
<210> 43
<211> 367
<212> DNA
<213> 人工序列
<220>
<223> CBA启动子序列
<400> 43
gtcgaggtga gccccacgtt ctgcttcact ctccccatct cccccccctc cccaccccca 60
attttgtatt tatttatttt ttaattattt tatgcagcga tgggggcggg gggggggggg 120
gcgcgcgcca ggcggggcgg ggcggggcga ggggcggggc ggggcgaggc ggagaggtgc 180
ggcggcagcc aatcagagcg gcgcgctccg aaagtttcct tttatggcga ggcggcggcg 240
gcggcggccc tataaaaagc gaagcgcgcg gcgggcggga gtcgctgcgt tgccttcgcc 300
ccgtgccccg ctccgcgccg cctcgcgccg cccgccccgg ctctgactga ccgcgttact 360
cccacag 367
<210> 44
<400> 44
000
<210> 45
<211> 16
<212> DNA
<213> 人工序列
<220>
<223> 剪接受体(SA)DNA序列
<400> 45
cctttctctc ttcagg 16
<210> 46
<211> 23
<212> DNA
<213> 人工序列
<220>
<223> 支链剪接受体(bSA)DNA序列
<400> 46
tgctaatcct ttctctcttc agg 23
<210> 47
<400> 47
000
<210> 48
<211> 13
<212> RNA
<213> 人工序列
<220>
<223> 起始密码子的实例
<220>
<221> misc_feature
<222> (11)..(11)
<223> R是腺嘌呤或鸟嘌呤
<400> 48
gccgccrcca ugg 13
<210> 49
<211> 551
<212> DNA
<213> 人工序列
<220>
<223> 内部核糖体进入序列(IRES)
<400> 49
cgttactggc cgaagccgct tggaataagg ccggtgtgcg tttgtctata tgttattttc 60
caccatattg ccgtcttttg gcaatgtgag ggcccggaaa cctggccctg tcttcttgac 120
gagcattcct aggggtcttt cccctctcgc caaaggaatg caaggtctgt tgaatgtcgt 180
gaaggaagca gttcctctgg aagcttcttg aagacaaaca acgtctgtag cgaccctttg 240
caggcagcgg aaccccccac ctggcgacag gtgcctctgc ggccaaaagc cacgtgtata 300
agatacacct gcaaaggcgg cacaacccca gtgccacgtt gtgagttgga tagttgtgga 360
aagagtcaaa tggctcccct caagcgtatt caacaagggg ctgaaggatg cccagaaggt 420
accccattgt atgggatctg atctggggcc tcggtgcaca tgcttttcat gtgtttagtc 480
gaggttaaaa aacgtctagg ccccccgaac cacggggacg tggttttcct ttgaaaaaca 540
cgatgataat a 551
<210> 50
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> P2A肽
<400> 50
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
1 5 10 15
Glu Glu Asn Pro Gly Pro
20
<210> 51
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> F2A肽
<400> 51
Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu
1 5 10 15
Glu Asn Pro Gly Pro
20
<210> 52
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> E2A肽
<400> 52
Gly Ser Gly Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp
1 5 10 15
Val Glu Ser Asn Pro Gly Pro
20
<210> 53
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> T2A肽
<400> 53
Gly Ser Gly Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala
1 5 10 15
Gly Asp Val Glu Ser Asn Pro Gly Pro
20 25
<210> 54
<211> 192
<212> DNA
<213> 人工序列
<220>
<223> 聚腺苷酸化(polyA)序列
<400> 54
cagacatgat aagatacatt gatgagtttg gacaaaccac aactagaatg cagtgaaaaa 60
aatgctttat ttgtgaaatt tgtgatgcta ttgctttatt tgtaaccatt ataagctgca 120
ataaacaagt taacaacaac aattgcattc attttatgtt tcaggttcag ggggaggtgt 180
gggaggtttt tt 192
<210> 55
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 前导序列
<400> 55
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser
<210> 56
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 前导序列
<400> 56
Met Asp Trp Thr Trp Arg Val Phe Cys Leu Leu Ala Val Ala Pro Gly
1 5 10 15
Ala His Ser
<210> 57
<211> 166
<212> PRT
<213> 人工序列
<220>
<223> IFNγ氨基酸序列
<400> 57
Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu
1 5 10 15
Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu
20 25 30
Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn
35 40 45
Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp
50 55 60
Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe
65 70 75 80
Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile
85 90 95
Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg
100 105 110
Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val
115 120 125
Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser
130 135 140
Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg
145 150 155 160
Gly Arg Arg Ala Ser Gln
165
<210> 58
<211> 188
<212> PRT
<213> 人工序列
<220>
<223> IFNα氨基酸序列
<400> 58
Met Ala Leu Thr Phe Ala Leu Leu Val Ala Leu Leu Val Leu Ser Cys
1 5 10 15
Lys Ser Ser Cys Ser Val Gly Cys Asp Leu Pro Gln Thr His Ser Leu
20 25 30
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
35 40 45
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
50 55 60
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
65 70 75 80
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
85 90 95
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
100 105 110
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
115 120 125
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
130 135 140
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
145 150 155 160
Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu
165 170 175
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
180 185
<210> 59
<211> 233
<212> PRT
<213> 人工序列
<220>
<223> TNFα氨基酸序列
<400> 59
Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala
1 5 10 15
Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe
20 25 30
Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe
35 40 45
Cys Leu Leu His Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro
50 55 60
Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser
65 70 75 80
Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro
85 90 95
Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu
100 105 110
Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser
115 120 125
Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly
130 135 140
Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala
145 150 155 160
Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro
165 170 175
Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu
180 185 190
Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp Arg Leu
195 200 205
Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly
210 215 220
Gln Val Tyr Phe Gly Ile Ile Ala Leu
225 230
<210> 60
<211> 5288
<212> DNA
<213> 人工序列
<220>
<223> 对应于EnAd基因组的E2B区的DNA序列(bp 10355-5068)
<400> 60
ctatggcatc tcgatccagc agacctcctc gtttcgcggg tttggacggc tcctggaata 60
gggtatgaga cgatgggcgt ccagcgctgc cagggttcgg tccttccagg gtctcagtgt 120
tcgagtcagg gttgtttccg tcacagtgaa ggggtgtgcg cctgcttggg cgcttgccag 180
ggtgcgcttc agactcatcc tgctggtcga aaacttctgt cgcttggcgc cctgtatgtc 240
ggccaagtag cagtttacca tgagttcgta gttgagcgcc tcggctgcgt ggcctttggc 300
gcggagctta cctttggaag ttttcttgca taccgggcag tataggcatt tcagcgcata 360
caacttgggc gcaaggaaaa cggattctgg ggagtatgca tctgcgccgc aggaggcgca 420
aacagtttca cattccacca gccaggttaa atccggttca ttggggtcaa aaacaagttt 480
tccgccatat tttttgatgc gtttcttacc tttggtctcc atgagttcgt gtcctcgttg 540
agtgacaaac aggctgtccg tgtccccgta gactgatttt acaggcctct tctccagtgg 600
agtgcctcgg tcttcttcgt acaggaactc tgaccactct gatacaaagg cgcgcgtcca 660
ggccagcaca aaggaggcta tgtgggaggg gtagcgatcg ttgtcaacca gggggtccac 720
cttttccaaa gtatgcaaac acatgtcacc ctcttcaaca tccaggaatg tgattggctt 780
gtaggtgtat ttcacgtgac ctggggtccc cgctgggggg gtataaaagg gggcggttct 840
ttgctcttcc tcactgtctt ccggatcgct gtccaggaac gtcagctgtt ggggtaggta 900
ttccctctcg aaggcgggca tgacctctgc actcaggttg tcagtttcta agaacgagga 960
ggatttgata ttgacagtgc cggttgagat gcctttcatg aggttttcgt ccatctggtc 1020
agaaaacaca atttttttat tgtcaagttt ggtggcaaat gatccataca gggcgttgga 1080
taaaagtttg gcaatggatc gcatggtttg gttcttttcc ttgtccgcgc gctctttggc 1140
ggcgatgttg agttggacat actcgcgtgc caggcacttc cattcgggga agatagttgt 1200
taattcatct ggcacgattc tcacttgcca ccctcgatta tgcaaggtaa ttaaatccac 1260
actggtggcc acctcgcctc gaaggggttc attggtccaa cagagcctac ctcctttcct 1320
agaacagaaa gggggaagtg ggtctagcat aagttcatcg ggagggtctg catccatggt 1380
aaagattccc ggaagtaaat ccttatcaaa atagctgatg ggagtggggt catctaaggc 1440
catttgccat tctcgagctg ccagtgcgcg ctcatatggg ttaaggggac tgccccatgg 1500
catgggatgg gtgagtgcag aggcatacat gccacagatg tcatagacgt agatgggatc 1560
ctcaaagatg cctatgtagg ttggatagca tcgcccccct ctgatacttg ctcgcacata 1620
gtcatatagt tcatgtgatg gcgctagcag ccccggaccc aagttggtgc gattgggttt 1680
ttctgttctg tagacgatct ggcgaaagat ggcgtgagaa ttggaagaga tggtgggtct 1740
ttgaaaaatg ttgaaatggg catgaggtag acctacagag tctctgacaa agtgggcata 1800
agattcttga agcttggtta ccagttcggc ggtgacaagt acgtctaggg cgcagtagtc 1860
aagtgtttct tgaatgatgt cataacctgg ttggtttttc ttttcccaca gttcgcggtt 1920
gagaaggtat tcttcgcgat ccttccagta ctcttctagc ggaaacccgt ctttgtctgc 1980
acggtaagat cctagcatgt agaactgatt aactgccttg taagggcagc agcccttctc 2040
tacgggtaga gagtatgctt gagcagcttt tcgtagcgaa gcgtgagtaa gggcaaaggt 2100
gtctctgacc atgactttga ggaattggta tttgaagtcg atgtcgtcac aggctccctg 2160
ttcccagagt tggaagtcta cccgtttctt gtaggcgggg ttgggcaaag cgaaagtaac 2220
atcattgaag agaatcttgc cggccctggg catgaaattg cgagtgatgc gaaaaggctg 2280
tggtacttcc gctcggttat tgataacctg ggcagctagg acgatctcgt cgaaaccgtt 2340
gatgttgtgt cctacgatgt ataattctat gaaacgcggc gtgcctctga cgtgaggtag 2400
cttactgagc tcatcaaagg ttaggtctgt ggggtcagat aaggcgtagt gttcgagagc 2460
ccattcgtgc aggtgaggat tcgctttaag gaaggaggac cagaggtcca ctgccagtgc 2520
tgtttgtaac tggtcccggt actgacgaaa atgccgtccg actgccattt tttctggggt 2580
gacgcaatag aaggtttggg ggtcctgccg ccagcgatcc cacttgagtt ttatggcgag 2640
gtcataggcg atgttgacga gccgctggtc tccagagagt ttcatgacca gcatgaaggg 2700
gattagctgc ttgccaaagg accccatcca ggtgtaggtt tccacatcgt aggtgagaaa 2760
gagcctttct gtgcgaggat gagagccaat cgggaagaac tggatctcct gccaccagtt 2820
ggaggaatgg ctgttgatgt gatggaagta gaactccctg cgacgcgccg agcattcatg 2880
cttgtgcttg tacagacggc cgcagtagtc gcagcgttgc acgggttgta tctcgtgaat 2940
gagttgtacc tggcttccct tgacgagaaa tttcagtggg aagccgaggc ctggcgattg 3000
tatctcgtgc tttactatgt tgtctgcatc ggcctgttca tcttctgtct cgatggtggt 3060
catgctgacg agccctcgcg ggaggcaagt ccagacctcg gcgcggcagg ggcggagctc 3120
gaggacgaga gcgcgcaggc tggagctgtc cagggtcctg agacgctgcg gactcaggtt 3180
agtaggcagt gtcaggagat taacttgcat gatcttttgg agggcgtgcg ggaggttcag 3240
atagtacttg atctcaacgg gtccgttggt ggagatgtcg atggcttgca gggttccgtg 3300
tcccttgggc gctaccaccg tgcccttgtt tttcattttg gacggcggtg gctctgttgc 3360
ttcttgcatg tttagaagcg gtgtcgaggg cgcgcaccgg gcggcagggg cggctcggga 3420
cccggcggca tggctggcag tggtacgtcg gcgccgcgcg cgggtaggtt ctggtactgc 3480
gccctgagaa gactcgcatg cgcgacgacg cggcggttga catcctggat ctgacgcctc 3540
tgggtgaaag ctaccggccc cgtgagcttg aacctgaaag agagttcaac agaatcaatc 3600
tcggtatcgt tgacggcggc ttgcctaagg atttcttgca cgtcaccaga gttgtcctgg 3660
taggcgatct ccgccatgaa ctgctcgatc tcttcctctt gaagatctcc gcggcccgct 3720
ctctcgacgg tggccgcgag gtcgttggag atgcgcccaa tgagttgaga gaatgcattc 3780
atgcccgcct cgttccagac gcggctgtag accacggccc ccacgggatc tctcgcgcgc 3840
atgaccacct gggcgaggtt gagctccacg tggcgggtga agaccgcata gttgcatagg 3900
cgctggaaaa ggtagttgag tgtggtggcg atgtgctcgg tgacgaagaa atacatgatc 3960
catcgtctca gcggcatctc gctgacatcg cccagagctt ccaagcgctc catggcctcg 4020
tagaagtcca cggcaaaatt aaaaaactgg gagtttcgcg cggacacggt caactcctct 4080
tccagaagac ggataagttc ggcgatggtg gtgcgcacct cgcgctcgaa agcccctggg 4140
atttcttcct caatctcttc ttcttccact aacatctctt cctcttcagg tggggctgca 4200
ggaggagggg gaacgcggcg acgccggcgg cgcacgggca gacggtcgat gaatctttca 4260
atgacctctc cgcggcggcg gcgcatggtt tcagtgacgg cgcggccgtt ctcgcgcggt 4320
cgcagagtaa aaacaccgcc gcgcatctcc ttaaagtggt gactgggagg ttctccgttt 4380
gggagggaga gggcgctgat tatacatttt attaattggc ccgtagggac tgcacgcaga 4440
gatctgatcg tgtcaagatc cacgggatct gaaaaccttt cgacgaaagc gtctaaccag 4500
tcacagtcac aaggtaggct gagtacggct tcttgtgggc gggggtggtt atgtgttcgg 4560
tctgggtctt ctgtttcttc ttcatctcgg gaaggtgaga cgatgctgct ggtgatgaaa 4620
ttaaagtagg cagttctaag acggcggatg gtggcgagga gcaccaggtc tttgggtccg 4680
gcttgctgga tacgcaggcg attggccatt ccccaagcat tatcctgaca tctagcaaga 4740
tctttgtagt agtcttgcat gagccgttct acgggcactt cttcctcacc cgttctgcca 4800
tgcatacgtg tgagtccaaa tccgcgcatt ggttgtacca gtgccaagtc agctacgact 4860
ctttcggcga ggatggcttg ctgtacttgg gtaagggtgg cttgaaagtc atcaaaatcc 4920
acaaagcggt ggtaagctcc tgtattaatg gtgtaagcac agttggccat gactgaccag 4980
ttaactgtct ggtgaccagg gcgcacgagc tcggtgtatt taaggcgcga ataggcgcgg 5040
gtgtcaaaga tgtaatcgtt gcaggtgcgc accagatact ggtaccctat aagaaaatgc 5100
ggcggtggtt ggcggtagag aggccatcgt tctgtagctg gagcgccagg ggcgaggtct 5160
tccaacataa ggcggtgata gccgtagatg tacctggaca tccaggtgat tcctgcggcg 5220
gtagtagaag cccgaggaaa ctcgcgtacg cggttccaaa tgttgcgtag cggcatgaag 5280
tagttcat 5288
<210> 61
<211> 1560
<212> DNA
<213> 人工序列
<220>
<223> 抗FAP BiTE DNA编码序列,具有N末端信号序列,不具有C末端
deca-His亲和标签
<400> 61
atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt ccattcggac 60
atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg ggcgactatc 120
aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta cctggcctgg 180
tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc cacccgcgaa 240
agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac tctgaccatt 300
agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt ctcctatccg 360
ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag cgggggaggc 420
ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga agtcaagaag 480
ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac tgagtacacg 540
atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg gatcaaccca 600
aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat caccgtggat 660
acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga caccgcggtc 720
tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc gatggattac 780
tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaga tgtgcaactc 840
gtgcagtccg gtgcggaagt gaaaaagccg ggcgcgagcg tcaaagtgtc atgcaaggcg 900
tcaggatata cgtttactag atacactatg cactgggtgc gccaggcacc tggtcagggc 960
cttgaatgga tcggctacat caatccgtcg agaggctaca ctaattacgc ggactcagtc 1020
aaagggcgct tcacgattac gaccgacaag tccacctcga ctgcatacat ggaactgtcc 1080
tcgctgagaa gcgaggacac cgctacttac tactgcgcta gatactacga tgatcactac 1140
tgcctcgatt actggggcca gggaaccact gtcacggtgt catcgggaga gggcacctca 1200
accggatcag ggggatcggg aggctcgggc ggcgcagacg acatcgtcct gacccagtcg 1260
cccgccacct tgtcgctgtc cccaggagaa agagcgaccc tgtcatgccg ggcgtcgcaa 1320
agcgtgagct atatgaattg gtatcagcag aagccaggaa aggcgccgaa gagatggatc 1380
tacgacacct ccaaggtcgc ttcaggtgtc ccggctagat tctcaggatc gggatcagga 1440
acggactact ccctgaccat caattcactg gaagcagaag atgcggccac ctactactgt 1500
cagcagtggt cctccaaccc gctgactttc ggaggcggaa ctaaggtcga gatcaagtag 1560
<210> 62
<211> 519
<212> PRT
<213> 人工序列
<220>
<223> 抗FAP BiTE氨基酸序列,具有N末端信号序列,不具有C末端
deca-His亲和标签
<400> 62
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val
20 25 30
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu
35 40 45
Leu Tyr Ser Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu
65 70 75 80
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe
85 90 95
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
100 105 110
Cys Gln Gln Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
145 150 155 160
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe
165 170 175
Thr Glu Tyr Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
180 185 190
Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn
195 200 205
Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser
210 215 220
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
225 230 235 240
Tyr Tyr Cys Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His
245 250 255
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
260 265 270
Gly Gly Gly Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
275 280 285
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr
290 295 300
Phe Thr Arg Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly
305 310 315 320
Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr
325 330 335
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr
340 345 350
Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala
355 360 365
Thr Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr
370 375 380
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser
385 390 395 400
Thr Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val
405 410 415
Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
420 425 430
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr
435 440 445
Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser
450 455 460
Lys Val Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly
465 470 475 480
Thr Asp Tyr Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala
485 490 495
Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly
500 505 510
Gly Thr Lys Val Glu Ile Lys
515
<210> 63
<211> 1599
<212> DNA
<213> 人工序列
<220>
<223> 对照(抗FHA)BiTE DNA编码序列,具有N末端信号序列,不具有C末端
deca-His亲和标签
<400> 63
atgggttggt catgcatcat cctgtttctc gtcgcaactg cgaccggcgt gcattcggaa 60
ctggacatcg tgatgaccca ggcacctgca tcactggcag tgagcctggg acagagagcc 120
accatttcat gccgggccag caagagcgtg tcgtcatccg gatacaatta tctgcactgg 180
tatcagcaga aaccaggaca acctccaaag ctactcatct acctggcgtc gaacctcgaa 240
tcgggcgtcc cagctagatt ctcagggagc ggttcgggaa ccgatttcac cctgaacatc 300
caccctgtgg aggaggaaga cgcggcaacg tactattgcc agcattcccg cgagttccct 360
ctcactttcg gtgcgggaac taagctggag atcaagtcca gcggcggcgg aggtagcggt 420
ggaggtggcg gaggaagctc ccggtcgtcg ctggaggtgc agctgcaaca atccggcccg 480
gaactggtca agccaggcgc atccgtcaag atttcatgca agacctcggg gtacaccttc 540
accgggtaca cgatgcattg ggtcaggcag agccacggca agtccctgga atggatcgga 600
ggaatcaacc ccaaaaacgg cggcatcatc tacaaccaaa agttccaggg aaaagccact 660
ctgaccgtgg acaagtcgtc gagcacggcc agcatggagc tgcggtccct cacttccgac 720
gactcagccg tgtattactg cgcgagacgg gtctacgatg actacccata ctactacgct 780
atggactact ggggacaagg aaccagcgtg accgtctcat cggcgaaaac tactccgccg 840
tcggtgacgt cgggaggtgg tggaagcgac gtgcagctcg tccagtcggg tgccgaggtg 900
aagaagccag gagcctccgt gaaggtctcg tgcaaagcca gcggctacac ttttactagg 960
tacactatgc actgggtgcg gcaagcgccg ggacaaggtc tggagtggat cggatacatc 1020
aatccgtcgc ggggatacac taattacgcg gactccgtca agggacggtt tactatcact 1080
acggataagt ccactagcac cgcctacatg gaactgtcct cgctgcggtc ggaagacact 1140
gcgacctact actgcgctag atattacgat gaccactact gcctcgacta ttgggggcag 1200
ggcactacgg tcaccgtctc gtcgggagaa ggaacctcaa ctggatcggg cggatcggga 1260
ggctccggag gagccgacga catcgtgctt acccagtcgc ctgcgaccct gtccctgtcc 1320
ccaggagaga gagcgactct ttcatgcagg gcttcccaat cagtctccta catgaattgg 1380
tatcaacaaa aacccggcaa ggccccgaaa cgctggatct acgatacttc aaaggtggcc 1440
agcggtgtgc ctgcccgctt ctccgggtcg gggtccggca ccgattactc gttgactatc 1500
aatagcctgg aggccgagga cgctgcaact tactactgcc agcagtggtc ctccaaccct 1560
ctcaccttcg gaggcgggac caaggtggaa atcaaatag 1599
<210> 64
<211> 532
<212> PRT
<213> 人工序列
<220>
<223> 对照(抗FHA)BiTE氨基酸序列,具有N末端信号序列,不具有C末端
deca-His标签
<400> 64
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu
20 25 30
Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys
35 40 45
Ser Val Ser Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu
65 70 75 80
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
85 90 95
Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr
100 105 110
Cys Gln His Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys
115 120 125
Leu Glu Ile Lys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly
130 135 140
Gly Ser Ser Arg Ser Ser Leu Glu Val Gln Leu Gln Gln Ser Gly Pro
145 150 155 160
Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser
165 170 175
Gly Tyr Thr Phe Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His
180 185 190
Gly Lys Ser Leu Glu Trp Ile Gly Gly Ile Asn Pro Lys Asn Gly Gly
195 200 205
Ile Ile Tyr Asn Gln Lys Phe Gln Gly Lys Ala Thr Leu Thr Val Asp
210 215 220
Lys Ser Ser Ser Thr Ala Ser Met Glu Leu Arg Ser Leu Thr Ser Asp
225 230 235 240
Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Val Tyr Asp Asp Tyr Pro
245 250 255
Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val
260 265 270
Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Thr Ser Gly Gly Gly Gly
275 280 285
Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
290 295 300
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg
305 310 315 320
Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
325 330 335
Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser
340 345 350
Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala
355 360 365
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr
370 375 380
Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln
385 390 395 400
Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser Thr Gly Ser
405 410 415
Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val Leu Thr Gln
420 425 430
Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser
435 440 445
Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
450 455 460
Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala
465 470 475 480
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
485 490 495
Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
500 505 510
Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys
515 520 525
Val Glu Ile Lys
530
<210> 65
<211> 532
<212> PRT
<213> 人工序列
<220>
<223> 对照BiTe(抗FHA),不具有C末端deca-His标签
<400> 65
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Glu Leu Asp Ile Val Met Thr Gln Ala Pro Ala Ser Leu
20 25 30
Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys
35 40 45
Ser Val Ser Ser Ser Gly Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu
65 70 75 80
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
85 90 95
Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr
100 105 110
Cys Gln His Ser Arg Glu Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys
115 120 125
Leu Glu Ile Lys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly
130 135 140
Gly Ser Ser Arg Ser Ser Leu Glu Val Gln Leu Gln Gln Ser Gly Pro
145 150 155 160
Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser
165 170 175
Gly Tyr Thr Phe Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His
180 185 190
Gly Lys Ser Leu Glu Trp Ile Gly Gly Ile Asn Pro Lys Asn Gly Gly
195 200 205
Ile Ile Tyr Asn Gln Lys Phe Gln Gly Lys Ala Thr Leu Thr Val Asp
210 215 220
Lys Ser Ser Ser Thr Ala Ser Met Glu Leu Arg Ser Leu Thr Ser Asp
225 230 235 240
Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Val Tyr Asp Asp Tyr Pro
245 250 255
Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val
260 265 270
Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Thr Ser Gly Gly Gly Gly
275 280 285
Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
290 295 300
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg
305 310 315 320
Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
325 330 335
Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Ala Asp Ser
340 345 350
Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr Ser Thr Ala
355 360 365
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr
370 375 380
Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln
385 390 395 400
Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser Thr Gly Ser
405 410 415
Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val Leu Thr Gln
420 425 430
Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser
435 440 445
Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
450 455 460
Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala
465 470 475 480
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
485 490 495
Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
500 505 510
Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys
515 520 525
Val Glu Ile Lys
530
<210> 66
<211> 34865
<212> DNA
<213> 人工序列
<220>
<223> NG-605(EnAd-CMV-FAPBiTE)不具有deca-His标签
<400> 66
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccagggg ctcccgccag atctagtaat caattacggg 29400
gtcattagtt catagcccat atatggagtt ccgcgttaca taacttacgg taaatggccc 29460
gcctggctga ccgcccaacg acccccgccc attgacgtca ataatgacgt atgttcccat 29520
agtaacgcca atagggactt tccattgacg tcaatgggtg gagtatttac ggtaaactgc 29580
ccacttggca gtacatcaag tgtatcatat gccaagtacg ccccctattg acgtcaatga 29640
cggtaaatgg cccgcctggc attatgccca gtacatgacc ttatgggact ttcctacttg 29700
gcagtacatc tacgtattag tcatcgctat taccatgctg atgcggtttt ggcagtacat 29760
caatgggcgt ggatagcggt ttgactcacg gggatttcca agtctccacc ccattgacgt 29820
caatgggagt ttgttttggc accaaaatca acgggacttt ccaaaatgtc gtaacaactc 29880
cgccccattg acgcaaatgg gcggtaggcg tgtacggtgg gaggtctata taagcagagc 29940
tggtttagtg aaccgtcaga tcagatcttt gtcgatccta ccatccactc gacacacccg 30000
ccagcggccg ctgccaagct tccgagctct cgaattcaaa ggaggtaccc accatgggct 30060
ggagctgcat catcttgttc ctggtcgcaa ctgctaccgg agtccattcg gacatcgtca 30120
tgacccaaag ccctgactcg ctcgctgtgt cactgggaga gcgggcgact atcaactgca 30180
aatcatccca gagcctgctg tattcacgca atcagaaaaa ctacctggcc tggtatcagc 30240
agaagccggg ccagcctccc aagctgctga tcttctgggc ctccacccgc gaaagcggcg 30300
tgccggaccg cttcagcgga agcggattcg gaactgactt tactctgacc attagctcct 30360
tgcaggcgga ggacgtggcc gtctactact gccagcagta tttctcctat ccgctcacct 30420
ttgggcaagg caccaaggtg gagattaagg gagggggcgg cagcggggga ggcggcagcg 30480
gcggcggggg atcgcaggtc cagctcgtcc aatccggagc cgaagtcaag aagccgggag 30540
cgtcggtcaa ggtcagctgc aaaacttcgc gctacacctt cactgagtac acgatccact 30600
gggtccgcca ggcgcccggc cagcggctgg agtggatcgg cgggatcaac ccaaacaacg 30660
gaatcccaaa ttacaatcag aaatttaaag ggcgggtgac tatcaccgtg gatacctcgg 30720
cctccacggc gtacatggag ctctcatcac tcagatcgga ggacaccgcg gtctattact 30780
gcgcccgccg ccggatcgct tatggatacg atgaaggaca tgcgatggat tactggggcc 30840
agggcaccct cgtcacggtg tcgtcaggag gcggcggttc agatgtgcaa ctcgtgcagt 30900
ccggtgcgga agtgaaaaag ccgggcgcga gcgtcaaagt gtcatgcaag gcgtcaggat 30960
atacgtttac tagatacact atgcactggg tgcgccaggc acctggtcag ggccttgaat 31020
ggatcggcta catcaatccg tcgagaggct acactaatta cgcggactca gtcaaagggc 31080
gcttcacgat tacgaccgac aagtccacct cgactgcata catggaactg tcctcgctga 31140
gaagcgagga caccgctact tactactgcg ctagatacta cgatgatcac tactgcctcg 31200
attactgggg ccagggaacc actgtcacgg tgtcatcggg agagggcacc tcaaccggat 31260
cagggggatc gggaggctcg ggcggcgcag acgacatcgt cctgacccag tcgcccgcca 31320
ccttgtcgct gtccccagga gaaagagcga ccctgtcatg ccgggcgtcg caaagcgtga 31380
gctatatgaa ttggtatcag cagaagccag gaaaggcgcc gaagagatgg atctacgaca 31440
cctccaaggt cgcttcaggt gtcccggcta gattctcagg atcgggatca ggaacggact 31500
actccctgac catcaattca ctggaagcag aagatgcggc cacctactac tgtcagcagt 31560
ggtcctccaa cccgctgact ttcggaggcg gaactaaggt cgagatcaag taggctagct 31620
tgactgactg agatacagcg taccttcagc tcacagacat gataagatac attgatgagt 31680
ttggacaaac cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg 31740
ctattgcttt atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca 31800
ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc 31860
tctacaaatg tggtagtcgt cagctatcct gcaggaactt gtttatttga aaatcaattc 31920
acaaaatccg agtagttatt ttgcctcccc cttcccattt aacagaatac accaatctct 31980
ccccacgcac agctttaaac atttggatac cattagatat agacatggtt ttagattcca 32040
cattccaaac agtttcagag cgagccaatc tggggtcagt gatagataaa aatccatcgg 32100
gatagtcttt taaagcgctt tcacagtcca actgctgcgg atgcgactcc ggagtctgga 32160
tcacggtcat ctggaagaag aacgatggga atcataatcc gaaaacggta tcggacgatt 32220
gtgtctcatc aaacccacaa gcagccgctg tctgcgtcgc tccgtgcgac tgctgtttat 32280
gggatcaggg tccacagtgt cctgaagcat gattttaata gcccttaaca tcaactttct 32340
ggtgcgatgc gcgcagcaac gcattctgat ttcactcaaa tctttgcagt aggtacaaca 32400
cattattaca atattgttta ataaaccata attaaaagcg ctccagccaa aactcatatc 32460
tgatataatc gcccctgcat gaccatcata ccaaagttta atataaatta aatgacgttc 32520
cctcaaaaac acactaccca catacatgat ctcttttggc atgtgcatat taacaatctg 32580
tctgtaccat ggacaacgtt ggttaatcat gcaacccaat ataaccttcc ggaaccacac 32640
tgccaacacc gctcccccag ccatgcattg aagtgaaccc tgctgattac aatgacaatg 32700
aagaacccaa ttctctcgac cgtgaatcac ttgagaatga aaaatatcta tagtggcaca 32760
acatagacat aaatgcatgc atcttctcat aatttttaac tcctcaggat ttagaaacat 32820
atcccaggga ataggaagct cttgcagaac agtaaagctg gcagaacaag gaagaccacg 32880
aacacaactt acactatgca tagtcatagt atcacaatct ggcaacagcg ggtggtcttc 32940
agtcatagaa gctcgggttt cattttcctc acaacgtggt aactgggctc tggtgtaagg 33000
gtgatgtctg gcgcatgatg tcgagcgtgc gcgcaacctt gtcataatgg agttgcttcc 33060
tgacattctc gtattttgta tagcaaaacg cggccctggc agaacacact cttcttcgcc 33120
ttctatcctg ccgcttagcg tgttccgtgt gatagttcaa gtacaaccac actcttaagt 33180
tggtcaaaag aatgctggct tcagttgtaa tcaaaactcc atcgcatcta atcgttctga 33240
ggaaatcatc caagcaatgc aactggattg tgtttcaagc aggagaggag agggaagaga 33300
cggaagaacc atgttaattt ttattccaaa cgatctcgca gtacttcaaa ttgtagatcg 33360
cgcagatggc atctctcgcc cccactgtgt tggtgaaaaa gcacagctag atcaaaagaa 33420
atgcgatttt caaggtgctc aacggtggct tccagcaaag cctccacgcg cacatccaag 33480
aacaaaagaa taccaaaaga aggagcattt tctaactcct caatcatcat attacattcc 33540
tgcaccattc ccagataatt ttcagctttc cagccttgaa ttattcgtgt cagttcttgt 33600
ggtaaatcca atccacacat tacaaacagg tcccggaggg cgccctccac caccattctt 33660
aaacacaccc tcataatgac aaaatatctt gctcctgtgt cacctgtagc gaattgagaa 33720
tggcaacatc aattgacatg cccttggctc taagttcttc tttaagttct agttgtaaaa 33780
actctctcat attatcacca aactgcttag ccagaagccc cccgggaaca agagcagggg 33840
acgctacagt gcagtacaag cgcagacctc cccaattggc tccagcaaaa acaagattgg 33900
aataagcata ttgggaaccg ccagtaatat catcgaagtt gctggaaata taatcaggca 33960
gagtttcttg taaaaattga ataaaagaaa aatttgccaa aaaaacattc aaaacctctg 34020
ggatgcaaat gcaataggtt accgcgctgc gctccaacat tgttagtttt gaattagtct 34080
gcaaaaataa aaaaaaaaac aagcgtcata tcatagtagc ctgacgaaca gatggataaa 34140
tcagtctttc catcacaaga caagccacag ggtctccagc tcgaccctcg taaaacctgt 34200
catcatgatt aaacaacagc accgaaagtt cctcgcggtg accagcatga ataattcttg 34260
atgaagcata caatccagac atgttagcat cagttaacga gaaaaaacag ccaacatagc 34320
ctttgggtat aattatgctt aatcgtaagt atagcaaagc cacccctcgc ggatacaaag 34380
taaaaggcac aggagaataa aaaatataat tatttctctg ctgctgttca ggcaacgtcg 34440
cccccggtcc ctctaaatac acatacaaag cctcatcagc catggcttac cagacaaagt 34500
acagcgggca cacaaagcac aagctctaaa gtgactctcc aacctctcca caatatatat 34560
atacacaagc cctaaactga cgtaatggga gtaaagtgta aaaaatcccg ccaaacccaa 34620
cacacacccc gaaactgcgt caccagggaa aagtacagtt tcacttccgc aatcccaaca 34680
ggcgtaactt cctctttctc acggtacgtg atatcccact aacttgcaac gtcattttcc 34740
cacggtcgca ccgccccttt tagccgttaa ccccacagcc aatcaccaca cgatccacac 34800
tttttaaaat cacctcattt acatattggc accattccat ctataaggta tattatatag 34860
ataga 34865
<210> 67
<211> 34186
<212> DNA
<213> 人工序列
<220>
<223> NG-606(EnAd-SA-FAPBiTE)不具有deca-His标签
<400> 67
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cagatgtgca actcgtgcag tccggtgcgg aagtgaaaaa 30240
gccgggcgcg agcgtcaaag tgtcatgcaa ggcgtcagga tatacgttta ctagatacac 30300
tatgcactgg gtgcgccagg cacctggtca gggccttgaa tggatcggct acatcaatcc 30360
gtcgagaggc tacactaatt acgcggactc agtcaaaggg cgcttcacga ttacgaccga 30420
caagtccacc tcgactgcat acatggaact gtcctcgctg agaagcgagg acaccgctac 30480
ttactactgc gctagatact acgatgatca ctactgcctc gattactggg gccagggaac 30540
cactgtcacg gtgtcatcgg gagagggcac ctcaaccgga tcagggggat cgggaggctc 30600
gggcggcgca gacgacatcg tcctgaccca gtcgcccgcc accttgtcgc tgtccccagg 30660
agaaagagcg accctgtcat gccgggcgtc gcaaagcgtg agctatatga attggtatca 30720
gcagaagcca ggaaaggcgc cgaagagatg gatctacgac acctccaagg tcgcttcagg 30780
tgtcccggct agattctcag gatcgggatc aggaacggac tactccctga ccatcaattc 30840
actggaagca gaagatgcgg ccacctacta ctgtcagcag tggtcctcca acccgctgac 30900
tttcggaggc ggaactaagg tcgagatcaa gtaggctagc ttgactgact gagatacagc 30960
gtaccttcag ctcacagaca tgataagata cattgatgag tttggacaaa ccacaactag 31020
aatgcagtga aaaaaatgct ttatttgtga aatttgtgat gctattgctt tatttgtaac 31080
cattataagc tgcaataaac aagttaacaa caacaattgc attcatttta tgtttcaggt 31140
tcagggggag gtgtgggagg ttttttaaag caagtaaaac ctctacaaat gtggtagtcg 31200
tcagctatcc tgcaggaact tgtttatttg aaaatcaatt cacaaaatcc gagtagttat 31260
tttgcctccc ccttcccatt taacagaata caccaatctc tccccacgca cagctttaaa 31320
catttggata ccattagata tagacatggt tttagattcc acattccaaa cagtttcaga 31380
gcgagccaat ctggggtcag tgatagataa aaatccatcg ggatagtctt ttaaagcgct 31440
ttcacagtcc aactgctgcg gatgcgactc cggagtctgg atcacggtca tctggaagaa 31500
gaacgatggg aatcataatc cgaaaacggt atcggacgat tgtgtctcat caaacccaca 31560
agcagccgct gtctgcgtcg ctccgtgcga ctgctgttta tgggatcagg gtccacagtg 31620
tcctgaagca tgattttaat agcccttaac atcaactttc tggtgcgatg cgcgcagcaa 31680
cgcattctga tttcactcaa atctttgcag taggtacaac acattattac aatattgttt 31740
aataaaccat aattaaaagc gctccagcca aaactcatat ctgatataat cgcccctgca 31800
tgaccatcat accaaagttt aatataaatt aaatgacgtt ccctcaaaaa cacactaccc 31860
acatacatga tctcttttgg catgtgcata ttaacaatct gtctgtacca tggacaacgt 31920
tggttaatca tgcaacccaa tataaccttc cggaaccaca ctgccaacac cgctccccca 31980
gccatgcatt gaagtgaacc ctgctgatta caatgacaat gaagaaccca attctctcga 32040
ccgtgaatca cttgagaatg aaaaatatct atagtggcac aacatagaca taaatgcatg 32100
catcttctca taatttttaa ctcctcagga tttagaaaca tatcccaggg aataggaagc 32160
tcttgcagaa cagtaaagct ggcagaacaa ggaagaccac gaacacaact tacactatgc 32220
atagtcatag tatcacaatc tggcaacagc gggtggtctt cagtcataga agctcgggtt 32280
tcattttcct cacaacgtgg taactgggct ctggtgtaag ggtgatgtct ggcgcatgat 32340
gtcgagcgtg cgcgcaacct tgtcataatg gagttgcttc ctgacattct cgtattttgt 32400
atagcaaaac gcggccctgg cagaacacac tcttcttcgc cttctatcct gccgcttagc 32460
gtgttccgtg tgatagttca agtacaacca cactcttaag ttggtcaaaa gaatgctggc 32520
ttcagttgta atcaaaactc catcgcatct aatcgttctg aggaaatcat ccaagcaatg 32580
caactggatt gtgtttcaag caggagagga gagggaagag acggaagaac catgttaatt 32640
tttattccaa acgatctcgc agtacttcaa attgtagatc gcgcagatgg catctctcgc 32700
ccccactgtg ttggtgaaaa agcacagcta gatcaaaaga aatgcgattt tcaaggtgct 32760
caacggtggc ttccagcaaa gcctccacgc gcacatccaa gaacaaaaga ataccaaaag 32820
aaggagcatt ttctaactcc tcaatcatca tattacattc ctgcaccatt cccagataat 32880
tttcagcttt ccagccttga attattcgtg tcagttcttg tggtaaatcc aatccacaca 32940
ttacaaacag gtcccggagg gcgccctcca ccaccattct taaacacacc ctcataatga 33000
caaaatatct tgctcctgtg tcacctgtag cgaattgaga atggcaacat caattgacat 33060
gcccttggct ctaagttctt ctttaagttc tagttgtaaa aactctctca tattatcacc 33120
aaactgctta gccagaagcc ccccgggaac aagagcaggg gacgctacag tgcagtacaa 33180
gcgcagacct ccccaattgg ctccagcaaa aacaagattg gaataagcat attgggaacc 33240
gccagtaata tcatcgaagt tgctggaaat ataatcaggc agagtttctt gtaaaaattg 33300
aataaaagaa aaatttgcca aaaaaacatt caaaacctct gggatgcaaa tgcaataggt 33360
taccgcgctg cgctccaaca ttgttagttt tgaattagtc tgcaaaaata aaaaaaaaaa 33420
caagcgtcat atcatagtag cctgacgaac agatggataa atcagtcttt ccatcacaag 33480
acaagccaca gggtctccag ctcgaccctc gtaaaacctg tcatcatgat taaacaacag 33540
caccgaaagt tcctcgcggt gaccagcatg aataattctt gatgaagcat acaatccaga 33600
catgttagca tcagttaacg agaaaaaaca gccaacatag cctttgggta taattatgct 33660
taatcgtaag tatagcaaag ccacccctcg cggatacaaa gtaaaaggca caggagaata 33720
aaaaatataa ttatttctct gctgctgttc aggcaacgtc gcccccggtc cctctaaata 33780
cacatacaaa gcctcatcag ccatggctta ccagacaaag tacagcgggc acacaaagca 33840
caagctctaa agtgactctc caacctctcc acaatatata tatacacaag ccctaaactg 33900
acgtaatggg agtaaagtgt aaaaaatccc gccaaaccca acacacaccc cgaaactgcg 33960
tcaccaggga aaagtacagt ttcacttccg caatcccaac aggcgtaact tcctctttct 34020
cacggtacgt gatatcccac taacttgcaa cgtcattttc ccacggtcgc accgcccctt 34080
ttagccgtta accccacagc caatcaccac acgatccaca ctttttaaaa tcacctcatt 34140
tacatattgg caccattcca tctataaggt atattatata gataga 34186
<210> 68
<211> 1551
<212> DNA
<213> 人工序列
<220>
<223> FAP BiTE核酸序列(OKT3)
<400> 68
atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt ccattcggac 60
atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg ggcgactatc 120
aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta cctggcctgg 180
tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc cacccgcgaa 240
agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac tctgaccatt 300
agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt ctcctatccg 360
ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag cgggggaggc 420
ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga agtcaagaag 480
ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac tgagtacacg 540
atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg gatcaaccca 600
aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat caccgtggat 660
acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga caccgcggtc 720
tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc gatggattac 780
tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca ggtgcagctg 840
cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc ctgcaaggct 900
tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc tggacagggt 960
ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa tcagaagttc 1020
aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat gcaactgagc 1080
agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga tgatcattac 1140
tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg cggtggctcg 1200
ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc tccagcaatc 1260
atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc aagtgtaagt 1320
tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat ttatgacaca 1380
tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg gacctcttac 1440
tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg ccagcagtgg 1500
agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg g 1551
<210> 69
<211> 1557
<212> DNA
<213> 人工序列
<220>
<223> FAP BiTE核酸序列(aCD3)
<400> 69
atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt ccattcggac 60
atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg ggcgactatc 120
aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta cctggcctgg 180
tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc cacccgcgaa 240
agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac tctgaccatt 300
agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt ctcctatccg 360
ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag cgggggaggc 420
ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga agtcaagaag 480
ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac tgagtacacg 540
atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg gatcaaccca 600
aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat caccgtggat 660
acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga caccgcggtc 720
tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc gatggattac 780
tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaga tgtgcaactc 840
gtgcagtccg gtgcggaagt gaaaaagccg ggcgcgagcg tcaaagtgtc atgcaaggcg 900
tcaggatata cgtttactag atacactatg cactgggtgc gccaggcacc tggtcagggc 960
cttgaatgga tcggctacat caatccgtcg agaggctaca ctaattacgc ggactcagtc 1020
aaagggcgct tcacgattac gaccgacaag tccacctcga ctgcatacat ggaactgtcc 1080
tcgctgagaa gcgaggacac cgctacttac tactgcgcta gatactacga tgatcactac 1140
tgcctcgatt actggggcca gggaaccact gtcacggtgt catcgggaga gggcacctca 1200
accggatcag ggggatcggg aggctcgggc ggcgcagacg acatcgtcct gacccagtcg 1260
cccgccacct tgtcgctgtc cccaggagaa agagcgaccc tgtcatgccg ggcgtcgcaa 1320
agcgtgagct atatgaattg gtatcagcag aagccaggaa aggcgccgaa gagatggatc 1380
tacgacacct ccaaggtcgc ttcaggtgtc ccggctagat tctcaggatc gggatcagga 1440
acggactact ccctgaccat caattcactg gaagcagaag atgcggccac ctactactgt 1500
cagcagtggt cctccaaccc gctgactttc ggaggcggaa ctaaggtcga gatcaag 1557
<210> 70
<211> 1856
<212> DNA
<213> 人工序列
<220>
<223> NG-611转基因盒
<400> 70
caggcccacc atgggatgga gctgcatcat cctattcctc gtggcgacgg ccactggagt 60
gcatagcgaa ctggtgatga ctcagtcccc gtcatccctg acggtgaccg ccggcgagaa 120
ggtcaccatg tcgtgcaagt cctcgcaaag cctgcttaac agcggcaacc agaaaaacta 180
cctcacgtgg tatcagcaaa agccaggtca acccccaaaa ctgctcatct actgggcgag 240
cacccgcgag tcgggggtgc cagaccggtt caccggctcc gggtcaggaa ctgatttcac 300
cctaaccatc agctcggtgc aagcggagga cctggccgtg tactactgcc aaaatgatta 360
ctcgtaccct ctgacctttg gagcgggcac caagctcgaa atcaagggcg gtggaggaag 420
cggcggggga ggctcaggtg ggggaggatc agaagtccaa ctgctggagc agtcaggagc 480
cgaactggtc cgcccgggaa cctccgtcaa gatttcctgt aaggcttccg gctacgcttt 540
taccaattac tggctgggct gggtcaagca aagaccgggg catggcctgg agtggatcgg 600
cgacatcttc ccagggagcg gcaacatcca ctacaacgag aagttcaagg ggaaagcgac 660
tctgactgcc gacaaatcat ccagcaccgc ctacatgcag ctgtcgtcgc tcactttcga 720
agacagcgcg gtgtactttt gtgctcggct ccggaactgg gatgaaccaa tggactactg 780
gggacaagga actaccgtga ccgtctcctc cggcggcggt ggaagccagg tgcagctgca 840
gcagtctggg gctgaactgg caagacctgg ggcctcagtg aagatgtcct gcaaggcttc 900
tggctacacc tttactaggt acacgatgca ctgggtaaaa cagaggcctg gacagggtct 960
ggaatggatt ggatacatta atcctagccg tggttatact aattacaatc agaagttcaa 1020
ggacaaggcc acattgacta cagacaaatc ctccagcaca gcctacatgc aactgagcag 1080
cctgacatct gaggactctg cagtctatta ctgtgcaaga tattatgatg atcattactg 1140
ccttgactac tggggccaag gcaccactct cacagtctcc tcaggtggcg gtggctcggg 1200
cggtggtgga tctggtggcg gcggatctga tatcgtgctc actcagtctc cagcaatcat 1260
gtctgcatct ccaggggaga aggtcaccat gacctgcagt gccagctcaa gtgtaagtta 1320
catgaactgg taccagcaga agtcaggcac ctcccccaaa agatggattt atgacacatc 1380
caaactggct tctggagtcc ctgctcactt caggggcagt gggtctggga cctcttactc 1440
tctcacaatc agcggcatgg aggctgaaga tgctgccact tattactgcc agcagtggag 1500
tagtaaccca ttcacgttcg gctcggggac aaagttggaa ataaaccggc atcaccatca 1560
ccatcaccac catcaccatt aggctagctt gactgactga gatacagcgt accttcagct 1620
cacagacatg ataagataca ttgatgagtt tggacaaacc acaactagaa tgcagtgaaa 1680
aaaatgcttt atttgtgaaa tttgtgatgc tattgcttta tttgtaacca ttataagctg 1740
caataaacaa gttaacaaca acaattgcat tcattttatg tttcaggttc agggggaggt 1800
gtgggaggtt ttttaaagca agtaaaacct ctacaaatgt ggtagtcgtc agctat 1856
<210> 71
<211> 1868
<212> DNA
<213> 人工序列
<220>
<223> NG-612转基因盒
<400> 71
caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt 60
ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg 120
ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta 180
cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc 240
cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac 300
tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt 360
ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag 420
cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga 480
agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac 540
tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg 600
gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat 660
caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga 720
caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc 780
gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca 840
ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc 900
ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc 960
tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa 1020
tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat 1080
gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga 1140
tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg 1200
cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc 1260
tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc 1320
aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat 1380
ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg 1440
gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg 1500
ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg 1560
gcatcaccat caccatcacc accatcacca ttaggctagc ttgactgact gagatacagc 1620
gtaccttcag ctcacagaca tgataagata cattgatgag tttggacaaa ccacaactag 1680
aatgcagtga aaaaaatgct ttatttgtga aatttgtgat gctattgctt tatttgtaac 1740
cattataagc tgcaataaac aagttaacaa caacaattgc attcatttta tgtttcaggt 1800
tcagggggag gtgtgggagg ttttttaaag caagtaaaac ctctacaaat gtggtagtcg 1860
tcagctat 1868
<210> 72
<211> 1878
<212> DNA
<213> 人工序列
<220>
<223> NG-613转基因盒
<400> 72
tttctctctt caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg 60
ctaccggagt ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac 120
tgggagagcg ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc 180
agaaaaacta cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct 240
tctgggcctc cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa 300
ctgactttac tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc 360
agcagtattt ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag 420
ggggcggcag cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat 480
ccggagccga agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct 540
acaccttcac tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt 600
ggatcggcgg gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc 660
gggtgactat caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca 720
gatcggagga caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg 780
aaggacatgc gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg 840
gcggttcaca ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag 900
tgaagatgtc ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa 960
aacagaggcc tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata 1020
ctaattacaa tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca 1080
cagcctacat gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa 1140
gatattatga tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct 1200
cctcaggtgg cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc 1260
tcactcagtc tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca 1320
gtgccagctc aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca 1380
aaagatggat ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca 1440
gtgggtctgg gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca 1500
cttattactg ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg 1560
aaataaaccg gcatcaccat caccatcacc accatcacca ttaggctagc ttgactgact 1620
gagatacagc gtaccttcag ctcacagaca tgataagata cattgatgag tttggacaaa 1680
ccacaactag aatgcagtga aaaaaatgct ttatttgtga aatttgtgat gctattgctt 1740
tatttgtaac cattataagc tgcaataaac aagttaacaa caacaattgc attcatttta 1800
tgtttcaggt tcagggggag gtgtgggagg ttttttaaag caagtaaaac ctctacaaat 1860
gtggtagtcg tcagctat 1878
<210> 73
<211> 1884
<212> DNA
<213> 人工序列
<220>
<223> NG-614转基因盒
<400> 73
tttctctctt caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg 60
ctaccggagt ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac 120
tgggagagcg ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc 180
agaaaaacta cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct 240
tctgggcctc cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa 300
ctgactttac tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc 360
agcagtattt ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag 420
ggggcggcag cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat 480
ccggagccga agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct 540
acaccttcac tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt 600
ggatcggcgg gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc 660
gggtgactat caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca 720
gatcggagga caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg 780
aaggacatgc gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg 840
gcggttcaga tgtgcaactc gtgcagtccg gtgcggaagt gaaaaagccg ggcgcgagcg 900
tcaaagtgtc atgcaaggcg tcaggatata cgtttactag atacactatg cactgggtgc 960
gccaggcacc tggtcagggc cttgaatgga tcggctacat caatccgtcg agaggctaca 1020
ctaattacgc ggactcagtc aaagggcgct tcacgattac gaccgacaag tccacctcga 1080
ctgcatacat ggaactgtcc tcgctgagaa gcgaggacac cgctacttac tactgcgcta 1140
gatactacga tgatcactac tgcctcgatt actggggcca gggaaccact gtcacggtgt 1200
catcgggaga gggcacctca accggatcag ggggatcggg aggctcgggc ggcgcagacg 1260
acatcgtcct gacccagtcg cccgccacct tgtcgctgtc cccaggagaa agagcgaccc 1320
tgtcatgccg ggcgtcgcaa agcgtgagct atatgaattg gtatcagcag aagccaggaa 1380
aggcgccgaa gagatggatc tacgacacct ccaaggtcgc ttcaggtgtc ccggctagat 1440
tctcaggatc gggatcagga acggactact ccctgaccat caattcactg gaagcagaag 1500
atgcggccac ctactactgt cagcagtggt cctccaaccc gctgactttc ggaggcggaa 1560
ctaaggtcga gatcaagcat caccatcacc atcaccacca tcaccattag gctagcttga 1620
ctgactgaga tacagcgtac cttcagctca cagacatgat aagatacatt gatgagtttg 1680
gacaaaccac aactagaatg cagtgaaaaa aatgctttat ttgtgaaatt tgtgatgcta 1740
ttgctttatt tgtaaccatt ataagctgca ataaacaagt taacaacaac aattgcattc 1800
attttatgtt tcaggttcag ggggaggtgt gggaggtttt ttaaagcaag taaaacctct 1860
acaaatgtgg tagtcgtcag ctat 1884
<210> 74
<211> 1838
<212> DNA
<213> 人工序列
<220>
<223> NG-617转基因盒
<400> 74
caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt 60
ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg 120
ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta 180
cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc 240
cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac 300
tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt 360
ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag 420
cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga 480
agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac 540
tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg 600
gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat 660
caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga 720
caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc 780
gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca 840
ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc 900
ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc 960
tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa 1020
tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat 1080
gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga 1140
tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg 1200
cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc 1260
tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc 1320
aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat 1380
ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg 1440
gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg 1500
ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg 1560
gtaggctagc ttgactgact gagatacagc gtaccttcag ctcacagaca tgataagata 1620
cattgatgag tttggacaaa ccacaactag aatgcagtga aaaaaatgct ttatttgtga 1680
aatttgtgat gctattgctt tatttgtaac cattataagc tgcaataaac aagttaacaa 1740
caacaattgc attcatttta tgtttcaggt tcagggggag gtgtgggagg ttttttaaag 1800
caagtaaaac ctctacaaat gtggtagtcg tcagctat 1838
<210> 75
<211> 517
<212> PRT
<213> 人工序列
<220>
<223> FAP BiTE氨基酸序列(OKT3)
<400> 75
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val
20 25 30
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu
35 40 45
Leu Tyr Ser Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu
65 70 75 80
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe
85 90 95
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
100 105 110
Cys Gln Gln Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
145 150 155 160
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe
165 170 175
Thr Glu Tyr Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
180 185 190
Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn
195 200 205
Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser
210 215 220
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
225 230 235 240
Tyr Tyr Cys Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His
245 250 255
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
260 265 270
Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala
275 280 285
Arg Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr
290 295 300
Phe Thr Arg Tyr Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly
305 310 315 320
Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr
325 330 335
Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser
340 345 350
Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala
355 360 365
Val Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr
370 375 380
Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser
385 390 395 400
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln
405 410 415
Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr
420 425 430
Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys
435 440 445
Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala
450 455 460
Ser Gly Val Pro Ala His Phe Arg Gly Ser Gly Ser Gly Thr Ser Tyr
465 470 475 480
Ser Leu Thr Ile Ser Gly Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr
485 490 495
Cys Gln Gln Trp Ser Ser Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys
500 505 510
Leu Glu Ile Asn Arg
515
<210> 76
<211> 519
<212> PRT
<213> 人工序列
<220>
<223> FAP BiTE氨基酸序列(aCD3)
<400> 76
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val
20 25 30
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu
35 40 45
Leu Tyr Ser Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys
50 55 60
Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu
65 70 75 80
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe
85 90 95
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
100 105 110
Cys Gln Gln Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
145 150 155 160
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe
165 170 175
Thr Glu Tyr Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
180 185 190
Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn
195 200 205
Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser
210 215 220
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
225 230 235 240
Tyr Tyr Cys Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His
245 250 255
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
260 265 270
Gly Gly Gly Ser Asp Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
275 280 285
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr
290 295 300
Phe Thr Arg Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly
305 310 315 320
Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr
325 330 335
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Thr Thr Asp Lys Ser Thr
340 345 350
Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala
355 360 365
Thr Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr
370 375 380
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Glu Gly Thr Ser
385 390 395 400
Thr Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ala Asp Asp Ile Val
405 410 415
Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
420 425 430
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Tyr Met Asn Trp Tyr
435 440 445
Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Trp Ile Tyr Asp Thr Ser
450 455 460
Lys Val Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly
465 470 475 480
Thr Asp Tyr Ser Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala
485 490 495
Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly
500 505 510
Gly Thr Lys Val Glu Ile Lys
515
<210> 77
<211> 34198
<212> DNA
<213> 人工序列
<220>
<223> NG-611基因组
<400> 77
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatggga tggagctgca tcatcctatt 29400
cctcgtggcg acggccactg gagtgcatag cgaactggtg atgactcagt ccccgtcatc 29460
cctgacggtg accgccggcg agaaggtcac catgtcgtgc aagtcctcgc aaagcctgct 29520
taacagcggc aaccagaaaa actacctcac gtggtatcag caaaagccag gtcaaccccc 29580
aaaactgctc atctactggg cgagcacccg cgagtcgggg gtgccagacc ggttcaccgg 29640
ctccgggtca ggaactgatt tcaccctaac catcagctcg gtgcaagcgg aggacctggc 29700
cgtgtactac tgccaaaatg attactcgta ccctctgacc tttggagcgg gcaccaagct 29760
cgaaatcaag ggcggtggag gaagcggcgg gggaggctca ggtgggggag gatcagaagt 29820
ccaactgctg gagcagtcag gagccgaact ggtccgcccg ggaacctccg tcaagatttc 29880
ctgtaaggct tccggctacg cttttaccaa ttactggctg ggctgggtca agcaaagacc 29940
ggggcatggc ctggagtgga tcggcgacat cttcccaggg agcggcaaca tccactacaa 30000
cgagaagttc aaggggaaag cgactctgac tgccgacaaa tcatccagca ccgcctacat 30060
gcagctgtcg tcgctcactt tcgaagacag cgcggtgtac ttttgtgctc ggctccggaa 30120
ctgggatgaa ccaatggact actggggaca aggaactacc gtgaccgtct cctccggcgg 30180
cggtggaagc caggtgcagc tgcagcagtc tggggctgaa ctggcaagac ctggggcctc 30240
agtgaagatg tcctgcaagg cttctggcta cacctttact aggtacacga tgcactgggt 30300
aaaacagagg cctggacagg gtctggaatg gattggatac attaatccta gccgtggtta 30360
tactaattac aatcagaagt tcaaggacaa ggccacattg actacagaca aatcctccag 30420
cacagcctac atgcaactga gcagcctgac atctgaggac tctgcagtct attactgtgc 30480
aagatattat gatgatcatt actgccttga ctactggggc caaggcacca ctctcacagt 30540
ctcctcaggt ggcggtggct cgggcggtgg tggatctggt ggcggcggat ctgatatcgt 30600
gctcactcag tctccagcaa tcatgtctgc atctccaggg gagaaggtca ccatgacctg 30660
cagtgccagc tcaagtgtaa gttacatgaa ctggtaccag cagaagtcag gcacctcccc 30720
caaaagatgg atttatgaca catccaaact ggcttctgga gtccctgctc acttcagggg 30780
cagtgggtct gggacctctt actctctcac aatcagcggc atggaggctg aagatgctgc 30840
cacttattac tgccagcagt ggagtagtaa cccattcacg ttcggctcgg ggacaaagtt 30900
ggaaataaac cggcatcacc atcaccatca ccaccatcac cattaggcta gcttgactga 30960
ctgagataca gcgtaccttc agctcacaga catgataaga tacattgatg agtttggaca 31020
aaccacaact agaatgcagt gaaaaaaatg ctttatttgt gaaatttgtg atgctattgc 31080
tttatttgta accattataa gctgcaataa acaagttaac aacaacaatt gcattcattt 31140
tatgtttcag gttcaggggg aggtgtggga ggttttttaa agcaagtaaa acctctacaa 31200
atgtggtagt cgtcagctat cctgcaggaa cttgtttatt tgaaaatcaa ttcacaaaat 31260
ccgagtagtt attttgcctc ccccttccca tttaacagaa tacaccaatc tctccccacg 31320
cacagcttta aacatttgga taccattaga tatagacatg gttttagatt ccacattcca 31380
aacagtttca gagcgagcca atctggggtc agtgatagat aaaaatccat cgggatagtc 31440
ttttaaagcg ctttcacagt ccaactgctg cggatgcgac tccggagtct ggatcacggt 31500
catctggaag aagaacgatg ggaatcataa tccgaaaacg gtatcggacg attgtgtctc 31560
atcaaaccca caagcagccg ctgtctgcgt cgctccgtgc gactgctgtt tatgggatca 31620
gggtccacag tgtcctgaag catgatttta atagccctta acatcaactt tctggtgcga 31680
tgcgcgcagc aacgcattct gatttcactc aaatctttgc agtaggtaca acacattatt 31740
acaatattgt ttaataaacc ataattaaaa gcgctccagc caaaactcat atctgatata 31800
atcgcccctg catgaccatc ataccaaagt ttaatataaa ttaaatgacg ttccctcaaa 31860
aacacactac ccacatacat gatctctttt ggcatgtgca tattaacaat ctgtctgtac 31920
catggacaac gttggttaat catgcaaccc aatataacct tccggaacca cactgccaac 31980
accgctcccc cagccatgca ttgaagtgaa ccctgctgat tacaatgaca atgaagaacc 32040
caattctctc gaccgtgaat cacttgagaa tgaaaaatat ctatagtggc acaacataga 32100
cataaatgca tgcatcttct cataattttt aactcctcag gatttagaaa catatcccag 32160
ggaataggaa gctcttgcag aacagtaaag ctggcagaac aaggaagacc acgaacacaa 32220
cttacactat gcatagtcat agtatcacaa tctggcaaca gcgggtggtc ttcagtcata 32280
gaagctcggg tttcattttc ctcacaacgt ggtaactggg ctctggtgta agggtgatgt 32340
ctggcgcatg atgtcgagcg tgcgcgcaac cttgtcataa tggagttgct tcctgacatt 32400
ctcgtatttt gtatagcaaa acgcggccct ggcagaacac actcttcttc gccttctatc 32460
ctgccgctta gcgtgttccg tgtgatagtt caagtacaac cacactctta agttggtcaa 32520
aagaatgctg gcttcagttg taatcaaaac tccatcgcat ctaatcgttc tgaggaaatc 32580
atccaagcaa tgcaactgga ttgtgtttca agcaggagag gagagggaag agacggaaga 32640
accatgttaa tttttattcc aaacgatctc gcagtacttc aaattgtaga tcgcgcagat 32700
ggcatctctc gcccccactg tgttggtgaa aaagcacagc tagatcaaaa gaaatgcgat 32760
tttcaaggtg ctcaacggtg gcttccagca aagcctccac gcgcacatcc aagaacaaaa 32820
gaataccaaa agaaggagca ttttctaact cctcaatcat catattacat tcctgcacca 32880
ttcccagata attttcagct ttccagcctt gaattattcg tgtcagttct tgtggtaaat 32940
ccaatccaca cattacaaac aggtcccgga gggcgccctc caccaccatt cttaaacaca 33000
ccctcataat gacaaaatat cttgctcctg tgtcacctgt agcgaattga gaatggcaac 33060
atcaattgac atgcccttgg ctctaagttc ttctttaagt tctagttgta aaaactctct 33120
catattatca ccaaactgct tagccagaag ccccccggga acaagagcag gggacgctac 33180
agtgcagtac aagcgcagac ctccccaatt ggctccagca aaaacaagat tggaataagc 33240
atattgggaa ccgccagtaa tatcatcgaa gttgctggaa atataatcag gcagagtttc 33300
ttgtaaaaat tgaataaaag aaaaatttgc caaaaaaaca ttcaaaacct ctgggatgca 33360
aatgcaatag gttaccgcgc tgcgctccaa cattgttagt tttgaattag tctgcaaaaa 33420
taaaaaaaaa aacaagcgtc atatcatagt agcctgacga acagatggat aaatcagtct 33480
ttccatcaca agacaagcca cagggtctcc agctcgaccc tcgtaaaacc tgtcatcatg 33540
attaaacaac agcaccgaaa gttcctcgcg gtgaccagca tgaataattc ttgatgaagc 33600
atacaatcca gacatgttag catcagttaa cgagaaaaaa cagccaacat agcctttggg 33660
tataattatg cttaatcgta agtatagcaa agccacccct cgcggataca aagtaaaagg 33720
cacaggagaa taaaaaatat aattatttct ctgctgctgt tcaggcaacg tcgcccccgg 33780
tccctctaaa tacacataca aagcctcatc agccatggct taccagacaa agtacagcgg 33840
gcacacaaag cacaagctct aaagtgactc tccaacctct ccacaatata tatatacaca 33900
agccctaaac tgacgtaatg ggagtaaagt gtaaaaaatc ccgccaaacc caacacacac 33960
cccgaaactg cgtcaccagg gaaaagtaca gtttcacttc cgcaatccca acaggcgtaa 34020
cttcctcttt ctcacggtac gtgatatccc actaacttgc aacgtcattt tcccacggtc 34080
gcaccgcccc ttttagccgt taaccccaca gccaatcacc acacgatcca cactttttaa 34140
aatcacctca tttacatatt ggcaccattc catctataag gtatattata tagataga 34198
<210> 78
<211> 34210
<212> DNA
<213> 人工序列
<220>
<223> NG-612基因组
<400> 78
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg aactggcaag 30240
acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta ctaggtacac 30300
gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat acattaatcc 30360
tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat tgactacaga 30420
caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg actctgcagt 30480
ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg gccaaggcac 30540
cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg gtggcggcgg 30600
atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag gggagaaggt 30660
caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc agcagaagtc 30720
aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg gagtccctgc 30780
tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg gcatggaggc 30840
tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca cgttcggctc 30900
ggggacaaag ttggaaataa accggcatca ccatcaccat caccaccatc accattaggc 30960
tagcttgact gactgagata cagcgtacct tcagctcaca gacatgataa gatacattga 31020
tgagtttgga caaaccacaa ctagaatgca gtgaaaaaaa tgctttattt gtgaaatttg 31080
tgatgctatt gctttatttg taaccattat aagctgcaat aaacaagtta acaacaacaa 31140
ttgcattcat tttatgtttc aggttcaggg ggaggtgtgg gaggtttttt aaagcaagta 31200
aaacctctac aaatgtggta gtcgtcagct atcctgcagg aacttgttta tttgaaaatc 31260
aattcacaaa atccgagtag ttattttgcc tcccccttcc catttaacag aatacaccaa 31320
tctctcccca cgcacagctt taaacatttg gataccatta gatatagaca tggttttaga 31380
ttccacattc caaacagttt cagagcgagc caatctgggg tcagtgatag ataaaaatcc 31440
atcgggatag tcttttaaag cgctttcaca gtccaactgc tgcggatgcg actccggagt 31500
ctggatcacg gtcatctgga agaagaacga tgggaatcat aatccgaaaa cggtatcgga 31560
cgattgtgtc tcatcaaacc cacaagcagc cgctgtctgc gtcgctccgt gcgactgctg 31620
tttatgggat cagggtccac agtgtcctga agcatgattt taatagccct taacatcaac 31680
tttctggtgc gatgcgcgca gcaacgcatt ctgatttcac tcaaatcttt gcagtaggta 31740
caacacatta ttacaatatt gtttaataaa ccataattaa aagcgctcca gccaaaactc 31800
atatctgata taatcgcccc tgcatgacca tcataccaaa gtttaatata aattaaatga 31860
cgttccctca aaaacacact acccacatac atgatctctt ttggcatgtg catattaaca 31920
atctgtctgt accatggaca acgttggtta atcatgcaac ccaatataac cttccggaac 31980
cacactgcca acaccgctcc cccagccatg cattgaagtg aaccctgctg attacaatga 32040
caatgaagaa cccaattctc tcgaccgtga atcacttgag aatgaaaaat atctatagtg 32100
gcacaacata gacataaatg catgcatctt ctcataattt ttaactcctc aggatttaga 32160
aacatatccc agggaatagg aagctcttgc agaacagtaa agctggcaga acaaggaaga 32220
ccacgaacac aacttacact atgcatagtc atagtatcac aatctggcaa cagcgggtgg 32280
tcttcagtca tagaagctcg ggtttcattt tcctcacaac gtggtaactg ggctctggtg 32340
taagggtgat gtctggcgca tgatgtcgag cgtgcgcgca accttgtcat aatggagttg 32400
cttcctgaca ttctcgtatt ttgtatagca aaacgcggcc ctggcagaac acactcttct 32460
tcgccttcta tcctgccgct tagcgtgttc cgtgtgatag ttcaagtaca accacactct 32520
taagttggtc aaaagaatgc tggcttcagt tgtaatcaaa actccatcgc atctaatcgt 32580
tctgaggaaa tcatccaagc aatgcaactg gattgtgttt caagcaggag aggagaggga 32640
agagacggaa gaaccatgtt aatttttatt ccaaacgatc tcgcagtact tcaaattgta 32700
gatcgcgcag atggcatctc tcgcccccac tgtgttggtg aaaaagcaca gctagatcaa 32760
aagaaatgcg attttcaagg tgctcaacgg tggcttccag caaagcctcc acgcgcacat 32820
ccaagaacaa aagaatacca aaagaaggag cattttctaa ctcctcaatc atcatattac 32880
attcctgcac cattcccaga taattttcag ctttccagcc ttgaattatt cgtgtcagtt 32940
cttgtggtaa atccaatcca cacattacaa acaggtcccg gagggcgccc tccaccacca 33000
ttcttaaaca caccctcata atgacaaaat atcttgctcc tgtgtcacct gtagcgaatt 33060
gagaatggca acatcaattg acatgccctt ggctctaagt tcttctttaa gttctagttg 33120
taaaaactct ctcatattat caccaaactg cttagccaga agccccccgg gaacaagagc 33180
aggggacgct acagtgcagt acaagcgcag acctccccaa ttggctccag caaaaacaag 33240
attggaataa gcatattggg aaccgccagt aatatcatcg aagttgctgg aaatataatc 33300
aggcagagtt tcttgtaaaa attgaataaa agaaaaattt gccaaaaaaa cattcaaaac 33360
ctctgggatg caaatgcaat aggttaccgc gctgcgctcc aacattgtta gttttgaatt 33420
agtctgcaaa aataaaaaaa aaaacaagcg tcatatcata gtagcctgac gaacagatgg 33480
ataaatcagt ctttccatca caagacaagc cacagggtct ccagctcgac cctcgtaaaa 33540
cctgtcatca tgattaaaca acagcaccga aagttcctcg cggtgaccag catgaataat 33600
tcttgatgaa gcatacaatc cagacatgtt agcatcagtt aacgagaaaa aacagccaac 33660
atagcctttg ggtataatta tgcttaatcg taagtatagc aaagccaccc ctcgcggata 33720
caaagtaaaa ggcacaggag aataaaaaat ataattattt ctctgctgct gttcaggcaa 33780
cgtcgccccc ggtccctcta aatacacata caaagcctca tcagccatgg cttaccagac 33840
aaagtacagc gggcacacaa agcacaagct ctaaagtgac tctccaacct ctccacaata 33900
tatatataca caagccctaa actgacgtaa tgggagtaaa gtgtaaaaaa tcccgccaaa 33960
cccaacacac accccgaaac tgcgtcacca gggaaaagta cagtttcact tccgcaatcc 34020
caacaggcgt aacttcctct ttctcacggt acgtgatatc ccactaactt gcaacgtcat 34080
tttcccacgg tcgcaccgcc ccttttagcc gttaacccca cagccaatca ccacacgatc 34140
cacacttttt aaaatcacct catttacata ttggcaccat tccatctata aggtatatta 34200
tatagataga 34210
<210> 79
<211> 34220
<212> DNA
<213> 人工序列
<220>
<223> NG-613基因组
<400> 79
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgctttctc tcttcaggcc caccatgggc tggagctgca 29400
tcatcttgtt cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa 29460
gccctgactc gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc 29520
agagcctgct gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg 29580
gccagcctcc caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc 29640
gcttcagcgg aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg 29700
aggacgtggc cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag 29760
gcaccaaggt ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg 29820
gatcgcaggt ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca 29880
aggtcagctg caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc 29940
aggcgcccgg ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa 30000
attacaatca gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg 30060
cgtacatgga gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc 30120
gccggatcgc ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc 30180
tcgtcacggt gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg 30240
aactggcaag acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta 30300
ctaggtacac gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat 30360
acattaatcc tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat 30420
tgactacaga caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg 30480
actctgcagt ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg 30540
gccaaggcac cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg 30600
gtggcggcgg atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag 30660
gggagaaggt caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc 30720
agcagaagtc aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg 30780
gagtccctgc tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg 30840
gcatggaggc tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca 30900
cgttcggctc ggggacaaag ttggaaataa accggcatca ccatcaccat caccaccatc 30960
accattaggc tagcttgact gactgagata cagcgtacct tcagctcaca gacatgataa 31020
gatacattga tgagtttgga caaaccacaa ctagaatgca gtgaaaaaaa tgctttattt 31080
gtgaaatttg tgatgctatt gctttatttg taaccattat aagctgcaat aaacaagtta 31140
acaacaacaa ttgcattcat tttatgtttc aggttcaggg ggaggtgtgg gaggtttttt 31200
aaagcaagta aaacctctac aaatgtggta gtcgtcagct atcctgcagg aacttgttta 31260
tttgaaaatc aattcacaaa atccgagtag ttattttgcc tcccccttcc catttaacag 31320
aatacaccaa tctctcccca cgcacagctt taaacatttg gataccatta gatatagaca 31380
tggttttaga ttccacattc caaacagttt cagagcgagc caatctgggg tcagtgatag 31440
ataaaaatcc atcgggatag tcttttaaag cgctttcaca gtccaactgc tgcggatgcg 31500
actccggagt ctggatcacg gtcatctgga agaagaacga tgggaatcat aatccgaaaa 31560
cggtatcgga cgattgtgtc tcatcaaacc cacaagcagc cgctgtctgc gtcgctccgt 31620
gcgactgctg tttatgggat cagggtccac agtgtcctga agcatgattt taatagccct 31680
taacatcaac tttctggtgc gatgcgcgca gcaacgcatt ctgatttcac tcaaatcttt 31740
gcagtaggta caacacatta ttacaatatt gtttaataaa ccataattaa aagcgctcca 31800
gccaaaactc atatctgata taatcgcccc tgcatgacca tcataccaaa gtttaatata 31860
aattaaatga cgttccctca aaaacacact acccacatac atgatctctt ttggcatgtg 31920
catattaaca atctgtctgt accatggaca acgttggtta atcatgcaac ccaatataac 31980
cttccggaac cacactgcca acaccgctcc cccagccatg cattgaagtg aaccctgctg 32040
attacaatga caatgaagaa cccaattctc tcgaccgtga atcacttgag aatgaaaaat 32100
atctatagtg gcacaacata gacataaatg catgcatctt ctcataattt ttaactcctc 32160
aggatttaga aacatatccc agggaatagg aagctcttgc agaacagtaa agctggcaga 32220
acaaggaaga ccacgaacac aacttacact atgcatagtc atagtatcac aatctggcaa 32280
cagcgggtgg tcttcagtca tagaagctcg ggtttcattt tcctcacaac gtggtaactg 32340
ggctctggtg taagggtgat gtctggcgca tgatgtcgag cgtgcgcgca accttgtcat 32400
aatggagttg cttcctgaca ttctcgtatt ttgtatagca aaacgcggcc ctggcagaac 32460
acactcttct tcgccttcta tcctgccgct tagcgtgttc cgtgtgatag ttcaagtaca 32520
accacactct taagttggtc aaaagaatgc tggcttcagt tgtaatcaaa actccatcgc 32580
atctaatcgt tctgaggaaa tcatccaagc aatgcaactg gattgtgttt caagcaggag 32640
aggagaggga agagacggaa gaaccatgtt aatttttatt ccaaacgatc tcgcagtact 32700
tcaaattgta gatcgcgcag atggcatctc tcgcccccac tgtgttggtg aaaaagcaca 32760
gctagatcaa aagaaatgcg attttcaagg tgctcaacgg tggcttccag caaagcctcc 32820
acgcgcacat ccaagaacaa aagaatacca aaagaaggag cattttctaa ctcctcaatc 32880
atcatattac attcctgcac cattcccaga taattttcag ctttccagcc ttgaattatt 32940
cgtgtcagtt cttgtggtaa atccaatcca cacattacaa acaggtcccg gagggcgccc 33000
tccaccacca ttcttaaaca caccctcata atgacaaaat atcttgctcc tgtgtcacct 33060
gtagcgaatt gagaatggca acatcaattg acatgccctt ggctctaagt tcttctttaa 33120
gttctagttg taaaaactct ctcatattat caccaaactg cttagccaga agccccccgg 33180
gaacaagagc aggggacgct acagtgcagt acaagcgcag acctccccaa ttggctccag 33240
caaaaacaag attggaataa gcatattggg aaccgccagt aatatcatcg aagttgctgg 33300
aaatataatc aggcagagtt tcttgtaaaa attgaataaa agaaaaattt gccaaaaaaa 33360
cattcaaaac ctctgggatg caaatgcaat aggttaccgc gctgcgctcc aacattgtta 33420
gttttgaatt agtctgcaaa aataaaaaaa aaaacaagcg tcatatcata gtagcctgac 33480
gaacagatgg ataaatcagt ctttccatca caagacaagc cacagggtct ccagctcgac 33540
cctcgtaaaa cctgtcatca tgattaaaca acagcaccga aagttcctcg cggtgaccag 33600
catgaataat tcttgatgaa gcatacaatc cagacatgtt agcatcagtt aacgagaaaa 33660
aacagccaac atagcctttg ggtataatta tgcttaatcg taagtatagc aaagccaccc 33720
ctcgcggata caaagtaaaa ggcacaggag aataaaaaat ataattattt ctctgctgct 33780
gttcaggcaa cgtcgccccc ggtccctcta aatacacata caaagcctca tcagccatgg 33840
cttaccagac aaagtacagc gggcacacaa agcacaagct ctaaagtgac tctccaacct 33900
ctccacaata tatatataca caagccctaa actgacgtaa tgggagtaaa gtgtaaaaaa 33960
tcccgccaaa cccaacacac accccgaaac tgcgtcacca gggaaaagta cagtttcact 34020
tccgcaatcc caacaggcgt aacttcctct ttctcacggt acgtgatatc ccactaactt 34080
gcaacgtcat tttcccacgg tcgcaccgcc ccttttagcc gttaacccca cagccaatca 34140
ccacacgatc cacacttttt aaaatcacct catttacata ttggcaccat tccatctata 34200
aggtatatta tatagataga 34220
<210> 80
<211> 34226
<212> DNA
<213> 人工序列
<220>
<223> NG-614基因组
<400> 80
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgctttctc tcttcaggcc caccatgggc tggagctgca 29400
tcatcttgtt cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa 29460
gccctgactc gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc 29520
agagcctgct gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg 29580
gccagcctcc caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc 29640
gcttcagcgg aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg 29700
aggacgtggc cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag 29760
gcaccaaggt ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg 29820
gatcgcaggt ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca 29880
aggtcagctg caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc 29940
aggcgcccgg ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa 30000
attacaatca gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg 30060
cgtacatgga gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc 30120
gccggatcgc ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc 30180
tcgtcacggt gtcgtcagga ggcggcggtt cagatgtgca actcgtgcag tccggtgcgg 30240
aagtgaaaaa gccgggcgcg agcgtcaaag tgtcatgcaa ggcgtcagga tatacgttta 30300
ctagatacac tatgcactgg gtgcgccagg cacctggtca gggccttgaa tggatcggct 30360
acatcaatcc gtcgagaggc tacactaatt acgcggactc agtcaaaggg cgcttcacga 30420
ttacgaccga caagtccacc tcgactgcat acatggaact gtcctcgctg agaagcgagg 30480
acaccgctac ttactactgc gctagatact acgatgatca ctactgcctc gattactggg 30540
gccagggaac cactgtcacg gtgtcatcgg gagagggcac ctcaaccgga tcagggggat 30600
cgggaggctc gggcggcgca gacgacatcg tcctgaccca gtcgcccgcc accttgtcgc 30660
tgtccccagg agaaagagcg accctgtcat gccgggcgtc gcaaagcgtg agctatatga 30720
attggtatca gcagaagcca ggaaaggcgc cgaagagatg gatctacgac acctccaagg 30780
tcgcttcagg tgtcccggct agattctcag gatcgggatc aggaacggac tactccctga 30840
ccatcaattc actggaagca gaagatgcgg ccacctacta ctgtcagcag tggtcctcca 30900
acccgctgac tttcggaggc ggaactaagg tcgagatcaa gcatcaccat caccatcacc 30960
accatcacca ttaggctagc ttgactgact gagatacagc gtaccttcag ctcacagaca 31020
tgataagata cattgatgag tttggacaaa ccacaactag aatgcagtga aaaaaatgct 31080
ttatttgtga aatttgtgat gctattgctt tatttgtaac cattataagc tgcaataaac 31140
aagttaacaa caacaattgc attcatttta tgtttcaggt tcagggggag gtgtgggagg 31200
ttttttaaag caagtaaaac ctctacaaat gtggtagtcg tcagctatcc tgcaggaact 31260
tgtttatttg aaaatcaatt cacaaaatcc gagtagttat tttgcctccc ccttcccatt 31320
taacagaata caccaatctc tccccacgca cagctttaaa catttggata ccattagata 31380
tagacatggt tttagattcc acattccaaa cagtttcaga gcgagccaat ctggggtcag 31440
tgatagataa aaatccatcg ggatagtctt ttaaagcgct ttcacagtcc aactgctgcg 31500
gatgcgactc cggagtctgg atcacggtca tctggaagaa gaacgatggg aatcataatc 31560
cgaaaacggt atcggacgat tgtgtctcat caaacccaca agcagccgct gtctgcgtcg 31620
ctccgtgcga ctgctgttta tgggatcagg gtccacagtg tcctgaagca tgattttaat 31680
agcccttaac atcaactttc tggtgcgatg cgcgcagcaa cgcattctga tttcactcaa 31740
atctttgcag taggtacaac acattattac aatattgttt aataaaccat aattaaaagc 31800
gctccagcca aaactcatat ctgatataat cgcccctgca tgaccatcat accaaagttt 31860
aatataaatt aaatgacgtt ccctcaaaaa cacactaccc acatacatga tctcttttgg 31920
catgtgcata ttaacaatct gtctgtacca tggacaacgt tggttaatca tgcaacccaa 31980
tataaccttc cggaaccaca ctgccaacac cgctccccca gccatgcatt gaagtgaacc 32040
ctgctgatta caatgacaat gaagaaccca attctctcga ccgtgaatca cttgagaatg 32100
aaaaatatct atagtggcac aacatagaca taaatgcatg catcttctca taatttttaa 32160
ctcctcagga tttagaaaca tatcccaggg aataggaagc tcttgcagaa cagtaaagct 32220
ggcagaacaa ggaagaccac gaacacaact tacactatgc atagtcatag tatcacaatc 32280
tggcaacagc gggtggtctt cagtcataga agctcgggtt tcattttcct cacaacgtgg 32340
taactgggct ctggtgtaag ggtgatgtct ggcgcatgat gtcgagcgtg cgcgcaacct 32400
tgtcataatg gagttgcttc ctgacattct cgtattttgt atagcaaaac gcggccctgg 32460
cagaacacac tcttcttcgc cttctatcct gccgcttagc gtgttccgtg tgatagttca 32520
agtacaacca cactcttaag ttggtcaaaa gaatgctggc ttcagttgta atcaaaactc 32580
catcgcatct aatcgttctg aggaaatcat ccaagcaatg caactggatt gtgtttcaag 32640
caggagagga gagggaagag acggaagaac catgttaatt tttattccaa acgatctcgc 32700
agtacttcaa attgtagatc gcgcagatgg catctctcgc ccccactgtg ttggtgaaaa 32760
agcacagcta gatcaaaaga aatgcgattt tcaaggtgct caacggtggc ttccagcaaa 32820
gcctccacgc gcacatccaa gaacaaaaga ataccaaaag aaggagcatt ttctaactcc 32880
tcaatcatca tattacattc ctgcaccatt cccagataat tttcagcttt ccagccttga 32940
attattcgtg tcagttcttg tggtaaatcc aatccacaca ttacaaacag gtcccggagg 33000
gcgccctcca ccaccattct taaacacacc ctcataatga caaaatatct tgctcctgtg 33060
tcacctgtag cgaattgaga atggcaacat caattgacat gcccttggct ctaagttctt 33120
ctttaagttc tagttgtaaa aactctctca tattatcacc aaactgctta gccagaagcc 33180
ccccgggaac aagagcaggg gacgctacag tgcagtacaa gcgcagacct ccccaattgg 33240
ctccagcaaa aacaagattg gaataagcat attgggaacc gccagtaata tcatcgaagt 33300
tgctggaaat ataatcaggc agagtttctt gtaaaaattg aataaaagaa aaatttgcca 33360
aaaaaacatt caaaacctct gggatgcaaa tgcaataggt taccgcgctg cgctccaaca 33420
ttgttagttt tgaattagtc tgcaaaaata aaaaaaaaaa caagcgtcat atcatagtag 33480
cctgacgaac agatggataa atcagtcttt ccatcacaag acaagccaca gggtctccag 33540
ctcgaccctc gtaaaacctg tcatcatgat taaacaacag caccgaaagt tcctcgcggt 33600
gaccagcatg aataattctt gatgaagcat acaatccaga catgttagca tcagttaacg 33660
agaaaaaaca gccaacatag cctttgggta taattatgct taatcgtaag tatagcaaag 33720
ccacccctcg cggatacaaa gtaaaaggca caggagaata aaaaatataa ttatttctct 33780
gctgctgttc aggcaacgtc gcccccggtc cctctaaata cacatacaaa gcctcatcag 33840
ccatggctta ccagacaaag tacagcgggc acacaaagca caagctctaa agtgactctc 33900
caacctctcc acaatatata tatacacaag ccctaaactg acgtaatggg agtaaagtgt 33960
aaaaaatccc gccaaaccca acacacaccc cgaaactgcg tcaccaggga aaagtacagt 34020
ttcacttccg caatcccaac aggcgtaact tcctctttct cacggtacgt gatatcccac 34080
taacttgcaa cgtcattttc ccacggtcgc accgcccctt ttagccgtta accccacagc 34140
caatcaccac acgatccaca ctttttaaaa tcacctcatt tacatattgg caccattcca 34200
tctataaggt atattatata gataga 34226
<210> 81
<211> 34180
<212> DNA
<213> 人工序列
<220>
<223> NG-617基因组
<400> 81
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg aactggcaag 30240
acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta ctaggtacac 30300
gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat acattaatcc 30360
tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat tgactacaga 30420
caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg actctgcagt 30480
ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg gccaaggcac 30540
cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg gtggcggcgg 30600
atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag gggagaaggt 30660
caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc agcagaagtc 30720
aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg gagtccctgc 30780
tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg gcatggaggc 30840
tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca cgttcggctc 30900
ggggacaaag ttggaaataa accggtaggc tagcttgact gactgagata cagcgtacct 30960
tcagctcaca gacatgataa gatacattga tgagtttgga caaaccacaa ctagaatgca 31020
gtgaaaaaaa tgctttattt gtgaaatttg tgatgctatt gctttatttg taaccattat 31080
aagctgcaat aaacaagtta acaacaacaa ttgcattcat tttatgtttc aggttcaggg 31140
ggaggtgtgg gaggtttttt aaagcaagta aaacctctac aaatgtggta gtcgtcagct 31200
atcctgcagg aacttgttta tttgaaaatc aattcacaaa atccgagtag ttattttgcc 31260
tcccccttcc catttaacag aatacaccaa tctctcccca cgcacagctt taaacatttg 31320
gataccatta gatatagaca tggttttaga ttccacattc caaacagttt cagagcgagc 31380
caatctgggg tcagtgatag ataaaaatcc atcgggatag tcttttaaag cgctttcaca 31440
gtccaactgc tgcggatgcg actccggagt ctggatcacg gtcatctgga agaagaacga 31500
tgggaatcat aatccgaaaa cggtatcgga cgattgtgtc tcatcaaacc cacaagcagc 31560
cgctgtctgc gtcgctccgt gcgactgctg tttatgggat cagggtccac agtgtcctga 31620
agcatgattt taatagccct taacatcaac tttctggtgc gatgcgcgca gcaacgcatt 31680
ctgatttcac tcaaatcttt gcagtaggta caacacatta ttacaatatt gtttaataaa 31740
ccataattaa aagcgctcca gccaaaactc atatctgata taatcgcccc tgcatgacca 31800
tcataccaaa gtttaatata aattaaatga cgttccctca aaaacacact acccacatac 31860
atgatctctt ttggcatgtg catattaaca atctgtctgt accatggaca acgttggtta 31920
atcatgcaac ccaatataac cttccggaac cacactgcca acaccgctcc cccagccatg 31980
cattgaagtg aaccctgctg attacaatga caatgaagaa cccaattctc tcgaccgtga 32040
atcacttgag aatgaaaaat atctatagtg gcacaacata gacataaatg catgcatctt 32100
ctcataattt ttaactcctc aggatttaga aacatatccc agggaatagg aagctcttgc 32160
agaacagtaa agctggcaga acaaggaaga ccacgaacac aacttacact atgcatagtc 32220
atagtatcac aatctggcaa cagcgggtgg tcttcagtca tagaagctcg ggtttcattt 32280
tcctcacaac gtggtaactg ggctctggtg taagggtgat gtctggcgca tgatgtcgag 32340
cgtgcgcgca accttgtcat aatggagttg cttcctgaca ttctcgtatt ttgtatagca 32400
aaacgcggcc ctggcagaac acactcttct tcgccttcta tcctgccgct tagcgtgttc 32460
cgtgtgatag ttcaagtaca accacactct taagttggtc aaaagaatgc tggcttcagt 32520
tgtaatcaaa actccatcgc atctaatcgt tctgaggaaa tcatccaagc aatgcaactg 32580
gattgtgttt caagcaggag aggagaggga agagacggaa gaaccatgtt aatttttatt 32640
ccaaacgatc tcgcagtact tcaaattgta gatcgcgcag atggcatctc tcgcccccac 32700
tgtgttggtg aaaaagcaca gctagatcaa aagaaatgcg attttcaagg tgctcaacgg 32760
tggcttccag caaagcctcc acgcgcacat ccaagaacaa aagaatacca aaagaaggag 32820
cattttctaa ctcctcaatc atcatattac attcctgcac cattcccaga taattttcag 32880
ctttccagcc ttgaattatt cgtgtcagtt cttgtggtaa atccaatcca cacattacaa 32940
acaggtcccg gagggcgccc tccaccacca ttcttaaaca caccctcata atgacaaaat 33000
atcttgctcc tgtgtcacct gtagcgaatt gagaatggca acatcaattg acatgccctt 33060
ggctctaagt tcttctttaa gttctagttg taaaaactct ctcatattat caccaaactg 33120
cttagccaga agccccccgg gaacaagagc aggggacgct acagtgcagt acaagcgcag 33180
acctccccaa ttggctccag caaaaacaag attggaataa gcatattggg aaccgccagt 33240
aatatcatcg aagttgctgg aaatataatc aggcagagtt tcttgtaaaa attgaataaa 33300
agaaaaattt gccaaaaaaa cattcaaaac ctctgggatg caaatgcaat aggttaccgc 33360
gctgcgctcc aacattgtta gttttgaatt agtctgcaaa aataaaaaaa aaaacaagcg 33420
tcatatcata gtagcctgac gaacagatgg ataaatcagt ctttccatca caagacaagc 33480
cacagggtct ccagctcgac cctcgtaaaa cctgtcatca tgattaaaca acagcaccga 33540
aagttcctcg cggtgaccag catgaataat tcttgatgaa gcatacaatc cagacatgtt 33600
agcatcagtt aacgagaaaa aacagccaac atagcctttg ggtataatta tgcttaatcg 33660
taagtatagc aaagccaccc ctcgcggata caaagtaaaa ggcacaggag aataaaaaat 33720
ataattattt ctctgctgct gttcaggcaa cgtcgccccc ggtccctcta aatacacata 33780
caaagcctca tcagccatgg cttaccagac aaagtacagc gggcacacaa agcacaagct 33840
ctaaagtgac tctccaacct ctccacaata tatatataca caagccctaa actgacgtaa 33900
tgggagtaaa gtgtaaaaaa tcccgccaaa cccaacacac accccgaaac tgcgtcacca 33960
gggaaaagta cagtttcact tccgcaatcc caacaggcgt aacttcctct ttctcacggt 34020
acgtgatatc ccactaactt gcaacgtcat tttcccacgg tcgcaccgcc ccttttagcc 34080
gttaacccca cagccaatca ccacacgatc cacacttttt aaaatcacct catttacata 34140
ttggcaccat tccatctata aggtatatta tatagataga 34180
<210> 82
<211> 35749
<212> DNA
<213> 人工序列
<220>
<223> NG-615基因组
<400> 82
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg aactggcaag 30240
acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta ctaggtacac 30300
gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat acattaatcc 30360
tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat tgactacaga 30420
caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg actctgcagt 30480
ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg gccaaggcac 30540
cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg gtggcggcgg 30600
atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag gggagaaggt 30660
caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc agcagaagtc 30720
aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg gagtccctgc 30780
tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg gcatggaggc 30840
tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca cgttcggctc 30900
ggggacaaag ttggaaataa accggggaag cggacagtgt actaattatg ctctcttgaa 30960
attggctgga gatgttgaga gcaaccctgg acctacagtg ctggcgccag cctggagccc 31020
aacaacctat ctcctcctgc tgctgctgct gagctcggga ctcagtggga cccaggactg 31080
ctccttccaa cacagcccca tctcctccga cttcgctgtc aaaatccgtg agctgtctga 31140
ctacctgctt caagattacc cagtcaccgt ggcctccaac ctccaggacg aggagctctg 31200
cgggggcctc tggcggctgg tcctggcaca gcgctggatg gagcggctca agactgtcgc 31260
tgggtccaag atgcaaggct tgctggagcg cgtgaacacg gagatacact ttgtcaccaa 31320
atgtgccttt cagccccccc ccagctgtct tcgcttcgtc cagaccaaca tctcccgcct 31380
cctacaggag acctccgagc agctggtggc gctgaagccc tggatcactc gccagaactt 31440
ctcccggtgc ctggagctgc agtgtcagcc cgactcctca accctgccac ccccatggag 31500
tccccggccc ctggaggcca cagccccggg aagcggagct actaacttca gcctgctgaa 31560
gcaggctgga gacgtggagg agaaccctgg acctcaggtc tccactgctg cccttgccgt 31620
cctcctctgc accatggctc tctgcaacca ggtcctctct gcaccacttg ctgctgacac 31680
gccgaccgcc tgctgcttca gctacacctc ccgacagatt ccacagaatt tcatagctga 31740
ctactttgag acgagcagcc agtgctccaa gcccagtgtc atcttcctaa ccaagagagg 31800
ccggcaggtc tgtgctgacc ccagtgagga gtgggtccag aaatacgtca gtgacctgga 31860
gctgagtgcc ggaagcggag agggcagagg aagtctgcta acatgcggtg acgtcgagga 31920
gaatcctgga cctgccttga cctttgcttt actggtggcc ctcctggtgc tcagctgcaa 31980
gtcaagctgc tctgtgggct gtgatctgcc tcaaacccac agcctgggta gcaggaggac 32040
cttgatgctc ctggcacaga tgaggagaat ctctcttttc tcctgcttga aggacagaca 32100
tgactttgga tttccccagg aggagtttgg caaccagttc caaaaggctg aaaccatccc 32160
tgtcctccat gagatgatcc agcagatctt caatctcttc agcacaaagg actcatctgc 32220
tgcttgggat gagaccctcc tagacaaatt ctacactgaa ctctaccagc agctgaatga 32280
cctggaagcc tgtgtgatac agggggtggg ggtgacagag actcccctga tgaaggagga 32340
ctccattctg gctgtgagga aatacttcca aagaatcact ctctatctga aagagaagaa 32400
atacagccct tgtgcctggg aggttgtcag agcagaaatc atgagatctt tttctttgtc 32460
aacaaacttg caagaaagtt taagaagtaa ggaataagct agcttgactg actgagatac 32520
agcgtacctt cagctcacag acatgataag atacattgat gagtttggac aaaccacaac 32580
tagaatgcag tgaaaaaaat gctttatttg tgaaatttgt gatgctattg ctttatttgt 32640
aaccattata agctgcaata aacaagttaa caacaacaat tgcattcatt ttatgtttca 32700
ggttcagggg gaggtgtggg aggtttttta aagcaagtaa aacctctaca aatgtggtag 32760
tcgtcagcta tcctgcagga acttgtttat ttgaaaatca attcacaaaa tccgagtagt 32820
tattttgcct cccccttccc atttaacaga atacaccaat ctctccccac gcacagcttt 32880
aaacatttgg ataccattag atatagacat ggttttagat tccacattcc aaacagtttc 32940
agagcgagcc aatctggggt cagtgataga taaaaatcca tcgggatagt cttttaaagc 33000
gctttcacag tccaactgct gcggatgcga ctccggagtc tggatcacgg tcatctggaa 33060
gaagaacgat gggaatcata atccgaaaac ggtatcggac gattgtgtct catcaaaccc 33120
acaagcagcc gctgtctgcg tcgctccgtg cgactgctgt ttatgggatc agggtccaca 33180
gtgtcctgaa gcatgatttt aatagccctt aacatcaact ttctggtgcg atgcgcgcag 33240
caacgcattc tgatttcact caaatctttg cagtaggtac aacacattat tacaatattg 33300
tttaataaac cataattaaa agcgctccag ccaaaactca tatctgatat aatcgcccct 33360
gcatgaccat cataccaaag tttaatataa attaaatgac gttccctcaa aaacacacta 33420
cccacataca tgatctcttt tggcatgtgc atattaacaa tctgtctgta ccatggacaa 33480
cgttggttaa tcatgcaacc caatataacc ttccggaacc acactgccaa caccgctccc 33540
ccagccatgc attgaagtga accctgctga ttacaatgac aatgaagaac ccaattctct 33600
cgaccgtgaa tcacttgaga atgaaaaata tctatagtgg cacaacatag acataaatgc 33660
atgcatcttc tcataatttt taactcctca ggatttagaa acatatccca gggaatagga 33720
agctcttgca gaacagtaaa gctggcagaa caaggaagac cacgaacaca acttacacta 33780
tgcatagtca tagtatcaca atctggcaac agcgggtggt cttcagtcat agaagctcgg 33840
gtttcatttt cctcacaacg tggtaactgg gctctggtgt aagggtgatg tctggcgcat 33900
gatgtcgagc gtgcgcgcaa ccttgtcata atggagttgc ttcctgacat tctcgtattt 33960
tgtatagcaa aacgcggccc tggcagaaca cactcttctt cgccttctat cctgccgctt 34020
agcgtgttcc gtgtgatagt tcaagtacaa ccacactctt aagttggtca aaagaatgct 34080
ggcttcagtt gtaatcaaaa ctccatcgca tctaatcgtt ctgaggaaat catccaagca 34140
atgcaactgg attgtgtttc aagcaggaga ggagagggaa gagacggaag aaccatgtta 34200
atttttattc caaacgatct cgcagtactt caaattgtag atcgcgcaga tggcatctct 34260
cgcccccact gtgttggtga aaaagcacag ctagatcaaa agaaatgcga ttttcaaggt 34320
gctcaacggt ggcttccagc aaagcctcca cgcgcacatc caagaacaaa agaataccaa 34380
aagaaggagc attttctaac tcctcaatca tcatattaca ttcctgcacc attcccagat 34440
aattttcagc tttccagcct tgaattattc gtgtcagttc ttgtggtaaa tccaatccac 34500
acattacaaa caggtcccgg agggcgccct ccaccaccat tcttaaacac accctcataa 34560
tgacaaaata tcttgctcct gtgtcacctg tagcgaattg agaatggcaa catcaattga 34620
catgcccttg gctctaagtt cttctttaag ttctagttgt aaaaactctc tcatattatc 34680
accaaactgc ttagccagaa gccccccggg aacaagagca ggggacgcta cagtgcagta 34740
caagcgcaga cctccccaat tggctccagc aaaaacaaga ttggaataag catattggga 34800
accgccagta atatcatcga agttgctgga aatataatca ggcagagttt cttgtaaaaa 34860
ttgaataaaa gaaaaatttg ccaaaaaaac attcaaaacc tctgggatgc aaatgcaata 34920
ggttaccgcg ctgcgctcca acattgttag ttttgaatta gtctgcaaaa ataaaaaaaa 34980
aaacaagcgt catatcatag tagcctgacg aacagatgga taaatcagtc tttccatcac 35040
aagacaagcc acagggtctc cagctcgacc ctcgtaaaac ctgtcatcat gattaaacaa 35100
cagcaccgaa agttcctcgc ggtgaccagc atgaataatt cttgatgaag catacaatcc 35160
agacatgtta gcatcagtta acgagaaaaa acagccaaca tagcctttgg gtataattat 35220
gcttaatcgt aagtatagca aagccacccc tcgcggatac aaagtaaaag gcacaggaga 35280
ataaaaaata taattatttc tctgctgctg ttcaggcaac gtcgcccccg gtccctctaa 35340
atacacatac aaagcctcat cagccatggc ttaccagaca aagtacagcg ggcacacaaa 35400
gcacaagctc taaagtgact ctccaacctc tccacaatat atatatacac aagccctaaa 35460
ctgacgtaat gggagtaaag tgtaaaaaat cccgccaaac ccaacacaca ccccgaaact 35520
gcgtcaccag ggaaaagtac agtttcactt ccgcaatccc aacaggcgta acttcctctt 35580
tctcacggta cgtgatatcc cactaacttg caacgtcatt ttcccacggt cgcaccgccc 35640
cttttagccg ttaaccccac agccaatcac cacacgatcc acacttttta aaatcacctc 35700
atttacatat tggcaccatt ccatctataa ggtatattat atagataga 35749
<210> 83
<211> 34972
<212> DNA
<213> 人工序列
<220>
<223> NG-640基因组
<400> 83
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg aactggcaag 30240
acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta ctaggtacac 30300
gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat acattaatcc 30360
tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat tgactacaga 30420
caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg actctgcagt 30480
ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg gccaaggcac 30540
cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg gtggcggcgg 30600
atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag gggagaaggt 30660
caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc agcagaagtc 30720
aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg gagtccctgc 30780
tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg gcatggaggc 30840
tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca cgttcggctc 30900
ggggacaaag ttggaaataa accggggaag cggagctact aacttcagcc tgctgaagca 30960
ggctggagac gtggaggaga accctggacc taatcaaact gccattctga tttgctgcct 31020
tatctttctg actctaagtg gcattcaagg agtacctctc tctagaactg tacgctgtac 31080
ctgcatcagc attagtaatc aacctgttaa tccaaggtct ttagaaaaac ttgaaattat 31140
tcctgcaagc caattttgtc cacgtgttga gatcattgct acaatgaaaa agaagggtga 31200
gaagagatgt ctgaatccag aatcgaaggc catcaagaat ttactgaaag cagttagcaa 31260
ggaaaggtct aaaagatctc ctggaagcgg agagggcaga ggaagtctgc taacatgcgg 31320
tgacgtcgag gagaatcctg gacctaagaa aagtggtgtt cttttcctct tgggcatcat 31380
cttgctggtt ctgattggag tgcaaggaac cccagtagtg agaaagggtc gctgttcctg 31440
catcagcacc aaccaaggga ctatccacct acaatccttg aaagacctta aacaatttgc 31500
cccaagccct tcctgcgaga aaattgaaat cattgctaca ctgaagaatg gagttcaaac 31560
atgtctaaac ccagattcag cagatgtgaa ggaactgatt aaaaagtggg agaaacaggt 31620
cagccaaaag aaaaagcaaa agaatgggaa aaaacatcaa aaaaagaaag ttctgaaagt 31680
tcgaaaatct caacgttctc gtcaaaagaa gactacataa gctagcttga ctgactgaga 31740
tacagcgtac cttcagctca cagacatgat aagatacatt gatgagtttg gacaaaccac 31800
aactagaatg cagtgaaaaa aatgctttat ttgtgaaatt tgtgatgcta ttgctttatt 31860
tgtaaccatt ataagctgca ataaacaagt taacaacaac aattgcattc attttatgtt 31920
tcaggttcag ggggaggtgt gggaggtttt ttaaagcaag taaaacctct acaaatgtgg 31980
tagtcgtcag ctatcctgca ggaacttgtt tatttgaaaa tcaattcaca aaatccgagt 32040
agttattttg cctccccctt cccatttaac agaatacacc aatctctccc cacgcacagc 32100
tttaaacatt tggataccat tagatataga catggtttta gattccacat tccaaacagt 32160
ttcagagcga gccaatctgg ggtcagtgat agataaaaat ccatcgggat agtcttttaa 32220
agcgctttca cagtccaact gctgcggatg cgactccgga gtctggatca cggtcatctg 32280
gaagaagaac gatgggaatc ataatccgaa aacggtatcg gacgattgtg tctcatcaaa 32340
cccacaagca gccgctgtct gcgtcgctcc gtgcgactgc tgtttatggg atcagggtcc 32400
acagtgtcct gaagcatgat tttaatagcc cttaacatca actttctggt gcgatgcgcg 32460
cagcaacgca ttctgatttc actcaaatct ttgcagtagg tacaacacat tattacaata 32520
ttgtttaata aaccataatt aaaagcgctc cagccaaaac tcatatctga tataatcgcc 32580
cctgcatgac catcatacca aagtttaata taaattaaat gacgttccct caaaaacaca 32640
ctacccacat acatgatctc ttttggcatg tgcatattaa caatctgtct gtaccatgga 32700
caacgttggt taatcatgca acccaatata accttccgga accacactgc caacaccgct 32760
cccccagcca tgcattgaag tgaaccctgc tgattacaat gacaatgaag aacccaattc 32820
tctcgaccgt gaatcacttg agaatgaaaa atatctatag tggcacaaca tagacataaa 32880
tgcatgcatc ttctcataat ttttaactcc tcaggattta gaaacatatc ccagggaata 32940
ggaagctctt gcagaacagt aaagctggca gaacaaggaa gaccacgaac acaacttaca 33000
ctatgcatag tcatagtatc acaatctggc aacagcgggt ggtcttcagt catagaagct 33060
cgggtttcat tttcctcaca acgtggtaac tgggctctgg tgtaagggtg atgtctggcg 33120
catgatgtcg agcgtgcgcg caaccttgtc ataatggagt tgcttcctga cattctcgta 33180
ttttgtatag caaaacgcgg ccctggcaga acacactctt cttcgccttc tatcctgccg 33240
cttagcgtgt tccgtgtgat agttcaagta caaccacact cttaagttgg tcaaaagaat 33300
gctggcttca gttgtaatca aaactccatc gcatctaatc gttctgagga aatcatccaa 33360
gcaatgcaac tggattgtgt ttcaagcagg agaggagagg gaagagacgg aagaaccatg 33420
ttaattttta ttccaaacga tctcgcagta cttcaaattg tagatcgcgc agatggcatc 33480
tctcgccccc actgtgttgg tgaaaaagca cagctagatc aaaagaaatg cgattttcaa 33540
ggtgctcaac ggtggcttcc agcaaagcct ccacgcgcac atccaagaac aaaagaatac 33600
caaaagaagg agcattttct aactcctcaa tcatcatatt acattcctgc accattccca 33660
gataattttc agctttccag ccttgaatta ttcgtgtcag ttcttgtggt aaatccaatc 33720
cacacattac aaacaggtcc cggagggcgc cctccaccac cattcttaaa cacaccctca 33780
taatgacaaa atatcttgct cctgtgtcac ctgtagcgaa ttgagaatgg caacatcaat 33840
tgacatgccc ttggctctaa gttcttcttt aagttctagt tgtaaaaact ctctcatatt 33900
atcaccaaac tgcttagcca gaagcccccc gggaacaaga gcaggggacg ctacagtgca 33960
gtacaagcgc agacctcccc aattggctcc agcaaaaaca agattggaat aagcatattg 34020
ggaaccgcca gtaatatcat cgaagttgct ggaaatataa tcaggcagag tttcttgtaa 34080
aaattgaata aaagaaaaat ttgccaaaaa aacattcaaa acctctggga tgcaaatgca 34140
ataggttacc gcgctgcgct ccaacattgt tagttttgaa ttagtctgca aaaataaaaa 34200
aaaaaacaag cgtcatatca tagtagcctg acgaacagat ggataaatca gtctttccat 34260
cacaagacaa gccacagggt ctccagctcg accctcgtaa aacctgtcat catgattaaa 34320
caacagcacc gaaagttcct cgcggtgacc agcatgaata attcttgatg aagcatacaa 34380
tccagacatg ttagcatcag ttaacgagaa aaaacagcca acatagcctt tgggtataat 34440
tatgcttaat cgtaagtata gcaaagccac ccctcgcgga tacaaagtaa aaggcacagg 34500
agaataaaaa atataattat ttctctgctg ctgttcaggc aacgtcgccc ccggtccctc 34560
taaatacaca tacaaagcct catcagccat ggcttaccag acaaagtaca gcgggcacac 34620
aaagcacaag ctctaaagtg actctccaac ctctccacaa tatatatata cacaagccct 34680
aaactgacgt aatgggagta aagtgtaaaa aatcccgcca aacccaacac acaccccgaa 34740
actgcgtcac cagggaaaag tacagtttca cttccgcaat cccaacaggc gtaacttcct 34800
ctttctcacg gtacgtgata tcccactaac ttgcaacgtc attttcccac ggtcgcaccg 34860
ccccttttag ccgttaaccc cacagccaat caccacacga tccacacttt ttaaaatcac 34920
ctcatttaca tattggcacc attccatcta taaggtatat tatatagata ga 34972
<210> 84
<211> 35602
<212> DNA
<213> 人工序列
<220>
<223> NG-641基因组
<400> 84
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggc tggagctgca tcatcttgtt 29400
cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa gccctgactc 29460
gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc agagcctgct 29520
gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg gccagcctcc 29580
caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc gcttcagcgg 29640
aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg aggacgtggc 29700
cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag gcaccaaggt 29760
ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg gatcgcaggt 29820
ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca aggtcagctg 29880
caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc aggcgcccgg 29940
ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa attacaatca 30000
gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg cgtacatgga 30060
gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc gccggatcgc 30120
ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc tcgtcacggt 30180
gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg aactggcaag 30240
acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta ctaggtacac 30300
gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat acattaatcc 30360
tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat tgactacaga 30420
caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg actctgcagt 30480
ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg gccaaggcac 30540
cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg gtggcggcgg 30600
atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag gggagaaggt 30660
caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc agcagaagtc 30720
aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg gagtccctgc 30780
tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg gcatggaggc 30840
tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca cgttcggctc 30900
ggggacaaag ttggaaataa accggggaag cggagctact aacttcagcc tgctgaagca 30960
ggctggagac gtggaggaga accctggacc taatcaaact gccattctga tttgctgcct 31020
tatctttctg actctaagtg gcattcaagg agtacctctc tctagaactg tacgctgtac 31080
ctgcatcagc attagtaatc aacctgttaa tccaaggtct ttagaaaaac ttgaaattat 31140
tcctgcaagc caattttgtc cacgtgttga gatcattgct acaatgaaaa agaagggtga 31200
gaagagatgt ctgaatccag aatcgaaggc catcaagaat ttactgaaag cagttagcaa 31260
ggaaaggtct aaaagatctc ctggaagcgg agagggcaga ggaagtctgc taacatgcgg 31320
tgacgtcgag gagaatcctg gacctaagaa aagtggtgtt cttttcctct tgggcatcat 31380
cttgctggtt ctgattggag tgcaaggaac cccagtagtg agaaagggtc gctgttcctg 31440
catcagcacc aaccaaggga ctatccacct acaatccttg aaagacctta aacaatttgc 31500
cccaagccct tcctgcgaga aaattgaaat cattgctaca ctgaagaatg gagttcaaac 31560
atgtctaaac ccagattcag cagatgtgaa ggaactgatt aaaaagtggg agaaacaggt 31620
cagccaaaag aaaaagcaaa agaatgggaa aaaacatcaa aaaaagaaag ttctgaaagt 31680
tcgaaaatct caacgttctc gtcaaaagaa gactacagga agcggacagt gtactaatta 31740
tgctctcttg aaattggctg gagatgttga gagcaaccct ggacctgcct tgacctttgc 31800
tttactggtg gccctcctgg tgctcagctg caagtcaagc tgctctgtgg gctgtgatct 31860
gcctcaaacc cacagcctgg gtagcaggag gaccttgatg ctcctggcac agatgaggag 31920
aatctctctt ttctcctgct tgaaggacag acatgacttt ggatttcccc aggaggagtt 31980
tggcaaccag ttccaaaagg ctgaaaccat ccctgtcctc catgagatga tccagcagat 32040
cttcaatctc ttcagcacaa aggactcatc tgctgcttgg gatgagaccc tcctagacaa 32100
attctacact gaactctacc agcagctgaa tgacctggaa gcctgtgtga tacagggggt 32160
gggggtgaca gagactcccc tgatgaagga ggactccatt ctggctgtga ggaaatactt 32220
ccaaagaatc actctctatc tgaaagagaa gaaatacagc ccttgtgcct gggaggttgt 32280
cagagcagaa atcatgagat ctttttcttt gtcaacaaac ttgcaagaaa gtttaagaag 32340
taaggaataa gctagcttga ctgactgaga tacagcgtac cttcagctca cagacatgat 32400
aagatacatt gatgagtttg gacaaaccac aactagaatg cagtgaaaaa aatgctttat 32460
ttgtgaaatt tgtgatgcta ttgctttatt tgtaaccatt ataagctgca ataaacaagt 32520
taacaacaac aattgcattc attttatgtt tcaggttcag ggggaggtgt gggaggtttt 32580
ttaaagcaag taaaacctct acaaatgtgg tagtcgtcag ctatcctgca ggaacttgtt 32640
tatttgaaaa tcaattcaca aaatccgagt agttattttg cctccccctt cccatttaac 32700
agaatacacc aatctctccc cacgcacagc tttaaacatt tggataccat tagatataga 32760
catggtttta gattccacat tccaaacagt ttcagagcga gccaatctgg ggtcagtgat 32820
agataaaaat ccatcgggat agtcttttaa agcgctttca cagtccaact gctgcggatg 32880
cgactccgga gtctggatca cggtcatctg gaagaagaac gatgggaatc ataatccgaa 32940
aacggtatcg gacgattgtg tctcatcaaa cccacaagca gccgctgtct gcgtcgctcc 33000
gtgcgactgc tgtttatggg atcagggtcc acagtgtcct gaagcatgat tttaatagcc 33060
cttaacatca actttctggt gcgatgcgcg cagcaacgca ttctgatttc actcaaatct 33120
ttgcagtagg tacaacacat tattacaata ttgtttaata aaccataatt aaaagcgctc 33180
cagccaaaac tcatatctga tataatcgcc cctgcatgac catcatacca aagtttaata 33240
taaattaaat gacgttccct caaaaacaca ctacccacat acatgatctc ttttggcatg 33300
tgcatattaa caatctgtct gtaccatgga caacgttggt taatcatgca acccaatata 33360
accttccgga accacactgc caacaccgct cccccagcca tgcattgaag tgaaccctgc 33420
tgattacaat gacaatgaag aacccaattc tctcgaccgt gaatcacttg agaatgaaaa 33480
atatctatag tggcacaaca tagacataaa tgcatgcatc ttctcataat ttttaactcc 33540
tcaggattta gaaacatatc ccagggaata ggaagctctt gcagaacagt aaagctggca 33600
gaacaaggaa gaccacgaac acaacttaca ctatgcatag tcatagtatc acaatctggc 33660
aacagcgggt ggtcttcagt catagaagct cgggtttcat tttcctcaca acgtggtaac 33720
tgggctctgg tgtaagggtg atgtctggcg catgatgtcg agcgtgcgcg caaccttgtc 33780
ataatggagt tgcttcctga cattctcgta ttttgtatag caaaacgcgg ccctggcaga 33840
acacactctt cttcgccttc tatcctgccg cttagcgtgt tccgtgtgat agttcaagta 33900
caaccacact cttaagttgg tcaaaagaat gctggcttca gttgtaatca aaactccatc 33960
gcatctaatc gttctgagga aatcatccaa gcaatgcaac tggattgtgt ttcaagcagg 34020
agaggagagg gaagagacgg aagaaccatg ttaattttta ttccaaacga tctcgcagta 34080
cttcaaattg tagatcgcgc agatggcatc tctcgccccc actgtgttgg tgaaaaagca 34140
cagctagatc aaaagaaatg cgattttcaa ggtgctcaac ggtggcttcc agcaaagcct 34200
ccacgcgcac atccaagaac aaaagaatac caaaagaagg agcattttct aactcctcaa 34260
tcatcatatt acattcctgc accattccca gataattttc agctttccag ccttgaatta 34320
ttcgtgtcag ttcttgtggt aaatccaatc cacacattac aaacaggtcc cggagggcgc 34380
cctccaccac cattcttaaa cacaccctca taatgacaaa atatcttgct cctgtgtcac 34440
ctgtagcgaa ttgagaatgg caacatcaat tgacatgccc ttggctctaa gttcttcttt 34500
aagttctagt tgtaaaaact ctctcatatt atcaccaaac tgcttagcca gaagcccccc 34560
gggaacaaga gcaggggacg ctacagtgca gtacaagcgc agacctcccc aattggctcc 34620
agcaaaaaca agattggaat aagcatattg ggaaccgcca gtaatatcat cgaagttgct 34680
ggaaatataa tcaggcagag tttcttgtaa aaattgaata aaagaaaaat ttgccaaaaa 34740
aacattcaaa acctctggga tgcaaatgca ataggttacc gcgctgcgct ccaacattgt 34800
tagttttgaa ttagtctgca aaaataaaaa aaaaaacaag cgtcatatca tagtagcctg 34860
acgaacagat ggataaatca gtctttccat cacaagacaa gccacagggt ctccagctcg 34920
accctcgtaa aacctgtcat catgattaaa caacagcacc gaaagttcct cgcggtgacc 34980
agcatgaata attcttgatg aagcatacaa tccagacatg ttagcatcag ttaacgagaa 35040
aaaacagcca acatagcctt tgggtataat tatgcttaat cgtaagtata gcaaagccac 35100
ccctcgcgga tacaaagtaa aaggcacagg agaataaaaa atataattat ttctctgctg 35160
ctgttcaggc aacgtcgccc ccggtccctc taaatacaca tacaaagcct catcagccat 35220
ggcttaccag acaaagtaca gcgggcacac aaagcacaag ctctaaagtg actctccaac 35280
ctctccacaa tatatatata cacaagccct aaactgacgt aatgggagta aagtgtaaaa 35340
aatcccgcca aacccaacac acaccccgaa actgcgtcac cagggaaaag tacagtttca 35400
cttccgcaat cccaacaggc gtaacttcct ctttctcacg gtacgtgata tcccactaac 35460
ttgcaacgtc attttcccac ggtcgcaccg ccccttttag ccgttaaccc cacagccaat 35520
caccacacga tccacacttt ttaaaatcac ctcatttaca tattggcacc attccatcta 35580
taaggtatat tatatagata ga 35602
<210> 85
<400> 85
000
<210> 86
<211> 537
<212> DNA
<213> 人工序列
<220>
<223> FLT3配体核酸序列
<400> 86
atgacagtgc tggcgccagc ctggagccca acaacctatc tcctcctgct gctgctgctg 60
agctcgggac tcagtgggac ccaggactgc tccttccaac acagccccat ctcctccgac 120
ttcgctgtca aaatccgtga gctgtctgac tacctgcttc aagattaccc agtcaccgtg 180
gcctccaacc tccaggacga ggagctctgc gggggcctct ggcggctggt cctggcacag 240
cgctggatgg agcggctcaa gactgtcgct gggtccaaga tgcaaggctt gctggagcgc 300
gtgaacacgg agatacactt tgtcaccaaa tgtgcctttc agcccccccc cagctgtctt 360
cgcttcgtcc agaccaacat ctcccgcctc ctacaggaga cctccgagca gctggtggcg 420
ctgaagccct ggatcactcg ccagaacttc tcccggtgcc tggagctgca gtgtcagccc 480
gactcctcaa ccctgccacc cccatggagt ccccggcccc tggaggccac agccccg 537
<210> 87
<400> 87
000
<210> 88
<211> 279
<212> DNA
<213> 人工序列
<220>
<223> MIP1α核酸序列
<400> 88
atgcaggtct ccactgctgc ccttgccgtc ctcctctgca ccatggctct ctgcaaccag 60
gtcctctctg caccacttgc tgctgacacg ccgaccgcct gctgcttcag ctacacctcc 120
cgacagattc cacagaattt catagctgac tactttgaga cgagcagcca gtgctccaag 180
cccagtgtca tcttcctaac caagagaggc cggcaggtct gtgctgaccc cagtgaggag 240
tgggtccaga aatacgtcag tgacctggag ctgagtgcc 279
<210> 89
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 89
Ser Pro Gln Tyr Pro Ser Pro Leu Thr Leu Thr Leu Pro Pro His Pro
1 5 10 15
Ser Leu
<210> 90
<211> 564
<212> DNA
<213> 人工序列
<220>
<223> IFNα核酸序列
<400> 90
atggccttga cctttgcttt actggtggcc ctcctggtgc tcagctgcaa gtcaagctgc 60
tctgtgggct gtgatctgcc tcaaacccac agcctgggta gcaggaggac cttgatgctc 120
ctggcacaga tgaggagaat ctctcttttc tcctgcttga aggacagaca tgactttgga 180
tttccccagg aggagtttgg caaccagttc caaaaggctg aaaccatccc tgtcctccat 240
gagatgatcc agcagatctt caatctcttc agcacaaagg actcatctgc tgcttgggat 300
gagaccctcc tagacaaatt ctacactgaa ctctaccagc agctgaatga cctggaagcc 360
tgtgtgatac agggggtggg ggtgacagag actcccctga tgaaggagga ctccattctg 420
gctgtgagga aatacttcca aagaatcact ctctatctga aagagaagaa atacagccct 480
tgtgcctggg aggttgtcag agcagaaatc atgagatctt tttctttgtc aacaaacttg 540
caagaaagtt taagaagtaa ggaa 564
<210> 91
<211> 294
<212> DNA
<213> 人工序列
<220>
<223> CXCL10核酸序列
<400> 91
atgaatcaaa ctgccattct gatttgctgc cttatctttc tgactctaag tggcattcaa 60
ggagtacctc tctctagaac tgtacgctgt acctgcatca gcattagtaa tcaacctgtt 120
aatccaaggt ctttagaaaa acttgaaatt attcctgcaa gccaattttg tccacgtgtt 180
gagatcattg ctacaatgaa aaagaagggt gagaagagat gtctgaatcc agaatcgaag 240
gccatcaaga atttactgaa agcagttagc aaggaaaggt ctaaaagatc tcct 294
<210> 92
<211> 372
<212> DNA
<213> 人工序列
<220>
<223> CXCL9核酸序列
<400> 92
aagaaaagtg gtgttctttt cctcttgggc atcatcttgc tggttctgat tggagtgcaa 60
ggaaccccag tagtgagaaa gggtcgctgt tcctgcatca gcaccaacca agggactatc 120
cacctacaat ccttgaaaga ccttaaacaa tttgccccaa gcccttcctg cgagaaaatt 180
gaaatcattg ctacactgaa gaatggagtt caaacatgtc taaacccaga ttcagcagat 240
gtgaaggaac tgattaaaaa gtgggagaaa caggtcagcc aaaagaaaaa gcaaaagaat 300
gggaaaaaac atcaaaaaaa gaaagttctg aaagttcgaa aatctcaacg ttctcgtcaa 360
aagaagacta ca 372
<210> 93
<211> 3407
<212> DNA
<213> 人工序列
<220>
<223> NG-615转基因盒
<400> 93
caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt 60
ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg 120
ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta 180
cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc 240
cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac 300
tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt 360
ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag 420
cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga 480
agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac 540
tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg 600
gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat 660
caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga 720
caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc 780
gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca 840
ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc 900
ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc 960
tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa 1020
tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat 1080
gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga 1140
tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg 1200
cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc 1260
tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc 1320
aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat 1380
ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg 1440
gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg 1500
ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg 1560
gggaagcgga cagtgtacta attatgctct cttgaaattg gctggagatg ttgagagcaa 1620
ccctggacct acagtgctgg cgccagcctg gagcccaaca acctatctcc tcctgctgct 1680
gctgctgagc tcgggactca gtgggaccca ggactgctcc ttccaacaca gccccatctc 1740
ctccgacttc gctgtcaaaa tccgtgagct gtctgactac ctgcttcaag attacccagt 1800
caccgtggcc tccaacctcc aggacgagga gctctgcggg ggcctctggc ggctggtcct 1860
ggcacagcgc tggatggagc ggctcaagac tgtcgctggg tccaagatgc aaggcttgct 1920
ggagcgcgtg aacacggaga tacactttgt caccaaatgt gcctttcagc ccccccccag 1980
ctgtcttcgc ttcgtccaga ccaacatctc ccgcctccta caggagacct ccgagcagct 2040
ggtggcgctg aagccctgga tcactcgcca gaacttctcc cggtgcctgg agctgcagtg 2100
tcagcccgac tcctcaaccc tgccaccccc atggagtccc cggcccctgg aggccacagc 2160
cccgggaagc ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa 2220
ccctggacct caggtctcca ctgctgccct tgccgtcctc ctctgcacca tggctctctg 2280
caaccaggtc ctctctgcac cacttgctgc tgacacgccg accgcctgct gcttcagcta 2340
cacctcccga cagattccac agaatttcat agctgactac tttgagacga gcagccagtg 2400
ctccaagccc agtgtcatct tcctaaccaa gagaggccgg caggtctgtg ctgaccccag 2460
tgaggagtgg gtccagaaat acgtcagtga cctggagctg agtgccggaa gcggagaggg 2520
cagaggaagt ctgctaacat gcggtgacgt cgaggagaat cctggacctg ccttgacctt 2580
tgctttactg gtggccctcc tggtgctcag ctgcaagtca agctgctctg tgggctgtga 2640
tctgcctcaa acccacagcc tgggtagcag gaggaccttg atgctcctgg cacagatgag 2700
gagaatctct cttttctcct gcttgaagga cagacatgac tttggatttc cccaggagga 2760
gtttggcaac cagttccaaa aggctgaaac catccctgtc ctccatgaga tgatccagca 2820
gatcttcaat ctcttcagca caaaggactc atctgctgct tgggatgaga ccctcctaga 2880
caaattctac actgaactct accagcagct gaatgacctg gaagcctgtg tgatacaggg 2940
ggtgggggtg acagagactc ccctgatgaa ggaggactcc attctggctg tgaggaaata 3000
cttccaaaga atcactctct atctgaaaga gaagaaatac agcccttgtg cctgggaggt 3060
tgtcagagca gaaatcatga gatctttttc tttgtcaaca aacttgcaag aaagtttaag 3120
aagtaaggaa taagctagct tgactgactg agatacagcg taccttcagc tcacagacat 3180
gataagatac attgatgagt ttggacaaac cacaactaga atgcagtgaa aaaaatgctt 3240
tatttgtgaa atttgtgatg ctattgcttt atttgtaacc attataagct gcaataaaca 3300
agttaacaac aacaattgca ttcattttat gtttcaggtt cagggggagg tgtgggaggt 3360
tttttaaagc aagtaaaacc tctacaaatg tggtagtcgt cagctat 3407
<210> 94
<211> 2630
<212> DNA
<213> 人工序列
<220>
<223> NG-640转基因盒
<400> 94
caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt 60
ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg 120
ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta 180
cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc 240
cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac 300
tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt 360
ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag 420
cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga 480
agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac 540
tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg 600
gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat 660
caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga 720
caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc 780
gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca 840
ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc 900
ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc 960
tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa 1020
tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat 1080
gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga 1140
tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg 1200
cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc 1260
tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc 1320
aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat 1380
ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg 1440
gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg 1500
ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg 1560
gggaagcgga gctactaact tcagcctgct gaagcaggct ggagacgtgg aggagaaccc 1620
tggacctaat caaactgcca ttctgatttg ctgccttatc tttctgactc taagtggcat 1680
tcaaggagta cctctctcta gaactgtacg ctgtacctgc atcagcatta gtaatcaacc 1740
tgttaatcca aggtctttag aaaaacttga aattattcct gcaagccaat tttgtccacg 1800
tgttgagatc attgctacaa tgaaaaagaa gggtgagaag agatgtctga atccagaatc 1860
gaaggccatc aagaatttac tgaaagcagt tagcaaggaa aggtctaaaa gatctcctgg 1920
aagcggagag ggcagaggaa gtctgctaac atgcggtgac gtcgaggaga atcctggacc 1980
taagaaaagt ggtgttcttt tcctcttggg catcatcttg ctggttctga ttggagtgca 2040
aggaacccca gtagtgagaa agggtcgctg ttcctgcatc agcaccaacc aagggactat 2100
ccacctacaa tccttgaaag accttaaaca atttgcccca agcccttcct gcgagaaaat 2160
tgaaatcatt gctacactga agaatggagt tcaaacatgt ctaaacccag attcagcaga 2220
tgtgaaggaa ctgattaaaa agtgggagaa acaggtcagc caaaagaaaa agcaaaagaa 2280
tgggaaaaaa catcaaaaaa agaaagttct gaaagttcga aaatctcaac gttctcgtca 2340
aaagaagact acataagcta gcttgactga ctgagataca gcgtaccttc agctcacaga 2400
catgataaga tacattgatg agtttggaca aaccacaact agaatgcagt gaaaaaaatg 2460
ctttatttgt gaaatttgtg atgctattgc tttatttgta accattataa gctgcaataa 2520
acaagttaac aacaacaatt gcattcattt tatgtttcag gttcaggggg aggtgtggga 2580
ggttttttaa agcaagtaaa acctctacaa atgtggtagt cgtcagctat 2630
<210> 95
<211> 3260
<212> DNA
<213> 人工序列
<220>
<223> NG-641转基因盒
<400> 95
caggcccacc atgggctgga gctgcatcat cttgttcctg gtcgcaactg ctaccggagt 60
ccattcggac atcgtcatga cccaaagccc tgactcgctc gctgtgtcac tgggagagcg 120
ggcgactatc aactgcaaat catcccagag cctgctgtat tcacgcaatc agaaaaacta 180
cctggcctgg tatcagcaga agccgggcca gcctcccaag ctgctgatct tctgggcctc 240
cacccgcgaa agcggcgtgc cggaccgctt cagcggaagc ggattcggaa ctgactttac 300
tctgaccatt agctccttgc aggcggagga cgtggccgtc tactactgcc agcagtattt 360
ctcctatccg ctcacctttg ggcaaggcac caaggtggag attaagggag ggggcggcag 420
cgggggaggc ggcagcggcg gcgggggatc gcaggtccag ctcgtccaat ccggagccga 480
agtcaagaag ccgggagcgt cggtcaaggt cagctgcaaa acttcgcgct acaccttcac 540
tgagtacacg atccactggg tccgccaggc gcccggccag cggctggagt ggatcggcgg 600
gatcaaccca aacaacggaa tcccaaatta caatcagaaa tttaaagggc gggtgactat 660
caccgtggat acctcggcct ccacggcgta catggagctc tcatcactca gatcggagga 720
caccgcggtc tattactgcg cccgccgccg gatcgcttat ggatacgatg aaggacatgc 780
gatggattac tggggccagg gcaccctcgt cacggtgtcg tcaggaggcg gcggttcaca 840
ggtgcagctg cagcagtctg gggctgaact ggcaagacct ggggcctcag tgaagatgtc 900
ctgcaaggct tctggctaca cctttactag gtacacgatg cactgggtaa aacagaggcc 960
tggacagggt ctggaatgga ttggatacat taatcctagc cgtggttata ctaattacaa 1020
tcagaagttc aaggacaagg ccacattgac tacagacaaa tcctccagca cagcctacat 1080
gcaactgagc agcctgacat ctgaggactc tgcagtctat tactgtgcaa gatattatga 1140
tgatcattac tgccttgact actggggcca aggcaccact ctcacagtct cctcaggtgg 1200
cggtggctcg ggcggtggtg gatctggtgg cggcggatct gatatcgtgc tcactcagtc 1260
tccagcaatc atgtctgcat ctccagggga gaaggtcacc atgacctgca gtgccagctc 1320
aagtgtaagt tacatgaact ggtaccagca gaagtcaggc acctccccca aaagatggat 1380
ttatgacaca tccaaactgg cttctggagt ccctgctcac ttcaggggca gtgggtctgg 1440
gacctcttac tctctcacaa tcagcggcat ggaggctgaa gatgctgcca cttattactg 1500
ccagcagtgg agtagtaacc cattcacgtt cggctcgggg acaaagttgg aaataaaccg 1560
gggaagcgga gctactaact tcagcctgct gaagcaggct ggagacgtgg aggagaaccc 1620
tggacctaat caaactgcca ttctgatttg ctgccttatc tttctgactc taagtggcat 1680
tcaaggagta cctctctcta gaactgtacg ctgtacctgc atcagcatta gtaatcaacc 1740
tgttaatcca aggtctttag aaaaacttga aattattcct gcaagccaat tttgtccacg 1800
tgttgagatc attgctacaa tgaaaaagaa gggtgagaag agatgtctga atccagaatc 1860
gaaggccatc aagaatttac tgaaagcagt tagcaaggaa aggtctaaaa gatctcctgg 1920
aagcggagag ggcagaggaa gtctgctaac atgcggtgac gtcgaggaga atcctggacc 1980
taagaaaagt ggtgttcttt tcctcttggg catcatcttg ctggttctga ttggagtgca 2040
aggaacccca gtagtgagaa agggtcgctg ttcctgcatc agcaccaacc aagggactat 2100
ccacctacaa tccttgaaag accttaaaca atttgcccca agcccttcct gcgagaaaat 2160
tgaaatcatt gctacactga agaatggagt tcaaacatgt ctaaacccag attcagcaga 2220
tgtgaaggaa ctgattaaaa agtgggagaa acaggtcagc caaaagaaaa agcaaaagaa 2280
tgggaaaaaa catcaaaaaa agaaagttct gaaagttcga aaatctcaac gttctcgtca 2340
aaagaagact acaggaagcg gacagtgtac taattatgct ctcttgaaat tggctggaga 2400
tgttgagagc aaccctggac ctgccttgac ctttgcttta ctggtggccc tcctggtgct 2460
cagctgcaag tcaagctgct ctgtgggctg tgatctgcct caaacccaca gcctgggtag 2520
caggaggacc ttgatgctcc tggcacagat gaggagaatc tctcttttct cctgcttgaa 2580
ggacagacat gactttggat ttccccagga ggagtttggc aaccagttcc aaaaggctga 2640
aaccatccct gtcctccatg agatgatcca gcagatcttc aatctcttca gcacaaagga 2700
ctcatctgct gcttgggatg agaccctcct agacaaattc tacactgaac tctaccagca 2760
gctgaatgac ctggaagcct gtgtgataca gggggtgggg gtgacagaga ctcccctgat 2820
gaaggaggac tccattctgg ctgtgaggaa atacttccaa agaatcactc tctatctgaa 2880
agagaagaaa tacagccctt gtgcctggga ggttgtcaga gcagaaatca tgagatcttt 2940
ttctttgtca acaaacttgc aagaaagttt aagaagtaag gaataagcta gcttgactga 3000
ctgagataca gcgtaccttc agctcacaga catgataaga tacattgatg agtttggaca 3060
aaccacaact agaatgcagt gaaaaaaatg ctttatttgt gaaatttgtg atgctattgc 3120
tttatttgta accattataa gctgcaataa acaagttaac aacaacaatt gcattcattt 3180
tatgtttcag gttcaggggg aggtgtggga ggttttttaa agcaagtaaa acctctacaa 3240
atgtggtagt cgtcagctat 3260
<210> 96
<211> 154
<212> PRT
<213> 人工序列
<220>
<223> FLT3配体氨基酸序列
<400> 96
Met Thr Gln Asp Cys Ser Phe Gln His Ser Pro Ile Ser Ser Asp Phe
1 5 10 15
Ala Val Lys Ile Arg Glu Leu Ser Asp Tyr Leu Leu Gln Asp Tyr Pro
20 25 30
Val Thr Val Ala Ser Asn Leu Gln Asp Glu Glu Leu Cys Gly Gly Leu
35 40 45
Trp Arg Leu Val Leu Ala Gln Arg Trp Met Glu Arg Leu Lys Thr Val
50 55 60
Ala Gly Ser Lys Met Gln Gly Leu Leu Glu Arg Val Asn Thr Glu Ile
65 70 75 80
His Phe Val Thr Lys Cys Ala Phe Gln Pro Pro Pro Ser Cys Leu Arg
85 90 95
Phe Val Gln Thr Asn Ile Ser Arg Leu Leu Gln Glu Thr Ser Glu Gln
100 105 110
Leu Val Ala Leu Lys Pro Trp Ile Thr Arg Gln Asn Phe Ser Arg Cys
115 120 125
Leu Glu Leu Gln Cys Gln Pro Asp Ser Ser Thr Leu Pro Pro Pro Trp
130 135 140
Ser Pro Arg Pro Leu Glu Ala Thr Ala Pro
145 150
<210> 97
<211> 93
<212> PRT
<213> 人工序列
<220>
<223> MIP1α氨基酸序列
<400> 97
Met Gln Val Ser Thr Ala Ala Leu Ala Val Leu Leu Cys Thr Met Ala
1 5 10 15
Leu Cys Asn Gln Val Leu Ser Ala Pro Leu Ala Ala Asp Thr Pro Thr
20 25 30
Ala Cys Cys Phe Ser Tyr Thr Ser Arg Gln Ile Pro Gln Asn Phe Ile
35 40 45
Ala Asp Tyr Phe Glu Thr Ser Ser Gln Cys Ser Lys Pro Ser Val Ile
50 55 60
Phe Leu Thr Lys Arg Gly Arg Gln Val Cys Ala Asp Pro Ser Glu Glu
65 70 75 80
Trp Val Gln Lys Tyr Val Ser Asp Leu Glu Leu Ser Ala
85 90
<210> 98
<211> 188
<212> PRT
<213> 人工序列
<220>
<223> IFNα氨基酸序列
<400> 98
Met Ala Leu Thr Phe Ala Leu Leu Val Ala Leu Leu Val Leu Ser Cys
1 5 10 15
Lys Ser Ser Cys Ser Val Gly Cys Asp Leu Pro Gln Thr His Ser Leu
20 25 30
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
35 40 45
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
50 55 60
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
65 70 75 80
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
85 90 95
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
100 105 110
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
115 120 125
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
130 135 140
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
145 150 155 160
Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu
165 170 175
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
180 185
<210> 99
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> CXCL9氨基酸序列
<400> 99
Met Lys Lys Ser Gly Val Leu Phe Leu Leu Gly Ile Ile Leu Leu Val
1 5 10 15
Leu Ile Gly Val Gln Gly Thr Pro Val Val Arg Lys Gly Arg Cys Ser
20 25 30
Cys Ile Ser Thr Asn Gln Gly Thr Ile His Leu Gln Ser Leu Lys Asp
35 40 45
Leu Lys Gln Phe Ala Pro Ser Pro Ser Cys Glu Lys Ile Glu Ile Ile
50 55 60
Ala Thr Leu Lys Asn Gly Val Gln Thr Cys Leu Asn Pro Asp Ser Ala
65 70 75 80
Asp Val Lys Glu Leu Ile Lys Lys Trp Glu Lys Gln Val Ser Gln Lys
85 90 95
Lys Lys Gln Lys Asn Gly Lys Lys His Gln Lys Lys Lys Val Leu Lys
100 105 110
Val Arg Lys Ser Gln Arg Ser Arg Gln Lys Lys Thr Thr
115 120 125
<210> 100
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> CXCL10氨基酸序列
<400> 100
Met Asn Gln Thr Ala Ile Leu Ile Cys Cys Leu Ile Phe Leu Thr Leu
1 5 10 15
Ser Gly Ile Gln Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys
20 25 30
Ile Ser Ile Ser Asn Gln Pro Val Asn Pro Arg Ser Leu Glu Lys Leu
35 40 45
Glu Ile Ile Pro Ala Ser Gln Phe Cys Pro Arg Val Glu Ile Ile Ala
50 55 60
Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro Glu Ser Lys
65 70 75 80
Ala Ile Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Arg Ser Lys Arg
85 90 95
Ser Pro
<210> 101
<211> 35788
<212> DNA
<213> 人工序列
<220>
<223> NG-618基因组
<400> 101
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgccaggcc caccatgggt tggagctgta ttattctctt 29400
cctcgtcgcc accgcgaccg gagtgcattc cgagctcgtg atgacccagt caccatcatc 29460
cttgaccgtg actgcgggcg agaaggtcac gatgtcatgc aagtcgtcac aaagcctgct 29520
gaactccggc aatcagaaga attacctgac ctggtaccag cagaaaccgg gtcagccgcc 29580
aaaactgctg atctactggg catccacccg ggaaagcggg gtccctgacc ggttcactgg 29640
atcaggatca ggaaccgact ttaccctcac gatctcaagc gtccaagccg aggacttggc 29700
tgtgtactac tgccaaaatg actactcgta ccccctgact ttcggagctg ggaccaagct 29760
ggagatcaaa ggcggcggag ggtccggagg aggggggtcg ggaggggggg gaagcgaggt 29820
gcagctgctg gaacagagcg gagccgagct ggtgagacca ggcaccagcg tgaaaatctc 29880
gtgcaaggcc tcggggtacg ctttcacgaa ctactggttg ggttgggtga agcagcggcc 29940
gggtcatgga ctggagtgga tcggagacat ctttcccgga agcggaaata tccattacaa 30000
cgaaaagttt aaaggcaagg ccacccttac tgcggataag tcaagctcca ccgcttacat 30060
gcaactgtcc tcactgactt ttgaagacag cgctgtgtat ttctgcgctc gcctgcgcaa 30120
ttgggatgaa cctatggact actggggcca aggaaccacc gtgactgtgt cgtcgggagg 30180
gggaggctca caagtgcagc tgcagcagtc aggtgcagaa ttggccaggc cgggagccag 30240
cgtgaagatg tcgtgcaaag cctccggcta caccttcact cgctacacta tgcattgggt 30300
gaaacagcgg ccgggacaag ggctggagtg gatcggatac atcaatccat caagaggtta 30360
caccaactac aatcagaagt tcaaggacaa ggctaccctg acgactgata agagctcgtc 30420
aactgcatac atgcagctgt cgagcctgac cagcgaggat tccgccgtgt actactgcgc 30480
gagatactat gatgaccact actgcttgga ttactggggc caagggacca ctctgaccgt 30540
gtcctccggc ggagggggct cgggcggcgg gggctcgggg ggcggcggca gcgacatcgt 30600
gctgacgcag agccccgcaa tcatgtcagc ctcccctggc gaaaaagtga cgatgacctg 30660
ctccgcttcc tcatcagtct cctacatgaa ctggtatcaa cagaagagcg gaacctcgcc 30720
gaagcgctgg atctacgata cctccaaact ggccagcgga gtgccggcgc attttcgggg 30780
atcgggcagc ggtacctcct actcgctcac catctcagga atggaagccg aagacgccgc 30840
cacctactac tgccagcagt ggtcctcaaa cccattcacc ttcggatccg gcactaagct 30900
ggaaatcaac cgcgggagcg gagcgactaa cttcagcttg ctcaagcaag ccggagatgt 30960
cgaggagaac ccgggacctg gttggtcgtg catcatccta ttccttgtcg cgaccgcaac 31020
tggcgtccat tccgacatcg tcatgaccca atccccagat tcgctggcgg tgtcgcttgg 31080
ggaacgggca accatcaact gcaagagctc gcagtcactg ctatacagcc ggaatcagaa 31140
aaactacctg gcgtggtacc agcaaaagcc gggtcagcct ccgaagctgc tgattttctg 31200
ggcctcaacc cgggaatccg gagtccctga cagattcagc gggtccggat tcgggaccga 31260
cttcactctg actatttcga gcctgcaagc agaagatgtg gcagtgtact attgccaaca 31320
gtatttttca tacccgctga ccttcggcca gggtacgaag gtggagatca agggtggagg 31380
gggtagcggc gggggaggca gcggcggggg gggaagccag gtgcagctgg tccaatcagg 31440
cgccgaggtc aagaaacctg gagcgtcggt caaggtctcc tgcaagacta gccgctacac 31500
ttttaccgaa tacaccatcc actgggtcag acaggcgccc ggtcagcgcc tggagtggat 31560
cggcgggatc aacccgaata atggaatccc gaactacaat caaaaattca aaggccgcgt 31620
gactatcacc gtggatactt cagcctcaac tgcttacatg gaactgtcat cgctgagatc 31680
agaggacact gcggtctact actgtgcgcg cagaagaatc gcttacggat acgacgaggg 31740
gcacgcaatg gactactggg gacagggaac cctggtgacc gtgtcgtcag gcggaggagg 31800
atcggatgtg cagttggtgc agtcgggcgc cgaagtgaaa aaaccggggg cctcagtgaa 31860
agtgtcctgc aaggcctccg gatacacctt cacccgctac actatgcact gggtcaggca 31920
ggcgcccggg cagggcctgg agtggatcgg gtatatcaac ccgtcaaggg gatacactaa 31980
ctacgccgac tccgtgaagg gaagattcac tatcaccact gacaaatcaa cttcgacggc 32040
gtatatggaa ctgtcatcct tgagatcgga agataccgcg acctactact gtgcgcgcta 32100
ctacgatgac cattactgcc tcgattactg gggacagggc accacggtga ccgtctcatc 32160
aggagaagga acttcaactg gttccggagg ctccggcggc tcaggcggcg ctgacgacat 32220
tgtgctgacc cagagcccgg cgaccctgtc actctcgccg ggggaaaggg ctactctgtc 32280
atgcagagcg tcacaatcgg tctcatacat gaactggtac cagcagaaac cgggcaaggc 32340
tccaaagcgg tggatctacg atacttcgaa ggtggcttca ggagtgccgg ctcgcttcag 32400
cggatccggc tcgggaaccg attacagctt gaccattaac tcgctggagg cggaggatgc 32460
agcgacctac tactgtcaac aatggtcctc gaacccactc acttttgggg gcgggaccaa 32520
ggtggagatt aagtaggcta gcttgactga ctgagataca gcgtaccttc agctcacaga 32580
catgataaga tacattgatg agtttggaca aaccacaact agaatgcagt gaaaaaaatg 32640
ctttatttgt gaaatttgtg atgctattgc tttatttgta accattataa gctgcaataa 32700
acaagttaac aacaacaatt gcattcattt tatgtttcag gttcaggggg aggtgtggga 32760
ggttttttaa agcaagtaaa acctctacaa atgtggtagt cgtcagctat cctgcaggaa 32820
cttgtttatt tgaaaatcaa ttcacaaaat ccgagtagtt attttgcctc ccccttccca 32880
tttaacagaa tacaccaatc tctccccacg cacagcttta aacatttgga taccattaga 32940
tatagacatg gttttagatt ccacattcca aacagtttca gagcgagcca atctggggtc 33000
agtgatagat aaaaatccat cgggatagtc ttttaaagcg ctttcacagt ccaactgctg 33060
cggatgcgac tccggagtct ggatcacggt catctggaag aagaacgatg ggaatcataa 33120
tccgaaaacg gtatcggacg attgtgtctc atcaaaccca caagcagccg ctgtctgcgt 33180
cgctccgtgc gactgctgtt tatgggatca gggtccacag tgtcctgaag catgatttta 33240
atagccctta acatcaactt tctggtgcga tgcgcgcagc aacgcattct gatttcactc 33300
aaatctttgc agtaggtaca acacattatt acaatattgt ttaataaacc ataattaaaa 33360
gcgctccagc caaaactcat atctgatata atcgcccctg catgaccatc ataccaaagt 33420
ttaatataaa ttaaatgacg ttccctcaaa aacacactac ccacatacat gatctctttt 33480
ggcatgtgca tattaacaat ctgtctgtac catggacaac gttggttaat catgcaaccc 33540
aatataacct tccggaacca cactgccaac accgctcccc cagccatgca ttgaagtgaa 33600
ccctgctgat tacaatgaca atgaagaacc caattctctc gaccgtgaat cacttgagaa 33660
tgaaaaatat ctatagtggc acaacataga cataaatgca tgcatcttct cataattttt 33720
aactcctcag gatttagaaa catatcccag ggaataggaa gctcttgcag aacagtaaag 33780
ctggcagaac aaggaagacc acgaacacaa cttacactat gcatagtcat agtatcacaa 33840
tctggcaaca gcgggtggtc ttcagtcata gaagctcggg tttcattttc ctcacaacgt 33900
ggtaactggg ctctggtgta agggtgatgt ctggcgcatg atgtcgagcg tgcgcgcaac 33960
cttgtcataa tggagttgct tcctgacatt ctcgtatttt gtatagcaaa acgcggccct 34020
ggcagaacac actcttcttc gccttctatc ctgccgctta gcgtgttccg tgtgatagtt 34080
caagtacaac cacactctta agttggtcaa aagaatgctg gcttcagttg taatcaaaac 34140
tccatcgcat ctaatcgttc tgaggaaatc atccaagcaa tgcaactgga ttgtgtttca 34200
agcaggagag gagagggaag agacggaaga accatgttaa tttttattcc aaacgatctc 34260
gcagtacttc aaattgtaga tcgcgcagat ggcatctctc gcccccactg tgttggtgaa 34320
aaagcacagc tagatcaaaa gaaatgcgat tttcaaggtg ctcaacggtg gcttccagca 34380
aagcctccac gcgcacatcc aagaacaaaa gaataccaaa agaaggagca ttttctaact 34440
cctcaatcat catattacat tcctgcacca ttcccagata attttcagct ttccagcctt 34500
gaattattcg tgtcagttct tgtggtaaat ccaatccaca cattacaaac aggtcccgga 34560
gggcgccctc caccaccatt cttaaacaca ccctcataat gacaaaatat cttgctcctg 34620
tgtcacctgt agcgaattga gaatggcaac atcaattgac atgcccttgg ctctaagttc 34680
ttctttaagt tctagttgta aaaactctct catattatca ccaaactgct tagccagaag 34740
ccccccggga acaagagcag gggacgctac agtgcagtac aagcgcagac ctccccaatt 34800
ggctccagca aaaacaagat tggaataagc atattgggaa ccgccagtaa tatcatcgaa 34860
gttgctggaa atataatcag gcagagtttc ttgtaaaaat tgaataaaag aaaaatttgc 34920
caaaaaaaca ttcaaaacct ctgggatgca aatgcaatag gttaccgcgc tgcgctccaa 34980
cattgttagt tttgaattag tctgcaaaaa taaaaaaaaa aacaagcgtc atatcatagt 35040
agcctgacga acagatggat aaatcagtct ttccatcaca agacaagcca cagggtctcc 35100
agctcgaccc tcgtaaaacc tgtcatcatg attaaacaac agcaccgaaa gttcctcgcg 35160
gtgaccagca tgaataattc ttgatgaagc atacaatcca gacatgttag catcagttaa 35220
cgagaaaaaa cagccaacat agcctttggg tataattatg cttaatcgta agtatagcaa 35280
agccacccct cgcggataca aagtaaaagg cacaggagaa taaaaaatat aattatttct 35340
ctgctgctgt tcaggcaacg tcgcccccgg tccctctaaa tacacataca aagcctcatc 35400
agccatggct taccagacaa agtacagcgg gcacacaaag cacaagctct aaagtgactc 35460
tccaacctct ccacaatata tatatacaca agccctaaac tgacgtaatg ggagtaaagt 35520
gtaaaaaatc ccgccaaacc caacacacac cccgaaactg cgtcaccagg gaaaagtaca 35580
gtttcacttc cgcaatccca acaggcgtaa cttcctcttt ctcacggtac gtgatatccc 35640
actaacttgc aacgtcattt tcccacggtc gcaccgcccc ttttagccgt taaccccaca 35700
gccaatcacc acacgatcca cactttttaa aatcacctca tttacatatt ggcaccattc 35760
catctataag gtatattata tagataga 35788
<210> 102
<211> 1557
<212> DNA
<213> 人工序列
<220>
<223> NG-618 FAP BiTE核酸序列
<400> 102
atgggttggt cgtgcatcat cctattcctt gtcgcgaccg caactggcgt ccattccgac 60
atcgtcatga cccaatcccc agattcgctg gcggtgtcgc ttggggaacg ggcaaccatc 120
aactgcaaga gctcgcagtc actgctatac agccggaatc agaaaaacta cctggcgtgg 180
taccagcaaa agccgggtca gcctccgaag ctgctgattt tctgggcctc aacccgggaa 240
tccggagtcc ctgacagatt cagcgggtcc ggattcggga ccgacttcac tctgactatt 300
tcgagcctgc aagcagaaga tgtggcagtg tactattgcc aacagtattt ttcatacccg 360
ctgaccttcg gccagggtac gaaggtggag atcaagggtg gagggggtag cggcggggga 420
ggcagcggcg gggggggaag ccaggtgcag ctggtccaat caggcgccga ggtcaagaaa 480
cctggagcgt cggtcaaggt ctcctgcaag actagccgct acacttttac cgaatacacc 540
atccactggg tcagacaggc gcccggtcag cgcctggagt ggatcggcgg gatcaacccg 600
aataatggaa tcccgaacta caatcaaaaa ttcaaaggcc gcgtgactat caccgtggat 660
acttcagcct caactgctta catggaactg tcatcgctga gatcagagga cactgcggtc 720
tactactgtg cgcgcagaag aatcgcttac ggatacgacg aggggcacgc aatggactac 780
tggggacagg gaaccctggt gaccgtgtcg tcaggcggag gaggatcgga tgtgcagttg 840
gtgcagtcgg gcgccgaagt gaaaaaaccg ggggcctcag tgaaagtgtc ctgcaaggcc 900
tccggataca ccttcacccg ctacactatg cactgggtca ggcaggcgcc cgggcagggc 960
ctggagtgga tcgggtatat caacccgtca aggggataca ctaactacgc cgactccgtg 1020
aagggaagat tcactatcac cactgacaaa tcaacttcga cggcgtatat ggaactgtca 1080
tccttgagat cggaagatac cgcgacctac tactgtgcgc gctactacga tgaccattac 1140
tgcctcgatt actggggaca gggcaccacg gtgaccgtct catcaggaga aggaacttca 1200
actggttccg gaggctccgg cggctcaggc ggcgctgacg acattgtgct gacccagagc 1260
ccggcgaccc tgtcactctc gccgggggaa agggctactc tgtcatgcag agcgtcacaa 1320
tcggtctcat acatgaactg gtaccagcag aaaccgggca aggctccaaa gcggtggatc 1380
tacgatactt cgaaggtggc ttcaggagtg ccggctcgct tcagcggatc cggctcggga 1440
accgattaca gcttgaccat taactcgctg gaggcggagg atgcagcgac ctactactgt 1500
caacaatggt cctcgaaccc actcactttt gggggcggga ccaaggtgga gattaag 1557
<210> 103
<211> 3169
<212> DNA
<213> 人工序列
<220>
<223> NG-618转基因盒
<400> 103
caggcccacc atgggttgga gctgtattat tctcttcctc gtcgccaccg cgaccggagt 60
gcattccgag ctcgtgatga cccagtcacc atcatccttg accgtgactg cgggcgagaa 120
ggtcacgatg tcatgcaagt cgtcacaaag cctgctgaac tccggcaatc agaagaatta 180
cctgacctgg taccagcaga aaccgggtca gccgccaaaa ctgctgatct actgggcatc 240
cacccgggaa agcggggtcc ctgaccggtt cactggatca ggatcaggaa ccgactttac 300
cctcacgatc tcaagcgtcc aagccgagga cttggctgtg tactactgcc aaaatgacta 360
ctcgtacccc ctgactttcg gagctgggac caagctggag atcaaaggcg gcggagggtc 420
cggaggaggg gggtcgggag gggggggaag cgaggtgcag ctgctggaac agagcggagc 480
cgagctggtg agaccaggca ccagcgtgaa aatctcgtgc aaggcctcgg ggtacgcttt 540
cacgaactac tggttgggtt gggtgaagca gcggccgggt catggactgg agtggatcgg 600
agacatcttt cccggaagcg gaaatatcca ttacaacgaa aagtttaaag gcaaggccac 660
ccttactgcg gataagtcaa gctccaccgc ttacatgcaa ctgtcctcac tgacttttga 720
agacagcgct gtgtatttct gcgctcgcct gcgcaattgg gatgaaccta tggactactg 780
gggccaagga accaccgtga ctgtgtcgtc gggaggggga ggctcacaag tgcagctgca 840
gcagtcaggt gcagaattgg ccaggccggg agccagcgtg aagatgtcgt gcaaagcctc 900
cggctacacc ttcactcgct acactatgca ttgggtgaaa cagcggccgg gacaagggct 960
ggagtggatc ggatacatca atccatcaag aggttacacc aactacaatc agaagttcaa 1020
ggacaaggct accctgacga ctgataagag ctcgtcaact gcatacatgc agctgtcgag 1080
cctgaccagc gaggattccg ccgtgtacta ctgcgcgaga tactatgatg accactactg 1140
cttggattac tggggccaag ggaccactct gaccgtgtcc tccggcggag ggggctcggg 1200
cggcgggggc tcggggggcg gcggcagcga catcgtgctg acgcagagcc ccgcaatcat 1260
gtcagcctcc cctggcgaaa aagtgacgat gacctgctcc gcttcctcat cagtctccta 1320
catgaactgg tatcaacaga agagcggaac ctcgccgaag cgctggatct acgatacctc 1380
caaactggcc agcggagtgc cggcgcattt tcggggatcg ggcagcggta cctcctactc 1440
gctcaccatc tcaggaatgg aagccgaaga cgccgccacc tactactgcc agcagtggtc 1500
ctcaaaccca ttcaccttcg gatccggcac taagctggaa atcaaccgcg ggagcggagc 1560
gactaacttc agcttgctca agcaagccgg agatgtcgag gagaacccgg gacctggttg 1620
gtcgtgcatc atcctattcc ttgtcgcgac cgcaactggc gtccattccg acatcgtcat 1680
gacccaatcc ccagattcgc tggcggtgtc gcttggggaa cgggcaacca tcaactgcaa 1740
gagctcgcag tcactgctat acagccggaa tcagaaaaac tacctggcgt ggtaccagca 1800
aaagccgggt cagcctccga agctgctgat tttctgggcc tcaacccggg aatccggagt 1860
ccctgacaga ttcagcgggt ccggattcgg gaccgacttc actctgacta tttcgagcct 1920
gcaagcagaa gatgtggcag tgtactattg ccaacagtat ttttcatacc cgctgacctt 1980
cggccagggt acgaaggtgg agatcaaggg tggagggggt agcggcgggg gaggcagcgg 2040
cgggggggga agccaggtgc agctggtcca atcaggcgcc gaggtcaaga aacctggagc 2100
gtcggtcaag gtctcctgca agactagccg ctacactttt accgaataca ccatccactg 2160
ggtcagacag gcgcccggtc agcgcctgga gtggatcggc gggatcaacc cgaataatgg 2220
aatcccgaac tacaatcaaa aattcaaagg ccgcgtgact atcaccgtgg atacttcagc 2280
ctcaactgct tacatggaac tgtcatcgct gagatcagag gacactgcgg tctactactg 2340
tgcgcgcaga agaatcgctt acggatacga cgaggggcac gcaatggact actggggaca 2400
gggaaccctg gtgaccgtgt cgtcaggcgg aggaggatcg gatgtgcagt tggtgcagtc 2460
gggcgccgaa gtgaaaaaac cgggggcctc agtgaaagtg tcctgcaagg cctccggata 2520
caccttcacc cgctacacta tgcactgggt caggcaggcg cccgggcagg gcctggagtg 2580
gatcgggtat atcaacccgt caaggggata cactaactac gccgactccg tgaagggaag 2640
attcactatc accactgaca aatcaacttc gacggcgtat atggaactgt catccttgag 2700
atcggaagat accgcgacct actactgtgc gcgctactac gatgaccatt actgcctcga 2760
ttactgggga cagggcacca cggtgaccgt ctcatcagga gaaggaactt caactggttc 2820
cggaggctcc ggcggctcag gcggcgctga cgacattgtg ctgacccaga gcccggcgac 2880
cctgtcactc tcgccggggg aaagggctac tctgtcatgc agagcgtcac aatcggtctc 2940
atacatgaac tggtaccagc agaaaccggg caaggctcca aagcggtgga tctacgatac 3000
ttcgaaggtg gcttcaggag tgccggctcg cttcagcgga tccggctcgg gaaccgatta 3060
cagcttgacc attaactcgc tggaggcgga ggatgcagcg acctactact gtcaacaatg 3120
gtcctcgaac ccactcactt ttgggggcgg gaccaaggtg gagattaag 3169
<210> 104
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 104
Ser Gly Gly Gly Gly Ser Glu
1 5
<210> 105
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 105
Asp Lys Thr His Thr Ser
1 5
<210> 106
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> SITE
<222> (1)..(1)
<223> Ser是任选的
<400> 106
Ser Gly Gly Gly Gly Ser
1 5
<210> 107
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> SITE
<222> (1)..(1)
<223> Ser是任选的
<400> 107
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10
<210> 108
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> SITE
<222> (1)..(1)
<223> Ser是任选的
<400> 108
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 109
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> SITE
<222> (1)..(1)
<223> Ser是任选的
<400> 109
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
Gly Gly Gly Gly Ser
20
<210> 110
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> SITE
<222> (1)..(1)
<223> Ser是任选的
<400> 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25
<210> 111
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 111
Ala Ala Ala Gly Ser Gly Gly Ala Ser Ala Ser
1 5 10
<210> 112
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<400> 112
Ala Ala Ala Gly Ser Gly Xaa Gly Gly Gly Ser Gly Ala Ser Ala Ser
1 5 10 15
<210> 113
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa可以是任何天然存在的氨基酸
<400> 113
Ala Ala Ala Gly Ser Gly Xaa Gly Gly Gly Ser Xaa Gly Gly Gly Ser
1 5 10 15
Gly Ala Ser Ala Ser
20
<210> 114
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (17)..(17)
<223> Xaa可以是任何天然存在的氨基酸
<400> 114
Ala Ala Ala Gly Ser Gly Xaa Gly Gly Gly Ser Xaa Gly Gly Gly Ser
1 5 10 15
Xaa Gly Gly Gly Ser Gly Ala Ser Ala Ser
20 25
<210> 115
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (17)..(17)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (22)..(22)
<223> Xaa可以是任何天然存在的氨基酸
<400> 115
Ala Ala Ala Gly Ser Gly Xaa Gly Gly Gly Ser Xaa Gly Gly Gly Ser
1 5 10 15
Xaa Gly Gly Gly Ser Xaa Gly Gly Gly Ser Gly Ala Ser Ala Ser
20 25 30
<210> 116
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<400> 116
Ala Ala Ala Gly Ser Gly Xaa Ser Gly Ala Ser Ala Ser
1 5 10
<210> 117
<211> 28
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 117
Pro Gly Gly Asn Arg Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr Thr
1 5 10 15
Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr
20 25
<210> 118
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 118
Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr
1 5 10
<210> 119
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 119
Ala Thr Thr Thr Gly Ser
1 5
<210> 120
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 120
Met Pro Ser Leu Ser Gly Val Leu Gln Val Arg Tyr Leu Ser Pro Pro
1 5 10 15
Asp Leu
<210> 121
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 121
Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Ser Pro Pro Ser Lys Glu
1 5 10 15
Ser His Lys Ser Pro
20
<210> 122
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 122
Gly Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
1 5 10 15
<210> 123
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 123
Gly Gly Gly Gly Ile Ala Pro Ser Met Val Gly Gly Gly Gly Ser
1 5 10 15
<210> 124
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 124
Gly Gly Gly Gly Lys Val Glu Gly Ala Gly Gly Gly Gly Gly Ser
1 5 10 15
<210> 125
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 125
Gly Gly Gly Gly Ser Met Lys Ser His Asp Gly Gly Gly Gly Ser
1 5 10 15
<210> 126
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 126
Gly Gly Gly Gly Asn Leu Ile Thr Ile Val Gly Gly Gly Gly Ser
1 5 10 15
<210> 127
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 127
Gly Gly Gly Gly Val Val Pro Ser Leu Pro Gly Gly Gly Gly Ser
1 5 10 15
<210> 128
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 128
Gly Gly Glu Lys Ser Ile Pro Gly Gly Gly Gly Ser
1 5 10
<210> 129
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 129
Arg Pro Leu Ser Tyr Arg Pro Pro Phe Pro Phe Gly Phe Pro Ser Val
1 5 10 15
Arg Pro
<210> 130
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 130
Tyr Pro Arg Ser Ile Tyr Ile Arg Arg Arg His Pro Ser Pro Ser Leu
1 5 10 15
Thr Thr
<210> 131
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 131
Thr Pro Ser His Leu Ser His Ile Leu Pro Ser Phe Gly Leu Pro Thr
1 5 10 15
Phe Asn
<210> 132
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 132
Arg Pro Val Ser Pro Phe Thr Phe Pro Arg Leu Ser Asn Ser Trp Leu
1 5 10 15
Pro Ala
<210> 133
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 133
Ser Pro Ala Ala His Phe Pro Arg Ser Ile Pro Arg Pro Gly Pro Ile
1 5 10 15
Arg Thr
<210> 134
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 134
Ala Pro Gly Pro Ser Ala Pro Ser His Arg Ser Leu Pro Ser Arg Ala
1 5 10 15
Phe Gly
<210> 135
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 135
Pro Arg Asn Ser Ile His Phe Leu His Pro Leu Leu Val Ala Pro Leu
1 5 10 15
Gly Ala
<210> 136
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 136
Asn Pro Ser Leu Asn Pro Pro Ser Tyr Leu His Arg Ala Pro Ser Arg
1 5 10 15
Ile Ser
<210> 137
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 137
Leu Pro Trp Arg Thr Ser Leu Leu Pro Ser Leu Pro Leu Arg Arg Arg
1 5 10 15
Pro
<210> 138
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 138
Pro Pro Leu Phe Ala Lys Gly Pro Val Gly Leu Leu Ser Arg Ser Phe
1 5 10 15
Pro Pro
<210> 139
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 139
Val Pro Pro Ala Pro Val Val Ser Leu Arg Ser Ala His Ala Arg Pro
1 5 10 15
Pro Tyr
<210> 140
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 140
Leu Arg Pro Thr Pro Pro Arg Val Arg Ser Tyr Thr Cys Cys Pro Thr
1 5 10 15
Pro
<210> 141
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 141
Pro Asn Val Ala His Val Leu Pro Leu Leu Thr Val Pro Trp Asp Asn
1 5 10 15
Leu Arg
<210> 142
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 柔性连接子序列
<400> 142
Cys Asn Pro Leu Leu Pro Leu Cys Ala Arg Ser Pro Ala Val Arg Thr
1 5 10 15
Phe Pro
<210> 143
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 刚性连接子
<400> 143
Gly Ala Pro Ala Pro Ala Ala Pro Ala Pro Ala
1 5 10
<210> 144
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 刚性连接子
<400> 144
Pro Pro Pro Pro
1
<210> 145
<400> 145
000
<210> 146
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa可以是任何天然存在的氨基酸
<400> 146
Asp Lys Thr His Thr Cys Xaa Xaa
1 5
<210> 147
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 147
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10
<210> 148
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 148
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala
<210> 149
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 149
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 150
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 150
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr
20 25 30
<210> 151
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 151
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys Tyr
20 25 30
<210> 152
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 152
Asp Lys Thr His Thr Cys Cys Val Glu Cys Pro Pro Cys Pro Ala
1 5 10 15
<210> 153
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 153
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala
20 25
<210> 154
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 154
Asp Lys Thr His Thr Cys Pro Ser Cys Pro Ala
1 5 10
<210> 155
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa可以是任何天然存在的氨基酸
<400> 155
Asp Lys Thr His Thr Ser Xaa Xaa
1 5
<210> 156
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 156
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala
1 5 10
<210> 157
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 157
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala
1 5 10
<210> 158
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 158
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala
1 5 10
<210> 159
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 159
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala
<210> 160
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 160
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala
<210> 161
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 161
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala
<210> 162
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 162
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala
<210> 163
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 163
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala
<210> 164
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 164
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala
<210> 165
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 165
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala
<210> 166
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 166
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala
<210> 167
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 167
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala
<210> 168
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 168
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala
<210> 169
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 169
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala
<210> 170
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 170
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala
<210> 171
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 171
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala
<210> 172
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 172
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala
<210> 173
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 173
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala
<210> 174
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 174
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 175
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 175
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 176
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 176
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 177
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 177
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 178
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 178
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 179
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 179
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 180
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 180
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 181
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 181
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 182
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 182
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 183
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 183
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 184
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 184
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 185
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 185
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 186
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 186
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 187
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 187
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 188
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 188
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 189
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 189
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 190
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 190
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 191
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 191
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 192
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 192
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 193
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 193
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 194
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 194
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 195
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 195
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 196
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 196
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 197
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 197
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 198
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 198
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 199
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 199
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 200
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 200
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 201
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 201
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 202
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 202
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 203
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 203
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 204
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 204
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 205
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 205
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 206
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 206
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 207
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 207
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 208
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 208
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 209
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 209
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 210
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 210
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 211
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 211
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 212
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 212
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 213
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 213
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Cys Pro Ala
20 25
<210> 214
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 214
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 215
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 215
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 216
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 216
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 217
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 217
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 218
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 218
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Cys Pro Ala
20 25
<210> 219
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 219
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 220
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 220
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Cys Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 221
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 221
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Cys
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 222
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 222
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Cys Pro Pro Ser Pro Ala
20 25
<210> 223
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 223
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Thr Ser Pro Pro Ser
1 5 10 15
Pro Ala Thr Ser Pro Pro Ser Pro Ala
20 25
<210> 224
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 224
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Ser Tyr
20 25 30
<210> 225
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 225
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr
20 25 30
<210> 226
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 226
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr
20 25 30
<210> 227
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 227
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Ser Tyr
20 25 30
<210> 228
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 228
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr
20 25 30
<210> 229
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 229
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Ser Tyr
20 25 30
<210> 230
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 230
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Gly Lys Pro Thr Leu
1 5 10 15
Tyr Asn Ser Leu Val Met Ser Asp Thr Ala Gly Thr Ser Tyr
20 25 30
<210> 231
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 231
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Ser Tyr
20 25 30
<210> 232
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 232
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys Tyr
20 25 30
<210> 233
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 233
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys Tyr
20 25 30
<210> 234
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 234
Asp Lys Thr His Thr Cys Pro Pro Ser Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Ser Tyr
20 25 30
<210> 235
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 235
Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Ser Tyr
20 25 30
<210> 236
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 236
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys Tyr
20 25 30
<210> 237
<211> 31
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 237
Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Gly Lys Pro Thr His
1 5 10 15
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Ser Tyr
20 25 30
<210> 238
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 238
Asp Lys Thr His Thr Cys Cys Val Glu Cys Pro Pro Ser Pro Ala
1 5 10 15
<210> 239
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 239
Asp Lys Thr His Thr Cys Cys Val Glu Ser Pro Pro Cys Pro Ala
1 5 10 15
<210> 240
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 240
Asp Lys Thr His Thr Cys Ser Val Glu Cys Pro Pro Cys Pro Ala
1 5 10 15
<210> 241
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 241
Asp Lys Thr His Thr Ser Cys Val Glu Cys Pro Pro Cys Pro Ala
1 5 10 15
<210> 242
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 242
Asp Lys Thr His Thr Cys Cys Val Glu Ser Pro Pro Ser Pro Ala
1 5 10 15
<210> 243
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 243
Asp Lys Thr His Thr Cys Ser Val Glu Cys Pro Pro Ser Pro Ala
1 5 10 15
<210> 244
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 244
Asp Lys Thr His Thr Ser Cys Val Glu Cys Pro Pro Ser Pro Ala
1 5 10 15
<210> 245
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 245
Asp Lys Thr His Thr Cys Ser Val Glu Ser Pro Pro Cys Pro Ala
1 5 10 15
<210> 246
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 246
Asp Lys Thr His Thr Ser Ser Val Glu Cys Pro Pro Cys Pro Ala
1 5 10 15
<210> 247
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 247
Asp Lys Thr His Thr Cys Ser Val Glu Ser Pro Pro Ser Pro Ala
1 5 10 15
<210> 248
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 248
Asp Lys Thr His Thr Ser Ser Val Glu Cys Pro Pro Ser Pro Ala
1 5 10 15
<210> 249
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 249
Asp Lys Thr His Thr Ser Ser Val Glu Ser Pro Pro Cys Pro Ala
1 5 10 15
<210> 250
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 250
Asp Lys Thr His Thr Ser Ser Val Glu Ser Pro Pro Ser Pro Ala
1 5 10 15
<210> 251
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 251
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 252
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 252
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Cys Pro Ala
20 25
<210> 253
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 253
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala
20 25
<210> 254
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 254
Asp Lys Thr His Thr Cys Pro Arg Ser Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala
20 25
<210> 255
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 255
Asp Lys Thr His Thr Ser Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala
20 25
<210> 256
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 256
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 257
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 257
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 258
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 258
Asp Lys Thr His Thr Cys Pro Arg Ser Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 259
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 259
Asp Lys Thr His Thr Ser Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 260
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 260
Asp Lys Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 261
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 261
Asp Lys Thr His Thr Cys Pro Arg Ser Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 262
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 262
Asp Lys Thr His Thr Ser Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 263
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 263
Asp Lys Thr His Thr Cys Pro Arg Ser Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 264
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 264
Asp Lys Thr His Thr Ser Pro Arg Cys Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 265
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 265
Asp Lys Thr His Thr Ser Pro Arg Ser Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 266
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 266
Asp Lys Thr His Thr Cys Pro Arg Ser Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Cys Pro Ala
20 25
<210> 267
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 267
Asp Lys Thr His Thr Ser Pro Arg Cys Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Cys Pro Ala
20 25
<210> 268
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 268
Asp Lys Thr His Thr Ser Pro Arg Ser Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala
20 25
<210> 269
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 269
Asp Lys Thr His Thr Cys Pro Arg Ser Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 270
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 270
Asp Lys Thr His Thr Ser Pro Arg Ser Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Cys Pro Arg Ser Pro Ala
20 25
<210> 271
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 271
Asp Lys Thr His Thr Ser Pro Arg Ser Pro Glu Pro Lys Ser Cys Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 272
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 272
Asp Lys Thr His Thr Ser Pro Arg Cys Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 273
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 273
Asp Lys Thr His Thr Ser Pro Arg Ser Pro Glu Pro Lys Ser Ser Asp
1 5 10 15
Thr Pro Pro Pro Ser Pro Arg Ser Pro Ala
20 25
<210> 274
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 274
Asp Lys Thr His Thr Cys Pro Ser Ser Pro Ala
1 5 10
<210> 275
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 275
Asp Lys Thr His Thr Ser Pro Ser Cys Pro Ala
1 5 10
<210> 276
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 276
Asp Lys Thr His Thr Ser Pro Ser Ser Pro Ala
1 5 10
<210> 277
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 连接子序列
<400> 277
Gly Gly Gly Ser
1
<210> 278
<211> 35759
<212> DNA
<213> 人工序列
<220>
<223> NG-616基因组序列
<400> 278
tctatctata taatatacct tatagatgga atggtgccaa tatgtaaatg aggtgatttt 60
aaaaagtgtg gatcgtgtgg tgattggctg tggggttaac ggctaaaagg ggcggtgcga 120
ccgtgggaaa atgacgtttt gtgggggtgg agtttttttg caagttgtcg cgggaaatgt 180
gacgcataaa aaggcttttt tctcacggaa ctacttagtt ttcccacggt atttaacagg 240
aaatgaggta gttttgaccg gatgcaagtg aaaattgttg attttcgcgc gaaaactgaa 300
tgaggaagtg tttttctgaa taatgtggta tttatggcag ggtggagtat ttgttcaggg 360
ccaggtagac tttgacccat tacgtggagg tttcgattac cgtgtttttt acctgaattt 420
ccgcgtaccg tgtcaaagtc ttctgttttt acgtaggtgt cagctgatcg ctagggtatt 480
tatacctcag ggtttgtgtc aagaggccac tcttgagtgc cagcgagaag agttttctcc 540
tctgcgccgg cagtttaata ataaaaaaat gagagatttg cgatttctgc ctcaggaaat 600
aatctctgct gagactggaa atgaaatatt ggagcttgtg gtgcacgccc tgatgggaga 660
cgatccggag ccacctgtgc agctttttga gcctcctacg cttcaggaac tgtatgattt 720
agaggtagag ggatcggagg attctaatga ggaagctgta aatggctttt ttaccgattc 780
tatgctttta gctgctaatg aagggttaga attagatccg cctttggaca cttttgatac 840
tccaggggta attgtggaaa gcggtacagg tgtaagaaaa ttacctgatt tgagttccgt 900
ggactgtgat ttgcactgct atgaagacgg gtttcctccg agtgatgagg aggaccatga 960
aaaggagcag tccatgcaga ctgcagcggg tgagggagtg aaggctgcca atgttggttt 1020
tcagttggat tgcccggagc ttcctggaca tggctgtaag tcttgtgaat ttcacaggaa 1080
aaatactgga gtaaaggaac tgttatgttc gctttgttat atgagaacgc actgccactt 1140
tatttacagt aagtgtgttt aagttaaaat ttaaaggaat atgctgtttt tcacatgtat 1200
attgagtgtg agttttgtgc ttcttattat aggtcctgtg tctgatgctg atgaatcacc 1260
atctcctgat tctactacct cacctcctga gattcaagca cctgttcctg tggacgtgcg 1320
caagcccatt cctgtgaagc ttaagcctgg gaaacgtcca gcagtggaaa aacttgagga 1380
cttgttacag ggtggggacg gacctttgga cttgagtaca cggaaacgtc caagacaata 1440
agtgttccat atccgtgttt acttaaggtg acgtcaatat ttgtgtgaca gtgcaatgta 1500
ataaaaatat gttaactgtt cactggtttt tattgctttt tgggcgggga ctcaggtata 1560
taagtagaag cagacctgtg tggttagctc ataggagctg gctttcatcc atggaggttt 1620
gggccatttt ggaagacctt aggaagacta ggcaactgtt agagaacgct tcggacggag 1680
tctccggttt ttggagattc tggttcgcta gtgaattagc tagggtagtt tttaggataa 1740
aacaggacta taaacaagaa tttgaaaagt tgttggtaga ttgcccagga ctttttgaag 1800
ctcttaattt gggccatcag gttcacttta aagaaaaagt tttatcagtt ttagactttt 1860
caaccccagg tagaactgct gctgctgtgg cttttcttac ttttatatta gataaatgga 1920
tcccgcagac tcatttcagc aggggatacg ttttggattt catagccaca gcattgtgga 1980
gaacatggaa ggttcgcaag atgaggacaa tcttaggtta ctggccagtg cagcctttgg 2040
gtgtagcggg aatcctgagg catccaccgg tcatgccagc ggttctggag gaggaacagc 2100
aagaggacaa cccgagagcc ggcctggacc ctccagtgga ggaggcggag tagctgactt 2160
gtctcctgaa ctgcaacggg tgcttactgg atctacgtcc actggacggg ataggggcgt 2220
taagagggag agggcatcta gtggtactga tgctagatct gagttggctt taagtttaat 2280
gagtcgcaga cgtcctgaaa ccatttggtg gcatgaggtt cagaaagagg gaagggatga 2340
agtttctgta ttgcaggaga aatattcact ggaacaggtg aaaacatgtt ggttggagcc 2400
tgaggatgat tgggaggtgg ccattaaaaa ttatgccaag atagctttga ggcctgataa 2460
acagtataag attactagac ggattaatat ccggaatgct tgttacatat ctggaaatgg 2520
ggctgaggtg gtaatagata ctcaagacaa ggcagttatt agatgctgca tgatggatat 2580
gtggcctggg gtagtcggta tggaagcagt aacttttgta aatgttaagt ttaggggaga 2640
tggttataat ggaatagtgt ttatggccaa taccaaactt atattgcatg gttgtagctt 2700
ttttggtttc aacaatacct gtgtagatgc ctggggacag gttagtgtac ggggatgtag 2760
tttctatgcg tgttggattg ccacagctgg cagaaccaag agtcaattgt ctctgaagaa 2820
atgcatattt caaagatgta acctgggcat tctgaatgaa ggcgaagcaa gggtccgcca 2880
ctgcgcttct acagatactg gatgttttat tttgattaag ggaaatgcca gcgtaaagca 2940
taacatgatt tgcggtgctt ccgatgagag gccttatcaa atgctcactt gtgctggtgg 3000
gcattgtaat atgctggcta ctgtgcatat tgtttcccat caacgcaaaa aatggcctgt 3060
ttttgatcac aatgtgatga cgaagtgtac catgcatgca ggtgggcgta gaggaatgtt 3120
tatgccttac cagtgtaaca tgaatcatgt gaaagtgttg ttggaaccag atgccttttc 3180
cagaatgagc ctaacaggaa tttttgacat gaacatgcaa atctggaaga tcctgaggta 3240
tgatgatacg agatcgaggg tacgcgcatg cgaatgcgga ggcaagcatg ccaggttcca 3300
gccggtgtgt gtagatgtga ctgaagatct cagaccggat catttggtta ttgcccgcac 3360
tggagcagag ttcggatcca gtggagaaga aactgactaa ggtgagtatt gggaaaactt 3420
tggggtggga ttttcagatg gacagattga gtaaaaattt gttttttctg tcttgcagct 3480
gtcatgagtg gaaacgcttc ttttaagggg ggagtcttca gcccttatct gacagggcgt 3540
ctcccatcct gggcaggagt tcgtcagaat gttatgggat ctactgtgga tggaagaccc 3600
gtccaacccg ccaattcttc aacgctgacc tatgctactt taagttcttc acctttggac 3660
gcagctgcag ctgccgccgc cgcttctgtt gccgctaaca ctgtgcttgg aatgggttac 3720
tatggaagca tcatggctaa ttccacttcc tctaataacc cttctaccct gactcaggac 3780
aagttacttg tccttttggc ccagctggag gctttgaccc aacgtctggg tgaactttct 3840
cagcaggtgg tcgagttgcg agtacaaact gagtctgctg tcggcacggc aaagtctaaa 3900
taaaaaaatc ccagaatcaa tgaataaata aacaagcttg ttgttgattt aaaatcaagt 3960
gtttttattt catttttcgc gcacggtatg ccctagacca ccgatctcta tcattgagaa 4020
ctcggtggat tttttccagg atcctataga ggtgggattg aatgtttaga tacatgggca 4080
ttaggccgtc tttggggtgg agatagctcc attgaaggga ttcatgctcc ggggtagtgt 4140
tgtaaatcac ccagtcataa caaggtcgca gtgcatggtg ttgcacaata tcttttagaa 4200
gtaggctgat tgccacagat aagcccttgg tgtaggtgtt tacaaaccgg ttgagctggg 4260
atgggtgcat tcggggtgaa attatgtgca ttttggattg gatttttaag ttggcaatat 4320
tgccgccaag atcccgtctt gggttcatgt tatgaaggac caccaagacg gtgtatccgg 4380
tacatttagg aaatttatcg tgcagcttgg atggaaaagc gtggaaaaat ttggagacac 4440
ccttgtgtcc tccaagattt tccatgcact catccatgat aatagcaatg gggccgtggg 4500
cagcggcgcg ggcaaacacg ttccgtgggt ctgacacatc atagttatgt tcctgagtta 4560
aatcatcata agccatttta atgaatttgg ggcggagagt accagattgg ggtatgaatg 4620
ttccttcggg ccccggagca tagttcccct cacagatttg catttcccaa gctttcagtt 4680
ccgagggtgg aatcatgtcc acctgggggg ctatgaaaaa caccgtttct ggggcggggg 4740
tgattaattg tgatgatagc aaatttctga gcaattgaga tttgccacat ccggtggggc 4800
cataaatgat tccgattacg ggttgcaggt ggtagtttag ggaacggcaa ctgccgtctt 4860
ctcgaagcaa gggggccacc tcgttcatca tttcccttac atgcatattt tcccgcacca 4920
aatccattag gaggcgctct cctcctagtg atagaagttc ttgtagtgag gaaaagtttt 4980
tcagcggttt cagaccgtca gccatgggca ttttggagag agtttgctgc aaaagttcta 5040
gtctgttcca cagttcagtg atgtgttcta tggcatctcg atccagcaga cctcctcgtt 5100
tcgcgggttt ggacggctcc tggaataggg tatgagacga tgggcgtcca gcgctgccag 5160
ggttcggtcc ttccagggtc tcagtgttcg agtcagggtt gtttccgtca cagtgaaggg 5220
gtgtgcgcct gcttgggcgc ttgccagggt gcgcttcaga ctcatcctgc tggtcgaaaa 5280
cttctgtcgc ttggcgccct gtatgtcggc caagtagcag tttaccatga gttcgtagtt 5340
gagcgcctcg gctgcgtggc ctttggcgcg gagcttacct ttggaagttt tcttgcatac 5400
cgggcagtat aggcatttca gcgcatacaa cttgggcgca aggaaaacgg attctgggga 5460
gtatgcatct gcgccgcagg aggcgcaaac agtttcacat tccaccagcc aggttaaatc 5520
cggttcattg gggtcaaaaa caagttttcc gccatatttt ttgatgcgtt tcttaccttt 5580
ggtctccatg agttcgtgtc ctcgttgagt gacaaacagg ctgtccgtgt ccccgtagac 5640
tgattttaca ggcctcttct ccagtggagt gcctcggtct tcttcgtaca ggaactctga 5700
ccactctgat acaaaggcgc gcgtccaggc cagcacaaag gaggctatgt gggaggggta 5760
gcgatcgttg tcaaccaggg ggtccacctt ttccaaagta tgcaaacaca tgtcaccctc 5820
ttcaacatcc aggaatgtga ttggcttgta ggtgtatttc acgtgacctg gggtccccgc 5880
tgggggggta taaaaggggg cggttctttg ctcttcctca ctgtcttccg gatcgctgtc 5940
caggaacgtc agctgttggg gtaggtattc cctctcgaag gcgggcatga cctctgcact 6000
caggttgtca gtttctaaga acgaggagga tttgatattg acagtgccgg ttgagatgcc 6060
tttcatgagg ttttcgtcca tctggtcaga aaacacaatt tttttattgt caagtttggt 6120
ggcaaatgat ccatacaggg cgttggataa aagtttggca atggatcgca tggtttggtt 6180
cttttccttg tccgcgcgct ctttggcggc gatgttgagt tggacatact cgcgtgccag 6240
gcacttccat tcggggaaga tagttgttaa ttcatctggc acgattctca cttgccaccc 6300
tcgattatgc aaggtaatta aatccacact ggtggccacc tcgcctcgaa ggggttcatt 6360
ggtccaacag agcctacctc ctttcctaga acagaaaggg ggaagtgggt ctagcataag 6420
ttcatcggga gggtctgcat ccatggtaaa gattcccgga agtaaatcct tatcaaaata 6480
gctgatggga gtggggtcat ctaaggccat ttgccattct cgagctgcca gtgcgcgctc 6540
atatgggtta aggggactgc cccatggcat gggatgggtg agtgcagagg catacatgcc 6600
acagatgtca tagacgtaga tgggatcctc aaagatgcct atgtaggttg gatagcatcg 6660
cccccctctg atacttgctc gcacatagtc atatagttca tgtgatggcg ctagcagccc 6720
cggacccaag ttggtgcgat tgggtttttc tgttctgtag acgatctggc gaaagatggc 6780
gtgagaattg gaagagatgg tgggtctttg aaaaatgttg aaatgggcat gaggtagacc 6840
tacagagtct ctgacaaagt gggcataaga ttcttgaagc ttggttacca gttcggcggt 6900
gacaagtacg tctagggcgc agtagtcaag tgtttcttga atgatgtcat aacctggttg 6960
gtttttcttt tcccacagtt cgcggttgag aaggtattct tcgcgatcct tccagtactc 7020
ttctagcgga aacccgtctt tgtctgcacg gtaagatcct agcatgtaga actgattaac 7080
tgccttgtaa gggcagcagc ccttctctac gggtagagag tatgcttgag cagcttttcg 7140
tagcgaagcg tgagtaaggg caaaggtgtc tctgaccatg actttgagga attggtattt 7200
gaagtcgatg tcgtcacagg ctccctgttc ccagagttgg aagtctaccc gtttcttgta 7260
ggcggggttg ggcaaagcga aagtaacatc attgaagaga atcttgccgg ccctgggcat 7320
gaaattgcga gtgatgcgaa aaggctgtgg tacttccgct cggttattga taacctgggc 7380
agctaggacg atctcgtcga aaccgttgat gttgtgtcct acgatgtata attctatgaa 7440
acgcggcgtg cctctgacgt gaggtagctt actgagctca tcaaaggtta ggtctgtggg 7500
gtcagataag gcgtagtgtt cgagagccca ttcgtgcagg tgaggattcg ctttaaggaa 7560
ggaggaccag aggtccactg ccagtgctgt ttgtaactgg tcccggtact gacgaaaatg 7620
ccgtccgact gccatttttt ctggggtgac gcaatagaag gtttgggggt cctgccgcca 7680
gcgatcccac ttgagtttta tggcgaggtc ataggcgatg ttgacgagcc gctggtctcc 7740
agagagtttc atgaccagca tgaaggggat tagctgcttg ccaaaggacc ccatccaggt 7800
gtaggtttcc acatcgtagg tgagaaagag cctttctgtg cgaggatgag agccaatcgg 7860
gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat ggaagtagaa 7920
ctccctgcga cgcgccgagc attcatgctt gtgcttgtac agacggccgc agtagtcgca 7980
gcgttgcacg ggttgtatct cgtgaatgag ttgtacctgg cttcccttga cgagaaattt 8040
cagtgggaag ccgaggcctg gcgattgtat ctcgtgcttt actatgttgt ctgcatcggc 8100
ctgttcatct tctgtctcga tggtggtcat gctgacgagc cctcgcggga ggcaagtcca 8160
gacctcggcg cggcaggggc ggagctcgag gacgagagcg cgcaggctgg agctgtccag 8220
ggtcctgaga cgctgcggac tcaggttagt aggcagtgtc aggagattaa cttgcatgat 8280
cttttggagg gcgtgcggga ggttcagata gtacttgatc tcaacgggtc cgttggtgga 8340
gatgtcgatg gcttgcaggg ttccgtgtcc cttgggcgct accaccgtgc ccttgttttt 8400
cattttggac ggcggtggct ctgttgcttc ttgcatgttt agaagcggtg tcgagggcgc 8460
gcaccgggcg gcaggggcgg ctcgggaccc ggcggcatgg ctggcagtgg tacgtcggcg 8520
ccgcgcgcgg gtaggttctg gtactgcgcc ctgagaagac tcgcatgcgc gacgacgcgg 8580
cggttgacat cctggatctg acgcctctgg gtgaaagcta ccggccccgt gagcttgaac 8640
ctgaaagaga gttcaacaga atcaatctcg gtatcgttga cggcggcttg cctaaggatt 8700
tcttgcacgt caccagagtt gtcctggtag gcgatctccg ccatgaactg ctcgatctct 8760
tcctcttgaa gatctccgcg gcccgctctc tcgacggtgg ccgcgaggtc gttggagatg 8820
cgcccaatga gttgagagaa tgcattcatg cccgcctcgt tccagacgcg gctgtagacc 8880
acggccccca cgggatctct cgcgcgcatg accacctggg cgaggttgag ctccacgtgg 8940
cgggtgaaga ccgcatagtt gcataggcgc tggaaaaggt agttgagtgt ggtggcgatg 9000
tgctcggtga cgaagaaata catgatccat cgtctcagcg gcatctcgct gacatcgccc 9060
agagcttcca agcgctccat ggcctcgtag aagtccacgg caaaattaaa aaactgggag 9120
tttcgcgcgg acacggtcaa ctcctcttcc agaagacgga taagttcggc gatggtggtg 9180
cgcacctcgc gctcgaaagc ccctgggatt tcttcctcaa tctcttcttc ttccactaac 9240
atctcttcct cttcaggtgg ggctgcagga ggagggggaa cgcggcgacg ccggcggcgc 9300
acgggcagac ggtcgatgaa tctttcaatg acctctccgc ggcggcggcg catggtttca 9360
gtgacggcgc ggccgttctc gcgcggtcgc agagtaaaaa caccgccgcg catctcctta 9420
aagtggtgac tgggaggttc tccgtttggg agggagaggg cgctgattat acattttatt 9480
aattggcccg tagggactgc acgcagagat ctgatcgtgt caagatccac gggatctgaa 9540
aacctttcga cgaaagcgtc taaccagtca cagtcacaag gtaggctgag tacggcttct 9600
tgtgggcggg ggtggttatg tgttcggtct gggtcttctg tttcttcttc atctcgggaa 9660
ggtgagacga tgctgctggt gatgaaatta aagtaggcag ttctaagacg gcggatggtg 9720
gcgaggagca ccaggtcttt gggtccggct tgctggatac gcaggcgatt ggccattccc 9780
caagcattat cctgacatct agcaagatct ttgtagtagt cttgcatgag ccgttctacg 9840
ggcacttctt cctcacccgt tctgccatgc atacgtgtga gtccaaatcc gcgcattggt 9900
tgtaccagtg ccaagtcagc tacgactctt tcggcgagga tggcttgctg tacttgggta 9960
agggtggctt gaaagtcatc aaaatccaca aagcggtggt aagctcctgt attaatggtg 10020
taagcacagt tggccatgac tgaccagtta actgtctggt gaccagggcg cacgagctcg 10080
gtgtatttaa ggcgcgaata ggcgcgggtg tcaaagatgt aatcgttgca ggtgcgcacc 10140
agatactggt accctataag aaaatgcggc ggtggttggc ggtagagagg ccatcgttct 10200
gtagctggag cgccaggggc gaggtcttcc aacataaggc ggtgatagcc gtagatgtac 10260
ctggacatcc aggtgattcc tgcggcggta gtagaagccc gaggaaactc gcgtacgcgg 10320
ttccaaatgt tgcgtagcgg catgaagtag ttcattgtag gcacggtttg accagtgagg 10380
cgcgcgcagt cattgatgct ctatagacac ggagaaaatg aaagcgttca gcgactcgac 10440
tccgtagcct ggaggaacgt gaacgggttg ggtcgcggtg taccccggtt cgagacttgt 10500
actcgagccg gccggagccg cggctaacgt ggtattggca ctcccgtctc gacccagcct 10560
acaaaaatcc aggatacgga atcgagtcgt tttgctggtt tccgaatggc agggaagtga 10620
gtcctatttt ttttttttgc cgctcagatg catcccgtgc tgcgacagat gcgcccccaa 10680
caacagcccc cctcgcagca gcagcagcag caatcacaaa aggctgtccc tgcaactact 10740
gcaactgccg ccgtgagcgg tgcgggacag cccgcctatg atctggactt ggaagagggc 10800
gaaggactgg cacgtctagg tgcgccttca cccgagcggc atccgcgagt tcaactgaaa 10860
aaagattctc gcgaggcgta tgtgccccaa cagaacctat ttagagacag aagcggcgag 10920
gagccggagg agatgcgagc ttcccgcttt aacgcgggtc gtgagctgcg tcacggtttg 10980
gaccgaagac gagtgttgcg ggacgaggat ttcgaagttg atgaaatgac agggatcagt 11040
cctgccaggg cacacgtggc tgcagccaac cttgtatcgg cttacgagca gacagtaaag 11100
gaagagcgta acttccaaaa gtcttttaat aatcatgtgc gaaccctgat tgcccgcgaa 11160
gaagttaccc ttggtttgat gcatttgtgg gatttgatgg aagctatcat tcagaaccct 11220
actagcaaac ctctgaccgc ccagctgttt ctggtggtgc aacacagcag agacaatgag 11280
gctttcagag aggcgctgct gaacatcacc gaacccgagg ggagatggtt gtatgatctt 11340
atcaacattc tacagagtat catagtgcag gagcggagcc tgggcctggc cgagaaggtg 11400
gctgccatca attactcggt tttgagcttg ggaaaatatt acgctcgcaa aatctacaag 11460
actccatacg ttcccataga caaggaggtg aagatagatg ggttctacat gcgcatgacg 11520
ctcaaggtct tgaccctgag cgatgatctt ggggtgtatc gcaatgacag aatgcatcgc 11580
gcggttagcg ccagcaggag gcgcgagtta agcgacaggg aactgatgca cagtttgcaa 11640
agagctctga ctggagctgg aaccgagggt gagaattact tcgacatggg agctgacttg 11700
cagtggcagc ctagtcgcag ggctctgagc gccgcgacgg caggatgtga gcttccttac 11760
atagaagagg cggatgaagg cgaggaggaa gagggcgagt acttggaaga ctgatggcac 11820
aacccgtgtt ttttgctaga tggaacagca agcaccggat cccgcaatgc gggcggcgct 11880
gcagagccag ccgtccggca ttaactcctc ggacgattgg acccaggcca tgcaacgtat 11940
catggcgttg acgactcgca accccgaagc ctttagacag caaccccagg ccaaccgtct 12000
atcggccatc atggaagctg tagtgccttc ccgctctaat cccactcatg agaaggtcct 12060
ggccatcgtg aacgcgttgg tggagaacaa agctattcgt ccagatgagg ccggactggt 12120
atacaacgct ctcttagaac gcgtggctcg ctacaacagt agcaatgtgc aaaccaattt 12180
ggaccgtatg ataacagatg tacgcgaagc cgtgtctcag cgcgaaaggt tccagcgtga 12240
tgccaacctg ggttcgctgg tggcgttaaa tgctttcttg agtactcagc ctgctaatgt 12300
gccgcgtggt caacaggatt atactaactt tttaagtgct ttgagactga tggtatcaga 12360
agtacctcag agcgaagtgt atcagtccgg tcctgattac ttctttcaga ctagcagaca 12420
gggcttgcag acggtaaatc tgagccaagc ttttaaaaac cttaaaggtt tgtggggagt 12480
gcatgccccg gtaggagaaa gagcaaccgt gtctagcttg ttaactccga actcccgcct 12540
attattactg ttggtagctc ctttcaccga cagcggtagc atcgaccgta attcctattt 12600
gggttaccta ctaaacctgt atcgcgaagc catagggcaa agtcaggtgg acgagcagac 12660
ctatcaagaa attacccaag tcagtcgcgc tttgggacag gaagacactg gcagtttgga 12720
agccactctg aacttcttgc ttaccaatcg gtctcaaaag atccctcctc aatatgctct 12780
tactgcggag gaggagagga tccttagata tgtgcagcag agcgtgggat tgtttctgat 12840
gcaagagggg gcaactccga ctgcagcact ggacatgaca gcgcgaaata tggagcccag 12900
catgtatgcc agtaaccgac ctttcattaa caaactgctg gactacttgc acagagctgc 12960
cgctatgaac tctgattatt tcaccaatgc catcttaaac ccgcactggc tgcccccacc 13020
tggtttctac acgggcgaat atgacatgcc cgaccctaat gacggatttc tgtgggacga 13080
cgtggacagc gatgtttttt cacctctttc tgatcatcgc acgtggaaaa aggaaggcgg 13140
cgatagaatg cattcttctg catcgctgtc cggggtcatg ggtgctaccg cggctgagcc 13200
cgagtctgca agtccttttc ctagtctacc cttttctcta cacagtgtac gtagcagcga 13260
agtgggtaga ataagtcgcc cgagtttaat gggcgaagag gagtatctaa acgattcctt 13320
gctcagaccg gcaagagaaa aaaatttccc aaacaatgga atagaaagtt tggtggataa 13380
aatgagtaga tggaagactt atgctcagga tcacagagac gagcctggga tcatggggat 13440
tacaagtaga gcgagccgta gacgccagcg ccatgacaga cagaggggtc ttgtgtggga 13500
cgatgaggat tcggccgatg atagcagcgt gctggacttg ggtgggagag gaaggggcaa 13560
cccgtttgct catttgcgcc ctcgcttggg tggtatgttg taaaaaaaaa taaaaaaaaa 13620
actcaccaag gccatggcga cgagcgtacg ttcgttcttc tttattatct gtgtctagta 13680
taatgaggcg agtcgtgcta ggcggagcgg tggtgtatcc ggagggtcct cctccttcgt 13740
acgagagcgt gatgcagcag cagcaggcga cggcggtgat gcaatcccca ctggaggctc 13800
cctttgtgcc tccgcgatac ctggcaccta cggagggcag aaacagcatt cgttattcgg 13860
aactggcacc tcagtacgat accaccaggt tgtatctggt ggacaacaag tcggcggaca 13920
ttgcttctct gaactatcag aatgaccaca gcaacttctt gaccacggtg gtgcaaaaca 13980
atgactttac ccctacggaa gccagcaccc agaccattaa ctttgatgaa cgatcgcggt 14040
ggggcggtca gctaaagacc atcatgcata ctaacatgcc aaacgtgaac gagtatatgt 14100
ttagtaacaa gttcaaagcg cgtgtgatgg tgtccagaaa acctcccgac ggtgctgcag 14160
ttggggatac ttatgatcac aagcaggata ttttgaaata tgagtggttc gagtttactt 14220
tgccagaagg caacttttca gttactatga ctattgattt gatgaacaat gccatcatag 14280
ataattactt gaaagtgggt agacagaatg gagtgcttga aagtgacatt ggtgttaagt 14340
tcgacaccag gaacttcaag ctgggatggg atcccgaaac caagttgatc atgcctggag 14400
tgtatacgta tgaagccttc catcctgaca ttgtcttact gcctggctgc ggagtggatt 14460
ttaccgagag tcgtttgagc aaccttcttg gtatcagaaa aaaacagcca tttcaagagg 14520
gttttaagat tttgtatgaa gatttagaag gtggtaatat tccggccctc ttggatgtag 14580
atgcctatga gaacagtaag aaagaacaaa aagccaaaat agaagctgct acagctgctg 14640
cagaagctaa ggcaaacata gttgccagcg actctacaag ggttgctaac gctggagagg 14700
tcagaggaga caattttgcg ccaacacctg ttccgactgc agaatcatta ttggccgatg 14760
tgtctgaagg aacggacgtg aaactcacta ttcaacctgt agaaaaagat agtaagaata 14820
gaagctataa tgtgttggaa gacaaaatca acacagccta tcgcagttgg tatctttcgt 14880
acaattatgg cgatcccgaa aaaggagtgc gttcctggac attgctcacc acctcagatg 14940
tcacctgcgg agcagagcag gtctactggt cgcttccaga catgatgaag gatcctgtca 15000
ctttccgctc cactagacaa gtcagtaact accctgtggt gggtgcagag cttatgcccg 15060
tcttctcaaa gagcttctac aacgaacaag ctgtgtactc ccagcagctc cgccagtcca 15120
cctcgcttac gcacgtcttc aaccgctttc ctgagaacca gattttaatc cgtccgccgg 15180
cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac gggaccctgc 15240
cgttgcgcag cagtatccgg ggagtccaac gtgtgaccgt tactgacgcc agacgccgca 15300
cctgtcccta cgtgtacaag gcactgggca tagtcgcacc gcgcgtcctt tcaagccgca 15360
ctttctaaaa aaaaaaaaaa tgtccattct tatctcgccc agtaataaca ccggttgggg 15420
tctgcgcgct ccaagcaaga tgtacggagg cgcacgcaaa cgttctaccc aacatcctgt 15480
ccgtgttcgc ggacattttc gcgctccatg gggcgccctc aagggccgca ctcgcgttcg 15540
aaccaccgtc gatgatgtaa tcgatcaggt ggttgccgac gcccgtaatt atactcctac 15600
tgcgcctaca tctactgtgg atgcagttat tgacagtgta gtggctgacg ctcgcaacta 15660
tgctcgacgt aagagccggc gaaggcgcat tgccagacgc caccgagcta ccactgccat 15720
gcgagccgca agagctctgc tacgaagagc tagacgcgtg gggcgaagag ccatgcttag 15780
ggcggccaga cgtgcagctt cgggcgccag cgccggcagg tcccgcaggc aagcagccgc 15840
tgtcgcagcg gcgactattg ccgacatggc ccaatcgcga agaggcaatg tatactgggt 15900
gcgtgacgct gccaccggtc aacgtgtacc cgtgcgcacc cgtccccctc gcacttagaa 15960
gatactgagc agtctccgat gttgtgtccc agcggcgagg atgtccaagc gcaaatacaa 16020
ggaagaaatg ctgcaggtta tcgcacctga agtctacggc caaccgttga aggatgaaaa 16080
aaaaccccgc aaaatcaagc gggttaaaaa ggacaaaaaa gaagaggaag atggcgatga 16140
tgggctggcg gagtttgtgc gcgagtttgc cccacggcga cgcgtgcaat ggcgtgggcg 16200
caaagttcga catgtgttga gacctggaac ttcggtggtc tttacacccg gcgagcgttc 16260
aagcgctact tttaagcgtt cctatgatga ggtgtacggg gatgatgata ttcttgagca 16320
ggcggctgac cgattaggcg agtttgctta tggcaagcgt agtagaataa cttccaagga 16380
tgagacagtg tcgataccct tggatcatgg aaatcccacc cctagtctta aaccggtcac 16440
tttgcagcaa gtgttacccg taactccgcg aacaggtgtt aaacgcgaag gtgaagattt 16500
gtatcccact atgcaactga tggtacccaa acgccagaag ttggaggacg ttttggagaa 16560
agtaaaagtg gatccagata ttcaacctga ggttaaagtg agacccatta agcaggtagc 16620
gcctggtctg ggggtacaaa ctgtagacat taagattccc actgaaagta tggaagtgca 16680
aactgaaccc gcaaagccta ctgccacctc cactgaagtg caaacggatc catggatgcc 16740
catgcctatt acaactgacg ccgccggtcc cactcgaaga tcccgacgaa agtacggtcc 16800
agcaagtctg ttgatgccca attatgttgt acacccatct attattccta ctcctggtta 16860
ccgaggcact cgctactatc gcagccgaaa cagtacctcc cgccgtcgcc gcaagacacc 16920
tgcaaatcgc agtcgtcgcc gtagacgcac aagcaaaccg actcccggcg ccctggtgcg 16980
gcaagtgtac cgcaatggta gtgcggaacc tttgacactg ccgcgtgcgc gttaccatcc 17040
gagtatcatc acttaatcaa tgttgccgct gcctccttgc agatatggcc ctcacttgtc 17100
gccttcgcgt tcccatcact ggttaccgag gaagaaactc gcgccgtaga agagggatgt 17160
tgggacgcgg aatgcgacgc tacaggcgac ggcgtgctat ccgcaagcaa ttgcggggtg 17220
gttttttacc agccttaatt ccaattatcg ctgctgcaat tggcgcgata ccaggcatag 17280
cttccgtggc ggttcaggcc tcgcaacgac attgacattg gaaaaaaacg tataaataaa 17340
aaaaaaaaaa tacaatggac tctgacactc ctggtcctgt gactatgttt tcttagagat 17400
ggaagacatc aatttttcat ccttggctcc gcgacacggc acgaagccgt acatgggcac 17460
ctggagcgac atcggcacga gccaactgaa cgggggcgcc ttcaattgga gcagtatctg 17520
gagcgggctt aaaaattttg gctcaaccat aaaaacatac gggaacaaag cttggaacag 17580
cagtacagga caggcgctta gaaataaact taaagaccag aacttccaac aaaaagtagt 17640
cgatgggata gcttccggca tcaatggagt ggtagatttg gctaaccagg ctgtgcagaa 17700
aaagataaac agtcgtttgg acccgccgcc agcaacccca ggtgaaatgc aagtggagga 17760
agaaattcct ccgccagaaa aacgaggcga caagcgtccg cgtcccgatt tggaagagac 17820
gctggtgacg cgcgtagatg aaccgccttc ttatgaggaa gcaacgaagc ttggaatgcc 17880
caccactaga ccgatagccc caatggccac cggggtgatg aaaccttctc agttgcatcg 17940
acccgtcacc ttggatttgc cccctccccc tgctgctact gctgtacccg cttctaagcc 18000
tgtcgctgcc ccgaaaccag tcgccgtagc caggtcacgt cccgggggcg ctcctcgtcc 18060
aaatgcgcac tggcaaaata ctctgaacag catcgtgggt ctaggcgtgc aaagtgtaaa 18120
acgccgtcgc tgcttttaat taaatatgga gtagcgctta acttgcctat ctgtgtatat 18180
gtgtcattac acgccgtcac agcagcagag gaaaaaagga agaggtcgtg cgtcgacgct 18240
gagttacttt caagatggcc accccatcga tgctgcccca atgggcatac atgcacatcg 18300
ccggacagga tgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18360
acacctactt caatctggga aataagttta gaaatcccac cgtagcgccg acccacgatg 18420
tgaccaccga ccgtagccag cggctcatgt tgcgcttcgt gcccgttgac cgggaggaca 18480
atacatactc ttacaaagtg cggtacaccc tggccgtggg cgacaacaga gtgctggata 18540
tggccagcac gttctttgac attaggggtg tgttggacag aggtcccagt ttcaaaccct 18600
attctggtac ggcttacaac tccctggctc ctaaaggcgc tccaaataca tctcagtgga 18660
ttgcagaagg tgtaaaaaat acaactggtg aggaacacgt aacagaagag gaaaccaata 18720
ctactactta cacttttggc aatgctcctg taaaagctga agctgaaatt acaaaagaag 18780
gactcccagt aggtttggaa gtttcagatg aagaaagtaa accgatttat gctgataaaa 18840
catatcagcc agaacctcag ctgggagatg aaacttggac tgaccttgat ggaaaaaccg 18900
aaaagtatgg aggcagggct ctcaaacccg atactaagat gaaaccatgc tacgggtcct 18960
ttgccaaacc tactaatgtg aaaggcggtc aggcaaaaca aaaaacaacg gagcagccaa 19020
atcagaaagt cgaatatgat atcgacatgg agttttttga tgcggcatcg cagaaaacaa 19080
acttaagtcc taaaattgtc atgtatgcag aaaatgtaaa tttggaaact ccagacactc 19140
atgtagtgta caaacctgga acagaagaca caagttccga agctaatttg ggacaacaat 19200
ctatgcccaa cagacccaac tacattggct tcagagataa ctttattgga cttatgtact 19260
ataacagtac tggtaacatg ggggtgctgg ctggtcaagc gtctcagtta aatgcagtgg 19320
ttgacttgca ggacagaaac acagaacttt cttaccaact cttgcttgac tctctgggcg 19380
acagaaccag atactttagc atgtggaatc aggctgtgga cagttatgat cctgatgtac 19440
gtgttattga aaatcatggt gtggaagatg aacttcccaa ctactgtttt ccactggacg 19500
gcataggtgt tccaacaacc agttacaaat caatagttcc aaatggagac aatgcgccta 19560
attggaagga acctgaagta aatggaacaa gtgagatcgg acagggtaat ttgtttgcca 19620
tggaaattaa ccttcaagcc aatctatggc gaagtttcct ttattccaat gtggctctat 19680
atctcccaga ctcgtacaaa tacaccccgt ccaatgtcac tcttccagaa aacaaaaaca 19740
cctacgacta catgaacggg cgggtggtgc cgccatctct agtagacacc tatgtgaaca 19800
ttggtgccag gtggtctctg gatgccatgg acaatgtcaa cccattcaac caccaccgta 19860
acgctggctt gcgttaccga tccatgcttc tgggtaacgg acgttatgtg cctttccaca 19920
tacaagtgcc tcaaaaattc ttcgctgtta aaaacctgct gcttctccca ggctcctaca 19980
cttatgagtg gaactttagg aaggatgtga acatggttct acagagttcc ctcggtaacg 20040
acctgcgggt agatggcgcc agcatcagtt tcacgagcat caacctctat gctacttttt 20100
tccccatggc tcacaacacc gcttccaccc ttgaagccat gctgcggaat gacaccaatg 20160
atcagtcatt caacgactac ctatctgcag ctaacatgct ctaccccatt cctgccaatg 20220
caaccaatat tcccatttcc attccttctc gcaactgggc ggctttcaga ggctggtcat 20280
ttaccagact gaaaaccaaa gaaactccct ctttggggtc tggatttgac ccctactttg 20340
tctattctgg ttctattccc tacctggatg gtaccttcta cctgaaccac acttttaaga 20400
aggtttccat catgtttgac tcttcagtga gctggcctgg aaatgacagg ttactatctc 20460
ctaacgaatt tgaaataaag cgcactgtgg atggcgaagg ctacaacgta gcccaatgca 20520
acatgaccaa agactggttc ttggtacaga tgctcgccaa ctacaacatc ggctatcagg 20580
gcttctacat tccagaagga tacaaagatc gcatgtattc atttttcaga aacttccagc 20640
ccatgagcag gcaggtggtt gatgaggtca attacaaaga cttcaaggcc gtcgccatac 20700
cctaccaaca caacaactct ggctttgtgg gttacatggc tccgaccatg cgccaaggtc 20760
aaccctatcc cgctaactat ccctatccac tcattggaac aactgccgta aatagtgtta 20820
cgcagaaaaa gttcttgtgt gacagaacca tgtggcgcat accgttctcg agcaacttca 20880
tgtctatggg ggcccttaca gacttgggac agaatatgct ctatgccaac tcagctcatg 20940
ctctggacat gacctttgag gtggatccca tggatgagcc caccctgctt tatcttctct 21000
tcgaagtttt cgacgtggtc agagtgcatc agccacaccg cggcatcatc gaggcagtct 21060
acctgcgtac accgttctcg gccggtaacg ctaccacgta agaagcttct tgcttcttgc 21120
aaatagcagc tgcaaccatg gcctgcggat cccaaaacgg ctccagcgag caagagctca 21180
gagccattgt ccaagacctg ggttgcggac cctatttttt gggaacctac gataagcgct 21240
tcccggggtt catggccccc gataagctcg cctgtgccat tgtaaatacg gccggacgtg 21300
agacgggggg agagcactgg ttggctttcg gttggaaccc acgttctaac acctgctacc 21360
tttttgatcc ttttggattc tcggatgatc gtctcaaaca gatttaccag tttgaatatg 21420
agggtctcct gcgccgcagc gctcttgcta ccaaggaccg ctgtattacg ctggaaaaat 21480
ctacccagac cgtgcagggt ccccgttctg ccgcctgcgg acttttctgc tgcatgttcc 21540
ttcacgcctt tgtgcactgg cctgaccgtc ccatggacgg aaaccccacc atgaaattgc 21600
taactggagt gccaaacaac atgcttcatt ctcctaaagt ccagcccacc ctgtgtgaca 21660
atcaaaaagc actctaccat tttcttaata cccattcgcc ttattttcgc tcccatcgta 21720
cacacatcga aagggccact gcgttcgacc gtatggatgt tcaataatga ctcatgtaaa 21780
caacgtgttc aataaacatc actttatttt tttacatgta tcaaggctct gcattactta 21840
tttatttaca agtcgaatgg gttctgacga gaatcagaat gacccgcagg cagtgatacg 21900
ttgcggaact gatacttggg ttgccacttg aattcgggaa tcaccaactt gggaaccggt 21960
atatcgggca ggatgtcact ccacagcttt ctggtcagct gcaaagctcc aagcaggtca 22020
ggagccgaaa tcttgaaatc acaattagga ccagtgcttt gagcgcgaga gttgcggtac 22080
accggattgc agcactgaaa caccatcagc gacggatgtc tcacgcttgc cagcacggtg 22140
ggatctgcaa tcatgcccac atccagatct tcagcattgg caatgctgaa cggggtcatc 22200
ttgcaggtct gcctacccat ggcgggcacc caattaggct tgtggttgca atcgcagtgc 22260
agggggatca gtatcatctt ggcctgatcc tgtctgattc ctggatacac ggctctcatg 22320
aaagcatcat attgcttgaa agcctgctgg gctttactac cctcggtata aaacatcccg 22380
caggacctgc tcgaaaactg gttagctgca cagccggcat cattcacaca gcagcgggcg 22440
tcattgttag ctatttgcac cacacttctg ccccagcggt tttgggtgat tttggttcgc 22500
tcgggattct cctttaaggc tcgttgtccg ttctcgctgg ccacatccat ctcgataatc 22560
tgctccttct gaatcataat attgccatgc aggcacttca gcttgccctc ataatcattg 22620
cagccatgag gccacaacgc acagcctgta cattcccaat tatggtgggc gatctgagaa 22680
aaagaatgta tcattccctg cagaaatctt cccatcatcg tgctcagtgt cttgtgacta 22740
gtgaaagtta actggatgcc tcggtgctcc tcgtttacgt actggtgaca gatgcgcttg 22800
tattgttcgt gttgctcagg cattagttta aaagaggttc taagttcgtt atccagcctg 22860
tacttctcca tcagcagaca catcacttcc atgcctttct cccaagcaga caccaggggc 22920
aagctaatcg gattcttaac agtgcaggca gcagctcctt tagccagagg gtcatcttta 22980
gcgatcttct caatgcttct tttgccatcc ttctcaacga tgcgcacggg cgggtagctg 23040
aaacccactg ctacaagttg cgcctcttct ctttcttctt cgctgtcttg actgatgtct 23100
tgcatgggga tatgtttggt cttccttggc ttctttttgg ggggtatcgg aggaggagga 23160
ctgtcgctcc gttccggaga cagggaggat tgtgacgttt cgctcaccat taccaactga 23220
ctgtcggtag aagaacctga ccccacacgg cgacaggtgt ttctcttcgg gggcagaggt 23280
ggaggcgatt gcgaagggct gcggtccgac ctggaaggcg gatgactggc agaacccctt 23340
ccgcgttcgg gggtgtgctc cctgtggcgg tcgcttaact gatttccttc gcggctggcc 23400
attgtgttct cctaggcaga gaaacaacag acatggaaac tcagccattg ctgtcaacat 23460
cgccacgagt gccatcacat ctcgtcctca gcgacgagga aaaggagcag agcttaagca 23520
ttccaccgcc cagtcctgcc accacctcta ccctagaaga taaggaggtc gacgcatctc 23580
atgacatgca gaataaaaaa gcgaaagagt ctgagacaga catcgagcaa gacccgggct 23640
atgtgacacc ggtggaacac gaggaagagt tgaaacgctt tctagagaga gaggatgaaa 23700
actgcccaaa acaacgagca gataactatc accaagatgc tggaaatagg gatcagaaca 23760
ccgactacct catagggctt gacggggaag acgcgctcct taaacatcta gcaagacagt 23820
cgctcatagt caaggatgca ttattggaca gaactgaagt gcccatcagt gtggaagagc 23880
tcagccgcgc ctacgagctt aacctctttt cacctcgtac tccccccaaa cgtcagccaa 23940
acggcacctg cgagccaaat cctcgcttaa acttttatcc agcttttgct gtgccagaag 24000
tactggctac ctatcacatc ttttttaaaa atcaaaaaat tccagtctcc tgccgcgcta 24060
atcgcacccg cgccgatgcc ctactcaatc tgggacctgg ttcacgctta cctgatatag 24120
cttccttgga agaggttcca aagatcttcg agggtctggg caataatgag actcgggccg 24180
caaatgctct gcaaaaggga gaaaatggca tggatgagca tcacagcgtt ctggtggaat 24240
tggaaggcga taatgccaga ctcgcagtac tcaagcgaag catcgaggtc acacacttcg 24300
catatcccgc tgtcaacctg ccccctaaag tcatgacggc ggtcatggac cagttactca 24360
ttaagcgcgc aagtcccctt tcagaagaca tgcatgaccc agatgcctgt gatgagggta 24420
aaccagtggt cagtgatgag cagctaaccc gatggctggg caccgactct cccagggatt 24480
tggaagagcg tcgcaagctt atgatggccg tggtgctggt taccgtagaa ctagagtgtc 24540
tccgacgttt ctttaccgat tcagaaacct tgcgcaaact cgaagagaat ctgcactaca 24600
cttttagaca cggctttgtg cggcaggcat gcaagatatc taacgtggaa ctcaccaacc 24660
tggtttccta catgggtatt ctgcatgaga atcgcctagg acaaagcgtg ctgcacagca 24720
ccctgaaggg ggaagcccgc cgtgattaca tccgcgattg tgtctatctg tacctgtgcc 24780
acacgtggca aaccggcatg ggtgtatggc agcaatgttt agaagaacag aacttgaaag 24840
agcttgacaa gctcttacag aaatctctta aggttctgtg gacagggttc gacgagcgca 24900
ccgtcgcttc cgacctggca gacctcatct tcccagagcg tctcagggtt actttgcgaa 24960
acggattgcc tgactttatg agccagagca tgcttaacaa ttttcgctct ttcatcctgg 25020
aacgctccgg tatcctgccc gccacctgct gcgcactgcc ctccgacttt gtgcctctca 25080
cctaccgcga gtgccccccg ccgctatgga gtcactgcta cctgttccgt ctggccaact 25140
atctctccta ccactcggat gtgatcgagg atgtgagcgg agacggcttg ctggagtgtc 25200
actgccgctg caatctgtgc acgccccacc ggtccctagc ttgcaacccc cagttgatga 25260
gcgaaaccca gataataggc acctttgaat tgcaaggccc cagcagccaa ggcgatgggt 25320
cttctcctgg gcaaagttta aaactgaccc cgggactgtg gacctccgcc tacttgcgca 25380
agtttgctcc ggaagattac cacccctatg aaatcaagtt ctatgaggac caatcacagc 25440
ctccaaaggc cgaactttcg gcctgcgtca tcacccaggg ggcaattctg gcccaattgc 25500
aagccatcca aaaatcccgc caagaatttc tactgaaaaa gggtaagggg gtctaccttg 25560
acccccagac cggcgaggaa ctcaacacaa ggttccctca ggatgtccca acgacgagaa 25620
aacaagaagt tgaaggtgca gccgccgccc ccagaagata tggaggaaga ttgggacagt 25680
caggcagagg aggcggagga ggacagtctg gaggacagtc tggaggaaga cagtttggag 25740
gaggaaaacg aggaggcaga ggaggtggaa gaagtaaccg ccgacaaaca gttatcctcg 25800
gctgcggaga caagcaacag cgctaccatc tccgctccga gtcgaggaac ccggcggcgt 25860
cccagcagta gatgggacga gaccggacgc ttcccgaacc caaccagcgc ttccaagacc 25920
ggtaagaagg atcggcaggg atacaagtcc tggcgggggc ataagaatgc catcatctcc 25980
tgcttgcatg agtgcggggg caacatatcc ttcacgcggc gctacttgct attccaccat 26040
ggggtgaact ttccgcgcaa tgttttgcat tactaccgtc acctccacag cccctactat 26100
agccagcaaa tcccggcagt ctcgacagat aaagacagcg gcggcgacct ccaacagaaa 26160
accagcagcg gcagttagaa aatacacaac aagtgcagca acaggaggat taaagattac 26220
agccaacgag ccagcgcaaa cccgagagtt aagaaatcgg atctttccaa ccctgtatgc 26280
catcttccag cagagtcggg gtcaagagca ggaactgaaa ataaaaaacc gatctctgcg 26340
ttcgctcacc agaagttgtt tgtatcacaa gagcgaagat caacttcagc gcactctcga 26400
ggacgccgag gctctcttca acaagtactg cgcgctgact cttaaagagt aggcagcgac 26460
cgcgcttatt caaaaaaggc gggaattaca tcatcctcga catgagtaaa gaaattccca 26520
cgccttacat gtggagttat caaccccaaa tgggattggc ggcaggcgcc tcccaggact 26580
actccacccg catgaattgg ctcagcgccg ggccttctat gatttctcga gttaatgata 26640
tacgcgccta ccgaaaccaa atacttttgg aacagtcagc tcttaccacc acgccccgcc 26700
aacaccttaa tcccagaaat tggcccgccg ccctagtgta ccaggaaagt cccgctccca 26760
ccactgtatt acttcctcga gacgcccagg ccgaagtcca aatgactaat gcaggtgcgc 26820
agttagctgg cggctccacc ctatgtcgtc acaggcctcg gcataatata aaacgcctga 26880
tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctctccg cttggtctac 26940
gaccagacgg aatctttcag attgccggct gcgggagatc ttccttcacc cctcgtcagg 27000
ctgttctgac tttggaaagt tcgtcttcgc aaccccgctc gggcggaatc gggaccgttc 27060
aatttgtgga ggagtttact ccctctgtct acttcaaccc cttctccgga tctcctgggc 27120
attacccgga cgagttcata ccgaacttcg acgcgattag cgagtcagtg gacggctacg 27180
attgatgtct ggtgacgcgg ctgagctatc tcggctgcga catctagacc actgccgccg 27240
ctttcgctgc tttgcccggg aactcattga gttcatctac ttcgaactcc ccaaggatca 27300
ccctcaaggt ccggcccacg gagtgcggat ttctatcgaa ggcaaaatag actctcgcct 27360
gcaacgaatt ttctcccagc ggcccgtgct gatcgagcga gaccagggaa acaccacggt 27420
ttccatctac tgcatttgta atcaccccgg attgcatgaa agcctttgct gtcttatgtg 27480
tactgagttt aataaaaact gaattaagac tctcctacgg actgccgctt cttcaacccg 27540
gattttacaa ccagaagaac gaaacttttc ctgtcgtcca ggactctgtt aacttcacct 27600
ttcctactca caaactagaa gctcaacgac tacaccgctt ttccagaagc attttcccta 27660
ctaatactac tttcaaaacc ggaggtgagc tccaaggtct tcctacagaa aacccttggg 27720
tggaagcggg ccttgtagtg ctaggaattc ttgcgggtgg gcttgtgatt attctttgct 27780
acctatacac accttgcttc actttcttag tggtgttgtg gtattggttt aaaaaatggg 27840
gcccatacta gtcttgcttg ttttactttc gcttttggaa ccgggttctg ccaattacga 27900
tccatgtcta gacttcgacc cagaaaactg cacacttact tttgcacccg acacaagccg 27960
catctgtgga gttcatcgcc tctcttacga acttggcccc caacgacaaa aatttacctg 28020
catggtggga atcaacccca tagttatcac ccagcaaagt ggagatacta agggttgcat 28080
tcactgctcc tgcgattcca tcgagtgcac ctacaccctg ctgaagaccc tatgcggcct 28140
aagagacctg ctaccaatga attaaaaaat gattaataaa aaatcactta cttgaaatca 28200
gcaataaggt ctctgttgaa attttctccc agcagcacct cacttccctc ttcccaactc 28260
tggtattcta aaccccgttc agcggcatac tttctccata ctttaaaggg gatgtcaaat 28320
tttagctcct ctcctgtacc cacaatcttc atgtctttct tcccagatga ccaagagagt 28380
ccggctcagt gactccttca accctgtcta cccctatgaa gatgaaagca cctcccaaca 28440
cccctttata aacccagggt ttatttcccc aaatggcttc acacaaagcc caaacggagt 28500
tcttacttta aaatgtttaa ccccactaac aaccacaggc ggatctctac agctaaaagt 28560
gggaggggga cttacagtgg atgacaccaa cggttttttg aaagaaaaca taagtgccac 28620
cacaccactc gttaagactg gtcactctat aggtttacca ctaggagccg gattgggaac 28680
gaatgaaaat aaactttgta tcaaattagg acaaggactt acattcaatt caaacaacat 28740
ttgcattgat gacaatatta acaccttatg gacaggagtc aaccccaccg aagccaactg 28800
tcaaatcatg aactccagtg aatctaatga ttgcaaatta attctaacac tagttaaaac 28860
tggagcacta gtcactgcat ttgtttatgt tataggagta tctaacaatt ttaatatgct 28920
aactacacac agaaatataa attttactgc agagctgttt ttcgattcta ctggtaattt 28980
actaactaga ctctcatccc tcaaaactcc acttaatcat aaatcaggac aaaacatggc 29040
tactggtgcc attactaatg ctaaaggttt catgcccagc acgactgcct atcctttcaa 29100
tgataattct agagaaaaag aaaactacat ttacggaact tgttactaca cagctagtga 29160
tcgcactgct tttcccattg acatatctgt catgcttaac cgaagagcaa taaatgacga 29220
gacatcatat tgtattcgta taacttggtc ctggaacaca ggagatgccc cagaggtgca 29280
aacctctgct acaaccctag tcacctcccc atttaccttt tactacatca gagaagacga 29340
ctgacaaata aagtttgcga tcgctttctc tcttcaggcc caccatgggc tggagctgca 29400
tcatcttgtt cctggtcgca actgctaccg gagtccattc ggacatcgtc atgacccaaa 29460
gccctgactc gctcgctgtg tcactgggag agcgggcgac tatcaactgc aaatcatccc 29520
agagcctgct gtattcacgc aatcagaaaa actacctggc ctggtatcag cagaagccgg 29580
gccagcctcc caagctgctg atcttctggg cctccacccg cgaaagcggc gtgccggacc 29640
gcttcagcgg aagcggattc ggaactgact ttactctgac cattagctcc ttgcaggcgg 29700
aggacgtggc cgtctactac tgccagcagt atttctccta tccgctcacc tttgggcaag 29760
gcaccaaggt ggagattaag ggagggggcg gcagcggggg aggcggcagc ggcggcgggg 29820
gatcgcaggt ccagctcgtc caatccggag ccgaagtcaa gaagccggga gcgtcggtca 29880
aggtcagctg caaaacttcg cgctacacct tcactgagta cacgatccac tgggtccgcc 29940
aggcgcccgg ccagcggctg gagtggatcg gcgggatcaa cccaaacaac ggaatcccaa 30000
attacaatca gaaatttaaa gggcgggtga ctatcaccgt ggatacctcg gcctccacgg 30060
cgtacatgga gctctcatca ctcagatcgg aggacaccgc ggtctattac tgcgcccgcc 30120
gccggatcgc ttatggatac gatgaaggac atgcgatgga ttactggggc cagggcaccc 30180
tcgtcacggt gtcgtcagga ggcggcggtt cacaggtgca gctgcagcag tctggggctg 30240
aactggcaag acctggggcc tcagtgaaga tgtcctgcaa ggcttctggc tacaccttta 30300
ctaggtacac gatgcactgg gtaaaacaga ggcctggaca gggtctggaa tggattggat 30360
acattaatcc tagccgtggt tatactaatt acaatcagaa gttcaaggac aaggccacat 30420
tgactacaga caaatcctcc agcacagcct acatgcaact gagcagcctg acatctgagg 30480
actctgcagt ctattactgt gcaagatatt atgatgatca ttactgcctt gactactggg 30540
gccaaggcac cactctcaca gtctcctcag gtggcggtgg ctcgggcggt ggtggatctg 30600
gtggcggcgg atctgatatc gtgctcactc agtctccagc aatcatgtct gcatctccag 30660
gggagaaggt caccatgacc tgcagtgcca gctcaagtgt aagttacatg aactggtacc 30720
agcagaagtc aggcacctcc cccaaaagat ggatttatga cacatccaaa ctggcttctg 30780
gagtccctgc tcacttcagg ggcagtgggt ctgggacctc ttactctctc acaatcagcg 30840
gcatggaggc tgaagatgct gccacttatt actgccagca gtggagtagt aacccattca 30900
cgttcggctc ggggacaaag ttggaaataa accggggaag cggacagtgt actaattatg 30960
ctctcttgaa attggctgga gatgttgaga gcaaccctgg acctacagtg ctggcgccag 31020
cctggagccc aacaacctat ctcctcctgc tgctgctgct gagctcggga ctcagtggga 31080
cccaggactg ctccttccaa cacagcccca tctcctccga cttcgctgtc aaaatccgtg 31140
agctgtctga ctacctgctt caagattacc cagtcaccgt ggcctccaac ctccaggacg 31200
aggagctctg cgggggcctc tggcggctgg tcctggcaca gcgctggatg gagcggctca 31260
agactgtcgc tgggtccaag atgcaaggct tgctggagcg cgtgaacacg gagatacact 31320
ttgtcaccaa atgtgccttt cagccccccc ccagctgtct tcgcttcgtc cagaccaaca 31380
tctcccgcct cctacaggag acctccgagc agctggtggc gctgaagccc tggatcactc 31440
gccagaactt ctcccggtgc ctggagctgc agtgtcagcc cgactcctca accctgccac 31500
ccccatggag tccccggccc ctggaggcca cagccccggg aagcggagct actaacttca 31560
gcctgctgaa gcaggctgga gacgtggagg agaaccctgg acctcaggtc tccactgctg 31620
cccttgccgt cctcctctgc accatggctc tctgcaacca ggtcctctct gcaccacttg 31680
ctgctgacac gccgaccgcc tgctgcttca gctacacctc ccgacagatt ccacagaatt 31740
tcatagctga ctactttgag acgagcagcc agtgctccaa gcccagtgtc atcttcctaa 31800
ccaagagagg ccggcaggtc tgtgctgacc ccagtgagga gtgggtccag aaatacgtca 31860
gtgacctgga gctgagtgcc ggaagcggag agggcagagg aagtctgcta acatgcggtg 31920
acgtcgagga gaatcctgga cctgccttga cctttgcttt actggtggcc ctcctggtgc 31980
tcagctgcaa gtcaagctgc tctgtgggct gtgatctgcc tcaaacccac agcctgggta 32040
gcaggaggac cttgatgctc ctggcacaga tgaggagaat ctctcttttc tcctgcttga 32100
aggacagaca tgactttgga tttccccagg aggagtttgg caaccagttc caaaaggctg 32160
aaaccatccc tgtcctccat gagatgatcc agcagatctt caatctcttc agcacaaagg 32220
actcatctgc tgcttgggat gagaccctcc tagacaaatt ctacactgaa ctctaccagc 32280
agctgaatga cctggaagcc tgtgtgatac agggggtggg ggtgacagag actcccctga 32340
tgaaggagga ctccattctg gctgtgagga aatacttcca aagaatcact ctctatctga 32400
aagagaagaa atacagccct tgtgcctggg aggttgtcag agcagaaatc atgagatctt 32460
tttctttgtc aacaaacttg caagaaagtt taagaagtaa ggaataagct agcttgactg 32520
actgagatac agcgtacctt cagctcacag acatgataag atacattgat gagtttggac 32580
aaaccacaac tagaatgcag tgaaaaaaat gctttatttg tgaaatttgt gatgctattg 32640
ctttatttgt aaccattata agctgcaata aacaagttaa caacaacaat tgcattcatt 32700
ttatgtttca ggttcagggg gaggtgtggg aggtttttta aagcaagtaa aacctctaca 32760
aatgtggtag tcgtcagcta tcctgcagga acttgtttat ttgaaaatca attcacaaaa 32820
tccgagtagt tattttgcct cccccttccc atttaacaga atacaccaat ctctccccac 32880
gcacagcttt aaacatttgg ataccattag atatagacat ggttttagat tccacattcc 32940
aaacagtttc agagcgagcc aatctggggt cagtgataga taaaaatcca tcgggatagt 33000
cttttaaagc gctttcacag tccaactgct gcggatgcga ctccggagtc tggatcacgg 33060
tcatctggaa gaagaacgat gggaatcata atccgaaaac ggtatcggac gattgtgtct 33120
catcaaaccc acaagcagcc gctgtctgcg tcgctccgtg cgactgctgt ttatgggatc 33180
agggtccaca gtgtcctgaa gcatgatttt aatagccctt aacatcaact ttctggtgcg 33240
atgcgcgcag caacgcattc tgatttcact caaatctttg cagtaggtac aacacattat 33300
tacaatattg tttaataaac cataattaaa agcgctccag ccaaaactca tatctgatat 33360
aatcgcccct gcatgaccat cataccaaag tttaatataa attaaatgac gttccctcaa 33420
aaacacacta cccacataca tgatctcttt tggcatgtgc atattaacaa tctgtctgta 33480
ccatggacaa cgttggttaa tcatgcaacc caatataacc ttccggaacc acactgccaa 33540
caccgctccc ccagccatgc attgaagtga accctgctga ttacaatgac aatgaagaac 33600
ccaattctct cgaccgtgaa tcacttgaga atgaaaaata tctatagtgg cacaacatag 33660
acataaatgc atgcatcttc tcataatttt taactcctca ggatttagaa acatatccca 33720
gggaatagga agctcttgca gaacagtaaa gctggcagaa caaggaagac cacgaacaca 33780
acttacacta tgcatagtca tagtatcaca atctggcaac agcgggtggt cttcagtcat 33840
agaagctcgg gtttcatttt cctcacaacg tggtaactgg gctctggtgt aagggtgatg 33900
tctggcgcat gatgtcgagc gtgcgcgcaa ccttgtcata atggagttgc ttcctgacat 33960
tctcgtattt tgtatagcaa aacgcggccc tggcagaaca cactcttctt cgccttctat 34020
cctgccgctt agcgtgttcc gtgtgatagt tcaagtacaa ccacactctt aagttggtca 34080
aaagaatgct ggcttcagtt gtaatcaaaa ctccatcgca tctaatcgtt ctgaggaaat 34140
catccaagca atgcaactgg attgtgtttc aagcaggaga ggagagggaa gagacggaag 34200
aaccatgtta atttttattc caaacgatct cgcagtactt caaattgtag atcgcgcaga 34260
tggcatctct cgcccccact gtgttggtga aaaagcacag ctagatcaaa agaaatgcga 34320
ttttcaaggt gctcaacggt ggcttccagc aaagcctcca cgcgcacatc caagaacaaa 34380
agaataccaa aagaaggagc attttctaac tcctcaatca tcatattaca ttcctgcacc 34440
attcccagat aattttcagc tttccagcct tgaattattc gtgtcagttc ttgtggtaaa 34500
tccaatccac acattacaaa caggtcccgg agggcgccct ccaccaccat tcttaaacac 34560
accctcataa tgacaaaata tcttgctcct gtgtcacctg tagcgaattg agaatggcaa 34620
catcaattga catgcccttg gctctaagtt cttctttaag ttctagttgt aaaaactctc 34680
tcatattatc accaaactgc ttagccagaa gccccccggg aacaagagca ggggacgcta 34740
cagtgcagta caagcgcaga cctccccaat tggctccagc aaaaacaaga ttggaataag 34800
catattggga accgccagta atatcatcga agttgctgga aatataatca ggcagagttt 34860
cttgtaaaaa ttgaataaaa gaaaaatttg ccaaaaaaac attcaaaacc tctgggatgc 34920
aaatgcaata ggttaccgcg ctgcgctcca acattgttag ttttgaatta gtctgcaaaa 34980
ataaaaaaaa aaacaagcgt catatcatag tagcctgacg aacagatgga taaatcagtc 35040
tttccatcac aagacaagcc acagggtctc cagctcgacc ctcgtaaaac ctgtcatcat 35100
gattaaacaa cagcaccgaa agttcctcgc ggtgaccagc atgaataatt cttgatgaag 35160
catacaatcc agacatgtta gcatcagtta acgagaaaaa acagccaaca tagcctttgg 35220
gtataattat gcttaatcgt aagtatagca aagccacccc tcgcggatac aaagtaaaag 35280
gcacaggaga ataaaaaata taattatttc tctgctgctg ttcaggcaac gtcgcccccg 35340
gtccctctaa atacacatac aaagcctcat cagccatggc ttaccagaca aagtacagcg 35400
ggcacacaaa gcacaagctc taaagtgact ctccaacctc tccacaatat atatatacac 35460
aagccctaaa ctgacgtaat gggagtaaag tgtaaaaaat cccgccaaac ccaacacaca 35520
ccccgaaact gcgtcaccag ggaaaagtac agtttcactt ccgcaatccc aacaggcgta 35580
acttcctctt tctcacggta cgtgatatcc cactaacttg caacgtcatt ttcccacggt 35640
cgcaccgccc cttttagccg ttaaccccac agccaatcac cacacgatcc acacttttta 35700
aaatcacctc atttacatat tggcaccatt ccatctataa ggtatattat atagataga 35759
<210> 279
<211> 18
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 279
tacatgcaca tcgccgga 18
<210> 280
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 引物
<400> 280
Cys Gly Gly Gly Cys Gly Ala Ala Cys Thr Gly Cys Ala Cys Cys Ala
1 5 10 15
<210> 281
<211> 27
<212> PRT
<213> 人工序列
<220>
<223> 探针
<400> 281
Cys Cys Gly Gly Ala Cys Thr Cys Ala Gly Gly Thr Ala Cys Thr Cys
1 5 10 15
Cys Gly Ala Ala Gly Cys Ala Thr Cys Cys Thr
20 25

Claims (20)

1.一种包括式(I)的序列的腺病毒:
5'ITR-B1-BA-B2-BX-BB-BY-B3-3'ITR(I)
其中:
B1是键或包括:E1A、E1B或E1A到E1B;
BA包括-E2B-L1-L2-L3-E2A-L4;
B2是键或包括:E3;
BX是键或DNA序列,其包括:限制性位点、一个或多个转基因或两者;
BB包括L5;
BY包括含有四个转基因的转基因盒,所述基因编码FAP-双特异性T细胞衔接器、CXCL10、CXCL9和IFNα;
B3是键或包括:E4。
2.根据权利要求1所述的腺病毒,其中编码的FAP-双特异性T细胞衔接器包括SEQ IDNO:5中所示的抗CD3。
3.根据权利要求1或2所述的腺病毒,其中所述FAP-双特异性T细胞衔接器包括SEQ IDNO:9中所示的抗FAP。
4.根据权利要求1所述的腺病毒,其中编码的FAP-双特异性T细胞衔接器包括选自SEQID NO:75和76的序列。
5.根据权利要求1到2中任一项所述的腺病毒,其中所述转基因盒编码SEQ ID NO:100中所示的CXCL10。
6.根据权利要求1到2中任一项所述的腺病毒,其中所述转基因盒编码SEQ ID NO:99中所示的CXCL9。
7.根据权利要求1到2中任一项所述的腺病毒,其中所述转基因盒编码SEQ ID NO:98中所示的IFNα。
8.根据权利要求1到2中任一项所述的腺病毒,其中所述转基因被可操作地连接。
9.根据权利要求1到2中任一项所述的腺病毒,其中所述转基因被3种不同的高效自切割肽分开。
10.根据权利要求9所述的腺病毒,其中所述自切割肽独立地选自E2A、F2A、P2A和T2A。
11.根据权利要求1到2中任一项所述的腺病毒,其中从L5到E4的转基因的相对顺序是FAP-双特异性T细胞衔接器、CXCL10、CXCL9和IFNα。
12.根据权利要求1到2中任一项所述的腺病毒,其中所述转基因盒具有SEQ ID NO:95中所示的多核苷酸序列或编码相同氨基酸序列的多核苷酸。
13.根据权利要求1到2中任一项所述的腺病毒,其中所述腺病毒包括SEQ ID NO:84。
14.根据权利要求1到2中任一项所述的腺病毒,其中所述腺病毒具有复制能力。
15.根据权利要求1到2中任一项所述的腺病毒,其中所述腺病毒是溶瘤的。
16.根据权利要求1到2中任一项所述的腺病毒,其中所述病毒具有六邻体和来自Ad11的纤维。
17.一种药物组合物,其包括根据权利要求1到16中任一项所述的腺病毒和赋形剂、稀释剂或载剂。
18.根据权利要求1到2中任一项所述的腺病毒或根据权利要求17所述的药物组合物,其用于治疗。
19.根据权利要求18所述的腺病毒或药物组合物,其用于治疗癌症。
20.根据权利要求1到16中任一项所述的腺病毒或根据权利要求17所述的药物组合物用于制造用于癌症治疗的药物的用途。
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