CN1863913B - 通过mar序列的多次转染过程在哺乳动物细胞中实现高效基因转移和表达 - Google Patents
通过mar序列的多次转染过程在哺乳动物细胞中实现高效基因转移和表达 Download PDFInfo
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Abstract
本发明涉及纯化及分离的具有提高的蛋白产量活性的DNA序列,尤其涉及利用核基质附着区(MAR)来提高真核细胞中的蛋白产量活性。同时还披露了一种用于识别所述活性区域,尤其是MAR核苷酸序列的方法,以及这些特征性的活性MAR序列在一种新的多次转染方法中的用途。
Description
技术领域
本发明涉及纯化和分离具有提高的蛋白产量活性的DNA序列,更具体而言,涉及利用核基质附着区(MAR)来提高真核细胞中的蛋白产量活性。同时还披露了一种用于识别所述活性区域,尤其是MAR核苷酸序列的方法,以及这些特征性的活性MAR序列在一种新的多次转染方法中的用途。
背景技术
现在,真核染色体的环结构域组织模型已经被广为接受(Boulikas T,“Nature of DNA sequences at the attachment regions ofgenes to the nuclear matrix”,J.Cell Biochem.,52:14-22,1993)。根据这个模型,染色质被组织成50-100kb跨度的环,其连接到核基质上,一种由RNP和其它非组蛋白蛋白质构成的蛋白质网络,(BodeJ,Stengert-Iber M,Kay V,Schalke T and Dietz-Pfeilstetter A,Crit.Rev.Euk.Gene Exp.,6:115-138,1996)。
连接到核基质上的DNA区域称为SAR或MAR,分别对应支架附着区(中期期间)或核基质附着区(间期)(Hart C and LaemmliU(1998),“Facilitation of chromatin dynamics by SARs”Curr OpinGenet Dev 8,519-525.)。
因此,这些区域可以限定独立的染色质结构域的边界,这样只由涵盖顺式-调节元件来控制该结构域内基因的表达。
然而,在经稳定转染的细胞中还没有看到它们充分遮蔽染色体基因座(chromosomal locus)使其不受邻近染色质元件影响、从而提供独立于位点(position-independent)的基因表达的能力(PoljakL.,Seum C,Mattioni T and Laemmli.U.(1994)“SARs stimulate but donot confer position independent gene expression”,Nucleic Acids Res 22,4386-4394)。另一方面,MAR(或S/MAR)序列已经显示出当与增强子相互作用,以此提高了局部染色质的可接近性(Jenuwein T,Forrester W,Fernandez-Herrero L,Laible G,Dull M,and Grosschedl R.(1997)“Extension of chromatin accessibility by nuclear matrixattachment regions”Nature 385,269-272)。特别是,MAR元件在细胞培养系中(Kalos M and Fournier R(1995)“Position-independenttransgene expression mediated by boundary elements from theapolipoprotein B chromatin domain”Mol Cell Biol 15,198-207)、转基因小鼠中(Castilla J,Pintado B,Sola,I,Sanchez-Morgado J,andEnjuanes L(1998)“Engineering passive immunity in transgenic micesecreting virus-neutralizingantibodies in milk”Nat Biotechnol 16,349-354)、和植物中(Allen G,Hall GJ,Michalowski S,Newman W,Spiker S,Weissinger A,and Thompson W(1996),“High-leveltransgene expression in plant cells:effects of a strong scaffoldattachment region from tobacco”Plant Cell 8,899-913)可以增强异源基因的表达。利用MAR序列来开发用于基因治疗的改良载体也已经被认可(Agarwal M,Austin T,Morel F,Chen J,Bohnlein E,andPlavec I(1998),“Scaffold attachment region-mediated enhancement ofretroviral vector expression in primary T cells”J Virol 72,3720-3728)。
最近,已经有资料显示,以鸡溶菌酶5’MAR为例,包括MAR在内的染色质-结构修饰序列能够显著地增强稳定的中国仓鼠卵巢细胞(CHO)群(pools)中的报道基因的表达(Zahn-Zabal M,et al.,“Development of stable cell lines for production or regulatedexpression using matrix attachment regions”J Biotechnol,2001,87(1):p.29-42)。这一性能可用于增加高产克隆的比例,从而减少需要筛选的克隆的数量。这些益处不仅在侧面具有MAR的转基因表达盒子的结构中观察到,而且当用位于单独质粒上的MAR进行结构共转染时也可以观察到。然而,用MAR共转染的表达水平不如在两个MAR限定的转基因表达单元的结构中观察到的表达水平高。第三种且优选的方法是用连接于转基因并且位于单独质粒上的MAR进行转基因的转染(Girod et al.,submitted for publication)。然而,这种技术的一个始终存在的限制因素是每个细胞可以被转染的DNA的量。已经开发了很多种多次转染方案用来实现高效转染,用以表征有关基因(gene of interest)的功能。这种于1999年由Yamamoto等人使用的方案(“High efficiency gene transfer bymultiple transfection protocol”,Histochem.J.31(4),241-243)导致5次转染过程后达到约80%的转染效率,相反,传统的转染方法仅能达到<40%的比率。当希望提高表达细胞的比例时,这种技术可能是有用的,但它不能使细胞具有更高的内在生产力。因此,它不能用于产生高产的单克隆细胞系。因此,前述的技术具有两个主要的缺点:
i)这种技术不能产生转染的同源细胞群,因为它既不能有利于进一步基因拷贝的整合,又不能指导转基因到有利的染色体位点;
ii)在多次转染过程中使用同样的可选择的标记物,不允许选择双重或三重转染的细胞。
在专利申请WO02/074969中,也展示了利用MAR开发的稳定的真核细胞系。然而,该申请的披露中既没有任何用于MAR DNA元件的保守的同源性,也没有任何用于预测一个DNA序列能够为MAR序列的技术。
事实上,还没有发现明确的MAR共有序列(Boulikas T,“Natureof DNA sequences at the attachment regions of genes to the nuclearmatrix”,J.Cell Biochem.,52:14-22,1993),但是从进化而言,这些序列的结构看起来在功能上是保留在真核基因组中,因为动物MAR可以与植物支架结合,或反之亦然(Mielke C,Kohwi Y,Kohwi-Shigematsu T and Bode J,“Hierarchicalbinding of DNAfragments derived from scaffold-attached regions:correlation ofproperties in vitro and function in vivo”,Biochemistry,29:7475-7485,1990)。
通过生物化学研究的MAR识别是一种耗时且不可预知的过程;根据测试可以得到各种不同的结果(Razin SV,“Functionalarchitecture of chromosomal DNA domains”,Crit Rev Eukaryot GeneExpr.,6:247-269,1996)。考虑到在真核基因组中大量期待的MAR以及产生于基因组项目的序列的数量,因而一种能够筛选潜在的MAR,从而可以完成目标实验的工具将会是非常有用的。
目前,通过因特网可以得到两种不同的用于MAR的预测工具。
第一种,MAR-Finder(http://futuresoft.org/MarFinder;Singh GB,Kramer JA and Krawetz SA,“Mathematical model to predict regions ofchromatin attachment to the nuclear matrix”,Nucleic Acid Research,25:1419-1425,1997)是基于数种MAR中识别出的一组模式以及这些模式同时存在率的统计分析。MAR-Finder预测依赖于序列的前后关系,即预测的MAR依赖于所提交序列的前后关系。另一个预 测软件,SMARTest(http://www.genomatix.de;Frisch M,Frech K,Klingenhoff A,Cartharius K,Liebich I and Werner T,“In silicoprediction of scaffold/matrix attachment regions in large genomicsequences”,Genome Research,12:349-354,2001)利用由实验识别出的MAR得到的加权矩阵(weight-matrices)。
据说SMARTest适用于进行大规模的分析。但是,实际上除了它相对较差的特异性之外,当用它进行大规模分析时,假设的(hypothetical)MAR的量快速激增,并且没有办法增加其特异性来限制假设的MAR的数量,因而对于从大量的DNA序列中筛选有效的MAR,SMARTest变得几乎毫无用处。
另外还存在其它一些不能通过因特网得到的软件;它们也是基于MAR基序的频率(MRS criterion;Van Drunen CM et al.,“Abipartite sequence element associated with matrix/scaffold attachmentregions”,Nucleic Acids Res,27:2924-2930,1999),(ChrClass;GlazkoGV et al.,“Comparative study and prediction of DNA fragmentsassociated with various elements of the nuclear matrix”,Biochim.Biophys.Acta,1517:351-356,2001)或基于应力-诱导的DNA双链的位点识别(SIDD;Benham C and al.,“Stress-induced duplex DNAdestabilization in scaffold/matrix attachment regions”,J.Mol.Biol.,274:181-196,1997)。然而,它们对于分析全部基因组序列的适用性还不清楚,并且这些工具是否可以用来识别提高蛋白产量的序列还没有报道。
而且,由于这些软件相对较差的特异性(Frisch M,Frech K,Klingenhoff A,Cartharius K,Liebich I and Werner T,“In silicoprediction of scaffold/matrix attachment regions in large genomicsequences”,Genome Research,12:349-354,2001),当进行大规模分析时,在基因组中识别的假设的MAR的量迅速激增到难以处理的地 步,尤其是在如果大多数这些结果实际上没有活性或活性很差时。因此没有办法提高预测的特异性来限制假拟MAR的数量,从有效提高重组蛋白产量的角度看,很多可获得的程序对于识别有效的基因元件变得几乎毫无用处。
由于所有上述可获得的预测方法都具有某些缺点而阻碍用大规模分析基因组来可靠地识别新颖的和有效的MAR,因此本发明的目的是:1)了解MAR能够改善重组蛋白表达的功能特征;2)获得一种新的生物信息学工具,使MAR结构特征编译为功能的预测,从而3)进行大规模的基因组分析,来识别新颖的和更有效的MAR,以及,最终4)证明当利用新识别的MAR序列时,用来提高来自真核细胞或生物体的重组蛋白产量的改善的功效。
发明内容
本发明的目的是通过如下途径达到的:提供一种改进的和可靠的方法用于识别具有提高的蛋白产量活性的DNA序列,尤其是MAR核苷酸序列,以及这些特征性的活性MAR序列在新的多次转染方法中用来提高真核细胞中的重组蛋白的产量中的用途。
附图说明
图1示出了MAR和非MAR序列的分布图。频率分布图为相对于观测到的参数得分的密度图(相对频率除以双态(bin)宽度)。在SMARt DB数据库中用于人MAR的密度频率分布图以黑色表示,而用于人染色体22的密度频率分布图以灰色表示。
图2示出了由SMAR Scan 使用的四个不同指标以及来自SMARt DB的带有人MAR的AT-含量的散点图。
图3示出了来自生物体MAR序列的分布图。从其它生物体的SMARt DB得到的MAR序列被收集和分析。对小鼠、鸡、两色蜀黍和人的MAR序列密度分布一起作图。
图4示出了在人类染色体22上以及在混合(shuffled)的染色体22上的SMAR Scan 的预测。顶图:通过SMAR Scan 得到的命中平均数,分为5组:在10bp的非重叠窗口中打碎的(rubbled)、混杂的(scrambled)、混合的、1阶马尔可夫链(Markov chain)模型和天然的染色体22。底图:由SMAR Scan 预测的MAR的平均数量,分为5组:在10bp的非重叠窗口中打碎的、混杂的、混合的、1阶马尔可夫链模型和天然染色体22。
图5示出了鸡溶菌酶基因5’-MAR在CHO-DG44细胞中刺激转基因表达的能力的分解图。片段B、K和F显示出对刺激转基因表达的最高能力。这表明这些元件的相对强度基于高表达细胞的数量。
图6示出了连续删除5’-MAR的5’-端(上部)和3’-端(下部)对刺激转基因表达能力丧失的影响。从提高的活性到降低的活性的转变与B-、K-和F-片段相吻合。
图7示出了显著刺激转基因表达的F片段的部分。用亮灰色箭头指示的该F片段区域被多聚化,插入到pGEGFP对照中并转染到CHO细胞内。显示最高活性的元件位于该元件的中间部分,并且对应于片段FIII(黑色条带标记的最小MAR)。另外,增强子的活性位于该FIII片段的3’-侧翼部分(暗灰色条带标记的MAR增强子)。
图8示出了cLysMAR中的用于各种DNA序列基序的位置图。图8(B)表示cLysMAR中的用于各种DNA序列基序的位置图。 纵向线表示沿着cLysMAR的3034个碱基对的计算机预测的位点的位置或序列基序以及它的活性区,如图5所示。用于转录的活化子(MEF205、Oct-1、USF-02、GATA、NFAT)和用于转录的阻遏物(CDP、SATB1、CTCF、ARBP/MeCP2)的推定的转录因子位点是利用MatInspector(Genomatix)来识别,并且CpG岛是用CPGPLOT来识别。以前与MAR元件关联的基序被标记为黑色,并且包括CpG二核苷酸和CpG岛、解链基序(AATATATT和AATATT)、聚A和T、聚G和C、具有对6bp核心身份的果蝇拓扑异构酶II结合位点(GTNWAYATTNATTNATNNR)以及高可动性的组I(HMG-I/Y)蛋白结合位点。其它的结构基序包括核小体结合位点和憎核小体位点以及认为能够松弛DNA的超螺旋链的基序。图8(A)表示cLysMAR的各部分激活转录的能力与用MarFinder得到的MAR预测得分图的对比。顶图示出如图5所示的MAR片段的活性,而中间和底部曲线分别示出MARFinder对MAR活性以及对弯曲DNA结构的预测潜能。
图9示出了DNA物理-化学性质与MAR活性之间的相关性。图9(A)示出5’-MAR的DNA解链温度、双螺旋弯曲、大沟深度和小沟宽度图,并且是利用Levitsky等人的算法来测定(Levitsky VG,Ponomarenko MP,Ponomarenko JV,Frolov AS,Kolchanov NA“Nucleosomal DNA property database”,Bioinformatics,15;582592,1999)。绘于顶部的是在图1中示出的最有活性的B、K和F片段。图9(B)示出图框A中示出的数据的放大图,用来展示与相关的解链温度(顶部曲线)和DNA弯曲(底部曲线)的描记线对齐的F片段图。已经标出了最有活性的FIB片段的位置以及用于特异性转录因子的蛋白结合位点。
图11示出了MAR的不同部分的装配图。所指出的cLysMAR部分由PCR扩增,在每一端引入BgIII-BamHI连接元件,并装配起来产生所述的复合元件。例如,顶部结构是由所有的CUE和侧翼序列在它们的初始位置装配构成,除外将每个元件分隔开的BgII-BamHII连接序列。
图12表示质粒图。
图13示出了再次转染的初级转染子对GFP表达的影响。细胞(CHO-DG44)用pSV40EGFP(左管)或pMAR-SV40EGFP(中间管)以及作为抗性质粒的pSVneo共转染。用pMAR-SV40EGFP转染的细胞在24小时后用同样的质粒和一种不同的选择质粒,pSVpuro(右管)再次转染。经过两周的选择,经稳定转染的细胞群的表型由FACS分析。
图14示出了多次载入含有MAR的质粒的影响。该pMAR-SV40EGFP/pMAR-SV40EGFP二级转染子在选择过程结束后用于第三周期的转染。用pMAR或pMAR-SV40EGFP进行三级转染以产生三级转染子。24小时后,将细胞用上述两种质粒的任一种再次转染,从而产生四级转染子(参见表4)。
图15示出了由WP18A10A7区示例的SMAR预测算法的比较性能。(A)用默认设置进行SMAR Scan 分析。(B)SIDD分析(顶部曲线和左手边的刻度),以及来自Goetze等人的在体外将一些DNA片段结合到核基质上(条形图,右手边的刻度)(Goetze S,Gluch A,Benham C,Bode J,“Computational and in vitro analysis ofdestabilized DNA regions in the interferon gene cluster:potential ofpredicting functional gene domains.”Biochemistry,42:154-166,2003)。
图16表示利用MAR的一个类似基因治疗方案的结果。
用MAR-网络注射的这组小鼠,从实验开始进行诱导,与注入不含有MAR的原始网络的小鼠相比较显示出更好的血细胞比容诱导。两个月后,在“含有MAR的组”中的血细胞比容与正常的血细胞比容水平(45-55%)相比仍然处于一个较高的值(65%)。
图18表示对于1757个非S/MAR序列的二核苷酸百分比的分布图。
图19示出了各种S/MAR元件对重组绿色荧光蛋白(GFP)产量的影响。如所示出的,通过荧光活化的细胞分选仪( )分析用含有或不含有MAR元件的GFP表达载体转染的CHO细胞群,并示出了典型的分布图。这些分布图显示了作为GFP荧光水平的函数的细胞计数。
图20绘出了注入MAR-网络后在小鼠中诱导血细胞比容的结果。
具体实施方式
本发明涉及一种纯化及分离的具有提高的蛋白产量活性的DNA序列,其特征在于,所述DNA序列包括至少一个弯曲DNA元件,以及至少一个用于DNA结合蛋白的结合位点。
已知某些DNA序列形成一种相对“静态的弯曲”,其中该DNA遵循一个独特的三维路经。因此,能够形成扁平的、平面曲线的DNA片段也称作弯曲DNA,而不是仅仅以通常的B-DNA构象(“直线型”)存在(Marini,et al.,1982″Bent helical structure in kinetoplastDNA″,Proc.Natl.Acad.Sci.USA,79:7664-7664)
令人惊奇的是,申请人已经表明本发明的具有提高的蛋白产量活性的纯化及分离的DNA序列的弯曲DNA元件通常在100个连续碱基对的链上含有至少10%的二核苷酸TA,和/或至少12%的二核苷酸AT。优选地,该弯曲DNA元件在100个连续碱基对的链上含有至少33%的二核苷酸TA,和/或至少33%的二核苷酸AT。这些数据已经通过下面描述的方法得到了。
根据本发明,该纯化及分离的DNA序列通常包括一种选自包括序列SEQ ID No 1至27或cLysMAR元件或其片段的组中的MAR核苷酸序列。优选地,该纯化及分离的DNA序列是一种选自包括序列SEQ ID No 1至27的组中的MAR核苷酸序列,更优选的是选自序列SEQ ID No 24至27的组中的MAR核苷酸序列。
本发明还包括上述序列SEQ ID No 1至27以及cLysMAR元件或片段的互补序列,这些互补序列可以利用PCR或其它方法产生。
“元件”是一具有普通功能性质(即,用于转录因子的结合位点)或结构特征(即,弯曲DNA序列)的保守的核苷酸序列。
序列SEQ ID No 1至27的一部分以及cLysMAR元件或片段是指在长度上与对应的序列SEQ ID No 1至27共享至少70%的核苷酸的各个序列。只要它们与由其衍生的天然序列具有同样的性质即可以使用这些序列。优选在长度上与对应的SEQ ID No 1-至27序 列共享超过80%的核苷酸,特别是超过90%的核苷酸,的那些序列。
本发明还包括上述序列SEQ ID No 1至27和cLysMAR元件或片段的各种变体,即通过保守的核苷酸取代(由此一个或多个核苷酸被具有同样性质的另一个核苷酸取代),该核苷酸序列不同于参照序列。
通过利用SMAR Scan 扫描人类染色体1和2已经识别出序列SEQ ID No 1至23,表明利用下文介绍的工具识别新的MAR序列也是可行的,而SEQ ID No 24至27是用组合的SMAR Scan 方法扫描全部人类基因组进行识别的。
第一步,筛选全部染色体1和2以便识别弯曲DNA元件作为如图3所示的相应的最大弯曲、最大大沟深度、最大小沟宽度和最低解链温度的区域。第二步,对这些序列的集合进行扫描,以找出产生序列SEQ ID 1-23的调节蛋白的结合位点(如图8B所示的SATB1、GATA等)。而且,序列21-23进一步显示位于人类基因组数据库(Human Genome Data Base)中的已知基因附近。
至于SEQ ID No 24至27,这些序列是根据组合方法通过扫描人类基因组得到的,并且是在这样检测到的1757个MAR元件中作为实例选出的。
在本发明中还考虑了MAR序列的分子嵌合体。分子嵌合体是指可以包括一个MAR元件的功能部分的核苷酸序列,并且它可以由本领域技术人员通过已知的分子生物学方法得到。
在本发明中还考虑了MAR元件或片段或其亚部分的特定组合。这些片段可以用本领域已知的各种方法制备。这些方法包括但 不限于:用限制酶消化并回收该片段、化学合成或聚合酶链反应(PCR)。
因此,取决于要得到的功能结果,本发明中考虑了序列SEQ IDNo 1至27的元件或片段与cLysMAR元件或片段的特定组合。cLysMAR元件是如在WO 02/074969中所描述的B、K和F区域,将这些公开的全部内容通过引证的方式合并于本申请中。用于本发明的优选的cLysMAR元件是B、K和F区域。可以仅使用一个元件或者可以使用同样或不同元件的多重拷贝(多聚元件)(见图8A)。
片段是指对应核苷酸序列的一个部分。MAR核苷酸序列的片段可能残留生物活性,从而结合到纯化的核基质上和/或改变可操作地连接于一启动子的编码序列的表达模式。MAR核苷酸序列的片段的范围可以是从最少约100至1000bp,优选从约200至700bp,更优选为约300至500bp的核苷酸。也可以考虑片段的任意组合,其具有存在于由天然MAR元件和/或片段构成的合成MAR序列中的同样数目的核苷酸。这些片段优选通过连接子序列装配。优选的连接子是BgIII-BamHI连接子。
“提高的蛋白产量活性”是指一种纯化及分离的DNA序列的活性,定义如下:在适当的条件下被引入到真核宿主细胞后,与用不含有所述DNA序列转染的细胞进行培养比较,该序列在细胞培养时能够提高蛋白产量的水平。通常这种提高是1.5到10倍,优选为4到10倍。这对应的产率或特定的细胞产力为至少每天10pg/细胞(参见实施例11和图13)。
如在本文中所使用的,下述定义是为了有助于理解本发明。
“染色质”是构成真核细胞染色体的蛋白质和核酸物质,并涉及DNA、RNA和相关蛋白。
“染色质元件”是指一个在染色体上的核酸序列,当整合到染色体上时具有改变染色质结构的性质。
“顺式”是指在同一个核酸分子(如同一载体、质粒或染色体)上的两个或多个元件(如染色质元件)的排列。
“反式”是指在两个或多个不同的核酸分子(如两个载体或两个染色体)上的两个或多个元件(如染色质元件)的排列。
染色质修饰元件能够潜在地克服位置影响,因此对于开发稳定的细胞系是有意义的,这些元件包括边界元件(BE)、核基质附着区(MAR)、基因座控制区(LCR)、和通用的染色质开放元件(UCOE)。
边界元件(″BE″)、或隔离元件,在很多情况下界定了染色质的边界(Bell A and Felsenfeld G.1999;“Stopped at the border:boundaries and insulators,Curr Opin Genet Dev 9,191-198),并且在体内可能扮演定义转录结构域的角色。BE缺少内在的启动子/增强子活性,但是被认为能保护基因免受周围染色质中的调节元件的转录影响。增强子阻断测试通常用于识别隔离元件。在这种测试中,该染色质元件被置于增强子和启动子之间,并测定增强子激活的转录。边界元件已经显示出能够保护稳定转染的报道基因在果蝇、酵母和哺乳动物细胞中免受位置影响。它们也已经显示出可提高带有可诱导转基因表达的转基因小鼠的比例。
基因座控制区(″LCR″)是基因座的初始染色质活化以及在它们的原始位置上进行随后的基因转录所需的顺式-调节元件 (Grosveld,F.1999,“Activation by locus controlregions?”Curr OpinGenet Dev 9,152-157)。LCR的活化功能也允许用于转基因小鼠的适当的组织中的一种偶联的转基因的表达,而不用考虑整合到宿主基因组中的位点。虽然LCR一般对连接的基因提供组织特异性水平的表达,但是已经报道在转基因小鼠的几乎所有组织中对于截短型人T-细胞受体LCR和大鼠LAP LCR都能有效表达。最广泛特征化的LCR是球蛋白基因座的LCR。目前正在测评它在用于镰状细胞病和3-地中海贫血的基因疗法的载体中的应用。
根据已广泛接受的模型,“MAR”可以介导特异性DNA序列锚接到核基质上,从而产生从异染色质核心向外伸展的染色质环形结构域。虽然MAR不含有任何明显的共有或可识别的序列,但是它们最一致的特征似乎是具有非常高的A/T含量,并且C碱基主要位于一条链上(Bode J,Schlake T,RiosRamirez M,Mielke C,Stengart M,Kay V and KlehrWirth D,“Scaffold/matrixattached regions:structuralpropreties creating transcriptionally active loci”,Structural andFunctional Organization of the Nuclear Matrix:International Reviewof Citology,162A:389453,1995)。这些区域倾向于形成弯曲的二级结构从而可以易于链的分离。它们经常被称作碱基分离区(BUR),并且它们含有一个核心解链元件(CUE),这可能代表链分离的成核位点(Benham C and al.,Stress induced duplex DNA destabilizationin scaffold/matrix attachment regions,J.Mol.Biol.,274:181196,1997)。在MAR序列中经常发现几种简单的富含AT的序列基序,但是对于大多数部分,它们功能的重要性以及其潜在的作用模式还不清楚。这些包括A-box(AATAAAYAAA)、T-box(TTWTWTTWTT)、DNA解链基序(AATATATT、AATATT)、SATB1结合位点(H-box、A/T/C25)以及对于脊椎动物共有的拓扑异构酶II位点(RNYNNCNNGYNGKTNYNY)或对于果蝇共有的拓扑异构酶II位点(GTNWAYATTNATNNR)。
广泛存在的染色质开放元件(″UCOE″,也称作“广泛起作用的染色质开放元件”)在WO 00/05393中已有报道。
“增强子”是一种不依赖于基因类别、相对于基因的序列位置、或序列的方向而用于增强基因转录的核苷酸序列。本发明的载体可选择包括增强子。
“基因”是一种为给定的成熟蛋白进行编码的脱氧核糖核苷酸(DNA)序列。在本文中,术语“基因”将不包括未翻译的侧翼区域,如RNA转录起始信号、聚腺苷化加入位点、启动子或增强子。
“产物基因”是一种为具有如诊断或治疗用途的所期望特性的蛋白产物进行编码的基因。一种产物基因包括如结构基因和调节基因。
“结构基因”是指一种为结构蛋白进行编码的基因。结构基因的实例包括但不限于:细胞骨架蛋白、细胞外基质蛋白、酶、核孔蛋白和核支架蛋白、离子通道和转运蛋白、收缩蛋白、和侣伴蛋白。优选的结构基因用于编码抗体或抗体片段。
“调节基因”是指一种为调节蛋白进行编码的基因。调节蛋白的实例包括但不限于:转录因子、激素、生长因子、细胞因子、信号转导分子、癌基因、原癌基因、跨膜受体、和蛋白激酶。
“方向”是指在一给定的DNA序列中的核苷酸顺序。例如一个DNA序列的反转方向是指当与获得该序列的DNA中的一个参照点相比时,该序列的5′到3′的顺序相对于另一序列是相反的。这样的参照点可以包括在源DNA中的其它特异性DNA序列的转录的方向和/或含有该序列的可复制载体的复制起点。
“真核细胞”是指源于真核生物体的任何哺乳动物或非哺乳动物细胞。作为非限制性实例,能够在细胞培养条件下生活并且可以随后被转染的任何真核细胞都将包括在本发明中。特别优选的细胞类型包括:如干细胞、胚胎干细胞、中国仓鼠卵巢细胞(CHO)、COS、BHK21、NIH3T3、HeLa、C2C12、癌细胞、以及初级分化或未分化的细胞。其它适宜的宿主细胞是本领域技术人员已知的。
术语“宿主细胞”和“重组宿主细胞”在本文中可以混用,用以表示一种已经引入一种或多种本发明载体的真核细胞。应当理解,这些术语不仅指特定的受试验细胞,而且也指这些细胞的后代或潜在的后代。由于突变或环境影响,在随后的几代中会发生一定改变,因此实际上这样的后代可能与亲代细胞不完全一样,但是也包括在如本文所使用的术语的范围内。
术语“将一纯化的DNA引入一种真核宿主细胞中”或“转染”是指其中带有或不带有附加物质的一种细胞外DNA进入到一种宿主细胞内的任何过程。术语“细胞被转染”或“转染的细胞”是指细胞外DNA已经被引入其中因此含有该细胞外DNA的细胞。该DNA可以被引入到细胞内以使该核酸可以复制作为染色体的组成部分或者作为染色体外元件。
如在本文中所使用的,“启动子”是指一种调节基因表达的核酸序列。
“共转染”是指利用多于一种的来自细胞以外的外源基因、或载体、或质粒转染一种真核细胞的过程,其中的一种可以为该细胞提供可选择的表型。
该纯化和分离的具有提高的蛋白产量活性的DNA序列,除了包括一个或多个弯曲DNA元件之外,还包括至少一个用于DNA结合蛋白的结合位点。
通常DNA结合蛋白是一种转录因子。转录因子的实例是包括polyQpolyP结构域蛋白的组。
转录因子的另外的实例是选自包括SATB1、NMP4、MEF2、S8、DLX1、FREAC7、BRN2、GATA1/3、TATA、Bright、MSX、AP1、C/EBP、CREBP1、FOX、Freac7、HFH1、HNF3α、Nkx25、POU3F2、Pit1、TTF1、XFD1、AR、C/EBPγ、Cdc5、FOXD3、HFH3、HNF3β、MRF2、Oct1、POU6F1、SRF、V$MTATA_B、XFD2、Bach2、CDP CR3、Cdx2、FOXJ2、HFL、HP1、Myc、PBX、Pax3、TEF、VBP、XFD3、Brn2、COMP1、Evil、FOXP3、GATA4、HFN1、Lhx3、NKX3A、POU1F1、Pax6、TFIIA的组中的一种转录因子,或者这些转录因子的两种或多种的组合是优选的。最优选的是SATB1、NMP4、MEF2和polyQpolyP结构域蛋白。
例如,已知SATB1、NMP4和MEF2在哺乳动物中能调节发育和/或组织特异性基因表达。这些转录因子具有改变DNA几何形状的能力,而反过来,与DNA结合作为一变构配体改变它们的结构。近来,发现SATB1围绕异染色质形成一种类似笼状的结构(Cai S,Han HJ,and Kohwi-Shigematsu T,“Tissue-specific nuclear architectureand gene expression regulated by SATB1”Nat Genet,2003.34(1):p.42-51)。
本发明的又一目的是提供一种纯化及分离的cLysMAR元件和/或片段、其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。
更优选的是,该cLysMAR元件和/或片段由至少一个选自B、K和F区中的核苷酸序列构成。
本发明的另一目的是提供一种合成的MAR序列,其包括在连接序列之间装配的天然的MAR元件和/或片段。
优选地,该合成的MAR序列包括cLysMAR元件和/或片段、其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。另外优选的连接序列是BgIII-BamHI连接子。
本发明的另外一个方面是提供一种利用生物信息学工具识别MAR序列的方法,包括计算一个或多个DNA序列对应于DNA弯曲、大沟深度和小沟宽度的可能值以及解链温度的特征值。优选的是对一个或多个DNA序列特征的识别进一步包括另外的对应于DNA结合蛋白结合位点的DNA序列特征,这也可以用这种方法计算得到。
优选地,所述生物信息学工具的图形或加权矩阵(weight-matrices)是基于二核苷酸的识别。用于本方法的生物信息学工具优选为SMAR Scan 它包含有由Gene Express开发的算法(http://srs6.bionet.nsc.ru/srs6bin/cgi-bin/wgetz?-e+[FEATURES-SiteID:’nR’])并基于Levitsky等人1999年的工作。这些算法基于二核苷酸加权矩阵来识别图形,用以计算DNA构象和物理化学性质的理论值。
优选地,SMAR Scan 使用4种也指定为DNA序列特征的理论指标,该序列特征利用不同大小的扫描窗口以所有可能的组合方式对应于DNA弯曲、大沟深度和小沟宽度的可能值、解链温度(参 见图3)。使用每一种功能时,必须设定一个截止值。该程序每次在指定区域的计算值超过为所有选中的指标设定的截止值时返回一次命中。可以用两种数据输出模式处理这些命中,第一种(称作“类似图形”)简单地返回在质疑序列上的所有命中位置以及它们对于不同选定指标的对应值。第二种模式(称作“连续命中”)仅返回多次连续命中的位置以及它们的相应序列。对于这种模式,连续命中的最小值是可以被设定的另外一个截止值,也可调窗口的大小。第二种模式是SMAR Scan 的默认模式。实际上从字面上看,一次命中可以认为是一个核心解链元件(CUE),而成串的CUE连同用于相关蛋白的多串结合位点可以认为是一个MAR。因此,SMARScan 仅将多次连续命中认为是一个潜在的MAR。
为了调整四个理论结构的指标默认的截止值,使用来自SMARtDB(http://transfac.gbf.de/-SMARt DB)的实验确认的MAR。将来自该数据库的所有人类MAR序列收集起来,并用SMAR Scan 分析,使用4个指标,采用“类似图形”模式,且不设定截止值。这允许对序列的各个位置设定每一种功能。然后根据这些数据计算每一种指标的分布(参见图1和图3)。
对于弯曲、大沟深度和小沟宽度,将SMAR Scan 的默认截止值设定为第75分位数和中数的平均值。对于解链温度,将默认截止值设定为第75分位数。对于“连续命中”模式的最小长度应将其设定为300,因为这被看作是MAR的最小长度(参见图8和9)。然而,对于指定的生物体,本领域技术人员能够在最少的试验情况下为上述指标确定这些截止值。
优选的DNA弯曲值为3-5°之间(径向度)。最优选它们处于3.8-4.4°之间,对应于图1最小的峰。
优选的解链温度为55-75℃(摄氏度)之间。最优选的解链温度为55-62℃之间。
通过该方法能够计算数值的DNA结合蛋白通常是一种转录因子,优选为polyQpolyP结构域、或一种选自包括SATB1、NMP4、MEF2、S8、DLX1、FREAC7、BRN2、GATA1/3、TATA、Bright、MSX、AP1、C/EBP、C REBP1、FOX、Freac7、HFH1、HNF3alpha、Nkx25、POU3F2、Pit1、TTF1、XFD1、AR、C/EBPgamma、Cdc5、FOXD3、HFH3、HNF3 beta、MRF2、Oct1、POU6F1、SRF、V$MTATA_B、XFD2、Bach2、CDP CR3、Cdx2、FOXJ2、HFL、HP1、Myc、PBX、Pax3、TEF、VBP、XFD3、Brn2、COMP1、Evil、FOXP3、GATA4、HFN1、Lhx3、NKX3A、POU1F1、Pax6、TFIIA的组中的转录因子,或两种或多种这些转录因子的组合。
但是,本领域技术人员能够确定其它种类的转录因子以便实施根据本发明的方法。
例如,当考虑将SMAR Scan 用于进行大规模分析时,这时上述方法优选进一步包括至少一种用于DNA转录因子的预测DNA结合位点的筛选程序(filter),从而减少计算量。
这种方法的原理是将如前所述用于计算结构特征的SMARScan 与一种如pfsearch(如在Bucher P、Karplus K、Moeri N和Hofmann K,“A flexible search technique based on generalized profiles”,Computers and Chemistry,20:324,1996中所描述的来自pftools的数据包)这样的用于预测一些转录因子结合的筛选程序结合起来。
筛选程序的实例包括但不限于pfsearch、MatInspector、RMatchProfessional以及TRANSFAC Professional。
这种组合方法利用SMAR Scan 的结构特征和该筛选程序所预测的特定转录因子的结合,这些筛选程序可以随后以任何顺序用于筛选MAR,因此,取决于筛选程序用于方法的开始还是结束。
首先从初始输入的序列中筛选出序列,第二步通过利用该筛选程序可以用以限制那些在所选出的序列中满足该筛选程序中所使用寸旨标的序列。
在这种组合方法中,该筛选程序利用图形或加权矩阵从例如MatInspector(Quandt K,Frech K,Karas H,Wingender E,Werner T,“MatInd and MatInspector New fast and versatile tools for detection ofconsensus matches in nucleotide sequence data”,Nucleic AcidsResearch,23,48784884,1995.)中检测DNA结合位点簇。该筛选程序也能够检测DNA结合位点簇的密度。
该组合方法实际上是用Perl语言为SMAR Scan 写的一个“wrapper”,而且一旦如此,来自pftools的pfsearch将作为一种筛选程序。这种组合方法进行两步操作,在每一步时利用这些工具(SMAR Scan 或筛选程序)之一作为潜在的“筛选程序”,每一种筛选程序是可选择的,并且能够不用进行任何筛选来计算所预测的特征。
如果第一步利用SMAR Scan 筛选亚序列,则为了返回序列它应该使用“全部连续命中”模式。如果第一步利用pfsearch作为第一筛选程序,则必须只使用一个图形并且需要提供核苷酸中的一个距离。这个距离用于将位于小于给定距离的距离内的pfsearch命中聚集在一起从而返回序列;该组合方法启动pfsearch,解析其输出 并返回对应于pfsearch命中的序列,该pfsearch命中根据所提供的距离聚集在一起。然后,无论第一步使用什么工具,由此选择的亚序列的长度根据被称作“命中扩展”的参数都可以在两端系统地延伸。
第二个并且可选择的步骤可以用于筛选出序列(已经被筛选的序列或未被筛选的输入序列),或在对这些序列不做任何筛选的情况下用于获得SMAR Scan 和/或pfsearch的结果。如果组合方法的第二步用于筛选,需要提供针对于每一种指标所考虑的截止值(每个核苷酸的命中)来筛选出那些序列(参见图20)。
本发明的另一个方面也是提供一种用于识别MAR序列的方法,该方法包括至少一个利用图形或加权矩阵检测DNA结合位点簇的筛选程序。该方法优选包括两步筛选程序,并且在这种情况下,SMAR Scan 在所述方法中完全不存在。通常这两步存在于pfsearch中。
本发明还包括一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别。通过该组合方法分析全部人类基因组得到了代表总计1065305个碱基对的总计1757个假设的MAR。为了减少结果的数量,对这1757个MAR进行二核苷酸分析,对于每一个序列从5’到3’方向对两条链均考虑,计算16种可能的二核苷酸的每一种的百分率。
令人惊奇的是,申请人已发现用该组合方法检测的所有的“超级”MAR在100个连续碱基对的一段上含有至少10%的二核苷酸TA。优选的是这些序列在100个连续碱基对的一段上含有至少33%的二核苷酸TA。
申请人同时还发现这些同样的序列在100个连续碱基对的一段上另外含有至少12%的二核苷酸AT。优选的是它们在100个连续碱基对的一段上含有至少33%的二核苷酸AT。
本发明的另一个方面是提供一种任一前述MAR的纯化及分离的MAR DNA序列,包括选自序列SEQ ID No 1至27中的一个序列、其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。
优选地,所述纯化及分离的MAR DNA序列包括选自序列SEQID Nos 24至27中的一个序列、其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。序列24至27对应于通过组合方法检测的那些序列,并且显示出比序列1至23具有更高的提高的蛋白产量活性。
本发明还包括一种纯化及分离的包括第一分离的核基质附着区(MAR)核苷酸序列的DNA序列用于提高真核宿主细胞中蛋白产量的活性的用途,该MAR核苷酸序列是选自如下构成的组中的一个MAR核苷酸序列:
-一种具有提高的蛋白产量活性的纯化及分离的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法来识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体,或一种cLysMAR元件和/或片段的MAR核苷酸序列、其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。
所述纯化及分离的DNA序列通常另外含有一个或多个本领域已知的调节序列,如启动子和/或增强子,聚腺苷化位点以及通常用于蛋白表达的剪接点或可以可选编码的可选择性标记物。所述纯化及分离的DNA序列优选包括一启动子,它可操作地连接到一有关基因上。
本发明的DNA序列可以根据本领域熟知的指标PCR程序和方法进行分离。
所提供的可以使用的启动子是与宿主细胞相兼容的那些启动子,例如从病毒基因组中得到的启动子,如多瘤病毒、腺病毒(如腺病毒2)、乳头状瘤病毒(如牛乳头状瘤病毒)、鸟肉瘤病毒、巨细胞病毒(如鼠或人巨细胞病毒立即早期启动子)、反转录病毒、乙肝病毒、和猿猴病毒40(如SV 40早期和晚期启动子)或从异源哺乳动物启动子中得到的启动子,如肌动蛋白启动子或免疫球蛋白启动子或热休克启动子。这些调节序列指导组成型表达。
此外,该纯化及分离的DNA序列可能另外包括调节序列,其在特定细胞类型中(如将组织特异性调节元件用于表达该核酸)能够优先指导核酸表达。组织特异性调节元件是本领域已知的。适宜的组织特异性启动子的非限制性实例包括:白蛋白启动子(肝特异性;Pinkert,et al.,1987.Genes Dev.1:268-277)、淋巴特异性启动子(Calame and Eaton,1988.Adv.Immunol.43:235-275),特别是T细胞受体启动子(Winoto and Baltimore,1989.EMBOJ.8:729-733)和 免疫球蛋白(Banerji,etal.,1983.Cell 33:729-740;Queen andBaltimore,1983.Cell 33:741-748),神经元特异性启动子(例如神经丝启动子;Byrne and Ruddle,1989.Proc.Natl.Acad.Sci.USA 86:5473-5477)、胰特异性启动子(Edlund,et al.,1985.Science 230:912-916)、以及乳腺特异性启动子(例如牛奶乳清启动子;美国专利第4,873,316号和欧洲专利申请第264,166号)。
调节发育的启动子也包括在内。这样的启动子的实例包括如鼠hox启动子(Kessel and Gruss,1990.Science 249:374-379)和thea-胎蛋白启动子(Campes and Tilghman,1989.Genes Dev.3:537-546)。
可调节基因表达启动子是本领域所熟知的,并且以非限制性实例的方式包括任何通过结合一外源分子能够调节编码所希望蛋白基因表达的启动子,如CRE/LOX系统、TET系统、强力霉素系统、NFkappaB/紫外光系统、Leu3p/异丙基苹果酸盐系统、以及GLVPc/GAL4系统(参见,例如Sauer,1998,Methods 14(4):381-92;Lewandoski,2001,Nat.Rev.Genet 2(10):743-55;Legrand-Poels etal.,1998,J.Photochem.Photobiol.B.45:18;Guo et al.,1996,FEBSLett.390(2):191-5;Wang et al.,PNAS USA,1999,96(15):84838)。然而,本领域技术人员将能够确定适用于实施本发明的其它种类的启动子。
增强子可以选择性地包括在本发明纯化的DNA序列中,并且属于调节序列,例如启动子。
“有关基因”或“转基因”优先编码一种蛋白(结构或调节蛋白)。如在本文中所使用的,“蛋白”一般是指具有超过约10个氨基酸的肽或多肽。该蛋白对于宿主可以是“同源的”(即对于所用的宿主细胞是内源性的)或“异源的”(即对于所用的宿主细胞是 外源性的),如由酵母产生的人蛋白。该蛋白可以作为不溶性聚集体或者作为可溶性蛋白的形式产生于细胞的周质间隙或细胞质中、或在细胞外的介质中。蛋白的实例包括:激素如生长激素或促红细胞生成素(EPO),生长因子如表皮生长因子,止痛物质如脑啡肽,酶如胰凝乳蛋白酶,激素或生长因子的受体,抗体,并且还包括常用作可视标记物的蛋白如绿色荧光蛋白。
优选的纯化DNA序列进一步包括至少一个第二分离的核基质附着区(MAR)核苷酸序列,其选自如下构成的组中:
-一纯化及分离的具有提高的蛋白产量活性的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。该分离的核基质附着区(MAR)核苷酸序列可以是相同的或不同的。可替换地,可以使用第一和第二相同的MAR核苷酸序列。
优选地,该MAR核苷酸序列位于含有启动子和有关基因的序列的5’端和3’端。但是本发明也考虑这种情况,即所述第一和/或至少第二MAR核苷酸序列位于与含有启动子和有关基因的序列不同的一个序列上。
包括在本发明的范围内的还有纯化及分离的含有第一分离的核基质附着区(MAR)核苷酸序列的DNA序列,其是选自如下构成的组中的一种MAR核苷酸序列:
-一纯化及分离的具有提高的蛋白产量活性的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体,根据熟知的方法通过将纯化及分离的DNA序列引入到真核宿主细胞中,它们可以用于在真核宿主细胞中提高蛋白产量活性。用于将DNA引入到真核宿主细胞中的常用方法是:例如通过显微注射或微粒子轰击直接引入克隆的DNA;电转移;使用病毒载体;封装入一载体系统;以及使用转染试剂,如磷酸钙、二乙胺基乙基(DEAE)-葡聚糖或商购的转染系统,如Lipofect-AMINE 2000(Invitrogen)。优选地,用于将纯化的DNA序列引入到真核宿主细胞内的转染方法是如下文所描述的用于转染真核细胞的方法。
纯化及分离的DNA序列可以以环形载体的形式使用。优选地,纯化及分离的DNA序列以线性DNA序列的形式作为载体使用。
如在本文中所使用的,“质粒”和“载体”是可互换使用的,因为质粒是最常用的载体形式。然而,本发明也包括其它形式的表 达载体,包括但不限于,病毒载体(如复制缺陷型反转录病毒,腺病毒和腺相关病毒),它们具有同样的功能。
本发明进一步包括一种用于转染真核宿主细胞的方法,所述方法包括:
a)向所述真核宿主细胞中引入至少一个纯化的包括至少一个有关DNA序列的和/或至少一个纯化及分离的包括一MAR核苷酸序列或其它染色质修饰元件的DNA序列,
b)在限定的时间内对所述转染的真核宿主细胞进行至少一次另外的转染步骤,用至少一个纯化的包括至少一个有关DNA序列和/或用至少一个纯化及分离的包括一MAR核苷酸序列或其它染色质修饰元件的DNA序列,
c)选择所述经转染的真核宿主细胞。
优选在步骤b)中至少进行2至4次转染步骤。
为了选出成功转染的细胞,通常将一种对可选择性标记物进行编码(如对抗生素有抗性)的基因连同有关基因一起引入到宿主细胞中。对可选择性标记物编码的基因可以位于纯化的包括至少一个有关DNA序列的和/或至少一个纯化及分离的由一MAR核苷酸序列或其它染色质修饰元件构成的DNA序列上,或者可以以分离形式(如位于质粒上)选择性地共同引入。各种可选择性标记物包括那些对药物如G418、潮霉素和甲氨蝶呤提供抗性的标记物。为了提高产量,可以根据需要调整药物的量。
通常使用一种或多种可选择性标记物。在每一不同的转染步骤中优选使用不同的可选择性标记物。通过使用例如两种不同的抗生素筛选,允许对“多次转化”的转化细胞进行筛选。
任何能够进行蛋白生产而且没有细胞壁的真核宿主细胞都能使用本发明的方法。有用的哺乳动物宿主细胞系的实例包括:人细胞,如人胚肾细胞系(在悬浮培养中生长的293细胞或亚克隆的293细胞,Graham et al.,J.Gen Virol 36,59(1977))、人宫颈癌细胞(HELA,ATCC CCL 2)、人肺细胞(W138,ATCC CCL 75)、人肝细胞(Hep G2,HB 8065);啮齿动物细胞,如幼仓鼠肾细胞(BHK,ATCC CCL 10)、中国仓鼠卵巢细胞/-DHFR(CHO,Urlaub and Chasin,Proc.Natl.Acad.Sci.USA,77,4216(1980))、小鼠支持细胞(TM4,Mather,Biol.Reprod 23,243-251(1980))、小鼠乳房肿瘤(MMT060562,ATCC CCL51);以及来自其它哺乳动物的细胞,如用SV4O(COS-7,ATCC CRL 1651)转化的猴肾CV1细胞系;猴肾细胞(CV1ATCC CCL 70);非洲绿猴肾细胞(VERO-76,ATCC CRL-1587);犬肾细胞(MDCK,ATCC CCL 34);布法罗大鼠肝细胞(BRL 3A,ATCC CRL 1442);骨髓瘤(例如NS0)/杂交瘤细胞。选出的转染真核宿主细胞优选是高蛋白产量细胞,产率至少为10pg/天·细胞。本文中最优选使用的是哺乳动物细胞,更优选的是CHO细胞。
该纯化及分离的DNA序列的有关DNA序列通常是优选编码可操作地连接到如前所述的一启动子的蛋白的一有关基因。该包括至少一个有关DNA序列的纯化及分离的DNA序列除了有关DNA序列之外,可以另外包括有关MAR核苷酸序列或其它染色质修饰元件的DNA序列。
纯化及分离的包括一MAR核苷酸序列的DNA序列选自例如前述的由序列SEQ ID No 1至27和/或cLysMAR的特定元件(如B、K和F区域),以及其片段和元件及其组合构成的组。其它染色质修饰元件是:例如,边界元件(BE)、基因座控制区(LCR)、和广泛存在的染色质开放元件(UCOE)(参见Zahn-Zabal et al.,已经引述过)。多次转染宿主细胞的一个实例在实施例12(表3)中示出。 第一转染步骤(初级转染)单独用有关基因(SV40EGFP)、单独用MAR核苷酸序列(MAR)或用该有关基因与一MAR核苷酸序列(MAR-SV40EGFP)进行。第二转染步骤(二级转染)单独用该有关基因(SV40EGFP)、单独使用一MAR核苷酸序列(MAR)或用该有关基因与一MAR核苷酸序列(MAR-SV40EGFP),在从第一转染步骤得到的所有可能的组合中进行。
优选的是该真核宿主细胞通过如下方式转染:
a)引入一纯化的包括一个有关DNA序列和另外一MAR核苷酸序列的DNA序列,
b)在指定的时间内对所述转染的真核宿主细胞进行至少一次另外的转染步骤,用同样的包括一有关DNA序列和另外的步骤a)的MAR核苷酸序列的纯化的DNA序列。
同样优选的是该纯化及分离的DNA序列的MAR核苷酸序列选自如下构成的组中:
-一纯化及分离的具有提高的蛋白产量活性的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。
令人惊奇的是,观察到了第一和第二转染之间的协同作用。当MAR元件出现在一次或两次转染步骤中时,已经观测到了一种特殊的协同作用。单独使用pMAR或与各种表达质粒联合使用,利用上述方法进行细胞的多重转染。例如,表3显示用pMAR-SV40EGFP质粒转染细胞两次产生了GFP的最高表达以及所有条件中最高程度的增强(4.3倍)。相反,用没有MAR的载体转染两次产生很少的增强或没有增强,为2.8倍,而不是所预期的两倍的提高。这说明MAR元件在每一个转染步骤中的存在对于实现最大程度的蛋白合成是非常重要的。作为该转染方法的特定实例,包括至少一个有关DNA序列的所述纯化DNA序列可以以多种解链的质粒形式引入,它包括一可操作地连接到启动子的有关基因、一可选择性标记基因、和/或提高蛋白产量的元件如MAR序列。
为了使用特定的细胞类型,第一与随后的DNA序列的比率可以根据需要调整,这对于本领域普通技术人员来说是常规的实验。
初级转化的细胞用于另外的转化的限定时间严格依赖于细胞周期和它的持续时间。通常该限定时间对应于细胞分裂周期的间期。因此,为了使用特定的细胞类型,可以根据需要调整这种精确定时,并且这对于本领域普通技术人员来说是常规的实验。优选的是该限定时间是宿主细胞刚进入第二个或下一个细胞分裂周期的同一期,优选为第二个周期。该时间通常设定为前一次转染发生后6h至48h之间,优选为20h至24h。
本发明还包括一种用于转染真核宿主细胞的方法,所述方法包括向所述真核宿主细胞中共转染入至少一个第一纯化及分离的包括至少一个有关DNA序列的DNA序列以及第二纯化的包括至少一个选自如下构成的组中的MAR核苷酸的DNA:
-一纯化及分离的具有提高的蛋白产量活性的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。
所述的第一纯化及分离的DNA序列也能够包括至少一个如前所述的MAR核苷酸。
还可考虑一种用于生产蛋白的方法,其中一种真核宿主细胞根据本发明定义的转染方法进行转染,并且在适于蛋白表达的条件下在培养基中进行培养。所述蛋白最后按照本领域技术人员已知的任何一种回收方法进行回收。
作为一个实例,可以使用下面的蛋白生产过程。
将用本发明的转染方法转染的真核宿主细胞,通过在适宜表达所述蛋白的条件下培养所述细胞并回收所述蛋白,从而用于蛋白的生产过程。适宜的培养条件是通常用于体外培养真核细胞如WO96/39488中所述的那些条件。该蛋白可以用常规的分离技术从细胞培养物中分离,如在免疫亲和柱或离子交换柱上分离;沉淀;反相HPLC;层析;聚焦层析;SDS-PAGE;凝胶过滤。本领域技术人员会明了,适用于有关多肽的纯化方法可能需要调整以适应于在重组细胞培养中表达的多肽的性质变化。
根据本发明产生的蛋白可以用各种方法检测功能。例如,抗原决定部位的存在以及蛋白与配体结合的能力可以通过蛋白质印记测定、荧光细胞分选测定、免疫沉淀、免疫化学测定和/或竞争结合测定、以及任何其它的测定特异性结合活性的测定方法进行检测。
本发明的蛋白可以用于多种实际应用领域,包括但不限于:
1.用重组的宿主蛋白抗原作为病毒/病原体拮抗剂的免疫。
2.生产膜蛋白用于诊断或筛选测定。
3.生产膜蛋白用于生化研究。
4.生产膜蛋白用于结构研究。
5.生产抗原用来产生抗体用于免疫-组织化学绘图,包括绘制孤儿受体和离子通道。
本发明还提供了一种根据任一前述的转染方法转染的真核宿主细胞。优选地,该真核宿主细胞优选是一哺乳动物宿主细胞系。
如前所述,有用的哺乳动物宿主细胞系的实例包括:人细胞,如人胚肾细胞系(在悬浮培养中生长的293细胞或亚克隆的293细胞,Graham et al.,J.Gen Virol 36,59(1977))、人宫颈癌细胞(HELA,ATCC CCL 2)、人肺细胞(W138,ATCC CCL 75)、人肝细胞(HepG2,HB 8065);啮齿动物细胞,如幼仓鼠肾细胞(BHK,ATCC CCL10)、中国仓鼠卵巢细胞/-DHFR(CHO,Urlaub and Chasin,Proc.Natl.Acad.Sci.USA,77,4216(1980))、小鼠支持细胞(TM4,Mather,Biol.Reprod 23,243-251(1980))、小鼠乳腺瘤(MMT 060562,ATCCCCL51);以及来自其它哺乳动物的细胞,如用SV4O(COS-7,ATCCCRL 1651)转化的猴肾CV1细胞系;猴肾细胞(CV1ATCC CCL 70);非洲绿猴肾细胞(VERO-76,ATCC CRL-1587);犬肾细胞(MDCK,ATCC CCL 34);布法罗大鼠肝细胞(BRL 3A,ATCC CRL 1442); 骨髓瘤(例如NS0)/杂交瘤细胞。本文中最优选使用的是CHO细胞。
本发明还提供了一种包括根据本发明的至少一种纯化及分离的DNA序列的细胞转染混合物或试剂盒。
本发明进一步包括一种转基因生物,其中至少它的一些细胞具有稳定整合的至少一种如下的DNA序列:
-一纯化及分离的具有提高的蛋白产量活性的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。优选地,该转基因生物的一些细胞按照本发明描述的方法进行转染。
在本发明中也可以预期一种转基因生物,其中它的基因组具有稳定整合的至少一种如下的DNA序列:
-一纯化及分离的具有提高的蛋白产量活性的DNA序列,
-一种纯化及分离的MAR DNA序列,其可根据利用所述生物信息学工具来识别MAR序列的方法、组合方法或包括至少一种筛选程序的方法识别,
-序列SEQ ID No 1至27,
-一种纯化及分离的cLysMAR元件和/或片段,
-一种包括装配在连接序列间的天然MAR元件和/或片段的合成MAR序列,
其互补序列、在长度上与其共享至少70%的核苷酸的部分、其分子嵌合体、其组合物以及变体。
对本发明有用的转基因真核生物选自例如包括哺乳动物(小鼠、人、猴等)以及尤其是实验动物,如常见的啮齿类、昆虫(果蝇等)、鱼类(斑马鱼等)、两栖类(蛙、蝾螈等)和其它更简单的生物,如线虫(c.elegans)、酵母等...的组中。
本发明的又一个目的是提供一种包括计算机可执行指令的计算机可读介质,用来实现本发明中所述的用于识别MAR序列的方法。
参照下面的实施例,前面的描述将会被更充分地理解。然而,这些实施例是本发明实施方法的示例,并不用来限制本发明的保护范围。
实施例
首先通过分析已被实验确定的人MAR和非-MAR序列对SMAR Scan 进行第一个粗略评价。如图1所示,作为MAR序列,用从SMARt Db得到的分析人MAR的以前的分析结果针对每个指标作密度频率分布图。类似地,同样分析非-MAR序列并且作图。作为非-MAR序列,使用所有来自染色体22的参考-序列-重叠群 (Ref-Seq-contigs),考虑到后者足够大,其足以包含相对于非-MAR序列部分可忽略不计的MAR序列部分。
如图1所示的密度分布都为具有长尾的倾斜形状。对于最大弯曲、最大大沟深度和最大小沟宽度,该分布是右斜的。对于最低解链温度,该分布是左斜的,给定该指标与另外三个指标相反的对应性,这很自然。对于MAR序列,实际上出现了具有第二弱峰的两相分布。并且在每个图中,在MAR和非-MAR序列分布之间可以看到清楚的转换。
在所有使用的人MAR序列中,平均而言仅有约70%的具有高于人MAR分布的第75分位点的值,这适用于这四个不同的指标。类似的是,考虑到每个人MAR分布的第二弱峰,只有15%的人MAR序列造成这些边远值(outlying value)。在这15%的人MAR序列中,大多数是已经明确证明的MAR,它们用于隔绝转基因以免受位置影响,如干扰素位点MAR、β-球蛋白位点MAR(RamezaniA,Hawley TS,Hawley RG,“Performance-and safety-enhancedlentiviral vectors containing the human interferon-beta scaffoldattachment region and the chicken beta-globin insulator”,Blood,101:4717-4724,2003)、或载脂蛋白MAR(Namciu,S,Blochinger KB,Fournier REK,“Human matrix attachment regions in-sulate transgeneexpression from chromosomal position effects in Drosophilamelanogaster”,Mol.Cell.Biol.,18:2382-2391,1998)。通常具有同样的数据,人MAR序列也可以用于确定四个计算的理论结构特征与AT-含量之间的关系。图2表示散点图以及相应的针对每对指标的相关系数r。
实施例2:不同生物体的MAR序列的分布图
从其它生物体的SMARt DB也可以获得MAR序列,并且如前所述作类似的分析。将针对小鼠、鸡、双色蜀黍和人MAR序列的密度分布一同绘于图3中。
实施例3:整个染色体22的MAR预测
这次将所有来自染色体22的参考序列重叠群(RefSeq contigs)使用默认设置通过SMAR Scan 进行分析。其结果是SMAR Scan 预测了一共803个MAR,它们的平均长度为446bp,这意味着平均每42777bp预测出一个MAR。预测出的MAR总长度相当于染色体22长度的1%。预测区域的AT-含量范围为65.1%至93.3%,所有这些区域平均的AT-含量为73.5%。因此,预测的MAR是富含AT的,相反,染色体22并不富含AT(52.1%AT)。
SMARTest也用于分析整个染色体22,并且得到了1387个MAR候选序列,其平均长度为494bp,相当于平均每24765bp预测出1个MAR。预测出的MAR的总长度相当于染色体22的2%。在由两个软件预测出的所有MAR中,154个预测MAR为两个程序都找出来的,分别相当于SMAR Scan 和SMARTest预测出的MAR的19%和11%。给定SMAR Scan 和SMARTest预测MAR的平均长度,每次预测在SMAR Scan 和SMARTest之间有机会重叠的可能性是0.0027%。
为了评估SMAR Scan 预测的特异性,对染色体22的随机混合的序列进行SMAR Scan 分析(图4)。混合的序列利用4种不同的方法产生:通过将染色体22分割成为非重叠的10bp的窗口,并且在每个窗口中分别混合这些核苷酸;通过“混杂(scrmbling)”,即重排染色体的所有的核苷酸;通过“打碎(rubbling)”,即将染色 体分割成10bp的片段并随机装配这些片段;最后,通过1阶马尔可夫链,这些不同的状态成为所有不同的DNA二核苷酸,并且在这些状态之间转变的可能性是基于染色体22的扫描。对于每一种混合的方法,产生五个混合的染色体22,并且利用默认设置通过SMAR Scan 进行分析。关于命中数,对于重排的染色体22其中的非重叠窗口为10bp时,发现平均命中3 519 170次(标准偏差:18353),对于混杂的序列为171 936,4次命中(标准偏差:2 859,04),而对于打碎的染色体22为24 708,2次命中(标准偏差:1 191,59),对于根据染色体22的1阶马尔可夫链模型产生的染色体平均为2282次命中(标准偏差:334,7),分别代表用天然染色体22发现的185%(标准偏差:平均值的0.5%)、9%(标准偏差:1.5%)、1%(标准偏差:5%)和0.1%(标准偏差:15%)的命中数。对于预测的MAR的数量,即长度超过300的连续命中,对于具有10bp窗口的混合的染色体22有1997个MAR被预测到(标准偏差:31.2),在混杂的序列中只发现2.4个MAR候选序列(标准偏差:0.96),而对于打碎的和根据马尔可夫链模型产生的序列没有发现候选序列,其分别代表用天然染色体22发现的预测的MAR数量的249%和小于0.3%。这些数据提供了SMAR Scan 检测特异性DNA元件(当DNA序列被混合时,该DNA元件的组织结构消失了)的指征。
通过SMAR Scan 预测MAR的相关性通过分析最新发表的位于染色体9(9p22)短臂上的人干扰素基因簇的MAR区进行研究。Goetze等人(已经引用)报道了对WP18A10A7基因座的详尽的分析,用以分析BUR(在此处称作应力-诱导的双链不稳定或SIDD)与体外结合于核基质之间待测的相关性(图9,下部)。三个SIDD 峰与体外结合测定相一致,而其它的不能与基质附着位点相符合。用SMAR Scan 检测干扰素位点(图9,顶部)表明三个主峰伴随的SATB1、NMP4和MEF2的各串调节子结合位点与活性MAR很好地关连。因此,我们得出的结论是预测的CUE以及用于这些转录因子的结合位点的出现并不限于cLysMAR,而可能是所有MAR的普遍特征。这些结果还暗示了SMAR Scan 程序可从基因组序列中有效地识别了MAR元件。
SMAR Scan 的准确性利用六个基因组序列来评估,对于这些基因组已经对实验测定的MAR作图。为了与其它的预测工具进行比较,分析序列与以前用于比较MAR-Finder和SMARTest的序列相同。这些基因组序列是三种植物序列和三种人序列(表1),总计为310 151 bp和37个实验确定的MAR。表1中用于SMARTest和MAR-Finder的结果来自于以前的比较(Frisch M,Frech K,Klingenhoff A,Cartharius K,Liebich I and Werner T,In silicopre-diction of scaffold/matrix attachment regions in large genomicsequences,Genome Research,12:349-354,2001.)。
使用MAR-Finder时除了阈值被设为0.4并对精蛋白基因座分析之外采用默认参数,不使用AT-富含规则(如同对精蛋白基因座所作的用以识别非富含AT的MAR)。
六种不同的基因组序列,三种植物序列和三种人序列,其中实验确定的MAR是已知的,用MAR-Finder、SMARTest和SMAR Scan 进行分析。将真阳性匹配标记为黑体,减号(-)表示假阴性匹配。一些更长的实验确定的MAR含有多于1个的计算机(in silico)预测,它们每一个都算作真阳性匹配。因此,计算机生物预测中的真阳性数量超过所发现的实验确定的MAR的数量。将特异性定义为真阳性预测的比率,而将灵敏度定义为所发现的实验确定的MAR的比率。*用MAR-Finder时不使用富含AT的规则。
SMARTest预测了28个区域为MAR,其中的19个(真阳性)与实验确定的MAR相关(特异性:68%),而9个(32%)位于非-MAR(假阳性)。由于一些最长的实验确定的MAR包含多于一个的计算机预测,因此这19个真阳性实际上相当于14个不同的实验确定的MAR(灵敏度:38%)。MARFinder预测了25个区域作为MAR,其中20个(特异性:80%)与实验确定的MAR相关,相当于12个不同的实验确定的MAR(灵敏度:32%)。SMAR Scan 预测了22个区域,17个是真阳性(特异性:77%),匹配14个不同的实验确定的MAR(灵敏度:38%)。
作为另一实例,将同样的分析用于人染色体1和2,并且导致确定了23个MAR序列(SEQ ID N°1至23)。这些序列以ST25格式列于附件1中。
为了证实通过SMAR Scan 计算的结构特征和S/MAR功能活性之间的潜在相关性,用组合方法以非常严格的参数对全部人类基因组进行分析,目的是得到具有最高的经计算的理论结构特征值的序列,这在下文将称作“超级”S/MAR。进行这项工作是希望得到非常可能提高转基因表达和重组蛋白产量的预测的MAR元件。因此,得到的假设S/MAR首先由生物信息在整体上进行分析,目的是对它们进行表征和分类。
6.1从全部人类基因组的分析预测的S/MAR
作为全部人类基因组序列,使用所有的人参考序列(NationalCenter for Biotechnology Information,The NCBI handbook[Internet].Bethesda(MD):National Library of Medicine(US),Oct.Chapter 17,The Reference Sequence(RefSeq)Project,2002(Available fromhttp://www.ncbi.nih.gov/entrez/query.fcgi?db=Books))重叠群(第5版)并用组合方法分析,在第一处理阶段用SMAR Scan 作为筛选程序,除了最大弯曲截止值之外使用默认设置,而用4.0度(而不是3.202度)的严格阈值作为DNA弯曲的指标。
在第二处理阶段,在由上一步选择的序列中寻找预测的转录因子结合,并且对这些序列不作任何筛选。
通过组合方法分析全部人类基因组得到共1757个假设“超级”S/MAR,相应的总长为1065305bp(0.35%的全部人类基因组)。表2对每个染色体进行显示:其大小、其基因数量、其预测的S/MAR数量、其每个基因的S/MAR密度和其每个S/MAR的kb数。该表显示对于不同的染色体每个预测的S/MAR具有非常不同的基因密度(标准偏差代表超过50%的每个预测的S/MAR基因密度的平均值,并且每个S/MAR基因密度的高值和低值之间的倍数差为6.5)。表2还显示每个S/MAR的kb值变化小于每个S/MAR的基因密度变化(标准偏差代表25%的每个S/MAR的kb的平均值,并且每个S/MAR的kb的高值和低值之间的倍数差为3.2)。
染色体 | 每个染色体上基因的数目 | 染色体的大小(百万bp) | 预测的S/MAR的数目 | 每个S/MAR的基因密度 | 每个S/MAR的Kb |
12345678910111213141516171819202122XY | 2544177214061036123312471383942110010031692127850611688951107142139616217243557071168251 | 2302411981901801701601451191331321319788838180755660343415425 | 851431011181169417977487167787036354137513628182817030 | 29.912.313.98.710.613.27.712.222.914.125.216.37.232.425.52738.47.745.0225.819.725.26.88.3 | 2705168519601610155118081754188324791873197016791385244423711975216214701555214218881214905833 |
总和平均值标准偏差 | 269551123510 | 305012772.8 | 17577345 | 4571910 | 433121804462 |
表2:每个染色体预测的S/MAR数量。每个染色体的基因数量对应于基于GenBank注释的NCBI人类基因组统计表(第34卷 第3版)(National Center for Biotechnology Information,The NCBIhandbook[Internet].Bethesda(MD):National Library of Medicine(US),Oct.Chapter 17,The Reference Sequence(RefSeq)Project,2002(可从http://www.ncbi.nih.gov/entrez/query.fcgi?db=Books得到))。染色体大小是相应的人类参考序列重叠群长度的总和(National Center for Biotechnology Information,The NCBI handbook[Internet].Bethesda(MD):National Library of Medicine(US),Oct.Chapter 17,The Reference Sequence(RefSeq)Project,2002(可从http://www.ncbi.nih.gov/entrez/query.fcgi?db=Books得到)(第五版))。
6.2用于转录因子结合位点的“超级”MAR的生物信息学分析
将通过SMAR Scan 先前获得的1757个预测的“超级”S/MAR序列再进行分析,用于寻找潜在的转录因子结合位点。这已经利用RMatchTM Professional(Kel AE,Gossling E,Reuter I,Cheremushkin E,KelMargoulis OV,Wingender E,MATCH:A tool for searchingtranscription factor binding sites in DNA sequences,Nucleic Acids Res.31(13):35769,2003),一种基于TRANSFAC的以加权矩阵为基础的工具来实现(Wingender E,Chen X,Fricke E,Geffers R,Hehl R,Liebich I,Krull M,Matys V,Michael H,Ohnhauser R,Pruss M,Schacherer F,Thiele S,Urbach S,The TRANSFAC system on geneexpression regulation,Nucleic Acids Research,29(1):2813,2001)。Match TM 2.0 Professional已经使用具有大多数默认设置的基于TRANSFAC Professional、版本8.2(20040630)的MatchTM analysis。将根据Match TM所分析的所有转录因子在1757个序列上的结合预测的总数列于表3中。根据这张表,只有在分析的1757个序列中总计至少20次命中的转录因子才考虑进行进一步分析。
下面是一些最经常被预测结合到这1757个假设的S/MAR序列上的人类转录因子以及它们的匹配描述:Cdc5(细胞分裂控制蛋白5),一种转录调节子/阻遏物;Nkx3A,一种被雄性激素调节的同源异型域蛋白;POU1F1(垂体特异性的阳性转录因子1),它对垂体具有特异性并且刺激细胞增殖。因此,除了SATB1、NMP4和MEF2,其它转录因子也能参与MAR的活性。
表3是在分析的1757个序列上所有的转录因子结合预测(总计20次或更多命中)的汇总。
6.3用于二核苷酸频率预测的“超级”MAR的生物信息学分析
使用无需计算即可识别的明确的指标,进行各种计算机分析以便寻找容易识别的“超级”S/MAR序列。其中,在这1757个超级MAR上进行二核苷酸分析,对于每个序列考虑两条链的5’>3’方向,从而计算16个可能二核苷酸的每一个的百分数。
在这1757个S/MAR序列上每个二核苷酸百分数的汇总(最小值、最大值、中位数、均值、第25个百分位和第75个百分位)以及频率分布图分别列于表4中。在从人类基因组中随机选择的序列 上进行类似的分析,代表随机选择的非-S/MAR序列(但是其中可能含有一些MAR)。表5分别表示对这些序列的二核苷酸含量分析的汇总。
表4:在1757个S/MAR序列上的二核苷酸百分数
AA% | AC% | AG% | AT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 0.0004.2347.8437.18410.11017.290 | 0.00000.93722.24083.21174.771812.9479 | 0.00000.14080.47771.08651.50968.1230 | 18.5032.1134.6834.3236.9450.00 |
CA% | CC% | CG% | CT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 0.00000.96951.97762.69773.754310.4061 | 0.000000.000000.000000.141230.094224.24837 | 0.00000.00000.00000.27090.12567.4410 | 0.00000.14080.47771.08651.50968.1230 |
GA% | GC% | GG% | GT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 0.000000.086960.326160.633470.833335.77889 | 0.00000.00000.00000.21040.19149.8795 | 0.000000.000000.000000.141230.094224.24837 | 0.00000.93722.24083.21174.771812.9479 |
TA% | TC% | TG% | TT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 28.6333.4835.2235.2937.1450.00 | 0.000000.086960.326160.633470.833335.77889 | 0.00000.96951.97762.69773.754310.4061 | 0.0004.2347.8437.18410.11017.290 |
从汇总表中预测的S/MAR元件和非S/MAR序列的结果可以看出,这两组序列之间的AT和TA二核苷酸含量明显不同。预测的S/MAR序列的AT和TA二核苷酸含量分别最少达到18.5%和28.6%,相反在非S/MAR序列中同样的二核苷酸的最小百分数分别为0.3%和0%。类似的,在S/MAR序列中最大的CC和GG含量为 4.2%,相反在非S/MAR序列中这两个二核苷酸的百分数可以总计达到20.8%。
对于预测的S/MAR序列用SMAR Scan 计算AT和TA二核苷酸百分含量与DNA最大弯曲之间的相关性,并绘于图17中,并且将对于非S/MAR序列的相关性绘于图18中。这些图形的不同散点图表明TA百分含量与用SMAR Scan 预测的DNA弯曲很好地相关。
表5:在1757个非S/MAR序列上的二核苷酸百分含量汇总
AA% | AC% | AG% | AT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 0.0007.0969.1068.97610.93917.922 | 1.7354.5865.0165.0545.49413.816 | 1.5126.4667.2797.1847.96912.232 | 0.32575.10336.86957.01088.791323.1788 |
CA% | CC% | CG% | CT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 3.5716.7657.4107.4118.01015.714 | 0.82784.10775.55565.90887.246020.8415 | 0.00000.47270.84391.27071.576012.6074 | 1.5126.4667.2797.1847.96912.232 |
GA% | GC% | GG% | GT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 1.3195.4956.0326.0656.60210.423 | 0.49673.26154.40924.74685.882416.0000 | 0.82784.10775.55565.90887.246020.8415 | 1.7354.5865.0165.0545.49413.816 |
TA% | TC% | TG% | TT% | |
最小值第25个百分位中位数均值第75个百分位最大值 | 0.0003.8765.6255.7747.46424.338 | 1.3195.4956.0326.0656.60210.423 | 3.5716.7657.4107.4118.01015.714 | 0.0007.0969.1068.97610.93917.922 |
随机挑出4个新的超级MAR并分析AT和TA二核苷酸含量,并且与前面已知的鸡lysMAR进行比较,考虑100个碱基对的窗口(表6)。
令人惊奇的是,申请人已经表明在100个DNA碱基对的窗口中所有的超级MAR都具有占分析的总二核苷酸超过12%的AT二核苷酸频率和超过10%的TA二核苷酸。最有效的MAR显示了数值约为34%的二核苷酸对。
表6:实验确认的MAR的%AT和TA二核苷酸频率的汇总
CLysMAR(CUE的平均值) | AT%:12.03 | TA%:10.29 | SEQ ID No |
P1_68 | AT%:33.78 | TA%:33.93 | SEQ ID No |
P1_6 | AT%:34.67 | TA%:34.38 | SEQ ID No |
P1_42 | AT%:35.65 | TA%:35.52 | SEQ ID No |
所有人类“超级”MAR的均值 | AT%:34.32 | TA%:35.29 | |
所有人类非-MAR的均值 | AT%:7.01 | TA%:5.77 |
6.4人类和小鼠基因组直向同源(orthologous)基因间区域的分析
为了得到对于S/MAR进化的知识,已经用SMAR Scan 分析了人和小鼠基因组的直向同源基因间区域。所使用的数据组由87对来自人与小鼠基因组的全部直向同源基因间区域构成(ShabalinaSA,Ogurtsov AY, Kondrashov VA,Kondrashov AS,Selectiveconstraint in intergenic regions of human and mouse genomes,TrendsGenet,17(7):3736,2001)(平均长度为~12 000bp),其位于12个人染色体和12个小鼠染色体上,这些序列的同线性用配对的序列比对得到确认,并且考虑到侧翼基因(实验测试或预测的)的情况。
采用它的默认设置,用SMAR Scan 分析这87个人和小鼠的直向同源基因间序列。分析人的序列产生了总计12个预测的S/MAR(相应的总长度为4750bp),位于5个不同的基因间序列上。
在这三个利用SMAR Scan 严格设置所预测的含有一“超级”S/MAR的人基因间序列中,对应于小鼠的直向同源基因间序列之一也被预测含有一S/MAR(人EMBL ID:Z96050,位置28010至76951直向同源于小鼠EMBL ID:AC015932,位置59884至89963)。当进行这两个直向同源基因间序列的局部比对时,这两个大区域的最佳局部比对与通过SMAR Scan 预测的S/MAR元件的区域相对应。对所预测的含有一“超级”S/MAR的两个其它的人基因间序列的小鼠直向同源序列进行的手工寻找使用Ensembl Genome Browser(http://ensembl.org)。利用Ensembl直向同源预测(基于基因名)在该直向同源小鼠基因上寻找这些基因间区域侧翼成对的人类基因,得到了这两个人序列的小鼠直向同源基因间序列。
因为SMAR Scan 已经被调试为用于人序列并且由此产生很少量具有小鼠基因组序列的“超级”MAR,所以为了被认为是S/MAR(用200bp而不是300bp)连续命中的最小值,将它的默认截止值稍微放宽一些。通过SMAR Scan 分析这些小鼠序列预测了数种S/MAR对于不同的所计算的结构特征具有很高的值。这些结果表明人MAR元件在物种间是保守的。
实施例7:鸡溶菌酶基因5’-MAR的分割
将3000个碱基对的5’-MAR分成更小的片段,监控它们在中国仓鼠卵巢(CHO)细胞中对转基因表达的影响。为了完成这项工作,通过聚合酶链反应(PCR)产生了七个~400bp的片段。这些PCR-扩增片段是彼此相邻的,并且当端到端放置时覆盖整个MAR 序列。每一个这些片段的四个拷贝以头至尾的方向连接,得到长度大约相当于天然MAR的一半。将该四聚体插入到pGL3Control载体(Promega)的一修饰变体pGEGFPControl的SV40启动子的上游。质粒pGEGFPControl通过将pGL3Control的荧光素酶基因交换为来自pEGFP-N1(Clontech)的EGFP基因而产生。由此产生的含有5’-MAR片段的质粒与抗性质粒pSVneo在CHO-DG44细胞中共转染,使用LipofectAmine 2000(Invitrogen)作为转染试剂,如先前的那样进行(Zahn-Zabal,M.,et al.,“Development of stable celllines for production or regulated expression using matrix attachmentregions”J Biotechnol,2001.87(1):p.29-42.)。在选出抗生素(G-418)抗性细胞后,通过FACS分析多克隆细胞群的EGFP荧光。
以高表达细胞的百分位进行转基因表达,高表达细胞定义为其荧光水平至少比用无MAR的pGEGFPControl载体转染的细胞的平均荧光高4个数量级的细胞。图5显示了多聚片段B、K和F增强转基因表达,尽管与原始MAR序列相比较它们的尺寸更小。相反,其它片段活性很差或完全没有活性。
实施例8:在MAR前后结构中B、K和F区的特异性
将5’-MAR分别连续从5’-端(图6,上部)或3’-端(图6,下部)删除。在与前文所描述的类似的测定中监视删除元件的影响。图6显示在CHO细胞中刺激转基因表达能力的丧失不是平均分布的。
在该删除研究中,MAR活性的丧失分别与和5’-MAR B-、K-和F-片段相重叠的转换离散区域相吻合。在5’删除中,当片段K和F被删除后活性绝大部分丧失了。去除F和b元件的3’删除具有最明显的影响。与此对照,侧翼区域A、D、E和G本身具有很小 或没有刺激转基因表达的能力(图5),相应地在5’-和3’-端删除研究中不对MAR活性作贡献(图6)。
实施例9:F元件的结构
将该465bp的F片段进一步分割成分别为234、243、213bp和122、125和121bp的更小的亚-片段。前一组片段是头至尾方向的八聚体(8个拷贝),而后一组是类似的十六聚体(16个拷贝),用以保持MAR序列的恒定长度。将这些元件克隆到pGEGFPControl载体中,并且用如前所述的方法在CHO细胞中测试它们的作用。令人感兴趣的是,片段FIII保留了全长F片段的绝大部分活性,而包含有片段FIII的右手侧部分的片段FII丧失了所有的刺激转基因表达的能力(图7)。这表明在FIB片段中包括在nt 132和nt 221之间的一个活性区域。而且,涵盖这个区域的片段FI和FIB的多重拷贝显示出相似的活性。FIIA本身没有活性。然而,当添加到FIB上时,从而构成FIII,它增强前者的活性。因此,FIIA似乎含有一本身只有很小活性的辅助序列,但是该辅助序列增强了位于FIB的最小结构域的活性。
溶菌酶基因5’-MAR内部的各单独基序分布的分析示于图8A,连同一些另外的我们加入该分析的基序。已经发现这些基序的大多数遍布该MAR元件,并且不是特异性地与活性部分结合。例如,转录因子的结合位点和其它与MAR结合的基序并不优先局限于于该活性区。还有一种观点认为活性MAR序列可能由不同基序的组合构成。已经报道了一些计算机软件(MAR Finder、SMARTest、SIDD duplex stability)用于将MAR识别为与DNA核基质相关的DNA区域。它们通常是基于那些利用预先定义的一系列序列-特异性模式的算法,这些模式以前认为是包含MAR活性的,如以MARFinder为示范例、现在称作MAR Wiz。这些程序的输出与cLysMAR 的转录活性部分不能很好地关联。例如,用MAR Finder得到的活性峰不能与活性MAR亚-部分明确地匹配,例如B片段在体内明显具有活性但是用MAR Finder得到负值(图8B,比较顶部和中间条带)。用该程序预测的弯曲DNA结构也不能与活性很好地关联(图8B,比较顶部和底部条带)。用其它可用的程序得到了相似的结果(数据没有示出)。
因此通过可用的MAR预测计算方法识别的基序不可能成为用以提高cLysMAR基因表达能力的主要决定簇。因此,测试了许多其它计算工具。令人惊奇的是,发现预测的核小体结合序列和憎核小体序列以反复间杂的簇在整个MAR上排列,同时亲核小体位点重叠了活性B、K和F区。有人提出核小体位置序列含有能够容易包裹该核小体组蛋白的DNA链,并且它们以前没有与MAR序列关联。
亲核小体序列可以通过DNA特征的集合模型化,这些特征包括能够使正确相位和方向的DNA跨过弯曲的组蛋白表面的适度重复的序列和其它物理-化学参数。很多这些DNA性质的识别可以通过计算得到,并且已经用到多达38个不同的这样的性质来预测潜在的核小体位点。因此,我们开始判定是否核小体预测程序的特异性部分能够与MAR活性关联,带着这个目的构造了一种可以从基因组序列中识别新的而且可能是更有效的MAR的工具。
为了测定是否DNA初级序列的任何方面都能够从周围的MAR序列中区别活性B、K和F区,我们用MAR Scan 分析5’-MAR。38个核小体阵列预测工具中,发现三个与活性MAR亚-结构域的位置相关联(图9A)。MAR B、K和F区的位置与DNA弯曲、大沟深度和小沟宽度的最大值相吻合。通过GC含量测定,还发现与DNA解链温度的最小值有较弱的关联。对全部MAR F片段的精确 作图表明解链温度谷和DNA弯曲顶点实际上对应于含有MAR最小结构域的FIB亚-片段(图9B)。因此,活性MAR部分可能对应于由该软件预测为弯曲DNA的区域,并且我们将在下文中称这些区域为CUE-B、CUE-K和CUE-F。然而,是否这些区域对应于实际的弯曲DNA和碱基对解链区还不清楚,因为它们与MAR Wiz预测的弯曲DNA不对应(图9B)。
实施例10:在F片段中其它调节元件的特征
可以将核小体位置特征认为是包含在基因组DNA中的多种特异性染色质编码之一。尽管这种特殊的编码可能对F区的活性有贡献,但它不太可能单独决定MAR的活性,因为F区的3’部分增强了包含在FIB部分中的最小MAR结构域的活性。使用MatInspector程序(Genomatix),我们以高于0.92的值寻找转录因子结合位点,并且在F片段的3’部分发现了用于NMP4和MEF2蛋白的DNA结合序列(图8B)。为了确定是否这些转录因子结合位点的任意一个都可能定位于靠近B和K活性区,分析了全部5’-MAR序列寻找由NMP4和MEF2以及报道的可以结合到BUR的单链或双链形式上的蛋白的结合。其中,SATB1(特异性富含AT结合蛋白1)属于一类DNA结合转录因子,它能够激活或阻遏临近基因的表达。这项研究表明特异性蛋白,如SATB1、NMP4(核基质蛋白4)和MEF2(肌源增强因子2),具有独特的分布并且围绕cLysMAR的最小MAR结构域形成了一构架(图10)。通过EMSA分析纯化的重组蛋白,NMP4和SATB1的一些结合位点的存在已经被实验证实(数据没有示出)。
实施例11:通过结合确定的遗传元件构造人造的MAR
为了进一步评估各种MAR成分的相对作用,cLysMAR被删除了所有的三个CUE区(图11,中间部分),与完全MAR序列对比这导致了它丧失部分活性的,该完全序列以类似方式由所有它的部件组装而成以作为对照(图11,顶部)。一致地,在没有侧翼序列时,每个单独CUE的一个拷贝,或每三个CUE头尾相接组装的一个拷贝只有很小的活性。这些结果支持这样一个结论,即最佳的转录活性需要CUE与侧翼序列结合。令人感兴趣的是,由其每一个部件产生的完整的MAR序列,但是还含有用于装配每个DNA片段的BgIII-BamHI连接序列(AGATCC),当与在这一系列分析中原始的MAR元件的4.8倍活性相比较时,显示出很高的转录活性(6倍的活性)(参见图5)。
我们随后研究了这些潜在的弯曲DNA区域在与在它们的天然MAR状况下所发现的环境中不同时是否也可有活性。因此,我们开始交换CUE-F、CUE-B和CUE-K元件,保持侧翼序列不变。将CUE-F元件的侧翼序列通过PCR扩增,并且与各种CUE装配在一起,保持它们最初的方向和距离,或者没有CUE。然后如上所述分析这些基因工程化的~1.8kb MAR的增强转基因表达的能力。这种状况下所有这三个CUE都是具有活性的,因此它们的作用并不受一个给定的侧翼序列的限制。令人感兴趣的是,当插入CUE-F的侧翼序列之间时CUE-K元件甚至比CUE-F具有更高的活性,而且前者的复合结构表现出与完整的天然MAR所观察到的一样高的活性(4.8倍活性)。除了它们的CUE特征之外,CUE-K元件与CUE-F和CUE-B的区别在于存在针对MEF-2和SatB1蛋白的重叠结合位点。因此,将CUE-B与CUE-F侧翼结构域融合导致所有三个结合位点的较高的密度,这可能对提高的活性作出解释。这些结果表明 将CUE与含有如NMP4、MEF-2、SatB1和/或polyPpolyQ蛋白的蛋白结合位点的序列装配在一起构造出有效的人造MAR序列。
实施例12:表达载体
根据本发明的三个表达载体在图12中列出。
质粒pPAG01是一5640bp的pUC19的衍生物。它含有一克隆于BamH1和XbaI限制位点中的2960bp的鸡DNA片段。该插入件来自鸡溶菌酶基因座的5’-端边缘,并且具有高A/T-含量。
质粒pGEGFP(也称为pSV40EGFP)对照是一pGL3-对照载体(Promega)的衍生物,其中荧光素酶基因序列被EGFP基因序列取代形成了pEGFP-N1载体(Clontech)。pGEGFP质粒的大小为4334bp。
质粒pUbCEGFP对照是一种具有一泛素启动子的pGL3的衍生物。
质粒pPAG01GFP(也称作pMAR-SV40EGFP)是一种克隆于MCS刚好位于SV40启动子上游具有5’-Lys MAR元件的pGEGFP的衍生物。pPAG01EGF质粒的大小为7285bp。
实施例13:初级转染细胞的另外转染对转基因表达的影响
在转染前一天,将细胞铺于24孔板,CHO-DG44细胞在生长培养基中的密度为1.35×105细胞/孔。在接种16小时后,当达到30-40%融合时细胞被转染,根据制造商的说明书(Invitrogen)使用Lipofect-AMINE 2000(下文中表示为LF2000)。将27ml含1.4μl的LF2000的无血清培养基(Opti-MEM;Invitrogen)与27μl含830ng 线型质粒DNA的Opti-MEM混合。该抗生素选择质粒(pSVneo)相当于带有GFP转基因的报道质粒的1/10。该混合物在室温下孵育20分钟,以使形成DNA-LF2000复合物。将该混合物用300μlOpti-MEM稀释并且倒入预先排空的含有细胞的孔中。随后在CO2 培养箱中于37℃使细胞与DNA混合物孵育3小时,每孔加入1ml的DMEM-基的培养基。使细胞在CO2培养箱中于37℃再孵育24小时。除了抗性质粒携带有另一种抗性基因(pSVpuro)之外,然后使细胞按照前述的方法进行第二次转染。第二次转染24小时后,使细胞迁移和延伸进入一含有补加的500μg/ml G-418和5μg/ml嘌呤霉素的选择培养基的T-75烧瓶中。经过两周的筛选期,在6孔板上培养稳定转染的细胞。可选替换的是,该细胞群可以用同样的方法再次转染,但是用pTKhygro(Clontech)和pSVdhfr作为抗性质粒。用荧光细胞分选仪(FACS)和荧光扫描仪分析GFP的表达。
图13示出了二次转染细胞的表型(此后称作二级转染子),不但被强烈着色,从而不需要专用的灯泡和滤光片来观测GFP蛋白的绿颜色,而且与亲代细胞群(中间频率分布图)比较,含有大量的生产细胞(底部右手边FACS频率分布图)。该荧光水平相当于特异性细胞产量为至少10pg/细胞·天。实际上,不表达标记蛋白的仅转染一次的细胞(初级转染子)再次转染后几乎全部从细胞群中消失。低于101单位的GFP荧光条带占中间频率分布图的30%,占右侧频率分布图的不足5%。这表明另外的细胞被转染并且成功地表达GFP。
令人惊奇的是,通过再转染细胞表现出的荧光的量表明:已经两次整合DNA的细胞亚群所表达的GFP远高于预期2倍的提高。实际上,表2中的结果表明:该二级转染子平均而言要高于假如两组序列一个接一个转染、并被独立地以相似的效率整合、其预期的 两倍的GFP增加。令人感兴趣的是,这不依赖于驱动报道基因的启动子序列,这是因为含有病毒和细胞启动子的载体具有相似的GFP增强(比较带1和2)。然而,当与不含MAR-质粒(带3)比较时可知对含有MAR的载体影响是特别明显的,其中在两个独立的实验中两个连续的转染导致表达提高5.3倍和4.6倍。
质粒的类型 | 初级转染 | 二级转染 | EGFP荧光增加倍数 |
pUbCEGFP | 4’992 | 14’334 | 2.8 |
pSV40EGFP | 4’324 | 12’237 | 2.8 |
pMAR-SV40EGFP | 6’996 | 36’748 | 5.3 |
质粒的类型 | 初级转染 | 二级转染 | EGFP荧光增加倍数 |
pUbCEGFP | 6’452 | 15’794 | 2.5 |
pSV40EGFP | 4’433 | 11’735 | 2.6 |
pMAR-SV40EGFP | 8’116 | 37’475 | 4.6 |
表7.初级转染子间隔24小时的再转染对GFP表达的影响。表示两个独立的试验。抗性质粒pSVneo与各种GFP表达载体共转染。转染1天后,细胞用同样的质粒再转染,不同的是抗性质粒变为pSVpuro。带有两种抗性基因的细胞在500μg/mlG-418和5μg/ml嘌呤霉素上筛选,并且报道基因标记物的表达用荧光扫描仪定量。将对应于从两次连续转染中得到的荧光比率增加倍数与相应的单独转染得到的荧光总和相比较。判定为显著更高的倍数增加用黑体表示,并且对应于始终比单独转染得到的数值之和2倍还高的荧光值。
在多次转染的细胞中,GFP表达水平的提高是目前的公知常识所意料不到的,并且这种影响在以前也没有被观察到。
总体而言,此处提供的数据支持这样的观点,即初始整合到宿主基因组中的质粒序列通过与第二个进入的质粒分子的同源重组有利于其它质粒的整合。质粒重组过程是在质粒DNA到达核之后的1小时间隔内发生的,并且已经显示出在培养的哺乳动物细胞中 共注入的质粒分子之间同源重组的频率非常高,接近整体(Folger,K.R.,K.Thomas,and M.R.Capecchi,Nonreciprocal exchanges ofinformation between DNA duplexes coinjected into mammalian cellnuclei.Mol Cell Biol,1985.5(1):p.59-69),这解释了多质粒拷贝的整合。然而,新引入的DNA与其染色体同源序列正常发生同源重组的情况非常少,频率最多为1/103个细胞收到DNA(Thomas,K.R.,K.R.Folger,and M.R.Capecchi,High frequency targeting ofgenes to specific sites in the mammalian genome.Cell,1986.44(3):p.419-28.)。因此,该结果可能表明MAR元件令人惊奇地起到促进这种重组过程的作用。MAR在体内不但改变基因的组织,也可能允许DNA复制与病毒DNA序列相关联,但它们也可能作为DNA重组的信号起作用。
实施例14:MAR在多次转染的细胞中介导意外的高水平表达
如果MAR驱动的重组过程能够在多次转染过程中发生,我们可以设想一级和二级质粒DNA之间的协同作用将会由于MAR元件的存在而在转染的一步或两步中受到影响。我们通过只具有pMAR的细胞或具有与各种表达质粒组合的细胞进行多次转染来检测这种可能性,使用的方法如前所述。表3显示用pMAR-SV40EGFP质粒转染细胞两次得到了GFP的最高表达量,并且在所有条件下都具有最高程度的增强(4.3倍)。相反,用无MAR的质粒转染载体两次得到了很少增强或没有增强的结果,2.8倍,而不是预期的提高2倍。我们的结论是在每一个转染步骤中存在MAR元件对于实现最大量的蛋白合成是必要的。
表8
令人感兴趣的是,当细胞首先单独用pMAR转染然后用pSV40EGFP或pMAR-SV40EGFP再次转染,GFP水平比后面的质粒单独转染的结果高两倍多(分别为2.5倍和2.7倍,而不是预期的1倍)。这表明前面的MAR转染可以提高二次转染过程中所使用的质粒的表达。由于MAR只局部作用于染色质结构及基因表达,这意味着这两类DNA可能已经整合到染色体相似基因座上。相反,用GFP表达载体单独转染,随后在第二步用MAR元件,产生很少的或没有产生GFP的改进。这表明质粒转染的顺序是重要的,而且首次转染过程应该包含有MAR元件以允许显著更高的转基因表达水平。
如果MAR元件有利于第一次和第二次转染过程中保持为游离基因形式的质粒的同源重组,随后通过它们共整合到一个染色体基因座,则可以预期质粒转染的顺序不会影响GFP水平。然而,上述结果表明在第一次转染过程中转染MAR元件更有利,而不是第二次转染过程于。这表明了如下的分子机制:在第一次转染过程中,MAR元件,至少部分MAR元件,可能连接并整合到细胞染色体中。该整合的MAR DNA可以反过来有利于在第二次转染过程中,在同一染色体基因座或邻近的染色体基因座上更多质粒的进一步整合。
实施例15:MAR作为长期DNA转移易化子(facilitator)
如果整合的MAR介导了一稳定的重组许可的染色体结构,即使在第一次转染很长时间后进行第二次转染,这时大多数短暂引入的游离基因DNA已经被消除,也可以期望高水平的表达。为了研究这种可能性,由表3中挑选抗生素抗性持续三周的细胞,将其再转染一次或两次,并且选择整合的另外的DNA抗性标记物。第三、或第三及第四轮转染用pMAR或pMAR-SV40EGFP的组合来完成,并且如前所述分析GFP表达。
表9
表9.MAR作为DNA整合的易化子(facilitator)。
在挑选过程结束后将pMAR-SV40EGFP/pMAR-SV40EGFP二级转染子用于第三轮转染。用pMAR或pMAR-SV40EGFP进行第三次转染,并且将pTKhygro作为挑选的质粒,从而得到了三级转染子。24小时之后,用质粒和pSVdhfr将细胞再次转染,最后在含有500μg/ml G-418和5μg/ml嘌呤霉素、300μg/ml潮霉素B和5μM甲氨蝶呤的生长培养基中选择第四级转染子。二级转染子最初显示了8300的GFP荧光。与从相应的独立转染中得到的荧光的总和相比,从两个连续转染中得到的相应的荧光比率成倍增加。判断倍数增加很多时用黑体表示,并且对应于高于独立转染获得的荧光值之和为2倍的荧光值。
这些结果显示载入了更多的pMAR或pMAR-SV40EGFP拷贝,结果是类似的全细胞荧光的2倍增强。在第四级转染中载入更多的MAR进一步增强了其活性达另一个2.4倍。这与我们的假设相吻合,即新引入的MAR序列可能通过同源重组整合到染色体的转基因基因座,并从而进一步增强了转基因表达。
当用pMAR-SV40EGFP质粒进行细胞的第三和第四次转染时,GFP活性进一步增强,再一次超过预期的独立转染所获得的荧光水平之和。GFP表达达到了可以在白天看到细胞发出的绿光的水平(图14)。这些结果进一步表明四级转染的效率比预期的第三次DNA转移效率高很多,从而表明转染期间恰当的时机对于获得最佳的基因表达的提高是至关重要的,一天比3周更为优选。
我们认为MAR元件通过松弛紧密的染色质结构在染色体整合位点提高了重组频率从而有利于二级整合,如同它们介导了组蛋白乙酰化作用的局部增加(Yasui,D.,et al.,SATB1 targets chromatinremodelling to regulate genes over long distances.Nature,2002.419(6907):p.641-5.)。可选替换的或随之而来的是,MAR潜在地将邻近的基因重新定位到亚核位点,该位点被认为是富含包括能够参与重组蛋白如拓扑异构酶的反式作用因子。这可以产生一基因座,其中MAR序列能够与pSV40EGFP重复在一起,有效地保护了转基因免受染色质-介导的沉默效应。
从用SMAR Scan 或组合方法分析全部人类基因组序列得到的序列中随机选出四个MAR元件。它们命名为1_6、1_42、1_68、(其中第一个数字代表该序列来源的染色体,而第二个数字是沿着 该染色体预测的MAR独有的)以及在染色体X上识别的“超级”MAR,X_S29。如前所述,将这些预测的MAR插入到驱动绿荧光蛋白表达的SV40启动子和增强子的pGEGFPControl载体的上游,并且将这些质粒转染进入培养的CHO细胞(Zahn-Zabal,M.,et al.,Development of stable cell lines for production or regulated expressionusing matrix attachment regions.J Biotechnol,2001.87(1):p.29-42)。随后用荧光细胞分选仪(FACS)在稳定转染的所有细胞群中分析该转基因的表达。如图19所示,所有这些新识别的MAR都提高了转基因的表达,显著地超过了由鸡溶菌酶MAR驱动的表达,“超级”MAR X_S29是所有新识别的MAR中最有效的。
实施例17:通过电转移带有和不带有人MAR(1-68)的网络系统对于mEpo体内表达的血细胞比容的影响
编码EPO(促红细胞生成素)的治疗基因用作一种治疗贫血症的激素。将该EPO基因置于一种强力霉素可诱导的启动子的控制下,位于一在下面称做网络系统的前述基因转换系统中(Imhof,M.O.,Chatellard,P.,and Mermod,N.(2000).A regulatory network forefficient control of transgene expression.J.Gene.Med.2,107-116.)。随后将该EPO和调节基因利用称作电转移的体内电穿孔过程注入到小鼠的肌肉中,从而该基因被转移到肌肉纤维的核中。当将强力霉素抗生素加入到小鼠的饮用水中时,该化合物预期会诱导EPO的表达,由于高水平的循环EPO介导的红细胞数量增加,这将会导致血细胞比容的增高。因此,如果MAR改善了EPO的表达,则可以预期更高水平的血细胞比容。
对5周龄的C57BL6雌性小鼠进行体内实验(Iffa Credo-CharlesRiver,France)。将30μg溶于正常盐溶液的质粒DNA通过透皮注射进入胫骨前肌肉内。所有的注射都是在Ketaminol(75mg/kg)和 Narcoxyl(10mg/kg)麻醉下进行的。随后进行DNA肌肉内注射,对该处肌肉施加电场。以8ms脉冲在1Hz下施加200V/cm的电压(Bettan M,Darteil R,Caillaud JM,Soubrier F,Delaere P,Branelec D,Mahfoudi A,Duverger N,Scherman D.2000.“High-level proteinsecretion into blood circulation after electric pulse-mediated genetransfer into skeletal muscle”.Mol Ther.2:204-10)
将16只小鼠用无1_68MAR的表达EPO的网络系统注射,而另外16只小鼠用加入5’MAR的网络系统注射,该5’MAR具有驱动激活剂和EPO基因表达的启动子/增强子序列。在每一组中,将一半的小鼠从开始实验时(第0天-电转移那天)即在饮用水中施用强力霉素,而另一半从第21天开始在饮用水中放入强力霉素。
注入质粒后,在不同的时间使用肝素处理过的毛细管通过后眼窝穿刺来收集血样。毛细管在室温下以5000rpm离心10分钟,并将血细胞的体积分数通过与全血体积比较来进行测定,并表示为百分数,从而决定血细胞比容水平。
从图16可推出,与注入无MAR原始网络的小鼠相比,通过注入MAR-网络从实验开始进行诱导的这组小鼠表现出更好的血细胞比容诱导。2个月后,“含有MAR组”中的血细胞比容(65%)仍然比正常的血细胞比容(44-55%)具有更高的数值。
更为重要的是,后诱导(第21天)只有在MAR存在时才可能发生,当小鼠注入无MAR的网络时无后诱导发生。因此MAR可能保护转基因免受沉默,而且即使在非诱导条件下经过了很长时间后,也可以诱导其表达。
总而言之,MAR元件能够提高治疗基因的表达,如同所观测到的它对于血细胞比容的提高的生理影响那样。
P7388RWS.ST25
P7388RWS.ST25
SEQUENCE LISTING
<110>思兰克斯有限公司
<120>通过MAR序列的多次转染过程在哺乳动物细胞中实现高效基因转移和表达
<130>P7388RWS
<140>PCT/EP2004/011974
<141>2004-10-22
<150>US 60/513,574
<151>2003-10-24
<150>EP 04 002 722.9
<151>2004-02-06
<160>241
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agtaaatata tatagtatat atatagtaaa tatatatata gtatatatat agtaaatata 360
tatatagtat atatatagta aatatatata tagtatatat atagtaaata tatatagtat 420
atatatagta aatatatata gtatatatat agtaaatata tatagtatat atatagtaaa 480
tatatataca ctgtatatat atagtaaata tatatacact gtatatatat agtaaatata 540
tatacactgt atatatatag taaatatata tacactgtat atatatagta aatatatata 600
cactgtatat acatagtaaa tatatataca ctgtatatac atagtaaata tatatacact 660
gtatatacat agtaaatata tatacactgt atatacatag taaatatata tacagtgtat 720
atacatagta aatatatata cagtgtatat acatagtaaa tatatataca gt772
<210>10
<211>304
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(304)
<223>人染色体1的MAR,基因基序;6221897至6222200
<400>10
atatataata tatataatta tattatatat aatatataat atatataatt atattatata 60
ttatatataa tatattatat attatatata taatatatat tatatattaa atatatatta 120
tatatataat atatattata tattaaatat atattatata tataatatat attatatata 180
atatatataa tatatattat atatatatta tatattatat atatatatta tatatatata 240
atatatataa tatatattat atataatata tattatatat atataatata tataatatat 300
atta304
<210>11
<211>311
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(311)
<223>人染色体1的MAR,基因基序;9418531至9418841
<400>11
tatatataat atttatatat aatattcatg tatttatata taaatattta tatatttata 60
tataaatatt tatatattta tatataaata tttatatatt tatatataat atttatacat 120
tatatataat atttatatat tatatataat atttatatat aatatttata tattatatat 180
aatatttata tatttatatg tataatatat attttatata tgtatgtata atatatattt 240
tatatatgta tgtataatat attttatata tgtatgtata atatattatt atatataata 300
tataatttat a311
<210>12
<211>302
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(302)
<223>人染色体1的MAR,基因基序;15088789至15089090
<400>12
atataatata tatattatat atataaatat atataaatat ataacatata tattatatat60
aaatatatat aaatatataa catatatatt atatatataa atatatataa atatataaca 120
tatatattat atatataaat atatataaat atataacata tatattatat atataaatat 180
atattatata tttatatata taatatatat aaatatataa tatatattta tatatataat240
atatataaat atataatata tatatttata tataatatat ataaatatat aatatataat300
at302
<210>13
<211>461
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(461)
<223>人染色体1的MAR,基因基序;6791827至6792287
<400>13
tatataatat atattatata tacacatata taatatatat tatatataca catatataat60
atatattata tatacacata tataatatat attatatata cacatatata atatatatta120
tatatacaca tatataatat atattatata tacacatata taatatatat tatatataca180
catatataat atatattata tatacacata tataatatat attatatata cacatatata240
atatatatta tatatacaca tatgtaatat atattataca cacacatata atatatatta300
tatacacata tataatatat attatatata catatataat atatattata tatacacata360
tataatatat attatatata cacatatata atatatatta tatatacaca tataatatat420
aatatataca catatataat atatatatta tatatgcaca t461
<210>14
<211>572
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(572)
<223>人染色体1的MAR,基因基序;163530至164101
<400>14
atattataat tatatatatt atatataatt atataaaata tatattataa ttatatatat60
tttatataat atatatatta taattaatat attatatata atatatatat tatatataat120
atatatatta tatatattat atataatata tataatatat ataatatata atataatata180
tatattatat ataatatata atatatataa tatattataa tataatatat ataatatata240
atataatata tataatatat aatataatat ataatatata atatatataa tatataatat300
aatatataat atatataata tataatataa tatataatat atataatata ttataatata360
atatatataa tatataatat aatatatata atatataata taatatataa tatataatat420
atatttaata tatttattaa ttatttgtta tatatttatt aatatataat atataatata480
tttaatatat tataactata tattatatta taattatata tattatatat atacaattat540
aattatatat tatatatact tataatatat at572
<210>15
<211>357
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(357)
<223>人染色体1的MAR,基因基序;1842332至1842688
<400>15
tatatctata tatatctata tatatataat atagataata tctatatata taatatagat 60
aatattatct atatataata tagataatat tatctatata taatatagat aatattatct 120
atatataaaa ttatattata tctatatata ttatatatat aaaattatat tatatctata 180
tataatatag ataatatcta tatataaata gataatatct atatatataa tatagatatt 240
atctatatta tagatataga taatattatc tatattatag atattatcta tatataatat 300
agataatatt atctatatta tatatataat atatctatat tatctataat attatct357
<210>16
<211>399
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(399)
<223>人染色体1的MAR,基因基序;2309560至2309958
<400>16
attatatata atatatatta tatattatat atatcaagca gcagatataa tatataatat 60
atataatata tataatatat attgtatatt atataatata taatatatat aatatatatt 120
gtatattata taatatataa tatatataat atatattgta tattatataa tatataatat 180
atataatata tattgtatat tatataatat ataatatatg taatatatta tgtaatatat 240
tatataatat atattatata ttatatataa tatatattat atataatata tattacataa 300
tatattacat atattacgta atatatgtta tatattacat ataatatata acatatatta 360
cgtaatatat gtaatatatt acatataata tatacatta399
<210>17
<211>394
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(394)
<223>人染色体1的MAR,基因基序;2231759至2232152
<400>17
atatatactt ataaattata tacttatata tacttataaa ttatatactt atatatactt 60
ataaattata tacttatata tacttataaa ttatatactt atatatactt ataaattata 120
tacttatata tacttataaa ttatatactt atatatactt ataaattata tacttatata 180
tacttataaa ttatatactt atatataatt ataaattata tacttatata taattataaa 240
ttatatactt atatataatt ataaattata tacttatata taattataaa ttatatactt 300
atatataatt ataaattata tacatatata taattataaa ttatatacat atataattat 360
aaattatata catatataat tataaattat atac394
<210>18
<211>387
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(387)
<223>人染色体1的MAR,基因基序;7406524至7406910
<400>18
tatattatat ataatatata ttatatataa tataaataat atatattata tataatatat60
aaataatata taatatataa ataatatata atatataata tataaataat atataatata120
taacatataa ataatatata taatatataa ataatatata taatatataa ataatatata180
taatatataa aaatatataa tatataatac atatataaat aatatattat attatatatg240
atacataata tattatatat aatatattat atgatacata atatattata tagaatatat300
tatatgatac ataatatatt atatagaata tattatatga tacataatat attatatgat360
acataatata ttatatataa tatatta387
<210>19
<211>370
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(370)
<223>人染色体1的MAR,基因基序;9399572至9399941
<400>19
catatataca tatatacaca tatatacaca tatatataca catacatatg tacacatata60
tatacacata tgtatacaca tatatacaca tatatacaca catatataca catatataca120
cacatatata cacatatata cacatatata cacatataca catatataca catatataca180
tatatacaca tatatataat atacacacat atatatacac atatatacac acatatatac240
acatatatac acatatatat acacatatat acacatatat acatatatac acatatatat300
acatatatac acatatatac atatatacac atatatacat atatacacac atatatacac360
atacatatac370
<210>20
<211>377
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>msc_binding
<222>(1)..(377)
<223>人染色体1的MAR,基因基序;12417411至12417787
<400>20
attatatata atacatataa ttatatattt atatataaat tataataaat acatataatt60
atatatttat atataaatta tatataataa atacatataa ttacatatat ttataaatta120
taataaatac atataattac atatatttat atatgaatta tatataataa atacatataa180
ttatatatat ttatatgtag attatatata aatatatata atttatatat ataataatat240
atataattta tatatataat tatatatata ataaatatat ataatttata tatataatta300
tatatataat aaatatataa taatatatat aatttatata tataattata tatataataa360
atatatataa tttatat377
<210>21
<211>1524
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1524)
<223>人染色体1的MAR,基因基序;1643307至1644830
<400>21
tataaatata tataaatata taaatatata taaatatata aatatatata aatatatata 60
aatatataaa aatatataaa tatatataaa tatatataaa tatataaaaa cataaaaata 120
tatataaata tatataaata tataaaaata tataaatata taaatatata aaaatataca 180
aatatataaa tatatacata aatatatata aatatatata aatatataaa aatatatata 240
aatatataaa tatatataaa tatatataaa tatatataaa tatataaaaa tatatataaa 300
tatataaata tataaaaata tatataaata tataaatata taaatatata taaatatata 360
aatatataaa taaatataag tatttatgaa tatatatgaa tatataaata tataaaaaat 420
atatataaat atataaatat atataaatat ataaatatat acatatatac atatataaat 480
aaataaatat aagtatttat gaatatatat gaatatataa atatataaaa aatatatata 540
aatatataaa tatatataaa tataaatata taaaaatata taaaaatata tataaatata 600
taaatatata taaatatata aatatatata aatatatata aatatataaa tatatataaa 660
tatatataaa tatataaata tataaatata tataaatata tataaatata taaatatata 720
aatataaata tataaatata tataaatata tataaatata taaatatata taaatatata 780
taaatatata taaatatata taaatatata aatatatata aatatatata taaatatata 840
taaatatata aatatataaa tatataaaaa tatataacaa tatataaata tatataaaaa 900
tatataacaa tatataaata taaatatata taaaaatata taacaatata taaatataaa 960
tatatataaa tatataaata taaatataaa aaatatatat aaatatataa atatatataa 1020
atatataaat gtataaatat atataaaaat atataacaat atataaatat ataaatatat 1080
aacaatatat aaatatataa aaatatataa caatatataa atataaatat atataaaaat 1140
atataacaat atataaatat aaatatatat ataaatatat aaatataaat ataaaaaata 1200
tatataaata tataaatata tatataaata tatataaata tataaatgta taaatatata 1260
taaatatata aatatataaa aatatataaa tatatataaa tatatataaa tatataaata 1320
taaatatata aatatatata aatatataaa tataaatata taaacatata taaatatata 1380
taaataaaca tatataaaga tatataaaga tataaagata tataaatata taaatatata 1440
aagatatata aatatataaa gatatataaa tatataaaga tatataaata tataaagata 1500
tataaatata atatataaat atat1524
<210>22
<211>664
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(664)
<223>人染色体1的MAR,基因基序;1398763至1399426
<400>22
acacatatat atataaaata tatatatata cacacatata tataaaatat atatatatac 60
acacatatat ataaaatata tatatacaca catatatata aaatatatat atacacacat 120
atatataaaa tatatatata cacacatata tataaaatat atatatacac acatatatat 180
aaaatatata tatacacaca tatatataaa atatatatat acacacatat atataaaata 240
tatatataca cacatatata taaaatatat atatacacac atatatataa aatatatata 300
tacacacata tatataaaat atatatatac acacatatat aaaatatata tatacacaca 360
tatataaaat atatatatac acatatatat aaaatatata tatacacata tatataaaat 420
atatatacac acatatatat aaaatatata tatacacaca tatatataaa atatatatat 480
acacatatat ataaaatata tatatacaca tatatataaa atatatatat atacacatat 540
atataaaata tatatacaca catatatata aagtatatat atacacacat atatataaaa 600
tatatatata cacatatata taaaatatat atatacacat atatataaaa tatatatata 660
caca664
<210>23
<211>1428
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1428)
<223>人染色体2的MAR,基因基序;17840365至17841792
<400>23
aatttattat atattatata ttatatatat tatatatatt atatattata tatattatat 60
atattatata ttatatatat tatatattat atatttatat ataatatata tctaatatat 120
atattagata taatatatat ctaatatata tatattttat atatataata tatctctaat 180
atatatattt tatatgtata taatatatct ctaatatata tatattttat atgtatataa 240
tatatctcta atatatatat tttttatata taatatatct ctaatatata tattttatat 300
atataatata tatctaatat atataatata tatattagat atatataaaa tatatatgat 360
atatttatta tatatataat atataatata taatatatat attatattat atacatatat 420
attatataca atatatatta tatatatttt atatacatta tatattatat atattttata 480
tacaatatat attatatatt ttatatacaa tatatattat atatatttta tatttttata 540
tacaatatat attatatata ttttatatat aatatatatt atatatattt tatataatat 600
atattatata tattttatat ataatatata ttatataaat tatatataat atatattata 660
ataaattata atatttttta tatatataat atgtatttta tatataatat attataatat 720
atattttata tataatatat tataatatat attttatata taatatatta taatatatat 780
tttatattat aatatattat aatatatatt ttatatataa tatattataa tatatatttt 840
atatataata tattataata tatattttat atataatata ttataatata tatattataa 900
tatatatttt atatataata tattatcata tatatattaa atatatattt tatatataat 960
atattataat atatatatta taatatatat tttatatata atatattata atatatatat 1020
tataatatat attttatata taatatatta taatatatat tttatatata atatattata 1080
atatatattt tatatataat atattataat atatatttta tatataatat aatatatatt 1140
ttatatataa tatattataa tatatatttt atatataata tattataata tatattttat 1200
atataatata ttataatata tattttatat ataatatatt ataatatata ttttatatat 1260
aatatattat aatatatatt ttatatataa tatattataa tatatatttt atatataata 1320
tattataata tatattttat atataatata ttaattaaat ttattaattt attaattatt 1380
aatatttatt atattattaa ttaataatat ataaattatt aatatata1428
<210>24
<211>4624
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(4624)
<223>染色体1的MAR 1_6
<400>24
ggatcttaaa tctattttat ttatttattt ttcatgtggc caataccctc cacccccttc 60
ttctgtctct ttcaacttat tgtggttacc ttgaggctac ctgagacagt aggcttgggt 120
ggggaagtat gcattctaag tgtaaagttt gatgagcttt gacaaatgtc aacccatgta 180
ccagaacatt ttcatcaccc ataaaatctc ccttgtgtca cttgccagtc agtgtctatt 240
ctagtatcca actcctggct ccaagaaacc attgaactgt tttctgtcac tataaattag 300
atttgtcttt tctagagttt catgtaaatg gaatcataca ctaagtactc tttgtgcctg 360
gcttctgctc agcataatgt ttttgagaat cattcatgct gctgcatgtt ttcagtagtt 420
cattttttta aataggtgaa ttgtaactca ttctgtgaat ataccatatt ctgtcttcca 480
tttatctgtt agtggatctt taggtcgttt ctagttttgg gctattgcaa ataaagctgc 540
tgtaaatatt aatgcacaag ttttccatgt tcatatgttt catttcactt aggaaaatac 600
ctaagagagg aattgcacat attaaaaaaa ttttaaaaac tactaagctg ttctccaaaa 660
tggttgtaca atttttattc ccaagagcaa tatgagtgtt taattgctcc acattctcac 720
caacacttgg tgcttgttag ttttattttc attgttttca ttgttatgtc tgtgaggcag 780
cattgatgtg catgtctctg agtgtcatct tagcggtgat gctgagcatc agttcacgtc 840
cttataggcc gtttgtatat ctgctttgtg aaatgtctgt tcaaatcttt tgcctatttt 900
aaattgagtt gtgttcgtct tcttaggatt aagtaatgag ttaaaaatat ttctgataca 960
aatctttcat tatatatttc taatgctttc tcatctatag tttattttct catattcttt 1020
aactgtatct tttgaagagc aaattttact tttgattatg cccaatttat caagttttta 1080
tatggctctt ttgattatgc ccataatcac attagacttt gcctaaccca agtttgcaga 1140
gattttttct tttatgcttt tatctagaaa ttttgtagtt ttaggtttta aaaaagttta 1200
atttatttat ttgagacagg gtattgctct ttacatatac tggagtgcag tgatgcaatc 1260
atggctcact gcagcctcaa cctcttgggc tcaagcggtt ctcccatctc agagtcctga 1320
gtagctggcc aggtgcatgc cagcttcaat gtgtttttca tttgcatttc cctgataatt 1380
attgacgttg agcatttttt tcatatatca gttagctatt tgtacgtctt cttttgagaa 1440
acatctattc gggtcttttg cccattttaa agtcagatgg tttgtttgtc agctattgag 1500
ttgtttgagt tccttgtata ttctggatat taccatcttg tcagatgcac agtttgcaaa 1560
tttttttttt ctattttgta ggttgtctct ttctctgttg tttcctccgg tatgcagaag 1620
ttttttagtg tgatgtaatt tcatttgtct gtttttgctt ttgttgcctg tactttctta 1680
ttcttatcca aaaaatcttt atctagatca atgtcacgaa gagtttctcc tctgttttct 1740
tcgagtagtt ttttataatt ttgggtatac atttaagtct ttaatctatt tggaattgat1800
ttttgcatat ggtgagagat cagagtctaa tttcatactt ttggatgtgg aaagctagtt1860
ttttcagcac catttattga agagactgtc tcttctccaa tgtgtgttct ttgtgccttc1920
gtcaaaaatc agttggctgt gcgtggattt atttctgtgt tctctatttt gttccattgg1980
tctagtttta gccttaaatt taggtctgca attttttttt ttttgtatat ggtgtgaagt2040
aagagtcaaa gttcattatt tttcatatgg atatgtaatt actccagtac catcatttag2100
tttgaatgga ctgtcctttc tccatggaat tacatgggca tcttttgtct gaaaccaatt2160
atgtatgttt acgtatgtgt atgtttatgc atatgttata ggtttaatat atattaatat2220
atataatata taatatataa atattaatat gtattatata atatatatta atatattata2280
ttatattact atataaataa tattaatata ttatattaaa atattaataa atatatcata2340
ttaaatatta tattaattaa atattaataa atatattata ttaatatatt tatatattaa2400
acctataaca tatgcatata cttatttata tataacatgc atgtacttat ttatatatac2460
aatatatatt tatatattat ataatatatt atatgtattt atatattata tatcatatat2520
tatatgtatt tatatattat atatcatata atatatatat ttatattata tatattatat2580
gatatataat attatataat gtattaatat atattaaacc tatatttata attctggact2640
cactattttg tttcattggt gtctgtgtgt atctaaccct atgccaataa tgtactatct2700
taattaccat agctttatag taagctttga aatcagatag tgtatttttt atcattgttt2760
tttaaaataa tagtttatct ttttatttga atttgtaatc agctagtcag tttctgcaaa2820
aagcttactg ggattttgct tggaattatg ttacatctgt agcatgtact atccaatatt2880
ctagccttta tccacatgtg gctattaagg tttaaattaa ttaaattaaa atttaattaa2940
ttaaaattaa aacttaataa ttggttcctc attcacacta ccatatgtca agtgttcaat3000
agccacatat ggtcaatgtc ttggaaaagt caatacagta catttccatt attgcagtaa3060
gttctgtcaa acagcactat cgtagaccga ttaggagaga actgacttaa cagtattgga3120
tgctccagtc aatgaacatc tttttttttt tcatttattt cagtagtctc tgcagtatat3180
tatagatttc agtttacata ttttgcatat attttattaa atgtataacg gtagaagtac3240
tattattgga tgatgtgttc tatagatgta ttttaggtca agtttgttga tagtgttgtt3300
taaatctcgt atacctcttg atttttttat ttacttgttc tttgaattac tgagacagga3360
atgttatatc cttaactata tttgtgaatt tattcacttc ttccttcagt tctgttaact3420
tttgcttagg tgctttttaa aaatgaaact ttcaatctct gccttttaat tgtagcattt3480
agaccattta cattcaatgt aattatcaat atcagtttat ttaagtctga agttgtgcaa3540
tttttcctct acctatatta taaatctttc tatatacaaa acacatgcta tgttttctgc3600
atatgtttta aatgacaccc ggaaagcatt gacactattt ttgctttagg ttatctttca3660
aagatgttaa aaatgagaaa gaaatattct gcatttatcc atacacttat tatttgcaaa3720
ggttttttta aatacctttg tgtagatttc agttaccaac ttgtatttcc ttcagcttga3780
agaacttaca atttcttgta ggacaggtct ctgacaacaa attatctcag cttttctttg3840
tctaaaaaag ttattgcctt tatttttaaa atatattttc actggatatt gaattttagg3900
tgataatctt tttttttttg ttagcacttt aaatatgtct tctaatgtcc tcttgctttc3960
atagtttctg atgagaagtc tactgttatt agtatctctt tgtgtgtgtc tctctttttt 4020
ccctctctgc tattatggct attttttttt tttttttttt ttttggtcac tggtgtcagc 4080
aatttaatta tggtgtgcct tggtatgttt tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg 4140
tgtgtgtgtg tagctgatgt tctttgagct ttagaatctg tgagtttgta gttttcatca 4200
attatttttt cttttcattc cttttattta ctcatgttcg tgttttattt tatattttta 4260
agaattttgt gcgtatttgt aataactgtt taaatgtcat ttgtgaattc cattgcttct 4320
aggtaggatt ctattgacag atattttttc cctgacgaga ggtcatactt tccttattct 4380
tcatgtatct agtggttttt ggttgaatac tggatatttt gaattttatg ggagtgctga 4440
attctacaat attccttaaa aatgtgttgg attttgtttt agcagatagc tatcttactt 4500
gaagatcaat ttcatatttt ttgatgttca ttttttcatt tattaaagaa taggtccatg 4560
gtagagttta ctgatatcaa cctttctggt gtctctaata aatgcaacat attcaataag 4620
atcc4624
<210>25
<211>3616
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(3616)
<223>染色体1的MAR 1_68
<400>25
gactctagat tataccaacc tcataaaata agagcatata taaaagcaaa tgctcttatc 60
ttgcagatcc ctgaactgag gaggcaagat cagtttggca gttgaagcag ctggaatctg 120
caattcagag aatctaagaa aagacaaccc tgaagagaga gacccagaaa cctagcagga 180
gtttctccaa acattcaagg ctgagggata aatgttacat gcacagggtg agcctccaga 240
ggcttgtcca ttagcaactg ctacagtttc attatctcag ggatcacaga ttgtgctacc 300
tattgcctac catctgaaaa cagttgcttc ctatatttca tccagtttaa tatttattta 360
aaccaagaag gttaatctgg caccagctat tccgttgtga gtggatgtga aagtaccaat 420
tccattctgt tttactatta actatccttt gccttaatat gtatcagtag gtggcttgtt 480
gctaggaaat attaaatgaa tggcatgttt cataggttgt gtttaaagtt gttttttgag 540
ttaaatcttt ctttaataat actttctgat gtcaaaaaca cttagaagtc atggtgttga 600
acatctatat agggttggat ctaaaatagc ttcttaacct ttcctaacca ctgtttttgt 660
ttgtttgttt ttaactaagc atccagtttg ggaaattctg aattagggga atcataaaag 720
gtttcatttt agctgggcca cataaggaaa gtaagatatc aaattgtaaa aatcgttaag 780
aacttctatc ccatctgaag tgtgggttag gtgcctcttc tctgtgctcc cttaacatcc 840
tattttatct gtatatatat atattcttcc aaatatccat gcatgggaaa aaaaatctga 900
tcataaaaat attttaggct gggagtggtg gctcacgcct gtaatcccag cactttggga 960
ggctgaggtg ggcggatcat gaggtcaaga gatcgagacc atcctgacca atatggtgaa 1020
accccatctc tactaaagat acaaaactat tagctggacg tggtggcacg tgcctgtagt 1080
cccagctact cgggaggctg aggcaggaga acggcttgaa cccaggaggt ggaggttgca 1140
gtgagctgag atcgcgccac tgcactccag cctgggcgac agagcgagac tctgtctcaa 1200
aaaaaaaata tatatatata tatatataca catatatata taaaatatat atatatacac1260
acatatatat ataaaatata tatatataca cacatatata taaaatatat atatatacac1320
acatatatat aaaatatata tatacacaca tatatataaa atatatatat acacacatat1380
atataaaata tatatataca cacatatata taaaatatat atatacacac atatatataa1440
aatatatata tacacacata tatataaaat atatatatac acacatatat ataaaatata1500
tatatacaca catatatata aaatatatat atacacacat atatataaaa tatatatata1560
cacacatata tataaaatat atatatacac acatatataa aatatatata tacacacata1620
tataaaatat atatatacac atatatataa aatatatata tacacatata tataaaatat1680
atatacacac atatatataa aatatatata tacacacata tatataaaat atatatatac1740
acatatatat aaaatatata tatacacata tatataaaat atatatatat acacatatat1800
ataaaatata tatacacaca tatatataaa gtatatatat acacacatat atataaaata1860
tatatataca catatatata aaatatatat atacacatat atataaaata tatatataca1920
catatatata aaaatatata tatatatttt ttaaaatatt ccaattgtct cactttgtgg1980
atgagaaaaa gaagtagtta gaggtcaagt aacttggcct acatcttttc tcaagattgt2040
aaactcctag tgagcaataa ccacatcttc attttctttg tataaaacaa gaaagtttag2100
catgaaaaag gtactcaatt acaaatgtgt tggattgaat tgaagaccct tggaagggga2160
ttttgtacct gaggatctct ttcttttggc catattgttc aatggacaaa atttagcctt2220
cgaaggcagg ccgatttgag gttaatacta cctttaccac ttgatagcta tgtgaccttg2280
gccatgtggt ttcaacagtc tgaacctcat tttctctgtg tatgtgtggt cctccttaca2340
agtttgtgaa aaatgtgaag tccttagcca tgatagccca atataacagg ctaaatgata2400
ataggtttat gttcttttcc tttatattct cagataagca ctgtccaagt ttgaggtgtt2460
ttgaggtctc gcctgatttg gattgtttga gtttatgcta ttctttgaat tctttgagct2520
gttctgaagc agtgtatcat gaacaaaaac atccccagtt cagtccaaac ccctggttac2580
atatcattct tatgccatgt tataaccagt ttgagagtgt tccctctgtt attgcattta2640
agtttcagcc tcacacagaa attcagcagc caatttctaa gccctaagca taaaatctgg2700
ggtggggggg ggggatggcc tgaagagcag cattatgaat agcaccatta taattaatga2760
tctctcagga agatttacaa tcacaggtag cagataaaac aaatagtact gcttctgcac2820
ttcccctcct tttattcgct atgaaatttt atgggaaatc agtccagtga aaaatgtaag2880
ctcttaatct ttcccagaaa tcctacctca tttgatgaat actttgaggg aatgaattag2940
agcatttttt tcttttatag tctacttcgc atttacgaag tgaggacggt agcttaggct3000
gcctggccaa ctgatgagaa ggtcagaggc atttttagag acctctgttg tctttcattc3060
atgttcattt tccacaaggc aagtaatttc caacaaatca gtgtcttcat tagtaataag3120
attattaaca acaataatag tcatagtaac tattcagtga gagtccatta tatatcaggc3180
attctacaag gtactttata tacatctgag taaacctcac acaattctac agggaggtat3240
ttctatcccc atttaacaaa taaggaaacg aagtccaagt aaattaactt gcccaaggtc3300
acacagatag tacctggcag aacaggaatt taaacctaaa tttgtccaac tccaaaagca3360
gccttctatt tgttataaat gctgcctctc attatcacat attttattat taacaacaac3420
aaacatacca attagcttaa gatacaatac aaccagataa tcatgatgac aacagtaatt 3480
gttatactat tataataaaa tagatgtttt gtatgttact ataatcttga atttgaatag 3540
aaatttgcat ttctgaaagc atgttcctgt catctaatat gattctgtat ctattaaaat 3600
agtactacat ctagag3616
<210>26
<211>4660
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(4660)
<223>染色体1的MAR 1_42
<400>26
gatcccttga ggtcagtagt ttaagaccag cctgaccaac atggtgaaac ccatctctac 60
taaaaataca aaaattagcc aggcgtggtg gcgggggcct gtaaccccag ctactcagga 120
ggctgaggca caagaatctc ttgaacccgg gaggcggagg ttgcagtgag ctgagattgt 180
gtcactgcac tccagcctgg gcaacagtgc cagactctgc cttaaaaaaa aaaaaaaaaa 240
aaaaaaggcc gggcgcggtg gctgacgcct gtaatcccag cactttggga ggccgaggcg 300
ggtggatcat gaggtcagga gatcgagacc acagtgaaac cccgtctcaa ctaaaaatac 360
aaaaaattag ccgggcgcgg tggtgggcgc ttgtagtccc agctactcag gaggctgagg 420
caggagaatg gcgtgaacct gggaggcgga gcttgcagtg agccgagatg gcaccactgc 480
actccagcct gggcgaaaga gtgagactcc gtctcaaaaa aaaaaaaaaa ttagctgggt 540
atggtggtgc gtgcctgtaa tcccagctac tcgggaggct gaggcaggag aatcccttga 600
acctgggagg cggaggttgc agtgatctgc catcctgtca ctgcatcact acactccagc 660
ctgggtgaca gagcgagact ctgtctcaaa aaaaaaaaaa aaaaaaaaag ctgggtgtgg 720
tggtatgcac cagctgtagt cccagctact tgggaggctg agttgggggg attgcctgag 780
ccagggaggt cgaggcttca gggagccatg attatgccac tgcactccag cctgggccac 840
agagtgaaac cttctgtcaa aaacaaaaaa acaaaaaaac acagtgtgtt agatcttgct 900
agacttggtg atataattaa gaggccatta tgggcagaac tgtgccccct tccaaaattc 960
atatataaat atatataaat atatataaat atataaatat atataaatat ataaatatat 1020
ataaatatat aaatatatat aaatatataa atatatataa atatatataa atatataaaa 1080
atatataaat atatataaat atatataaat atataaaaac ataaaaatat atataaatat 1140
atataaatat ataaaaatat ataaatatat aaatatataa aaatatacaa atatataaat 1200
atatacataa atatatataa atatatataa atatataaaa atatatataa atatataaat 1260
atatataaat atatataaat atatataaat atataaaaat atatataaat atataaatat 1320
ataaaaatat atataaatat ataaatatat aaatatatat aaatatataa atatataaat 1380
aaatataagt atttatgaat atatatgaat atataaatat ataaaaaata tatataaata 1440
tataaatata tataaatata taaatatata catatataca tatataaata aataaatata 1500
agtatttatg aatatatatg aatatataaa tatataaaaa atatatataa atatataaat 1560
atatataaat ataaatatat aaaaatatat aaaaatatat ataaatatat aaatatatat 1620
aaatatataa atatatataa atatatataa atatataaat atatataaat atatataaat 1680
atataaatat ataaatatat ataaatatat ataaatatat aaatatataa atataaatat1740
ataaatatat ataaatatat ataaatatat aaatatatat aaatatatat aaatatatat1800
aaatatatat aaatatataa atatatataa atatatatat aaatatatat aaatatataa1860
atatataaat atataaaaat atataacaat atataaatat atataaaaat atataacaat1920
atataaatat aaatatatat aaaaatatat aacaatatat aaatataaat atatataaat1980
atataaatat aaatataaaa aatatatata aatatataaa tatatataaa tatataaatg2040
tataaatata tataaaaata tataacaata tataaatata taaatatata acaatatata2100
aatatataaa aatatataac aatatataaa tataaatata tataaaaata tataacaata2160
tataaatata aatatatata taaatatata aatataaata taaaaaatat atataaatat2220
ataaatatat atataaatat atataaatat ataaatgtat aaatatatat aaatatataa2280
atatataaaa atatataaat atatataaat atatataaat atataaatat aaatatataa2340
atatatataa atatataaat ataaatatat aaacatatat aaatatatat aaataaacat2400
atataaagat atataaagat ataaagatat ataaatatat aaatatataa agatatataa2460
atatataaag atatataaat atataaagat atataaatat ataaagatat ataaatataa2520
tatataaata tataaagata tataaatata atataaaaat atataaatat atattaaaaa2580
tatatacata taaatatatg tatatttttt tgagatgggg tctcgctcag ccacccacgc2640
tggagtgcag tggcacgagc tcggctcact gcaaccactg tctctcgggt ccaagcaatt2700
ctgtctcagc ctcccaagta gctgggatta caggcacctg ccatcatgcc cggctaattt2760
ttgtatttta gtagagatgg agtttcacca tgttggccag gttggtctcg aattcctgac2820
ctcaggtgat ctgccggcct cggcctccca gtgctgggat tacaggcatg agtcaccacg2880
cccggcccta tatatatttt tgagacaagc tctgtgtctc ccaggctgga gtgcagcagc2940
atgatcatga ctcactgtag cctagacctc cagggctcaa gtgattctcc cacctcagcc3000
tcccaagtag ctgggattac aggcatgcac caccacaccc agctaatttt tgttttgttt3060
tgttttggag acagaatctc tctctgtcac ccaggctgga gtgcagtggt gtgatctcag3120
ctcagtgcaa cctccacctc ctgggttcaa gtgattctca tgcctcagcc tcctgagtag3180
ctgggactac aggcgtgagc caccacgccc tgataaattt tgtatttttt ttttcagatg3240
gagtctcact ctgtcatact caggctggag tgcagtggcg tgattttggt ttattgcaac3300
ctctgcttcc tgggttcaag cgattctcct gcctcagcct ccagagtagc tgggattaca3360
ggcgcctgcc accatgccca cctagctaac tttttttttt ttttttttga gatagagtct3420
cactctgtca cccaggctgg agtgcaatgg ggcgatattg gctcactaca acctccacct3480
cccaggttca agcgattctc ctgcctcagc ctcctgagta gctgggatta caggtgggtg3540
ccaccacgcc agactaatat ttgtattatt agtagagacg gggtttcacc acattggtca3600
ggctggtttc gaactcctgg cctcaggtga tctgcctgcc tcggcctccc aaagtgctgg3660
gattacaggc atgagccact gcggctggcc caatttttgc atttttttgg tagagacggg3720
ggtttcacta tgcttcccag gctggtctca aactcctgga ctcaagcgat ctgcctgtct3780
cagcctccca aagtgcaggg attacagtca tgagccacca ctgcacggcc ccaaaattta3840
tttattttat tattattatt attttttaga tggagtctcc ttctgttgcc agattggaat3900
gcagtgccac gatctcagct cactgcaacc tccccctcct gggatcaagt gattcttttt 3960
tttttaagac tctgtctcaa aaaaaaagaa aaaaaaaaaa aatatatata tatatatata 4020
tatacacgaa ttttgggcca ggcacagtgg cttatgcctg taatcccagc actttgggag 4080
ggccgaggtg ggtggatcac aaggtcagga gtttgagacc agcctggcca atatggtgaa 4140
accctgtctc tactaaaaaa tacaaaaatt agctgggcgt ggtggcacga gcctgtaatc 4200
ctggctactc tggaggctaa ggcaggagaa tcgcttgaac cggggaggca gaggttgcag 4260
tgagccagga tcgcatcact gcactccagc ctgggtaaca gagcaagact ctgtctcaaa 4320
aaacaaacaa aacaaaacaa aacaaaataa ataacggtgc aaaattgaat atgccttttt 4380
gactctctaa atgcctcaga tccatttacc ctggggattt gtcctttcta gccccaccac 4440
catctcccct ctggaagact gctgacctat aaggataaag accagactct tgagcaggca 4500
cttagggtct tcctgcccat ccctatcccc aactccccct cagtaatttt ggctactagt 4560
atttctccac atctgaggct atcgtgggtc tcccttcagt ggtcatgaag gacaaggttg 4620
gagaagtttg ccctcgtgag tctgatgagg gattgggtgg4660
<210>27
<211>3354
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(3354)
<223>染色体X的MAR X_S29
<400>27
gatcccttta taaaaccaca atataatgga gtgctataat ttcaaacagt gtttggtctg 60
ctggcagagt ggtcattcta acagcagtca cagtagagta gaaataagac tgcagtatat 120
ctaaggcaaa aagctgaggt ttcaggagct tgaaggtaaa gaggaagaaa gaaatgggaa 180
tgggaattgg aaagacaaat atcgttaaga gaaaattgct tttaggagag gggaaagaat 240
ctatgtgtac ttaagactat ggaatcaatc ccatttaagc tgggaaacta gtttcatata 300
taactaataa attttattta cagaatatct atttacctga tctaggcttc aagccaaagg 360
gactgtgtga aaaaccatca gttctgtcat attcctaaaa aaaaattaaa aagttaaaaa 420
taaataaata ataaaacttc ttttctttca aaataatcaa ggtgcttatt cacatccatt 480
ccaatttggg gaaatactta ttttcctatg attagcgaag agaaaagtaa cttgcatttc 540
aattcaagtt gatacatgtc acttttaaga ggtcaactaa tatttgctag ttgagctaac 600
catataggct ttaaatactt tcatagtaga aagaaaatga aaatcattag tgaactgtat 660
aaaatagatc atactttttg aaagaatcag actgaagttt ccgaaaaaaa gaagtaagct 720
tcaatgaaaa ggtaagtgaa tttagcattt actcagcatc tactatggac ttaacaccta 780
acagtagata atctgaaggc aaacatattt gtatagggac tgcagaatga tagatgataa 840
atatcatctc ttctatttga atgaatattt tttcaaatct ttcacacaca gtggtttgct 900
atggaaagat ttgtagtaca ttaaacaaat ctgaagatgg agttagaaag cttaggctat 960
gttttgagca caacatataa tttctctgtg attgtttctt catctttcaa atgaggttac 1020
tgtgaagatt aaatgagata actaaatgat gataaaataa tgtaatctta gcagcacctt 1080
atttaatctg tgcaacaact ctgtgaagtg agtagggctc agcttcagtc acttctctgc 1140
catttattaa ctaagatagt ttggaaagtt acccatctct tcagctgtaa aatgatgagg1200
atcataccta ttttatgggg ctgcttttag gtacaaatat acaggcaagc actttgttaa1260
tactaaagca ttacaccaat tagttttact cttttccatt cacacatgaa attaatgtaa1320
tcagaattct gtagattacc taaatcttct gttaacacgt gatatgcagt tcaggttaaa1380
tgtcagttga gttaccaaag cacatacata ctcaccaccc tatccaaatc tacaagcctc1440
ccagtttgtc ttcactattt tggttaaatt aatatgaatt cctagatgaa aatttcactg1500
atccaaatga aataaaaaat atattacaaa actcacacct gtaatctcaa cattttggga1560
ggccaaggca ggtagatcac ttgaggccag gagttcaaga ccagcctgat caacatggtg1620
aaaccctgtc tctactaaaa atacaaaaat tagccaggtg tggtggcatg tgcctgtagt1680
cctacctact cgggaggctg aggcacaaga atcgcttgaa tgtgggaggt ggaggttgca1740
gtgacctgag atcgtgccac tgcactccag cctaggcaac agagtgagat catgtgtcat1800
atatatatat atatatatat atatatatat atatatatac acacacacac acatatatat1860
atacacatat atatacgtat atatatatat gtatatatat acatatatat acatatatat1920
atatacgtat atatatacgt atatatatat caatgtaaat tatttgggaa atttggtatg1980
aatagtcttc cctgtgaaca cagatcataa aatcatatat caagcagaca aataagtagt2040
agtcacttat atgcttatac ttgtaactta aagtaaaaga attacaaaag catatgacaa2100
agactaattt taagatatcc taatttaaat tgttttctaa aagtgtgtat accattttac2160
ctatcatatg aataatttag aaacatgttt ataaaattaa tgtccaaatc cattcaaaag2220
ttttgtaatg cagatcaccc acaacaacaa agaatcctag cctattaaaa aagcaacacc2280
acctacatat aatgaaatat tagcagcatc tatgtaacca aagttacaca gtgaatttgg2340
gccatccaac actttgagca aagtgttgaa ttcatcaaat gaatgtgtaa tcatttactt2400
actaatgcca atacacttta aggtaatctt aagtagaaga gatagagttt agaatttttt2460
aaatttatct cttgttgtaa agcaatagac ttgaataaat aaattagaag aatcagtcat2520
tcaagccacc agagtatttg atcgagattt cacaaactct aactttctga tacccattct2580
cccaaaaacg tgtaacctcc tgtcgatagg aacaacccac tgcagggatg tttctcgtgg2640
aaaaaggaaa tttcttttgc attggtttca gacctaactg gttacaagaa aaaccaaagg2700
ccattgcaca atgctgaagt acttttttca aatttaaaat ttgaaagttg ttcttaaaat2760
ctatcattta ttttaaaata cggatgaatg agaaagcata gatttgataa agtgaattct2820
tttctgcaat ctacagacac ttccaaaaat cactacagac actacagaca ctacagaaaa2880
tcataaataa acaagtgcta gtatcaatat ttttaccaaa aaatggcatt cttagaattt2940
tttataggct agaaggtttg tacaaactaa tctgccacgg attttaaaat atgagtgaat3000
aaattatatt gcaaaaaaaa tcaggttaca gagaactggc aaggaagact cttatgtaaa3060
acacagaaaa catacaaaac gtatttttaa gacaaataaa aacagaactt gtacctcaga3120
tgatactgga gattgtgttg acatattagc attatcactg tcttgctaaa acataaaaat3180
aaaaagatgg aagatgaaat tacaatacaa atgatgattt aaacatataa aaggaaaata3240
aaaattgttc tgaccaacta ctaaaggaag acctactaaa gatatgccat ccagcacatt3300
gccactctac atgtggtctg taaaccagca gcatagggat cctctagcta gagt3354
<210>28
<211>677
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(677)
<223>染色体1的MAR基因基序;12803267..12803943
<400>28
ttatatagta tatataatag tatatattat atagtataca taatagtata tattatatag 60
tatacataat agtatatatt ataatataca taattgtata tatcatatag tatacattat 120
agtatatatc atatagtata cattatagta tatatcatat agtatacatt atatagtata 180
tatcatatag tatacattat agtatatatc atatagtata cattatagta tatatcatat 240
agtatacgta atagtatata tcatatagta tacgtaatag tatatatcat atagtatacg 300
taatagtata tatcatatag tatacgtaat agtatatatc atatagtata cgtaatagta 360
tatatcatat agtatacgta atagtatata tcatatagta tacgtaatag tatatatcat 420
atagtatacg taatagtata tatcatatag tatacgtaat agtatatatc atatagtata 480
tattatatag tatatatcat atagtatata ttatatagta tatatcatat agtatatatt 540
atatagtata tatcatatag tatatattat atagtatata tcatatagta tatataatag 600
tatatatcat atagtatata taatagtata tatcatatag tatatatact atactatatt 660
atatatagta tacataa677
<210>29
<211>332
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(332)
<223>染色体1的MAR基因基序;13079684..13080015
<400>29
ttaattatat tatatatatt atataattat atattaatat atattaatta tattatatat 60
attatataat tatatattaa tatatattaa ttatattata tatattatat aattatatat 120
taatatatat taattatatt atatatatta tataattata tattaatata tattaattat 180
attatatata ttatatatta taattatata ttatataatt ataatatata tgttaatata 240
atatatataa ttaatatata attaaaacta tttaattata tgtatattat atataatatg 300
tattatttaa ataataaata tattatttat at332
<210>30
<211>479
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(479)
<223>染色体1的MAR基因基序;15682296..15682774
<400>30
acaagtacat atatatatag tatatatata caagtacata tatatagtat atatatatat 60
acaagtacat atatatagta tatatatata tacaagtaca tatatatagt atatatatat 120
acaagtacat atatatagta tatatatata caagtacata tatatatagt atatatatat 180
acaagtacat atatatagta tatatatata caagtacata tatatatagt atatatatat 240
acaagtacat atatatagta tatatatata caagtacata tatatatagt atatatatat 300
acaagtacat atatatatag tatatatata tacaagtaca tatatatata gtatatatat 360
atacaagtac atatatatag tatatataca tatatacaag tacatatata tagtgtatat 420
atatatatac aagtacatat atatacttgt attagtatat atatatatat atacaagta479
<210>31
<211>531
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(531)
<223>染色体1的MAR基因基序;15694611..15695141
<400>31
tataatatat ataatacata atagatatat tatattatat aatagatata taattataaa 60
cataataata tataatgaat ataatataaa ataaatataa taaaatatat aatatatcta 120
ttatgtatta tatattatat atgtttatat ataatataat tatatatgtt tatatataat 180
ataattatat atgtttatat ataatataat tatatattat atattataga tataatatat 240
aatatactat atattataga tataatatat aatatactat atattataga tataatatat 300
aatatactat atattataga tataatatat aatatactat atattataga tataatatat 360
aatatactat atattataga tataatatat aatatatatt atatattata gatataatat 420
ataatatatt atatattata tctatatata atatattgta tattatatat aatatattgt 480
atattatata taatatattg tatattatat ataatatatt gtatattata t531
<210>32
<211>378
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(378)
<223>染色体1的MAR基因基序;886276..886653
<400>32
ttatattata tatcttacat aaattatata tatatattac ataaattata tacaatataa 60
attatataca atataattta tatataaaat ataaattata taaataattt atatataaaa 120
tataaattat ataaataatt tatatataaa atataaatta tgtataaaat ttatatataa 180
aatataaatt gtgtataaaa ttatatataa aatataaatt gtgtataaaa tttatatata 240
aaatataaat tatatataat ttatatatta taatataaat tatatataat atatatcata 300
aaatataaat tatatataat atatatcata agatataaat tatatataat atatatcata 360
agatataaaa tatataat378
<210>33
<211>595
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(595)
<223>染色体1的MAR基因基序;3326732..3327326
<400>33
aaaatatata aatatatata aaaatatata aaaatatata aatatatata aaaatatata 60
aatatatata aatatatata aaaatatata aatatatata aatatatata aaatatataa 120
atatatataa aatatatata aatatatata aatatatata aaaatataaa tatatataaa 180
aatataaata tatataaata tatataaaaa tataaatata tataaatata tataaatata 240
taaatatata taaatatata taaatatata aatatatata aatatatata aatatatata 300
aatatataaa tatataaaaa tatatataaa tatataaata tatataaata tataaatata 360
taaaaatata tataaatata taaatatata taaatatata taaatatata tataaatata 420
tataaatata tatatatata aatatatata aatatatata taaatatata taaatatata 480
tatatatata taaatatata taaatatata taaatatata tataaatata tataaatata 540
tataaatata tatataaata tatataaata tatatataaa tatatataaa tatat595
<210>34
<211>738
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(738)
<223>染色体1的MAR基因基序;4485716..4486453
<400>34
ataatagata atatatatta tatgatagat atataatata ttatataata tataatatat 60
tatatatcta tcatataata tatataatat ataatatatt atatatctat catataatat 120
aatatatata atatataata tatatcatat tatattgtat ataatatata tcatattata 180
ttgtatataa tatatatcat attatattgt atataatata tatcatatta tattgtatat 240
aatatatatc atattatatt gtatataata tatatcatat tatattgtat ataatatata 300
tcatattata ttgtatataa tatatatcat attatattgt atataatata tatcatatta 360
tattgtatat aatatatatc atattatatt gtatataata tatatcatat tatattgtat 420
ataatatata tcatattata ttgtatataa tatatatcat attatattgt atataatata 480
tatcatatta tattgtatat aatatatatc atatattatc tattatattg tatataatat 540
atattatata ttatctatta tattgtatat aatatatatt atatattatc tattatattg 600
tatataatat atattatata ttatctatta tattgtatat aatatataat aaatatagta 660
tatataatag ataatatata gtatatatga tatattatat atactatata ttatatatca 720
tatatactat atactata738
<210>35
<211>386
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(386)
<223>染色体1的MAR基因基序;5423067..5423452
<400>35
taaatatata aaaatatata taaaaatata aaaatattta tataaatata taaaaatatt 60
tatataaata tataaatata taaatatata tttatataaa tatataaata tataaatata 120
taaatatata tttatataaa tatataaata tatatttata taaatatata aatatatata 180
aaatatataa atatatattt atataaatat ataaatatat ataaaatata taaatatata 240
tattttatat aaatatataa atatatataa aatatataaa tatatatatt ttatataaat 300
atataaatat atataaaata tataaatata tatattttat atatttatat atataaatac 360
atatatttca tatatcacat atatga386
<210>36
<211>584
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(584)
<223>染色体1的MAR基因基序;5805559..5806142
<400>36
taaatatttt taaaatatat atattttata atatataatt tatattataa tgtgtacata 60
atatatatta taatataata tatataatac tgtatattat attatatata ttataatata 120
tattattata tattatatta tatataatat aatatatatt ataatatatt atattataca 180
tattataatg tattataata tatattatat tatatattat aatatatatt atattatata 240
ttataatata tattatatta tatattataa tatatattat attatattat atatattata 300
atacatatta taatacatat tatataatat attataatat gtattataat acatattata 360
taatatatta taatatatta tatataataa tatattataa tacatattat atataatata 420
tattatgtat attatatata atatatatta caatgtatat tatgtatatt atatatatta 480
tatatcatat aatatatatt atatataata tgatatataa tatatattat ataatatatt 540
atatgatata tataatatgt attacatgta atatatatca taat584
<210>37
<211>345
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(345)
<223>染色体1的MAR基因基序;10802644..10802988
<400>37
tgtatatata tactatatat atactatata tatagtgtat atatatacta tatatatact 60
atatatatag tgtatatata tactatatat atagtatata gtatatatag taatatatat 120
atatagtata tatatacact atatatagta tatatagtat atatatattg tgtatatagt 180
atatatatag tgtatatata gtatatatat attgtatata tagtatatat attgtgtata 240
tatagtatat atatagtata tatagtatat atagtatata tatagtatat atatactata 300
tatatagtat atatatattg tatatatata ctatatatat agtat345
<210>38
<211>474
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(474)
<223>染色体1的MAR基因基序;13496468..13496941
<400>38
atattatata taatataatt atatctataa ttatatatta tatataatat aattatatat 60
ctataattat atattatata taatatatat tatatataat atataattat atataattta 120
tataatataa tatataatat ataattatat ataattatat aatataatat ataatatata 180
attatatata atttatataa tataatatat aatatataat tatatatatt tatataatat 240
aattatatat aatatataat tatatataat ttatataata taattatata taatatataa 300
ttatatataa tttatataat ataattatat ataattatat attatatata atttatataa 360
tataattata tataatatat aattatatat aatatataat tatatataat tatatataat 420
atataattat atataattta tataatataa ttatatatta tatatattat atat474
<210>39
<211>483
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(483)
<223>染色体1的MAR基因基序;2509163..2509645
<400>39
caaaatacat aatatataat agtattatat aatagtatgt atagttataa tatatagtat 60
aattacaata tatgatatgg tttatatatt atatatagta taatataata taacataata 120
ctattataat atataaacta tataatatat actattataa tatatgaact attataatat 180
ataaactata tataatatat aatatgtact attataatat ataaactatt ataatataat 240
atataaacta ttataataca taaactatta taatatatat aatactatgt atacatatat 300
tacattatgt acatactaca ttatgtatta tgtatgtata tatacacaaa atacataata 360
tataatagta ttatataata gtatatatag ttataatata tagtataatt acaatatata 420
atatggttta tatattatat atagtataat acaatataac ataatactat tatatataaa 480
cta483
<210>40
<211>641
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(641)
<223>染色体1的MAR基因基序;2776349..2776989
<400>40
tgttatatat atataacata gatattatat atacatgtta tatatataac atagatatta 60
tatatacatg ttatatatat aacatagata ttatatatat aacatagata ttatatatac 120
atgttatata taacatagat attatatata catgttatat ataacagata ttatatatac 180
atgttatata taacatagat attatatatg tatgttatat ataacataga tattatatat 240
gtttatataa tatataacat atgtttaaca tatataatat ataacatgtt tatataatat 300
ataacataat tatatgttat atatgatata aaacatatat attatatacg ttatatgtaa 360
tatataacat atattgtata cgttatatgt aatatataac atatattgta tacgttatat 420
gtaatatata acatatattg tatacgttat atgtaatata taacatatat tgcatacgtt 480
atatgtaata tataacatat attgtatacg ttatatgtaa tatgtaacat atattgtata 540
cgttatatgt aatatgtaat atataataca tataacatgt atatataaca tatatgtata 600
taacatatat ataacatata taacatatat gttatattat a641
<210>41
<211>745
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(745)
<223>染色体1的MAR基因基序;2858703..2859447
<400>41
atatttatat atgtaataat atataatata tttatatgta tttgtatatg taataatata 60
tatataataa aatatgtaat aatatataat atatttatat ataaatatat tatattatat 120
atatattatt atatttataa tataatatat atttatatta tatattataa atatatatta 180
tataatatat attataaata tatattatat aatatatatt ataaatatat attatattat 240
atattataaa tatatattat ataatatata ttataaatat atattatata atatatatta 300
taaatatata ttatatttat aatatatatt tttgtatatt atatattata tattataaat 360
attattatat ttataatata ttatatattt tatatataat atatgatata tattataaat 420
atatcttata aatatatata tttatatata tatattataa atatataaat ataaatatat 480
aatataatat aatataatat aataaatata atatataata tatataatat ataataaata 540
taataaatat aaatatatca tataaatata aatataaata taaatatatc atataaatat 600
atatatttat atgatatatt atagtatata taaatatatt tatatattat aaaatattta 660
tataatatat aattataata tatttatata tataaattaa ctaatatata taaactaata 720
taatatataa tgtaataata tagta745
<210>42
<211>307
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(307)
<223>染色体1的MAR基因基序;945522..945828
<400>42
catatataat atatattacc tatgttatat aggtcatata taacataaat atattacata 60
tatgtaatat atattaaata taaatatata acatatatgt gtaactatat atgtaaatat 120
gtacatatac atatatgtaa atatataata tatatttaca ttatattata taatatatat 180
ttacattata tatttatata tacattatat atatttacat tataaatatt tatataatat 240
atatttacat tatattacat tatataaaat acaatatatt acattataat acattataac 300
agataaa307
<210>43
<211>357
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(357)
<223>染色体1的MAR基因基序;3402743..3403099
<400>43
aatattatat taaatataat atattaatat ttaatatatt taatataata ttaaataaat 60
atattataaa taaattataa tatataaata tatattatgt atttatgtat aatatataaa 120
aattatatat aatatatata tttttataaa tatataaata tataataaat aaatatatta 180
aataaataat aatatattaa atattaatat attaaatatt atatattaaa tataatatgt 240
aatatgaaat atattaaata ttatatatta aatataatat ataatgtgaa atatattaaa 300
tattatatat taaatataat atataatatg aaatatatta aatattatat attaaat357
<210>44
<211>323
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(323)
<223>染色体1的MAR基因基序;3485830..3486152
<400>44
atatttatag actatatatt tatatattta gtgtatttgt atactatata tttatatagt 60
tagtatattt gtatactata tatttatata tttagtatat ttgtatacta tatatttata 120
tatttagaat atttgtatac tatatattta tatatttagt atatttgtat actatatatt 180
tagtatattt gtatactata tatttatata tttagtatat ttgtatacta tatatttata 240
tatttagtat atttatatac tatatactta tatatttagt atatttatat actatatact 300
tatatattta gtatatttat ata323
<210>45
<211>498
<212>DNA
<213>智人(Homo sapien)
<220>
<221>misc_binding
<222>(1)..(498)
<223>染色体1的MAR基因基序;3548336..3548833
<400>45
aattattact atattgttaa tataattatt atataatata atataattat atcactatta 60
ttatattata gtattaatat aatagtgtat aacattaata taatatagta ttaatataat 120
agcgtataac attaatataa tatagtatta atataatagc gtataacatt aatataatat 180
agtattaata taatagtgta tattaatata atatagtatt aatatataat attaatataa 240
tatatcaata taatagtata taatataata taatatatca atataatagt atataatata 300
atataatata tcaatataat agtatataat ataatataat atatcaatat aatagtatat 360
aatattaata taatataata tcaatataat agtatataat attaatatat taatataata 420
gtatataata ttaatgtaat ataatattaa cataatgtat ataataatat aatagtatat 480
aatactaata taatataa498
<210>46
<211>400
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(400)
<223>染色体1的MAR基因基序;4595109..4595508
<400>46
aaatatatta tattatatat tatatattat tcaatatact ataatatata ttatatatgt 60
ttaatacaat atataatatt tacatatatt cccatttatt tatataacat atattatatg 120
atattatata ttactccata taatataata tattatacat aatatattac tcagtataat 180
acataatata tataatatat tactcggtat aatatataat attatatgtt atgcaatata 240
atatataata ttatatataa tacattattc aatataatat ataatattat atataataca 300
ttattcaata taatatataa tacactattc aatataatat acaatattat atataataca 360
ttattcaata taatatatat tatataatat atatatttat400
<210>47
<211>403
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(403)
<223>染色体1的MAR基因基序;7205509..7205911
<400>47
agtatatata tgtgtatata tatgagtata tatatgtgta tatatatgag tatatatatg 60
tgtatatata tgagtatata tatgtgtata tatatgagta tatatatgtg tatatatatg 120
agtatatata tgtgtatata tatgagtata tatatgtgta tatatatgag tatatatatg 180
tgtatatata tgagtatata tatgtgtata tatgagtata tatatgtgta tatatgagta 240
tatatatatg tgtatatatg tgagtatata tatgtgtata tatatgagta tatatgtgta 300
tatatatgag tatacatatg tgtatatata tgagcatata tgtgtatata tatgagtata 360
tatatgtgta tatatatgag tatatatgtg tatatatatg agt403
<210>48
<211>309
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(309)
<223>染色体1的MAR基因基序;7507280..7507588
<400>48
tataaaatat atattattta tatattatat ataaaatata tattatatta tatattatag 60
atataataaa taaataatat ataatatatt atataattat ttatacataa ttatatataa 120
ttatatgtaa ttgtacaatt atatataatt atatacaatt atacacataa ttatatacaa 180
ttatacaatt atatacataa ttatatatat aatatacata attatatatt aattatacaa 240
ttatatacat aattatatat aattatacaa ttatatacat aattattatg tatattatat 300
tatataata309
<210>49
<211>516
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(516)
<223>染色体1的MAR基因基序;3581085..3581600
<400>49
atatatatat atatatatat atttatatat atatatatta atatatatta tatataaaaa 60
tatataaaat ttatatatat aatttatata tataaaaata tataaaattt atatatataa 120
tttatatata taaaaatata taaaatttat atatataatt tatatatata aaaatatata 180
aaatttatat atataattta tatatataaa aatatataaa atttatatat ataatttata 240
tatataaaaa tatataaaat ttatatatat aatttatata tataaaaata tataaaattt 300
atatatataa tttatatata taaaatatat aaattatata tataattata tatataatat 360
aaaattatat atataattat atatataata taaaattata tatataatta tatatataat 420
ataaaattat atatatattg tatatatata aaatatacaa aatttatata tataaaatat 480
aaaatataca taaaaataaa tatatataat ttatat516
<210>50
<211>534
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(534)
<223>染色体1的MAR基因基序;3084851..3085384
<400>50
atataatata tatgactata tattttatat tatattctat ttcaataaaa tatttatatt 60
ttattatata ttataatata taattatata tgtaataata tataatatat aatatatatt 120
ttatattata ttttatattt atttttatat tttatattat attttattat atatattata 180
atatataatt atatatgcaa taatatatta tatattataa tatataatta tatatgcaat 240
aatatattat atattataat atataattat atatgcaata atatattata gattataata 300
tataattata tatgcaataa tatattatat attatatatt agataatata ttaatatata 360
ttataacata taatatataa catataatat ataatatatt atctaatata taatataaca 420
tataatatat aatatattat ataatatatt attacatata taatatattg taatatataa 480
tattacatat atcttcaaaa agagttatgt gtatataata catatatata ccat534
<210>51
<211>583
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(583)
<223>染色体1的MAR基因基序;160087..160669
<400>51
tatttatata aaatatataa aatatattat atataaatat attatatata atatatttat60
atattataca atatatttat atattatata taatatattt tatataatat acataatata 120
ttttatatat tatatataat atattttata tataatgtac aatatatttt atatattata 180
tataatatat tttatatata ctatacaata tattttatat attatatatt ttatatatat 240
ttttcatgta acatatatat tttatatata atatatatac catatataat atattttata 300
tataatatat ataccatata taatatattt tatatataat atgtatatca tatatagtat 360
attttatata taataggtat accatatata atatatttta tatataatag gtataacata 420
tataatatat tttatatata atatgtatac catatataat atattttata tattatagat 480
accatatgta atatacttta tatataatat agataccata tgtaatatac tttatatata 540
atatagatac catatgtaat atactttata tataatatag ata583
<210>52
<211>314
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>mi sc_binding
<222>(1)..(314)
<223>染色体1的MAR基因基序;4350424..4350737
<400>52
tatgtgtata taaatatatg tatatatgtg tatataaata tatataaata tatgtatata 60
tgtatatata catatattta tatataaata tatgcatata tttatatata aaatatatgc 120
atatatgtat atatataaaa tatatacata tatgtatata tataaaatat atacatatat 180
gtatatatat aaaatatata catatatgta tatatataaa atatatacat atatgtatat 240
atataaaata tatacatata tgtatatata taaaatatat acatatattt atatatataa 300
aataccaagt ctta314
<210>53
<211>828
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding<
222>(1)..(828)
<223>染色体1的MAR基因基序;8443267..8444094
<400>53
tattatataa ttatatatac tatataatta tataatatat agttatatag tatatataat 60
atatataata tatactatag tatatataat atatataata tatactatag tatatataat 120
atataattat atataatata tataatatag tatatattat atatatatta tatatatata 180
atatatatat aatatatata atatagtata tataatatat aattatatat aatatataat 240
atagtatata taatatataa tatatatata attatatact ataatatata taatatataa 300
ttatatatta tatactatag tatatattat tatatataat agatataata tatataatta 360
ttatataata tagtatatat aatatataat tatatataat agatataata taatataatt 420
atatataata tagtatatat aatatataat tatattatat tatatataat atataattat 480
aatatataat tatattatat aatatatata atatataatt atattatata attatattat 540
ataatatata taatatataa ttatattata taatatatat aatatataat tatattatat 600
aatatatata atatataatt atattatata atatatataa tatataatta tattatataa 660
tatatataat atataattat atattatata taatatagta tatataatat gtaattatat 720
atcatataat atataacatt gtatataata tataattaca tattatataa tgtatataat 780
atataattat atacattata taatatagta tataattata tattatgt828
<210>54
<211>573
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(573)
<223>染色体1的MAR基因基序;8703190..8703762
<400>54
tatattatat ataaaatata catataatat acctataata tacatataat atataatata 60
tattatgtac atataatata catataatat atataatata taatgtacat ataatataca 120
tataatatat gttatatatt atatataaaa tataggatat atataatata gaatatatat 180
actatattgt atatataaga tatataatat atagtatata tactatataa tatataatat 240
atagtatata taatatataa tatagaatat atatacaata tataatatag aatataggat 300
atatatagaa tatacatata taatatgtat atattatata ttatattata tattatataa 360
aaatatataa tatataatat aaaaatatat tatatattat ataatataaa atatattata 420
tattatatat tatataatat aaaatatatt atatattata tattatatat aaaatatatt 480
atatattata tattatatat aaaaatatat tatatattat atattatata taaaaatata 540
ttatatatta tatataaaaa tatatattat tac573
<210>55
<211>597
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(597)
<223>染色体1的MAR基因基序;8819076..8819672
<400>55
acatatctta tatataaaat atataaatat acacatattt tatatataat atatattata 60
tatatgaaat atacacatat ttttatatat ataatatata tattatatat aatatatgca 120
tatattatat ataaaatata tatattatat ataaaatatg catatattat atataatata 180
tataatataa aatatataat atatattata tattatatat aatatatatt atatataata 240
catatatata atatataata tatataaaat ataatatata tattatataa tatatatata 300
aatatatata atatatatat aatatatata ttatatataa aatatatatt atatgtaaaa 360
tatataatat atataatata tatattatat gtaaaatata tattatatat aaaatatata 420
atatataaaa tatatattat atataaaata tataatatat aaaatatata atatatataa 480
aatatataat atatataaat atatattata tataaaatat ataatatata taaatatata 540
ttatatataa aatatataat atatataaat atatattata tataaaatat atattat597
<210>56
<211>646
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(646)
<223>染色体1的MAR基因基序;759619..760264
<400>56
taatatatat aatatatatt atataataat atataatata tattatatta taatatataa 60
tatattatat aataatatat attatataat atataataat atatataata catattattt 120
aataatatat aatatatatt atataataat atataatata tattatataa taatatacat 180
tatattatat aatatataat atatataata tatattatat aataatatat aatatatatt 240
atagaatgat atattagata ttatataatt atatatataa tattatatat tatataataa 300
tatataatat atattatata attatatata taatattata tattatataa ttatatataa 360
tatattatat aattatatat ataatattat atattatata attatatata atatatatta 420
tataattata tatataatac tatatattat ataattatat ataatactat atattatata 480
atttatataa ttatatatat tatatattat ataattatat atattatata ttatataata 540
acatatatat tatatattat ataataacat atatattata tattatataa tacatatata 600
ttatatatta tataatacat tattatataa tatataatat atatta646
<210>57
<211>752
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(752)
<223>染色体1的MAR基因基序;1226710..1227461
<400>57
taaacatata tataaatata tataaatata tatataaata tatataaata tataaatata 60
taaatatata tgaatatata aatatatata aatatatatg aatatataaa tatatatata 120
aatatatata aatatatata taaatatata taaatatata taaatatata taaatatata 180
taaataaata tataaatata tataaatata taaatatata tataaatatg taaataaata 240
tatataaata tataaatata tataaatata tataaatata tatagaaata tatatagaaa 300
tatatataaa tatatataga aatatataga aatatatata gaaatatata taaatatata 360
taaatataga aatatatata aatatatata aatatatata gaaatatata atatatataa 420
atatatataa atatataaat atatatataa atatatatat aaatatatat aaatatatat 480
aaatatatat aaatatatat aaatatatat attaatatat aaatctatat taatatatat 540
taatatataa atctatatta atatatatta atatatatat taatatatat taatatataa 600
atatatatat taatatataa atatatataa atatatatgt aaatatatat ataaatatat 660
ataaatatat atataaatac atataaatat atatataaat atatataaat atatatataa 720
atatatataa atatatatat aaatatatat aa752
<210>58
<211>300
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(300)
<223>染色体1的MAR基因基序;1119049..1119348
<400>58
taatatacat tttatataat atatgtaata tatattttat atatatgtaa tatatatttt 60
atataatata tgtaatatat attttatata tatgtaatat atattttata taatatatgt 120
aatatatatt ttatataata tatgtaatat atattttata taatatatgt aatatatatt 180
ttatataata tatgtaatat atattttata taatatatgt aatatatatt ttatataata 240
tatgtaatat atattttata taatatatgt aatatatatt ttatatatat gtaatacata 300
<210>59
<211>617
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(617)
<223>染色体1的MAR基因基序;3603613..3604229
<400>59
aaaatataat atatataata tataatatat ataatatatt atatataaaa tatataatat 60
ataatatata taataaaata tacataatat ataatgtata ataaaatata cataatatat 120
aatatataat aaatatataa tatataatat ataataaaat atataatata taatatataa 180
taaaatatat aatatattat atataataaa atatataata tattatatat aataaaatat 240
ataatatatt atatataata aaatatataa tatattatat ataataaaat atataatata 300
ttatatataa taaaatatat aatatattat atataataaa atatataata tataatatat 360
aataatatat ataatatata atatatataa taaaatatat ataatatata atatatataa 420
taaaatatat aatatataat atatataata aaatatatat gatatataat atatataata 480
aaatatatga tatataatat atataataaa atatataata tataatataa tatataatat 540
atatactaaa aaatatataa tatataataa aaaatatata atatataata tatataatat 600
ataataaaat atatata617
<210>60
<211>674
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(674)
<223>染色体1的MAR基因基序;2592460..2593133
<400>60
taagcttata tatatatata agcttatata tatatatata agcttatata tatatagaaa 60
gcttatatat atatagaaag cttatatata taagaagctt atatataaaa gcttatgtat 120
aaatatatat aaatatattt atttatgctt atagatacat atataaatat atttatttat 180
atttatatat aaacatatat ttatatatat ttatataata tttatttatt atataaataa 240
atatataata aataataaat atatataata tatttattgt attatttata taaatttatt 300
aatataatat ataataaaat aataattata taaatatata aatatctata aatatatata 360
aatatatata atatctataa atatatataa atataaatat atataatatc tataaatata 420
gataaatata aatatatata atatctataa atatagataa atataaatat atataactat 480
atataaatat atataactat atataaatat atatataaat atatataact atatatataa 540
ctatatatat aaatatatat aactatatat ataaatatat atataaatat atataactat 600
atatataaat atatataact atatataaat atatatataa atatatataa ctatatatat 660
aaatatatat ataa674
<210>61
<211>1694
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1694)
<223>染色体1的MAR基因基序;2891680..2893373
<400>61
atatgtaata catatattat atatgcatat atacatgcat atgtatatac atatattata 60
tatgcatata tacatgcata tgtatataca tatataaagt atgattatat ataatatata 120
catgtatatg tatatacatg tatatattat attatatatt atttatacat attattatgt 180
ctatatataa tataatatat acatattaat aatataatac ataatataat ataatatatt 240
atataataca taatataata taatatatta tataatacat aatataatat aatatattat 300
atgatacata atataatata atatattata tgatacataa tataatataa tacatattaa 360
taatatatta ttattattaa tataatatat acatattaat atacatacat atatattata 420
ttatatataa tatacatata atataatatg taatattata tataatataa tacataatat 480
aatacatatt aataatatat tattaataag ataatatata tgtatctata atatatacat 540
atatgtatat gtatgtatat attatagata tacatgttta tacatgtata tattatagat 600
atatacatgt atatacatgt atatattata gatatataca tgtatatacg tatatattat 660
agatatacat gtatatatgt atatatatta tagatataat atatacaaga atataagaat 720
atatataata taatatataa tacacataat acgtatatat tatatataca tgtatattat 780
atatgtacat atatacatgt atattatata tacatgtata ttatatatac atgcatatta 840
tatatatttt tatatataat atccatgtat attatgtata tttgtgtata ttatatatac 900
atgtatatta tatatacatg catattatat atatttttat atataatatc catatatatt 960
atgtatattt gtgtatatta tatatacaca tatattatat atacatggat attatatata 1020
cacatatatt atatatacat atatattata tatacacata tattatatat acatgtatat 1080
tatatataca cgtatattat atatacacac gtatattata tatacacgta tattatatat 1140
acacacgtat attatatata cacgtatatt atatatacac acgtatatta tatatacacg 1200
tatattatat atacacacgt atattatata tacacgtata ttatatatac acacgtatat 1260
tatatataca cgtatattat atatacacac gtatattata tatacacgta tattatatat 1320
acacacgtat attatatata cacgtatatt atatatacac acgtatatta tatatacatg 1380
tatattatat atacatgtat attatatata cacatgtata ttatatatac atgtatatta 1440
tatatacaca tgtatattat atatgcatgt atattatata tacacatgta tattatatat 1500
acacatgtat attatatata catatatatt atatatacat gtatattatg tatacatata 1560
tattatatat acatgtatat tatagataca tatatattaa atatacatgt atattatgta 1620
tacatatata ttaaatatac atgtatattg tatatacata tatattatat acatgtatat 1680
tacatgtata cata1694
<210>62
<211>587
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(587)
<223>染色体1的MAR基因基序;3432560..3433146
<400>62
gaattatata tatatagctg aattatatac atatataata tatacaatat atattatata 60
tttatatatg atatatacaa tatatattac atattatata tacaatatat aatatataat 120
atataatatt atatattata tattgtatat aatatatatt atataacatt atataatata 180
taatattata tattatatat tgtatataat atatattata taacattata taatatatac 240
tattatatat tataatatat aatatataat aatatataat agtatatatt atatatattg 300
tatatattat atataaatat ataatatata atatatatta tataatatat attatataat 360
atatattatt atatattata tatttatata taatatatat tatatatatt atattttata 420
tataaatata taatatataa taatatataa tttaatatat ataatatata caatatataa 480
tatataatat attaatatat ataatatata caatatataa tatataatat ataatatata 540
atataaatta ttatatataa tatatattat atatagctga attatat587
<210>63
<211>313
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(313)
<223>染色体1的MAR基因基序;3805392..3805704
<400>63
tatataatat gtatattatg taatatttta tatagcatat atgtatatta tatataatct 60
tttatatata gtatataata tgtatattat atattatata attatataat tatgtattat 120
ataaaatata ttatataata tataattata tattttttga aatatagatt atatataata 180
tatatggcag tgagctgaga tataatatat attatctata ctatataata tatattatat 240
atactctata ttatatatgt atatattata tataatatat acatatataa tgtgtatata 300
ttatatataa taa313
<210>64
<211>349
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(349)
<223>染色体1的MAR基因基序;4521378..4521726
<400>64
ttatatacac tatataatat gtatttatat atacttatat acactatata tgtatttata 60
tataattata tacactatat aatatgtatt tatatataat tatatacact atataatatg 120
tatttatata taattatata cactatataa tatgtattta tatataattg tatacactat 180
ataatgtata tttatatata attgtataca ctatataatg tatatttatg tataattgta 240
tacactatat aatgtatatt tatgtataat tgtatacact atataatgta tatttatgta 300
taattgtata taccatataa tgtatattta tgtataattg tatatacca349
<210>65
<211>500
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(500)
<223>染色体1的MAR基因基序;3240166..3240665
<400>65
ttaatatata atatatatta tatatttata tattaatata taatatatat ttatatataa 60
tatatattat atatttatat tacatatatt tatatgttaa tatatatttt atatatttat 120
atattttata tatttatata ttatatattt atatattata tttatatatt atatatttat 180
attatatatt tatatattat atttatatat tatatattta tattatatat ttatatattg 240
tatatttata ttatatattt atatattgta tttatatatt atatatttat atactatata 300
tatttatata tattatatat ttatatatta tatatattta tatatattat atatttatat 360
attatatata tttatatata ttatatattt atatattata tatatttata tatattatat 420
atatttatat atattatata tttatatata atatatatta tatattttat ctatatattt 480
atatattaat atatattata500
<210>66
<211>866
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(866)
<223>染色体1的MAR基因基序;409429..410294
<400>66
atatatataa tatattatat atattatata ttatatatat aatacatata ttatatatat 60
aatatataat acatatatta tatatattat atattatata taatatataa tacatatatt 120
atatataata tataatatat aatatattat ataatataat tatataatta tataatataa 180
tataatatat aatattatat aattatataa tatatataat tatattatat attataaata 240
ttatataata tatatattac aaatatatat tatatatatt ataaatatta tataacatat 300
atattatata atatatataa tatataatat atataaaaat ataatatata agatatatat 360
aatatatgat atatatgata tataatatat gatatatatg atatatataa tatatgatat 420
atatgatata tatgatatat ataatatatg atatatatga tatatatgat atatgatata 480
tatgatatat gatatatatg atatatatga tatatgatat atatgatata tatgatatat 540
gatatatatg atatatatga tatatgatat gatatatata atatatgata tgatatatat 600
aatatatgat atatatgata tatgatatgt aatatatatg atatattata tataatatat 660
aatatataca taatatataa tatataatat ataatatata taatatgtga tatatataat 720
atatgatata tgatatatga tatatattat ataatatata taatatatat tatatataat 780
atatattata taatatatat aatatatatt atatataata tataagatat aagatataat 840
atatataata tataatatat ataata866
<210>67
<211>335
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(335)
<223>染色体1的MAR基因基序;614754..615088
<400>67
acccaatata tgtgtatata tgtatgtata tatacatata catacataca tatatgtaca 60
tacatatata catacataca tatatatgta catacatata tacatacata catatataca 120
tataacatat atacacacat atatacagat atacatatat acatacatat atacatataa 180
catatataca tacatatata catataacac atacatacat acatatatac atacaacata 240
tatacataca tatatacata tgtatacata catatatgta tacatatatg tatacatata 300
tgtatacata tatgtatata tatattgtta tatat335
<210>68
<211>455
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(455)
<223>染色体1的MAR基因基序;1299520..1299974
<400>68
ggatatatat attattagtt gttatattat tatatattat atatattatt atatataata 60
tattatatca tatatattat tatatataat atattatatc atatatatta ttatataata 120
tattatatca tatatattat tatatataat atatattata tatattatta tatataatat 180
atattatata tattattatg tataatatat atattatata ttatttatat atatataaat 240
tatataataa tatataatta attatacata tatacatata taagtataca tataatatat 300
ttatatagta tatataaata tatatacaat atatttatat attatatatt atatataaat 360
atatacaata tatttatatc atatatttta tatatgatac atataatata tattatatat 420
gatatataat atatatcata tatgatatat aacat455
<210>69
<211>404
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(404)
<223>染色体1的MAR基因基序;1970778..1971181
<400>69
atatataata tgtataatat ataatatata tcatatattg ttctatgtat attacatata 60
atatgcatta tatattatat attgcatata atatgcatta tatattatat attgcatata 120
atatgcatta tatattatat attgcatata atatgcatta tatattatat attgcatata 180
atatgcatta tatattatat attgcatata atatgcatta tatattatat attgcatata 240
atatgcatta tatattatat aatatataca catataatat atataattta tatatattta 300
tatatattta catttattat atatttatta tatataaata tatttttata tattacttat 360
atattatata taatatatat aatatatata ttatatataa tata404
<210>70
<211>605
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(605)
<223>染色体1的MAR基因基序;3562918..3563522
<400>70
tatatatata aaatacatat atattatata tattatatat aatacatata ttatatatta 60
tatataatac acgtatataa tatataatat ataatacata taatatatat gatatataat 120
acatataata tatatgatat ataatacata tataatatat atgatatata atacatatat 180
aatatatatt atatataata catatataat atatattata tataatacat atataatata 240
tattatatat aatacatata taatatatat tatatataat acatatataa tatatattat 300
ataatacata tataatatat attatataat acatgtatat aatatatatt atatataata 360
catatatatt atataataca tgtatataat atatattata tataatacat atatattata 420
tattatatat taatatattt atataatagt aatatataat attaatatat tatatatatt 480
aatattatat ataatacata tattatatat aatataaata tatataatac atatataata 540
cacatattat atataataca tatattatat ataatatata tattatatat aatatatatg 600
taata605
<210>71
<211>317
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(317)
<223>染色体1的MAR基因基序;189743..190059
<400>71
tattttttat atttatatat tatatatatt tttatatgta atatattata tataaaatta 60
tataatttta ctacatataa tatataaaat tatataattt tactacatat aatatataaa 120
attatataat tttactatat ataatatata aaattatata attttatata taatatatat 180
tataatatat attatatgca atatatatta tatattatat tataatatat tgtatatttt 240
tgtatataaa atatataata tataatatat ttatagacaa taatatataa tataatatat 300
aaaattttat atataaa317
<210>72
<211>522
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(522)
<223>染色体1的MAR基因基序;229111..229632
<400>72
gatatatata tttatatata taaaagatat atattattta tatataaaga tatatattta 60
tatatataaa agatatatat tatttatata tataaaagat atatatttat atatatgata 120
tatattattt atatatataa aagatatata tttatatata tgatatatat tatttatata 180
taaaagatat atataaaaga tatatattat ttatatatat aaaagatata tatataaaag 240
atatatatta tttatatata taaatgatat atattattta tatataaaag atatatatta 300
tttatatata aaagatatat attatttata tatataaaag atatacatat aaaagatata 360
tatttatata taaaagatat atatatttat atataaaaga tacatatatt tatatatata 420
aaagatatat atatttttat atataaaata tatattatat atataaaaga tatatataaa 480
tatatatatc ttttatatat aaaagatata tataaatata ta522
<210>73
<211>1110
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1110)
<223>染色体1的MAR基因基序;1138030..1139139
<400>73
tatgtatgta tacataatat attatatatg tatattatgt atacataata tattatatat 60
gtatattatg tatacataat atattatata tgtatattat gtatacataa tatattatat 120
attatatgta tattatgtat acataatata ttatatatta tatgtatatt atgtatacat 180
aatatattat atattatatg tatattatgt atacataata tattatatat tatatgtata 240
ttatgtatac ataatatatt atatattata tgtatattat gtatacataa tatattatat 300
attatatgta tattatgtat acataatata ttatatatta tatgtatatt atgtatacat 360
aatatattat atattatatg tatattatgt atacataata tattatatat tatatgtata 420
ttatgtatac ataatatatt atatattata tgtatattat gtatacataa tatattatat 480
attatatgta tattatgtat acataatatt tatatattat atgtatatta tgtatacata 540
atatattata tattatatgt atattatgta tacataatat gtacacataa tatttatata 600
ttatatgtat attatgtata cataatattt atatattata tgtatattat gtatacataa 660
tatttatata ttatatgtat attatgtata cataatattt atatattata tgtatattat 720
gtatacataa tatttatata ttatatgtat attatgtata cataatatat tatatattat 780
atgtatatta tgtatacata atatattata tattatatgt atattatgta tacataatat 840
attatatatt atatgtatat tatgtataca taatatttat atattatatg tatattatgt 900
atacataata tattatatat tatatgtata ttatgtatac ataatatatt atatattata 960
tgtatattat gtatacataa tatattatat attatatatg tatattatgt atacataata 1020
tattatatat tatatatgta tattatgtat tatattatat attatgtata ttatagatta 1080
tgtatgcata cataatatgt attgtatatt1110
<210>74
<211>521
<212>DNA
<213>智人(Homo sapiens)
<220
<221>misc_binding
<222>(1)..(521)
<223>染色体1的MAR基因基序;2863407..2863927
<400>74
aatatatata aatatataaa tatatataaa tatatataca tataaatata taaatatata 60
tatgtaaata tatgtaaata tatgtaaata tatgtatatg tatatatatg taaatgtatg 120
taaatatata taaatatatg taaatatata taaatatacg taaatatata aatatatata 180
actatatata aatatatata aatataaata tataaatata tataaatata tataaatata 240
taaataaata catataaata tataaataaa tacatataaa tatatataaa tatataaaaa 300
tatatataaa tatatatata aatatataaa catatataaa tatataaata tatataaata 360
tataaataca taaaatatat aaatatatat aaatatataa atatatataa atatagataa 420
atatagataa atatataaat atatataaat atataaatat agataaatat ataaatatat 480
aaatataaat atataaaaat atatataaat atataaaaat a521
<210>75
<211>560
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(560)
<223>染色体1的MAR基因基序;5712303..5712869
<400>75
atataattat atatatatta tatattatat ataattatat attatatata atgtataatt 60
atatattata tataatatat ataaatatat atatttttta tataaatata ttatatattt 120
atatattata tataaattta tatatataaa tttttatata ttatatatat ttatatatta 180
tatattgtat atatttatat attacatatt gtatatattt atatattata tattatatat 240
ttatatatta tatattatat atttatatat tatatattat atatatttat atattatata 300
taaattattt atatataata tataaatata tattatataa tataaatttg tatatataat 360
atatatttat attatatata aaatatttat attatatata aaatataata taaatatata 420
catataatat atatattata tatttataat tatatattat atataataca tataatatat 480
aatatataat acatatatat catatatgaa atatatatca tatattatac atattatata 540
taacatatat attatatatc560
<210>76
<211>479
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(479)
<223>染色体1的MAR基因基序;8578812..8579290
<400>76
tatggtatac atatagtata tatggggtac atatatggta tatatatggg ttatatatat 60
gatatatatt atatatgtat atggtatata tatggtatat atattataca tgcatatggt 120
atgtatatgg tatatatatg atatatacat atggtgtata tatatgttat atatgatata 180
tataaggtat atatatggta tatataaggt atatatagta tatatatggt atatataagg 240
tatatattgt atatatatgg tatatataag gtatatatat tgtatatatg gtatatatat 300
ggtttatata tatggtgtgt atatatggtg tttatataca cactttatat actatatatt 360
atatacacac tatatataat atatattata tatagttaaa tatatggtat atgcaattag 420
atatatggta tatgtaatta tatatatggt atatagatgg tgtatatatg gtatatata479
<210>77
<211>477
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(477)
<223>染色体1的MAR基因基序;8579294..8579770
<400>77
tatagtatat atacacacta taggtaatat actacatatt atatacacac tataaataaa 60
atatataata tataatattt tctatatagt atatattata tattgtatat actatatata 120
atatatacta tagacagtag atactttata tactatagac agtatatact atatactgta 180
tacactatag acagtatata ctatatactg tatacagtat atgtagtgta tatgtagtgt 240
atataatata tagtatatat tatctatact atatacagta tatatagtgt atacataata 300
tatattatat attatatata ctatatacag tatacatagt gtatatgtag tgtataatat 360
atataatgtg tatataaaat atatatacta tatataatat atattatata taatatatac 420
actatatata ctatagatac actatatatt cactatatat actatatata ctatata477
<210>78
<211>331
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(331)
<223>染色体1的MAR基因基序;8580024..8580354
<400>78
actatatgtt atatacataa gatatagtat ataccatata ttatatacat tatatatagt 60
gtatactata tataatgtat ataatatata gtatatatac actatatata ctatgtatat 120
atacactata tatactatgt atatatacac tatatatact atgtatatat acactatata 180
tactatgtat atatacacta tatatactat gtatatatac actatatata ctatgtatat 240
atacactata tatactatgt atatatacac tatatatact atgtatatat agtgtatata 300
tactgtatat gttatagtgt atatatagta t331
<210>79
<211>410
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(410)
<223>染色体1的MAR基因基序;8580705..8581114
<400>79
tatagtctat attatataca gtctatataa tatatagtat atactatata tacttttcct 60
cattctgact atatactata tatatactat atatagtata tgtagtgtat atatacacca 120
tatatactat atatagtata cataccatat atagtatact atacatacca tatatagtat 180
acataccgta tatagtatac tatacttacc atatatagta tacatactat atataatata 240
tctggtgtat atatacacta tatatactat atatactata tatagtatat gtacactatt 300
tatagtattt atagtatata tactgtatat atagtatgta gtatatatac tatatattat 360
gtagactata tataatatag actatgtgta gagtatatat actatatata410
<210>80
<211>433
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(433)
<223>染色体1的MAR基因基序;12979167..12979599
<400>80
atatataata tatatatgtc ctatatataa aatatatcat atatataaat atatatgata 60
tattttatat attaaatata taattatata taaatatata tttatatata aatatattat 120
ttcaatatat ataaatatat ttaaatatat ttaaatagaa tattaaatat ataaatatat 180
aattatattt aatatataaa tatatattaa atatataatt atatttaata tatataaata 240
tatattaaat atataattat atatttatat atttattata tataaatata tatttgttct 300
aaataaatat atattctaaa tatataatat tttatattat ataatatata atataaaata 360
tataataaat atataatata taaataaata aatatttatt ataaaataca tataaatatt 420
aaatatatat taa433
<210>81
<211>385
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(385)
<223>染色体1的MAR基因基序;16336644..16337028
<400>81
tttatataaa tatctatata aataaatata taaatatata aatataaata tatataaata 60
tataaataaa tatataaata tatataaata taaatatata tataactatg aatttatatt 120
tatataaata tatatctata tgaatataaa tatatattta tataaatata aatatatata 180
taaatatata tatttatata gatataaata tatatataaa tatatatatt tatatagata 240
taaatatata tctatatatg aatatatatc tataggaata taaatatata tctatataaa 300
tataaatata tataagtata aatatatata aatatatatc tatataaata taaatatata 360
tataaatata aatatatata taaat385
<210>82
<211>363
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(363)
<223>染色体1的MAR基因基序;20624448..20624810
<400>82
tatatatata gttatatata tatttatata tatagttata tatatatttt tatatagtta 60
tatatatagt tatatatata gttatatata tatagttata tatatagtta tatatatagt 120
tatatatata tagttatata tatagttata tatatagtta tatatatagt tatatatata 180
tagttatata tatagttata tatatatagt tatatatata gttatatata tatagttata 240
tatatagtta tatatatagt tatatatata gttatatata tagttatata tatatagtta 300
tatatatata gttatatata tatagttata tatatagtta tatatatata gttatatata 360
tag363
<210>83
<211>310
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(310)
<223>染色体1的MAR基因基序;566025..566334
<400>83
tatatataat atatattgta tatattatat attgtatata taatatatat tgtatatatt 60
atatattgta tatataatat atattgtata tattatatat tgtatatata atatatatat 120
tgtatatatt atatattgta tatataatat atatattgta tatattatat attgtatata 180
taatatatat attgtatata ttatatattg tatatataat atatatattg tatatattat 240
atattgtata tataatatat atattgtata tattatatat agtatatatt atatatagta 300
tatataatat310
<210>84
<211>1236
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>mi sc_binding
<222>(1)..(1236)
<223>染色体1的MAR基因基序;1171429..1172664
<400>84
aaagtattat atgtattata tgtatatgta ttatatatta catatgtatt atatataata 60
tatattatat attattatat attatatatt atatattatt atttatataa tgtattatat 120
attatatagt atatatagta tatataatgt attatatatt atatagtata tatagtatat 180
ataatgtatt atatatagta tatataatgt attatatagt atatatacta tataatgtat 240
tacatattat gtatagtata tgtaatgtat tatatattat atagtatatg taatgtatta 300
tatgtattat atagtatata ttatatatga tgtattattt agtatatata atatatatga 360
tgtattatat aacatatata atatatatga tgtattatat agcatgtata gtatatatga 420
tgtattatat agcatgtata gtatatatga tgtattatat atagcatgta tagtatatat 480
gatgtattat atatagcatg tatagtatat atgatgtatt atatatagca tgtatagtat 540
atatgatgta ttatatatag catgtatagt atatatgatg tattatatat agcatgtata 600
gtatatatga tgtattatat atagcatgta tagtatatat gatgtattat atatagcatg 660
tatagtatat atgatgtatt atatatagca tgtatagtat atatgatgta ttatatatag 720
catgtatagt atatatgatg tattatatat agcatgtata gtatatatga tgtattatat 780
attatatatg gtatatatga tgtattatat attatatatg gtatatatga tgtattatat 840
attatatatg gtatatatga tgtattatat attatatata atatatatga tgtattatat 900
attatatata atatatatga tgtattatat atgatgtatt atatataata tatatgatgt 960
attatatata ttattatcta ttatatacga tgtattatat gcaagttatt atgtataata 1020
tataatgtat tatatattat ataatgtata atatataaat atataaatat ataattatgt 1080
ataaatatag aaatatatac attatacatt atatacatta taatgtataa tatataaata 1140
tattatatat aaatgtatac attatatata aatatattat atacattata tataaaatat 1200
gtatatagtt attatacctt atatatacta aacagt1236
<210>85
<211>309
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(309)
<223>染色体1的MAR基因基序;1925173..1925481
<400>85
atatatttat ataaatatat tttatataaa tatatattat ataatattat aatatatgtt 60
atattatata tattttatac aatatataat atatattata tatattttat acaatatata 120
atatatatta tatatatttt atataatata taatatatat tatatatatt ttatacaata 180
tataatatat attatatatt atataatata tattatatat attttatata atatataata 240
tatattttat acaatatata atgtatatca ttatattata taatgtatat catattatat 300
aatgtatat309
<210>86
<211>312
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(312)
<223>染色体1的MAR基因基序;4396756..4397067
<400>86
cacagtgtat atatagtata tatactgtat atatactgtg tatatacact gtatatacac 60
agtgtatata cagtatatat actatatata cactgtgtat atatagtata tataaattct 120
aggaatatat atactatata tatactatat atataaattc taggaatata tacacactat 180
atatacacta tatatacaca tatatacact atatatatta tacacatata ttatatatat 240
acactatata tacacgagat atataacata tacactatat actatacata acatatatac 300
tatatatact at312
<210>87
<211>398
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(398)
<223>染色体1的MAR基因基序;56057..56454
<400>87
atatatatta catattatat atataatata tattatataa tatatattat attatataat 60
atataatata aatataatat aaattatatt atataatata taatataaat ataatataaa 120
ttatataaat ataatatata ttttattata taatataata tatattatat aaatataata 180
tataaattat ataatataat atatattata taatataata tattttatta tataaatata 240
tattatatta tataatatat attttattat ataatatata ttatatattt atagaatata 300
atatatattt tattatataa tatatattat ataatatata ttatatttat atataacata 360
tattattata taaaatatgt ataatatata ttatataa398
<210>88
<211>391
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(391)
<223>染色体1的MAR基因基序;56984..57374
<400>88
tactataata catattatat ataatattat atactatata ttactatatt attatattat 60
atataattaa actatattat agtatataat atataatata tactatatgt aatattacta 120
tgatactgat attatattat atataattaa attatattat attaatatat aaattatata 180
taatacataa tatataaatt atattatatt atttatatat aatgtatgcc atataattta 240
tatataatgc attatatata atttatatat aatgcattaa atataaatta tatataatgc 300
attatatata attatatata atgcattata tataatttat atttaatata taaatttata 360
tttaatatat ttatatatta tatataataa a391
<210>89
<211>309
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(309)
<223>染色体1的MAR基因基序;469547..469855
<400>89
atatatatgt aatatatatg ttatatatgt aatatatatg ttatgttata tatgttatat 60
atatgttata tataatatat atgttatata tacgttatat gttatatata tgttatatat 120
aatatatgtt atatatacgt tatatgttat atatgttata tataatatat gttatatata 180
atatatgtta tatatgttat atataatata tgttatatat attatatata atatatgtta 240
tatatattat atataatata taatatatgt gatatataat ataaaatata tgtgatatat 300
attatatat309
<210>90
<211>441
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(441)
<223>染色体1的MAR基因基序;546190..546630
<400>90
atacacaaca tatgtgtata tatatagtat atatacacaa catatgtgta tatatatagt 60
atatatacac aatatatgtg tatatatata gtatatatac acaatatatg tgtatatata 120
gtataaatat atactatata tagtatatat agtataaata tatactatat atagtatata 180
catagtataa atatatacta tatatagtat atacatagta taaatatata ctatatatag 240
tatatacata gtataaatat atactatata tagtatatac atagtataaa tatatactat 300
atatagtata tacatagtat aaatatatac tatatatagt atatacatag tataaatata 360
tactatatat agtatataca tagtataaat atatactata tatagtatat acatagtata 420
aatatatact atatatagta t441
<210>91
<211>1367
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1367)
<223>染色体1的MAR基因基序;124643..126009
<400>91
atatttatat gatatataat atatataata ttatatataa tattatatat gatatataac 60
attatataat attatatatg atatatatta tatatattat atatgatata taatatatat 120
aatattatat atgatattat atatcatata taatatataa aatattatat atgatatata 180
atatatataa tattatatat attatatata ttatatatca tatataatat tctaaatata 240
taatattata tgatatataa gattatatac attatatata atatataata ttatatatga 300
tatataatat tatatacatt atatataata tataatgtat ataatattat atattatata 360
tttatattat atacaatgta tataatatta tatatcatat atatttatat tatatacaat 420
gtatataata ttatatatca tatataatat tatatacaat gtatataata tatattatat 480
atatttatat tatatacaat gtatataata tatattatat atatttatat tatatacaat 540
gtatataata tatattatat atatttatat tatatacaat gtatacaata ttatatatta 600
tatattatat atttatatta tatacaatgt atatattata tattatatat ttatattata 660
tacaatgtat atattatata ttatatattt atattatata caatgtatat attatatatt 720
atatatttat attatataca atgtatatat tatatattat atatttatat tatatacaat 780
gtatatatta tatattatat atttatatta tatataatgt atgtaatatt atatattata 840
tatttatatt atatataatg tatgtaatat tatatattat atatttatat tatatataat 900
gtatgtaata ttatatatta tatatttata ttatatataa tgtatgtaat attatatatt 960
atatatttat attatatata atgtatgtaa tattatatat tatatattta tattatatat 1020
aatgtatgta atattatata ttatatattt atattatata taatgtatgt aatattatat 1080
attatatatt tatattatat ataatgtatg taatattata tattatatat ttatattata 1140
tataatgtat gtaatattat atattatata tttatattat atataatgta tgtaatatta 1200
tatattatat atttatatta tatataatgt atataatatt atatattata tatttatatt 1260
gtatataata ttatatatta tatatttata ttgtatataa tatatattat atatttatat 1320
tgtatataat attatatatt atatatttat attatatata atgtata1367
<210>92
<211>458
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(458)
<223>染色体1的MAR基因基序;58908..59365
<400>92
tatatgatat atatgatata tatgggatat atatgatata tatgatatat atggtatata 60
tatgatatat agtatatatg atatatatgg tatatatatg atatatagta tatatgatat 120
atatggtata tatgatatat agtatatatg atatatatgg tatatatggt atatatatga 180
tatatgatat atatgatata tatgatatat gatatatatg atatatatga tatatatggt 240
atatatgata tatatggtat atatggtata tatatgatat atatgatata tatggtatat 300
atatgatata tatgatatat atggtatata tatgatatat atgatatata tggtatatat 360
atgatatata tgatatatat ggtatatata tgatatatat gatatatatc atatatatgg 420
tatatatatg atatatatga tatatatcat atatatgg458
<210>93
<211>330
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(330)
<223>染色体1的MAR基因基序;306867..307196
<400>93
ataatatata aatatatatg atatatatct atatatatca tatataaata tatatgatat 60
atatctatat atatcatata taaatatata tgatatataa atatatatga tatatatcta 120
tatatatcat atataaatat atatgatata taaatatata tgatatatat ctatatatat 180
catatataaa tatatatgat atatatctat atatcatata taaatatata tgatatatat 240
ctatatatat catatataaa tatatatgat atctatctat atatatcata tataaatata 300
tatgatatct atctatatat atcatatata330
<210>94
<211>353
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc binding
<222>(1)..(353)
<223>染色体1的MAR基因基序;636899..637251
<400>94
tatgtataca tatacacata tacgtatata tatacatata tacacatata cgtatatata 60
tacgtataca tacatatgta tatgtatacg tatacacaca tatgtatatg tatacgtata 120
cacacatata cgtatatatg tatacgtata cacacatata cgtatatgta tacatatata 180
tgtgtacata tacgtatata cgtatatgta tacatatata cgtttatgta tatatacgta 240
tatacgtata tatgtatatg tatacatata tacatatatg tgtatatacg tatatacgta 300
tatgtgtata tatacaatat acatacatgc acatatatgt gtatatgcac ata353
<210>95
<211>345
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(345)
<223>染色体1的MAR基因基序;1435510..1435854
<400>95
atcatatata ttatatatca tatatatgat atataaaaat tatatatcat atatatgata 60
tataaaaatt atatatatca tatataatat atataatata ttatatatat aaattatata 120
taatatatat aaattatata tatcatatat atgatatata atttatatat catatatatg 180
atatatataa tatattattt atatataata tattatatat tatataatat gtaatatata 240
ttatatatta catattatat tatttataaa taatatttta taatatatat aatattatat 300
aatatagaat attatatatt atatattaca tattatataa tatat345
<210>96
<211>521
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(521)
<223>染色体1的MAR基因基序;39695..40215
<400>96
tatatatata atagatatta tatatctatt atatatctat tatatatata atagatatta 60
tatatctatt atatatataa tagatattat atatctatta tatatataat agatattata 120
tatctattat atataatata tatctattat atattatata tctattatat ataatatata 180
tctattatat atattatata tctattatat atataataga tattatatat ctattatata 240
taatatatat ctattatata ttatatatct attatatata tgtatctatt atatatatta 300
tgtatctatt atatataata tatatctatt atatatatat tatatataat atatattata 360
tatattatat atctattata tataatatat atctattata tatattatat atctattata 420
tatattatat atctattata tataatatat atctattata tatattatat atctattata 480
tataatatat attatatata tattatatat tgtatatcta t521
<210>97
<211>484
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(484)
<223>染色体1的MAR基因基序;1286007..1286490
<400>97
atatcatata tattatatat catatatatg atatataaaa attatatatc atatatatga 60
tatatataaa ttatatatat catatataat atatataata tattatatat ataaattata 120
tataatatta tatataaatt atatatcaca tatatgacat ataaattata tatcacatat 180
atgatatata atttatatat cacatatatg atatataatt tatatatcat atatatgata 240
tataatttat atatcatata tatgatatat aatttatata tcatatatat gatatatata 300
atatattatt tatatataat atattatata ttatataata tgtaatatat attatatatt 360
atataatatg taatatatat tatatattac atattatatt atttataaat aatattttat 420
aatatatata atattatata atatagaata ttatatatta tatattacat attatataat 480
atat484
<210>98
<211>244
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(244)
<223>染色体1的MAR基因基序;73556..73879
<400>98
attatatatt atattatata atatataata atattatata attatatatt acattatata 60
atatataata atattatata ataatatata attatataat atataataat attatataat 120
attatataat attatataat atataaatat ataataatat atattatatt atataatagt 180
atatattata ttatataata tatgttatta tattatataa tataaactat tatataatat 240
aata244
<210>99
<211>463
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(463)
<223>染色体1的MAR基因基序;179038..179500
<400>99
tacaatatat tttctattat atatattttg tattatatat aatatacaat atattttcta 60
ttatatataa tatattttgt attatatata ttacaatata ttttgtatta tataatatat 120
aatacaatat aatatattgt attatataat atataatact atataatata ttgtattata 180
tattatatat aatactatat aatatatttt attatatatt atatataata ctatataata 240
tattttatta tatattatat ataatacaat atataatata ttgtattata atacaatgta 300
ttataatgta ttatatataa tatataatac aatatataat attatatata tttatatata 360
tatatatttt gtattatata ttttgtatta tatatatttt gtattatata tttatatttt 420
atattataat tatgttttgc attatatatt tcatattata tat463
<210>100
<211>390
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(390)
<223>染色体1的MAR基因基序;55617..56006
<400>100
tgtataatat atatacttta tatataatat atatacttta tatatatact atatactaat 60
atatataata tatactatat ataatatata ctaatatata taatatatac actatatata 120
atatatacta atatatatta tatatacttt atataatata tactaatata tataatatat 180
atactttata tataatatat actaatatat ataatgtata tactttatat ataatatata 240
ctaatatata atatatatac tttatatata atatatacta atatatatta tatatacttt 300
atatatataa tatatactta tatattatat atgcttatat ataatatata cactaatata 360
taatatatat actttatata ttatatttta390
<210>101
<211>582
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(582)
<223>染色体2的MAR基因基序;1157405..1157986
<400>101
tgtatatgta tatatacaca tacgcacata tatgtatatg tatatataca catacgcaca 60
tatatgtata tgtatatata cacatacgca catatatgta tatgtatatg tatatgtata 120
tatacacata tacacatata tgtatatgta tatatacaca tatacacata tatgtatatg 180
tatatataca catatacaca tatatgtata tgtatatata cacatacaca tatatgtata 240
tgtatatgta tatatacaca tacacatata tgtatatgta tatgtatata tacacatata 300
cacatatata catatatgta tacatatatg tgtatatata tacacatata tatacatata 360
tgtatacata tatgtgtata tatacacata tatatacata tatacatata catatatatg 420
tgtatgtata tatacacata tacatatata tgtatatgtg tatatatatt agacagatat 480
atatgtacat atacatatat atgtatatgt atatgtatat gtatatgtat atgtatatgt 540
atatgcatat ataatataca tatacatata tgtatatgta ta582
<210>102
<211>322
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(322)
<223>染色体2的MAR基因基序;1858638..1858959
<400>102
acaccatata tacaccatat atatacatac catatatata ccatatatat acataccata 60
tatataccat atatatacat accatatata caccatatat atacatacca tatatataca 120
ccatatatat acataccata tatataccat atatatacat accatatata taccatatat 180
atacatacca tatatataca ccatatatat acataccata tatatacacc atatatatac 240
ataccatata tataccatat atacaccata tatatacacc atatatacac accatatata 300
ccatatatat acaccatata ta322
<210>103
<211>914
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(914)
<223>染色体2的MAR基因基序;5712196..5713109
<400>103
aaatatatat tctatatata gaaaatatat attctatata tatagaatat atatagaata 60
tatattctat atatattcta tatatataga atatatatat aaaacatata ttctatatat 120
aaaatatata ttctatatat ataaaatata tattctatat atatagaatg tatataaaat 180
atatattcta tatatataga atgtatataa aatatatatt ctatatatat agaatgtata 240
taaaatatat attctatata tatagaatgt atataaaata tatattctat atatatagaa 300
tatatataac atatatatga aatatatata aaatatatat aaatacatat ttctatatat 360
aaatatatat aaatacatat ttctatatat aaatatatat caatacatat ttctatatat 420
aaatatatat aaatatatat tcatatatat aaaaatatat aaatatatat tcatatatat 480
aaaatatata tgaatatata ttctctatat ataaaatata tataatatat attatatata 540
taaaatatat ataatatata ttatatatat aaaatatata taatatatat tcatatatat 600
aaattatata taaatatata ttcatatata taatatatat aaatatttat ttcatatata 660
aaatatattt aaatatatat ttctatatag aatatatatt ctatatataa aatatatata 720
taaatatatt ttctatatag aaatatatat gaaatatata gaatatatat aaatatatat 780
tatatatact atatatacaa tatatattat atataaaata tatatacaat atatattcta 840
tatattaata tatagaatat atattaacat atatttcaat atattaatat atgaaatata 900
tataaatatt tcat914
<210>104
<211>370
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(370)
<223>染色体2的MAR基因基序;5713613..5713982
<400>104
tatttcatat ataatatata tataaaatat atatttcata tacataatat atataatata 60
aataaaatat atatttcata tatataatat atataatata tataaaacat atatttcata 120
tataatatat ataaactata tatttcatat ataatatata taaactatat atttcatata 180
cataatatat ataatatata tttcatttat attatatata taatatatat ttcatatata 240
taatatataa aatagatata aatatatata aatatatatt tcatatataa tatatataaa 300
atatatatta atatatattt tatatataat atatatattt catatataaa tataaaaaaa 360
tatatatttc370
<210>105
<211>442
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(442)
<223>染色体2的MAR基因基序;7481647..7482088
<400>105
atataaatta tataatatgt tatataatat ataaatatat tatataacat gttatataat 60
atataacatg ttatataata tataacatgt tatataatat ataacatgtt atataatata 120
taacatgtta tataatatat tatgtaatat gttatataat atataatata ttatataaca 180
tgttatataa tatataacat gttatataat atgttatata atatataaat atattatatt 240
atatgttata taatatataa atatattata ttatatgtta tataatatat aaatatatta 300
tattatatgt tatataatat ataaatatat tatattgtat gttatataat atataaatat 360
attatattgt atgttatata atatataaat atattatatt gtatgttata taatatataa 420
atatattata ttatatatgt ta442
<210>106
<211>338
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(338)
<223>染色体2的MAR基因基序;9594557..9594894
<400>106
tatataaata tataccatat atataaatat atatattcca tatataaata tatatattcc 60
atatatataa atatatatat tccatatata aatatatata ttccatatat ataaatatat 120
atataaatat atatattcca tatatataaa tatatatata aatatatata ttcatatata 180
aatatatata tattccatat ataaaaatat atatatattc catatataaa aatatatata 240
tattccatat atataaatat atatatattc catatatata aatatatata tattccatat 300
atataaatat atatatattc catatatata aatatata338
<210>107
<211>364
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(364)
<223>染色体2的MAR基因基序;10519720..10520083
<400>107
ttatatatat ttataataat atatataagc tatatatatt tatatataat atattatata 60
tattagctat atatatttat ataataatat attatatatt agctatatat atttatatat 120
aataatatat ataagctata tatttatata tattatatat tagctatata tatttatata 180
taatatatta tatattagct atatatttat atataataaa taatatatat attagctata 240
tatatttata tataataata tatataagct atatatttat atataatata ttatatatta 300
gctatatata tttatatata ataatatatt atatattagc tatatatatt tatatataat 360
atat364
<210>108
<211>342
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(342)
<223>染色体2的MAR基因基序;11481943..11482284
<400>108
tacatataat atataattat atataatata tattatatat tacatatata atatatatat 60
tacatatgta atatatatat tatatatgta atatatatta tatatgtaat atatatatta 120
tatatgtaat atatattata tatatgtaat atatatatta tatatgtaat atatatatta 180
tatgtaatat atatatgtaa tatatatata atatatatgt aatatatata taatatatat 240
gtaatatata tataatatat atgtaatata tatattatat atatgtaata tatatcatat 300
atatgtaata tatatcatat atatgtaata tatatcatat at342
<210>109
<211>415
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(415)
<223>染色体2的MAR基因基序;13499598..13500012
<400>109
tatatatata tatatatata atataatata atatatatat aaatatatat aatataaatt 60
tatatatata tatttatata tacatatata aatatatatt tatatttata tataaatata 120
tataaatata tataaatata tatttatata tacatatata aatatatatg ttcatataaa 180
tatatatgta tatatacata tataaatata tattatatat gtatatatat aatataatat 240
ataataataa tataatatat attatataaa tataatatat tatatataat atatataata 300
tataatatat aatatataat atataatata tattatatat tatataatat ataaaatata 360
tattatataa tatatataca taatatatat aaataaatat atataaagat ataaa415
<210>110
<211>330
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(330)
<223>染色体2的MAR基因基序;16370976..16371305
<400>110
catttacata tgtatgtata agtatgtata ttacatactt atacatacat acttataaat 60
atataagtat aatacataca tacttataaa tatataagta taatacatac atacttatac 120
atatataagt ataatacata catacttata catatataag tataatacat acatacttat 180
acatatataa gtataataca tacatactta tacatataag tataatacat acatacttat 240
acatatataa gtataataca tacatactta tacatatata agtataatac atacttatta 300
catatgtata taagtatatt acatacttat330
<210>111
<211>702
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(702)
<223>染色体2的MAR基因基序;626641..627342
<400>111
tatatataca catatacata tataatatat atacatatac atatatatta tatatacata 60
tatattacat atatcatata tacatatata ttatatatac atatatatta tatatatcat 120
atatacatat atatattata tattatatat atcatatata catatatatt atatatatta 180
tatatatcat atatacatat atattatata tattatatat acatatatat tatatatatc 240
atataaacat atatattata tatatcatat atacatatat attatatata ttatatatat 300
catatataca tatatattat atatatcata tataatatat attatatata ttatatataa 360
tatatattat atatacatat atattatata tacatatata ttatatatac atatatatta 420
tatatacata tatattatat atacatatat attatatata tacatatata ttatatatac 480
atatatatta tatatacata tattatatat acatatatat tatatataca tatattatat 540
atatacatat atattatata tacatatatt atatatatac atatatatta tatatacata 600
tattatatat atacatatat attatatata catatattat atatacatat atattatata 660
tacatatata ttttatatat atataatata tattttatat at702
<210>112
<211>679
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(679)
<223>染色体2的MAR基因基序;3196047..3196725
<400>112
atatattata tattcatata tcataaatat atatattata tattcatata ttatatatct 60
atatatttat atattcatat attatatatc tatatattta tatattcata tattatatat 120
ctatttatat attcatatat tatatatcta tatattttat atattcgtat attatatatc 180
tatatattat atattcgtat attatatatc tatatattat gtattcatat atatctatat 240
attatatata ttcatatata ttataaatta tattcatata gtatatatct attataaatg 300
tatattcata tagtatatat ctatatatta taaatataca tatattatat atttatatat 360
tatatattca tatagatcta tatattatat atattcatat atgaatatat atattatatg 420
tatatatatt ataaatatat ttatatagta tagatattat atagtatatg catatttata 480
ttataaataa tttacatagt atatgtatat ttataaatta tatatattta catattacat 540
gtatatttat atattataaa tacatattta catattataa atatatttat atattatgaa 600
tataatttat atattattac atatttacat atatgcatag ttatatatta taaatatgca 660
tttatgtaaa tatatattt679
<210>113
<211>728
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(728)
<223>染色体2的MAR基因基序;3196778..3197505
<400>113
tacataaata tatatttaca atatgtaaat atctgatatg taaatatgta tttataatat 60
ataaatatac atataatatg taaatatata aatatacata tactatgtaa atatatgtta 120
tatatacata tactatataa atatagaata tataaatata catatactat ataaatatgt 180
aatatataaa tatatactat ataaatatac atatactata taaatgtatt tataatatat 240
aaatatacat atactatata aattcatata tgaatatata atatataaat atatataata 300
tatgaatata tactcatata taaatatata tgaatatata tttataatat atagatataa 360
tatgaatata tatttataat atatagatat atattatatg aatatatatt tataatatat 420
agatatatac catatgaata tatattatac actatatgaa tatatattta taatatataa 480
atagatatat actatatgaa tatataatat atatactcta tgaatatata atatatatac 540
tatatgaata tattatatac tgtatgaata tataatatat agatgtatac tatatgaata 600
tataatatat agatatatat actatatgaa tatatataat atatagatat atactatatg 660
aatatatatg atatatagat atatactata tgaatatata atatatagat atatatttat 720
gatatatg728
<210>114
<211>413
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(413)
<223>染色体2的MAR基因基序;2560638..2561050
<400>114
atataaatat atatttatat attttatata aatatatata tttatatatt tttatataaa60
tatatatatt tatatatatt tatataaata tatatattta tatatattta tataaatata120
taaatatata tatttatata aatatataaa atatataaat atatttatat aaatatataa180
aatatataaa tatatttata taaatatata aaatatataa atatatttat atataaatat240
ataaaatata taaatatctt tatatataaa tatataaaat atataaatat ctttatatat300
aaatatataa aatatataaa tatatttata tataaatata taaaatatat aaatatattt360
atatacaaat atataaaata tataaatata tttatatata aatatataaa ata413
<210>115
<211>361
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(361)
<223>染色体2的MAR基因基序;4965309..4965669
<400>115
tatacgtata tatacatata tatacgtata tatatacata tatatacgta tatatacata 60
tgtatatatg tgtgtacatg tatatatata catatgtaca tatatatgta cacatatata 120
tatacatata tatgtacaca tatacatata tatgtacaca tatacatata catatatatg 180
tacacatata tatacatata tatgtacaca catatatata catatatatg tacacacata 240
tatacgtata tatgtacaca catatatacg tatatatatg tacacacata tatacgtata 300
tatatgtaca cacatatata tacgtatata tatgtacaca tatatatata cgtatatata 360
t361
<210>116
<211>325
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(325)
<223>染色体2的MAR基因基序;5258150..5258474
<400>116
tacacacaca tatacatata tacatatata cgtgtatacg tatacgtata tacgtatata 60
tacatatatg tatacgtata cgtatatacg tatatataca tatatgtata cgtatacgta 120
tatacgtata tatacatata tgtatacgta tacgtatata cgtatatata catatatgta 180
tacgtatacg tatatacgta tatatacata catatgtata cgtatacgta tatatgtata 240
tatacgtata tgtatacgta tacatatata cgtatatata cgtatatgta tatgtatata 300
cgtatatgta tatatgtaca tatac325
<210>117
<211>1508
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1508)
<223>染色体2的MAR基因基序;6057499..6059006
<400>117
atataatata tataaattat ataatatata aaaattaata tataatatat ataaattata 60
taatatataa attaattata taatatatat aaattatata atatataaat taattatata 120
atatatataa attatataat acatataaat taattatata atatataaat tatataatat 180
atacaaatta tatactatat taattatata ttatataatt aattatataa tatatataaa 240
ttatatatta ttaaattaat tatataatat ataaattata taatatataa attaattata 300
taatatataa attatataat atataaatta attatataat atataaatta tataatatat 360
aaattaattg tataatatat aaattaatta tataatatat aatatataat taataaataa 420
ttatatatta attatataat taataaataa ataataaata tatataatta atatataata 480
tacatcatat atatcacata tagattatat aatagttata tattatataa taaattatat 540
ataatatata ataaacatat ataacatatg ttatatatta cataatatag tataatatat 600
aacatatgtt atatattaca taatatagta taatatataa catgttatat attacataat 660
atagtataat atataacata tgttatatat tacataatat agtataatat ataacatatg 720
ttatatatta cataatatag tataatatat aacatatgtt atatattaca taatatagta 780
taatatataa catatgttat atattacata atatagtata atatataaca tatgttatat 840
attacataat atagtataat atataacata tgttatatat tacataatat agtataatat 900
ataacatatg ttatatatta cataatatag tataatatat aacatatgtt atatattaca 960
taatatagta taatatataa catatgttat atattacata atatagtata atatataaca 1020
tatgttatat attacataat atagtataat atataacata tgttatatat tacataatat 1080
agtataatat ataacatatg ttatatatta cataatatag tataatatat aacatatgtt 1140
atatattaca taatatagta taatatataa catgttatat attacataat atagtataat 1200
atataacata tgctatatat tacataatat agtataatat atatgttata tattacataa 1260
tatagtataa tatataacat atgttatata ttacatatta tagtataata tatatgttat 1320
atattatata atatagtata atatataatg tatgttatat attatataat atagtataat 1380
atataacatg ttatatatta tataatatag tataatatat atgttatata ttatataata 1440
tagtataata tataatatat gttatatatt atataatata gtataatata tatgttatat 1500
attatata1508
<210>118
<211>415
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(415)
<223>染色体2的MAR基因基序;7996866..7997280
<400>118
caattatata atatacatat tatataattg tataaattat acaatcatat aattatatta 60
tatataatat acatataata taattatata taattatata attttataat ataattatat 120
ataattatat aattatatat aatatatatt ataattatat atataatata tatattatat 180
atattatata taatatataa ataatatata taatatatat ataattatat ataataatat 240
atgtaatata tataatatat atataatata ttatttataa ttatatatta tatatatatt 300
ataatatata taattataaa taatatatat tataatatat ataataatat atatataatt 360
atatataata atatatatta taattatata taataatata tataatttat ataat415
<210>119
<211>526
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(526)
<223>染色体2的MAR基因基序;8300930..8301455
<400>119
tatatcatat gatatattat acaatatatc atataatatg atatattata tgatatattg 60
tacaatatat catatgatat atgatatatt atacaatata tcatataagg tatatattat 120
atcatatata atatataata taatatatga tataatatat gatatatgat atataatata 180
tgatatatga tatatgatat ataatatatg atatatgata tatgatatat aatatatgat 240
atatgatata tgatatataa tatatgatat atgatatatg atatgatata tgatatatga 300
tataatatat gatataatat atgatatata ttatatgata tataatatat gatataattt 360
atatgatata taatatatga tatataatat ataatatatg atatgatata tattatatca 420
tatataatat ataatataat atatgatata tattatatat ttttatacat tatatatata 480
aactatataa caatataaca tattatgtgt ataatatata ttacat526
<210>120
<211>402
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(402)
<223>染色体2的MAR基因基序;8576553..8576954
<400>120
atgtatatta tatacaatat agtatatcat atatagtata tattatatag taatgtatta 60
tatataatgt ataatgtata aatatataat atatactaca tactatacta ttatatatac 120
tatatattat atatgataca tatactatat aatatgctat atattatact atataatatg 180
ctatatatta tactatataa tatgctatat attatactat ataatatgct atatattata 240
ctatataata tgctatatat tatactatat aatatactat ataatatgct atatattata 300
ctatataata tactatatat tatactatat aatatactat ataacatact atatattata 360
tatgatacat atactatatt acatatataa tatatatata ta402
<210>121
<211>477
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(477)
<223>染色体2的MAR基因基序;8785649..8786125
<400>121
tatttatata tatatttata tatatattta tatatattta tatatatatt tatatatata 60
tttatatata tatttatata tttatatata tatattttta tatatttata tatatattta 120
tatatttata tatatttata tttatatata tatttatata tatttatata tatttatata 180
tatatattta tatatattta tatatatata tttatatata tttatatata tttatatata 240
tatttatata tatatttata tatatattca tatatattta tatatatatt catatatatt 300
tatatatata ttcatatata tttatatata tatttatata tatatttata tatatttata 360
tatatttata tatatattta tatatatatt tatatatata tatttatata tatatttata 420
tatatatatt tatatatata tttatatata tatatttata tatatattta tatatat477
<210>122
<211>773
<212>DNA
<213>智人(Homo sapiens)
<220><221>misc_binding
<222>(1)..(773)
<223>染色体2的MAR基因基序;10064737..10065509
<400>122
atattatata tattacatat atattatatt gtatataata tatatattat attgtatata 60
atatatatat tatattgtat ataatatata tattatattg tatataatat atatattata 120
ttgtatataa tatattatat tgtatatatt atattgtata tattatattg tatacaatat 180
atattatatt gtatacaata tatattatat tgtatataat atattatatt gtatataata 240
tattatattg tatatattat attgtatata atatattata ttgtatataa tatattatat 300
tgtatatatt atattgtata taatatatta tatgtatata atatagtgta tactatatta 360
tataatatat attatataca atatataata tattgtatat catatatgat atattgtata 420
taatatataa tatatgatat attgtatata atatattata tatgatatat tgtatattat 480
atattatata tgatatattg tatattatat attatatatt gtatattgta tattatatat 540
tatatattgt atataatatg ttatatattg tatataatat gttatatatt atatattgta 600
tatatgttat atattatgta ttgtatataa tatgttatat attatatatt gtatataatg 660
tattatatat tatatatatt atatattgta tataatgtat tatatattgt atattatata 720
ttatatattg tatataatat attatataca ttatattata tattatatat tgt773
<210>123
<211>1554
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1554)
<223>染色体2的MAR基因基序;1039775..1041328
<400>123
ataatatatt aaatgtatat ataatatatt aaatataaat atatttataa tatataaata 60
tttatataaa tataaaatat atattaaata taaatatata taaaatatat attaaatata 120
taaaatataa atatatatta aatatatatt aaatatataa aatataaata tatattaaat 180
atattttaaa tatataaaat ataaatatat attaaatata ttttaaatat attaaatata 240
aatatatatt aaatatattt taaatatatt aaatataaat acatatatta aatatatatt 300
atatatataa aatatataaa atataaatat atattaaata tatataaaat atatatgtta 360
aatatataaa agatatataa aatataaata tatattaaat atatataaaa tatatatata 420
ttaaatatat atattaaata taaatatata taaaatataa atatatgtat taaatatata 480
tattaaatat aaatatatgt attaaatata tattaaatat gaatatatgt attaaatata 540
tattaaatat aaatatatgt attatatata tagaatataa atatatgtat taaatatagt 600
atattaaata taaatatata taaaatatat attaaatatg aatatatata aaatatatat 660
attaaaaata tatataatat aaatatatat aaaatatata tattaaaaat atatataata 720
taaatatata taaaatatat atattaaaaa tatatataaa atatatatat taaaaatata 780
tataaaatat atatattaaa aatatatata aaatatatat attaaaaata tatattaaat 840
ataaatatat atattaaaaa tatatattaa atataactat atattaaata tatattaaat 900
ataactatat attaaatata tattaaatat aactatatat taaatatata ttaaatataa 960
ctatatatta aatatatatt aaatataact atatattaaa tatatattaa atataactat 1020
atattaaata tatattaaat ataactatat attaaatata tattaaatat aactatatat 1080
taaatatata tgaaatataa ctatatatta aatatatatt aaatataact atatgtatta 1140
aatataaata tatgtcttaa atatatatta aatataaata tatgtattaa atatatatta 1200
aatataaata tgtgtattaa atatatatta aatataaata tgtgtattaa atatatatta 1260
aatataaata tgtgtattaa atatatatta aatataaata tgtgtattaa atatctatat 1320
taaatataaa tatatgtatt aaatatatat taaatataaa tatatattaa atatatatat 1380
taaatataaa tatatattaa atataaatat atatattaaa tatatatatt aaatataaat 1440
atatataaaa tatatatatt aaatataaat ataaatataa aatatatatt aaatataaat 1500
acatatatta aatatatgta ttaaatatat atataaaata tatgtattaa atat1554
<210>124
<211>650
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(650)
<223>染色体2的MAR基因基序;3944813..3945462
<400>124
catgatatat tatgtataat atatattata gattacatat aaattatata tataatatat 60
aattatataa tatataatat tatataatat attatatata ttatacaatt atataatata 120
tataatatac aattatataa tatataatat acaattatat aatatataat acaatataat 180
atatatttaa tatattatat aatacatatt taatatatta tatattatat gttatatact 240
aaatatataa tatgtattta atatatacta ttatatatgt aatatattat ataatttatg 300
taacatatta tatattatat atgcaatata ttacatgtta catatatatt acatataata 360
tatgtaatat ataatataca ctatattatt atagtatata atatactata ttatgtaatt 420
atataatata gtatattata cactatatta tattatcata taattatata ttatatacta 480
tattacatat atattatgta atataatatg caatatgtta catatataat atatatgtat 540
tatatagtat atatactata gtatatataa aatatatgct ataatatata ttttatatat 600
tatataatac atataatgta tcatatatta tatataatat attttataat650
<210>125
<211>441
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(441)
<223>染色体2的MAR基因基序;5314265..5314705
<400>125
tataaatata tatgaaatat atataaatta tatataattt atatatacat atataaatta 60
tatataaatt atatataaat tatatataca tatataaatt atatattata tataaaattg 120
tatatattta tatataaatt gtatatataa tttatatata aattgtatat ataatttata 180
tatacaatgt atatattaat ttatatatac attgtatata taatttatat atacattgta 240
tatacaattt atatatacat tgtatataca atttatatat acattgtata tacaatttat 300
atataaatta tattatttat atatagtata tataaatata tatactatat ataaattata 360
tatttattta tatattatat tatttatata taaattatat attatttata tatacattat 420
atataaatta tatattattt a441
<210>126
<211>1169
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1169)
<223>染色体2的MAR基因基序;5953971..5955139
<400>126
atgtattcat attatatatt tatatataaa taatatacat tcatattata tatttatata 60
taaataatat atattcatat tatatattta tatataaata tataatatat ttatgtataa 120
ataatatata tattcatatt atatatttct atataaataa tatatatatt catattatat 180
atttatatat aaatatataa tatatttata tataaatata taatatattt atatataata 240
tatatattca tattatatat ttatatataa atatataata tatttatata taaataatat 300
atatattcat attatatatt tatatataaa taatatatat tcatattata tatttatata 360
taaataatat atattcatat tatatactta tatataaata atatatattc atattatata 420
cttatatata aataatatat attcatatta tatatttata taaaaataat atatattcat 480
attatatatt tatatataat atatatattc atattatata tttatatatt ctatatattc 540
atattatata tttatatata aataatgtat attcatatta tatatttata tataaataat 600
gtatattcat attatatatt tatatataaa tatatattca tattatatat ttatatataa 660
atatatattc atattatata tttatatata aatatatatt catattatat atttatataa 720
aatatatata ttcatattat atttatatat aaatatatat attcatatat atatttatat 780
ataatatata tattcatatt atatatttat atataatata tatattcata ttatatattt 840
atatataaat aatatatata ttcatattat atatttatat ataaataatg tatattcata 900
ttatatattt atatataaat aatgtatatt catattatat atttatatat aaatatatat 960
attcatatta tatatttgta tataaatata tattcatatt atatatttgt atatatattc 1020
atatatattt atatataaat atataatatt catattatat ataaatatat atattcatat 1080
tatatattta tatatataaa taatatatat tcatattatt tatatatata aataatatat 1140
attcatatta tttatatata taaataata1169
<210>127
<211>653
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(653)
<223>染色体2的MAR基因基序;6427669..6428321
<400>127
tatatatgta tacatatatg tatatatgtg tatatatgta tacatatatg tatatatgtg 60
tatatatgta tacatatatg tatatatgtg tatatatgta tacatatatg tatatatgtg 120
tatatatgta tacatatatg tatatatgtg tatatatgta tacatatatg tatatatgtg 180
tatatatgta tacatatatg tatatatgtg tatatatgta tacatatatg tatacatgtg 240
tacatgtgta tacatatatg tatacatgtg tacatgtgta tacatatatg tatacatgtg 300
tacatgtgta tacatatatg tatatatgtg tatacatata tgtatatatg tgtatatatg 360
tatacatata tgtatataag tgtatatatg tgtatatgta tataagtgta tatatgtgta 420
tatgtatata agtgtatata tgtgtatatg tatataagtg tatatatgtg tatatatgta 480
tacatatatg tatatatgtg tatatatgtg tatatgtata taagtgtata tatgtgtata 540
tatgtataca tatatatgtg tatatatgta tacatatatg tatatatgtg tatatatgta 600
tacatatatg taaatatgtg tatatatgtg tatatgtata taagtgtata tat653
<210>128
<211>414
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(414)
<223>染色体2的MAR基因基序;10890453..10890866
<400>128
tatattttgt aaatatatat atagtaaata tatgtaaata tatatatttt gtaaatatat 60
atatattttg taaatatatg taaatatata tattttgtaa atatatgtaa atatatatat 120
tttgtaaata tatgtaaata tatatatttt gtaaatatat gtaaatatat atattttgta 180
aatatatgta aatatatata ttttgtaaat ttatgtaaat atatatattt tgtaaatata 240
tgtaaatata tatatatttt gtaaatatat atacatatat attttgtaaa tatataaaca 300
tatatatttt ataaatatat ttataaatat atatattgta aatatattta taaatatatt 360
tataatatat atattgtaaa tatgtttata aatatatata ttgtatatat aaat414
<210>129
<211>496
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(496)
<223>染色体2的MAR基因基序;13952568..13953063
<400>129
taatatacat attatatatt atatattgta tatataatat acatattata tattatatat 60
tgtatatata atatacatat tatatattat atattgtata tataatatac atattatata 120
ttatatattg tatatataat atacatatta tatattatat attgtatata taatatacat 180
attatatatt atatattgta tatataatat acatattata tattatatat tgtatatata 240
atatacatat tatatattat atattgtata tataatatac atattatata ttatatattg 300
tatatataat atacatatta tatattatat attgtatata taatatacat attatatatt 360
atatattgta tatataatat acatattata tattatatat tgtatatata atatacatat 420
tatatattat atattgtata tataatatac atattatata ttatatattg tatatataat 480
atacatatta tatatt496
<210>130
<211>317
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(317)
<223>染色体2的MAR基因基序;16942865..16943181
<400>130
tctcctagta gttatatata tatatatgtg tatatatata tatcctagta gatatatata 60
tatatatatc ctagtagata tatatatata tatatcctag tagatatata tatatatata 120
tcctagtagt tatatatata tatatatcct aacagttata tatatatata tcctagtagt 180
tatatatata tatatcctag tagttatata tatatatata tcctagtagt tatatatata 240
tatatcctag tagttatata tatatatatc ctagtagtta tatatatata ttatatatta 300
tataatatat atataat317
<210>131
<211>464
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(464)
<223>染色体2的MAR基因基序;17217049..17217512
<400>131
acatactata tatatacaca tactatatat actatataca gtatatagta tacatatact 60
atacatatac atatactata catatacata tacatatact aagtatacgt atatacagta 120
catagtatat gtatactata tagtatgtat atatagcata tagtatgcgt atactctata 180
tagcatatag tatgcatata cgctatatag catatagtat gcatatacta tatatagtat 240
agagtatgcg tatactatat atatagtata gagtatgcgt atactatata tatagtatag 300
agtatgcgta tactatatat atagtataga gtatgcgtat actatatata tagtatagag 360
tatgcgtata ctatatatat agtatagagt atgcgtatac tatatatata gtatagagta 420
tgcgtatact atatatatag tatagagtat gtatatatat agta464
<210>132
<211>430
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(430)
<223>染色体2的MAR基因基序;19647266..19647695
<400>132
tgtaaatata tgtaaatata tatttatatt atatattata taaaaatata atatataata 60
tataatatat aaactatata ttaatataat atatataaac tattatataa atacatatta 120
aatatattat atttttaata tttatatatt aaatataata tatatttaat atttatatat 180
taaatatata atatatttaa tatttatata atatatagca tattttatat ttatattata 240
tataacattt tatatttata tttatattta tatatattta atttatattt atattatatt 300
tatatttata ttatatataa cataattata tatattttca tattgtatat aataaagaaa 360
tgtatatttg ttatatataa tatatattat ataatttatt atatattata taatatatat 420
tatataatat430
<210>133
<211>2131
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(2131)
<223>染色体2的MAR基因基序;20481223..20483353
<400>133
tatatataaa tatatttata tttaatatat atttatataa atatattttt atataaatat 60
atatttaata taaatatctt tatatttaat atatatttaa tataaatatc tttatattta 120
atatatattt atatataaat atatatttat atttaatata tattaatatt taatatacgt 180
ttatatttaa tatatatttc tatataaata tatttatatt aacatatatt tatatataaa 240
tatatttata tttaatatat ttacatataa atatatttat atgtaatata tttacatata 300
aatatattta tatttaatat atatgcatat gtaaatatat ttatatttaa taatatttat 360
atataaatat atttatattt aataatattt atatataaat atatttatat ttaatatata 420
ttaaatatat atttatattt aatatatatt aatatttaat atatatttat atttaatata 480
tattatatat aaacatatat ttatatttaa tatatattat atataaacat atatttatat 540
ttaatatata ttatatataa acatatattt atatttaata tatatttata tttaatatat 600
tatatataaa catatattta tatttaatat atatttatat taaatatata ttatatataa 660
acatatattt atatttaata tatatttata ttaaatatat atttatattt aatatatata 720
tattaaatat atatttatat ttaatatata tttatattaa atatatattt atattaaata 780
tatttatatt taatatatat ttatattaaa tatatattaa atatttaata tatatttata 840
tttaatatat acatatatat ttatatttaa tatatacata tatatttata tttaatatat 900
acatatatat ttatatttaa tatatacata tatatttata tttaatatat aaatttatat 960
tttatatata taaaaatata tatttatatt taatatatat aaatatatat ttatatttaa 1020
tatatatatt tatattgaat atatacataa atatatattt atatttaata tataaacata 1080
tatttatatt tatatattaa atatatattt atatttaata tataaatata tatttatatt 1140
taatatattt atatatacta atatatttat atttaatata tttatatata gatatattta 1200
tatttaatat atttatgtgt attaatatat ttatatttaa tatatttata tattaatata 1260
tttatatttt atatttatat attaatatat ttatatttta tatttatatt ttatatattt 1320
atatattaat atatttatat ttatatatat ttttatatat taataaattt atattttata 1380
tatttatata ttaataaatt tatattttat acagttatat aaatatattt atattttata 1440
cagttatata aatatattta tattttatag ttatataaat atatttatat tttatacagt 1500
tatataaata tatttatatt ttatacagtt atataaatat atttatattt tatacagtta 1560
tataaatata tttatatttt atacagttat ataaatatat ttatatttta tacagttata 1620
taaatatatt tatattttat acagttatat aaatatattt atattttata cagttatata 1680
aatatattta tattttatac agttatataa atatatttat attttataca gttatataaa 1740
tatatttatg ttttatacat ttatataaat atatttatat tttatacatt tgtatttaat 1800
atatatttat atataaatat attttatatt taatatattt atatataaat atatattgat 1860
atttaatata tatttatata taaatatata ttgatattta atatgtttat atataaatat 1920
atatttatat ttaatatata tgtttatata tcaatatata tttatattta atatatattt 1980
acatataaat atatatttat atttgatata tatttatatt tgatatatat tttatatata 2040
ttaatatatt tacatttgat atatatttta tatatattaa tatatttaca tttgatatat 2100
attttatata tattaatata tttacatttg a2131
<210>134
<211>842
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(842)
<223>染色体2的MAR基因基序;20483478..20484319
<400>134
tatatattta tgtttaatat atatttatag ataaatatat atttacgttt aatatatatt 60
tatagataaa tatatattta cgtttaatat atatttatct ataaatatat ttacgtttaa 120
tatatattta tatattaata tatttatgtt taatatatat ttatatatat taatatattt 180
atgtttaata tatatttata tattaatata tttatgttta atatatttat atatattaat 240
atatttatgt ttaatatata tttatatgtt aatatattta ggtatatata tatttatatg 300
ttaatatata tttatattaa tatattatat ttatatataa aagtatatat aatatataaa 360
tattatataa attattatat agtattttta tatatattta tatataaatt ttatatattt 420
tatatatata aatatatatt tatatataca ttttatatat aaatatatat ttatatatac 480
attatatata taaatatata tatttatatt ttatatataa atatatatat ttatatatac 540
attttatata ttttatatat gtaaatatat atataaattt tatatattgt atatatattt 600
ataaatttta tatatatatt tatatatata atatatataa tatatataaa ttttatatat 660
attatatata tttatatttt atatattata tatttattta tatatattta tatgttatat 720
atatttatat ttatatttat tttttattta tatattttat atatatattt atatatgtat 780
attatatata ttatatatta tataatatat tatatatatt atattatata tttatattat 840
at842
<210>135
<211>645
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(645)
<223>染色体2的MAR基因基序;20897566..20898210
<400>135
gtatatttat attatatatt atataatata tattatatat taataaatta tatataatat 60
aatatatatg tatatttata tttatgttat aatatacata taattatata tgtatgtata 120
catgtataca tatacgtata tgtgtatatg tatacatata ggtatatgtg tacatgtata 180
catataggta tatgtatatg tatacatgta tacatataat ataattacat atgtatgtat 240
acatacatat gtaattatat tatatatgta tatgtatatt tatataatat ataatatgta 300
ttatatatta tacatgcata tttatatgta tattatatat acacatataa tataattata 360
tatgtatgta tatatacaca tatatattta tattatatat gtatattata tacatatatt 420
tatattatat atgtatatat atttatcata tttatatgta atatgcatgt gtaataaata 480
atatacacat ttatatatgt atattatata catatattta tattgtatat gtatatatat 540
ttatatatat ttgtatatca tatatttata tattgtatat ttatgtatat tatatattta 600
tatattatat atgtattata taatatatat gtaaatatat attat645
<210>136
<211>722
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(722)
<223>染色体2的MAR基因基序;21664541..21665262
<400>136
tataatatat attatattct atataatatg taaaatatat attatattct atataatgta 60
ttatatatag aatataatat attctatgta ttctataatc tatataatac atattatata 120
ttatatagaa tattataaat aatatattct atattatata tagaatatat tctatatgtt 180
tatattctat atattatata tgaaatagta tataaaatat atataatata tataaaatat 240
gatatataat atatataaaa taatatataa tgtataatat ataaaataat atataatgta 300
taatatataa aataatatat aatgtataat atataaaata atatataatg tatattatat 360
aaaataatat ataatgtata ttatatataa aataatatat aatgtatatt atatataaaa 420
taatatataa tgtatataaa ataatatata atatattata tataaaataa tatataatat 480
attatatata aaataatata tattatatat aaaataatat ataatatatt atatataaaa 540
taatatatat tatatataaa ataatatata atatattata tataaaataa tatatattat 600
atataaaata atatatatta tatataaaat aatataatat atattatata taaaataata 660
tataatatat tatataaaaa tataaatata ttatataaaa atataaaata taaaatatta 720
ca722
<210>137
<211>305
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc._binding
<222>(1)..(305)
<223>染色体2的MAR基因基序;22834991..22835295
<400>137
aatataaaat atatgatata taatacgtat tatatatgta taatacgtat tatatattaa 60
tatataatat ataatacata ttatatatgt atataatata tactaatata tataatgtat 120
acattatata tttacataat atataataca taatatagaa ttataattat atataataca 180
taatatataa ttatatatat tattatatat gtatttatat tatatataat atattatata 240
taatatatat tatataatta tataagtata taattatgtt atatacataa taatatataa 300
tatat305
<210>138
<211>352
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(352)
<223>染色体2的MAR基因基序;25277762..25278113
<400>138
taatatatat aatatattat atattatata taatatattt tataatatat aaaatatatt 60
atatataata tataatatat tttataatat atataatata ttatatataa tatataatat 120
attttataat atatataata tattatatat attatatatt tatatttatt tatatattca 180
taaatatata tttatatata atatatttta taatatatta tatataatat ataatatatt 240
ttataatata ttataatata taatatataa tatattttat aatatatata atatataata 300
tattatatat ttatatttat ttatatattc ataaatatat atatttatat ta352
<210>139
<211>342
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(342)
<223>染色体2的MAR基因基序;25378452..25378793
<400>139
tatgtacata tatattttat atattatata taatatatat tatatgatat atataatata 60
ttatataata taatatataa aatatatata atatatatta tattatataa attatattat 120
atatatcata taatatattt tatatattat ataatatata ttatattata tatattttat 180
atattatatt atatattata tatatcatat aatatatatt atattatata ttttatatat 240
tatataatat atattatata tttttatata ttatataata tatattatat attttatata 300
ttatataata catatattat atataatata atatatatta ta342
<210>140
<211>663
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(663)
<223>染色体2的MAR基因基序;30209437..30210099
<400>140
aatatatatt acatattgta tatatagtat atgtaatgta tataatatag tatattctat 60
attgtataat agtaatatat agtatatgat atactatata ttacttatca tatatacaat 120
atatattata tcgtatattg tatattatat attgtatata tgtaatatat gatatgtaca 180
tatgttatat atgtatataa tatactatat tatatattgt atattatata catatataac 240
actattatac aatatataat atagcatatt atatacaata tagcatatac aatatataat 300
atagcatatt atatataata tagtatatta tatacaatat ataatatagc atattatata 360
taatataata tagtatatta tatacaatat ataatatagc atatacaata tagtatacaa 420
tatataatat agcatataca atatagtata ttatatataa tatataatat agcatgtaca 480
atatagtatg ttatatacaa tatataatat agcatataca atatagtata ttatatacaa 540
tatataatat agcatataca atatattata ttatatacaa tatataatat agcatataca 600
atatagtata ttatatacaa tatataatac agcatataca atatagtata ttacatacag 660
tat663
<210>141
<211>1200
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1200)
<223>染色体2的MAR基因基序;31725089..31726288
<400>141
tgtacttata tattataatg tatatataaa gtatatactt tatatatact tatatattat 60
aatgtatatt attgtatata agtatatatc ataatatata cttacatatg ctcacatata 120
ttataatgta tattgtatat attatataca tattatatat gtataatgta tatatacatt 180
atatatgtat aatgtatata tacattatat atgtataatg tatatataca ttatatatgt 240
ataatgtata taatatatac aatatatgta taatatataa tatatacaat atatgtataa 300
tatacaatat atgtataata tacaatatat gtatagtata taatatatat tatatatgta 360
tagtatatta tatattatat atgtatagta tataatatgt ataatgtata tattataata 420
tattatatat aatatctata acaatataat atattgtata tattatatat aatatatatt 480
tatataatat atattatata taatatatta tgtatttatt tatattatat ataatataaa 540
tatatataat ataaataata tttattatat attaatataa atatttatat taatatatat 600
ttattatata taaataatat ctatgatata aataatatat aatatacatg tatatgttat 660
aatatataca tataatatac atgtgtatat atactataca tgtatatata acatgtatat 720
atatacatgt atatatatta tgtatacatg tatagtatat atacatgtat atatatacat 780
atatactata catgtatata tacatgtata tatatacata tatactatac atgtatatat 840
acatgtatat atacacatat atactataca tgtatatata catgtatata tatacatgta 900
tgttatatac attattataa tatacatata tagtatacat tatatacatt atataatatg 960
cattattata atataatata cattattata atatacatta ttataatata atatacatta 1020
ttataatata cattattata atatacatta taataatata cattattata atatacatta 1080
taatattgaa gtatatatac tataatatat gtatatatta taatgtatat aatatacatt 1140
attatatata agtatgtatt atatataagt atatattata atatatgtat atacatatat 1200
<210>142
<211>325
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(325)
<223>染色体2的MAR基因基序;32147252..32147576
<400>142
aaatacaaat atttatttat atataatata taatataata tatttattta tatataatat 60
ataatttata attatataaa tatataatat atttatatat aatatataat tttattatat 120
attaattata tatataataa atatatataa tatataattt tattatatat taattatata 180
tataataaat atatataata tataataata ttatatacat tatatataaa tataaatatt 240
tatataatat ataatataat atatttattt atatataaat atataatata taattatata 300
aatatataat atatttatat ataac325
<210>143
<211>507
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(507)
<223>染色体2的MAR基因基序;32312662..32313168
<400>143
attatttata taaatattat atttatatta tttatataaa tattatattt atattattta 60
tataaatatt atatttatat tatttatata aatattatat ttatattatt tatataaata 120
ttatatttat attatttata taaatattat atttatatta tttatataaa tattatattt 180
atattattta tataaatatt atatttatat tatttatata aatattatat ttatattatt 240
tatataaata ttatatttat attatttata taaatattta tttatattat ttatataaat 300
attatattta tattatttat ataaatattt atttatatta tttatataaa tatttattta 360
tatttatata aataatatat aaataaatat tttatatgta tataaatatt atttatatta 420
tttatttaaa taaataatat aaattaatat aaatattaat attatttatt ttattataaa 480
taatataaat attatattta tatttat507
<210>144
<211>339
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(339)
<223>染色体2的MAR基因基序;33651118..33651456
<400>144
aaatataata tattatttat atataatata aatgatatat tatgtatata taaaatataa 60
ataatatatt atgtatatat aaaatataaa tattatttat atataaaata taaataatat 120
ttatatataa aatataaata ttatattatt tatatataaa atataaataa tatattattt 180
atatataaaa tataaataat atattattta tatataaata atatataaaa tataaatata 240
tattatatat aaataaaata tatatattat atatataaat ttatatataa tatataaaat 300
ataatatata tatttaatat ttattatata atatataat339
<210>145
<211>461
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(461)
<223>染色体2的MAR基因基序;45073053..45073513
<400>145
tgtgtataca tatatacgtg tacatataca tatatacatg tgtatatata tacgtgtaca 60
tatacatata tacatgtgta tatatatgta catatacata tatacatgtg tatacataca 120
tatatacatg tacatataca tatatacatg tgtatacata catatataca tgtacatata 180
catatataca tgtgtatact tacatatata catgtacata tacatatata catgtgtata 240
tatacatata tacacgtaca tatacatata tacatgtaca tatatacatg tatacatata 300
tacatgtaca tatgtacata tatacatgta tacatatata catgtacata tgtacatata 360
tacatgtata catatataca tgtacatatg tacatatata catgtataca tatatacata 420
tgtacatacg cacagataga catatataca tatgtacata c461
<210>146
<211>1162
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1162)
<223>染色体2的MAR基因基序;45487691..45488852
<400>146
attatattat ctatataaat ctattatatc tattatatta tctatataat atctattata 60
tatattatat tatctatata aatctattat atatattata ttatctatat aaatctatta 120
tatatattat attatctata tatctattat atattatatt atattatatt atatataata 180
tctattatat atattatatt atattatatt atatataata tctattatat atattatatt 240
atctatataa tatctattat atattatata ttatattata tataatatct attatatata 300
ttatattata ttatatataa tatctattat atctattata tatattatat atatctatta 360
tatctattat atatattata tataatatct attatatcta ttatatatat tatatataat 420
atctattata tctattatat tatattatat ataatatcta ttatatctat tatatatatt 480
atatatatct attatatcta ttatatatat tatatataat atctattata tctattatat 540
atattatata taatatctat tatatctatt atatattata tatataatat ctattatatc 600
tattatatat tatatatata atatctatta tatctattat atctattata tatatatcta 660
ttatatctat tatatatatt atatacataa tatctattat atctattata tatattatat 720
atataatatc tattatatct attatatata tactatctat tatatctatt atatatatta 780
tatatgtact atctattata tctattatat ctattatata tatactatct attatatcta 840
ttatatatat tatatatata ctatctatta tatctattat atatattata tatatactat 900
ctattatata tctattatat atattatttt atattatata tagtatctat tacatatatt 960
atattatatt atatataata tctattatat atattatatt atattataaa taatatatat 1020
aatatctgtt atatataata gatattatat ataatatata atatatataa tagatattat 1080
atatattata ttatataata tataatatat aatataatta atataaaata tatataatat 1140
ataattaata taatatgtaa ta1162
<210>147
<211>562
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(562)
<223>染色体2的MAR基因基序;45516233..45516794
<400>147
acatattata tatattatat ataatatata ttatatatac atattatata tattatatat 60
aatatatatt atatatacat attatatata ttatatatac atatatatat tgtatataat 120
atatacatat tatatatatt atatatacat attatatatt atatataata tatacatatt 180
atatattata tataaatatt atatattata tataaatatt atatatataa atattatata 240
ttatatataa atattatata tcttatatat aaatataata tataatatat ataatattta 300
tatattatat ataaatatta tatatattat ataatattat atataatata taaatatata 360
tattatataa atattgtata tattatataa atattatata tattatatat aaatattata 420
tatattatat aaatatatat aaatatataa aatatataaa tatgtaaaat ttatatttat 480
aaatatataa tataaatata taaatataaa tataaattat atataatata taatatatta 540
tacataatat atactatata ta562
<210>148
<211>801
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(801)
<223>染色体2的MAR基因基序;45727251..45728051
<400>148
atatatatat ataatatata catatataga atatatatat tattatattc tatatataga 60
atatatatat agaatatata tatatagaat atatatatag aatatatata tagaatatat 120
atatagaata tatatataga atatatatat atagaatata tatatagaat atatatatat 180
agaatatata tatatagaat atatatatat agaatatata tatatagaat atatatatag 240
aatatatata tagaatatat atatatagaa tatatatata gaatatatat atatagaata 300
tatatataga atatatatat atagaatata tatatagaat atatatatat agaatatata 360
tatagaatat atatatatag aatatatata tagaatatat atatatagaa tatatatata 420
gaatatatat atatagaata tatatataga atatatatat atagaatata tatatagaat 480
atatatatat agaatatata tatagaatat atatatatag aatatatata tagaatatat 540
atatatagaa tatatatata gaatatatat atatagaata tatatataga atatatatat 600
atagaatata tatatagaat atatatatat agtatatata gaatatatat atatagtata 660
tatagaatat atatatatag aatatatata tagaatatat atatatagaa tatatatata 720
gaatatatat atatagaata tatatataga atatatatat atatagaata tatatataga 780
atatatatat atatatagaa t801
<210>149
<211>346
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(346)
<223>染色体2的MAR基因基序;50937238..50937583
<400>149
taaaattata tatattatat ataatatata atatattata tataatatat attataatat 60
atataatata tattatataa aatatattct atagaatata tattctatta tataatatat 120
attctattat aatatatatt atatataata tatattctat tataatatat attatatata 180
atatattcta ttatgatata tattatatat aataacatat attatatata atatatattc 240
tattatataa aatatatatt atataaaata tatattctat tatataaaat atatattata 300
taaaatatat attatattat ataaaatata tattatacta tatata346
<210>150
<211>462
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(462)
<223>染色体2的MAR基因基序;55672627..55673088
<400>150
taaatatata ttatatatta tattatatat aatatattta tatttatata tactataatt 60
tatatataat atatattata tatataatat atttataata tatatcatat aaataatata 120
tatttataat atatatcata taaataatat atatttataa tagatatcat ataaataata 180
tatatttata atagatatca tataaataat atatatttat aatagatatc atataaataa 240
tatatattta taatagatat catataaata atatatattt ataatatata tcatataaat 300
aatatatatt tataatatat atcatataaa taatatatat ttataatata tatcatataa 360
ataatatata tttataatag atatcatata aataatatat atttataata gatatcatat 420
aaataatata tatttataat agatatcata taaataatat at462
<210>151
<211>401
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(401)
<223>染色体2的MAR基因基序;56081352..56081752
<400>151
tatacatgta tgtattcgta tatgtatgtt atatatgtat atgtgttata tacatataca 60
tatatacatg tatatgtgtt atatacatat acatatatac atgtatatgt gttatataca 120
tatacatata tacatgtata tgtgttatat acatatacat atatacatgt atatgtgtta 180
tatacatgtg tatgtgtata tgtatatata catatatgtg tatgtgcatg tgtatatata 240
catatatgta tatgtgtata tgtatatata catatatgta tatgtgtatg tgtatacgta 300
tatatacata tatgtgtatg tgtatgtgta tacgtatata tatacatata tgtgtatgtg 360
tatacgtaca tatacatata tgtgtatgtg tatacgtaca t401
<210>152
<211>765
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(765)
<223>染色体2的MAR基因基序;56404208..56404972
<400>152
tatattatat aaagaatata tattatataa tatgtaaaga atatatatta tataatatgt 60
aaagaatata tattatatat tatgtaaaga atatatatta tatataatat ataaagaata 120
tatattatat aatatataaa gaatatatat tatatattat ataaagaata tatattatat 180
ataatatata aagaatatat aatatataat atataaagaa tatatattat atataatata 240
taaagaatat atattatata taatatataa agaatatata ttatatatta tataaagaat 300
acatatatat aatatataaa gaatatatat tatatataat atataaagaa tatatattat 360
atataatata taaagaatat atattatata taatatataa agaatatata ttatatataa 420
tatataaaga atatatatta tatataatat ataaagaata tatattatat atattatata 480
aagaatatta tatattatat aaagaatata tattatatat aatatataaa gaataaacat 540
atatactata tataaagaat atacattata tatactatat ataaagaata tacattatat 600
atactatata taaagaatat atataatata taaagaatat acattatata taatatataa 660
agaatatatt atatattata taaagaatac attataatat aaagaataca ttatatataa 720
tataaagaat acattataat atataaagaa tatatataat atata765
<210>153
<211>443
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(443)
<223>染色体2的MAR基因基序;61953416..61953858
<400>153
tttatatatt atagataaaa ttatattata ttacatgtaa tatataatat gtaaaatata 60
ttatattaca tatataatat ataatatgta aaatatatta tattacatat ataatatata 120
atatgtaaaa tatattatat tacatatata atataaaata ttacatataa tatattttac 180
ataaatatat attatctatt acatatttat tatatgtaat aatatgtaca tatgtataaa 240
tatgtatata tttatacata tgtatatatt atatatacat atatatgtat atattatata 300
tacatatata tgtatatatt atattatata tacatatata tgtatatatt atattatata 360
tacatatata tgtatatatt atattatata tacatatata tgtatatata ttataaatat 420
gtataataaa gatttatatg taa443
<210>154
<211>372
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(372)
<223>染色体2的MAR基因基序;62076211..62076582
<400>154
tatatataat tatatatgta attatatatc agtatatata attatatata attatcaata60
tatataatta tatataatta tcaatatata taattatcaa tagatatata taattatata120
tataattata tataattata tatcagtata tatacttata taattatata tatgtatata180
taattatatg tataaattat ctataagtat atataactat aatatatatc aattatatat240
acttatgtat aattatatat actgatatat aattatacat aattatatat atcaattata300
tataattatg tataattata tatacatata tataattata tatataaatt atatgtaatt360
atataattac ac372
<210>155
<211>484
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(484)
<223>染色体2的MAR基因基序;62158581..62159064
<400>155
attatatata atataaaaat tatacatatt attttattat atattatata cataatatat 60
atatttcata tataatatat attatatata atataaaata tatattatgt ataattatat 120
ataaaatata ttatataatt atatataaca taaaatatat ataatatata attatatata 180
atataaaata tatatataat ataaaatata tattatatgt aattatatat aatataaaat 240
atatatataa tataaaatat atattatata taattataat ataaaatata tattatatag 300
tatatattat ataaaatata tattatatat aattatatat tatataaaat atatattata 360
tataattata taatataaaa tatatattgt atataattat atataatata aaatatatat 420
aatatatgaa ataagatata tactatatat aatatatata atttacatat aagatatata 480
tcat484
<210>156
<211>644
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(644)
<223>染色体2的MAR基因基序;68145036..68145679
<400>156
tatatatatg ctaatatatg taatatatat tatatatatg ctaatatata tatgctaata 60
tataatatat attatatata aatatataat atatatttat ataaatatat aatatattat 120
atataaatat ataatataaa tatatataat atatactata ttatatatta tgtataacat 180
ataatacata tttgttatat ataatatata tattatatgt tatatattat atattatata 240
taatataaca atatatttta tatattatat gttatatatt atatattata tataatataa 300
cataatatat aatatatatt atattatata ttacatatat tagcaatatt atatataaaa 360
tatatataat atatataaaa tatatataaa aatataaaat atatatcaaa atataaacta 420
tataatatat aaaaatatat tatatataat atataaaaat ataaactata taatatataa 480
aaatatatta tatataatat ataaaaatat attatatatt atatataaaa atatattata 540
tataatatat aaaaatatat ataaaatata aaaaatatat ataaaatata aaaaatatat 600
aaaataatat aaaatatata atatataata atataatata taat644
<210>157
<211>530
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(530)
<223>染色体2的MAR基因基序;71257289..71257818
<400>157
atatctatta tatttatata ctttatataa attatatcta ttatatttat atactttata 60
taaattatat ctattatatt tatatacttt atataaatta tatctattat atttatatac 120
tttatataaa ttatatctat tatatttata tactttatat aaattatatc tattatattt 180
atatacttta tataaatata taattatatt tatatacttt atataaatat aattataaat 240
atatttatat actttatata aatataatta taaatatatt tatatacttt atataaatat 300
aattataaat atatttatat actttatata aatataatta taaatatatt tatatacttt 360
ataattatat gttatattta taattatatt tatataattc ataattatat acattatgtt 420
tatagttata taatttataa ttatatacat tatatttata tttatataat ttataattat 480
ataaattata taaattatat aaattatctt taatttatat tatataatct530
<210>158
<211>337
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(337)
<223>染色体2的MAR基因基序;73413615..73413951
<400>158
acttatatta tatataacta tattattgta tattaatata aattaatgat atataatata 60
ttaattatat attattatat gtgatataaa atacttatat ttatactgta tatatgtata 120
tacacacata tatgtatata tgtatatata cacatatgta tatatgtata tgtatatatg 180
tatactgtat atatgtatat acacacatat atgtatatat gtatatgtat atatgtatac 240
tgtatatatg tatatacata tatacatata tgatatatat cacatatatg tgatatataa 300
atatatttat ataaatataa tattaatatt tatatta337
<210>159
<211>1340
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1340)
<223>染色体2的MAR基因基序;77011049..77012388
<400>159
atgtatttta tatagtatat attatgtatt atattgatat aattatataa caattattta 60
tatataaaat aacaaataaa tatataaaat aataaatata tatttattat taaataataa 120
atatatattt attattaaat aataaatata taaagtaata aatatatatt tatatattaa 180
ataattcata tatatttata tattaaataa ttcatatata tttaaataat taatacatat 240
ttaaataatt aatatatatt tatataatat atatttatat attaaataat taatatatat 300
ttatagatta aattaatata tatttatata ttaaattaaa tttaatatat tatatattta 360
tataatttaa atttaataat ttatataatt taatttaatt taatataatt aaaatatatt 420
aaacattata taatatataa tatatttaat atataatata tatttaatat ataatatatt 480
taatatataa tatatttaat atataatata tatttaatat ataatatatt taatatataa 540
tatatttaat atataatata tatttaatat ataatatatt taatatataa tatatattta 600
atatataata tatttaatat ataatatata tttaatatat aatatattta atatataata 660
tatatttaat gtataatata tttaatatat aatatatatt taatgtataa tatatttaat 720
atataatata tatttgatgt ataatatatt taatatatat ttgatgtata atatatttaa 780
tatataatat atatttgatg tataatatat ttaatatata atatatattt gatgtataat 840
atatttaata tataatatat atttgatgta taatatattt aatatataat atatatttga 900
tgtataatat atttaatata taatatatat ttgatgtata atatatttaa tatataatat 960
atatttgatg tataatatat ttaatatata atatatattt gatgtataat atatttaata 1020
tataatatat atttgatata taatatattt aatatataat atatatttga tatatattta 1080
atatataata tatatttgat atataatata tttaatatat aatatatatt tgatatataa 1140
tatatttaat atataatata tatttgatat ataatatatt taatatataa tatatatttg 1200
atatataata tatttaatat ataatatata tttgatatat aatatattta atatataata 1260
tatatttgat atataatata ttttcttatt aattatttat atataatata taaatatata 1320
ttaattaatt atatattaaa1340
<210>160
<211>937
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(937)
<223>染色体2的MAR基因基序;78226855..78227791
<400>160
tgtgtatata tacatatatg tgtatctatg tgtatatata catatgtgta tatatacata 60
tatgtgtata tatacatatg tgtatatatg tgtatatatg tgtatatata catatatgtg 120
tatatatgtg tatatatgtg tatatataca tatatgtgta tatatgtgta tatatacata 180
tgtgtatata tgtgtatata tacatatatg tgtatatatg tgtatatata catatatgtg 240
tatatatgtg tatatataca tatatgtgta tatatgtgta tatatgtgta tatatacata 300
tatgtgtata tatgtgtata tatacatata tgtgtatata tgtgtatata tacatatatg 360
tgtatatatg tgtatatgtg tgtatatata catatatgtg tatatacaca catatatgtg 420
tatatatgtg tatatataca tatatgtata tatacatata tgtgtatata tgtgtatata 480
tacatatatg tgtatatatg tgtatatata catatatgtg tatacataca tatatgtgta 540
tatatgtgta tatatacata tatgtgtata catacatata tgtgtatata tgtgtataca 600
tacatatatg tgtatacata catatatgtg tgtatatgtg tatacataca tatatgtgtg 660
tatatatgtg tatacatatg tgtgtatatg tgtatatata catatatgtg tgtatatatg 720
tgtatatata catatatgtg tgtatatatg tgtatatata catatatgtg tgtatatatg 780
tgtatatata catatatgtg tgtatatatg tgtatatata catatatgtg tgtatatatg 840
tgtatatata catatatgtg tgtatatatg tgtatatata catatatgtg tgtatatatg 900
tgtatatata catatatgtg tgtatatatg tgtatat937
<210>161
<211>1350
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1350)
<223>染色体2的MAR基因基序;79287748..79289097
<400>161
tatatatatt atatatatag taactgttct attatatata tattatatat atttctgttc 60
tattatatat tatatatatt atattatata ttatatgtaa tatattatat atattataag 120
taatatatta tatatattat atgtaatata ttatatatat tatatgtaat atattatata 180
tattatatgc aatatgttat atatattata tgcaatatgt tatatatatt atatgcaata 240
tattatatat attatatgca atatattata tataatatat gtaatatatt atattatata 300
ttatatgtaa tatcttatat attatatgta atatattata tatattatat gtaatatctt 360
atatatatta tatgtaatat attatatatt atatgtaata tattatctta tatatattat 420
atgtaatata ttatattata tattatatgt aatatatatt atatgtaata tattacatat 480
tatatgtaat atatattata tgtaatatat tacatattat atgtaatata tattatatgt 540
aatatattac atattatatg taatatatta catattatat gtaatatatt atatgtatta 600
tatgtaatat attatatgta ttatatgtaa tatattatat gtattatatg tattatatgt 660
aatatattat atgtattata tgtaatatat tatatattat atgtaattat attatatgta 720
atatattata ttatatatta tatatattat atgtaatata ttatattata tattatatat 780
attatatgta atatattata ttatatatta tatatattat atgtaatata ttatattata 840
tattatatat attatatgta atatattata ttatatatta tatatattat atgtaatata 900
ttatattata tattatatat attatatgta atatattata ttatatatta tatatattat 960
atgtaatata ttatattata tattatatat attatatgta atatattata ttatatatta 1020
tatatattat atgtaatata ttatattata tattatatat attatatgta atatattata 1080
ttatatatta tatatattat atgtaatata ttatattata tattatatat attatatgta 1140
atatattata ttatatatta tatatattat atgtaatata ttttatatta tatatattat 1200
attatatatt atatgtaata tattatatta tttattatat attatatatt atatgtaata 1260
tattatatta tttattatat atattatatt atttattata tataatatat tatattatat 1320
atattatatt atatatattt ctgttctaat1350
<210>162
<211>332
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_difference
<222>(1)..(332)
<223>染色体2的MAR基因基序;81142998..81143329
<400>162
ctatgtatat aactatatat aactattata taacttaata agatatataa ctattatata 60
acttaataag ttatatataa ctattatata taacttaata agttatatat aactattata 120
taacttaata agttatatat aactattata taacttatta agttatatat aactatatat 180
aacttaataa gttatatata actattatat aacttaataa gttatatata actattatat 240
aacttaataa gttatatata actattatat aacttaataa gttatatata actatatata 300
acttatatac aacttattaa gctatatata ta332
<210>163
<211>327
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(327)
<223>染色体2的MAR基因基序;84019536..84019862
<400>163
actgacagta tacatactgt atatatatac agtatgtata catatacagt atgtatacta 60
tatacagtat gtatactgta tatatatata cagtatgtat actgtatata tatacagtat 120
gtatacgtat gtatactgta tatatgtatt atagtgtata tatgtattat agtgtatata 180
tgtattatat atattatagt gtatgtatta tatgtgtata tacatataat atattataca 240
tatacatatg cacaatatgt atatgtatta tatgtattca tatacatata tgtatatgta 300
taatatatgt atacatataa tacacat327
<210>164
<211>407
<212>DNA
<213>智人(Homo sapien)
<220>
<221>misc_binding
<222>(1)..(407)
<223>染色体2的MAR基因基序;1448030..1448436
<400>164
tatataatat atattacata tatattatat ctatattatt tatattacat atgtaatata 60
tattatattt atattattta tataatatat tatatatatt atattattta tatgtaatat 120
atttatattg tttatatata ttatatttat attatttata tataatacat attatattta 180
tattatttat atataatata tataataaat atataatata tataaaaata tatatattta 240
atatatctat aatatatatt atatatatta tatataatat atataattgt acatatattt 300
attatatata ttatatatat aatatatatt ataaatataa tatataaata tatttataaa 360
tatatataaa tattatattt atacattata tttatataca tattata407
<210>165
<211>1959
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(1959)
<223>染色体2的MAR基因基序;2117630.2119588
<400>165
tatacatgtt atagtgtata tagtatacta atatataatg tatgtatgtg tatacatata 60
cacatataat atacacatat ataatatata tagtatataa taatgtataa tatataatat 120
ataatataaa atgtatagta tactacatat ttatatatag tatatagtat gcatagtaca 180
tatatactat atatgtagta tactatagtg tatatatagt acaccatata tagtataaat 240
atactatata gtatatgtac tatatatata ctatatagta tatacagtat acatatatag 300
tatacctata ctatatagta tatatagtgt gcgtatacta tatagtatat atagtgtgcg 360
tatactatat agtatatata gtgtgcgtat actatatagt atatatagtg tgcgtatact 420
atatagtata tatagtgtgc gtatactata tagtatatat agtatacata tatagtgtgc 480
gtatactata tagtatatat agtatacata tatagtatgc gtatactata tatagtatac 540
atatatagta tatctagagt atatgtagta tgtatagtat atatagtcta catactgtat 600
atacagtata tatatactct atagtatact atacagtata gtatactata tagtatacaa 660
tatatgtata ctatagaaac acactatata tagtatacta tatatactat atactatata 720
ctatatatag tatactatat atactacata ctatatatag tgtatgtata gtatatataa 780
actatatata gtgtatatag tatatatatt atatataata tatattatat tatattatac 840
tatatattat atgtatatta tagtatatta tactattata tattatatat tatattatat 900
attatataat ataatataat tatatattat aaaatatata tttttatatt atatattttt 960
aaatatttta taatatatat tttataatat atatattata attattttat atataatata 1020
aaatataata aatattttat aatatatatt tttaaaatat aatatttata tattataaaa 1080
atataaatat ataatatatt atatattata tatagtataa tatataatat gttatatagt 1140
atcttatact attatactat atatattata tagtgtatat atagtatact atatatagtg 1200
tatatagtgt atactatagt gtatatagtg tatactatag tgtatatagt gtatactata 1260
tacactgtat atagtagtgt atactatata cactgtatat agtagtgtat actatataca 1320
ctgtatatag tagtgtatac tatatacact gtatatagta gtgtatacta tatacactgt 1380
atatagtagt gtatactata tacactgtat atagtagtgt atactatata cactgtatat 1440
agtagtgtat actatataca ctgtatatag tagtgtatac tatatacact gtatatagta 1500
gtgtatacta tatacactgt atatatagta tattatatat actatatatg tatatatagt 1560
atacatatat attatatata cagtatatat agtatatata ctatgtagta tatatagtat 1620
atatactata tagtatgtat agtatactat atagtatata tagtatatta tatagtatat 1680
atactatata gtatatatag tatattgtat atatagtata tatactatat agtatatata 1740
gtatattgta tatatagtat attgtatata tagtatacat agtatgtata tatagtatat 1800
atagtataca tatatagtat gtacacagta tatatagtct atatgtatac tacatatagt 1860
atacatgtat actatactac atatagtata catgtatact atactacata tagtatacat 1920
gtatagtata ctacatatac tatacatgta tagaatact1959
<210>166
<211>520
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(520)
<223>染色体2的MAR基因基序;2119984..2120503
<400>166
tatgtatgca tcgtatacat atatagtata tatatgtatg catcgtatac atatatacag 60
tatatatagt atgcatcgta tacatacagt atactatata tacagtatat acagtatact 120
atatatacag tatatacagt atactatata tacagtatat acagtatact gtatatacag 180
tatatacagt atatatagta tactatatat acagtatata tactatgtat tctatatata 240
gtatagtgta catagtatac atatagtata cactatacta tatatagtat actatatata 300
ctctatatag tatatatagt atactatata tagtatatat gtatactata tatagtgtat 360
atatatacta tatatagtgt atatatatac tatatatagt atatatatac actatatatt 420
gtatagtata gtgtatatat agtatagtat atgtatatat acacatgtat acatgtatat 480
atgtatacta atatatacta atatatgtat aaatatatat520
<210>167
<211>954
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(954)
<223>染色体2的MAR基因基序;2578285..2579238
<400>167
tattatatat aactttataa tatataatat atattatata taactttata atatataata 60
tatattatat ataactttat aatatataat atatattata tataacttta taatatataa 120
tatatattat atataacttt ataatatata atatatatta tatataactt tataatatat 180
aatatatatt atatataact ttataatata taatatatat tatatataac tttataatat 240
ataatatata ttatatataa ctttataata tataatatat attatatata actttataat 300
atataatata tattatatat aactttataa tatataatat atattatata taactttata 360
atatataata tatattatat actatatata atatataact ttataatata taatatatat 420
tatatactat atataacttt ataatatata atatatatta tatattatat ataactttat 480
aatatataat atatattata tataacttta taatatataa tgtatattat atattatata 540
ttatatatta tatataactt tataatatat aatgtatatt atatattata tataacttta 600
taatatataa tatataatat aatatataac tttataatat atatatcata tattatatat 660
aactttataa tatatatcat atattatata taactataat atatatatca tatattatat 720
ataactataa tatatatatc atatattata tataacttta taatatatat atcatatatt 780
atatataact ttataatata tatcatatat tatatataac tttataatat atatcatata 840
ttatatataa ctttataata tatattatat ataactttat aatatatatc atatattata 900
tataacttta taatatatat catatattat atataacttt ataatatata tcat954
<210>168
<211>452
<212>DNA
<213>智人(Homo sapiens)
<220>
<221>misc_binding
<222>(1)..(452)
<223>染色体2的MAR基因基序;3836217..3836668
<400>168
tttatatata aatatatatc ttatatatat ttatatataa tacatatata tcttatatat 60
ataaaatata tatacatatt tatatataaa atacatatgt attatataca tttatatata 120
atacatatgt attatataca attatataat acatatgtat tatatacaat tatataatac 180
atatttataa atatatatat ttatatttat atatatttat atataaataa atatatattt 240
atagatttat ttatataaat atatatttat ataaatatat atttatatat atttatataa 300
atatatattt atatatattt ctatatatat atataaatat atgtataaat atatatattt 360
atacatatat tcatataaat atatatattt atacatgtat ttatatgaat atatatttat 420
acatgtaatt atatgaatat atatttatac at452
<210>169
<211>417
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(417)
<223>染色体2的MAR基因基序;3837666..3838082
<400>169
gatatatata tttatataaa tatatatata aagagatata tttatatatt tatttatata 60
aatatatttc tttatataaa gatatatgta aatatattta tttatataaa tatatttata 120
tatgtaaata tatatttata tatttatata tttatatatt tatttatata aatatatata 180
tttatatatt tatttatata tataaaaata tataaatata aatatatata aatatatata 240
attataaata tagaaataaa tataaatata aatatataaa tatatataaa tataaatata 300
tataaatata aatatatata aatataaata tataaatgta taaatatata aatataaata 360
tatataaata tgtataaata tataaatata taaatatata aaaatatata taaatac417
<210>170
<211>1197
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1197)
<223>染色体2的MAR基因基序;6294846..6296042
<400>170
tatatactaa tatgtatata taaatatata aatatatata cacgtgtata tataaatata 60
tatgtatata taaatatata tacatatatg tatataaaaa tatatacgta tatacgtata 120
tacgtatata tagatatata cgtatatacg tatatacgta tatatagata tatacgtata 180
tacgtatata tagatatata cgtatatacg tatatacgta tacatgtgta tatacgtata 240
tacacatata cgtatacatg tgtatatacg tatatgtata cattatatat acgtatatat 300
acatatatgt atacatgtat atataaatat atacatatat gtatatatta tacatatatg 360
tatatataat atatatatta tatataatat atatattata tataatatat atattatata 420
taatatatat attatatata atatattata tattatatat aatatataca tatataatat 480
attatatatg tacatatgta cataatgtat atatgtatat atataatata tatgcacatg 540
tatatataat atatgtatat tatatataca tatgtatata tgtacatatt atatatgtat 600
atatgtacct attatatata catatgtata tatgtaccta ttatatatac atatgtatat 660
atgtacatat tatatataca tatgtatata tgtacatatt atatatacat atgtatatat 720
gtgcatgcat atataatata taatatatta tagattataa tattatatac atatcatata 780
ttatatactt atatatacat gtatatatta tatacatatt atatattata tacatataat 840
atatgtatat aatatataca tatattatat attatatata atacattatg ttatatatta 900
tgttatataa tatatattat ataatataca tatattatat ataatatata catatataat 960
aaataatata taattatata tataatatat gcatataaat atgtaatata ttttatatta 1020
tatatgatca tatataatat gacatattat atatgattat atatatgata tattatatat 1080
gattatatat attatatata aatatatgat tatatataat catatatata aatatatgat 1140
tatatgatta tatataaata tatatatatg attatatgat tatatataat tgattat1197
<210>171
<211>362
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(362)
<223>染色体2的MAR基因基序;6506971..6507332
<400>171
tatatatagt gtatactata tatacgctat atgcacacat aaactatata tacagtatat 60
aatatgcgta tactatatac acagtatata ctacatgtat actatatata gtatataaga 120
tatatactat gtatataata tatatactag gtatatatat ccatatatat actatatact 180
atagtatata catatatatg tacgtatata tgtatatgta catatatatg tagtatgtat 240
atatatacat atatacacac tatagtatat acatatatat actatatata ccctatatag 300
agtatattat atacagtata ctatatatac tatatatacc ctatatagag catgtctatg 360
ct362
<210>172
<211>2578
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(2578)
<223>染色体2的MAR基因基序;6507395..6509972
<400>172
ggtatactat atatactata gagtatactt tatagtatat atacctatat tatatatata 60
tacatacact gtatagtata tatggtatat atactatata tggcatatat agtttatata 120
tatactatat atggtatata tagtttatat atatactata tatggtatat atagtttata 180
tataccatat atggtatata tagtttatat agtacatata gtatatatac acactgtata 240
gtatatatta tgtagtatat atactatata tactgtatat atagtataaa tactatatat 300
agtatacact atatactata cactatatat actatatact atatactata tatagtatac 360
tatatagtat atagtatact ctatatgtac tatagagtat actatatata ctatacataa 420
aatattttta tatatagtac agcgtatact atatactata tatagtatac tctatatgta 480
ctatagagtg tagtatatac tatacagtat actctatata tactatacag tacactatat 540
atactatata tagtatattt tatatatagt acagtatata cagtatatat attatactat 600
atgtagtaca tatatagttt agtatatata gtatatatac tatactatat gtactacata 660
tataatagta tatatagtat atatactata ctatatgtag tacatatata gtttagtata 720
tatactagta tatagatata tagttatata gatatataat agtatatata gtatatatag 780
catatatagt atatatgcta tatatactat atagcatata ctatatacta tatatacagt 840
atatatagca tatatagcat atataatata tatacttttg atatacatac tatatacagt 900
atatatagta tatatactgt ataaatatac tatatatacc gtatatgcac actatatgct 960
atatatacta tatacactat atacagtata tatagtacac tatactatat aaagtatata 1020
tagtatacag tacactatac tatatacatt atatatagta tatattatac atagtatata 1080
gtatataaat agtatatata gtatatacag tatatatata gcatacttta tatagtatac 1140
acagtatata gatactatat atgctatata tagtatctat atactgtata ttatatatac 1200
taatatagta tatatgtata tatatactgt atatataata tatacatata tagtatatat 1260
actatacata cacactatac atatgtatat atactataca tactatatac tatatatcct 1320
atatatacta tatagtatat tatatatcct atatatacta tatagtatat tatatatcct 1380
atatatacta tatagtatat tatatatact atataccata tatactatat atactgtata 1440
gtatactata tatactatat agtatactgt atatactata tagtatactg tatatactat 1500
atagtatact gtatatacta tatagtatac tgtatatact atatagtata ctgtatatac 1560
tatatagtat actgtatata ctatatatac tatatagtat actgtatata ctatatagta 1620
tactatatat actatatacc atatatacta tgtatatact atatatagta tatactatgt 1680
atatgctata tatagtatat atagtatata tgctatatat agtatatata gtatatatgc 1740
tatatataca gtctatatat agtatatata ctatatagac tatatatata gcatatatac 1800
tatatatact atatataata tatatggtat atacatagta tctatatgta gtatctatat 1860
atagtaccta tatatactat atataggtac tatatatagt atatatactt tatatagata 1920
ctatatatag tatatatact ttatatagta tatatagtat atgtagcata tatagtatat 1980
atagtatata tagtatatag tatgtatagt atatatagat tatattgtat atacagtata 2040
tatactgtat atactatata aatagtacat acagtatata cagtatatat gtactatata 2100
tagtatatac agtatataca gtatatatgt accatatata gtatatacag tatatacagt 2160
atatatgcac tatatgttat atacagtata tacagtatat atgtactata taaatagaat 2220
atactctata tacagtatat atgtactata taaatatata cactatgtac agtatatatg 2280
tactatataa atagtatata cactatatac agtatatatg tactatatag tgtatacagt 2340
atatacagta tataggtact atatatggta tatacagtat atatgcacta tatggtatat 2400
acagtatata tgcactatat atggtatata cagtatatat gtactatata tggtatatac 2460
agtatatatg tactatatat ggtatataca gtatatatgt actatatatg gtatatacag 2520
tttatacagt atatatgcac tatatatggt atatacagta tacatgtact atatatgg2578
<210>173
<211>598
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(598)
<223>染色体2的MAR基因基序;7770400..7770997
<400>173
gtgtattgta tatacatata cgtatctacg tatatacata tatgtattgt atatacatat 60
atgtattgta tatacatata tgtatatacg tatatacata tatgtattgt atatacatat 120
atgtatatac gtatatacat atatgtatat acgtatatag atatacatat atatgtattg 180
tatatacata tatgtatata catatataca tatatattga tatacatata tatgtattgt 240
atatacatat acaatatatg tatatataca tatacatata caatatatgt atatacatat 300
atatgtattg tatatacata tatatgtatt gtatatacat atattgatat acatatatgt 360
atatatacat atatgcatat atgtatatat acatatatgc atatatgtat atatacatat 420
atacatatgt acatatatac atatatacat atatgtatat atacatatat acatatgtac 480
atatatacat atatacatat gtacatatat acatatatac atatgtacat atatacatat 540
atagatatat atacacatat atagatatac ttatatgtat atatacatac atacatat598
<210>174
<2t1>1048
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1048)
<223>染色体2的MAR基因基序;8332422..8333469
<400>174
cattatatat aatatataat atattattat atataatata tataacatta tatatagtat 60
atatgacata tataacatat attatatata acatatataa aatataacat attatatata 120
acatatataa aatataacat atattatata taacatatat aaaatataac atatattata 180
tataacatgt ataaaatata acatatatta tatataacat gtataaaata taacatatat 240
tatataacat gtataaacta taacatatat tatatataaa atatattata tgttatatat 300
tataaataaa atatattata tgttatatat tataacatat tatataaata atatataata 360
tataacatat attatataaa taatatataa catatattat ataaataata tataacataa 420
catatattat ataacatata acatataaca tatattatat ataacatata acatataaca 480
tatattatat ataacatata acatataaca tatattatat ataacatata acatatatta 540
tattatatat aacatataac atatattata ttatatataa catataacat atattatatt 600
atatataaca tataacatat attatattat atataacata taacatatat tatattatat 660
ataatatata acatatatat tatatataat atataacata taacatatat tatatataat 720
ataatatata acatatatta tatataatat aatatataac atatattata tataatataa 780
tatataacat atattatata taatataata tataacatat attatatata atataatata 840
taacatatat tatatataat ataatatata acatatatta tatataatat aatatataac 900
atatattata tataatataa tatataacat atataatata taacatatag catatataat 960
atataacata taacatatat tatatataac atataacata tattatatat aacatataac 1020
atatataata tgtaacatta tatataac1048
<210>175
<211>375
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(375)
<223>染色体2的MAR基因基序;8909678..8910052
<400>175
tatatacaca tatatacgta tgaatatata tacacatata cgtatgaata tatataccca 60
tatacgtatg aatatacaca tatatatacg tacgtatata tatacacata tatacgtacg 120
tatatatata cacatatata cgtacgtata tatatacaca tatatacgta cgaatatata 180
tacacatata tacgtacgaa tatatataca catatatacg tacgaatata tatacacata 240
tatacgtacg aatatatata cacatatata cgtacgaata tatatacaca tatatacgta 300
cgaatatata tacacatata tacgtacgaa tatatataca catatatacg tacgaatata 360
tatacacata tatac375
<210>176
<211>563
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(563)
<223>染色体2的MAR基因基序;10572503..10573065
<400>176
atttataata tatatgtata aatatatgta tatatttata tttaaatata tgtatatata 60
tttatattta aatatacgta tatatattta tatttaaata tacgtgtata tatttatatt 120
taaatatacg tgtatatatt tatatttaaa tatacgtgta tatatttata tttaaatata 180
cgtgtatata tttatattta aatatacgtg tatatattta tatttaaata tacgtgtata 240
tatttatatt taaatatacg tgtatatatt tatatttaaa tatacgtgta tatttatatt 300
taaatatacg tgtatattta tatttaaata tatgtatgta tttataaata tatatttaaa 360
gtatatattt ataaatgtat acatgtatat ataaatatat atattttaaa tatatattta 420
tatatatatt tatatattta tataagtata tatatattta aatatatgta tatatttata 480
tatttatata agtatatata tttaaatata tgtatatatt tataatatat attttaaata 540
tatatttata tatttattat ata563
<210>177
<211>595
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(595)
<223>染色体2的MAR基因基序;11609694..11610288
<400>177
tataaatact atatatagta tatataatat tatatatact atatataaat atatgtagta 60
taaataatat ataatataga tatataatat aatataatat gttataaata taaatatatt 120
tatataattt aatttataat atataatata taatatataa tttaatttta taatatataa 180
tatataattt aattttataa tatataatat ataatatgta aattatatat aatttaatat 240
atctaaatta tataatttaa atataaatat aatataaata tatctaacat aatatacata 300
acataaatat atatagtata tatagtacat ataaatatat atagtacata tagtatatat 360
aaatatatag tatatataaa tatagtatat ataaatatat agtatatata tagtatatat 420
aaatatatag tatatataaa tatatatagt atatataaat aatatatagt atataaataa 480
tatatattat taaatataat aataatttat tatatatact atatattatt atgtattata 540
ttatatatat tattttatat ttaatatata ttattttata tattatattt aatat595
<210>178
<211>662
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(662)
<223>染色体2的MAR基因基序;12699804..12700465
<400>178
gtatatatat atatatatat atggtgtata tatatatata tatatatggt gtatatatat 60
atatatatat atggtgtata tatatatata tggtgtatat atatatatgc tgtatatata 120
tatggtatat atatatggta tatatatatt tgctatatat atagcagatc tgctatatat 180
atatatttgc tatatatata gcagatctgc tatatatatt tgctatatat atgctatata 240
tatgctacat atatgctata tatatgctat atatatgcta tatatatgct atatatatgc 300
tatatatatg ctacatatat gctatatata tgctacatat atgctatata tatgctatat 360
atatatgcta tatatatgct atatatatat gctatatata tgctatatat atatgctata 420
tatatgctat atatatatgc tatatatatg ctatatatat gctatatata tagcatatat 480
atatagctat atatatgcta tatatatagc ttatatatat gctatatatg ctatatatat 540
gctatatata tagctatata tatgctatat atagctatat atatgctaca tatatgctat 600
atatatgcca tatgtatgct atatatatgc tatatatata tgctatatat atgctatata 660
ta662
<210>179
<211>649
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(649)
<223>染色体2的MAR基因基序;12821904..12822552
<400>179
tatgtaatat tatatatata aattatatat tatacatatg taatattata tatatataaa 60
ttatatatta tacatatgta atattatata tatataaatt atatattata catatgtaat 120
attatatata tataaattat atattataca tatgtaatat tatatatata taaattatat 180
attatacata tgtattatat atataaatta tatattatac atatataata tatatataaa 240
ttatatatta tacatgtata atatatataa attatatatt atacatatat aatatatata 300
aattatatat tatacatata taatatatat aaattatata ttatacatat ataatatata 360
taaattatat attatacata tataatatat ataaattata tattatacat atataatata 420
tataaattat atattataca tatataatat atataaatta tatattatac atatataata 480
tatataaatt atatattata catatataat atatataaat tatatattat acatatataa 540
tatatataaa ttatatatta tacatatata atatatataa attatatatt atacatatat 600
aatatatata aattatatat tatacatata taatatatat aaattatat649
<210>180
<211>3191
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(3191)
<223>染色体2的MAR基因基序;15356889..15360079
<400>180
tacaattata tataactata aatataatat aatatatatt atctatatta catattaata 60
tataatatat attacctatt aatatataat ataatatata taatatatat tacctattaa 120
tatataatat aatatatata atatatatta cctattaata tataataaaa tatatataat 180
atatattaca tattattata taatatatat tatataacat atataacata tactatatat 240
tatataacat atataattgt atatgtatta tatatattat atatacttat acataatata 300
taaataatta aatatatgtt ataaatataa caaatatata acatatataa catatataac 360
atatatataa ttacataaaa tatataatac ataatatata ttatgcaaca tattatataa 420
tatataacat ataatgtata ttatattata tcatatataa tacataatat ataatatatg 480
atataatata atatattata tatgatataa tataatatat tatatatgtt ataatataat 540
atatattata tataggatat attataacat attacatatg atataataaa ttttatctta 600
tatataggat atattataat atatcacata tagcatatat taaaatatat tacatatagt 660
atattatata tactatatgt atatatacat atagtatatt atagtatatt atacagtata 720
tattatatat actatatata gtagtataca gtatatatta tatatactat atatagtagt 780
atacagtata tattatacag tatatattat atacactata ttatatatta tgtataatat 840
atactatata tagtatatta tgtagtatat attaaacata atagatatat agtatatact 900
atagataata gatattatat agtatatagt atatattata tataatatat ataatatata 960
ttatatacat atatgatata tgatatatta tatataatat atataatata taatatatgt 1020
aatataatac atattatata taatatatgt aatataatat aatatataat atatgtaata 1080
taataatata tattatataa tataacatat ataaatataa taatatatat tatatgatat 1140
aacatacata aatataataa catatataat atatattata tattatattg tatatatgat 1200
atactatata ttacacatta tacattattt ataatatata attaatatat aacatatatt 1260
agataacata taattatatc tgtaacatat ataagatata attacatata taacatatat 1320
aattatatat atatttatct aattatatat gaaattatat atgacatata aaattatata 1380
ttatatatgt tatatgtatt atatattata tatgttatat atgttatata taacatatat 1440
aacatatata acacacacat ataacatata taacatatat tacatatata acatatataa 1500
cacatatata attatctaac atagataata tatataatat ataatataac atatatatta 1560
tatattatac actctattat attatatata ttatacataa tatataatat atatgatata 1620
atataataca ttgtatatac gatataatat atattgtaca tagtataata tacatatata 1680
gtatattatg tataacataa tatatagtat attatgtata acataatata tagtatatta 1740
tgtataacat aatatatagt atattatgta taacataata tatagtatat tatgtataac 1800
ataatatata gtatattatg tataacataa tatatagtat attatgtata acataatata 1860
tagtatatta tgtataacat aatatatagt atattatgta taacataata tatagtatat 1920
tatgtataac ataatatata gtatattatg tataacataa tatatagtat attatgtata 1980
tataatatac atattatata gtatattatg tatatataat atacatatta tatagtatat 2040
tatgtatata taatatacat attatatagt atattatgta tatataatat acatattata 2100
tagtatatta tgtatatata atatacatat tatatagtat attatgtata tataatatac 2160
atattatata gtatattatg tatatataat atacatatta tatagtatat tatgtatata 2220
taatatacat attatatagt atattatgta tatataatat acatattata tagtatatta 2280
tgtatatata atatacatat tatatagtat attatgtata tataatatac atattatata 2340
gtatattatg tatatataat atacatgtta tgtagtatat tatgtatata taatatacat 2400
gttatgtagt atattatgta tatataatat acatgttatg tagtatatta tgtatatata 2460
atatatataa ggtgtatata tattatgtat atataatata taaggtatat atattatgta 2520
tatataatat atataaggtg tttatataat gtatatataa tatataaggt atgtatatta 2580
tgtatatata atatgtatat tatatataat atatattatt tatatacatt atgtatctat 2640
ataatatata ttatgtatat attaggtatc tatataatat atattatgta tatatattat 2700
gtatctatat aatatatata ttatgtatat atattatgta tctatataat atatatatta 2760
tatgtatatt atgtatctat ataatatata taatgtatat agatatatta tatattatgt 2820
atatatatta tgtatctatt ttatatataa tgtatataga tatacaatat atattatgta 2880
tatattatgt atctatataa tatatattat ttatatagat atatatatta tgtatatata 2940
cataatatat tacatattat gtatatatac ataatatata atatattatg tatatataca 3000
taatatataa tatattatat attacatata ttatatataa tatattatat tatgtatata 3060
tattatgtat atataatgta tatataatat ataaagtgta tatatattgt gtatatataa 3120
tgtatatata ttacatatat tatgtgtata tatattatac ataatatata tactacatta 3180
tacataatat g3191
<210>181
<211>314
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(314)
<223>染色体2的MAR基因基序;728676..728989
<400>181
tgtgtatata tgtatatata atatatatta tataatatgc atatgtataa aatatgtata 60
ttatatatgt atattttata tatatgtata tattatatgt atattttata tatgtatatt 120
ttatatatat gtatatatta tatatgtata ttttatatat atgtatatat tatatgtata 180
ttttatatat atgtatatat tatatatgta tattttatat atatgtatat attatatatg 240
tatattttat atatatgtat attttatata tatgtatatc atatatatgt atatattata 300
tatatgtata tctt314
<210>182
<211>423
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(423)
<223>染色体2的MAR基因基序;737493..737915
<400>182
ataatatata gtgtctttta tattatctaa tatgtaatat aatgtatttt atattatgta 60
ttttatatta tataatatat aatataatgt attttatatt atatgttata taatatatag 120
tgcattatat attatgttat attatatata ttttatttat ataaattata tattatatgt 180
tattttatat atattatata acatataata taacaatgca ttatatatta taaaatatat 240
aatacattac atatattata taatatataa tacattacat atattatata atatataata 300
cattatcata tattacaaat attacattag tataatagta attataatat aatatattat 360
atattacata tattatatta atgtaatagt aattataata taatatatat tatattttat 420
att423
<210>183
<211>724
<212>DNA
<213>Homo sapiens
<220>
<221>mi sc_binding
<222>(1)..(724)
<223>染色体2的MAR基因基序;1069556..1070279
<400>183
tattataata tattatatac attatattgt atatatacta tatatggtat atatagtata 60
cataatataa aatgtatatt gtaatataca ttatatatat acatagtgta cattatataa 120
tataatataa tgtatattat aatatacatt ataatataat agtgtactat gtatatagta 180
tatataatgt atattataat gtattatata gtataatata atataatata cattatatag 240
tattgcatta tatatgctat ataatatata atatattatg tatatataca ttatatatac 300
tatattatat agtacatata atgtatatta tatagtatat ataatataat acattataca 360
tacaatatat aatgtatatt atatagtatg tataatgtaa tacattatac atagtacata 420
aagtatatta taatatatta taatatataa tatacattat atattataat gtatataata 480
tattgtatat atactatata taatgtatat acaattatat ataattgtat atatacatgt 540
atatgtatat gtatatatac atgtatatgt atgtgtatat atacatatat gtatatgtat 600
gtgtatatat gtatatgtat atatgtatat gtatacgtat atatgtatat acaatgtata 660
tataatgtat ataaaaatat ataatatata caatatgtat ataatgtata taattatata 720
atat724
<210>184
<211>383
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(383)
<223>染色体2的MAR基因基序;2719918..2720300
<400>184
atatttatat tttatatatt atttatatat aaatatatat ttatatttta tatattattt 60
atatataaat atatatttat attttatata ttatttatat ataaatatat atttatattt 120
tatatattat ttatatataa atatatattt atattttata tattatttat atataaatat 180
atatttatat tttatatatt atttatatat aaatatatat ttatatttta tatattattt 240
atatataaat atatatttat attttatata ttatatattt atatattata tatatttata 300
ttaatttgtg tataatatat attattaaat ataataaata tatttatttt tatatattat 360
ataaaaatat ataatatata aaa383
<210>185
<211>309
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(309)
<223>染色体2的MAR基因基序;4994249..4994557
<400>185
tataatatat aattgttata acattataac aattatatat tatatataat acaattatat 60
aatatatatt atataattgt aatatataat ataattatat aatatatatt atataatata 120
atatataata tatcatatat gttatatatt ttattatata atatatatta tatataatat 180
tatatataat atatattata tataatatta tatataatat atattatata taatatattt 240
atatatatta tatataatat atattatata ttaaatatta tatatataat atatataaca 300
ttattgtta309
<210>186
<211>740
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(740)
<223>染色体2的MAR基因基序;5034916..5035655
<400>186
tttatatata aaatattata tataatatta tatataatat tttctatata aaatgtgtat 60
ataattatat ataattatat aaaatataat atagaatatc taataatgta taatatataa 120
catataaaaa taatattatt taatatataa tattttatat ataatatttt tatatataat 180
ataatatata ttttatatat aattattaat tatataatta atatataata tatattttat 240
acataattat taattatata taattaatat ataatatatc ttatacataa ttatcaatta 300
tatataatta atatataata tatattttat acataattat taattatata taattaatat 360
ataatatatc ttatacataa tatatataaa tatattatat ataatatata ttatatataa 420
tattatatat aatatatatt atatatataa aatttatata taatattata tataatatta 480
tatattttat atacaatatg atatataata taatttatat attatatata tttatatata 540
attattatat aaattatata aatataaatt atatatttat atataattat tatataaatc 600
attatataat tattataatt ataatatata atataatata atattatata taatatatag 660
tattctatat aaataatata acatatattt tatatagaat attatatata atataatata 720
tattttatat agaatattat740
<210>187
<211>847
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(847)
<223>染色体2的MAR基因基序;6074678..6075524
<400>187
aatatagaca taaatatata tgcataaata tatatatgca taaatatata taaaaatata 60
tataaatata tacataaata tatataaata tatacaaaaa tatatataaa tatataaaaa 120
aatatataaa tatatataca catatataaa tatatataca tacatatata aacatatata 180
cataaatata tatgtataaa tatatataca cataaatata tgtatgaata tatatacata 240
aatatatatg tataaatata tatacataaa tatataaaga tatatacata aatatatata 300
aatatatata cataaatata tataaatata tataaataga tatataaata tatatataaa 360
tatataaata tatatataaa tatataaata tataaaaata gatatataaa tatatatata 420
aatatataaa tatatatata aatatatata aatatataaa tatatatata aatatatata 480
aatatataaa tatatataaa tatataaata tatatataaa tatatataaa tatataaata 540
tatataaata tatataaata tataaatata tatataaata tatataaata tataaatata 600
tatataaata tataaatata taaatatata tataaatata taaatatata taaatatata 660
taaatatata aatatatata aatatatata aatatataaa tatatataaa tatatataaa 720
tatatataaa tatataaata tatataaata tatataaata tatataaata tatataaata 780
tataaatata tatataaata taaatatata taaatatata aatatatata taaatatata 840
taaatat847
<210>188
<211>784
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(784)
<223>染色体2的MAR基因基序;6108986..6109769
<400>188
atttatttat atatttaata tataaaatat atatttaata tataaaatgt atatatatac 60
atatattata tataatacaa tatatattat atataatata tattatatat aatattatat 120
attatattat aatataatat atattatata taatataata tatattatat attattatat 180
ataatataat atatattata tattattata tataatataa tatatattat atattattat 240
atataatata atatatatta tatattatta tatataatat aatatatatt atatatatat 300
tttatatata taatatataa tatatatatt atatatatat tttatatata taatatataa 360
tatatatatt atatatatat tttatatata taatatataa tatatatatt atatatatat 420
tttatatgta taatatataa tatatatatt atatatatat tatatatata taatatgtaa 480
tatatatatt atatatatat tatatatata atatatatta tacataaaat atatattata 540
tataatatat ataatatata ttatatataa aatatatttt atgtataata tatattatat 600
ataatatata atgtatattt atatataaaa tatatattta tatacaatgt atatttatat 660
ataaaatata tatttatata caatgtatat ttatataaat atgtgtttaa tatatgaaat 720
atatatttat atataatata tatttaatct ataaaatata tattaaatat atatttatat 780
ttaa784
<210>189
<211>381
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(381)
<223>染色体2的MAR基因基序;10389032..10389412
<400>189
tatacacata tagagtatat agagtatata tagagtatat ctatagagta tatatgtata 60
tagagtatat aatacagcct accatatata tagtatacat atatatatac tctatatact 120
atatatatag tgtgtatata tatagtatag accctaccat atatatatat aggagtatat 180
atatatacac actcctacta tatatagtat gtatatagag agtatataga gtatatatac 240
agtatatata cacagtatat atatgccata tatagtatct atatacttat atatagtatg 300
tatctatata cttatatata gtatgtatct atatactata tatagtatgt atctatatac 360
tatatagagt atatatgtat a381
<210>190
<211>507
<212>DNA
<213>Homo sapiens
<220>
<221>misc_difference
<222>(1)..(507)
<223>染色体2的MAR基因基序;11097807..11098313
<400>190
aattatatat aatttattat atataatttt atatttataa tatttttata tacatatttt 60
atatatcttt ataattatat attacatata taatattata taatatatat aatatatata 120
atatatatta tatattatat aatatatatt atatatatta tatataatat atataatata 180
tataatatat ataatatata taatatataa tatatattat ataatatata ttatatataa 240
tatatattat atataatata tattatatat aatatataat atatataata tatataacat 300
ataataatat attatacata atttatatat aatttttata taattatata tatttatata 360
tttttatata attatatata tttatatatt tttatataat tatatatatt tatatatttt 420
tatataatta tatatataat ttttatataa atatatataa ttttatataa ttttatataa 480
ttataaaata tataattata tataatt507
<210>191
<211>329
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(329)
<223>染色体2的MAR基因基序;11234628..11234956
<400>191
ttatagttaa atatataaat ataaaatata cagttttata cagtatatat aaaatataca 60
atatataata cataatacat tagttatata tactatatat actatatata ctacacgtat 120
agtatatata tgaaactata tatatactat acgtgtagta tatatatgaa actatatata 180
tactatacgt gtagtatata tatgaaacta tatactatac gtatagtata tatatgaaac 240
tatatatact atatatactt aactataatt gtatatagtt aaaaatataa atataaaata 300
tacagttaaa tatattaata tataatagt329
<210>192
<211>584
<212>DNA
<213>Homo sapiens
<220>
<221>(1)..(584)
<223>染色体2的MAR基因基序;797844..798427
<400>192
tattatttta tgttataaat agataaaaat atatactaat atatatgtac ttatatatac 60
atcaatatat aatgtattat tttatactaa cgtatattat atatactagt atataatcta 120
tattatttta tatgttataa atatataata aaatatataa atattttatg catatattaa 180
tatataatat atactaacat gctaatttat atatacttat atataattta tatagtatat 240
aatatataaa tgtatataat acataattta tatatttata tattaatagt ttatatatta 300
gtatatatac taattttata tactaataaa taaattatat aatatataaa ttatatatta 360
tagtacataa tatatattat atagttaaat aactatgtaa ctataatata taactatata 420
tgatatacag ttatatataa tataaatttt acatacagta tataaattat atactataca 480
tttatataca tatggtatat aaattatata ctatacattt atatacatat ggtatataaa 540
ttgtatacta tataatgtgt attagtatat atactaatat atac584
<210>193
<211>363
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(363)
<223>染色体2的MAR基因基序;1093824..1094186
<400>193
tatacacaca catatatata cacatatata tacacatata tatatacaca tatatataca 60
catatatata cacgtatata tgtatacaca tatatatgta tatatataca catatataca 120
cacatatata cgtgtatata cgtatatacg tacatatata cgtgtatata cgtatatgcg 180
tacatatata cgtgtatata cgtatatgcg tacatatata cgtgtatata cgtatatgcg 240
tacatatata cgtgtatata cgtatatgcg tacatatata cgtgtatata cgtatatgcg 300
tacatatata cgtgtatata cgtatatgcg tacatatata cgtgtatata cgtatatgcg 360
tac363
<210>194
<211>545
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(545)
<223>染色体2的MAR基因基序;3456187..3456731
<400>194
tattataata tatatttata tattataata tatattatat tatatattta tatattataa 60
tatatattat attatatatt tatatattat aatatatatt atattataat atatatttat 120
attataatat attatattat aatatatatt atattattat atattataat ataatatata 180
ttataatata tattatatta taatttatat attatatata ttataatata tattatatta 240
tatatatatt tatattataa tatatattat tatatattat atattataat ttatattata 300
ttacaatata tattataaat atatatatta tattataaat atatattttt atattacaat 360
atatattata aatatatatt ttatattaca atatatatta taaatatata tattatatta 420
caatatatat tataaatata tattatatta caatatatat tatattataa tatatattta 480
tatatgatat attatattta atatattata taacataata tataatatat aatatattaa 540
tataa545
<210>195
<211>356
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(356)
<223>染色体2的MAR基因基序;5001567..5001922
<400>195
tataaaatat atgttatata tataatatat attatataat atataatata tataatatat 60
aaaatatata aaatatataa tatataatat aatatataat atatataata tataaaatat 120
atataatata aaatatatat aatatataat atatataata tataatacat ataatatata 180
atatataata tataatatat ataatatata atatataata tataatatat ataatatata 240
atatataata tatataatat ataatatata atatataata tataaatata taaatatata 300
tacacacata cacacacata tatgcatata tatacatata catgtgtaca tagata356
<210>196
<211>321
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(321)
<223>染色体2的MAR基因基序;5457330..5457650
<400>196
tatacaatat attataaatt atatataatt tatatataat atatattata tataaattat 60
atataattta tataatatat aaattatata taatataaat tatatataat ttatataata 120
tataaattat atattatata aattaaatat aatttatatt atatataaat tatatttaat 180
ttatataata tataaattat atttaattta tatataatat aaattatatt tttatatatt 240
atgtataatt tatatattta tacatatata cattataata tattgtatag tatatataat 300
atatagtata tataaagcat a321
<210>197
<211>361
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(361)
<223>染色体2的MAR基因基序;8124469..8124829
<400>197
tatatataat atatattata tatattatat aaattatata taatatgtaa tataaatttt 60
gtaatataaa ttatatatat aaattatata taatatatat taatatatat aatataaatt 120
aatatatata atatataatt atatataatt tatatgatat atataaatat atattatata 180
taaattatat atatcataaa ttatatatca tataaattat atataatata cattatgtac 240
ataatatatg atatataata tataatatat attatatata attatatata tataattata 300
taatatatat aaattataat atataatata tataaattat aatatataat atatataaat 360
t361
<210>198
<211>418
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(418)
<223>染色体2的MAR基因基序;11151485..11151902
<400>198
atgtaactat atatatagta tatatagtat atatatacta tatagtgtgt atatatagta 60
tatatatact atatagtgtg tatatatagt atatatatag tgtatatatc gtatatacac 120
tatatactat atagtgtata tatagtatat gtagtatata tagtatatat agtatagtat 180
atatagtata tatagtgtat atatactgta tatatagtgt acatagtata ctatatagta 240
tacatatagt acactgtata gtatatatag tatagtatat atagtataca tagtatacta 300
tatatagtat agtatacata gtatactata tagtatatag agtatatata cagtatacta 360
tatagtatat agagtatata tacagtatac tatatcgtgt gtatagagta tatataca418
<210>199
<211>394
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(394)
<223>染色体2的MAR基因基序;13591477..13591870
<400>t99
ttatatatat tttatatata ttatatatat tttatatata ttatatatat attatatata 60
tattatatat aattatatat aatatatatt atatatatta tatataatta tatataatat 120
atattatata tattatatat ataatatata tataatatat atattttata tatgtattat 180
atatatttta tatatattat atatattata tatatatttt atatatatta tattttatat 240
atataatata acatatataa tatataatta tatattatat atatattata ttatatataa 300
tatatattat atataatata atatataatt atatatatta tatattttat atatttatat 360
aaaaattatt ttatattatt ttatatataa atat394
<210>200
<211>1194
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1194)
<223>染色体2的MAR基因基序;14996824..14998017
<400>200
taatatttat atatacatat aaaatttata tataatatat aatatttata tatacatata 60
aaatttatat atatatataa tatttatata tacatataaa atttatatat aatatataat 120
atttatatat acatataaaa tttatatata atatataata tttatatata catataaaat 180
ttatatataa taaatattta tatatacata taaaatttat atataattta tatataacat 240
ataatattta tatataaaat ttatatataa catatattta tatataattt atatataaca 300
tataatattt atatataata tatatttatt tatacaattt atatataata tataatactt 360
atatatacat acataattta tatgatatat attatatata taatttatat gatatataat 420
atatctaata tatattatat atattatata tattatatat aatttatata atatatatta 480
tatatataat ttatataata tatatattat atatataatt tatataatat atatattata 540
tatataattt atataatata tattatatat ataatttata taatatatat tatatatata 600
atttatataa tatatattat atataattta tatataacat attttatata catatataat 660
ttatatataa tatatattta catatacata tataattttt atataatata aaatatttct 720
atatacatat ataattttta tataatataa aatatttcta tatacatata taatttttat 780
ataatatata tttctatata catgtctaat ttttatataa tatatatttc tatatacata 840
tataattttt atataatata taatattttt atatacataa tttttatata atatatattt 900
acatatacat atataatttt tatataatat atatttatat atacatatat aatttttaca 960
taatatatat tatatataca tatataattt atatacaaca tataatatat acatatataa 1020
tttatataca acatataata tttatgtata catatataat gtatacacaa tatataatat 1080
ttatatatac atatataatt tatatgtaat atatacatat ataatttata tgtaatatat 1140
atacatgtat aatttatatg tagtatatat acatgtataa tttatatgta gtat1194
<210>201
<211>487
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(487)
<223>染色体2的MAR基因基序;14998429..14998915
<400>201
tagtatacat ttacacatac atgtataatt atatgtaata tataatattt acatatataa 60
ttatagataa tatatattta catatacata tataattata tataatatat aatgtttaca 120
tatacataca taattatata taatatatat ttaaatatac atatacaatt atatataata 180
tatatttaca tatgcatata taattataga taatatatat ttacatatac atatataatt 240
atatataata tataatgttt acatatacat atataattat atataatata tatttaaata 300
tacatataca attatatata atatatattt acatatgcat atataattat agataatata 360
tatttacata tacatatata attatatata atatataata tttacatata catatataat 420
gtatatataa tatataatat ttacatatac atatataatt tatatataat atatattata 480
tatatta487
<210>202
<211>421
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(421)
<223>染色体2的MAR基因基序;16562490..16562910
<400>202
tatatgaata tatatatgaa tatatacgta tatatgaata tatacatgta tgtatatatg 60
aatatatgta tatatatgaa tatatatgta tatatgaata tatgtatata tatgaatata 120
tatgtatata tgtatatata tgaatatata tgtatatatg tatatatatg aatatatatg 180
tatatatgta tatatgtata tatatgaata tatatgtata tatgaatata tatgaatata 240
tatgtatata tatgaatata tatgaatata tgtgtatata tatgaatata tatgtatata 300
tatgaatata tgtatatata tatgaatata tatgtatata tgtatatatg aatatatatg 360
tgtatatgaa tatatatatg aatatatatg tgtatatgaa tatatatgaa tatatatgtg 420
t421
<210>203
<211>479
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(479)
<223>染色体2的MAR基因基序;21592301..21592779
<400>203
tatatgtata cgtatataat atattatata ttatatacgt gtacgtatat atgtaatata 60
taatgtatat gtacacgtat ataatatata atatattata tacgtatacg tatacattat 120
atattacata tatacgtata tacgtatata aaatatatgt atatattata tatacgtata 180
taatatatat tatataatat ataatatata cgtatacata taatatatta tatatacata 240
ttatatatta tatatttaaa ttatatatta tatcatatat aatatatatg atataatata 300
taatatacat atattacata atatatatta tatacatata catatataat atataatata 360
ttatatacat atacatatat aatatataat atattatata catatacata tataatatat 420
aatatattat atacatatac atatataata tataatatat tatatataca tattatata479
<210>204
<211>870
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(870)
<223>染色体2的MAR基因基序;22557584..22558453
<400>204
tataatatat aatatacata atatgtatat tttatacaca atataaataa tatacataac 60
atatatgtat attttatata tgtatatttt atatatattt tatatatttt atatatatgt 120
atattttata tataatatat atattgtata taataatata taatatatta tattatatat 180
aatatatata atatatatat aaatatatat tatatataat atgtataata tataatattt 240
tatatataat atgtataata tatattttat atataataat atgtacaata tatattttat 300
atataataat atgtacaata tatattttat atataataat atgtacaata tatattttat 360
gtataatatg tataatatat attttatgta taatatatat tttatgtata atatatattt 420
tacgtatatt ttatatataa tatataatat tttatatata atatataaca ttttatatat 480
aatatataat attatatata ttatatattt tatatataat atatataaat atatatattt 540
tatatataat atattttata tataatatat ataaatatat atattatata taatatattt 600
tatatataat atattttata tataatatat aatatatttt atatattata tataatatat 660
tatatattat atataatata ttatatataa tatataatat ataatatatt atatataata 720
tataatatat aatatattat atataatata taatatataa tatataatat attatatata 780
atatataata tgtaatatat aatattttat atataatata taatataata tataatattt 840
tatatataat atataatata taatatataa870
<210>205
<211>1086
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1086)
<223>染色体2的MAR基因基序;30591960..30593045
<400>205
gtatatataa tatatattat attatgttat atattatgta gactatgtat taaatatatg 60
tatatattat atataaatat ataatatata tttataattt ataattataa atatatttat 120
aatatatttt tctaaatatt tatatattat atattatatc taatgatata taataaatat 180
atttctaata tattttatat ttataaatat tttatatata ttatatattt tatatatact 240
atatattata tattatatat tttatatata ctatatatta tatagtatat attttatata 300
tactatatat tatatattat atattttata tatactatat attatatatt atatatttta 360
tatatactat atactattta ttatatattt tatatatact atatactatt tattatatat 420
tttatatata ctatatacta tttattatat attttatata tactatatat tatatattat 480
atattttata tataatatat atttattata tattttatat attatatata ttatatatta 540
tatatttata tattatataa tatatattat atatagaata tataatatat attatatata 600
atataatata atatatatta tataaaatat atataatata taaaatatat aatatatgat 660
atatataata tatattctat atttatacat atatatttaa tattatatta atatataatt 720
atatattatc atatgtaata atagatataa tatgtaatat ataaattata attatatatt 780
aatattatat attatttaat atgtatattt acacatatat taattattaa atatatatat 840
ttaatatatt aaatattatg tattaaatat atataatata tttataaata ttttatatat 900
aatatataca tatattaaca tatatgtata tatgtatata ttatatataa cattatatat 960
attatgttac atatactata ttttatatgt tacatatact atatattata tgttacatat 1020
aatatatata acatatatta taatatgtaa catattatat ataacatata atatatagta 1080
tatata1086
<210>206
<211>406
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(406)
<223>染色体2的MAR基因基序;36233909..36234314
<400>206
attataaata tatattatag atattagata ttatagatat aatatatata atatatatta 60
tagatattat agatatagat ataatagata ttatagatat tatagatata atatatatta 120
tagatattat agatataata tatattatag atattataga tataatatat attatagata 180
ttatagatat aatatatatt atagatataa tatatattat agatattata gatatagata 240
ttatagatat tatatatatt atagatataa tatatattat agatattata gatatagata 300
ttatagatat aatatatatt atagatatta tagatataat atatattata gatattatag 360
atataatata tattatagat ataagatata ttatagatat tacaga406
<210>207
<211>797
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(797)
<223>染色体2的MAR基因基序;36271745..36272541
<400>207
atataaacat atacgtatat acacatatat acaaatacat atatacatat attatatata 60
tgtatatata ttatattata catatattat atatatatta tattatacat atatacatac 120
acacataaac atattacata catatacaaa ttatacacat atacatatat acatatatgt 180
atatacatac attatatata aatatatgta tataaaatgt acattatata tacatatata 240
ttatgtataa ataatatata aaataaacat aatatatatt tatagatatg atatatataa 300
tatatatgta tacatatata catatatgta tatataatgt acattataca tacataaaca 360
tcatatataa atgttatata tataatataa atatatataa tatataatat atactttata 420
tactatatat aatatatata atatgatata acatatacta tatatactat atataatata 480
tactatatat actgtatata atatataata taatatatac tatatatact aaatataata 540
tacataatat aatatatact atatataata tataatatat aatatagtat atatactata 600
tataataatt acatattata tattatacat tatatattat ataattatta tatataatta 660
tatattacat actttgtata taatgtaaat atacattaga atatataatg tatatatatg 720
tacatatata atgtatatat gtatacatta tataaactat atataaacat tatattatat 780
aaacattata tataaac797
<210>208
<211>423
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(423)
<223>染色体2的MAR基因基序;36498521..36498943
<400>208
tattatatta tatatttaat attatatatt taatatatta tatatttaat attatatatt 60
taatatatta tatatttaat attatatatt taatatatta tatatttaat attatatata 120
taatatatta tatatttaat attatatata taatattata tatataatat tatatattta 180
atattatata tataatatta tatatataat atattatata tttagtatta tgtatttaat 240
atattatata tttagtatta tgtatttaat atattattta tttagtatta tatatttaat 300
atattattta tttagtatta tatatttaat atattatata tttaatatat tatatattta 360
ttatatattg tatatttaat atattatata tttattatat attatatata attatatatt 420
taa423
<210>209
<211>304
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(304)
<223>染色体2的MAR基因基序;37179891..37180194
<400>209
gtgtatatat atcatatata ttatatcata tatatgtgta tatatatcat atattatatc 60
atatatatgt gtatatatat catatatata tcatatatgt gtatatatca tatatattat 120
atatcatata tgtgtatata tatcatatat tatatatcat atatatgtgt atatatcata 180
tatattatat atatctcata tgtgtatata tatcatatat aatatatatg tgtatatatc 240
atatatcata tataacatat atatgtgtat atatcatata tataacatat atcatatatg 300
tgta304
<210>210
<211>693
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(693)
<223>染色体2的MAR基因基序;38440448..38441140
<400>210
tatatattct tttatatatt atatataata tatattcttt tatatattat atatagtata 60
tattctttta tatattatat atagtatata ttcttttata tattatatat agtatatatt 120
cttttatata ttatatatag tatatattct tttatatatt atatatagta tatattcttt 180
tatatattat atatagtata tattctttta tatattatat atataatata tattctttta 240
tatatcatat ataatatata ttcttttata tattatatat aatatatatt cttttatata 300
ttatatatca tgtatatata atatacaaaa tatatataga ttttatatat agattattac 360
ataatagaat atattatata ttatatataa tatatacata atatataata ttatatatga 420
tataatatat atcatatata tcatataata tatattatat atcatatatt atatataata 480
atatatagat tatatataat tatatatata atatatataa ttatatatat tatctatata 540
tagataatat atataattat atataatata ttatatagat tatatataat tatattatat 600
acaaaatcta tatataatat atattatatt atatataata tacataacta tataaaaaat 660
ataatatata atatatataa tatataatat ata693
<210>211
<211>471
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(471)
<223>染色体2的MAR基因基序;38887582..38888052
<400>211
aacatatata ctatatatat tatatactat attatatatt atatatataa acatatatac 60
tatatataat atataaacat attatattat acatgatata gataaacata tatattatat 120
ataatataga taaaatatgt tatatataat ataatgtata gacatatatt atatatacat 180
atattctaca tatattatat atatattcta cacatattat attatatata catatattct 240
acatatatta tatatacata tattctacat atattatata tacatatatt ctacatatac 300
atatatacat atattatata tacatatatt atagatatat aatatataaa catatataat 360
attattatat ataatatata taataatatt atataatata taataatatt atatcttata 420
tataaataat atatatattt tatatatata atattatata tatataatat a471
<210>212
<211>1221
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding’
<222>(1)..(1221)
<223>染色体2的MAR基因基序;43885944..43887164
<400>212
catataaaca tatattatat gtaacatata aacatattat atgtaacata taatatataa 60
tatataaaca tatattttat atattatatg ttacatataa tatataatat ataaacatat 120
attatatatt atatgtaaca tataatatat aatatataaa catatatttt atatataata 180
tataaacata ttttatatat aatatataaa catattttat atataatata taaacatata 240
ttttatatat aatatataaa catattttat atataatata taaacatata ttttatataa 300
tatataaaca tataatatat ataatatata aaagtatata atataaatat atataatata 360
aacatatata atataaatat atataaaata taaacatatg taatatataa acatatatta 420
tatataatat ataaacatat attatacgta caatatataa acatatattg tacgtacaat 480
atataaacat atattatacg tacaatatat aaacatatat tatacgtaca atatataaac 540
atatattata cgtacaatat ataaacatat attatacgta caatatataa acatatatta 600
tacgtacaat atataaacat atattatacg tacaatatat aaacatatat tatacgtaca 660
atatataaac atatattata cgtacaatat ataaacatat attatacgta caataaacat 720
atattatacg tacaatatat aaacatatat tatacgtaca atatataaac atatattata 780
cgtacaatat ataaacatat attgtacgta caatatataa acatatatta tatgtataat 840
atataaacat ataatatata atatatatta tatatatgtt tattatatat gtttatatat 900
tatatataac atatattatt atattatata tgtttatata ttatatatta tataatatat 960
atgtttatat attatatatt atataatata tatgtttata tattatatat tatataatat 1020
atatgtttat atattatata ttatataata tatatgttta tatattatat attatataat 1080
atatatgttt atatattata tattatataa tatatatgtt tatatattat atattatata 1140
atatatatgt ttatatatta tatattatat aatatatatg tttatatatt atataaataa 1200
taaacttaca tattttatta a1221
<210>213
<211>543
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(543)
<223>染色体2的MAR基因基序;45818200..45818742
<400>213
tatgtatata tacatatata tttatacatg tatatatgta tatatacata tatatttata 60
catgtatata tatacatata tatttataca tgtatatata tacatatata tttatacatg 120
tatatatata catatatatt tatacatgta tgtatatata catatatatt tatacatgta 180
tgtatatata catatatatt tatacatgta tgtatatata catatatatt tatacatgta 240
tgtatatata catatatatt tatacatgta tgtatatata catatatatt tatacatgta 300
tgtatatata catatatatt tatacatgta tgtatatata catatatatt tatacatgta 360
tgtatatata catatatatt tatacatgta tgtatatata catatatatt tatacatgta 420
tgtatatata catgtatatt tatacatgta tgtatatata catgtatatt tatacatgta 480
tgtatatata catgtatatt tatacatgta tgtatatata catgtatatt tatacatgta 540
tac543
<210>214
<211>463
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(463)
<223>染色体2的MAR基因基序;47055478..47055940
<400>214
atacatacat atatacatat atacacatat atacatataa tacacacata tttacatata 60
tacacacata tatacatata tacatatata cacatatata catgcataca catatataca 120
tatatacaca catatacaca catatataca tatatacaca tatatacaca tatacacata 180
tatacacaca tatacatata tacacatata tacatatata catatataca cacatataca 240
catatataca tatacacata tatacacata tacatatata cacatatata cacatatata 300
catatataca catatataca tatatacaca tatatacaca catatacaca tatatacata 360
tatacatatg tatacacata tatacatatg tatacacata tatacacata tacatatata 420
catacacata tatacgtata tatgtgtata tatacacata tac463
<210>215
<211>2482
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(2482)
<223>染色体2的MAR基因基序;47492696..47495177
<400>215
aatatatata aaatatatta tattctatgt aatatataga atatataaaa tatattctat 60
atattatata gaatatatat tttataatat atattattta tatattttta tatatttata 120
ttatttatat atttatatat aatttatata atttatacat ataatttata tataatttat 180
ataaattata tatataattt atatataatt tatatataat ttatataaat tatatatata 240
atttatatat aatttatatg atttttatat ataatttata tataatttat ataattttta 300
tatataattt atatataatt tatataattt ttatatataa tttatataat atatatatat 360
aatttatata taatttatat aatttatata tataatttat atataattta tataatttat 420
atatataatt tatatataat ttatataatt tatatatata atttatatat aatttatata 480
atttatatat ataatttata cataatttat ataatttata tatataattt atataattta 540
tatatataat ttatatatat aatttatata atttatatat atgatttata taatttatat 600
atataattta tataatttat atatataaat tatatatata atttttatat aatttatata 660
tttataattt atatatttat ataatttata tatttataat ttatatattt atataattta 720
tatatttata atttatatat ttatataatt tatatataat tattcatata tttatataat 780
ttacatataa ttatttatat attcatatat aatttatata tttatatata atttatatat 840
aattatttac atatttatat atttatatat aatttatata tatttatata taatttataa 900
ataaaatata taatatataa tatataatat tataatagat aaaatatata ctatatatta 960
tatattttac attatattta atattatatg tataatttta tatcatatat aatatatatg 1020
atatatataa ttttatatca tatataatat atatggtata tataatttta tatcatatat 1080
aatatatatg gtatatataa ttttatatca tatataatat atgatatata attttatatc 1140
atataatata tattatatat aattttatat ctacatatta tatattatat atacaatttt 1200
atatctatct ataatatata ttatatatac aattttatat ctatataata tatattatat 1260
atacttttat attatatata aaatgtatat tatatatact tttatattat atataaaatg 1320
tatattatat ataattttat tttatatata aaatgtatat tatatataat tttattttat 1380
atataaaatg tatattatat ataattttat tttatatata aaatgtatat tatatataat 1440
tttattttat atataaaatg tatattatat ataattttat tttatataaa aaatgtatat 1500
tatatataat tttatattat atataatatg tatattatat ataattttat attatatata 1560
atatgtatat tatatataat tttatattat atataatatg tatattatat ataattttat 1620
attatatata atatgtatat tatatataat tttgtattat atataatatg tatattatat 1680
ataattttat attatatata atatgtatat tatatataat tttatattat atataatatg 1740
tatattatat ataattttat attatatata atatgtatat tatatataat tttatattat 1800
atataatatg tatattatat ataattttat attatatata aaatgtatat tatatataat 1860
tttatattat atataatatg tatattatat ataattttat attatatata atatgtatat 1920
tatatataat tttatattat atataaaatg tatattatat ataattttat attatatata 1980
aaatgtatat tatatatatt atatataaaa tgtatattat atatattata tataaaatgt 2040
atattatata tattatatat aaaatgtata ttatatatat tatatataaa atgtatatta 2100
tgtatattat atataatgta tattatgtat attatatata atgtatatta tatataatat 2160
atattatata taatgtatat tatataatat atattatata ttataatata taatatacat 2220
tatatattac atattatata taatatatta tatattatat attacatatt atatataata 2280
tattatatat tatattaaat atatatttta tatattatat attatatatt atataaaata 2340
tatatattat atattatata aaatatatat atattatatt atatattata ttaaatatat 2400
attttatata taatatatat aatatataat atataaaata tatattatat attatatata 2460
aattatatat attatatata aa2482
<210>216
<211>539
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(539)
<223>染色体2的MAR基因基序;47561069..47561607
<400>216
aacagtaata tatcactaat atataataat atataacagt aatatatcat taatatataa 60
tatatcatta gtatataata ttaatatata ttaatatata atatatcata tacaatatta 120
atatatatta atatataata atatattatt aatgtataat agtaatataa tatattatca 180
atatatatta ctaatatata ataatatatc gttaatatat aatagatcat taatatataa 240
tgttaatata ttatgaatag ataatatatc agtatataat attaatatat taatatatta 300
tatattattt aataatatat aatatattaa taaataatta tatattaata tagcaatata 360
ttaatatatg actgtattat attattaata tataacaata tattatatat tatataataa 420
tttattatat aatatataat aatatattat atattatata acatattaat aatacataat 480
aacattaata atatataata atgttaatat attattatat tatatattaa tatataata539
<210>217
<211>336
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(336)
<223>染色体2的MAR基因基序;52853648..52853983
<400>217
tatatacata aaatatatat attttatata tatacataat atatatatgt atattttatg 60
tatatatcta taatatatat aatataataa aatatacata tatattttat atatatataa 120
tatacatata aaatatacat acataaaata tacatgtata ttttatgtat atataatata 180
tatataaaat atacatgtat attttatata tataatatac atgtataatt aatatacatg 240
tatgttatat atattacatg tatattatat ataatataca tataaatttt aaatttagtg 300
tatattacat gtatattata tataatatat gtatat336
<210>218
<211>406
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(406)
<223>染色体2的MAR基因基序;54866263..54866668
<400>218
tacgtatata aaaatgtata tttacatata taaaataaat attttatata cgtatataaa 60
atatatattt attttatata cgtatataaa atatttattt tatatatgta tataaaatat 120
ttattttata tacatgtata ttaaatatat atttatatat gtatataaaa atatatatta 180
tatacatgta tataaaatat atattatata tgtatataaa aatatatatg tatataaaat 240
atatatatta tatagatata taaaatatat attatataga tatataaaat atatatatta 300
tatagatata taaaatatat atattatata gatatataaa atatatatat tatatagata 360
tataaaatat atatattata tagatatata aaatatatat attata406
<210>219
<211>1452
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1452)
<223>染色体2的MAR基因基序;55113305..55114756
<400>219
ataatatata atatatattg tatattatat tattatatat tatatattat taaatatata 60
tattatatta tatattatat aatatatatt atatataata atatagaata tataattata 120
tattatatta tatattatat aatatatatt atatataata atatagaata tataattata 180
tattatacta tatattatat aatatatatt atatataata atatagaata tataattata 240
tattatataa tatgtgaata atgtaatata taattatatt atttacatat tatataatat 300
ataattatat tatataatat ataattatat tatttgtata ttatatataa catatacatt 360
atattatata taatataatt atatataatt aattataaat taattatata taattatata 420
atataatata taatatacat aatatataat atataataca taatatacat aatataatat 480
atattatata taatataata tatataatat aatataatat aatgtataat ataattatat 540
attatatata atatataatg ttatataatt atattatatt atataattaa ttatatgtaa 600
ttaatataat ataattatta tatataattt tttatataat ataatatata attatataat 660
ataatataat tatattatat tatataatat atatatatta tataatataa tataattata 720
ttatataatt atataatata atataattat atattatatt atataataaa tataattata 780
taatataata tgattatata atatattatg tatattatat attatatatt gtattatgta 840
tattatatat tatatattat gtatattata tattatgtat attatatatt atgtatatta 900
tatattatat attatattat gtataatata ttatgtatgt tatatataat ataaattata 960
ttatatatta tgtatattat atataaatta tattatatat tatgtatatt atatataata 1020
taaagtatat attatgtata ttatatataa tataaagtat atattatgta tattatatat 1080
aatataaagt atatattatg tatattatat ataatataaa gtatatatta tgtatattat 1140
atataatata aagtatatat tatgtatatt atatataata taaagtatat attatgtata 1200
ttatatataa tataaagtat atattatgta tattatatat aatataaagt atatattatg 1260
tatattatat ataatataaa gtatatatta tgtatattat atataatata aagtatatat 1320
tatgtatatt atatataata taaagtatat attatgtata ttatatataa tataaagtat 1380
atattatgta tattatatat aatataaagt atatattata tgttataaat tatatattgt 1440
tatatattat at1452
<210>220
<211>502
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(502)
<223>染色体2的MAR基因基序;56350637..56351138
<400>220
atatattata gaaatataaa tatatagata tatctatata ttatagaaat ataaatatat 60
agatatatct atatattata gaaatataaa tatatagata tatctatata ttatagaaat 120
ataaatatat agatatacct atatattata gaaatataaa tatatagata tacctatata 180
ttatagaaat ataaatatat agatatacct atatattata gaaatataaa tatatagata 240
tatctatata ttatagaaat ataaatatat agatatatct atatattata gaaatataaa 300
tatatagata tatctatata ttatagaaat ataaatatat agatatatct atatattata 360
gaaatataaa tatatagata tatctatata ttatagaaat ataaatatat agatatatac 420
aacatatatg ttacatatta tatattatat atctatatat ctatataaca ttatatatct 480
atatatctat ataacatata ta502
<210>221
<211>794
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(794)
<223>染色体2的MAR基因基序;57051633..57052426
<400>221
aactatatat actatattat atagttatac tatatatact atattatata gttatataac60
tattatataa ctgtattata tagttatata actattatat aactgtatta tatagttata 120
taactattat ataactgtat tatatagtta tataactata ttatataact gtgttatata 180
gttatatatt atataactat attatataac tgtattatat agttatatat tatataacta 240
tattatataa ctgtattata tagttatata ttatataact atattatata actgtattat 300
atagttatat attatataac tgtattatat agttataaaa ctatattata taactgtatt 360
atatagttat aaaactacta tataactgta ttatataatt ataaaattat actatataac 420
tgtattatat agttataaaa ctatactata taactgtatt atatagttat aaaactatac 480
tatataactg tattatatag ttataaagct atactatata actgtattat atagttatat 540
aactatacta tataactgta ttatatagtt ataaaactat actatataac tgtattatat 600
agttataaaa ttatattata taactgtatt atatagttat ataactatat tatataactg 660
tattatatag ttatataact atattatata agtgtattat atagttatat aactatatta 720
tataactgta ttatacagtt atataactat attatataac tgtattatat acttatataa 780
ctatattata taac794
<210>222
<211>300
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(300)
<223>染色体2的MAR基因基序;57069272..57069571
<400>222
acacatacat atatgtatat atgcacacac atatatatgt atatatacac atacatatat 60
gtatatatac atatatgtat atacgcacat acatatatgt atatatacac gtacatatat 120
gtctctatat atacacatac acatatgtat atacatatat gtgtatatat acacaatcat 180
atatgtatat acatatatac acatatacac aaacatatat gtatatacat atatgtatat 240
acatatatac acatatacac aaacatatat gtatatacat atatgtatat acatacacaa 300
<210>223
<211>370
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(370)
<223>染色体2的MAR基因基序;57235143..57235512
<400>223
tatttttata tataactata tatattttat atataaatta tatatatgat catatatata 60
atcatatata taatcatata tgattatata tgatcatata tatatttata tatataatta 120
tatatactta tatataatta tatatatatt tatatatata attatgtata cttatatata 180
tttatatata taattatata tacaatttat atatataatt atatataatt tatatataat 240
tatatatata aattatatat aagtatatat aattatatat atgtttatat ataattatat 300
atataaatga tatgtataat atataactat atataattat atataaatat atatatagat 360
tttatatata370
<210>224
<211>306
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(306)
<223>染色体2的MAR基因基序;57693125..57693430
<400>224
tacgtatata cacgtataaa tataaatata tacatgtata tacgtatata catgtataaa 60
tataaatata tatatgtata tacgtatata catgtataaa tatatatatg tatatacgta 120
tatacatgta taaatatata tatatgtata tacgtatata catgtataaa tatatataca 180
tgtatatacg tatgttgtgt atacatacaa atctgtacat atatacatat atgttgtgtg 240
tatatataca tctatacatg tgtatgcgta tatatgtata tgtatatata gtatatataa 300
tacatg306
<210>225
<211>500
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(500)
<223>染色体2的MAR基因基序;59810331..59810830
<400>225
tttattatat gtaatatata ttgtattatt atatatatta tatataatat atattgtatt 60
attatatata ttatatataa tatatattgt attattatat atattatata taatatatat 120
tgtattatta tatatattat atataatata tattgtatat tatatatatt atatattata 180
ttattatata ttatatatat tatattatta tatattatat attatatata ttatattata 240
tattatatat tatattatat atattatatt atatattata tattatatta tatatattat 300
attatatatt atatattata ttatatatat tatattatat atattatata ttatatatta 360
tatatattat atattatata ttatatatat tatatattat atataatata tattatatta 420
ttatataata ttatatatta tatatattat atattatata taatatatat tatattatta 480
tataatatta tatattatat500
<210>226
<211>565
<212>DNA
<213>Homo sapiens
<220>
<221>misc binding
<222>(1)..(565)
<223>染色体2的MAR基因基序;59974589..59975153
<400>226
atatatgtat aatatgtata tatgtatata ttatgtatat gttatatatg taatatatgt 60
atgtatatat tatatatcat atataatata taatgtgtat atatgtatat atgtatgtat 120
acatgtatat actatgtata tattgtatat attatatatg tatatataca tatacatata 180
taatatatac atatattata tacaatatat acatgtatat tatatacgat atatacatat 240
atattatata caatatatac atagtatata aatgtataca tacatacata tatacatatt 300
atatatgtat atatgtatac ataaatgtat atataatata tatacatata taaatgtata 360
catacgtaca tatacgtata tgtatatgca tatatgtata tatgtgcata catatatatg 420
tatatacata tatgtacata tgtacatata cgtatatatg tacatatgta catatacgta 480
tatatgtaca tatgtacata tacgtatata tgtacatatg tacatatacg tatatatgta 540
catatgtaca tatatacata tatat565
<210>227
<211>427
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(427)
<223>染色体2的MAR基因基序;60605573..60605999
<400>227
tatataatgt atataatgga tatagatata gatatagata tatattttat ataatatata 60
ttatatatta tatataatat atgttatata tattatatat tttatataat atatatatta 120
tataaattat atatatataa tatataatat atatattata tatattttat ataatatata 180
tttaatatta tctattatat attttatata atatatattt tatataatat ataatatata 240
atatatattt tacataatat ataatatata atacgtatta tatataatat ataatacgta 300
ttttatataa tatataatac gtattatata taatacgtat tatatattat ataatatata 360
atacgtatta tataatatac gtaattatat tttattataa tacgtattat atattatata 420
atatata427
<210>228
<211>1199
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1199)
<223>染色体2的MAR基因基序;61229949..61231147
<400>228
gtatacatat ataaagtgta tatataatgt atatacatat atacatatat aaagtatata 60
tataatatat acatatataa agtatatata taatatatac atatataaag tatatataat 120
atatacatat ataaagtata tataatatat acatatataa agtatatata tcatatatac 180
atatataaag tatatatata atatatacat atatacatat ataaagtata tataacatat 240
atacatatat aaagtatata taacatatat acatatataa agtatatata taatatatac 300
atatatacat atataaagta tatataacat atatacatat atacagtata tataacatat 360
atacatatat acagtatata taacatatat acatatatac agtatatata acatatatac 420
atatatacag tatatataac atatatacat atatacatga agtatatata acatatatac 480
atatatacat gaagtatata taacatatat acatatatac atgaagtata tataacatat 540
atacatatat acatgaagta tatataacat atatacatat atacatatat aaagtatata 600
taacatatac atatatacat atataaagta taacatatac atatatacat atataaagta 660
tatataatat ataacatata catatataaa gtatatataa tatataacat atacatatat 720
aaagtatata taatatataa catatacata tataaagtat atataatata tacatatata 780
catatataaa gtatatataa tatatatata catatataaa gtatatataa tatatataca 840
tatatacata tataaagtat atataatata tatacatata taaagtatat ataatatata 900
tacatatata catatataaa gtatatataa tatatataca tatatacata tataaagtat 960
atataatata tatacatata tacatatata aagtatatat aatatatata catatataca 1020
tatataaagt atatataata tatatacata tatacatata taaagtatat ataatatata 1080
tacatatata catatataaa gtatatataa tatgtataca tatatacata tataaagtat 1140
atataatatg tatacatata tacatatata aagtatatat ataatatgta tacatatat1199
<210>229
<211>454
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(454)
<223>染色体2的MAR基因基序;62181058..62181511
<400>229
tatatatcat atattatata tgatatatat tatgtatata atacatatta tatataataa 60
atatttatta tatatgatat atattatgta tataatacat attatatata ataaatatat 120
attatattat atataataaa tatatattat attatatata atatatattt atatataaat 180
atattatata taaatatata ttatatataa aatatttata tattatatat aaatatatat 240
tatatataaa tatttatata ttatatataa atatttatat attatatata aatatttata 300
tattatatat aaaatatatt atatatatta tatatattat atattatata taatatattt 360
aatatataat atataaacat atattatata taatatataa acatatataa atatatttat 420
atataataga taaaaatata tataatatat ataa454
<210>230
<211>658
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(658)
<223>染色体2的MAR基因基序;62190919..62191576
<400>230
tatatacaca actatatata taactatata tatacaacta tatatacaac tatatatata 60
actatatata taactatata taactatata tataactata tataactata tatataacta 120
tatatataac tatatataac tatatatata actatatata actatatata actatatata 180
taactatata tataactata tatataacta tatatataac tatatatact atatatataa 240
ctatatatat ataactatat atataactat atatatataa ctatatataa ctatatatat 300
ataactatat atataactat atatatataa ctatatatat aactatatat atataactat 360
atatataact atatatatat aactatatat aactatatat atataactat atatataact 420
atatatatat aactatatat ataactatat atatataact atatatataa ctatatatat 480
ataactatat atataactat atatataact atatatataa ctatatatat ataactatat 540
atataactat atatatataa ctatatatat aactatatat ataactatat atataactat 600
atatatataa ctatatatat aactatatat atataactat atatataact atatatat658
<210>231
<211>1486
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(1486)
<223>染色体2的MAR基因基序;62384127..62385612
<400>231
attatatcta atctattata tattatatct aatacatatt atatctaatc tattgtatat 60
tatatctaat atataatata ttatatataa tatattatat attatatatt atatacaata 120
tattatatat tatataatat ataatatatt atatataata tattatatct aatatattac 180
atattatatc taatctatta tagatataat atgtaatata ttatatatta tatctaatag 240
atattagata taatatataa tatattatta atataatata ttagatataa tatataatat 300
aataatatat aatatatatt attggtaata tataatatat aattaataat atatattata 360
tataattatt atgaataata tatcatatat aatatctagt atattatata ttaataacat 420
ataaatatta tattaataat aaataacata ttaatattat attaataata tataatatac 480
taatattata ttaataatat ataatatact aatattatat taataatata taatatacta 540
atattatatt aataatatat aatatactaa tattatatta ataatatata atatactaat 600
attatattaa taatatataa tatactaata tattaagaat atataatata ctaatatatt 660
aagaatatat aatatactaa tattatatta ataatatata tttatattaa taatatatta 720
attattatta attaattatt aataattata taatattgat tatattaata ttatcaattt 780
aataatattg attatatatt atatattata tattatatat tatatattat atattatata 840
ttatatatta ataatatata ttagatataa tataatatat taataatata taagatataa 900
tataatatat taataatata tattagatat aatataatat attaataata tatattagat 960
ataatataat atattaataa tatatattag atataatata atatattaat aatatatatt 1020
agatgtaata taatatatta ataatatata ttagatgtaa tataatatat taataatata 1080
tattagatgt aatataatat attaataata tatattagat gtaatataat atattaataa 1140
tatatattag atgtaatata atatattaat aatatatatt agatgtaata taatatatta 1200
ataatatata ttagatgtaa tataatatat taatatatat tagatgtaat ataatatatt 1260
aataatatat attagatata atataatata ttaataatat attagatata atataatata 1320
ttaataatat ataagatata atataatata ttaataatat ataagatata atataatata 1380
ttaataatat ataagatata atataatata ttaataatat atattagata tataatatat 1440
taataatata tattagatat ctaatatcta ttagatatct aataga1486
<210>232
<211>333
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(333)
<223>染色体2的MAR基因基序;62538649..62538981
<400>232
ttatatatat tatatatata tattttatat atatattata tatatatttt atatatatat 60
tatatatata ttttatatat atattatata tatattttat atatatatta tatatatatt 120
ttatatatat tatatatata ttttatatat attatatata tattttatat atatattata 180
tatatatttt atatatatat tatatatata ttttatatat atattatata tatattttat 240
atatatatta tatatatatt ttatatatat attatatata tattttatat atatattata 300
tatatatttt atatatatat tatatatata ttt333
<210>233
<211>480
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(480)
<223>染色体2的MAR基因基序;63240325..63240804
<400>233
tatatataaa atatatattt tttaaatata aaatatatat atattttaat attaatatat 60
atatatttta atatataata tatatattat atattttata tataaaatat atatattata 120
tattttatat ataaaatata tatattatat attttatata ttaaaatata tattttatat 180
attttaatta ttaaaatata tatattatat attttaaata taaaatatat atattatata 240
ttttaatata taaaatatat atattatata ttttaatata taaaatatat atattttata 300
tttatatata taaatatata tattatatat tttaatatat aaaatatata tattatatat 360
tttaatatat aaaatatata tattatatat tttaatatat aaaatatata tattatatat 420
tttaatatat ataaaatata tatattatat attttatata tattaaatat atattttata 480
<210>234
<211>302
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(302)
<223>染色体2的MAR基因基序;63935480..63935781
<400>234
atatatataa atatatatat aattatatat agatatatat aattatatat agatatatat 60
attctatatt ctatatatat ataatatata atatataaat tatatataga atatatatta 120
tatataatat attatatata ttatatataa tatatatatt atatatatta tatataatat 180
atatattata tatattatat ataatttata tatattatat atagaatata tattatatat 240
agaatataga atatatataa tatatataga atacagaata tatatagaat atagaatata 300
ta302
<210>235
<211>407
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(407)
<223>染色体2的MAR基因基序;63935888..63936294
<400>235
tataatatat taatataata tatagacagt atataatata atatacagac agtatataat 60
atacagacag tatataatat ataatattat atataatatt atatataata ttatataata 120
tattatatta tatatattat ataatatatt atattatata taatatatgt aatattatat 180
attatattat acataatata ttatatataa tatattatat ataatattat atatattata 240
tataatatat ataataataa tattataata tataatatat aatagtacag tatatattat 300
atatataatt ctatatataa tatatagaat tctatctatt tataatatat atagaattct 360
atatataata tataatatac agaattctat atatattata tatagaa407
<210>236
<211>302
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(302)
<223>染色体2的MAR基因基序;66958350..66958651
<400>236
tattatatat attgtatata tatgtatatt atatatattg tatatataat gtatattata 60
tatattatat atatatgtat attatatata ttgtatatat atgtatatta tatatattgt 120
atatatgtat atgtatatat gtatgtgtat atatatacac atatacacat atatgtgtat 180
gtatatatat gtgtgtatat acgtatatat acatatatac aatttttgta tatatacata 240
tatacacata tatatgtgta tgtgtatata tatacacata tatgtgtgtg tatatacaca 300
ta302
<210>237
<211>651
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(651)
<223>染色体2的MAR基因基序;68307125..68307775
<400>237
gatattatat attgtatata ttatatatgt atataatata ctattatata ttatatatgt 60
atataatttt attaatatat atattatatt atattatata ttatattata ttatattata 120
tatataatat taatattata tattattata tattatatta tattaatatt atatatatat 180
aatatatata atatatataa tagtattata tataatatat ataatagtat tatatattat 240
atatatataa tactattata tatattatat ataatagtat tatatatatt atatatataa 300
tactattata tataatatat actattatat aatatatata atactattat atatattata 360
tataatacta ttatatataa tatatataat actattatat ataatatata taatactatt 420
atatataata tatataatac tattatatat aatatatata atactattat atataatata 480
tataatacta ttatatataa tatatatatt atatataatt atattaatat ataatagtat 540
catatataat aatagtatat ataatatata atatatatat tatatatatt ataatagtat 600
atataacata taatatagta tatatattat atattatata taaaatattt a651
<210>238
<211>367
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(367)
<223>染色体2的MAR基因基序;68308243..68308609
<400>238
atatatatat atgagtcaac catacacata tatatatata atgtttatat atataatgta 60
tatatataat gtttatatat aatgtatata tataatgttt atatatataa tgtatatata 120
taatgtttat atatataatg tatatatata atgtttatat atataatgtg tatatataat 180
gtttatatat ataatgtgta tatataatgt ttatatataa tgtgtatata taatgtttat 240
atatataatg tgtatatata atgtttatat atataatgtg tatatataat gtttatatat 300
ataatgtgta tatatataat gtttatatat ataatgtgta tatatataat gtttatatat 360
ataatgt367
<210>239
<211>499
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(499)
<223>染色体2的MAR基因基序;410241..410739
<400>239
ataatatgta tatatattat attatatatt atattacata ttatatatta tattacatat 60
tatatattta tatattacat attatatatt atattttata ttatatatta tatcatatat 120
atgttatgca ttatataata cataatatat tatatatgat ataatatata ttatatatta 180
ttatatataa tataattaat atattatgta ttatataata tatattatgt tataatatat 240
aatatatatt atataattat ataatatatt atgtattata taatatatat tatgttataa 300
tatattatat tatatatatt atatatatat tatatatata atgtatatta tatataatac 360
ataatatatt atatattata tattatttta tataatatat tatataatgt gatatattat 420
ataatatatt atataacata gtatattata taatatatta tataatgtaa tatattatat 480
attatataat atattgtat499
<210>240
<211>402
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(402)
<223>染色体2的MAR基因基序;31531..31932
<400>240
cacattatat atataaacat tatatatata cacattatat atataaacat tatatatata 60
cacattatat atataaacat tatatataca cattatatat ataaacatta tatatacaca 120
ttatatatat aaacattata tatacaaatt atatatataa acattatata tacaaattat 180
atatataaac attatatata tacattatat atataaacat tatatatata cattatatat 240
ataaacatta tatatataca ttatatatat aaacattata tatatacatt atatatataa 300
acattatata tatacattat atatataaac gttatatata tacattatat atataaacat 360
tatatgtata cattatatat ataaacatta tatatatatg tg402
<210>241
<211>421
<212>DNA
<213>Homo sapiens
<220>
<221>misc_binding
<222>(1)..(421)
<223>染色体2的MAR基因基序;32415..32835
<400>241
ataaatattt tatatataat atataatata tatactatat tatatgttat atatactatt60
ataatatata taatatatat attatatatt atatatacta ttattatata tgatactatt120
atatattaat ataattatat ataatatata tattatataa tatactatta tatattatat180
ataatagtat attatataat atatatatta tatataatag tattatatat actattatat240
attatatata ttatatatat ataaaatata atataatata tataatatat aatattaata300
ttatatatat aatataatat aatatataat ataatataat atatatatta ataaaattat360
attaatatat aatatataat agtatattat atacatatat aatatataca atatataata420
t421
Claims (11)
1.一种纯化及分离的具有提高的蛋白产量活性的DNA序列,其特征在于,所述DNA序列包括:
a)选自序列SEQ ID No 1至27的MAR核苷酸序列;或者
b)鸡溶菌酶基因5’MAR元件或片段,包括选自B、K和F区中至少一个区。
2.一种纯化及分离的具有提高的蛋白产量活性的鸡溶菌酶基因5’MAR元件或片段,由选自B、K和F区的至少一个鸡溶菌酶基因5’MAR区组成。
3.一种合成MAR序列,由包含根据权利要求2所述的鸡溶菌酶基因5’MAR元件和/或片段的序列组成。
4.根据权利要求3所述的合成MAR序列,其特征在于,所述连接序列是BgIII-BamHI连接子。
5.一种纯化及分离的MAR DNA序列用于提高真核宿主细胞中的蛋白产量活性的用途,其中MAR DNA序列选自包括如下的组中:
-根据权利要求1所述的纯化及分离的DNA序列,
-根据权利要求2所述的一种纯化及分离的鸡溶菌酶基因5’MAR元件或片段,以及
-根据权利要求3或4所述的合成MAR序列。
6.一种用于转染真核宿主细胞的方法,所述方法包括:
a)向所述真核宿主细胞中引入至少一个包括至少一个用于可操作地连接到启动子上的编码有关蛋白的基因的纯化DNA序列和至少一个选自下组的纯化及分离的MAR DNA序列,该组包括:
-权利要求1所述的纯化及分离的DNA序列,
-权利要求2所述的一种纯化及分离的鸡溶菌酶基因5’MAR元件或片段,以及
-权利要求3或4所述的合成MAR序列;
b)在宿主细胞刚进入第二细胞分裂周期的时刻用至少一个包括至少一个用于可操作地连接到启动子上的编码有关蛋白的基因的纯化DNA序列和至少一个选自下组的的纯化和分离的MAR DNA序列对所述转染的真核宿主细胞实施至少一次另外的转染步骤,该组包括:
-权利要求1所述的纯化及分离的DNA序列,
-权利要求2所述的一种纯化及分离的鸡溶菌酶基因5’MAR元件或片段,以及
-权利要求3或4所述的合成MAR序列;
c)挑选出所述转染的真核宿主细胞。
7.根据权利要求6所述的方法,其特征在于,所述挑选的转染真核宿主细胞是高产的蛋白生产细胞,其产率至少为10pg/细胞·天。
8.根据权利要求6所述的方法,其特征在于,所述MAR DNA序列是权利要求1所述的纯化和分离的DNA序列。
9.一种用于转染真核宿主细胞的方法,所述方法包括:将在第一载体内的可操作地连接到启动子上的编码有关蛋白的第一DNA序列,以及结合到第二载体上的选自下组的第二DNA序列共转染到所述真核宿主细胞内,该组包括:
-权利要求1所述的纯化和分离的DNA序列,
-权利要求2所述的纯化和分离的鸡溶菌酶基因5’MAR元件或片段,
-权利要求3或4所述的合成MAR序列。
10.一种用于制备重组蛋白的方法,其中
a)通过根据权利要求6至8或权利要求9中任一项所述的方法转染真核宿主细胞,
b)所述转染的细胞在适于表达所述蛋白的条件下在培养基中培养,以及
b)从所述细胞中回收所述蛋白。
11.一种通过根据权利要求6至8或权利要求9中任一项所述的方法转染的真核宿主细胞。
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PCT/EP2004/011974 WO2005040377A2 (en) | 2003-10-24 | 2004-10-22 | High efficiency gene transfer and expression in mammalian cells by a multiple transfection procedure of matrix attachment region sequences |
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