CN110205381B - 用于阿尔茨海默症检测的血细胞转录基因标志物及其应用 - Google Patents
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Abstract
本发明公开了一种用于阿尔茨海默症检测的外周血细胞转录基因标志物，所述基因标志物包含：SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列。本发明还公开了上述基因标志物在制备检测阿尔茨海默症的产品中的应用。本发明以临床上最易采集的外周血为检测样本，通过分析阿尔茨海默症引起的血细胞特征性基因表达信号变化，用于阿尔茨海默症的甄别诊断，敏感性高、特异性强，安全简便，可以作为脑组织活检的替代品，为阿尔茨海默症等中枢神经退行性疾病的检测提供了新的客观分子指标，有助于解决中枢神经疾病无法通过活组织取样进行诊断的难题，应用前景广阔。
Description
技术领域
本发明涉及分子生物学技术领域，尤其涉及一种用于阿尔茨海默症检测的血细胞转录基因标志物及其应用。
背景技术
阿尔茨海默症(Alzheimer’s Disease)是一种具有年龄相关性的神经退行性疾病，主要临床特征包括进行性记忆减退、认知功能障碍、行为障碍及日常生活能力下降等。据阿尔茨海默病国际协会(Alzheimer’s Disease International，ADI)2018年发布的公告，目前全球痴呆总人数已达5000万(Patterson,C.The State of the Art of DementiaResearch:New Frontiers.An Analysis of Prevalence,Incidence,Cost andTrends.Alzheimer’s Disease International.World Alzheimer Report 2018)，在整个痴呆人群中，AD可占50％～70％(Jia JP,The prevalence of dementia in urban andrural areas of China.[J].Alzheimer’s&Dementia,2014,10(1):1-9)。随着年龄的增长，发病率的迅速上升，加上疾病持续时间相对较长，在很大程度上导致了该病在世界范围内的高患病率。据统计，全球有13％的65岁以上老年人患有AD，而85岁以上老年人的患病率则高达45％。预计到2050年，全世界将有8000万人遭受AD的困扰(Humpel C.Identifying andvalidating biomarkers for Alzheimer’s disease.[J].Trends in Biotechnology,2011,29(1):26-32)。
目前，阿尔茨海默症的治疗是世界公认的医学难题。由于阿兹海默症存在长达15至20年的临床前期，该期患者脑内已经出现特异性病理改变，但无临床症状，随着疾病进展最终出现认知损害等临床表现，得到AD临床诊断的患者多数已处于中晚期，仅有有限的药物可以暂时缓解其症状。因此，AD的早期识别和干预是临床实践中的重点，也是难点。
长期以来，人类对中枢神经系统的疾病，尤其是非占位性疾病的研究颇有些力不从心。因为多数中枢神经疾病的早期、甚至中期，其临床表现很相似，除非到了后期，在疾病特异性的表现出现以后，方才能明确诊断。在此之前，由于缺乏脑组织的病理活检支持，诊断往往似是而非。虽然由于血-脑屏障的存在，大脑组织被认为很高程度地与血液隔绝，还是有不少学者专家致力于血液细胞的基因表达，是否能够找到“脑组织细胞”的替代品进行相应疾病的研究。
在阿尔茨海默症的血液转录研究方面，有学者分析了已发表的关于AD患者血液转录组的数据(Han G,Wang J,Zeng F,et al.Characteristic transformation of bloodtranscriptome in Alzheimer's disease.[J].Journal of Alzheimers Disease Jad,2013,35(2):373-386)，揭示了其细胞功能单元的特征性干扰，包括环境反应(免疫反应、生存/死亡信号和细胞循环)的上调和核心代谢(能量代谢和翻译/剪接)的下调，这种干扰是血液转录组在其他神经系统或者更复杂的疾病中独一无二的，并且在AD和轻度认知功能障碍(mild cognitive impairment,MCI,被认为是阿尔茨海默症的前兆)患者中组都存在，最终在此基础上得出了结论：阿尔兹海默病患者血液转录组的变化是疾病机制的一个组成部分，且该种转变可作为阿尔兹海默病早期诊断和监测的可靠生物标志物，有助于早期诊断和监测的目的。
上述阿尔茨海默症的血液转录研究从分子机制上解释了通过检测血液mRNA基因表达变化检测阿尔茨海默症的理论可能性，但并没有给出实际检测阿尔茨海默症的方法和技术方案，以及对阿尔茨海默症的主要诊断性能指标。因此，面对人口老龄化带来的阿尔茨海默症严峻发病形势，临床上迫切需要一种无创、简便、准确检测阿尔茨海默症的技术。
发明内容
本发明要解决阿尔茨海默症等中枢神经系统疾病难以通过组织活检进行诊断的技术问题，以血细胞作为组织细胞的替代品，提供一种用于检测阿尔茨海默症的血细胞转录基因标志物(信使RNA，message RNA)，该标志物用于阿尔茨海默症的检测，能够很灵敏的监测脑组织中的神经元细胞病变，具有很高的检测准确性、敏感性和特异性，而且采用临床上最易采集的外周血进行检测，以无创性的血细胞基因表达检测替代脑组织取样活检，取样安全简便，是阿尔茨海默症早期检测的理想技术。
为了解决上述技术问题，本发明通过如下技术方案实现:
在本发明的一个方面，提供了一种包含多个多核苷酸或其片段的组合产品，所述多个多核苷酸在阿尔茨海默症与同年龄分布正常人群的外周血细胞中差异表达，该多个多核苷酸的序列为SEQ ID NO.1～SEQ ID NO.10所示的阿尔茨海默症的血细胞特征基因序列。
在本发明的另一方面，提供了一种组合物，其包含用于检测在阿尔茨海默症与同年龄分布正常人群的外周血细胞中基因差异表达的引物和/或探针，所述基因的序列包括SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列。
在本发明的另一方面，还提供了上述包含多个多核苷酸或其片段的组合产品的用途，用于制备检测阿尔茨海默症的产品。
优选的，所述检测阿尔茨海默症的产品包括：用实时定量PCR、RNA测序、基因芯片对阿尔茨海默症进行检测的产品。
所述用实时定量PCR检测阿尔茨海默症的产品包含特异扩增SEQ ID NO.1～SEQID NO.10所示阿尔茨海默症的血细胞特征基因序列的引物。
所述用RNA测序检测阿尔茨海默症的产品包含检测SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列的信使RNA序列。
所述用基因芯片检测阿尔茨海默症的产品包含：与SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列杂交的探针。
在本发明的另一方面，还提供了一种用于阿尔茨海默症检测的试剂盒，该试剂盒包含特异性针对SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列的引物。
优选的，所述引物的序列如SEQ ID NO.11～SEQ ID NO.30所示。
在本发明的另一方面，还提供了一种用于阿尔茨海默症检测的试剂盒，该试剂盒包含特异性针对SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列的探针。
优选的，所述探针的序列包括SEQ ID NO.31～SEQ ID NO.40所示的核苷酸序列。
在本发明的另一方面，还提供了一种用于阿尔茨海默症检测的基因芯片，所述基因芯片包含与SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列杂交的寡核苷酸探针。
利用本发明的试剂盒或基因芯片，可以检测受检者外周血细胞中SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症特征基因序列的表达情况，然后根据这些基因表达上调或下调的信息结合boosting算法等统计学方法构建预测模型，判别受检者患阿尔茨海默症的概率，从而实现检测阿尔茨海默症的目的。
本发明用于阿尔茨海默症检测的血细胞转录基因标志物，应用于阿尔茨海默症的早期诊断和检测，敏感性高、特异性强，准确性超过80％。而且，本发明基于血细胞转录基因标志物(mRNA)的阿尔茨海默症检测方法，以临床上最易采集的外周血为检测样本，利用血细胞作为脑组织细胞检查的替代品，取代了创伤性的脑组织活检取样，安全简便，特别适用于阿尔茨海默症等难以进行组织活检的中枢神经疾病的诊断，具有广阔的应用前景。
附图说明
下面结合附图和具体实施方式对本发明作进一步详细的说明。
图1是本发明基于10个外周血细胞转录基因标志物构建的预测模型对285例阿尔茨海默症样本和240例同年龄分布正常对照样本的分类结果图；
图2是本发明利用10个外周血细胞转录基因标志物构建的预测模型对阿尔茨海默症诊断的ROC AUC图。
具体实施方式
本发明是以血细胞的基因表达检测为基础，通过定量分析外周血细胞的基因(信使RNA)表达状况，比较阿尔茨海默症与同年龄分布正常对照人群的外周血细胞基因表达差异，通过特征递归消除(Recursive Feature Elimination)方法从血细胞基因表达谱中筛选出10个阿尔茨海默症引起的血细胞特征性基因表达变化(基因表达上调或下调)，并将这10个阿尔茨海默症的特征性基因表达信号作为标志物，构建诊断模型，用于阿尔茨海默症的检测。通过荧光定量RT-PCR、基因表达谱芯片或RNA测序技术定量检测受检者外周血中这10个阿尔茨海默症基因标志物的相对表达量，并输入基于boosting算法构建的预测模型中，得到样本为阿尔茨海默症的概率，从而判别受检者是否患阿尔茨海默症。
实施例1阿尔茨海默症的血细胞特征基因标志物筛选
阿尔茨海默症的血细胞特征基因标志物筛选包括以下步骤：
1)采集195例确诊为阿尔茨海默症的患者、172例同年龄分布正常人群的外周肘静脉血样本(2ML/人)，采用Affymetrix Gene Expression Using Affymetrix U133Plus 2.0人类全基因表达谱芯片检测上述样本的血细胞基因表达谱。
2)利用Affymetrix MAS5芯片归一化方法(normalization)对上述每个血液样本的基因表达谱数据进行归一化处理。
3)选择在所有样本中均有适度表达的血细胞基因表达信号进行后续分析。
4)用特征递归消除方法筛选阿尔茨海默症引起的血细胞特征性基因表达信号，获得对阿尔茨海默症具有最高预测准确性(accuracy)的10个基因作为基因标志物。
5)采用实时荧光定量PCR方法对上述10个阿尔茨海默症的血细胞特征基因进行检测，结果显示10个特征基因在PCR平台与表达谱芯片平台的检测结果一致，10个阿尔茨海默症标志物的基因序列如下表1所示。
表1 10个阿尔茨海默症基因标志物的基因序列
6)基于筛选得到的10个基因标志物，利用boosting算法构建用于阿尔茨海默症诊断的多个分类器ft(x)，每个分类器都有一定的权重αt，把多个分类器预测结果进行加权，形成了最终的预测结果：
其中，x为10个基因标志物的信号；
ft(x)为构建的t个分类器(t＝1,2,…t)，αt为每一分类器在最终预测结果中所占的权重(t＝1,…,t)。分类器ft(x)的输出值为+1或-1，分别对应于阿尔茨海默症和非疾病；
F(x)为将t个分类器ft(x)进行加权计算后得到的最终预测结果，结果值为+1或-1，分别对应于阿尔茨海默症和非疾病。
实施例2利用筛选出的基因标志物对阿尔茨海默症患者及正常人群进行甄别诊断
1.方法步骤：
1)待检测样本外周血样品的收集：使用QIAGEN公司的BD PAXgeneRNA采血管收集受检者的肘静脉血样本(2ML/人)；
2)待检测样本外周血样品中总RNA的提取纯化：使用QIAGEN公司的PAXgeneBloodRNA Kit提取纯化外周血中的总RNA，并用Agilent BioAnalyzer 2100型微量电泳分析仪鉴定提取的总RNA片段完整性和产量；
3)反转录反应：使用Life Techonolgy公司的High-Capacity cDNA ReverseTranscription kit反转录试剂盒，使用总RNA为模板，以Olig(dT)为逆转录引物，进行逆转录反应合成cDNA；
4)荧光定量RT-PCR检测：根据10个阿尔茨海默症特征基因标志物(SEQ ID NO.1～SEQ ID NO.10)，设计特异性引物SEQ ID NO.11～SEQ ID NO.30(其中，引物SEQ ID NO.11～SEQ ID NO.12用于特异性扩增SEQ ID NO.1基因标志物，引物SEQ ID NO.13～SEQ IDNO.14用于特异性扩增SEQ ID NO.2基因标志物，引物SEQ ID NO.15～SEQ ID NO.16用于特异性扩增SEQ ID NO.3基因标志物，引物SEQ ID NO.17～SEQ ID NO.18用于特异性扩增SEQID NO.4基因标志物，引物SEQ ID NO.19～SEQ ID NO.20用于特异性扩增SEQ ID NO.5基因标志物，引物SEQ ID NO.21～SEQ ID NO.22用于特异性扩增SEQ ID NO.6基因标志物，引物SEQ ID NO.23～SEQ ID NO.24用于特异性扩增SEQ ID NO.7基因标志物，引物SEQ IDNO.25～SEQ ID NO.26用于特异性扩增SEQ ID NO.8基因标志物，引物SEQ ID NO.27～SEQID NO.28用于特异性扩增SEQ ID NO.9基因标志物，引物SEQ ID NO.29～SEQ ID NO.30用于特异性扩增SEQ ID NO.10基因标志物)，并设计特异性探针SEQ ID NO.31～SEQ IDNO.40(其中SEQ ID NO.31～SEQ ID NO.40分别为SEQ ID NO.1～SEQ ID NO.10特征基因序列的探针序列)，以该SEQ ID NO.11～SEQ ID NO.30为引物，以SEQ ID NO.31～SEQ IDNO.40为探针或者采用可与PCR扩增片段非特异性结合的SYBR Green染料，利用反转录获得的cDNA作为扩增模板，进行实时荧光定量RT-PCR反应，获得该10个基因标志物在外周血样本中的mRNA相对含量；
荧光定量PCR扩增引物序列如下：
RPL36AL基因
正向引物：5'AGGTGTCGGGCGCTGTT 3'(SEQ ID NO.11)
反向引物：5'TCTTTGCAGCAGGGCTGTT 3'(SEQ ID NO.12)
C1orf132基因
正向引物：5'CGACACCATCAGTCTGCTCTTAGA 3'(SEQ ID NO.13)
反向引物：5'GGTGCCCCGCAATCAAC 3'(SEQ ID NO.14)
RPS27A基因
正向引物：5'GCACCGGGTTGGATTGTC 3'(SEQ ID NO.15)
反向引物：5'CTTAGGCGACCACACCAAATG 3'(SEQ ID NO.16)
SNTB2基因
正向引物：5'CCAGCCTGCTTGAGGAGTAGA 3'(SEQ ID NO.17)
反向引物：5'GCTGCATCCTGTTGTTTTTGG 3'(SEQ ID NO.18)
MRPL51基因
正向引物：5'GGTGTGCCTAGATTGATCGGTAT 3'(SEQ ID NO.19)
反向引物：5'CTCCGAACATGGCCCTTTT 3'(SEQ ID NO.20)
GALNT4基因
正向引物：5'GGGACAGGCGGATATCAAGA 3'(SEQ ID NO.21)
反向引物：5'TGTGTCATACGTTCCAAGGTACTGA 3'(SEQ ID NO.22)
YDJC基因
正向引物：5'TGACTTCCCTGGGTAGGACACT 3'(SEQ ID NO.23)
反向引物：5'GCTGCTCAAACTCTAGATGCCATT 3'(SEQ ID NO.24)
ATP6V1E1基因
正向引物：5'TCTCTCACCTCACCTTTCAAACC 3'(SEQ ID NO.25)
反向引物：5'GCCATGGCGAGAGCAATG 3'(SEQ ID NO.26)
HRH2基因
正向引物：5'CAGGCCAAGAGGATCAATCAC 3'(SEQ ID NO.27)
反向引物：5'TGACGGCGGCCAGTGT 3'(SEQ ID NO.28)
AR基因
正向引物：5'AGCGCTTTTTGCGTGGTT 3'(SEQ ID NO.29)
反向引物：5'GCGGTAGTCGCTGCAGCTA 3'(SEQ ID NO.30)
荧光定量PCR探针序列如下：
RPL36AL基因
探针序列：5'CTCGTTTTCATCATATAGAC 3'(SEQ ID NO.31)
C1orf132基因
探针序列：5'CCCTGGAGTATTCG 3'(SEQ ID NO.32)
RPS27A基因
探针序列：5'CTGGGACGGCAGTCA 3'(SEQ ID NO.33)
SNTB2基因
探针序列：5'AAGCCAGCAATTCCGCACA 3'(SEQ ID NO.34)
MRPL51基因
探针序列：5'CTCTCCCGCCCCCCAAAGTGGT 3'(SEQ ID NO.35)
GALNT4基因
探针序列：5'ACCCCATCAGATCACCTACCATGGCTG 3'(SEQ ID NO.36)
YDJC基因
探针序列：5'CTCTGGGCTCAGGTCCTCATGCCTC 3'(SEQ ID NO.37)
ATP6V1E1基因
探针序列：5'AAACTCGAGCCTACTGTTCACCGGCCT 3'(SEQ ID NO.38)
HRH2基因
探针序列：5'AGCCACCATCAGGGAGCACAAAGC 3'(SEQ ID NO.39)
AR基因
探针序列：5'CTGGAGCTTCCCGCAGG 3'(SEQ ID NO.40)
5)待检测样本供体结果的诊断：根据荧光定量RT-PCR中10个阿尔茨海默症基因标志物在外周血样本中的mRNA相对含量，代入利用boosting算法构建的阿尔茨海默症预测模型：
对受检者是否患阿尔茨海默症进行判别，如结果为+1，则判定为阿尔茨海默症；结果为-1，则判定为不是阿尔茨海默症。
2.结果
用荧光定量RT-PCR方法分别检测了训练集(195例确诊为阿尔茨海默症的患者、172例同年龄分布正常人群)和测试集(90例确诊阿尔茨海默症患者、68例同年龄分布正常人群)外周血样本中10个阿尔茨海默症基因标志物相对表达量，利用阿尔茨海默症预测模型对上述样本进行判别，并将预测结果与上述样本的临床诊断检测结果比较，得出本发明提供的10个血细胞基因标志物对阿尔茨海默症诊断的敏感性(Sensitivity)、特异性Specificity)和准确性(Accuracy)，具体检测结果如图1-2和下表2所示。
表2 10个血细胞基因标志物对阿尔茨海默症检测的灵敏度、特异性和ROC AUC值
以上所述实施例仅表达了本发明的实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
序 列 表
<110> 阿尔恩艾前哨健康科技（北京）股份有限公司
<120> 用于阿尔茨海默症检测的血细胞转录基因标志物及其应用
<160> 40
<170> PatentIn version 3.3
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attggtttgc agtactgtcg ctcaggtgca gttcccactt ccgcctgttt cttccctttc 60
ctgttaggcg agagctgcga aaggcgagag ctgcgaaggg ccaggtgtcg ggcgctgttt 120
ctcgttttca tcatatagac aaaacagccc tgctgcaaag atggtcaacg tacctaaaac 180
ccgaagaacc ttctgtaaga agtgtggcaa gcatcagcct cacaaagtga cacagtataa 240
gaagggcaag gattctttgt atgcccaggg aaggaggcgc tatgatcgga agcagagtgg 300
ctatggtggg cagacaaagc caattttccg gaagaaggct aagaccacaa agaagattgt 360
gctaaggctg gaatgtgttg agcctaactg cagatccaag aggatgctgg ccattaagag 420
atgcaagcat tttgaactgg gaggagataa gaagagaaag ggccaagtga tccagttcta 480
aactttggga tatttttctt caattttgaa gagaaaatgg tgaagccata gaaaagttac 540
ccgagggaaa ataaatacag tgatattctt acgcaaaaaa aaaaaaaaaa aa 592
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<212> DNA
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ctgtccttaa acactcactc ctgaccttac aaccctggct gttacctggt taacaagccc 60
caggtgttgg ctacaggtgt catcactgag agcccttgtg tgcagatctg ccccagctct 120
cccacctgtg actgaggcta gcaagtcccc cgtgggctgt agagcctagc gctggtgtca 180
gaatcgcttg ttgcaggttc atcttcagtg tctttcccac agccacatgc tggggaaaga 240
cggcaaaggc gctagaggag caggagaaca aagcaagctg ccccagacca cccggctttc 300
gcagaaccca gatgatgctc ctgtctcccc ctaagtataa cgtgttattt agtcagtatg 360
atcccattca gtgcagaagt atcgcctagg aatttcctgc cccacccacc ctgttttgtt 420
cttaatgaag ttcaagaaca aaatgagatg atagtcaagt tatggagcag gctgcagtgg 480
atacaagggc agaaacacag tctttggagt tagacctggg atctgcattg attggttgtg 540
tgactgcaga caagttattt agcctcatta aggatgaatt tcttcgcaaa aattggaata 600
atacctgccc catacgactg ttgtgagaat taaacactgc aacttttgat gttcaaattc 660
tatttcttct ccttctagca acacatactg ttagtgccag gaaccataaa aattataagg 720
ctgtatctag aggcctgaaa ggaagctaaa atatacagtt tctactctgt ctcttttctc 780
ttggttatgg tatcagagga aatacacata ttttcttagc ttcaaaccac caaaaaagat 840
gatgcagtaa ggagatggga aatctaattt ggaatacagt gtgcaaatct tattttcaag 900
cagactttga aaataaaact caattcttac gttagaggat tatctgctta atacaattat 960
agggtaccag tttttgaagt cacatcgggg ttaaataaga ttgcaggttc atggggtcat 1020
atttgaatgt tctgatactt acatatgggg tgggaaggag gaatgcatgc ttttctcaag 1080
ttaagacaca taaaagagtt gtcctggccc aggtgagact cgcctttgtg tagcagctgg 1140
agcttcattg cacaggcaga tagggtgctt gtgtcctgat gaagtaagag aatatatctg 1200
gaaacacttt gtgtactgtg aaatactata caaatgcagg gcagtacaaa tgtaaatatt 1260
aatgtatttt agtaataatt ttagctttta tttcatcata tataataatt tgtagtgact 1320
ggtgtgaagt taaatagaat taacctagaa ttaatgagtt ttgtattgct ctcatctatt 1380
tgaagcatca gctgtgcctt tcatgttgcc ttgtgcagcc ctgtgtaacc tcctctgtgc 1440
ctttcccatg gagcactgtg tcatatcaca agtagaacta caggaagata tttctcctca 1500
gggcagaggc tgggtcttcc gattgaatct cccttctttc ttcattgaga tcctcttctt 1560
ctggaagctg gtttcacatg gtggcttaga tttttccatc tttgtatcta gcaccatttg 1620
aaatcagtgt tttaggagta agaattgcag cacagccaag ggtggactgc agaggaactg 1680
ctgctcatgg aactggctcc tctcctcttg ccacttgagt ctgttcgaga agtccaggga 1740
agaaacttga agagcaaaat acactcttga gtttgttggg ttttgggaga ggtgacagta 1800
gagaaggggg ttgtgtttaa aataaacaca gtggcttgag caggggcaga ggttgtgatg 1860
ctatttctgt tgactcctag cagccatcac cagcatgaat gtgttcgtag ggcctttgag 1920
tgtggcgatt gtcatattct gttggataac aatgtattgg gtgtcgattg tcatggggca 1980
ggggagaggg cagtacacct ggaggaccat tttgtccaca tcgacaccat cagtctgctc 2040
ttagaggatg ccctggagta ttcggcgttg attgcggggc acccgaaatc agacttgcca 2100
cctggactgt cgaggtgcag accctgggag caccactggc ccatctctta cacaggctga 2160
ccgatttctc ctggtgttca gagtctgttt ttgtctagca ccatttgaaa tcggttatga 2220
tgtaggggga aaagcagcag cctcgaagcc tcatgccaac tctgggcagc agcagcctgt 2280
ggtttcctgg aagatggatg ggcagagaat agggaaggaa gatcatgctt ttccctacta 2340
acttctgtaa ctgcatgtat gatacattat tgcagaggta agagatagtt taatggattt 2400
ttaaaaacaa attactataa tttatctgat gttctctagt tgcattttgc tgaaatgtag 2460
tgctgttcta aattctgtaa attgattgct gttgaattat ctttctgttg agaagagtct 2520
attcatgcat cctgacctta ataaatacta tgttcagttt 2560
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ctcgacctcc ttttaaaaat tctcttagcc acgttgattg tacgggaaaa gcctttttaa 60
aacatctttt acgttgctta aacctacagt ttcgaaagca ttccgaaggc taaagtgaga 120
aataagccca ggctagggag aggagaaacg aagttcacgt cctagtctgg caccgggttg 180
gattgtcgct gggacggcag tcaggcattt ggtgtggtcg cctaaggggt gggtccttcg 240
gcgggagctc cgggaaaccc cgtgggcctg cgcggcgttc ttccttttcg atccgccatc 300
tgcggtggag ccgccaccaa aatgcagatt ttcgtgaaaa cccttacggg gaagaccatc 360
accctcgagg ttgaaccctc ggatacgata gaaaatgtaa aggccaagat ccaggataag 420
gaaggaattc ctcctgatca gcagagactg atctttgctg gcaagcagct ggaagatgga 480
cgtactttgt ctgactacaa tattcaaaag gagtctactc ttcatcttgt gttgagactt 540
cgtggtggtg ctaagaaaag gaagaagaag tcttacacca ctcccaagaa gaataagcac 600
aagagaaaga aggttaagct ggctgtcctg aaatattata aggtggatga gaatggcaaa 660
attagtcgcc ttcgtcgaga gtgcccttct gatgaatgtg gtgctggggt gtttatggca 720
agtcactttg acagacatta ttgtggcaaa tgttgtctga cttactgttt caacaaacca 780
gaagacaagt aactgtatga gttaataaaa gacatgaact aacatttatt gttgggtttt 840
attgcagtaa aaagaatggt ttttaagcac caaattgatg gtcacaccat ttccttttag 900
tagtgctact gctatcgctg tgtgaatgtt gcctctgggg attatgtgac ccagtggttc 960
tgtatacctg ccaggtgcca accacttgta aaggtcttga tattttcaat tcttagacta 1020
cctatacttt ggcagaagtt atatttaatg taagttgtct aaatataa 1068
<210> 4
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<212> DNA
<213> 人类（Homo sapiens）
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gccgaggctg cctgactgga atgagggtag ctgcggcgac tgcggcggct ggagcggggc 60
cggccatggc ggtgtggacg cgggccacca aagcggggct ggtggagctg ctcctgaggg 120
agcgctgggt ccgagtggtg gccgagctga gcggggagag cctgagcctg acgggcgacg 180
ccgccgcggc cgagctggag cccgctctgg gacccgcggc cgccgccttc aacggcctcc 240
caaacggcgg cggcgcgggc gactcgctgc ccgggagccc aagccgcggc ctggggcccc 300
cgagcccgcc ggcgccgcct cggggccccg cgggtgaggc gggcgcgtcg ccgcccgtgc 360
gccgggtgcg ggtggtgaag caagaggcgg gcggcctggg catcagcatc aagggcggcc 420
gcgagaaccg gatgccgatc ctcatctcca agatcttccc cgggctggct gccgaccaga 480
gccgggcgct gcggctgggc gacgccatcc tgtcggtgaa cggcaccgac ctgcgccagg 540
ccacccacga ccaggccgtg caggcgctga agcgcgcggg caaggaggtg ctgctggagg 600
tcaagttcat ccgagaagta acaccatata tcaagaagcc atcattagta tcagatctgc 660
cgtgggaagg tgcagccccc cagtcaccaa gctttagtgg cagtgaggac tctggttcgc 720
caaaacacca gaacagcacc aaggacagga agatcatccc tctcaaaatg tgctttgctg 780
ctagaaacct aagcatgccg gatctggaaa acagattgat agagctacat tctcctgata 840
gcaggaacac gttgatccta cgctgcaaag atacagccac agcacactcc tggttcgtag 900
ctatccacac caacataatg gctctcctcc cacaggtgtt ggctgaactc aacgccatgc 960
ttggggcaac cagtacagca ggaggcagta aagaggtgaa gcatattgcc tggctggcag 1020
aacaggcaaa actagatggt ggaagacagc aatggagacc tgtcctcatg gctgtgactg 1080
agaaggattt gctgctctat gactgtatgc cgtggacaag agatgcctgg gcgtcaccat 1140
gccacagcta cccacttgtt gccaccaggt tggttcattc tggctccgga tgtcgatccc 1200
cctcccttgg atctgacctt acatttgcta ccaggacagg ctctcgacag ggcattgaga 1260
tgcatctctt cagggtggag acacatcggg atctgtcatc ctggaccagg atacttgttc 1320
agggttgcca tgctgctgct gagctgatca aggaagtctc tctaggctgc atgttaaatg 1380
gccaagaggt gaggcttact attcactatg aaaatgggtt caccatctca agggaaaatg 1440
gaggctccag cagcatattg taccgctacc cctttgaaag gctgaagatg tctgctgatg 1500
atggcatccg aaatctatac ttggattttg gtggtcccga gggagaactg accatggacc 1560
tgcactcttg tccgaagccg attgtatttg tgttgcacac gtttttatcg gccaaagtca 1620
ctcgtatggg actgcttgta tgagcaacaa aaaatcagaa aagagccttg actgtcacaa 1680
gaaatatttc cacctcaaaa aaaaaaaagc acaaaaagaa actctttgct ctccttcagc 1740
acagtgcctt cccaaggacc tgcaaataac tgctgaacca taaccgtgtt taaagaagag 1800
cctacctttc acagtctacc ttggccagat attctagcac tctaaaaggc tccaaaatga 1860
agctgttgat ttattctcat ttcaaaatat ggtttatgag taattaggtt tatttctact 1920
gctaaaaaga atggctcatt gttttctttt tttttcattg ttttcatttt tagacataat 1980
caaataccca agcattgttt tctttttctt ctccctgtag gatttgtgtt gtgcttagcc 2040
ttgatctctt gttcagaaca attgtccctt cccaggtgct agcttgcagc agcctgttgc 2100
ttcctgagca ttccagatag gtcgtatgtc ttggaattta ctgtcctcac tagctccttc 2160
caccatagga agtccttgaa ttgtatcacc aaagggttgt tccatttgcc ctggatctcc 2220
ctctatctca gcctggccat cacttcccac cttatcccaa gctttgccac tgtctctagg 2280
acttagaact tgtaaatttg atttgccttg ccttctactt cctttctagt ggtgactgag 2340
ttgaaaagca agttggaagc cactgctttt aaagaaaagt tttgcttggt ttaggttttt 2400
ccaattttat ttttgttagg agccagggga taagatttat tttaaatgaa aatcctcttc 2460
ctaggttaag ccattttttt tattgcttac caaatgtgcc tttggttagg gttagtggag 2520
ctttattagt cactatttga ataactggaa atcactgcca tttccaggag atcacctatc 2580
ctagttttga ggaatagtca ttgaggtggg tttccttaat ggcatctctt ctagtaggca 2640
gatctgtttg aacaagataa atcctaaaga gccagcctgc ttgaggagta gacttggtgg 2700
gtgaagccag caattccgca caaacgtcat gttgaattgt tttgggctgc ccaaaaacaa 2760
caggatgcag catcctggct gtggcctggc cctttgtggc agcagtggca tggacaagca 2820
actgctaatt cgagacttac tattggcttc acagcacacc ctacagtgag cagggtgatg 2880
agaccgtgga acagctacct gcttttggtt aagattgcca gatatcatta ggacacagta 2940
gcagcaagaa tgctgatttt gtagtgttag aaaatgaact cagcttgttt ttcctaattt 3000
tgaaggtggt atatatctgc aaacatttaa aatggtataa tatcatataa aatgtcaaaa 3060
ttagcacagt ccctggatct caaagaatag gtaatattga cttggatgtt ctttatgctc 3120
tctgaagaaa ggtctaggga aagttcttgt ttgcttgatt gatcaagagt gccacggaag 3180
aatgtgagcg ctgtggaggg tggaggaggg tgtcacttca gatggggcag gcacaggggg 3240
agaaaagaag agaaaaacac acctgtgtgc aaaatgagct atttggtttc agtgcggcct 3300
gaccgatggg gaggacccat gagcagagag agttctaggt caacattgta actccattgt 3360
cctccttcac ccataagtca gtcctccttc ctcattacag tgaaaccaac aatatgcaga 3420
ggttggggag agatgcctgt tcttccccca gcttcatata attgtcaaag ttccaaaaat 3480
gaattatctg aactgcttaa aactggaaat taaaatctag acaagaatat gtctttcaag 3540
agctttttat gttttgaaag ttcataaacc taagattggc tccatctgag ataaattttc 3600
ttttcttttt ttttttgaga cggagtctcg ttctgtctcc caggctggag tgcagtggca 3660
tgatctcggc tcactgcaac ctccacctcc taggttcaag tgattctcct gagtagctgg 3720
ggttatagct acccaccacc acacccagct aatttttgta tttttagtag aggcaggttt 3780
tcaccatgtt ggctaggctg gtcttgaact cccgacctca agtgatccac ctgccttggc 3840
ctcccaaagt gctgggatta taggtgtgag cccccgtgcc tggcccacaa taaattttca 3900
tttcagagaa ggaaaaaaat ctcttgaacg tccagaaatg atttctggaa tcagaatttc 3960
aatatgtaat accctcaggt aggcaatctt gaaccctcta tgcagtgaga gcattattaa 4020
tatgagatgt tgaatgatgc ctttacagac ttcagcagca aagccatttg gttgaggttt 4080
tctgtgttaa tgtgaaaagc taagccactg agatttgcag gggagcttct gagccaccct 4140
gcttgttggt tatatgagga tgtaaaatag gtggaattaa aatgtgagca ggaaaggcaa 4200
ggcatgtgtg cattttcact cattttggtc aaggttaaac tgacatgtat agcactgagg 4260
tctgtagggt tcttaatatc ttttgagtct tgctgtgaaa tgaaagtgtg ggaggtttcc 4320
tttgtccatt agcagcccca agaaccagaa cccttttgct gcttttctta catacctaac 4380
agctctccag tcatgatgac caaggttgtt cttcaatcaa atgtgtttgt gggattttca 4440
gtccgcaaat gaagtgctct ctaatgaatg ggacaccatg ataaatatgt atttatattt 4500
agatgccaaa gtatggcaaa ttatttccaa atgataacta caaatgggaa ttttcgatat 4560
tctacctttt ttatagaacc agctcacttt tcatttcttt ttcattttga attaagaaaa 4620
ttgttgagga tgtggtgggt tccagtgtgt ggaatggaaa ggaaactgca gaatagtgtc 4680
tgctccccat tcagagggac tgcttcctgt gccccccaga cccggggctt cgacagcttc 4740
tccacattcc acacagatgc ctaggagcag cgagttggta tatgaaaagt ctcccacctt 4800
ttctcctaaa acttctctcc tttctctcca taaaaagaaa aggaaaggaa caaaagaaaa 4860
acattcagtt tttctttttc tgaaaaaggt aagtcctttc ctgaagtcat caaatgaaac 4920
attatctgga aattagtttc taatgttgta tatgaagaaa tacttaaata taagttcctg 4980
cagtatttat tagatagttg taactgtaaa ctcacctccc tagtagataa gagtttcagg 5040
ttaaatactg gaacatatat aggcagtcaa aaatactact ttaaatgtca ttcacctatt 5100
ttaaagccat gttttagcac tttttaggcc aaagaaggtc tgatagtgcc tgtttttatg 5160
ttctgtactc tcacaaactt tgttactcaa aattattgca tggcaggaga gattggatta 5220
tttatttctt atatttttat aagtaaaaaa atctttctaa acaacaaata cctaacatta 5280
ttactgattg ttttcctaat ttatcctcct aagttgaatg gtaacaaagc ttttccagct 5340
gaatgaatgc acttagctga taaaccagaa tttgttcttt tttttccttc tttttttttt 5400
gagacaggtt ctcactctgt caccgaggtt ggagtgcagt ggtatgatca tagctgactg 5460
cagcctcaac cttctgggct caaatgatcc tttcacctca gcctcctgag tagctgggac 5520
cacaggtgtg tgccaccaca cctggctaat ttttatggat ttttttttct tttttttttt 5580
tcgccatgtt gcccaggctg gtcttgaact cttggcactc aagcagtcct tctgcctcag 5640
cctcccaaag tgctgggatt acagatgtga gccactgcac ctggccccag aaattatgct 5700
taaaaaaaaa attaagctgt gtggaatctg gacaaggcta tgtttctcct agaaacaggt 5760
tttgctgtaa atggttttga tgggcgaaag tgtgagaaaa ggttataata gattcttttt 5820
tttaattttg tgagaaattc caggtcttct tgcttaactt atatgcatgt ggatatattt 5880
gttttcaaag ccatggaaga atctctgttc atatatttta atgcaaatta ccttgtatgc 5940
tgctatgcaa attctattaa aaggcctacc tgcttaagaa ttaaacattt ttgaaacttt 6000
cagggaagac ctgtagactc aagcactttc tctgcttttt tgtatcttat cttggacact 6060
tatgctgaat tatgttctta ttattttcac tggttataag ctattccttg tacataatat 6120
ttaaactatc caaatatcca gcatacattt ccatgtggct gccatcggct gttgatgcca 6180
tgaatgaaat ggctggttag aaagccaaag gtcttctttt ttcaattcct aatgaataag 6240
taaaatgcca gatctctttg gtctcaaagc aaattgctct gatcagatca aatatctatg 6300
taatgaaaag agacttactt aaatttggga ttctgcttaa actttaagtt gaatttgact 6360
gtagtcattc attcttttta tatatctctg tcaggtatga cattaattac caggtggtat 6420
tatactctac tttgagtttg gacatcactt tcagttaaat ttctgttgtt attgtggctt 6480
tttttttttt ttaaccccac tgaagatgga agtagagcag tctgccatct cctgctgttc 6540
tttctctgtg ccccctaatt gcttggtaat ctaaaattat tctgactttc cacatactgt 6600
ctttaaaaac caattgtagc aatctgcccg cctccaccct ttaagctaaa tctttcactg 6660
tgctggatac atagacactc gataaatgtg tgatgatagt tctaaaataa ttatgctata 6720
tatcagggtt ctgtattttt gagcaatatc attattccta tgctgtgatg ttaaatggaa 6780
tttattttac actagtaata gactgcttaa gtggctgatt tgaaaccttt ctctaaaaaa 6840
acaaaaacat ctggcagatg agtgacacaa attcattctc ttaaaggata gaatttcaag 6900
ttaaggataa ggcacaataa ataggcacat agaggacatc tgtttttgtt tttggttttg 6960
gttttgtttt tttttgtctc tctgactagc taaactgcca actagaagaa tggttgttat 7020
gtagtaactc agaagaatct tttaataagt ttcttctttt gtttcaaaac aaacttgagc 7080
ttcatttctt gccacctcta ttctttcttc ccacgttggg tgactgaact gatgcttatt 7140
ctagttttag aagaggatcc acatttaatg taaggcataa atatgccttt tgcaaattat 7200
tgcttgttct ccagtgaaca tttgatcata ttcaacagaa atccaccata taaaccataa 7260
tccttgaatt gcccctttta aaatagattg gttaaaacca aaaacctata agagagaaat 7320
gatatttcat tgtattgtag gtttgggaat cctggttaga tttataattt ctggccgggt 7380
gcggtggctc atgcctgtat tcccagtact ttgggagccc aaggtgggtg gatcacctga 7440
ggtaaggagt ttgagaccag cctggccaac atggtgaaac cccatctcta ctaaaaatac 7500
aaaaagttag ctgggcatgg tggtgcgcgc ctgtggtccc agctactcgg gaggctgagg 7560
tgggagaatc ccttgaaccc aggaggcaga agttgcagtg agctgagatc atgccattgc 7620
actccagcct gggcaacaga gcgagacttc atctccaaaa aaagaaaaag aagaaaaaga 7680
tttataattt ctgagtcccc taagtccctt tctcagtttg caataatctt acgtccatgc 7740
tattgacact aattttgaaa ctggaaagct aattaatgac atattcatgt gttctttcat 7800
ctaataaaca tttattaatg tatagttcta caccaggcat tctgaagggt ccaaaagaaa 7860
gttcctgccc tctagtagca cataatccgt tatttctcag cacaccatgc catctgttta 7920
tcattcagca gttaagtaat tcatcacttc atatttttac caaagtatat ttacaagtct 7980
gtttatctgg atctggcaaa ctggaaaatg tttgaaggga tactcaggct ttgatccatg 8040
ccaacatgaa aggactccaa gcacatttaa gtaggctggt cttttcatca tgcatgattt 8100
tttttttagt gcaaatttag actttagttt gggaaagaga acagtataca gtatcctttg 8160
taagataaat cacaacaaca aaaattaagt tttattgcac aaagtagata aatgagaaag 8220
tctttcttaa aaaatgcttc tttaactgta acagcaaaac taaatgcata ttttatcaac 8280
cccttatttc taattgctgt attcatttcc acccttaaac tatttaagca tttcatctgc 8340
tgaaagtcct tatatacatg gtagacggaa tatttctcca ttaatgatag atcaaaatga 8400
agatatttaa aaattaacaa aatcaggcca aggcaggagg atcactttag cccaggaggt 8460
ccagaccagc ctgggcaaca cagcgggacc ccgactccat ttaaaaaatt aaaaaaaaaa 8520
aaaaaacttt taacatttaa aaaataaaaa ttaacaaaat ttcacttatt ccaggacacg 8580
ctggcatttg gactcaatga aaagggcacc taaagaaaat aaggctgact gaatgttttc 8640
cataattttc acacaataac agtccctttc tatccagctt gccttccatt tatctctagg 8700
gttagctttt caggcaacat ccttggtcat tgcccagaaa gtacctgagc tatcagtgat 8760
tggaatggca caggaaaccg aatcacatgg gtgccctccc cttggttttc aagtatcttg 8820
gagttgtgca caaaaattag gtcatgcctt cagtgtcttg ttctttaaac ctaccctttg 8880
acaatcaggt gctaatgatt gtatactatt aaaaccagca cataagtatt gtaaatgtgt 8940
gttcctccta ggttggaaga aatgtctttc cttctatctg ggtcctgtta aagcgggtgt 9000
cagttgtgtc ttttcacctc gatttgtgaa ttaatagaat tggggggaga ggaaatgatg 9060
atgtcaatta agtttcaggt ttggcatgat catcattctc gatgatattc tcactttgtc 9120
gcaaatctgc ccttatcgta agaacaagtt tcagaatttt ccctccacta tacgactcca 9180
gtattatgtt tacaatccat tggatgagtg cagcattata agaccttggt gcccagaaaa 9240
atctgtcctt tttggtacca aacctgaggt cttttggaag ataatgtaga aaaccactac 9300
ctattgaagg cctgttttgg ctaatctgtg caaactctga tgatacctgc ttatgtggat 9360
tcttttccac actgctttca tttttaagta taaagactta gaaaactaga ataatgcttt 9420
tacaaataat taaaagtatg tgatgttctg ggttttttcc ttctttttag aaccctgtat 9480
ttaaacaagc cttcttttta agtcttgttt gaaatttaag tctcagatct tctggatacc 9540
aaatcaaaaa cccaacgcgt aaaacagggc agtatttgtg ttcctaattt taaaaagctt 9600
tatgtatact ctataaatat agatgcataa acaacacttc cccttgagta gcacatcaac 9660
atacagcatt gtacattaca atgaaaatgt gtaacttaag ggtattatat atataaatac 9720
<210> 5
<211> 898
<212> DNA
<213> 人类（Homo sapiens）
<400> 5
acagctgcct gggtaaggcc caagatggct gtcttcgcct tagtactcgt gtgaagttgg 60
cggggacggt tcctgtcatc ttcttgggct tatttggtgt gctgttgaag gggggagact 120
agagaaatgg cagggaacct cttatccggg gcaggtaggc gcctgtggga ctgggtgcct 180
ctggcgtgca gaagcttctc tcttggtgtg cctagattga tcggtataag gctcactctc 240
ccgcccccca aagtggttga tcgttggaac gagaaaaggg ccatgttcgg agtgtatgac 300
aacatcggga tcctgggaaa ctttgaaaag caccccaaag aactgatcag ggggcccata 360
tggcttcgag gttggaaagg gaatgaattg caacgttgta tccgaaagag gaaaatggtt 420
ggaagtagaa tgttcgctga tgacctgcac aaccttaata aacgcatccg ctatctctac 480
aaacacttta accgacatgg gaagtttcga tagaagagaa agctgagaac ttcggaaaag 540
gctcatctgt caccctggag aagggaaact gtacttttcc ctgtgaggaa acggctttgt 600
attttctctg taataaaatg gggcttcttt ggaatttgat agccacatac ttttgttttc 660
ctctagatgc tgcctctact catgtagact atgaagtctt gactcatcct agatcttagg 720
atcttaggtt tgggcttcac accacttgcc ttttacagtc tagctatacc taattccttt 780
aaaaagaaaa gttggtgaga atgttattgg cgctttttga cataatgctg ttatgttaat 840
agtgtttcta aagagccttc cacactgaaa tgaaatataa gagaaaaatg gagtcata 898
<210> 6
<211> 5385
<212> DNA
<213> 人类（Homo sapiens）
<400> 6
gagtttgtga aaagttgtga gccgagcagg aggaagtagg gagagaggag ttgggctgtg 60
ccggaggccg aggaccgaga gggctcaggt gacccctgga aagcctgggt ggctggaaag 120
gagcctagcg cctgcatgaa aggaagaacc tgctgggaag tacctgagct cgagctgtgg 180
gttccgccgc ccttcccctg cgtggtggct tggtggccgc gtctgcgcct cagccctgag 240
aatccggatg gcggtgaggt ggacttgggc aggcaagagc tgcctgctgc tggcgttttt 300
aacagtggcc tatatcttcg tggagctctt ggtctctact tttcatgcct ccgcaggagc 360
cggccgtgcc agggagctgg ggtcaagaag gctctcagac ctccagaaaa atacggagga 420
tttgtctcga ccgctttata agaagccccc tgcagattcc cgtgcacttg gggagtgggg 480
gaaagccagc aaactccagc tcaacgagga tgaactgaag cagcaagaag aactcattga 540
gagatacgcc atcaatattt acctcagtga caggatttcc ctgcatcgac acatagagga 600
taaaagaatg tatgagtgta agtcccagaa gttcaactat aggacacttc ctaccacctc 660
tgttatcatt gctttctata acgaagcctg gtcgactttg ctccgtacca ttcacagtgt 720
tttagaaact tctcctgcag ttcttttgaa agagatcatc ttggtggatg acttgagtga 780
cagagtttat ttgaagacac aacttgaaac ttacatcagc aatcttgata gagtacgctt 840
gattaggacc aataagcgag aggggctggt tagggcccgt ctgattgggg ccactttcgc 900
cactggggac gtcctcactt tcctggattg tcactgtgag tgtaattccg gttggctgga 960
accgcttttg gaaaggattg ggagagatga aacagcagtt gtgtgtcctg ttatagacac 1020
aattgattgg aatacttttg aattctatat gcagataggg gagcccatga ttggtgggtt 1080
tgactggcgt ttaacatttc agtggcattc tgtccccaaa caggaaaggg acaggcggat 1140
atcaagaatt gaccccatca gatcacctac catggctgga ggactgtttg ctgtcagcaa 1200
gaaatatttt cagtaccttg gaacgtatga cacaggaatg gaagtgtggg gaggtgaaaa 1260
ccttgagctg tcttttaggg tgtggcagtg tggtggcaaa ttggagatcc acccgtgttc 1320
ccacgtgggc catgtgttcc ccaagcgggc accatatgct cgccccaatt tcctacagaa 1380
tactgctcgg gcagcagaag tttggatgga tgaatacaaa gagcacttct acaatagaaa 1440
ccctccagca agaaaagaag cttatggtga tatttctgaa agaaaattac tacgagagcg 1500
gttgagatgc aagagctttg actggtattt gaaaaacgtt tttcctaatt tacatgttcc 1560
agaggataga ccaggctggc atggggctat tcgcagtaga gggatctcgt ctgaatgttt 1620
agattataat tctcctgaca acaaccccac aggtgctaac ctttcactgt ttggatgcca 1680
tggtcaagga ggcaatcaat tctttgaata tacttcaaac aaagaaataa ggtttaattc 1740
tgtgacagag ttatgtgcag aggtacctga gcaaaaaaat tatgtgggaa tgcaaaattg 1800
tcccaaagat gggttccctg taccagcaaa cattatttgg cattttaaag aagatggaac 1860
tatttttcac ccacactcag gactgtgtct tagtgcttat cggacaccgg agggccgacc 1920
tgatgtacaa atgagaactt gtgatgctct agataaaaat caaatttgga gttttgagaa 1980
atagagcaca acagcacttt cgtcatgagc tgacagtagt gtcaagaaag tcaaagagcc 2040
ttaagagcct cagtgaagat tgtattttat tttatcaaaa gccacctagc agtcatctgt 2100
ggagcactgg aaagctgggg ttcattttgg tatatcacac tgaaactggg tacccagagt 2160
gctgctgttt aatatttcac aatgccttac ttattggttg ttttatataa gagttttgtc 2220
aatatggtct cttcttaaaa gaagttgact atgaattgaa acacacaaaa catttaagtg 2280
ccagacttaa tattaaagaa tgtaaaggtc caagtaaaat gaggtatgat ttatgttgat 2340
gtgtaagttc accgcacatc ccacttttta acaaaactca tgaatgtgca gtttgagcca 2400
ttgctatttt gattacatag aatttgtatt tcttttttag ccagcacatt aaattttaga 2460
ttttattttt taatctaatt tttttctaat caaaaagaaa attgagctta aggcaaaagg 2520
cctggtttta gagatatgtg taattggaag agggcatttg tttgagtgtg agtttggagg 2580
cctttttaac atgcagacat acccatattt aaatgaaatg gggagatatt tacattccgt 2640
actttgtaaa cttgagctat tggacttcac tgatgtatat attaatacct cagattcctc 2700
tgattttgta agctgtcttc tctgtgaacg tgtttgtgtg tgtagggcat tttctgattg 2760
cacttcctta agttatgaat gtactagaaa gggactcatc cagaatacta tgcctccctt 2820
tgttaatgct taatcattta aagtaaacac aattgaagcc tctctgaagt taaacccaac 2880
tatgtttatt aaaatgtgtg aaactgaaag tgggctaggt tctaccaagg ctgtggaact 2940
ctcctacgag ttctgctgat caggaaattt aagaatttat cttaaaaatg caaggaaaaa 3000
agactgcctt ggcaattgtg aatggtgctt tcaatctcct agcaccgagc ctggcactta 3060
ggcagctttc agtaagtggg tgaatgaatg actgaatgaa tgaatgaatg gctcagctga 3120
ggaatgtaac tttggtcaag ttattatgat gtgtttgggc ttagttttct cattggtaaa 3180
atgtgggtgc tggattggat cttaaagatc ccttccagct ctgaaatgct gattgtacag 3240
tatattcttc ccagattgac tcactgtgca atctttacaa tactttttat cttttcactt 3300
ttgacatagg taatgttgtt gagcagttga gcaatgttca gtccagttgt gaagctggag 3360
aagagaaatg ggttttaaaa attaagtgag gggaggccgg gtgcggtggc tcacgcatgt 3420
aatcccagca ctttgggagg ccaaggcagg tggatcacga ggtcaggaga tccagaccat 3480
cctggctaac atggtgaaac ctcgtctcta ctaaaaatac aaaaaattag ccagctgtgg 3540
tggcgggcgc ctgtagtccc agctactcag gaggctgagg caggagaatg gcgtgaacct 3600
gtgaggcaga gcttacagtg agccgagatc gtgccactgc actccagcct gggcgacaga 3660
gcaagactct gtctcaaaaa aaaaaaataa taataaaata agtgagctga actcacctga 3720
agtggtttac ttctgtgggt taagaagttc tagtcagtgt tcatagtcgt ttcgttttga 3780
taattgttga accaattttg tttttaaaac ctttagactc tgaaagtaat attttgacta 3840
agaatgtaaa tatttccaaa ctaaattact cgggaagtaa acgctttttt taaaagtatt 3900
tttactggtt ttataccaat attatatgca gaaatcacag gatgaattta gaattaaatc 3960
tcaattagtt cactttggcc tagatttatg aaaaatgcat gcctcgtaaa gagtccactg 4020
tattcacgag taaagttgct tttagtgttc acttgatgac ttggagagta ggaattttgc 4080
aaaatctgaa tttaaggaaa ttctttagga taaccatttc aaaaaataaa attgctatgc 4140
aatcttgaat attttctctt ttgcctcgta aaatgaaaat gcattcacag tttctgtaaa 4200
ttatttagca gccttaaagt ttatcaaaaa attgtccaga ttccacgtgc agcatgcttg 4260
gccctgcatt taatttaaga aggattaata ataatgctct gaatttttcg aaagggattc 4320
tcctaaaccc acccacttct cttgcccagg ctgcttttta aaaatatttt tttatttttt 4380
acttattttt aaattttctc tttttattta tttttggttt tcttgttagc cacctgttat 4440
atgggagaac gaaaattgtt atattttgaa agtacttatt acattatttt tattttagta 4500
tcttgatgct cctgtcaaaa gggaaatgag gcttttaaaa ataaagtacc ttaattcttt 4560
attgactttt tgccctaaat tgctaggtgt gacccagcaa tcttttagga agagatttta 4620
cagtggtgct ttatttatat caataatcca gtatagttag gctgttcatt cctcataata 4680
gagtacataa cagaaaagtg ggactttcac attttcatat ttaggcacgt tccaatttaa 4740
ttccaaaaat actctgtaat tctacatcta aaaaaaccga ttccctaatt cgaatttatt 4800
ggtaccaaag ctctctttgg ctatagacaa ttaagagttg accttttaag ttaatgtata 4860
tgcttaaaaa cagttttagg aaaatatttg gtagacaaag agtttcaact ttaaatgttc 4920
actatgtcat ttagtgtcca actttacgga taggttgact atctaaatag gcatttttag 4980
tcattaaaaa aaatctagtc accaggagga tccctataac tcaaaataac ttgtttgtaa 5040
aagaaaattt gtttacttac ccattagtaa gttcctgcat attcattata agatggcaaa 5100
tcaaactttt ctaggatgaa gacagcttat ttttaagttg tatagtctta gttggtttag 5160
ggtctcaatt ttaattaata aaatacttgg tttttatttg cttgtccttt tgaattcctg 5220
ttttaataat tttaaaatga gcacaaagaa cgttgaagtt cagattaatc tcttctgaat 5280
gatgtttttt tcctctgtga tgagttgttt ctgacttttt tccttttgta tttgtaatgt 5340
tgattaagat gtaaaataaa aagtgtgcct gattattttt gcaaa 5385
<210> 7
<211> 1350
<212> DNA
<213> 人类（Homo sapiens）
<400> 7
actcccctgg gagcgcgagc ggtggaccca ggcggccatg tcccgccctc gcatgcgcct 60
ggtggtcacc gcggacgact ttggttactg cccgcgacgc gatgagggta tcgtggaggc 120
ctttctggcc ggggctgtga ccagcgtgtc cctgctggtc aacggtgcgg ccacggagag 180
cgcggcggag ctggcccgca ggcacagcat ccccacgggc ctccacgcca acctgtccga 240
gggccgcccc gtgggtccgg cccgccgtgg cgcctcatcg ctgctcggcc cggaaggctt 300
cttccttggc aagatgggat tccgggaggc ggtggcggcc ggagacgtgg atttgcctca 360
ggtgcgggag gagctcgagg cccaactaag ctgcttccgg gagctgctgg gcagggcccc 420
cacgcacgcg gacgggcacc agcacgtgca cgtgctccca ggcgtgtgcc aggtgttcgc 480
cgaggcgctg caggcctatg gggtgcgctt tacgcgactg ccgctggagc gcggtgtggg 540
tggctgcact tggctggagg cccccgcgcg tgccttcgcc tgcgccgtgg agcgcgacgc 600
ccgggccgcc gtgggcccct tctcccgcca cggcctgcgg tggacagacg ccttcgtggg 660
cctgagcact tgcggccggc acatgtccgc tcaccgcgtg tccggggccc tggcgcgggt 720
cctggaaggt accctagcgg gccacaccct gacagccgag ctgatggcgc accccggcta 780
ccccagtgtg cctcccaccg gcggctgcgg tgaaggcccc gacgctttct cttgctcttg 840
ggagcggctg catgagctgc gcgtcctcac cgcgcccacg ctgcgggccc agcttgccca 900
ggatggcgtg cagctttgcg ccctcgacga cctggactcc aagaggccag gggaggaggt 960
cccctgtgag cccactctgg aacccttcct ggaaccctcc ctactctgac cccctacaga 1020
caaccaagca ctaatcccct tagtaccaag aaaggggagc caggatttag tcctggccca 1080
gcccagagct gggacctgga gcacgatctg ttgacttccc tgggtaggac actgccacct 1140
ctgggctcag gtcctcatgc ctccaaatgg catctagagt ttgagcagcc ttcttggctg 1200
caggcaggcc tagcctgtgg cagcgggcta gggcccgcag agcatttggt gcccctccat 1260
gttgcaatgc aaacaccttc accactgggg cagtggggag agatggctat attaataaaa 1320
taacgtgtgt ctttcaaaaa aaaaaaaaaa 1350
<210> 8
<211> 1316
<212> DNA
<213> 人类（Homo sapiens）
<400> 8
ctcttcccat tggctgagaa gggtcatgag gatgaactgt gcagtcacct ggcaggaacc 60
ggaacccgcg gttataaagt aaaggaaccc gagatctgcg caggggttcc ctttgccgat 120
ttctctcacc tcacctttca aacctaaact cgagcctact gttcaccggc ctagcattgc 180
tctcgccatg gctctcagcg atgctgacgt gcaaaagcag ataaagcata tgatggcttt 240
cattgaacaa gaagccaatg agaaagcaga agaaatagat gcaaaggcag aagaagagtt 300
caacatagag aaaggtcggc ttgtgcaaac ccaaagacta aagattatgg aatattatga 360
gaagaaagag aaacagattg agcagcagaa gaaaattcag atgtccaatt tgatgaatca 420
agcgagactc aaagtcctca gagcaagaga tgaccttatc acaggtttgt accagttgct 480
ggagccccga atgattgttc gttgcaggaa acaagatttc cctctggtaa aggctgcagt 540
gcagaaggca attcctatgt acaaaattgc caccaaaaac gatgttgatg tccaaattga 600
ccaggagtcc tacctgcctg aagacatagc tggtggagtt gagatctata atggagatcg 660
taaaataaag gtttccaaca ccctggaaag ccggctggat ctcatagccc agcagatgat 720
gccagaagtc cggggagcct tgtttggtgc aaatgccaac aggaagtttt tggactaagc 780
cttcaggagg tggagctcgt cgtcagctct cctgctgtga tgtggaagct tctgatattt 840
gaagaaacac gaatgtctct gtagcttcct cttcactgcc ccagtattgc tctgtattta 900
tcagcgatgc ccctctgtca ctcatgcctt gcctaattgt tcacaatggt ggaaagcttc 960
atgtaatatg atcaggaccc acctccagtt cttctgaaag tgtgacagtg tccagccggt 1020
tctgcagcac taggggaggg ggcagatggt ggttgcatgg gcttcctggg tctccactct 1080
ccgtctggcc taaaggtgat gtatttggtg tttggccctg cagtccccac tcttgaggct 1140
taaggcgcat gtggcacacc actccttcca gcagtagtcg ctttactgtt acctgtttag 1200
gcctagaagt tttccctcat ctgtaaatgt gatttaaaat ctaagccatg aatatgcttt 1260
atttattaaa agagttatgc ggatttaatg tgatttctag tgtaaggcac tacaaa 1316
<210> 9
<211> 5167
<212> DNA
<213> 人类（Homo sapiens）
<400> 9
cagggagaaa agggagagaa agagggggca gtgtggcaga aaggaagagg aaggggcaag 60
tgtcagagtc ggcgagatga ggagggaggg tgtaggagaa aggaaaatag aaagtgggtg 120
agaccgtggg agagggagac tgggggagaa aatgtgggcg tgtgcgcgct gagagagaga 180
gagagagaga gagacttgga gagggaagga agggaaggag cgttgagagc aaggaggagc 240
gagttggggg cggagacgag gaagtgggtg cgaggcgcgg ggcgcaggcc gtgcgcgcgc 300
cgcccgctgc atccctgccc ggagcgcagc cggcgcgggc gcgggaccga ggcgaaccgg 360
gtgcggagcc aatacccgcg gcagcagcac cagcctaggc cgattctcct gagctcacag 420
gcacattcca ctctccatcc taggctgatg attaactact gaccctccca ggcgatgcgt 480
ccgtgggaaa aacaagacca gctgtggtcc atctctgcca acaccccaaa attttatgca 540
atgagcatgt tctttaataa ttagtggact acctggcttc gagttctgag agcagggagg 600
agggtgcctg attgaaaaaa agctcctgcc ctccactgac tccagagagg gagatcccca 660
gtacttgact ccatcacgca gatgggagca ggcaccagct atggagaggg atacagctgc 720
gtctccacat gacccatcct gcatgacacc aaagccaccg ccagacagtg cctcggattc 780
tatgcaaaac ctgggaagcg gagacctacc ccagccccgg gaggaagcta gctcttcagg 840
ggaccgtctg aggactggag tttgatccat gaacctggct tcgaggcctt gcttttctct 900
cttcttcatt catattcatt cccaacacct tagaaggtgt tgcttaattt atttctagaa 960
aagcagccca gagtcagtca ttgaagcctt ccccaccccc tggccaaaaa aaaaaaaaaa 1020
aaaaaactgg acacattttg gatctgttgg gagcttggag tccagtggtt ggcatagttg 1080
tcacattggg agcagagaag aagcaaccag gggccctgat caggggactg agccgtagag 1140
tcccaggatg gcacccaatg gcacagcctc ttccttttgc ctggactcta ccgcatgcaa 1200
gatcaccatc accgtggtcc ttgcggtcct catcctcatc accgttgctg gcaatgtggt 1260
cgtctgtctg gccgtgggct tgaaccgccg gctccgcaac ctgaccaatt gtttcatcgt 1320
gtccttggct atcactgacc tgctcctcgg cctcctggtg ctgcccttct ctgccatcta 1380
ccagctgtcc tgcaagtgga gctttggcaa ggtcttctgc aatatctaca ccagcctgga 1440
tgtgatgctc tgcacagcct ccattcttaa cctcttcatg atcagcctcg accggtactg 1500
cgctgtcatg gacccactgc ggtaccctgt gctggtcacc ccagttcggg tcgccatctc 1560
tctggtctta atttgggtca tctccattac cctgtccttt ctgtctatcc acctggggtg 1620
gaacagcagg aacgagacca gcaagggcaa tcataccacc tctaagtgca aagtccaggt 1680
caatgaagtg tacgggctgg tggatgggct ggtcaccttc tacctcccgc tactgatcat 1740
gtgcatcacc tactaccgca tcttcaaggt cgcccgggat caggccaaga ggatcaatca 1800
cattagctcc tggaaggcag ccaccatcag ggagcacaaa gccacagtga cactggccgc 1860
cgtcatgggg gccttcatca tctgctggtt tccctacttc accgcgtttg tgtaccgtgg 1920
gctgagaggg gatgatgcca tcaatgaggt gttagaagcc atcgttctgt ggctgggcta 1980
tgccaactca gccctgaacc ccatcctgta tgctgcgctg aacagagact tccgcaccgg 2040
gtaccaacag ctcttctgct gcaggctggc caaccgcaac tcccacaaaa cttctctgag 2100
gtccaacgcc tctcagctgt ccaggaccca aagccgagaa cccaggcaac aggaagagaa 2160
acccctgaag ctccaggtgt ggagtgggac agaagtcacg gccccccagg gagccacaga 2220
caggaagcca gcactgtcct gcactacgtg ctccagcaac ctcctgagct gctgcaagag 2280
cctgtggggg ctcaggttcc ttcagagaca catgggaggc ccctcggagg agctatcggg 2340
ggagccactg tctgaggagc cacagaagag acctccccag aaagcggtga ggacgctgcc 2400
ctctgaggct gtctagacct agccccagga cactgaagat accgctcccg gtccccaaga 2460
tgtgactcct ggagctccta aggacccagt ctccaaagcc accaaggact caccctggac 2520
tgaatctggg ggctcccaga acacacagct gggtgtgggg tcctcaggcc tagggcggaa 2580
cagcctattc tgtgctcagc attcccagac aggcacgcaa gactcctctg ggcccgagtg 2640
ggctgaatcc catgggttca aagctcacgt tggtgctggc cctgggagtc atgagcagag 2700
acggtgggac agacggggat gcgtgcacat gtgtgtgcat gggtgcatac gtgtagggac 2760
gtgcatgacc tctgagcaag gcagagggta ttgaagaaag cattggcctc tcactccctc 2820
atgggttctg caggatgaag gaaaggaaag gaaaagacag agaaaggaag gaaatagctt 2880
ttcatgagca cctactgtgt accaggtgct tccctggcat gagctctcgt aacccttata 2940
gcaacatgag tttagagcaa gaatcacacc ccgactttac agagatggaa actgaggctc 3000
agagaagtaa gggacctgcc caaggccact cagcacctag aaagtgtgcc tagcacatag 3060
gaggcacaca aaaatatgtg ttgaatgggt gaatgaatga gagaacgggt gaaaagccag 3120
gcctcaagcc cacactactg acactgcact acaccacctc tcaggagaga aggcaaatat 3180
ttccttgact cagccacctt cctcctagca aggcttagac ccccaggctc tgggggtccc 3240
ttcctgctac agtatgaccc tctctggtgc ttgtcatcaa gaagtggtat gcggtggact 3300
tgctggagag agtgtctgca gccaggcatc atggagggag ggatggatct tgagggactg 3360
taatggttgt gaatggggga gttggccccc agcactctct ggtggccgta tgaccttggg 3420
cacgtctcct gaccactcta agcagctttt gattcccctg tccaagaggg taggccccct 3480
gttcctattt acaggatcca taaagagact caaagagata gggtagtgcc agccccagag 3540
agagggggct gtggagggac ttctaccccc agggcttctc agtggcatct cctggctggc 3600
ccctgacact caatcttcct tggtttccaa gatgcttcat gatcttcccc ctccctgaca 3660
tccccgacct cccttttctg tcccttttgc aactcattgt cctctacctg ccatcagatg 3720
tggctgttcc tcagtctcag tccagagtcc tctcttctca ctcagcatct ctcctcctgt 3780
gacctcgtct gcacccacaa ctccagttac aaggcacgag gtttggttat gaaatcactc 3840
acagatttat aactgcaggc ttggctcctt ccgggagctt gagacccact gccgcctccg 3900
caacacctcc acctgggagt ttcagaggcg ctctccctca gcgtgtctgc agctgcgtgc 3960
ctgcagctgc gtgcctgcct tctccctgca cctgctctgc tccccaggtc cctttctcag 4020
accaaagcct gcccgggctt cacaggctga gggtccacct tgccacctcc gtttgcctca 4080
gtcctcatgg agccctggct ccactgtctg ctggcttctc cccatctact ctgtgtcact 4140
ccatccgacc accattgtct ccatcaggac agttggaaca cctcttctca gcactctcgc 4200
ccccacccag tccaccccct acctgacagc cagagtgggc catgccagat gcaacccagg 4260
tcatgccaca caggtagata aaaccatctt cagcccagcc ctcaggccct gtgtgctggg 4320
accctgctgg gccctctcca gcctccccct gcgccaggcc tcctccgtca cttcactctg 4380
gccctgctgt tcttttcctt ttagtttgat taactcactc tgcccattcc atgctcaaag 4440
ctgtttccgt gaggaaaggc tcctcctgct cattttagtg ccctgaaatg tcacttcctt 4500
gaggaagtct tccttgaccc tccacaccaa accaggcccc ctgccacacc cctcagagct 4560
ctccttggaa ggcactggca tggctgtttg cgtgattcct tgaacgttgt ctgtctctcc 4620
tcctcaccag gctgtgggtc ctgtctgttt ctggtgaccg ttgtctgtct aacccctaga 4680
ggagagtttg tcacatggta ggagcttaat aaatatgtgt tggatgaatg atcagagaaa 4740
agagagtgca gagagtggcc aaaacagatg ctttcagcag tgtatctgcc aataaaccta 4800
aaggcatgat ttgccctggt gatcccccca gaggtgctta gtctcttggc tgaattcctt 4860
ctggaatccc cagaatcccc ctccttggaa gttttcccag gagtctgagg caggcaggtc 4920
tctcagtcac ggccacatga cctcaagtga aaacaaacca gtctggctgt tcacagactc 4980
agctggtcag agctctggcc cgaggggccc acgcaccacc cgccactgca gaagacgcct 5040
ccacgtctgt ctctgggctg cctccacctt ctgcaggcct cctggagcct ctgctggctg 5100
cagaagtggg gtgcatgctg cctggaggag gaacatctgt ggtgggaccc caaatccatg 5160
tttgtgt 5167
<210> 10
<211> 10257
<212> DNA
<213> 人类（Homo sapiens）
<400> 10
gcggagagaa ccctctgttt tcccccactc tctctccacc tcctcctgcc ttccccaccc 60
cgagtgcgga gccagagatc aaaagatgaa aaggcagtca ggtcttcagt agccaaaaaa 120
caaaacaaac aaaaacaaaa aagccgaaat aaaagaaaaa gataataact cagttcttat 180
ttgcacctac ttcagtggac actgaatttg gaaggtggag gattttgttt ttttctttta 240
agatctgggc atcttttgaa tctacccttc aagtattaag agacagactg tgagcctagc 300
agggcagatc ttgtccaccg tgtgtcttct tctgcacgag actttgaggc tgtcagagcg 360
ctttttgcgt ggttgctccc gcaagtttcc ttctctggag cttcccgcag gtgggcagct 420
agctgcagcg actaccgcat catcacagcc tgttgaactc ttctgagcaa gagaagggga 480
ggcggggtaa gggaagtagg tggaagattc agccaagctc aaggatggaa gtgcagttag 540
ggctgggaag ggtctaccct cggccgccgt ccaagaccta ccgaggagct ttccagaatc 600
tgttccagag cgtgcgcgaa gtgatccaga acccgggccc caggcaccca gaggccgcga 660
gcgcagcacc tcccggcgcc agtttgctgc tgctgcagca gcagcagcag cagcagcagc 720
agcagcagca gcagcagcag cagcagcagc agcagcagca gcaagagact agccccaggc 780
agcagcagca gcagcagggt gaggatggtt ctccccaagc ccatcgtaga ggccccacag 840
gctacctggt cctggatgag gaacagcaac cttcacagcc gcagtcggcc ctggagtgcc 900
accccgagag aggttgcgtc ccagagcctg gagccgccgt ggccgccagc aaggggctgc 960
cgcagcagct gccagcacct ccggacgagg atgactcagc tgccccatcc acgttgtccc 1020
tgctgggccc cactttcccc ggcttaagca gctgctccgc tgaccttaaa gacatcctga 1080
gcgaggccag caccatgcaa ctccttcagc aacagcagca ggaagcagta tccgaaggca 1140
gcagcagcgg gagagcgagg gaggcctcgg gggctcccac ttcctccaag gacaattact 1200
tagggggcac ttcgaccatt tctgacaacg ccaaggagtt gtgtaaggca gtgtcggtgt 1260
ccatgggcct gggtgtggag gcgttggagc atctgagtcc aggggaacag cttcgggggg 1320
attgcatgta cgccccactt ttgggagttc cacccgctgt gcgtcccact ccttgtgccc 1380
cattggccga atgcaaaggt tctctgctag acgacagcgc aggcaagagc actgaagata 1440
ctgctgagta ttcccctttc aagggaggtt acaccaaagg gctagaaggc gagagcctag 1500
gctgctctgg cagcgctgca gcagggagct ccgggacact tgaactgccg tctaccctgt 1560
ctctctacaa gtccggagca ctggacgagg cagctgcgta ccagagtcgc gactactaca 1620
actttccact ggctctggcc ggaccgccgc cccctccgcc gcctccccat ccccacgctc 1680
gcatcaagct ggagaacccg ctggactacg gcagcgcctg ggcggctgcg gcggcgcagt 1740
gccgctatgg ggacctggcg agcctgcatg gcgcgggtgc agcgggaccc ggttctgggt 1800
caccctcagc cgccgcttcc tcatcctggc acactctctt cacagccgaa gaaggccagt 1860
tgtatggacc gtgtggtggt ggtgggggtg gtggcggcgg cggcggcggc ggcggcggcg 1920
gcggcggcgg cggcggcggc ggcgaggcgg gagctgtagc cccctacggc tacactcggc 1980
cccctcaggg gctggcgggc caggaaagcg acttcaccgc acctgatgtg tggtaccctg 2040
gcggcatggt gagcagagtg ccctatccca gtcccacttg tgtcaaaagc gaaatgggcc 2100
cctggatgga tagctactcc ggaccttacg gggacatgcg taggtgctgc gagcagagag 2160
ggattcctcg gaggtcatct gttccatctt cttgcctatg caaatgcctg cctgaagctg 2220
ctggaggctg gctttgtacc ggactttgta cagggaacca gggaaacgaa tgcagagtgc 2280
tcctgacatt gcctgtcact ttttcccatg atactctggc ttcacagttt ggagactgcc 2340
agggaccatg ttttgcccat tgactattac tttccacccc agaagacctg cctgatctgt 2400
ggagatgaag cttctgggtg tcactatgga gctctcacat gtggaagctg caaggtcttc 2460
ttcaaaagag ccgctgaagg gaaacagaag tacctgtgcg ccagcagaaa tgattgcact 2520
attgataaat tccgaaggaa aaattgtcca tcttgtcgtc ttcggaaatg ttatgaagca 2580
gggatgactc tgggagcccg gaagctgaag aaacttggta atctgaaact acaggaggaa 2640
ggagaggctt ccagcaccac cagccccact gaggagacaa cccagaagct gacagtgtca 2700
cacattgaag gctatgaatg tcagcccatc tttctgaatg tcctggaagc cattgagcca 2760
ggtgtagtgt gtgctggaca cgacaacaac cagcccgact cctttgcagc cttgctctct 2820
agcctcaatg aactgggaga gagacagctt gtacacgtgg tcaagtgggc caaggccttg 2880
cctggcttcc gcaacttaca cgtggacgac cagatggctg tcattcagta ctcctggatg 2940
gggctcatgg tgtttgccat gggctggcga tccttcacca atgtcaactc caggatgctc 3000
tacttcgccc ctgatctggt tttcaatgag taccgcatgc acaagtcccg gatgtacagc 3060
cagtgtgtcc gaatgaggca cctctctcaa gagtttggat ggctccaaat caccccccag 3120
gaattcctgt gcatgaaagc actgctactc ttcagcatta ttccagtgga tgggctgaaa 3180
aatcaaaaat tctttgatga acttcgaatg aactacatca aggaactcga tcgtatcatt 3240
gcatgcaaaa gaaaaaatcc cacatcctgc tcaagacgct tctaccagct caccaagctc 3300
ctggactccg tgcagcctat tgcgagagag ctgcatcagt tcacttttga cctgctaatc 3360
aagtcacaca tggtgagcgt ggactttccg gaaatgatgg cagagatcat ctctgtgcaa 3420
gtgcccaaga tcctttctgg gaaagtcaag cccatctatt tccacaccca gtgaagcatt 3480
ggaaacccta tttccccacc ccagctcatg ccccctttca gatgtcttct gcctgttata 3540
actctgcact actcctctgc agtgccttgg ggaatttcct ctattgatgt acagtctgtc 3600
atgaacatgt tcctgaattc tatttgctgg gctttttttt tctctttctc tcctttcttt 3660
ttcttcttcc ctccctatct aaccctccca tggcaccttc agactttgct tcccattgtg 3720
gctcctatct gtgttttgaa tggtgttgta tgcctttaaa tctgtgatga tcctcatatg 3780
gcccagtgtc aagttgtgct tgtttacagc actactctgt gccagccaca caaacgttta 3840
cttatcttat gccacgggaa gtttagagag ctaagattat ctggggaaat caaaacaaaa 3900
acaagcaaac aaaaaaaaaa agcaaaaaca aaacaaaaaa taagccaaaa aaccttgcta 3960
gtgttttttc ctcaaaaata aataaataaa taaataaata cgtacataca tacacacata 4020
catacaaaca tatagaaatc cccaaagagg ccaatagtga cgagaaggtg aaaattgcag 4080
gcccatgggg agttactgat tttttcatct cctccctcca cgggagactt tattttctgc 4140
caatggctat tgccattaga gggcagagtg accccagagc tgagttgggc aggggggtgg 4200
acagagagga gaggacaagg agggcaatgg agcatcagta cctgcccaca gccttggtcc 4260
ctgggggcta gactgctcaa ctgtggagca attcattata ctgaaaatgt gcttgttgtt 4320
gaaaatttgt ctgcatgtta atgcctcacc cccaaaccct tttctctctc actctctgcc 4380
tccaacttca gattgacttt caatagtttt tctaagacct ttgaactgaa tgttctcttc 4440
agccaaaact tggcgacttc cacagaaaag tctgaccact gagaagaagg agagcagaga 4500
tttaaccctt tgtaaggccc catttggatc caggtctgct ttctcatgtg tgagtcaggg 4560
aggagctgga gccagaggag aagaaaatga tagcttggct gttctcctgc ttaggacact 4620
gactgaatag ttaaactctc actgccacta ccttttcccc acctttaaaa gacctgaatg 4680
aagttttctg ccaaactccg tgaagccaca agcaccttat gtcctccctt cagtgttttg 4740
tgggcctgaa tttcatcaca ctgcatttca gccatggtca tcaagcctgt ttgcttcttt 4800
tgggcatgtt cacagattct ctgttaagag cccccaccac caagaaggtt agcaggccaa 4860
cagctctgac atctatctgt agatgccagt agtcacaaag atttcttacc aactctcaga 4920
tcgctggagc ccttagacaa actggaaaga aggcatcaaa gggatcaggc aagctgggcg 4980
tcttgccctt gtcccccaga gatgataccc tcccagcaag tggagaagtt ctcacttcct 5040
tctttagagc agctaaaggg gctacccaga tcagggttga agagaaaact caattaccag 5100
ggtgggaaga atgaaggcac tagaaccaga aaccctgcaa atgctcttct tgtcacccag 5160
catatccacc tgcagaagtc atgagaagag agaaggaaca aagaggagac tctgactact 5220
gaattaaaat cttcagcggc aaagcctaaa gccagatgga caccatctgg tgagtttact 5280
catcatcctc ctctgctgct gattctgggc tctgacattg cccatactca ctcagattcc 5340
ccacctttgt tgctgcctct tagtcagagg gaggccaaac cattgagact ttctacagaa 5400
ccatggcttc tttcggaaag gtctggttgg tgtggctcca atactttgcc acccatgaac 5460
tcagggtgtg ccctgggaca ctggttttat atagtctttt ggcacacctg tgttctgttg 5520
acttcgttct tcaagcccaa gtgcaaggga aaatgtccac ctactttctc atcttggcct 5580
ctgcctcctt acttagctct taatctcatc tgttgaactc aagaaatcaa gggccagtca 5640
tcaagctgcc cattttaatt gattcactct gtttgttgag aggatagttt ctgagtgaca 5700
tgatatgatc cacaagggtt tccttccctg atttctgcat tgatattaat agccaaacga 5760
acttcaaaac agctttaaat aacaagggag aggggaacct aagatgagta atatgccaat 5820
ccaagactgc tggagaaaac taaagctgac aggttccctt tttggggtgg gatagacatg 5880
ttctggtttt ctttattatt acacaatctg gctcatgtac aggatcactt ttagctgttt 5940
taaacagaaa aaaatatcca ccactctttt cagttacact aggttacatt ttaataggtc 6000
ctttacatct gttttggaat gattttcatc ttttgtgata cacagattga attatatcat 6060
tttcatatct ctccttgtaa atactagaag ctctccttta catttctcta tcaaattttt 6120
catctttatg ggtttcccaa ttgtgactct tgtcttcatg aatatatgtt tttcatttgc 6180
aaaagccaaa aatcagtgaa acagcagtgt aattaaaagc aacaactgga ttactccaaa 6240
tttccaaatg acaaaactag ggaaaaatag cctacacaag cctttaggcc tactctttct 6300
gtgcttgggt ttgagtgaac aaaggagatt ttagcttggc tctgttctcc catggatgaa 6360
aggaggagga tttttttttt cttttggcca ttgatgttct agccaatgta attgacagaa 6420
gtctcatttt gcatgcgctc tgctctacaa acagagttgg tatggttggt atactgtact 6480
cacctgtgag ggactggcca ctcagaccca cttagctggt gagctagaag atgaggatca 6540
ctcactggaa aagtcacaag gaccatctcc aaacaagttg gcagtgctcg atgtggacga 6600
agagtgagga agagaaaaag aaggagcacc agggagaagg ctccgtctgt gctgggcagc 6660
agacagctgc caggatcacg aactctgtag tcaaagaaaa gagtcgtgtg gcagtttcag 6720
ctctcgttca ttgggcagct cgcctaggcc cagcctctga gctgacatgg gagttgttgg 6780
attctttgtt tcatagcttt ttctatgcca taggcaatat tgttgttctt ggaaagttta 6840
ttattttttt aactccctta ctctgagaaa gggatatttt gaaggactgt catatatctt 6900
tgaaaaaaga aaatctgtaa tacatatatt tttatgtatg ttcactggca ctaaaaaata 6960
tagagagctt cattctgtcc tttgggtagt tgctgaggta attgtccagg ttgaaaaata 7020
atgtgctgat gctagagtcc ctctctgtcc atactctact tctaaataca tataggcata 7080
catagcaagt tttatttgac ttgtacttta agagaaaata tgtccaccat ccacatgatg 7140
cacaaatgag ctaacattga gcttcaagta gcttctaagt gtttgtttca ttaggcacag 7200
cacagatgtg gcctttcccc ccttctctcc cttgatatct ggcagggcat aaaggcccag 7260
gccacttcct ctgccccttc ccagccctgc accaaagctg catttcagga gactctctcc 7320
agacagccca gtaactaccc gagcatggcc cctgcatagc cctggaaaaa taagaggctg 7380
actgtctacg aattatcttg tgccagttgc ccaggtgaga gggcactggg ccaagggagt 7440
ggttttcatg tttgacccac tacaaggggt catgggaatc aggaatgcca aagcaccaga 7500
tcaaatccaa aacttaaagt caaaataagc cattcagcat gttcagtttc ttggaaaagg 7560
aagtttctac ccctgatgcc tttgtaggca gatctgttct caccattaat ctttttgaaa 7620
atcttttaaa gcagttttta aaaagagaga tgaaagcatc acattatata accaaagatt 7680
acattgtacc tgctaagata ccaaaattca taagggcagg gggggagcaa gcattagtgc 7740
ctctttgata agctgtccaa agacagacta aaggactctg ctggtgactg acttataaga 7800
gctttgtggg tttttttttc cctaataata tacatgttta gaagaattga aaataatttc 7860
gggaaaatgg gattatgggt ccttcactaa gtgattttat aagcagaact ggctttcctt 7920
ttctctagta gttgctgagc aaattgttga agctccatca ttgcatggtt ggaaatggag 7980
ctgttcttag ccactgtgtt tgctagtgcc catgttagct tatctgaaga tgtgaaaccc 8040
ttgctgataa gggagcattt aaagtactag attttgcact agagggacag caggcagaaa 8100
tccttatttc tgcccacttt ggatggcaca aaaagttatc tgcagttgaa ggcagaaagt 8160
tgaaatacat tgtaaatgaa tatttgtatc catgtttcaa aattgaaata tatatatata 8220
tatatatata tatatatata tatatatagt gtgtgtgtgt gttctgatag ctttaacttt 8280
ctctgcatct ttatatttgg ttccagatca cacctgatgc catgtacttg tgagagagga 8340
tgcagttttg ttttggaagc tctctcagaa caaacaagac acctggattg atcagttaac 8400
taaaagtttt ctcccctatt gggtttgacc cacaggtcct gtgaaggagc agagggataa 8460
aaagagtaga ggacatgata cattgtactt tactagttca agacagatga atgtggaaag 8520
cataaaaact caatggaact gactgagatt taccacaggg aaggcccaaa cttggggcca 8580
aaagcctacc caagtgattg accagtggcc ccctaatggg acctgagctg ttggaagaag 8640
agaactgttc cttggtcttc accatccttg tgagagaagg gcagtttcct gcattggaac 8700
ctggagcaag cgctctatct ttcacacaaa ttccctcacc tgagattgag gtgctcttgt 8760
tactgggtgt ctgtgtgctg taattctggt tttggatatg ttctgtaaag attttgacaa 8820
atgaaaatgt gtttttctct gttaaaactt gtcagagtac tagaagttgt atctctgtag 8880
gtgcaggtcc atttctgccc acaggtaggg tgtttttctt tgattaagag attgacactt 8940
ctgttgccta ggacctccca actcaaccat ttctaggtga aggcagaaaa atccacatta 9000
gttactcctc ttcagacatt tcagctgaga taacaaatct tttggaattt tttcacccat 9060
agaaagagtg gtagatattt gaatttagca ggtggagttt catagtaaaa acagcttttg 9120
actcagcttt gatttatcct catttgattt ggccagaaag taggtaatat gcattgattg 9180
gcttctgatt ccaattcagt atagcaaggt gctaggtttt ttcctttccc cacctgtctc 9240
ttagcctggg gaattaaatg agaagcctta gaatgggtgg cccttgtgac ctgaaacact 9300
tcccacataa gctacttaac aagattgtca tggagctgca gattccattg cccaccaaag 9360
actagaacac acacatatcc atacaccaaa ggaaagacaa ttctgaaatg ctgtttctct 9420
ggtggttccc tctctggctg ctgcctcaca gtatgggaac ctgtactctg cagaggtgac 9480
aggccagatt tgcattatct cacaacctta gcccttggtg ctaactgtcc tacagtgaag 9540
tgcctggggg gttgtcctat cccataagcc acttggatgc tgacagcagc caccatcaga 9600
atgacccacg caaaaaaaag aaaaaaaaaa ttaaaaagtc ccctcacaac ccagtgacac 9660
ctttctgctt tcctctagac tggaacattg attagggagt gcctcagaca tgacattctt 9720
gtgctgtcct tggaattaat ctggcagcag gagggagcag actatgtaaa cagagataaa 9780
aattaatttt caatattgaa ggaaaaaaga aataagaaga gagagagaaa gaaagcatca 9840
cacaaagatt ttcttaaaag aaacaatttt gcttgaaatc tctttagatg gggctcattt 9900
ctcacggtgg cacttggcct ccactgggca gcaggaccag ctccaagcgc tagtgttctg 9960
ttctcttttt gtaatcttgg aatcttttgt tgctctaaat acaattaaaa atggcagaaa 10020
cttgtttgtt ggactacatg tgtgactttg ggtctgtctc tgcctctgct ttcagaaatg 10080
tcatccattg tgtaaaatat tggcttactg gtctgccagc taaaacttgg ccacatcccc 10140
tgttatggct gcaggatcga gttattgtta acaaagagac ccaagaaaag ctgctaatgt 10200
cctcttatca ttgttgttaa tttgttaaaa cataaagaaa tctaaaattt caaaaaa 10257
<210> 11
<211> 17
<212> DNA
<213> 人工序列（Artificial）
<400> 11
aggtgtcggg cgctgtt 17
<210> 12
<211> 19
<212> DNA
<213> 人工序列（Artificial）
<400> 12
tctttgcagc agggctgtt 19
<210> 13
<211> 24
<212> DNA
<213> 人工序列（Artificial）
<400> 13
cgacaccatc agtctgctct taga 24
<210> 14
<211> 17
<212> DNA
<213> 人工序列（Artificial）
<400> 14
ggtgccccgc aatcaac 17
<210> 15
<211> 18
<212> DNA
<213> 人工序列（Artificial）
<400> 15
gcaccgggtt ggattgtc 18
<210> 16
<211> 21
<212> DNA
<213> 人工序列（Artificial）
<400> 16
cttaggcgac cacaccaaat g 21
<210> 17
<211> 21
<212> DNA
<213> 人工序列（Artificial）
<400> 17
ccagcctgct tgaggagtag a 21
<210> 18
<211> 21
<212> DNA
<213> 人工序列（Artificial）
<400> 18
gctgcatcct gttgtttttg g 21
<210> 19
<211> 23
<212> DNA
<213> 人工序列（Artificial）
<400> 19
ggtgtgccta gattgatcgg tat 23
<210> 20
<211> 19
<212> DNA
<213> 人工序列（Artificial）
<400> 20
ctccgaacat ggccctttt 19
<210> 21
<211> 20
<212> DNA
<213> 人工序列（Artificial）
<400> 21
gggacaggcg gatatcaaga 20
<210> 22
<211> 25
<212> DNA
<213> 人工序列（Artificial）
<400> 22
tgtgtcatac gttccaaggt actga 25
<210> 23
<211> 22
<212> DNA
<213> 人工序列（Artificial）
<400> 23
tgacttccct gggtaggaca ct 22
<210> 24
<211> 24
<212> DNA
<213> 人工序列（Artificial）
<400> 24
gctgctcaaa ctctagatgc catt 24
<210> 25
<211> 23
<212> DNA
<213> 人工序列（Artificial）
<400> 25
tctctcacct cacctttcaa acc 23
<210> 26
<211> 18
<212> DNA
<213> 人工序列（Artificial）
<400> 26
gccatggcga gagcaatg 18
<210> 27
<211> 21
<212> DNA
<213> 人工序列（Artificial）
<400> 27
caggccaaga ggatcaatca c 21
<210> 28
<211> 16
<212> DNA
<213> 人工序列（Artificial）
<400> 28
tgacggcggc cagtgt 16
<210> 29
<211> 18
<212> DNA
<213> 人工序列（Artificial）
<400> 29
agcgcttttt gcgtggtt 18
<210> 30
<211> 19
<212> DNA
<213> 人工序列（Artificial）
<400> 30
gcggtagtcg ctgcagcta 19
<210> 31
<211> 20
<212> DNA
<213> 人工序列（Artificial）
<400> 31
ctcgttttca tcatatagac 20
<210> 32
<211> 14
<212> DNA
<213> 人工序列（Artificial）
<400> 32
ccctggagta ttcg 14
<210> 33
<211> 15
<212> DNA
<213> 人工序列（Artificial）
<400> 33
ctgggacggc agtca 15
<210> 34
<211> 19
<212> DNA
<213> 人工序列（Artificial）
<400> 34
aagccagcaa ttccgcaca 19
<210> 35
<211> 22
<212> DNA
<213> 人工序列（Artificial）
<400> 35
ctctcccgcc ccccaaagtg gt 22
<210> 36
<211> 27
<212> DNA
<213> 人工序列（Artificial）
<400> 36
accccatcag atcacctacc atggctg 27
<210> 37
<211> 25
<212> DNA
<213> 人工序列（Artificial）
<400> 37
ctctgggctc aggtcctcat gcctc 25
<210> 38
<211> 27
<212> DNA
<213> 人工序列（Artificial）
<400> 38
aaactcgagc ctactgttca ccggcct 27
<210> 39
<211> 24
<212> DNA
<213> 人工序列（Artificial）
<400> 39
agccaccatc agggagcaca aagc 24
<210> 40
<211> 17
<212> DNA
<213> 人工序列（Artificial）
<400> 40
ctggagcttc ccgcagg 17
Claims (6)
1.一种用于阿尔茨海默症检测的组合物，其包含用于检测在阿尔茨海默症与同年龄分布正常人群的外周血细胞中基因差异表达的引物和探针，所述基因为SEQ ID NO.1～SEQID NO.10所示阿尔茨海默症的血细胞特征基因。
2.根据权利要求1所述的用于阿尔茨海默症检测的组合物的用途，其特征在于，用于制备检测阿尔茨海默症的产品。
3.根据权利要求2所述的用于阿尔茨海默症检测的组合物的用途，其特征在于，所述检测阿尔茨海默症的产品包括：用实时定量PCR对阿尔茨海默症进行检测的产品。
4.根据权利要求3所述的用于阿尔茨海默症检测的组合物的用途，其特征在于，所述用实时定量PCR检测阿尔茨海默症的产品包含特异扩增SEQ ID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列的引物和探针。
5.一种用于阿尔茨海默症检测的试剂盒，其特征在于，所述试剂盒包含特异性针对SEQID NO.1～SEQ ID NO.10所示阿尔茨海默症的血细胞特征基因序列的引物和探针。
6.根据权利要求5所述的用于阿尔茨海默症检测试剂盒，其特征在于，所述引物的序列包括SEQ ID NO.11～SEQ ID NO.30所示的核苷酸序列，所述探针的序列包括SEQ ID NO.31～SEQ ID NO.40所示的核苷酸序列。
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| CN107779503A (zh) * | 2017-12-06 | 2018-03-09 | 北京泱深生物信息技术有限公司 | 阿尔茨海默相关的差异表达基因及其应用 |
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