一种体外检测口腔白斑癌变相关基因表达水平差异的方法

专利名称：一种体外检测口腔白斑癌变相关基因表达水平差异的方法
技术领域：
本发明关于检测癌变相关基因表达水平差异的方法，特别关于体外检测口腔白斑癌变相关基因表达水平差异的方法。
背景技术：
口腔鳞癌占全身恶性肿瘤的4％，由于口腔位于呼吸道与消化道的重要位置，病变结果严重影响患者的生活和生存质量。研究口腔鳞癌的发生发展机制是从根本上防治肿瘤的关键。
口腔白斑是口腔鳞癌的主要来源之一，对于白斑癌变机制研究，国内外学者多应用传统病理、免疫组化、电镜及分子生物学技术对单个或多个基因进行研究。随着基因芯片技术的出现，目前，已有许多学者应用芯片技术对膀胱癌、乳腺癌、口腔癌、食道癌等进行基因表达谱研究，并对新发现具有应用潜能的靶点进行专利保护。
传统的分子生物学检测手段一次实验仅检测一个或几个基因，不能总体把握白斑癌变相关靶基因群的作用。虽然已有学者使用芯片技术对口腔癌、食道癌等进行基因表达谱研究，但由于口腔粘膜白斑癌变过程较长，且其癌变不确定性，难以在临床患者中作动态性跟踪研究。因此，对于口腔白斑癌变过程可疑基因的研究缺乏系统报道。且目前常用的芯片数据处理方法Heirarchical clustering在芯片数据量大、数据复杂情况下，常会造成不准确甚至错误聚类影响结果分析。

发明内容
本发明的目的在于提供一种体外检测口腔白斑癌变相关基因表达水平差异的方法。
本发明的目的是通过以下技术方法来实现的使用基因芯片技术结合CPP-SOM数据分析方法对白斑癌变全过程的基因表达谱进行动态性跟踪研究，从而整体水平上把握白斑癌变相关靶基因群。本发明有以下步骤(1)4NQO诱导的大鼠白斑癌变模型的建立及样本收集；(2)样本总RNA提取和芯片杂交；(3)芯片扫描及数据分析。该方法包括(1)体外检测口腔白斑癌变相关基因表达水平增强的方法；(2)体外检测口腔白斑癌变相关基因表达水平降低的方法。口腔白斑癌变过程中，表达持续增强的基因有13条，它具有如SEQID1、SEQID2、SEQID3、SEQID4、SEQID5、SEQID6、SEQID7、SEQID8、SEQID9、SEQID10、SEQID11、SEQID12、SEQID13所示的核苷酸序列。SEQID1基因编码的蛋白是趋化因子(C-X-C基序)配基9、SEQID2基因编码的蛋白是细胞周期因子A2、SEQID3基因编码的蛋白是类似于细胞周期因子B2、SEQID4基因编码的蛋白是雌激素受体2、SEQID5基因编码的蛋白是Janus激酶3、SEQID6基因编码的蛋白是趋化因子C-X-C配基10、SEQID7基因编码的蛋白是运载体1，ATP-结合盒，B亚科、SEQID8基因编码的蛋白是细胞分裂周期2同系物A、SEQID9基因编码的蛋白是核转录因子KB p105亚单位、SEQID10基因编码的蛋白是跨膜域4，A亚科，7。
口腔白斑癌变过程中，表达持续降低的基因有10条，它具有如SEQID14、SEQI D15、SEQID16、SEQID17、SEQID18、SEQID19、SEQID20、SEQID21、SEQID22、SEQID23所示的核苷酸序列。
SEQID14基因编码的蛋白是羧酸酯酶1、SEQID16基因编码的蛋白是白细胞素2受体γ链、SEQID17基因编码的蛋白是CD80抗原、SEQID18基因编码的蛋白是甲状腺激素受体β、SEQID19基因编码的蛋白是ATP酶，Na+K+转运，α1、SEQID20基因编码的蛋白是解聚素及金属蛋白酶domain 6、SEQID21基因编码的蛋白是细胞外蛋白酶抑制剂、SEQID22基因编码的蛋白是泛激素类似物3。
本发明所公开一种体外检测口腔白斑癌变相关基因表达水平差异的方法，其优点表现在1、通过对口腔白斑癌变全过程的基因表达谱进行动态性跟踪研究，筛选出白斑癌变过程相关靶基因群，可从整体水平快速、全面把握白斑癌变机制；2、可推动口腔白斑诊治和预后判断等水平的提高；3、以此为基础，设计开发口腔癌前病变诊断、判断预后等用途生物芯片，进一步研究挖掘药物作用靶点，为个体化药物治疗提供依据。


图1显示总RNA提取结果图2显示CPP-SOM动态展示轻度异常增生阶段基因的变化情况，黑色代表基因上调，白色代表基因下调图3显示CPP-SOM动态展示中度异常增生阶段基因的变化情况，黑色代表基因上调，白色代表基因下调图4显示CPP-SOM动态展示重度异常增生阶段基因的变化情况，黑色代 表基因上调，白色代表基因下调图5显示CPP-SOM动态展示原位癌阶段基因的变化情况，黑色代表基因上调，白色代表基因下调图6显示CPP-SOM动态展示鳞癌阶段基因的变化情况，黑色代表基因上调，白色代表基因下调具体实施方式
下面结合实施例对本发明作进一步描述。
实施例11.14NQO诱导的大鼠白斑癌变模型的建立及样本收集1.1-1动物和材料Wistar雄性大鼠20只，体重220±10g，鼠龄160天，每4只一笼，室温23±2℃，湿度30-50％，精制颗粒饲料，24小时光暗循环条件下饲养。
4NQO美国Sigma公司产，用蒸馏水制成0.0002％浓度溶液4℃避光保存备用。
1.1-2分组35只大鼠按随机数字表分为2组，正常对照组5只，普通自来水喂养；实验组17只，4NQO饮水喂养；分别于9周、13周、16周、20周、24周、32周处死。观察大体变化，留取舌标本。将舌背后1/3病损处自中线剖开，一半置10％中性福尔马林溶液中固定，常规石蜡包埋，4um切片，HE染色后光镜观察。一半置于RNAlater(Qiagen公司)中，-80℃保存。
1.1-3组织病理学检查诊断标准根据WHO口腔癌前病变协作中心12项诊断标准(1978)对标本进行分级诊断(包括正常黏膜、轻度异常增生、中度异常增生、重度异常增生、原位癌、鳞癌)，所有诊断均采用双盲法证实。
收集正常组织5例，轻度异常增生4例，中度异常增生6例，重度异常增生6例，原位癌(24周)4例，鳞癌(32周)5例。
1.2样本总RNA提取和芯片杂交1.2-1RNase free(去RNA酶)条件下，使用Trizol法(Trizol试剂一步法的步骤1.冻存组织加入1mltrizol，匀浆器匀浆，室温放置5分钟；2.加0.2ml氯仿，震荡15秒；3.4度12000rpm离心15分钟；4.取上清，加入0.5ml异丙醇，摇匀室温放置10分钟；5.4度12000rpm离心10分钟；6.弃上清，在沉淀中加入1ml 75％乙醇洗涤RNA，4度7500rpm离心5分钟7.自然干燥RNA，溶于甲酰胺或纯水中分装。)提取样本总RNA。样品经分光光度计检测吸光度A值。经琼脂糖凝胶电泳检测28S、18S条带变化.Rneasy试剂盒(Qiagen公司)纯化总RNA。
1.2-2探针的制备和芯片杂交所用芯片为Amersham商品化芯片-codelink Uniset Rat I Bioarry。
利用CodeLink试剂盒制备探针，合成cDNA双链后体外反转成cRNA标记生物素。用T7引物和SuperScript II逆转录酶与10μg总RNA在42℃孵化1小时合成第一链cDNA。第一链cDNA同E.coliDNA聚合酶I和RNaseH混合，在16℃孵化2小时合成第二链cDNA，形成的双链cDNA使用QIAquickTMPCR纯化试剂盒(Qiagen公司)纯化。用T7RNA聚合酶和biot in-11-UTP体外转录合成生物素标记的cRNA。用RNeasy试剂盒(Qiagen公司)纯化cRNA。使用5×fragmentation buffer(片断化缓冲液)94℃加热20分钟片段化cRNA。片段化后的cRNA与Uniset bioarry放置于CodeLink提供的shaker上，摇床调整转速300rpm，37℃孵化过夜。0.75×TNT buffer 46℃洗涤孵化1小时。然后，使用Cy5-Streptavidin(Cy5-抗生物素蛋白链菌素)室温下避光孵化30分钟。1×TNT洗涤芯片4次(每次5分钟)，在0.1×SSC/0.05％TweenTM中冲洗芯片30秒后，2000rpm离心3min甩干。
1.3芯片扫描及数据分析用Array Scanner(Axon公司)扫描芯片。用codelink expressionanalysis software进行图像处理和数据的标准化。然后采用建立在Matlab 5软件包基础之上的CPP-SOM(自组织图结合成分平面展示方法)进行数据的进一步分析和展示。
2.结果2.1总RNA提取结果总RNA紫外分光度OD260/OD280Ratio值介于1.7-2.0之间。总RNA电泳清晰的28S、18S条带，且28S条带的亮度为18S带的两倍。(见图1示)。
CPP-SOM动态展示不同阶段基因的变化情况，黑色代表基因上调，白色代表基因下调。(见图2、3、4、5、6示)。
2.3差异表达基因分析口腔白斑癌变过程中，表达持续增强的基因有13条(表1).表达持续降低的基因有10条(表2).
表1部分表达显著增加的基因


表2部分表达显著降低的基因


SEQUENCE LISTING<110>上海第二医科大学附属第九人民医院<120>一种体外检测口腔白斑癌变相关基因表达水平差异的方法<130>/<160>23<170>PatentIn version 3.1<210>1<211>1185<212>DNA<213>褐家鼠(norway rat)<400>1gccttgactc cagcacggtg acttaataga gctcggctct gccatgaagt ccgttgctct60attcctcatg ggcatcatct tcctggatca ctgtggagtt cgaggaaccc tagtgataag120gaatcagcga tgctcctgca tcagcaccag ccaaggcaca ttccactaca aatccctcaa180agacctcaaa cagtttgccc caagccctaa ctgcaacaaa actgaaatca tcgctacact240gaagaacgga gatcaaacct gcctagaccc agattcagca agggtgaaga agctgatgaa300agaatgggag aaaaagatca gccaaaagaa aaagcaaaag agggggaaaa accatcaaag360gagcaagaaa acccgaaaag ctaaaacacc ccaccatccg gagtcaaaga agactgcata420agagaccact ttaccaacaa gcgctctgca tctaaacggc ttttagatca tactaaaacg480ccttcccttt aatacacaac tcgttcacta caaaacattg tgcgcgaatt tgaaattata540gctaaagcta ggaagtcaag tgtaaaactc aagtagtaag aatttctaga ggcgaaaact600gtctttgttc tacgcagcca acaaaatttc atcgagccct tgagcacagc cgtgatatca660aatctgggca agtgtcccac acacaacaga tgcctggctt ctaaagccac acatgacaaa720gcctccggag tcttctgagg cttgcatcac caagctccag gcttggtgct gccgtctggc780tgctggtgag ctagactttc agcagctgca ttttgagtca cccttgagcc cctgcacaaa840gtgtgtctca gagatccgta caaatggtct gggggttcca ccagggttgg agaccaccag900ggttggctac cagaaccttc catgtagctt tttgagacca tggaatttca tcattaattt960gatcccatgt tcaaggctta ttccacattt gcctcttaaa taaaaatccc ctagacggtt1020gtggatgtag cttagtggca gaatacttgg tgtttgcacg gacctgaccc ttgaaagaac1080atttcctggc ttctcaaatt cccttaaatc tatctcgctt gccgctcagc atttcagagt1140aaacacgtca ctgttatcta aaaaaaaaaa aaaaaaaaaa aaaaa1185<210>2
<211>2119<212>DNA<213>褐家鼠(norway rat)<400>2ttctaggggt agtcgggctg cagcctttgc ggtccgggcg tttttagtac caaatagccc60cacgagccct gcggacccgt gtatactgcc cttcagcact agtggagcgg tcttcctaaa120aattctaggg tcataccaag cagtgccccg cgtgtcgact tcggccatgt acctttccct180ccacttttaa agccaggcat tgcagtagga tatagatccc ttccccctca ccatctgctt240cacagattac tacttaaggg aaggacataa agcaagtatt ctgcttggta aattccgcca300ttttagccag acttgctgtt ttgctccacc ctgaggctaa agttgtgaat cagttctttc360ccctaacttt agtctttgat tagtttggaa ttccaatccg ttgcatttat agcctttgta420gaaatggctg tgacaaatcg gtttactcac cttacctgga ctttgactca tgaacttaca480tttttcttaa gagtatttgg aaataaaagt tggtacccac agggcaagaa gcaaagtatt540aaaaaagaat tccttctctt taggttgcgc ctcttaagga ccttcctata aacgatgagc600acgtccctac tgttccttca tggaaagcag tcagtaaaca gcctgccttc accattcatg660tggatgaagc tgaagagact cagaagaggc cagctgagca taaagaaact cagtgtgaag720atgccctggc ttttagtgcc gctgtctctt tacccggagc cagaaaacca ctggtacctc780ttgattatcc aatggatggt agttttgatt gcaggtcaga cacatggaag gcagaatagc840tgctatagac agctctgccg gtgctatgat ctcactgtgg agaccagaga tgttgaatca900ccccatgcta tggatatatc tattgtctta gaagacgaaa agccagtgaa tgttaatgaa960gtacctgact atcatgaaga tattcacacg taccttaggg aaatggaggt taaatgtaaa1020cctaaagtga gttatatgaa gaggcagcca gacatcacta acagtatgcg ggccatcctt1080gtggactggc tagttgaagt gggagaagaa tataaactac agaatgagac cctgcatttg1140gctgtgaact acattgatag attcctctcc tccatgtctg tgttaagagg aaagcttcag1200cttgtgggca cagctgctat gctgctagct tcaaagtttg aagaaatata ccccccagaa1260gtagcagagt ttgtgtatat tacggacgat acctattcca agaagcaggt tctgagaatg1320gagcaccttg tattgaaagt ccttgctttt gacttggctg caccaacagt aaatcagttc1380cttacccagt acttcctgca cctgcagcct gccaactgca aggtagaaag cttagcgatg1440tttttgggag agttaagttt gatagatgct gacccatacc tcaagtattt gccatcgctt1500attgctggag ctgccttcca cttagctctc tacacagtca caggacaaag ctggcctgag1560tcattggtac aaaagactgg atatacccta gaaagtctta agccttgtct catggacctt1620caccagacct acctcaaagc accacagcat gcccaacagt caataaggga aaagtacaag1680cattcaaaat atcacagtgt ttctcttctc aacccaccag agacactaaa tgtgtgagag1740tgaaagactg aaatggaaat cgctcagagt tcatgctgta cagtttttat ctttggtttt1800aatttcacaa tcatttctga atgtagatgg tatagccaca gacaaattat gttatccatt1860acttttaaaa tggttttaat ttgtatatct tttgtacatg tgtctatctt agattttggc1920taatttttaa ttggtttgtt aacattggtg ctgccaactg tcaagataat aagaataaat1980tgatttggaa atctttgaaa gtgatagata atttggctaa ttttaattgg tttgttaaca2040
ttggtgctgc caactgtcag gataataaga ataaattgat tcagaaagca aaaaaaaaaa2100aaaaaaaaaa aaaaaaaaa 2119<210>3<211>613<212>DNA<213>褐家鼠(norway rat)<220>
<221>misc_feature<222>(439)..()<223>n<220>
<221>misc_feature<222>(522)..()<223>n<220>
<221>misc_feature<222>(570)..()<223>n<400>3tttttttttt tttttttaag aaaatcaata gctttatttt tcatcaatac acaattagaa60aattaggttt tgtgatgtaa actagaatat atacaaatct gagaagcaca cgatggaagg120aagcccggct gcctagggtc tgcccatcag aggggaggcc aggtctttga tggttctgga180gttcagctga gggatcgtgc tgatcttcag gagcctgctg ctggcatatt tgttcttgac240agcgatgaac ttggtgaggt tttcattgac tttcacgacg ttcttggcca tgtgctgcat300gacttccagt atttcactct ccatgtagcc tgtgtaatac tgctgcttta aattccattt360tccttggccc agcaccttct gagagaggca ggaagcagca gctgcgacct gagaagggtg420gtaatgaacc atgtcgtaat cgacgagggt cagctccatc aggtacttgg ctaacgtgtg480ctgttcaaca tccacctccc cggcttttga ggctcgcctt aagaagtgga gtggcaaagg540ccggcccaac tcgaatttca actctttcaa aatcagagtc tccatttctc ggatttggga600actggtgtaa gca 613<210>4<211>2555<212>DNA<213>褐家鼠(norway rat)
<400>4cgggggagct ggcccagggg gagcggctgg tgctgccact ggcatcccta ggcacccagg60tctgcaataa agtctggcag ccactgcatg gctgagcgac aaccagtggc tgggagtccg120gctctgtggc tgaggaaagc acctgtctgc atttagagaa tgcaaaatag agaatgttta180cctgccagtc attacatctg agtcccatga gtctctgaga acataatgtc catctgtacc240tcttctcaca aggagttttc tcagctgcga ccctctgaag acatggagat caaaaactca300ccgtcgagcc ttagttccct gcttcctata actgtagcca gtccatccta cccctggagc360acggccccat ctacatccct tcctcctacg tagacaaccg ccatgagtat tcagctatga420cattctacag tcctgctgtg atgaactaca gtgttcccgg cagcaccagt aacctggacg480gtgggcctgt ccgactgagc acaagcccaa atgtgctatg gccaacttct gggcacctgt540ctcctttagc gacccattgc caatcatcgc tcctctatgc agaacctcaa aagagtcctt600ggtgtgaagc aagatcacta gagcacacct tacctgtaaa cagagagaca ctgaagagga660agcttagtgg gagcagttgt gccagccctg ttactagtcc aaacgcaaag agggatgctc720acttctgccc cgtctgcagc gattatgcat ctgggtatca ttacggcgtt tggtcatgtg780aaggatgtaa ggcctttttt aaaagaagca ttcaaggaca taatgattat atctgtccag840ccacgaatca gtgtaccata gacaagaacc ggcgtaaaag ctgccaggcc tgccgacttc900gcaagtgtta tgaagtagga atggtcaagt gtggatccag gagagaacgg tgtgggtacc960gtatagtgcg gaggcagaga agttctagcg agcaggtaca ctgcctgagc aaagccaaga1020gaaacggtgg gcatgcaccc cgggtgaagg agctactgct gagcaccttg agtccagagc1080aactggtgct caccctcctg gaagctgaac cacccaatgt gctggtgagc cgtcccagca1140tgcccttcac cgaggcctcc atgatgatgt ccctcactaa gctggcggac aaggaactgg1200tgcacatgat tggctgggcc aagaaaatcc ctggctttgt ggagctcagc ctgttggacc1260aagtccggct cttagaaagc tgctggatgg aggtgctaat ggtgggactg atgtggcgct1320ccatcgacca ccccggcaag ctcattttcg ctcccgacct cgttctggac agggatgagg1380ggaagtgcgt agaagggatt ctggaaatct ttgacatgct cctggcgacg acgtcaaggt1440tccgtgagtt aaaactccag cacaaggagt atctctgtgt gaaggccatg atcctcctca1500actccagtat gtaccccttg gcttctgcaa accaggaggc agaaagtagc cggaagctga1560cacacctact gaacgcggtg acagatgccc tggtctgggt gattgcgaag agtggtatct1620cctcccagca gcagtcagtc cgactggcca acctcctgat gcttctttct cacgtcaggc1680acatcagtaa caagggcatg gaacatctgc tcagcatgaa gtgcaaaaat gtggtcccgg1740tgtatgacct gctgctggag atgctgaatg ctcacacgct tcgagggtac aagtcctcaa1800tctcggggtc tgagtgcagc tcaacagagg acagtaagaa caaagagagc tcccagaacc1860tacagtctca gtgatggcca ggcctgaggc ggacagacta cagagatggt caaaagtgga1920acatgtaccc tagcatctgg gggttcctct tagggctgcc ttggttacgc accccttacc1980cacactgcac ttcccaggag tcagggtggt tgtgtggcgg tgttcctcat accaggatgt2040accaccgaat gccaagttct aacttgtata gccttgaagg ctctcggtgt acttactttc2100tgtctccttg cccacttgga aacatctgaa aggttctgga actaaaggtc aaagtctgat2160ttggaaggat tgtccttagt caggaaaagg aatatggcat gtgacacagc tataagaaat2220
ggactgtagg actgtgtggc cataaaatca acctttggat ggcgtcttct agaccacttg2280attgtaggat tgaaaaccac attgacaatc agctcatttc gcattcctgc ctcacgggtc2340tgtgaggact cattaatgtc atgggttatt ctatcaaaga ccagaaagat agtgcaagct2400tagatgtacc ttgttcctcc tcccagaccc ttgggttaca tccttagagc ctgcttattt2460ggtctgtctg aatgtggtca ttgtcatggg ttaagattta aatctctttg taatattggc2520ttccttgaag ctatgtcatc tttctctctc tcccg 2555<210>5<211>3778<212>DNA<213>褐家鼠(norway rat)<400>5gccttgaact tctaatcttc cgcctccatc tctggagttt tctggtaaca agctatactc60atggcacctc caagcgagga gacgcctctc atctctcagc gctcttgtag cctctcatcc120tcagaagcag gagccctgca tgtgctcctt cctccccggg gacctgggcc tccccagcga180ctgtcattct cttttgggga ctacttggct gaggatctgt gtgtgcgggc tgccaaggcc240tgtggcatcc tgcccgttta tcattcgctc ttcgctctgg ccaccgagga cttgtcttgc300tggttccccc caagccacat cttctccata gaggacgtgg acactcaagt cttggtctac360aggctacgct tttattttcc tggttggttt ggactggaga cctgtcaccg ctttgggtta420cacaaagatt tgaccagtgc catccttgac gtacatgttt tagaacacct ctttgcccag480caccgcagtg acctggtgag tgggcgtctc ccagtaggcc ttagcctgaa ggaccaggga540gagttcctga gcctagctgt gctggacctg gcccagatgg ctcgtaagca ggcccagcgg600ccaggagagc tgctgaagtc tgtcagttac aaagcctgtc tgccgcccag cctgcgcgac660ctgatccagg gccagagctt cgtgacgcgc aggcgcatcc gcaggaccgt ggtccaggcg720ctggcgccgt gtagtagcct gccaagccga ccctacgcac tcatggccaa gtacatccta780gaccttgagc ggctgcatcc agcggccacc actgagtcct tcctcgtggg actcccgggc840gcccaggagg agccgggttg cctgcgtgtg acaggggata atggcatcgc ctggagctcc900aaggaccagg agcttttcca gaccttctgt gactttcccg aaatcgtgga tgtcagcatc960aagcaggctc cacgcgtggg tccggcaggg gagcaccggc tagtcaccat caccaggatg1020gacggtcaca tcctggaagc ggagttcccg gggctgcctg aggcgctgtc tttcgtggcg1080ctcgtggatg ggtactttcg cctgatctgc gactccaggc atttcttctg caaggaggtg1140gcaccgccac ggctgctgga ggaggaggcg gagctgtgcc atggacccat cacgttagac1200tttgccatcc acaagctgaa ggctgctggc tccctcccgg gctcctacat tctccgacgc1260agcccgcagg actatgacag ctttcttctt actgcctgtg tccagactcc tcttggcccc1320gactacaagg gctgcctcat ccgccaagac cccagtgggg ctttctccct ggttggtctc1380agccagctgc acagaagcct acaggagctg ctcacagcct gctggcattc tggactgcaa1440gtagacggca ctgccctgaa cctcacatc ttgctgcgtcc ccagacccaa ggaaaagtcc1500aatttgatcg tggtgcgtag gggccgcaac cccacgcctg cccccgggca ctccccatcc1560
tgctgtgcgc tgactaagtt gagcttccac acaatcccag cagacagcct ggagtggcac1620gagaatcttg gtcacggctc ttttaccaag atcttccatg gccataggcg ggaggttgtg1680gatggtgaga cacatgacac agaagtcctc ctgaaggtta tggactccag acaccagaac1740tgcatggagt cctttctgga agccgcaagc ttgatgagcc aagtatccta cccgcacctg1800gtgttgctgc atggagtctg catggctgga gacagcatca tggtgcagga atttgtgtac1860cttggagcaa ttgacacgta cctgcgcaag cgtggtcacc tggtgccggc cagctggaaa1920ctgcaggtga ccaagcagct ggcctatgcc cttaactact tggaggacaa aggcctccct1980catggcaacg tctcagcgag gaaggtgctg ctagctcgtg agggggttga tgggaatcca2040cctttcatca agctgagtga tcctggtgtc agcccaactg ttttgagcct ggaaatgctc2100actgacagga ttccctgggt ggccccggag tgtctccagg aagctggaac gctcaacttg2160gaggctgaca agtggggctt tggcgccacc acgtgggagg tgttcagcgg ggcacccatg2220cacattacct cgctggagcc cgccaagaag ctgaagttct atgaggaccg gggacagctg2280ccggccctca aatggacaga gctggagggg ctcatcgcac agtgcatggc gtatgatcct2340ggccggcgcc cctccttccg agccatcctc agagacctca acggcctcat tacatcagat2400tacgagctcc tctcagaccc cacacctggc atcccgaatc cccgagatga gctgtgtggt2460ggtgcccagc tctatgcctg ccaggacccc gccatcttcg aggagagaca ccttaagtac2520atctccctgc tgggcaaggg gaacttcggc agcgtggagc tgtgccgcta cgaccctctg2580ggagacaata cgggacccct ggtagcagtg aagcagttac agcacagcgg gccagaacag2640cagagggact tccagcgaga gattcagatc ctcaaggctc tacactgtga cttcatcgtc2700aagtaccggg gagtcagcta tgggcctggt cgccaggagc tgcggttagt gatggagtac2760ctgcccagcg gctgcctgcg ggacttcctg cagcgccacc gcgcgcgcct gcacaacgac2820cgcctactgc tgttcgcctg gcagatctgc aagggcatgg agtacctggg cgcacgccgc2880tgcgtgcatc gtgacctggc tgcgcgcaac atcctggtgg agagtgaggc gcatgtgaag2940attgctgact tcggcctcgc taagctgctg cctcttggaa aagactacta cgtggtccgc3000gtgccgggcc aaagtcccat cttctggtac gcccctgagt ccctatctga caacatcttc3060tcccgccaat ctgacgtgtg gagcttcggc gtggtgctgt atgagctctt cacctacagc3120gacaagagct gcagcccatc cactgagttc ctgcgtatga ttgggcctga gcgtgaggga3180tccccgctct gccacctctt ggagctgctg gcagagggcc gccgtctccc accaccctcc3240acctgcccta ctgaggttca agagctcatg cagctgtgct ggtcgcccaa cccacaagac3300cggccagcgt ttgacaccct gagcccccag ctggatgcgc tgtggcgcgg aagccccgga3360tagcaagcag ccagggatga gcgtgagttt ggttcctatg atctggctgt gtgacttcca3420ggcgggaagc tgtccctctc tgggccccag cacccccaat cccctctggc cacctcttcc3480catcattctt ccctcccaga atggggatgt taaataagtg accccaggct ctgcacggtt3540gtcattacct ctggaaatgc tttactagca agtctgcctt ctgcagaact cacaacccca3600ggtcccaaga gcaccctaga cttggccaga aacccaccca gacccccaga ccctctcttg3660accctaggtc tgtgcccagt cccttgctct cctgtccatg ggtttcttgg gggctgtgaa3720acctcagcat ggtctcctga aagattgggt tctgggagtg tttgttgaat gaataaat 3778<210>6
<211>1133<212>DNA<213>褐家鼠(norway rat)<400>6cctcggctga gctgcattcc aatcccagct acatccggag cccagctaca ttcgagccca60gccacatccc gagccaacct tccagaagca ccatgaaccc aagtgctgct gtcgttctct120gcctcgtgct gctgagtctg agtgggactc aagggatccc tctcgcaaga acggtgcgct180gcacctgcat cgacttccat gaacagacgc tgagacccag ggccatagga aaacttgaaa240tcattcctgc aagtctatcc tgtccgcatg ttgagatcat tgccacaatg aagaagaaca300atgagaagag gtgtctgaat ccggaatctg aggccatcaa gagcttattg aaagcggtga360gccaaagaag gtcaaaaaga gctccgtaac tagagagaag ccactcgcca cagtgctgag420accgatggac agcagagaga cggtctctcc acctcccttt acccagtgtg cggctagtcc480taactgtccc tgtttctcct gaccatggtc ccatcagctg gtactcccac tacagcgtga540tggacaaggc ctggtcctga gacaaaagta actccagcag caaggcttcc caattctcta600agagctggtc cgaatcttcc ctcaggcagc tatgacggct ctcctagctc tgttccgtaa660gctatgtgca ggtactaatc tcttcagcat gtgccatgcc ccagcctgct ccacacaccc720tccttctccc tagctctaag ctcatcagtt ctgagttcac ctgagctcct ttatttcaaa780tgcagtccag gtgagatggc aaatcaagtt tgtcagaaca aacttaccac caccttccca840agggaatttc ataactcaga atactcacag gaacctagac atgcatgttt aaatattatt900taatgaccga ctgtacaaag tggaactcct agatgtattt tttgtacgat tttcattgta960tatgtaagaa cttgtgtggt taagtatgta tcaatgggta gttaaagttt acataggcaa1020atgctttgaa tgctacatat tacaagatgt gttggatggt tttcaaaata aaatgtactg1080tattgaatgt agtatgagac aaaaaagtaa taaagtaata ataactgaca tga 1133<210>7<211>2178<212>DNA<213>褐家鼠(norway rat)<400>7atggctgcgc acgcctggcc gacggccgcc ttgctgctgc tgctggtgga ctggctgctg60ctgcggtccg tgctcccggg aatcttctcc ctgttggttc ccgaggtgcc gctgctccgg120gtctgggccg tgggcctgag tcgctgggct atcctgggac taggggtccg cggggtcctc180ggggtcaccg cgggagcccg tggctggctg gctgctttgc agccactggt ggcggcgctg240ggtttggccc tgcctggact tgcctcgttc cgaaagctgg ccgcctgggg agcactccgg300gagggtgaca acgctggact gctccactgg aacagtcgct tagatgcctt cgttctcagt360tatgtggccg cattgcccgc agctgccctg tggcacaagt tggggagctt ctgggcgccc420agcggccaca agggcgctgg agacatgctg tgtcggatgc taggcttcct ggactccaag480aaggggcgtc tccacctggt tctggttctc ttgatcctct cctgccttgg ggaaatggcc540
attcccttct tcacaggccg catcactgac tggatccttc aggataagac agcccccagc600ttcgcccgca acatgtggct catgtgtatt cttaccatag ccagtacagc gctggagttt660gcaggagatg gaatctacaa catcaccatg ggccacatgc acagccgcgt gcatggagag720gtgtttcggg ccgtccttca ccaggagaca ggatttttcc tgaagaaccc aacaggttcc780atcacatctc gggtgactga ggacacctcc aacgtgtgcg agtccattag tgacaagctg840aacctgttcc tgtggtacct ggggcgaggc ctgtgtctcc tggcgttcat gatttggggg900tcattctacc tcactgtggt caccctgctc agcctgcctc tgcttttcct tctgcccagg960aggctgggga aagtgtacca gtcactggca gtgaaggtgc aggagtctct agcaaagtcc1020acgcaggtgg ccctcgaggc cctgtcggcg atgcctaccg tacggagctt tgccaacgag1080gagggagagg cccagaagtt taggcagaag ttggaagaaa tgaagccgct aaacaagaaa1140gaggccttgg cttacgtcac tgaagtctgg accatgagtg tctcgggaat gctgctgaag1200gtgggaattc tgtacctcgg tgggcagctg gtggtcagag gggctgtcag cagtggcaac1260ctcgtctcct ttgttctcta ccagcttcag ttcaccaggg ccgtggaggt cctgctctcc1320atctatccct ccatgcagaa gtccgtgggc gcctcggaga aaatattcga atacctggac1380cggactccct gctctccgct cagtggctca ctggcacctt taaacatgaa aggcctcgtc1440aagttccaag atgtctcctt tgcctaccca aaccatccca acgtccaggt gcttcagggg1500ctgactttta cgctgtatcc cgggaaggtg acctccttgg tgggacccaa tgggtcaggg1560aagagcaccg tggccgccct gctgcagaac ctgtaccagc ccaccggggg caaggtgctc1620ctggatggcg agcccctggt ccagtatgat caccactacc tgcacacgca ggtggccgca1680gtgggacaag agccactgct atttggaaga agttttcggg aaaatattgc ctatggcctg1740actcggactc caaccatgga ggaaatcaca gctgtggcca tggagtctgg agcccacgat1800ttcatctctg gattccctca gggctatgac acagaggtag gtgaaactgg gaaccagctg1860tcaggaggtc agcgacaggc ggtggccttg gctcgagcct tgatccggaa gccacgcctg1920cttatcttgg acgatgccac cagtgccctg gatgctggca accagctacg ggtccagcgg1980ctcctgtatg agagcccgga gtgggcctct cggacggttc ttctgatcac ccagcagctc2040agcctggcag agcgggccca ccacatcctc ttcctcaaag aaggctctgt ctgcgagcag2100ggcacccacc tgcagctcat ggagagagga gggtgttacc ggtccatggt ggaggctctt2160gcggctcctt cagactga 2178<210>8<211>1184<212>DNA<213>褐家鼠(norway rat)<400>8ctcggcctct aagctcccgg agtcgctgcg tccgcgcagt ccggaactcg tgtggccacc60gcgggaacag agagggtccg ttgtaacctg ttgagtaact atggaggact atatcaaaat120agagaaaatc ggagaaggga cttatggtgt ggtatataaa ggtagacaca ggactactgg180ccagatcgtg gccatgaaga aaatcagact tgaaagcgag gaagaaggag tgcccagtac240ggcaatccgg gaaatctctc tgttaaaaga acttcgacat ccaaatatag tcagcctgca300
ggatgtactc atgcaggact ccaggctgta tctcatcttc gagttcctgt ccatggatct360caagaagtac ctggactcta tccctcctgg ccagttcatg gattcttcgc tcgttaagag420ttacttgtac caaatcctcc aggggattgt gttttgtcac tcccgacgag ttcttcacag480agacttgaaa cctcaaaatc tattgattga tgacaaagga acaatcaaac tggcagattt540cggccttgcc agagcgtttg gaataccgat aagagtgtac acacacgagg tagtgacgct600gtggtaccgg tcgccagagg tgttgctggg ctcggctcgc tactccaccc cggttgacat660ctggagcata gggaccatat ttgcagagct ggcgaccaag aagccgcttt tccacggcga720ctcagagatt gaccagctct tcaggatctt cagagctctg ggcaccccta acaacgaagt780gtggccagaa gtagagtccc tgcaggacta caagaacact ttccccaagt ggaagccggg840gagcctcgcg tcccacgtca agaacctgga tgaaaacggc ttggacttgc tctcgaaaat900gctggtctat gatccagcca aacgaatctc tggaaaaatg gcccttaagc acccatactt960tgacgacttg gacaatcaga tcaagaagat gtaaccctct ggaagtcccg ccctgctgtg1020gcagggaaga tcgtggcgtt tactgttggc tcttcctgtc ttgtatagtt ttcttttctt1080tgtctgtaaa ccatcatctg gacttttcct attttcctac gtataactta attaacatgt1140aaatattatt ccatatgaat ttaaatataa ttctgtatat gtgt 1184<210>9<211>2245<212>DNA<213>褐家鼠(norway rat)<400>9agggagattc tgaatccccc tgagaaagaa acacaaggtg aggggcccag cctgttcatg60gccagcacca agaccgaagc aattgccccg gcatccacca tggaagacaa ggaagaggat120gtggggtttc aggataacct ctttcttgag aaggcgctgc agctcgccaa gcggcatgcc180aacgccctct tcgactacgc ggttacggga gatgtgaaga tgctgctggc ggtacagcgc240catctcaccg cggtgcagga tgagaacggg gacagtgtcc tacacttagc catcatccac300cttcatgctc agctcgtgag ggatctgcta gaagtgacat ctggttcgat ctctgatgac360atcatcaaca tgagaaacga tctgtatcag acacctttgc acttggccgt gatcaccaag420caggaagatg tggtggagga cttgctgagg gttggggctg acctgagtct tctggaccgc480tggggcaact ctgtcctgca cctagctgcc aaagaaggac atgataaaat cctcggggtc540ctactcaaga acagcaaggc agcactcctt atcaaccacc ccaacgggga aggtctgaat600gccattcaca tagctgtgat gagcaacagc ctgtcatgtc tgcagctgct tgtggctgct660ggggcagaag tcaacgctca ggagcagaag tctgggcgca cggcactgca cctggccgtg720gagtacgaca acatctcgtt ggccggctgc ctgctcctgg agggtgacgc cctcgtggac780agcaccacct acgatgggac gacacctcta cacatagcgg ctggaagagg gtccaccagg840ctggcagctc ttctcaaagc agcaggagca gaccccctgg tggagaactt tgagcctctc900tatgacctgg acgactcttg ggagaaggct ggagaagatg agggagtagt gccaggcacc960acacccctgg acatggctgc caactggcag gtatttgaca tactaaatgg gaaaccatat1020
gagccagtgt tcacatctga tgacatactc ccacaagggg acattaagca gctgacagaa1080gacacgaggc tgcaactctg caagctcttg gaaattcctg atcccgacaa gaactgggcc1140actctggcgc agaagttagg tctggggata ttgaacaatg ccttccggct gagtcccgcc1200ccttctaaaa ctcttatgga caactatgag gtctctgggg ggaccatcaa agagctggtg1260gaggccctgc gacagatggg ctacacagag gccattgaag tgatccaggc agccttccgc1320accccggaaa ccacagcctc cagccccgtg accactgctc aggcccactt gctgcctctc1380tcgtcctcct ccacaagaca gcacatagat gagctccgag ataatgacag cgtgtgtgac1440agtggtgtgg agacatcctt ccgcaaactc agcttctcgg agtccctcac tggagatggc1500ccactgctat ctctgaacaa aatgcctcac aattatgggc aggatggacc tatagaaggc1560aaaatttagc ctgctggcgg ttccccacac tgtaaaccaa agccctgaaa ggccatcata1620tcgttccgaa ggagaaggca aaaaacgcat cccaaggtgc tggaaggtca ccggcctgca1680gggtcaatct tgatgtcatt cgaggccttc cgaatttggc ttcctttctt ggctctgaaa1740tgaaatttag ttgtcatata cagatggtgt ctagcaatca cggctgcact cggtgtggct1800tggggtatgg tggcttgagc ttttccagct gctattggat tacacttgct ttgtgttgtc1860actgctgtcc ctctgctggg tccccgctgt cattaaggta tcgcagtccc cacctggtgt1920tctttctagc catctacagt acagtcatgc actcaaatta agattaagga aaaagatatt1980tttaagtgag taacttcatg cgcaataaaa aaaagacatg gctttttcta atgtggttta2040tctgtgattt aaaaaaaaaa aacacatgaa cttaacaata tttaaaacct gctacaatca2100gtgctgaaaa tagtattttc ccccttttct gcattttact attgtaaata tgttttctaa2160atcaaatact ttaaaagaag aaatgttgga tttataaatg ctatttttta ttttactttt2220ataataaaag tacaagcaca ctgtt 2245<210>10<211>966<212>DNA<213>褐家鼠(norway rat)<400>10gagcctgagt tctcccagga gcagagtgag caggcgcagg agctacaaca tacaccacag60ggctgtgagg acagactctc gtgcctgtga gtgtcggtga gtcaaaccct ggggactgag120tccagtgcct cttctagcgt ccttggcatc atgggtcttc ggcttggcac caagatcact180gcgtgggact gctttccaaa ggatgtcatt gtccacaaaa gagagaaagc tggacacaca240tatgaaaatg gagaggacct gctgattggt gtacctagtg aagccacagt tcttgggact300atccagctaa tatgtgccct gatgattgca agctttgggg gaattttggt gtcagcttcc360tactccaacc cagaagcttc caccactttg atgtctggat acctgtttac tggatccttc420tgttttgcca tggctggaat tctctccatc atctctgaga aaatctcaac caaagccttt480gcactgagca gcctggcctc cagtgtagca agctctgttg ttgctatgat cggtctcttc540ttcgtcacct attgcctgat agtcctgggg actgcctttc cacactgtaa ctcagaaaag600aaattcctgc ccttattgtc ttatttggaa tcccatgatt ggaagaatga agacaagaac660tgtcgcctgg cttatgtcag tgctataagt actctgggga tcatgctcct cttcatcgtg720
ctggaagttt tgctagctgt atacagttct atcttttggt ggaagcaagt ctactccaac780aagcctgggg gtgcattttt cttgcctcaa tcacaagatc atccctaact tgtcaaaagc840agtttgttgc agtaatggat atgaaataca gaagaagaaa gaagaaatct agtgcttgtg900gcagagcaca gctagacttt cctgaaatct caaccttggt agatcctaat aaacatctga960agaaaa 966<210>11<211>618<212>DNA<213>大鼠种(Rattus sp)<400>11acacttctat gaagacaaga gcatttatta atttgaaagc atatcatctt taatacaaac60atttatagac tgcataacac attgcaatta aacatttctg taaaatagag tttatttatt120agtataacct tactgtataa tatagtatta ggcaagaatt gaaagaacgt aatgagagaa180cagggttgga tgatgtcaat gttgtcaaat ttgtggattt tacttttcac tatctctctg240tttggacttc tacaccaact ttaaaattcc aaatgtgaga cataaatgct tgtgtggaag300tatgccatca tcatcatcat tcaagcactg attggtgtta ttttaatgtg gctcagtcac360ttattgagat agaaggtggc ccactctgca gatattggag atcattagca tgagcatgcg420ggtgtgaaca ggagtgttgc tctctctaat ggggaattgt tcctcagggt acatctgact480gcagagtgaa gtctcagata catacctggg ttaagacagt cccatttaat atgtagagag540aaatacatct ttataacaca tcttttggat tgcttaaaaa tggaagtgac caacagctaa600tctggagtca gaatgagt 618<210>12<211>503<212>DNA<213>褐家鼠(norway rat)<400>12cggccgctgc ggcgggagga gccccccagg aggaggacgg ggatccatgt gtctttcctg60gtgactagga tgtcgtcgga ggaggaccgg agcgcggagc agcagcagcc gccgccagca120ccccccgagg agcccggagc cccggccccg agccccgcag ccgcagacaa aagacctcgg180ggccggcctc gcaaagatgg cgcttcccct ttccagagag ccagaaagaa gcctcgaagt240agaggaaaat ctacagtgga agatgaggac agcacggatg gactggagac gacggagaca300gaaaatattg tggagacaga agtcaaagaa caatctgtgg aggaggacgc tgagacagaa360gtggagagca gcaagcagcc agcctcagct cttcagcggt ctgtgtctga ggactctgca420cactccctgg tctctgtcgg tgtagaagcc aaaatcagtg aacagctctg cgccttttgt480tactgtgggg agaaaagttc ctt503<210>13
<211>618<212>DNA<213>大鼠种(Rattus sp)<400>13caaaattcta aaaagtttat ttgaaatcaa gccacccttc ccttaggctg cacggtagtt60cctcaaaggc agacaggtct gcagtgatgg taacaattca gcatgatcca gcttggggtc120cacaggaaca ggtgagaaca aaccctgcag gagctttcca ctgaaagcat cctggtataa180caggtactta cgtgagttct cattccggca gcttctattc taatgaactt gtaaatgttg240gaagtccaat ggcctttaaa ccatagcttt taccataatt gagaggaggt gacaggcagg300caggagccgc agaaaccatg atacatccac ttgtgttccc agaccccaga aatggtctta360catgacaata gttaagctca cagcaaaatc tgccatcagt gctccagctg tctagcatgt420gagaggtgac gtgacatcat atcagagctg agaccacgca gcttgtattt aacatgtggg480tgaggaaaga ggtcaaagta gagactataa acctgacgtt ggtgcactga ggcccacact540gtcaagtgca ctctcttagc tgtaagcagc agcacaccct ttgccaatgt ccacagcaga600gagcagacac agaccggt 618<210>14<211>2661<212>DNA<213>褐家鼠(norway rat)<400>14gccttgactc cagcacggtg acttaataga gctcggctct gccatgaagt ccgttgctct60attcctcatg ggcatcatct tcctggatca ctgtggagtt cgaggaaccc tagtgataag120gaatcagcga tgctcctgca tcagcaccag ccaaggcaca ttccactaca aatccctcaa180agacctcaaa cagtttgccc caagccctaa ctgcaacaaa actgaaatca tcgctacact240gaagaacgga gatcaaacct gcctagaccc agattcagca agggtgaaga agctgatgaa300agaatgggag aaaaagatca gccaaaagaa aaagcaaaag agggggaaaa accatcaaag360gagcaagaaa acccgaaaag ctaaaacacc ccaccatccg gagtcaaaga agactgcata420agagaccact ttaccaacaa gcgctctgca tctaaacggc ttttagatca tactaaaacg480ccttcccttt aatacacaac tcgttcacta caaaacattg tgcgcgaatt tgaaattata540gctaaagcta ggaagtcaag tgtaaaactc aagtagtaag aatttctaga ggcgaaaact600gtctttgttc tacgcagcca acaaaatttc atcgagccct tgagcacagc cgtgatatca660aatctgggca agtgtcccac acacaacaga tgcctggctt ctaaagccac acatgacaaa720caggatccgt gtggtcccct tgtcataggc tggagatctc gctgtccccc aagcctgtag780ccttctatca tgtgcctcta tgctctgatc ctggtgtttc ttgcagcatt cacagcaggg840ggacacccat cgtcactacc cgtagtggac accctgcaag gcaaagtcct cgggaagtac900gtcagcttag aaggattcac acagcctgtg gccgtcttcc tgggagtccc ctttgccaag960ccccctctcg gatctctgag gtttgctcca ccacagcctg cagagccctg gagcttcgta1020
aagaacacca cctcctaccc tcctatgtgc tcccaagacc ccgtggcagg gcaaatagtc1080aatgaccttc taactaactg ggaagagaac atttctctcc agttttctga agactgtctc1140tacctaaata tttacacgcc tgctgacttg acaaaacgtg atagactgcc ggtgatggtg1200tggatccatg gaggtggact agtgttaggt ggggcatcca cctatgatgg actagccctg1260tctactcatg aaaatgtggt ggtagtggtc attcaatacc gtctgggtat ttggggattc1320ttcagcacag gggatgaaca cagccggggc aactggggtc acttggacca ggtggctgca1380ctgcactggg tccaggacaa cattgacaac tttggagggg acccaggctc tgtgaccatc1440tttggagagt cagcaggagg tgaaagtgtc tctgttcttg tgttgtctcc cttggccaag1500aatctctttc acaaggccat ttccgaaagt ggcgtggccc tcactgcagg cctggtcaag1560aagaacacca ggcccttggc tgagaaaatt gctgttgtat ctggttgtaa aagcacaact1620tcagcttcca tggttcactg ccttcgccag aagacagagg aagagctctt ggagaccaca1680ctaaaattga atcttttttc gctggatttg cacggagact ccaggcagag ctatccgttt1740gttcccactg tgcttgatgg agtggtgctg ccaaagatgc ctgaggagat cctggctgag1800aaggacttca acactgtgcc ctacatcgtg ggaatcaaca agcaagagtt tggctggatt1860ctgccaacaa tgatgaacta tccaccctct gatatgaaat tggacccgat gacagccaca1920tcgctcttga agaagtcttc ttttcttctt aaccttcctg aagaagcaat tccagtggcc1980gttgagaagt atttaagaca cacagatgac ccagacagaa ataaagacca acttctggaa2040ttgattgggg atgtgatctt cggtgtccca tcagtgattg tctcccgtgg acatagagat2100gctggagccc gcacatacat gtacgagttt caatatcgcc caagcttctc atcaaaaatg2160aaaccaagta cggtggtagg agatcatgga gacgaaatct actctgtctt tggtgctcca2220attttaagag gtggtacctc aaaagaggag atcaatctca gcaagatgat gatgaaattc2280tgggcaaact ttgctaggaa tgggaatccc aatggacagg gcctgcccca ttggccagag2340tatgaccaaa aggaaggtta tcttcagatt ggagccacca ctcaacaagc ccagaagcta2400aaagaaaaag aagtggcttt ctggtctgag cttctggcta tgaagccact gcatgcagga2460cacactgagc tatgaacggg agctctgcca gcctcatcct cagggcagct cacatggaag2520atggttttgg ccaaggcttt gaggagactt cagaactgtg tggtgggagt gggcagaggc2580cagggagagg atatttgcac atgtggactc aaactgaaaa ataaattttg ttttataaat2640caaaaaaaaa aaaaaaaaaa a 2661<210>15<211>533<212>DNA<213>褐家鼠(norway rat)<400>15agttacaact ggcactcagc ctcagagcac cgacaaggca ctggcacaca gacactatgg60caaatgaagt acaagttctg tcgtccccgc tgaaagggcg gcatgctcca gcagtgaaag120ctggagggat gcgaatttcc aaaaaacaag agatgggcgt tttggaaagg cacacaaaaa180aaacaggatt ggagaaaaca agtgccatca caaatgtggc caagatacag atgctggata240
ctctaacgga cacactggac aagctccacc ataaattccc agcaacagtt cacacagcac300atcaaaagcc cacacctgct ctggagaagg ctgcaccact gaagagggcc tacattatcc360agcagcctcg aaaatgttag gccaggatag aaaatacagc cgtcgggtca acttccccac420gatctgacag ctcaacaaaa atggccaaca cttcctgtag gcctgctgcc tttacttggt480aaataaaaac aacttttgta tcttcccttt ccactttaga taataaagtt tcc 533<210>16<211>1611<212>DNA<213>褐家鼠(norway rat)<400>16gaagagcaag cgccatgttg aaaccattat tgccatctag atccttctta ctccttcagc60tgcttctgct gagggtaggg tggagctcca aggtcctcat gtccagtggg aatgaagaca120ccaaatctga tctcttgctg acttctatgg accttaaaca tctcagtgtt cctactctgc180ccctcccaga ggttcaatgc tttgtgttca atgtcgagta tatgaattgc acttggaata240gcagttctga gcctcagccg accaacctca ctatgcacta taggtacaag ggatctgata300ataatacatt ccaggagtgc agccactatc tgttctcaaa agagattact tctggctgtc360agatacaaaa agaagatatc cagctctacc agacatttgt tgtccagctt caggaccccc420agaaacccca gaggcgagcc gaacagaagc taaacctaca gaatcttgtg atcccatggg480ctccagagaa tctaacactt tataacctga gtgaatctca ggtagaactg aggtggaaaa540gcagatacat agaacgctgt ttacaatact tggtgcagta ccggagcaac cgagatcgaa600gctggacgga acaaatagtg gatcatgagc ctagattctc cctgcctagt gtggatgaac660agaagctgta cacatttcgg gttcggagcc gctttaaccc gatctgtgga agtactcaac720agtggagtaa atggagccaa ccaatccact gggggagcca tactgcagag gagaatcctt780ccttgtttgc actggaagct gtgcttatcc ctgttggcac catggggttg attattaccc840tgatctttgt gtactgttgg ttggaacgaa tgcctcgaat tcccgccatc aagaatctag900aggatctggt tactgaatac catgggaact tttcggcctg gagtggtgtg tctaaagggc960tgactgagag tctgcagcca gactacagtg aacggttctg ccacgtcagt gagattcccc1020cgaaaggagg agccctagga gaggggcctg gaggctctcc ttgcagcctt catagccctt1080actggcctcc cccatgttat tctctgaagc ctgaagcctg agcctccaat cccttgatgg1140aacctcaaag tcctatagcc ctaagtgatg ctaacctccc cctacacatt ttgccaacct1200ggatccaatg cttattgcct cccgctatgg ctaattttca atttcatgtc ccatgtaact1260gcttttccat tccatacgcc ctacttgaga atgccccttg ccccctttcc ctgcacaagc1320cctcccgtgc ctagtctagt actttttcac tttttttttg agagagtctt accctgtagt1380ccggggtggc tgggaactta ctacgtaggc cagattggcc tataactcag aggcgatcat1440cccacttctt cttctcaagt gtcggcgttc ttggcaagca ccaccacatc cagcacggcc1500ctcttctttt acaggattct ccctcccttt ttctacctac cattcaactg ttgccaaatc1560aataagaaat aaagttttta accaataaaa aaaaaaaaaa aaaaaaaaaa a 1611
<210>17<211>1030<212>DNA<213>褐家鼠(norway rat)<400>17tcgagagcat ctgaagccat ggcttacagt tgccagccgc tgcaggaatc accactcctc60gggtttccac gtctcaggtt cattcatctc tttgtgctgc tgctggtagg tcttctccag120atatcttcag gtattgtcgg ccaagtgtcc aagtcggtga gagaaaaggc attgctgtcc180tgtgattaca aattttgttc tgaagagcag tccatacacc gaatctactg gcaaaaacat240gacaaaatgg tgctctctgt catctccggg gtaccggaag tgtggcccaa gtacaagaac300cggactgtat acgacatcgc taacaactac tcctttagcc tcctgggcct gatcctttca360gacaggggca catacacctg tgtcgttcaa aggtacgaag gaggatcgta cgtggtgaaa420cacctgacca ccgtggagct gtctgtcaga gctgacttcc ctacccccaa cataactgag480tatggaaatc catctgctga cataaagagg attacctgct ttgcttccgg gggtttccca540aagcctcgcc tctcttggtt ggaaaatgga agagaattaa atggcatcaa tacaacaatt600tcccaggatc ctgaatctga gctgtacacc attagtagcc aactagactt caacgcgacg660tacgaccact tcatcgattg tttcattgag tatggagatg ctcacgtgtc acagaacttc720acctgggtaa aacccccaga agaccctcct gatgaaaagc aaacagttcc gtttgcctgg780gcaggacctg atgcagtcaa agccatcatc atcttcttca tcgccatcac cgtcatcgcc840gtcatcgccg ccatcgccat catcatcttc tgcatcactg tcaaattccg acgctgcttc900agaagaagaa atgaggcaag cagagaaaca aacaagaacc tctacatagg gcctgtggaa960gcagcagctg aacagactgt ttgaaggtag ccatttgcct tcctttagct cttctctgcc1020cactcgagca 1030<210>18<211>4535<212>DNA<213>褐家鼠(norway rat)<400>18caccggctgc tcggccgcag ctcgcccgcg cgccgcctcg gggccaccgc caggctccag60cgctccggtt caagaggagc cacactgggg agtcccaagg aagcagccag gcagatgggg120agcccaggat ccgtggtttc cctctcctta gtctgctgga ggacgcgcgt ggtggtacca180agttccacac atgacttaat gaataaggga atgccagagc tgaagaggac ccagcatgac240tactaaccta tgactcctaa cagtatgaca gaaaaatgcc ttccagcctg ggacaaacag300aagccccatc cagaccgagg ccaggactgg aagctggtag gaatgtccga agcctgcctg360cacaggaaga gccatgtgga gaggcgtggt gcattgaaga atgagcaaac atcctcacac420ctcatccagg ccacttgggc gagctctata ttccatctgg atccagacga tgtgaacgat480cagagcgtct caagcgccca gactttccag accgaagaga agaaatgtaa agggtatatc540
cccagctatc tagacaagga tgagctctgc gtagtgtgcg gggacaaagc cacggggtac600cactatcgct gcatcacctg tgaaggctgc aagggtttct ttagaagaac cattcagaaa660agtctccatc catcttactc ctgtaaatat gaagggaagt gcatcataga caaagtcacc720cgtaaccagt gccaggaatg tcgctttaag aaatgcatct atgttggcat ggcaacagac780ctggtgctgg atgacagcaa gaggctagcc aagaggaagc tgatagaaga gaaccgtgag840aagaggcggc gggaagagct acagaaatcc attgggcata agccagagcc cacggatgag900gaatgggagc tcatcaagac agtcaccgag gcccacgtgg ccaccaatgc ccagggcagc960cactggaagc agaagcggaa atttctgcct gaagacattg gacaagcacc cattgtgaac1020gccccggaag gtggcaaggt tgatctggaa gccttcagcc attttacaaa aatcatcaca1080ccagcaatca ccagagtggt ggatttcgcc aaaaagttgc ccatgttttg tgagctgccc1140tgtgaagacc agatcatcct cctcaaaggc tgctgcatgg agatcatgtc cctccgagct1200gctgtgcgct atgacccaga cagcgagact ctaaccttga atggggaaat ggcagtgaca1260cggggccagc tgaaaaacgg aggtcttggg gtggtgtcag atgcgatctt tgacctgggc1320atgtctctgt cgtctttcaa cctggatgac acggaggttg ccctgcttca agccgtcctg1380ctgatgtctt cagatcgccc agggctagct tgtgttgaga gaattgagaa ataccaagac1440agtttcctgt tggcctttga acactatatc aattaccgga agcaccatgt gacacacttt1500tggcccaaac tcctgatgaa ggtgacggac ctgcggatga ttggagcgtg ccacgccagc1560cgcttcctgc acatgaaggt ggagtgcccc accgagctct tcccgcctct cttcttggaa1620gtctttgagg actgaacgga ctggacaggt tcttgtcatt cctgcagcac gactgggtgt1680cgctgcattc cacctgtagc tctttctgtt gtcgtttctt cgtttctttg tgtcaagtga1740gctcatcagt gggtcagcgg gtcatcagtg gcatagactt ggatgaagtg gtcctttgaa1800tgtgggtctt tgtaaccatt gcgtttcgtt ctccagtcct tagtgtgacg gctttgaggg1860gttcacagca gtgcaggccg agtgggggcg atcatctcac cagcaccacg tcgtcaccag1920ctcccatctg tccctgggca gactcaagca agccaaatgg cattacagaa gactaaagaa1980gccttaaaac cgagacgaca gtcatcttga tccaatgcga tccagttctg ttgtttgtaa2040ggtgaagctg gcagagctca ggccacctca ggttgggcgt ggcttttggc gcgtgagggg2100aggagccgtt ccagcttcag gaactcacag ctactcagga gcttaccgct tccagcaccc2160ttactctcca agcaggctga cttggaatgt gcaggatacc cacaccataa caaatcgacg2220ttactttcca tggccttctg taaccttgtg atttacttca agttgcgcaa gagtagaact2280tggagacttg actggtttga ggccacaagg aaagtctcct tttcaggatg cccatagagc2340ttggaaatca tccatgttac agcatagttt ccaaaaatgg tgttacctca agcaggaagg2400cacctttgca gcttagatag attcacaagc cattcccaca gagctcaaac ctgtttacag2460agtgccgtcc ctcttccgat ggcctatgaa ccagccctct ccccagcctg tggctgttga2520gctggtgatg tttccctgta cattgaatct tccaatcaga gagagacgtg ttgaaactcc2580agtcttgttt tggaaaaatc cctggaaaag atcaatgcag gaacaatcag attcaaagga2640aaagaactac tcatgctgta ggctgtccaa ttagggagaa tgctccccgt ggatcggcaa2700ggcgctttac ccattcacaa atgtctccca gtcccatccc gtctctgctc ccaaacccac2760ctcctcagat tctgagacac taaatagctt ctcttctctt ctcttctctt ctcttctctt2820ctcttctctt ctcttctctt ctcttccctt ctcttctctc tctcaacact aactcttctg2880
tagcttatac actattacct tggcaaatag tcctcataaa atataggaga ccatgcatag2940gaaacaccat tacgctgccc catccccagt gaccgtgtag agtagatgtc tctaagcaac3000cagtagtgac aacttaccca aaaatgggca gactgtaccc atgcaactga atgtacgact3060cttcactgat gtcacagatg tgaactactt cttgtctgcc tttcactgcc ttagcctgga3120aatgctggga aaaacaagcc atatcagtga gaattaccta aaagcaaagg aagtcactgt3180gaaaagcaag ggaactcact tcttcccacc gggctcggta gagcatcttt ggcctcacag3240caagtcaggg tgcctgcggc ctgggtcatt taggacctta tcagtgttag ttttcttacc3300tcctagtaaa tgagttgatc tccagaaacc cctcttccct tctctagtgt ttgacttttc3360agactaagga gggggcgtct ttgaaagatt ccttttctat tcaaacttct agcttcggaa3420acggaatgca tgtgggtgct catggagtga gaatgaggat ttgattcaga ggaaggcaga3480atgacctcgg aagcagagag gtacagccct gaaagtcttt ggaaataact gaggaaaagg3540gaacagtctg tgcagggaac taaagattta gcctgatgtt ttagcagata aaaacatcgc3600tgtagacttg gtgtggagat taaatagaaa caagaagccc ccagagagtc aagttcaagc3660atctgtctga gatttgcttt cccaggcaac ctgtacccag cctcctccct caggaatttc3720attaaaacat ctgtcccctc tgtcagctct cctggaatgc ctctgtccag acaattaaaa3780cacacttgct gtgagaccag ttctccgtcc aaagagggag agagggaggt gacaggtagg3840tgagtcccac acaggcatac aaacttctgg ggcaccagag tttctgagga agtttcctga3900tgctgacagt tttcaaatgg catcggaaac cctggcatta gtgcagggtt tgacccaggg3960tcattcagag cgctgtaaag attaagcgct gggcactagc ccggtcctca caatccagcc4020agccacagca cagtgaccct ccctctgtag aggctcacct ttcagggacg aaccaggctg4080tagcaaccgt ggagactgag tactgaacaa gacaagcaag cttcagtctt ctggcgggaa4140ggaacaagaa cggtaggcat tcagaatggc cttcgagaaa ctcattttat gcactagatt4200gtgagggatt tgctcccaat gttttttttt ttcttcttct tcttcttctt tttcaaagtc4260attcccttct aatcttgtcc agactttcaa ttcaagtgtg gacgcggtga caagaacctt4320tacacctgct ccaccgtggg gagactttcc agtcaaggag aacacgctca tcctgctggg4380gcactcactg acaaatggta ttcatgaacg agaaggctgt gcacatgcaa ccgacatgtg4440cgtgtgcaca catgtgcgta catccggtcg ttgcctcaag tgtactttgc acttcagtta4500aaatgtgcag aacttccaga aactggaaga agaag 4535<210>19<211>3636<212>DNA<213>褐家鼠(norway rat)<400>19ggagcctcgg cgggaggagg cggacacgtg gcagcggcgg cggcagcggc agcagcagcg60gcggcagcag cggcggcctc ggtccggggc gccggccgtc ctccctcttt cctccggcgg120cagccctagt tcccgcctct cggctccccc ggctccactc tcccagccgg gagctgctct180ctcctctttc tagtctccag ccacaggacc cggcgcgggg cccgcagcgc cgccaccatg240
gggaaggggg ttggacgaga caagtatgag cccgcagctg tatcagaaca tggggacaag300aagagcaaga aggcgaagaa ggaaagggac atggacgaac tcaagaagga agtgtctatg360gacgaccata aactcagcct ggatgaactc catcgtaaat acggaacaga tttgagccga420ggcctaacac ccgcaagggc cgctgagatc ctggctcggg atggccccaa cgccctcacg480ccccctccca ctactcccga gtgggtcaaa ttctgtcggc agctgttcgg tggcttctcc540atgttactgt ggattggagc cattctttgt ttcttggctt atggcatccg aagtgctaca600gaagaggaac caccaaatga tgatctgtac ctcggggtcg tgctgtctgc tgtcgtcatc660ataactggct gtttctccta ttatcaagaa gcaaaaagct ccaagatcat ggaatccttc720aagaacatgg tccctcagca agccctcgtg attcgaaatg gagagaagat gagcatcaac780gcagaggatg tcgtcgttgg tgatctggtg gaggtgaagg gcggagaccg aatccctgct840gatctcagaa tcatatctgc aaatggctgc aaggtggata actcctcact cactggtgaa900tcagaacccc agactcggtc cccggatttc acaaacgaga accccttgga gacaaggaac960attgccttct tctcaaccaa ctgtgttgaa ggaactgcac gtggcatcgt tgtgtacact1020ggggatcgca ccgtgatggg caggatcgcc acccttgctt ctgggctgga aggcggccag1080acccccattg ctgaagaaat cgagcacttc atccacctca tcacgggtgt ggccgtgttc1140ctgggggtgt ctttcttcat tctctctctg atccttgagt acacctggct cgaggctgtc1200atcttcctca ttggtatcat cgtagccaac gtgccggaag gtttgctggc caccgtcacg1260gtatgtctga cgctcactgc caagcgcatg gcgaggaaga actgcctggt gaagaacctg1320gaagctgtgg agaccttggg gtccacatcc accatctgct ccgacaagac tggaactctg1380actcagaacc ggatgacagt ggctcacatg tggtttgaca atcaaatcca tgaagctgac1440accacagaga atcagagtgg ggtctccttt gacaagacgt cagccacctg gttcgctctg1500tccagaattg ctggtctctg taacagggca gtgtttcagg ctaaccaaga aaacctgcct1560atccttaagc gtgcagtagc gggagatgct tccgagtcgg cgctcttaaa gtgcatcgag1620gtctgctgtg gctccgtgat ggagatgagg gagaagtaca ccaagatagt ggagattcct1680ttcaactcca ccaacaagta ccagctctcc attcacaaga acccaaacgc atcggagcct1740aagcacctgc tagtgatgaa gggcgcccca gaaaggatcc tggaccgatg cagttctatc1800ctcctccacg gcaaggagca gcccctggac gaagagctga aggacgcctt tcagaatgcc1860tacctagagc tggggggcct tggagagcgt gtgctaggtt tctgccacct ccttctgcct1920gacgaacagt ttcccgaagg cttccagttt gacactgatg aagtcaattt ccccgtggat1980aacctctgct tcgtgggtct tatctccatg attgaccctc ctcgagctgc tgtccccgat2040gctgtgggca aatgccgcag cgctgggatt aaggtcatca tggtcacagg agaccatcca2100atcacagcca aagccattgc taagggggtg ggcattatct cagaaggtaa cgagaccgtg2160gaagacattg ctgcccgcct caacattcca gtgaaccagg tgaaccccag agatgccaag2220gcctgtgtag tacatggcag tgacttgaag gacatgacct ctgaggagct ggatgacatt2280ttgcggtacc acacggagat tgtctttgct aggacctctc ctcaacagaa gctcatcatt2340gtggagggct gccagcggca gggtgccatc gtggctgtca caggggatgg tgtcaatgac2400tctccagctt tgaaaaaggc agatattggg gttgccatgg ggattgttgg ctcggatgtg2460tccaagcaag ctgctgacat gattcttctg gatgacaact ttgcctccat cgtgactgga2520gtagaagaag gtcgtctgat atttgataac ttgaagaaat ccattgctta caccctaaca2580
agtaacattc cggaaatcac ccccttcttg atatttatta ttgcaaacat tccactgccc2640ctgggcaccg tgaccatcct ctgcattgac ttgggcactg acatggttcc cgccatctct2700ctggcctatg aacaggctga aagtgacatc atgaagaggc agcccagaaa tcccaaaacg2760gacaaacttg tgaacgagcg tctgatcagc atggcctatg gacagatcgg tatgatccag2820gccctgggag gcttcttcac ttattttgtg attctggctg agaacggttt cctgcccttt2880cacctgttgg gcatccgaga gacctgggat gaccgctgga tcaatgatgt ggaggacagc2940tacgggcagc agtggaccta cgagcagagg aagattgtgg agttcacctg ccacacggcc3000ttctttgtca gtatcgtggt agtgcagtgg gctgacttgg tcatctgcaa gaccagaagg3060aattctgtct tccagcaggg aatgaagaac aagatcttaa tatttggcct ctttgaagag3120acagctcttg ctgctttcct gtcctactgc cctgggatgg gtgcagccct taggatgtat3180cccctcaaac ctacttggtg gttctgtgcc ttcccctact cccttctcat cttcgtgtat3240gacgaggtgc ggaagctcat catcaggcga cgccctggcg gctgggtgga gaaggaaacc3300tactactagc ccactgccct gcacgccgtg gaacattgtg ccacacactg cacctacccc3360taccccccct ttgtgtactt caagtcttgg agctcggaac tctaccctgg taggaaagca3420ccaaagcatg tggggatcca gacgtcctgg aatgaagcat gtagctgtaa tggggggcgg3480ggggagggct gcccgaaaaa caccgtggac ggggacgaca gcggggaagg tttatatgtg3540cctttttgtt tttgtaaaaa aggaaaacct ggaaagactg aaagattacg ttttatatct3600ggatttttac aaataaagat ggctattata acggaa 3636<210>20<211>2508<212>DNA<213>褐家鼠(norway rat)<400>20ggcagtggcc acagcagagg aatatagctt cacccaggat gttatctctg acctggggta60tgaagctagt ggaaagatct gtggtcccca gggtcctcct cttgctcttt gcactctggc120tgctcctcct ggttccagtc cggtgttctg aaggccaccc cacttggcgc tacatctcat180cagaggtggt tattcctcgg aaggagatct accacagcaa aggaattcaa acacaaggac240ggctctccta tagcttgcgt tttaggggcc agagacatat catccacctg cgaagaaaga300cactaatttg gcccagacac ttgttgctga caactcagga tgaccaagga gccttacaga360tggattaccc ttttttccct gtagattgtt actattttgg ctacctagag ggaatccctc420aatccatggt cactgtgaat acttgctatg gaggcctgga agggatcatg atgttggatg480accttgccta tgaaatcaaa cccctcaacg attcacaggg gtttgaacac attgtttctc540agatagtatc agagcctgat gtaacagggc ctacaaatac atggaaacgc ttgaacctta600atacaggtcc tcccttatcc aggacagagt atgccaatgg aactcccaga atgtctagta660agaactacgc ttcacatcca gctgctataa aaggccaatt ccaagcaact aattctatat720ataaggaaag caacaatatt gatactgcgg ccaggtattt gtttgagctc cttagtataa780cggacagctt tctgatcact attcatatgc ggtactatgc tattctctta actgtgttta840
ccgagagcga tccatttgca ctagagtata cggtaccagg gggctctatt tataactatt900atgtgtctaa cttttttaat cggttgaggc ctgatgcatc aaccgtactt aataaagatg960ggccctcgga taacgacttt catccagttg aacagagttt atgtactccc gcaggcctga1020cgattgttgg tcaacacaga cgaagttttc tagctctatc tgttatgatc accaatcgta1080ttgcgatgtc tttaggtata aaagctgatg atgagactta ctgcatctgc cacagaagga1140ccacttgcat tatgtacaaa aaccctgaaa taacagatgc tttcagcaat tgctcccttg1200tgcagataaa ccagatactg aatacccctg gtacaatgtc atgccttttc tatgaccacc1260atgtttatca taatataaca aaaacctaca ggttttgtgg aaacttcaag atagatatcg1320gtgagcagtg tgactgtggc tcacataagg catgttacgc agatccctgc tgcggaagta1380attgcaagtt aactgctggt agcatttgtg ataaagaatt atgctgtgca aactgcacct1440acagtccttc tgggacactc tgcagaccga tccagaacat atgtgatctt ccagaatact1500gtagtgggaa taatatcttt tgccctgcag acacttatct gcaagatggg acgccatgct1560cagaagaggg gtactgctat aaaggcaact gcacagatcg cagtgtgcag tgcaaggaaa1620tctttggtat gaatgctaag ggtgctaata tcaagtgcta tgacatcaac aaacaacggt1680ttcgatttgg gcactgcact agagcacaag agagcctcat gtttaatgct tgctctgatc1740atgataaact gtgtggaagg ctgcagtgta ccaacgtcac caatcttcca ttcctgcagg1800aacatgtttc attccatcaa tcggttatct ctgggtttac ctgctttggg cttgatgaac1860atcgtgggac agaaacaacg gatgctgggc tggtgaaaca tggtacccct tgctcccaaa1920ctaacttctg cgatcgagga gcttgcaatg gaagtttatc tcggttggat tatgactgca1980ccccagaaaa atgcaatttt agaggagtgt gtaataatca tcggcattgc cattgtcatt2040taggttggaa acctcctctg tgcagagagg aggggcctag cgggagcacg gacagtgggt2100cccctccgaa ggaaaggcgc acaataaaac agagcagaga accactgtta tatttaagaa2160tgctctttgg tcgtctttat ttattcattg tctcgctgct ctttggagtg gccactcgcg2220caggagttat taaggtcttt aagtttgaag acttgcaagc tgctctgcgg gctgcacaag2280ccaaggcgac ttaaagatga acgaggtcct cgtaagataa agagaatgca aaaatgcatg2340tcaagagggg acaaggtaga actccagtcc acagttctgg agagccttca tctatatcgt2400ggggacgcaa gaggttttgg atttggatac cacctgacat tggtgggtta ctgatgctca2460cactcgaata aatctttcaa aaccgcaaaa aaaaaaaaaa aaaaaaaa 2508<210>21<211>429<212>DNA<213>褐家鼠(norway rat)<400>21gacagcctca gtcttgcttc tggtggcttt gatcgccgtg ggaatgaaca ttacctatgc60tctgttttct cccacaaaat tagaaaaacc tggaaagtgt cccaagaatc ccccaagaag120tattggcact tgtgttgaat tatgctcagg agatcaatcg tgccccaaca tacagaagtg180ctgttccaat ggctgtggtc atgtttgcaa atctcctgtc ttttaagtta ctaacagcga240tctggaatat ggatttgatc ttcataagca cgactgatgg ccagccccag aagatttctt300
ctgaatccct agagcccatg cttggctcct cccttgtcct agaattgcat ccttggaaaa360ggaagatcta tactgtgatg acagcttcct aatgtgtttg tgtccacaaa taaactctcc420ttagcattc429<210>22<211>2722<212>DNA<213>褐家鼠(norway rat)<400>22caggaggcgg ccggggcgtg tgggattgag gagtggagga ggaggcggag agtcagggct60ctgaggggga gctgttccca agctaaggga ggagcccccg gaagacgccg cggaaggcag120cgaggcggag gcggccggag tacggacgcg atgtggcccg acccgcgctg ctgcgctgag180gcgcccgcgg cctgagcccc ccggcgctgc gctcggttcg gctcggcccg gttcggctcg240gctcggcggc cggcgaggtc gatgcccttg agcgcggctg cgcgcagctc ggctgtgcgg300ccccgcggcg cgcgctgagc ttctcggcgg ccccggccgc tctcagctcg gcgctcgatg360tgtagccaca tagttatctg tacacttcgt cgccggggct ttaatgagga cctgagtcgc420gagcgcgagt gaatcaccgc ctgggccggg gaaagaggac ggcgcattta accccctccc480accccactcc atgtccctgt gtcactcggc tctgtccacc tggcgcggcg ggtcctggag540ctgctactgc tgctgacgat cgactcccct cgcgcctctc gccccagaag ctcttgtgct600cccacgtaac ttctactttt tttttttcct tttgagaaag ctcagcacga accgatcaga660attgtgaagg gtttttgttt tttttttgtt ttttgttttg cttttgggtt ttccgaagct720ccagcacttc tgctcttgtt tttgttttgt tttctgcgta aacctctggc ccactctcaa780aaggcaagat gtccagtcat gtcccggcgg atatgattaa tttgcgcctc atcttggtga840gtggaaagac gaaagagttc ctcttctccc caaacgactc tgcctctgac atcgcaaagc900acgtgtatga caactggccc atggactggg aagaagagca ggtcagcagc ccgaacattc960ttcgactcat ttatcaaggc agatttctac acggaaacgt caccctagga gcattaaaac1020ttccttttgg caaaacaaca gtgatgcatt tggtggccag agagaccctg ccagagccca1080attcacaagg tcagagaaac cgggagaaaa ctggtgagag caactgctgt gtgatcctgt1140aacatcgtcg ccagcgcagg tgtggcagtc tgttaccact gcggggacag aggagactcg1200gcagcttccg acacctgtgg gacagtcgcc cgcacatcca gactgaacca ctcatgagct1260ctgtgatctc tcctcacaaa gtaaaaagaa ccaagaacat ttccagtctg gtcctttatt1320cctgtatctc ttgtctgtgt tgagcagtct gaaatgcaca gtggtctcca ggggaaatag1380caagtctctc aagtctctct ctgcagaaac cgccttgctg ccacaaagac tcctccacag1440aagtcagaag gcgagtgctg caagttcaat ttgcactaaa aacattatta ttttcctcat1500cagcgtaatc tgcacatgtc tgtggcgccc agacgttctc ctgtgtggag ttcaccctgg1560aggacgccca tcatcagtgc agttaatacc aggccagttg gaccggggaa atgggaagga1620atctaacatg ctgggtgaat tctaccaaag tcagccacag tggctgtcct cgaaggatgt1680cagactgggc atgactcttg tcaccacagc aaatgagaag ccatgcctgc tgctcacagc1740
actctgtaga gggtgcccct gctgcctgcc caccgagtcc tccccacagg gggctcatgc1800agacagcaca gaggggccgc agtgtgtccc tagccttaat gtggaggggc cagtgtctcg1860gtgccatcac tgtgcagaac tggtgggaag cctcagcggt tgtgtacttg agtatcagaa1920gattgatagc ttgcgccacc atcactcatt cgaaccctgc cgagtgtact cgctcactag1980agcagaggga tccttttaaa gtctccagat gctaattttg ttactttctg tagtttgcat2040tcggaatcag tgcttgcaat tgtattaaaa tcacaagctg agttttaagg catacatgat2100caatagcgcc actcttattt ttaccaataa tttaaagatt gagatgctat aaataaacaa2160tttgcacagc actaaagcat gagctaattt catctaaacc tgtaaaaaaa agattttata2220tttttttcac tgggaagaaa tcttcctgga tgaaattaca aatatgtgta gattatattt2280aataaaaaag acataataaa atatctaact gtagaatgca aatatagatt ggcgtgtagc2340atatagacca gtattccata tcaataactt tatccagcct tttaaaagat gaagttgcag2400actacgttgt gttctgtatt taatgagggt tcttggccct cggcagcatt aaatgtaaat2460ggtctctatg gtcatctttg tttaaatgca atcaggttac tttattcatt gttaatgctt2520ccatgagaag gctttatatg cagtagatct acgaaaatat tgttcatact gatcagaatt2580aaatttgtat agagcagagt tttaaaatga atgtaaatag cactaaacct tttctttctg2640cagcctgtac ttaatagatt tcttctgtaa actaaataaa aaaaaattgt agtgcaaaaa2700aaaaaaaaaa aaaaaaaaaa aa 2722<210>23<211>3471<212>DNA<213>褐家鼠(norway rat)<400>23ggcacgagga ccggctgagg attttatggt tcttaagcgg acttaagagc gttgtttcgg60attgttaaga ttcccgtttg ctgggttttc ctccctcaat cgtgctctcc cgcggctgcc120tggggactgg ctcggcgaag gaggatggag agggggctgc cgttgctgtg cgccacgctc180gcccttgccc tcgccctggc gggcgctttc cgcagcgata aatgtggcgg gactataaaa240attgaaaacc cggggtacct tacatctccc ggctaccctc attcttacca tccaagtgag300aaatgtgaat ggctaatcca agctccggag ccctaccaga gaatcatgat caacttcaac360ccacatttcg atttggagga cagagactgc aagtatgact atgtggaagt gatcgatgga420gagaatgaag gtggccgcct gtgggggaag ttctgtggga agatcgcacc ttcacctgtg480gtgtcttcag ggccatttct cttcatcaaa tttgtctctg actatgagac ccacggggca540ggattttcca tccgctatga aatcttcaag agagggcccg aatgttctca gaactataca600gcacctactg gagtgataaa gtcccctggg ttccctgaaa aataccccaa cagcttggag660tgcacctaca tcatctttgc accaaagatg tctgagataa tcctagagtt tgaaagtttt720gacctggagc aagactcaaa tcctcccgga ggagtgttct gtcgctatga ccggctggag780atctgggatg gattccctga agttggccct cacattgggc gttactgtgg gcagaaaact840cctggccgga tccgctcctc ttcaggcatt ctatccatgg tcttctacac tgacagcgca900atagcaaagg aaggtttctc agccaactac agcgtgctgc agagcagcat ctctgaagat960
ttcaagtgta tggaggctct gggcatggaa tctggagaga tccattctga ccagatcact1020gcatcttccc agtatggtac caactggtct gttgagcgct cccgcctgaa ctaccctgaa1080aacgggtgga caccaggaga ggactcctac agggagtgga tccaggtgga cttgggcctc1140ctgcgattcg ttactgctgt ggggacacag ggtgccattt ccaaggaaac caagaagaaa1200tattatgtca agacttacag agtagacatc agctccaacg gagaggactg gatcaccctg1260aaggagggaa ataaagccat tatctttcag ggaaacacca atcccacgga tgttgtcttt1320ggagttttcc ccaaaccact gataactcga tttgtccgaa tcaaacctgc atcctgggaa1380actggaatat ctatgagatt tgaagtttat ggctgcaaga taacagatta cccttgctct1440ggaatgttgg gcatggtgtc tggacttatt tcagactccc agattacagc atccaaccaa1500ggagacagga actggatgcc agaaaacatc cgcctggtga ccagtcgaac cggctgggcc1560ctgccaccct caccccaccc atacatcaat gaatggctcc aagtggacct gggagatgag1620aagatagtaa gaggtgtcat cattcaaggt gggaagcacc gagaaaacaa agtgttcatg1680aggaagttca agatcgccta cagtaacaat ggttctgact ggaaaatgat catggatgac1740agcaagcgca aggctaagtc ttttgaaggc aacaacaact atgacacacc tgagctccgg1800gcctttacac ctctctccac aagattcatc aggatctacc ccgagagagc cacacatagt1860gggctcggac tgaggatgga gctactgggc tgtgaagtag aagtgcctac agctggaccc1920acgacaccga atgggaaccc cgtggacgag tgtgacgatg accaggccaa ctgccacagt1980ggcacaggtg atgacttcca gctcacagga ggcaccactg tcctggccac agagaagcca2040accattatag acagcaccat ccaatcagag ttcccgacat acggttttaa ctgcgagttt2100ggctggggct ctcacaagac attctgccac tgggaacatg acagccacgc gcagctcagg2160tggagggtgc tgaccagcaa gacggggccc attcaggacc acacaggaga tggcaacttc2220atctattccc aagctgatga aaatcagaaa ggcaaagtag cccgcctggt gagccctgtg2280gtctattccc agagttctgc ccactgcatg accttctggt atcacatgtc cggctctcat2340gtgggtacac tgagggtcaa actgcactac cagaagccag aggaatatga tcaactggtc2400tggatggtgg tcgggcacca aggagaccac tggaaggaag ggcgtgtctt gctgcacaaa2460tctctgaaac tgtatcaggt tatttttgaa ggtgaaatcg gaaaaggaaa cctcggtggg2520attgctgtgg atgatatcag tattaacaac cacattcctc aggaggactg tgcaaaacca2580acagacctag ataaaaagaa cacagaaatt aaaatagatg aaacagggag caccccagga2640tatgaagaag ggaaaggcga caagaacatc tccaggaagc caggcaatgt gcttaagacc2700ctggacccca tcctgatcac catcatagcc atgagtgccc tgggggtgct cctgggtgca2760gtctgtggag ttgtgctgta ctgtgcctgt tggcacaatg ggatgtcgga aaggaaccta2820tctgccctgg agaactataa ctttgaactt gtggatggtg taaagttgaa aaaagataaa2880ctgaacccac agagtaatta ctcagaggcg tgaaggcacg gagctggagg gaacaaggga2940ggagcgcggc aggagaacag tggaggcgca gggactctgt tactctgctt tcactgtaag3000ctgggaaggg cggggactct gttactccgc tttcactgta agctcggaag ggcatccgcg3060atgccatgcc aggcttttct caggagcttc aatgagcatc acctacagac acaagcaggt3120gactgcggta acaacaggaa tcatgtacag cctgctttct tctcttggtt tcgtttgggt3180aatcagaagc cagttgagac caagtgtgac tgacttcatg gttcatccta cttggccccc3240
tttttcctct ctttctcctt accctgtggt ggattcttct cggaaactgc aaaatccaag3300atgctggcac taggcgttgt tcagtgggct ctttcgatgg acatgtgacc tatagcccag3360tgcctagagc atattagcat aaccacattt caggggacac caatgtccgc ttttgcatcg3420ctacgtgcag cgagcacagg aaaaagaaaa aaaaaaaaaa aaaaactcga g 347权利要求
1.一种体外检测口腔白斑癌变相关基因表达水平差异的方法，其特征在于它包括以下步骤(1)4NQ0诱导的大鼠白斑癌变模型的建立及样本收集(2)样本总RNA提取和芯片杂交(3)芯片扫描及数据分析。
2.根据权利要求1所述的方法，其特征在于体外检测口腔白斑癌变相关基因表达水平增强。
3.根据权利要求1所述的方法，其特征在于体外检测口腔白斑癌变相关基因表达水平降低。
4.根据权利要求2所述的方法，其特征在于相关基因它具有如SEQID1、SEQID2、SEQID3、SEQID4、SEQID5、SEQID6、SEQID7、SEQID8、SEQID9、SEQID10、SEQID11、SEQID12、SEQID13所示的核苷酸序列。
5.根据权利要求4所述的方法，其特征在于SEQID1基因编码的蛋白是趋化因子(C-X-C基序)配基9、SEQID2基因编码的蛋白是细胞周期因子A2、SEQID3基因编码的蛋白是类似于细胞周期因子B2、SEQI D4基因编码的蛋白是雌激素受体2、SEQID5基因编码的蛋白是Janus激酶3、SEQID6基因编码的蛋白是趋化因子C-X-C配基10、SEQID7基因编码的蛋白是运载体1，ATP-结合盒，B亚科、SEQID8基因编码的蛋白是细胞分裂周期2同系物A、SEQID9基因编码的蛋白是核转录因子KB p105亚单位、SEQID10基因编码的蛋白是跨膜域4，A亚科，7。
6.根据权利要求3所述的方法，其特征在于相关基因它具有如SEQID14、SEQID15、SEQID16、SEQID17、SEQID18、SEQID19、SEQID20、SEQID21、SEQID22、SEQID23所示的核苷酸序列。
7.根据权利要求6所述的方法，其特征在于SEQID14基因编码的蛋白是羧酸酯酶1、SEQID16基因编码的蛋白是白细胞素2受体γ链、SEQID17基因编码的蛋白是CD80抗原、SEQID18基因编码的蛋白是甲状腺激素受体β、SEQID19基因编码的蛋白是ATP酶，Na+K+转运，α1、SEQID20基因编码的蛋白是解聚素及金属蛋白酶domain 6、SEQID21基因编码的蛋白是细胞外蛋白酶抑制剂、SEQID22基因编码的蛋白是泛激素类似物3。
全文摘要
本发明涉及一种体外检测口腔白斑癌变相关基因表达水平差异的方法。本发明有以下步骤(1)4NQO诱导的大鼠白斑癌变模型的建立及样本收集；(2)样本总RNA提取和芯片杂交；(3)芯片扫描及数据分析。该方法包括(1)体外检测口腔白斑癌变相关基因表达水平增强的方法；(2)体外检测口腔白斑癌变相关基因表达水平降低的方法。本发明所公开一种体外检测口腔白斑癌变相关基因表达水平差异的方法，其优点表现在通过对口腔白斑癌变全过程的基因表达谱进行动态性跟踪研究，筛选出白斑癌变过程相关靶基因群，可从整体水平快速、全面把握白斑癌变机制；可推动口腔白斑诊治和预后判断等水平的提高。
文档编号C12N15/19GK1769490SQ20051002962
公开日2006年5月10日 申请日期2005年9月14日 优先权日2005年9月14日
发明者周曾同, 葛姝云 申请人:上海第二医科大学附属第九人民医院