北京和东京人群MYO9B单核苷酸多态性差异比较分析
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摘要
为探讨中国北京汉族人群(CHB)和日本东京人群(JPT)肌球蛋9B(MYO9B)单核苷酸基因多态性(SNP)、单体域和单体型的差异,我们利用人类基因组单体型图(Hap Map)公布的Ⅲ期MYO9B SNP数据,通过Haploview4.2软件选择合格SNP、标签SNP(tagSNP)、估计最小等位基因频率(minimum allele frequency,MAF)及构建单体域,并比较其差异。然后通过Phase2.1软件构建特殊tagSNP位点单体型并行置换检验以比较两个人群所构建单体型的差异。研究结果表明,从CHB及JPT MYO9B中分别筛选出52个及50个合格SNP,其中49个是一致的。两人群合格SNP MAF频数最高组段及最低组段相同,且整体比较无差别(p=0.07)。于两人群MYO9B各构建7个和5个单体域,其中两个基本相同,一个单体域为CHB独有,其余在两人群分布不同但互有重叠。从两人群MYO9B分别筛选出23个及17个tagSNP,其中17个tagSNP相同,另6个SNP在CHB单独成为tagSNP而不与其他SNP相关联。利用两人群MYO9B特殊tagSNP位点共构建10个频率>2%的相同的单体型,累计频率分别为51.37%和51.99%,且两者均以TCTCG和TTTCG单体型为主。两人群MYO9B特殊位点单体型构成基本相同(p=0.765)。综上所述,CHB和JPT的MYO9B SNP及单体域特征以共性为主,与人群的地域和种族属性一致;北京汉族与东京人群特殊SNP位点构建的MYO9B单体型构成及频率无差别。
To explore the differences of single nucleotide polymorphisms(SNP), haplotype block and haplotype of myosin IXB(MYO9B) between Han Chinese in Beijing(CHB) and Japanese in Tokyo(JPT) populations, we used the phase Ⅲ data of MYO9 B SNP released by Hap Map to select the eligible SNP, tagSNP, estimate minimum allele frequency(MAF) and construct haplotype block with Haploview4.2 software and compared their differences; then we constructed special tagging-SNP haplotypes with PHASE 2.1 program and analyzed the differences of haplotypes between two groups with permutation test. The results showed that 52 and 50 MYO9B eligible SNPs were selected from CHB and JPT respectively, in which 49 SNPs were identical. The highest and the lowest section of the MYO9B eligible SNP MAF frequency of two populations were the same and there was no difference between the whole MAF(p=0.07). Seven and five haplotype blocks of MYO9B in the two populations were constructed respectively, two of which were basically the same, a single haplotype block was unique to CHB,and other haplotype blocks were different but overlapping with each other. Two populations were screened 23 and 17 tagSNPs of MYO9B respectively, of which 17 tagSNP were identical, 6 SNPs were unique to CHB and they were not associated with other SNPs. Ten same haplotypes were constructed with the special MYO9B tagSNP sites of two people, which frequency were all over 2% and the cumulative frequency in CHB and JPT were 51.37% and51.99% respectively; TCTCG and TTTCG were the primary haplotypes of both. The haplotypes constructed by special MYO9B tagSNP sites of two populations were basically the same(p =0.765). In conclusion, SNPs and haplotype blocks in MYO9B had common features between CHB and JPT populations, which were consistent with the geographic and ethnic origins of the two populations. There were no difference of composition and frequency of MYO9B haplotypes constructed by special tagSNP sites of CHB and JPT.
To explore the differences of single nucleotide polymorphisms(SNP), haplotype block and haplotype of myosin IXB(MYO9B) between Han Chinese in Beijing(CHB) and Japanese in Tokyo(JPT) populations, we used the phase Ⅲ data of MYO9 B SNP released by Hap Map to select the eligible SNP, tagSNP, estimate minimum allele frequency(MAF) and construct haplotype block with Haploview4.2 software and compared their differences; then we constructed special tagging-SNP haplotypes with PHASE 2.1 program and analyzed the differences of haplotypes between two groups with permutation test. The results showed that 52 and 50 MYO9B eligible SNPs were selected from CHB and JPT respectively, in which 49 SNPs were identical. The highest and the lowest section of the MYO9B eligible SNP MAF frequency of two populations were the same and there was no difference between the whole MAF(p=0.07). Seven and five haplotype blocks of MYO9B in the two populations were constructed respectively, two of which were basically the same, a single haplotype block was unique to CHB,and other haplotype blocks were different but overlapping with each other. Two populations were screened 23 and 17 tagSNPs of MYO9B respectively, of which 17 tagSNP were identical, 6 SNPs were unique to CHB and they were not associated with other SNPs. Ten same haplotypes were constructed with the special MYO9B tagSNP sites of two people, which frequency were all over 2% and the cumulative frequency in CHB and JPT were 51.37% and51.99% respectively; TCTCG and TTTCG were the primary haplotypes of both. The haplotypes constructed by special MYO9B tagSNP sites of two populations were basically the same(p =0.765). In conclusion, SNPs and haplotype blocks in MYO9B had common features between CHB and JPT populations, which were consistent with the geographic and ethnic origins of the two populations. There were no difference of composition and frequency of MYO9B haplotypes constructed by special tagSNP sites of CHB and JPT.
引文
Carlson C.S.,Eberle M.A.,Rieder M.J.,Yi Q.,Kruglyak L.,and Nickerson D.A.,2004,Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium,Am.J.Hum.Genet,74(l):l06-l20
De Bakker P.I.,Yelensky R.,Pe'er I.,Gabriel S.B.,Daly M.J.,and Altshuler D.,2005,Efficiency and power in genetic association studies,Nat.Genet.,37(11):1217-2122
Gabriel S.B.,Schaffner F.S.,Nguyen H.,Moore J.M.,Roy J.Blumenstiel B.,Higgins J.,De Felice M.,Lochner A.,Faggart M.,Liu-Cordero S.N.,Rotimi C.,Adeyemo A.,Cooper R.Ward R.,Lander E.S.,Daly M.J.,and Altshuler D.,2002,The structure of haplotype blocks in the human genome,Science,296(5576):2252-2229
Hanley P.J.,Xu Y.,Kronlage M.,Grobe K.,Schn P.,Song J.Sorokin L.,Schwab A.,and B覿hler M.,2010,Motorized Rho GAP myosin IXb(Myo9b)controls cell shape and motility,Proc.Natl.Acad.Sci.USA,107(27):12145-12150
Huang M.,and Cai L.,2009,Using haploview and PHASE in haplotype research,Fujian Yike Daxue Xuebao(Journal of Fujian Medical University),43(4):310-313(黄萌,蔡琳,2009Haploview与PHASE在单体型研究中的应用,福建医科大学学报,43(4):310-313
Li J.,Pan Y.C.,Li Y.X.,and Shi T.L.,2005,Analysis and application of SNP and haplotype in the human genome,Yichuan Xuebao(Journal of Genetics and Genomics),32(8):879-889(李婧,潘玉春,李亦学,石铁流,2005,人类基因组单核苷酸多态性和单体型的分析及应用,遗传学报,32(8):879-889
Nijmeijer R.M.,Van Santvoort H.C.,Zhernakova A.,Teller S.,Scheiber J.A.,De Kovel C.G.,Besselink M.G.,Visser J.T.,Lutgendorff F.,Bollen T.L.,Boermeester M.A.,Rijkers G.T.,Weiss F.U.,Mayerle J.,Lerch M.M.,Gooszen H.G.,Akkermans L.M.,and Wijmenga C.,2013,Association analysis of genetic variants in the myosin IXB gene in acute pancreatitis,PLo S One,8(12):e85870
Santana R.,Mendiburu A.,Zaitlen N.,Eskin E.,and Lozano J.A.,2010,Multi-marker tagging single nucleotide polymorphism selection using estimation of distribution algorithms,Artif.Intell.Med.,50(3):193-201
Prager M.,Durmus T.,Büttner J.,Molnar T.,De Jong D.J.,Drenth J.P.,Baumgart D.C.,Sturm A.,Farkas K.,Witt H.,and Büning C.,2014,Myosin IXb variants and their pivotal role in maintaining the intestinal barrier:A study in Crohn's disease,Scand.J.Gastroenterol.,49(10):1191-1200
Wang H.,and Zhao K.P.,2011a,Comparison of minor allele frequency and haplotype frequencies for single nucleotide polymorphisms in receptor tyrosine kinase-like orphan receptor 2gene using Hap Map data from Han Chinese in Beijing(CHB)and Japanese in Tokyo(JPT),Zhonghua Liux ingbingxue Zazhi(Chinese Journal of Epidemiology),32(11):1162-1165(王红,赵凯平,2011a,中国北京汉族人群和日本东京人群ROR2基因单核苷酸多态性比较,中华流行病学杂志,32(11):1162-1165)
Wang H.,and Zhao K.P.,2011b,Comparison of minor allele frequencies and haplotype frequencies for single nucleotide polymorphisms in ROR2 gene using Hap Map data for Chinese Hans in Beijing and Yoruban in Ibadan in Nigeria(Journal of Peking University(Health Sciences),43(6):785-791(王红,赵凯平,2011b,北京汉族和约鲁巴人群ROR2基因单核苷酸多态性的比较研究,北京大学学报,43(6):785-791
Zhang K.,Calabrese P.,Nordborg M.,and Sun F.,2002,Haplotype block structure and its applications to association studies:power and study designs,Am.J.Hum.Genet.,71(6):1386-1394
Zhang Z.S.,Zhou Y.J.,Li Y.Y.,Du Y.L.,and Cao C.Y.,2012,The correlation of the adiponectin gene tagging single nucleotide polymorphism with non-alcoholic fatty fiver diseases,Guangdong Yixue(Guangdong Medical Journal),33(21):3225-3229(张宗胜,周永健,李瑜元,杜艳蕾,曹创裕,2012,脂联素基因标签单核苷酸多态性与非酒精性脂肪肝病的相关性,广东医学,33(21):3225-3229)
De Bakker P.I.,Yelensky R.,Pe'er I.,Gabriel S.B.,Daly M.J.,and Altshuler D.,2005,Efficiency and power in genetic association studies,Nat.Genet.,37(11):1217-2122
Gabriel S.B.,Schaffner F.S.,Nguyen H.,Moore J.M.,Roy J.Blumenstiel B.,Higgins J.,De Felice M.,Lochner A.,Faggart M.,Liu-Cordero S.N.,Rotimi C.,Adeyemo A.,Cooper R.Ward R.,Lander E.S.,Daly M.J.,and Altshuler D.,2002,The structure of haplotype blocks in the human genome,Science,296(5576):2252-2229
Hanley P.J.,Xu Y.,Kronlage M.,Grobe K.,Schn P.,Song J.Sorokin L.,Schwab A.,and B覿hler M.,2010,Motorized Rho GAP myosin IXb(Myo9b)controls cell shape and motility,Proc.Natl.Acad.Sci.USA,107(27):12145-12150
Huang M.,and Cai L.,2009,Using haploview and PHASE in haplotype research,Fujian Yike Daxue Xuebao(Journal of Fujian Medical University),43(4):310-313(黄萌,蔡琳,2009Haploview与PHASE在单体型研究中的应用,福建医科大学学报,43(4):310-313
Li J.,Pan Y.C.,Li Y.X.,and Shi T.L.,2005,Analysis and application of SNP and haplotype in the human genome,Yichuan Xuebao(Journal of Genetics and Genomics),32(8):879-889(李婧,潘玉春,李亦学,石铁流,2005,人类基因组单核苷酸多态性和单体型的分析及应用,遗传学报,32(8):879-889
Nijmeijer R.M.,Van Santvoort H.C.,Zhernakova A.,Teller S.,Scheiber J.A.,De Kovel C.G.,Besselink M.G.,Visser J.T.,Lutgendorff F.,Bollen T.L.,Boermeester M.A.,Rijkers G.T.,Weiss F.U.,Mayerle J.,Lerch M.M.,Gooszen H.G.,Akkermans L.M.,and Wijmenga C.,2013,Association analysis of genetic variants in the myosin IXB gene in acute pancreatitis,PLo S One,8(12):e85870
Santana R.,Mendiburu A.,Zaitlen N.,Eskin E.,and Lozano J.A.,2010,Multi-marker tagging single nucleotide polymorphism selection using estimation of distribution algorithms,Artif.Intell.Med.,50(3):193-201
Prager M.,Durmus T.,Büttner J.,Molnar T.,De Jong D.J.,Drenth J.P.,Baumgart D.C.,Sturm A.,Farkas K.,Witt H.,and Büning C.,2014,Myosin IXb variants and their pivotal role in maintaining the intestinal barrier:A study in Crohn's disease,Scand.J.Gastroenterol.,49(10):1191-1200
Wang H.,and Zhao K.P.,2011a,Comparison of minor allele frequency and haplotype frequencies for single nucleotide polymorphisms in receptor tyrosine kinase-like orphan receptor 2gene using Hap Map data from Han Chinese in Beijing(CHB)and Japanese in Tokyo(JPT),Zhonghua Liux ingbingxue Zazhi(Chinese Journal of Epidemiology),32(11):1162-1165(王红,赵凯平,2011a,中国北京汉族人群和日本东京人群ROR2基因单核苷酸多态性比较,中华流行病学杂志,32(11):1162-1165)
Wang H.,and Zhao K.P.,2011b,Comparison of minor allele frequencies and haplotype frequencies for single nucleotide polymorphisms in ROR2 gene using Hap Map data for Chinese Hans in Beijing and Yoruban in Ibadan in Nigeria(Journal of Peking University(Health Sciences),43(6):785-791(王红,赵凯平,2011b,北京汉族和约鲁巴人群ROR2基因单核苷酸多态性的比较研究,北京大学学报,43(6):785-791
Zhang K.,Calabrese P.,Nordborg M.,and Sun F.,2002,Haplotype block structure and its applications to association studies:power and study designs,Am.J.Hum.Genet.,71(6):1386-1394
Zhang Z.S.,Zhou Y.J.,Li Y.Y.,Du Y.L.,and Cao C.Y.,2012,The correlation of the adiponectin gene tagging single nucleotide polymorphism with non-alcoholic fatty fiver diseases,Guangdong Yixue(Guangdong Medical Journal),33(21):3225-3229(张宗胜,周永健,李瑜元,杜艳蕾,曹创裕,2012,脂联素基因标签单核苷酸多态性与非酒精性脂肪肝病的相关性,广东医学,33(21):3225-3229)