SUMO1基因单核苷酸多态性分析及rs7599810多态性与非综合征型唇/腭裂的关联研究  

Analysis of the HapMap data on SNPs in SUMO1 and association study of rs7599810 in trios with non-syndromic cleft lip with or without cleft palate

作　　者：岳青[1] 王红[1] 张博[2] 赵凯平[3,4] 

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]西安交通大学生物医学工程系,西安710049 [3]北京大学第四临床医学院 [4]北京积水潭医院病案统计科,北京100035

出　　处：《北京大学学报（医学版）》2014年第2期258-263,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(81273164);美国国立卫生研究院国家牙科与颅面研究院基金(R21-DE-013707;R01-DE-014581);Fogarty基金(D43-TW006176)资助~~

摘　　要：目的：对HapMap数据库四个不同人群SUM01基因的单核苷酸多态性（singlenucleotidepolymorphisms，SNPs）进行分析和比较，并探讨山东汉族人群rs7599810位点多态性与非综合征型唇／腭裂（non—syndromiccleftlipwithorwithoutcleftpalate，NSCL／P）的关联。方法：首先用Haploview软件确定HapMap四个人群，分别为：中国北京汉族（HanChineseinBeijing，China，CHB）、日本东京（JapaneseinTokyo，Japan，JPT）、西北欧后裔（UtahresidentswithNorthernandWesternEuropeanancestryfromtheCEPHcollection，CEU）和尼日利亚约鲁巴（YorubaninIbadan，Nigeria，YRI），四个人群中SUM01基因SNPs中最小等位基因频率（minorallelefrequency，MAF）〉0．01且符合Hardy—Weinberg平衡的SNPs为合格SNPs，用MAF全距相对比指标衡量人群间最小等位基因相同的共有合格SNPs的MAFs差异；然后对四个人群共有合格SNPs进行单体域和单体型的分析及比较；最后对本研究所测该基因中的rs7599810在山东地区183个NSCL／P核心家系中进行传递不平衡检验（transmission／disequilibriumtest，TDT）。结果：HapMap提供的24个SNPs中，纯合SNPs在CHB和JPT均为9个，在CEU为8个，在YRI为6个，四个人群共有合格SNPs为12个。这些SNPs在四个人群均形成了一个单体域，其中CHB、JPT、CEU人群的单体域包括全部12个SNPs，YRl人群的单体域包括第3～11个SNPs。CHB、JPT、CEU和YRI人群的单体域分别确定了3、3、5、6种单体型，且均以前两种单体型为主，频率为0．634～0．922。TDT结果显示SUM01基因rs7599810多态性与NSCL／P未见统计学关联（X^2=0．485，P=0．486，OR=0．898，95％C／：0．663～1．021）。结论：CHB、JPT和CEU人群SUM01基因SNPs在等位基因组成、MAF、单体域及单体型构成等方面以共性特征为主，与之相比，YRl人群SNPs表现出较大的独特性。山东汉族人群中SUM01基因rs7599810多态性与NSCL／P未见统计学关联。Objective ： To analyze the minor allele Irequenc：es q MAP s）, naptotype DIOCK ano napiotype frequencies for single nucleotide polymorphisms （SNPs） in SUM01 using HapMap data and perform association analysis between SNPs in SUM01 and non-syndromic cleft lip with or without cleft palate （ NSCL/ P） using 183 trios recruited from Shandong Province. Methods： SNPs with MAF 〉 0.01 and Hardy- Weinberg equilibrium （ P 〉 0.01 ） were identified as qualified SNPs by Haploview. The MAFs of qualified SNPs were analyzed and the relative range ratios of the MAFs were developed to measure the differences in MAFs for common qualified SNPs with mutual minor allele among the samples. Haplotype blocks and haplotype frequencies for common qualified SNPs in four samples were analyzed and compared among the samples. Transmission disequilibrium test （TDT） was carried out to identify the association between rs7599810 and NSCL/P using 183 NSCL/P case-parent trios. Results： Among the 24 SNPs released by HapMap project, the number of monotonic SNPs was 9 in Han Chinese in Beijing, China （CHB） and Japanese in Tokyo, Japan （JPT） samples, 8 in Utah residents with Northern and Western European ancestry from the CEPH collection （CEU） sample, and 6 in Yoruban in Ibadan, Nigeria （YRI） sample. The 12 common qualified SNPs in the four samples formed one haplotype in each sample. There were 3, 3, 5, and 6 forms of haplotypes in the CHB, JPT, CEU, and YRI samples respectively, and the cumulative frequencies for the 2 most common haplotypes ranged from 0. 634 to 0. 922. Significant transmission disequilibrium of G allele at rs7599810 from parents to offspring was not shown （X^2 = 0.485, P = 0. 486, OR = 0. 898, 95% CI：0. 663 - 1. 021 ） for rs7599810 in Shandong Han sample. Conclusion： SNPs in SUMO1 mainly showed common features in minor alleles, MAFs and haplotype blocks among CHB, JPT and CEU samples, other three samples. Although no association was P using data from Shandong Han population, our but

关 键 词：SUMO1 基因关联研究 多态性 单核苷酸 唇裂 腭裂 

分 类 号：R181.33[医药卫生—流行病学]