利用多个微卫星位点判断病例对照关联研究中的人群层化  

Use of unlinked genetic markers to detect population stratification: a case-control multicenter study

作　　者：张伟丽[1] 张红叶[1] 孙凯[1] 惠汝太 

机构地区：[1]中国医学科学院中国协和医科大学阜外心血管病医院中德分子生物学实验室,北京100037

出　　处：《中华医学杂志》2005年第17期1185-1189,共5页National Medical Journal of China

基　　金：国家"973"重点基础研究发展规划基金资助项目(G200056901)

摘　　要：目的利用多个与脑卒中无关的基因微卫星DNA多态性判断脑卒中病例对照人群的遗传背景。方法多中心病例对照研究,从7个临床中心随机选取294例脑卒中病例和325例对照,采用微卫星荧光标记、半自动基因分型技术,检测8个位于不同染色体上的微卫星多态性位点D11S1361、D19S927、D7S483、D14S990、D15S993、D1S2622、D1S2876和D3S3560,比较各等位基因片段在病例组和对照组的频率分布。结果D11S1361观察到3种等位基因;其余位点的多态性信息含量为0.63～0.81,各等位基因的片段大小、频率分布与白种人(法国人类多态研究中心提供)存在一定差异。7个微卫星多态的各主要等位基因频率在脑卒中病例组和对照组的分布,差异无统计学意义(P>0.05)。结论所选用的微卫星位点具有高度多态性和种族差异性,脑卒中病例对照人群的遗传背景有较好的一致性。Objective To evaluate whether population stratification exists in microsatellite polymorphic sites. Methods Eight microsatellite markers not related to stroke, D11S1361、D19S927、D7S483、D14S990、D15S993、D1S2622、D1S2876和D3S3560 located in different chromosomes were selected based on the GenBank database (http://www.gdb.org/). PCR assay was used to detect the alleles of these microsatellite in 294 patients of cerebral apoplexy, aged 58, and 325 sex, age and geographically-match controls in 7 cities in China. The PCR products were subjected to electrophoresis on the ABI 377 DNA sequencer and analyzed with Genescana and Genotypera software. The frequencies of these markers in these stroke patients and controls were compared by c2 test. Total 294 patients with stroke and 325 age, sex, and geographically matched controls were randomly selected from 973 case-control population. Eight loci including D11S1361, D19S927, D7S483, D14S990, D15S993, D1S2622, D1S2876 and D3S3560 were detected by fluorescence-based genotyping approach. Results Except for the alleles of D11S1361, the size, frequency, heterozygosity, and polymorphism information in the alleles of the other 7 microsatellite sites were in the range of 0.63-0.81 and their distribution varies in different races and populations. between Chinese and Caucasians. There were no differences in the frequencies of main alleles between the case group and control group (all P≥0.05). Conclusion The selected seven markers are highly polymorphic and variable between human populations, and the genomic control data indicate that there is no unequal genetic admixture and stratification in the case-control cohort.

关 键 词：微卫星位点 人群 关联研究 微卫星DNA多态性 多中心病例对照研究 基因分型技术 等位基因频率 遗传背景 频率分布 脑卒中 多态性位点 微卫星多态 种族差异性 病例-对照 荧光标记 基因片段 研究中心 对照组 病例组 半自动 

分 类 号：R743.3[医药卫生—神经病学与精神病学]