中国南方汉族人群D6S1624、D6S258、M6S211、D6S510遗传多态性及与HLA-A连锁不平衡分析

目的 研究中国南方湖南地区汉族人群HLA Ⅰ类区远着丝粒端D6S1624、D6S258、M6S211、D6S510遗传多态性及与HLA-A的连锁不平衡.方法 应用荧光聚合酶链式反应-基因分型和聚合酶链式反应-序列特异性引物技术分别检测湖南地区227份正常人群样本D6S1624、D6S258、M6S211、D6S510和HLA-A位点.结果 5个位点基因型分布均符合Hardy-Weinberg平衡(P＞0.05).在D6S1624、D6S258、M6S211和D6S510位点分别检出10、10、12、9种等位基因,各位点均有若干主要等位基因,分别以D6S1624*199、D6S258-*195、M6S211-*261、D6S510-*186最为常见.在该人群中,4个微卫星位点均具有较高的杂合度值(0.7142～0.8316)和多态性信息含量(0.6686～0.811),属高度多态性位点.D6S1624、D6S258位点与HLA-A位点之间均不存在总体连锁不平衡(P=0.2646;P=0.3481),M6S211、D6S510位点与HLA-A位点之间均存在非常显著的总体连锁不平衡(P＜0.0001;P＜0.0001).对观察频率≥3%的所有单倍型做连锁不平衡分析,显示10种D6S1624.HLA-A单倍型中,仅两种处于连锁不平衡状态;9种D6S258-HLA-A单倍型中,仅3种处于连锁不平衡;而8种M6S211-HLA-A单倍型、7种D6S510-HLA-A单倍型中,分别有7种、6种均处于连锁不平衡状态.结论 所获得的4个微卫星标记的群体遗传学数据将有助鉴定HLA Ⅰ区域内与疾病相关(如鼻咽癌)的遗传标志、法医学个体认定、人类学研究,亦将有助于评价、指导临床器官移植的组织相容性配型.

Polymorphisms of four microsatellite DNA markers from telomeric HLA Ⅰ region(D6S1624,D6s258,M6S211and D6S510)and their linkage disequilibrium with HLA-A in a southern Chinese Han population

Objective To explore the genetic polymorphisms of four microsatellite DNA markers from telomeric HLA Ⅰ region(D6S1624,D6S258,M6S211 and D6S510)and their linkage disequilibrium with HLA-A in a southern Chinese Han population residing in Hunan province.Methods Fluorescent PCR/Size-sequencing was carried out to analyze the polymorphisms of D6S1624,D6S258,M6S211 and D6S510 loci,and polymerase chain reaction-sequence specific prirning(PCR-SSP)technique was used for HLA-A typing.Results The genotypic distributions at the 5 loci were consistent with Hardy-Weinberg equilibrium(P＞0.05).The number of allelic variants for D6S1624,D6S258,M6S211 and D6S510 loci were 10,10,12 and 9,respectively.Each locus had several main alleles and the dominant alleles were D6S1624-*199,D6S258-*195,M6s211-*261 and D6S510-*186.All of the 4 microsatellite markers exhibited high heterozygosity values(0.7142-0.8316)and polymorphism information content values(0.6686-0.811).No global linkage disequilibrium(LD)was detected between D6S1624 and HLA-A(P=0.2646),or between D6S258 and HLA-A(P=0.3481).In contrast,very significant global LD was found between M6S211 and HLA-A(P＜0.0001),and between D6S510 and HLA-A(P＜0.0001).Subsequent analysis for haplotypes with an observed frequency of≥3%revealed that only 2 of the 10 D6S1624-HLA-A haplotypes and 3 of the 9 D6S258-HLA-A haplotypes displayed weak or moderate LD,while 7 out of the 8 M6S211-HLA-A haplotypes,6 among the 7 D6S510-HLA-A haplotypes were in tight LD.Conclusion Authors have characterized four microsatellite DNA markers,D6S1624,D6S258,M6S211 and D6S5 10 in a southern Chinese Han population.Findings shown here can be helpful for those studies mainly addressing the assoeiation between HLA Ⅰ sub-region and diseases.The data also provide basis for fluture study in forensics,HLA matching in clinical transplantation and anthropology.