4082名上海骨髓库汉族无关供者HLA-A、B、DRB1高分辨等位基因及单体型多态性研究

目的 了解上海地区汉族人群HLA-A、B、DRB1在高分辨分型水平上的等位基因及单体型频率分布特征.方法 采用PCR-测序分型技术(Sequence-based typing,SBT)对4 082名随机、无血缘关系、健康的中华骨髓库上海分库汉族造血干细胞捐献者进行HLA-A、B、DRB1高分辨基因分型,利用计数法和最大似然性原理方法分别计算HLA-A、B 、DRB1等位基因及单体型频率.结果 4082例样本中,共观察到204个HL4等位基因,其中频率＞0.1的HLA-A、B、DRB1等位基因分别有A*11:01、A*24:02、A*02:01、B*46:01、DRB1* 09:01、DRB1* 15:01.841条A-B单体型中,70条单体型呈现显著的连锁不平衡(ALD ＞0,HF≥3.67 ×10-4,x2 ＞3.84),8条表现为强连锁不平衡(RLD ＞0.40),17条单体型的频率高于0.01;1 027条B-DRB1单体型中,99条单体型呈现显著的连锁不平衡(ALD＞0,HF≥3.67×10-4,x2＞3.84),12条表现为强连锁不平衡(RLD＞0.40),12条单体型的频率高于0.01;3 344条A-B-DRB1单体型中,681条单体型是“可靠的”(频率≥3.67×10-4),单体型频率高于0.001有135条.结论 获得上海地区汉族人群HLA-A 、B、DRB1高分辨等位基因频率和单体型分布数据及相关遗传参数,为临床移植供者的选择、中国人群CWD表的制订、骨髓库最适库容的评估及人类遗传学研究提供参考数据.

Polymorphism analysis of HLA-A,-B,-DRB1 alleles and haplotypes at high-resolution level in 4 082 Han unrelated donors from marrow donor program registry of Shanghai

Objective To analyze the distribution of HLA-A,B,and DRB1 high-resolution alleles and haplotype frequencies in Shanghai Han population.Methods Polymerase-chain-reaction(PCR) sequence-based-typing(SBT) methods were used to genotype HLA-A,-B,and-DRB1 alleles of 4 082 randomly selected,unrelated and healthy Han people in Shanghai branch of China Marrow Donor Program(CMDP) registry,and haplotype frequencies were estimated using counting and maximum-likelihood method.Results A total of 204 HLA alleles were observed and the most frequent alleles(>0.1)were A*11∶01,A*24∶02,A*02∶01,B*46∶01,DRB1*09∶01,and DRB1*15∶01.Among the 841 HLA-A/B two loci haplotypes,17 had a frequency over 0.01,70 showed significant positive linkage disequilibrium(ALD>0,HF≥3.67×10-4,χ2 >3.84).Moreover,12 of the 1 027 HLA-B/DRB1 haplotypes identified had a frequency over 0.01,99 showed significant positive linkage disequilibrium(ALD>0,HF≥3.67×10-4,χ2 >3.84).In addition,681 of the 3 344 HLA-A-B-DRB1 haplotypes identified had a frequency over 3.67×10-4,135 had a frequency over 0.001.Conclusion The HLA-A,B and DRB1 allele frequencies and haplotype structure of the Shanghai Han population has their own characteristics.The results of the study provides useful information for transplant donor selection,formulation of the Chinese Han population CWD alleles,estimation of optimal bone marrow registry size and general human genetics studies.