2504例汉族人群HLA-A、B、C、DRB1和DQB1高分辨等位基因多态性研究

HLA-A,-B,-C,-DRB1 and-DQB1 high-resolution alleles polymorphism in 2,504 Han adults

目的分析2 504例汉族人群HLA-A、B、C、DRB1和DQB1高分辨等位基因多态性及分布特征。方法采用基于Illumina Miseq二代测序技术,对岳阳地区2 504例汉族造血干细胞捐献志愿者的HLA-A、B、C、DRB1和DQB1基因进行高分辨分型,采用Py Pop软件计算等位基因频率、单体型频率核对连锁不平衡参数。结果 HLA-Ⅰ类基因中,A、B和C基因座分别检出55、117和67个等位基因,其中频率>0.05常见等位基因为A*11:01:01:01、A*24:02:01:01、A*02:07:01、A*02:01:01:01、A*33:03:01,B*40:01:02、B*58:01:01、B*15:02:01、B*13:01:01、B*46:01:01、C*03:03:01、C*03:02:02:01、C*08:01:01、C*03:04:01:02、C*07:02:01:01、C*01:02:01;HLA-Ⅱ类基因中,共检出50个DRB1和26个DQB1等位基因,频率>0.05常见等位基因见于DRB1*11:01:01、DRB1*08:03:02、DRB1*12:02:01、DRB1*15:01、DRB1*09:01:02,DQB1*03:01:01、DQB1*03:02:01、DQB1*03:03:02、DQB1*05:02:01、DQB1*06:01:01。HLA-A、B、C、DRB1和DQB1位点基因型分布符合Hardy-Weinberg平衡(P>0.05)。任意2个HLA基因间均具有强的连锁不平衡,其中频率≥0.01有统计学意义的单体型有196条。结论获得了岳阳地区汉族人群HLA-A、B、C、DRB1和DQB1高分辨等位基因频率数据,为人类学、移植配型、疾病相关性等研究提供了参考数据。

Objective To analyze the HLA-A, -B, -C, -DRB1 and -DQB1 high-resolution alleles polymorphism and their distribution characteristics in 2,504 Han adults. Methods Totally, 2,504 Chinese Han hematopoietic stem cell donors in Yueyang region were genotyped by the Illumina Miseq next-generation sequencing method for their HLA-A, -C, -B, -DRB1 and -DQB1 genes, and then the allele frequencies, haplotype frequencies and the linkage disequilibrium parameters were computed by a PyPop software. Results For HLA class I genes, there were 55, 117 and 67 alleles observed in HLA-A, -B and -C locus respectively, of which the common alleles with frequencies greater than 0.05 were A＊11：01：01：01, A＊24：02：01：01, A＊02：07：01, A＊02：01：01：01, A＊33：03：01, B＊40：01：02, B＊58：01：01, B＊15：02：01, B＊13：01：01, B＊46：01：01, C＊03：03：01, C＊03：02：02：01, C＊08：01：01, C＊03：04：01：02, C＊07：02：01：01 and C＊01：02：01. For HLA class II genes, 50 DRB1 alleles and 26 DQB1 alleles were observed and the frequent alleles with frequencies greater than 0.05 included DRB1＊11：01：01, DRB1＊08：03：02, DRB1＊12：02：01, DRB1＊15：01, DRB1＊09：01：02, DQB1＊03：01：01, DQB1＊03：02：01, DQB1＊03：03：02, DQB1＊05：02：01 and DQB1＊06：01：01. The distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles coincided with the Hardy-Weinberg test （P〉0.05）. Strong linkage disequilibrium was observed between in any two HLA genes, and there were 196 halotypes with frequency ≥ 0.01 and statistical significance. Conclusions The data of the HLA-A, -B -C, -DRB1 and -DQB1 allelic frequencies at high-resolution level in Yueyang Han population are obtained, which provide reference data for the studies in anthropology, transplantation matching and disease association.