Abstract：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.
[1] Shaw BE, Arguello R, Garcia-Sepulveda CA, et al.The impact of HLA genotyping on survival following unrelated donor haematopoietic stem cell transplantation[J].Br J Haematol,2010,150(3):251-258. [2] De Santis D, Dinauer D, Duke J, et al.16(th) IHIW: review of HLA typing by NGS[J].Int J Immunogenet, 2013, 40(1):72-76. [3] Zhou M, Gao D, Chai X, et al.Application of high-throughput, high-resolution and cost-effective next generation sequencing-based large-scale HLA typing in donor registry[J].Tissue Antigens, 2015, 85(1):20-28. [4] Cheng LH, li Z, Jin SZ, et al.Sequence-based typing characterization of the novel HLA-Cw* 0340 allele in a Chinese individual[J].Tissue Antigens, 2008,72(5):495-497. [5] 苏湘晖,孙昂,粟玉萍,等.岳阳地区汉族人群HLA-A、-B、-DRB1高分辨等位基因多态性分析[J].实用预防医学,2012,19(9):1307-1310. [6] 孙昂.岳阳市汉族汉族造血干细胞捐献志愿者HLA-DRB1高分辨基因多态性研究[J].实用预防医学,2011,18(6):1002-1005. [7] 丁浩强,叶欣,梁华钦,等.广州地区献血人群HLA-A、B、DRB1高分辨等位基因及单体型的多态性研究[J].中国免疫学杂志,2010,26(9):810-813. [8] 王芳,廖群,黄霞,等.重庆汉族人群HLA-A、B、DRB1高分辨等位基因多态性研究[J].重庆医学,2014,43(26):3455-3460. [9] 李鑫,丁携,王鑫,等.黑龙江地区人群HLA-A、B、DRB1高分辨等位基因及单体型多态性研究[J].中国免疫学杂志,2016,32(1):83-89. [10] 夏玲,王钰,罗玫,等.直接测序法用于四川骨髓库汉族人群HLA-C等位基因分布的研究[J].中国输血杂志,2010,23(8):596-601. [11] 李桢,程良红,邹红岩,等.深圳汉族人群HLA-Cw,-DQB1基因座等位基因的多态性[J].中国组织工程研究与临床康复,2008,12(53):10517-10521. [12] 梁晓岚,韩俊领,李茜,等.中国北方汉族人群HLA-Cw高分辨等位基因频率分析[J].中国实验血液学杂志,2010,18(2):486-489. [13] 黑爱莲,李伟,刘娜,等.中华骨髓库造血干细胞捐献志愿者HLA-A、-B、-C、-DRB1、-DQB1高分辨等位基因频率分析[J].中国输血杂志,2009,22(4):285-287. [14] 潘斌.HLA多态性与疾病机制关联的研究进展[J].细胞与分子免疫学杂志,2011,27(10):1157-1160. [15] 张伟伦,王丽,洪坤学,等.中国前献血人群中HLA-A*03与HIV-1感染关系的研究[J].中国科学:生命科学,2012,42(9):709-715. [16] 范春梅,黄荣富,陈根旺.闽南地区HLA-B27基因亚型与强直性脊柱炎相关性研究[J].中国微生态学杂志,2016,28(3):256-258. [17] 尹璐,郭媛.绒毛滋养细胞HLA-C基因多态性与早期复发性流产关系研究[J].白求恩军医学院学报,2012,10(3):192-193. [18] 孙昂,方奎明,粟玉萍,等.新生儿溶血病与HLA-DQB1相关性研究[J].中国现代医药,2014,16(1):5-8.
2016, Vol. 23 
