中国北方汉族造血干细胞捐献者人类白细胞抗原-A、B、DRB1基因和单倍型高分辨水平的多态性研究

Study on alleleic and haplotypic polymorphism of human leukocyte antigen -A, -B, -DRB1 genes at highresolution level in Northern Chinese Han hematopoietic stem cell donor

目的从高分辨率水平研究中国北方汉族人群人类白细胞抗原（Human Leukocyte Antigens，HLA）-A、B、DRBI基因和单倍型的多态性。方法采用聚合酶链反应-测序分型方法（Polymerase Chain Reaction—Sequence Based Typing，PCR—SBT）对631名随机北方汉族个体的HLAA、B、DRB1基因进行序列分析，进而采用最大似然性方法计算等位基因和单倍型的分布频率。结果30个HLA—A等位基因中，频率高于0．05的5种常见等位基因A＊1101、A＊2402、A＊0207、A＊0201和A＊3303的频率总和为69．26％；64个HLA—B等位基因中，频率高于0．05的4种常见等位基因B＊4001、B＊4601、B＊5801和B＊1502的频率总和为38．11％；41个DRB1等位基因中，频率高于0．05的7种常见等位基因DRB1＊0901、DRB1＊1501、DRB1＊1202、DRB1＊0701、DRB1＊0803、DRB1＊1101和DRB1＊0405的频率总和为59．98％。499条AB、659条B—DRB1和2426条A—B-DRB1单倍型中，分别有38、39和31条单倍型频率高于0．005，其频率总和分别为59．82％、53．69％和32．38％，A＊0207-B＊4601、B＊4601-DRB1＊0901和A＊0207-B＊4601-DRB1＊0901分别为其最主要单倍型。结论中国北方汉族人群高分辨水平的HLA—A、B、DRBI等位基因和单倍型的多态性数据可作为人类学、法医学、移植配型和疾病相关性研究和应用的参考数据。

Objective To study the polymorphisms of human leukocyte antigen （HLA）-A, B and DRB1 genes and haplotypes at high resolution level in Northern Chinese Han population. Methods 631 randomly selected Northern Chinese Han individuals were genotyped by polymerase chain reaction-sequence based typing （PCR-SBT） method for their HLA-A, B and DRB1 genes, and then the frequencies of alleles and haplotypes were estimated by maximum-likehood estimation method. Results Thirty HLA A alleles were observed and five common alleles with frequencies higher than 0.05 which included A ＊ 1101, A 2402, A＊ 0207, A ＊ 0201 and A ＊ 3303 accounted for 69.26% of the total for HLA-A locus. Sixty-four alleles were seen at HLA-B locus, and B ＊ 4001,B ＊ 4601,B ＊ 5801 and B ＊ 1502 were the most frequent with frequencies higher than 0.05 which comprised 38.11% of the total. Among the forty-one HLA DRB1 alleles, seven alleles with frequencies higher than 0.05 included DRB1 ＊ 0901, DRB1 ＊ 1501, DRB1 ＊ 1202, DRB1＊ 0701, DRB1 ＊ 0803, DRB1 ＊ 1101and DRB1 ＊ 0405, which accounted for 59.98% of the total. 499 A-B, 659 B-DRB1 and 2 426 A-B-DRB1 haplotype were,observed,respectively. 38 A-B, 39 B-DRB1 and 31 A-B-DRB1 haplotypes showed frequencies higher than 0.005 which comprised 59.82%,53.69% and 32.38% of the total. The most frequent haplotype was A ＊ 0207-B ＊4601, B ＊ 4601-DRB1 ＊ 0901 and A 0207-B ＊ 4601-DRB1 ＊ 0901 for each type. Conclusion The presented allelic frequencies and haplotype diversities at high-resolution level in Northern Chinese Han population could be served as reference standard for the anthropology, legal medicine, transplantation matching and disease association studies.