Jung Kiwook, Kim Jisoo G, Shin Sue, Roh Eun Youn, Hong Yun Ji, Song Eun Young
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Laboratory Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.
HLA. 2023 Jun;101(6):602-612. doi: 10.1111/tan.14980. Epub 2023 Feb 27.
Data on HLA genotype distribution, including DQA1 and DPA1, in the Korean population are limited. We aimed to investigate the allele and haplotype frequencies of 11 HLA loci in 339 Korean subjects using next-generation sequencing (NGS)-based HLA typing. A total of 339 samples from unrelated healthy subjects were genotyped for HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1, -DQA1, -DPB1, and -DPA1 using two different NGS-based HLA typing kits (166 tested using the NGSgo-MX11-3 kit [GenDx, Netherlands] and 173 by the AllType NGS 11 Loci Amplification kit [One Lambda, USA]). PyPop software was used to estimate allele and haplotype frequencies and linkage disequilibrium between the loci. Additionally, a principal component analysis was performed to compare the allele distribution of Koreans with that of other populations. A total of 214 HLA alleles (97 class I and 117 class II alleles) were assigned. The most frequent alleles for each locus were A24:02:01 (24.78%), B15:01:01 (10.18%), C01:02:01 (18.44%), DRB104:05:01 (9.59%), DRB302:02:01 (13.72%), DRB401:03:01 (25.81%), DRB501:01:01 (9.0%), DQA101:02:01 (16.96%), DQB103:01:01 (14.31%), DPA101:03:01 (44.4%), and DPB105:01:01 (35.1%), respectively. The most frequent haplotypes were A33:03:01-C03:02:02-B58:01:01 for HLA class I (5.01%) and DRB104:05:01-DQA103:03:01-DQB104:01:01-DPA102:02:02-DPB1*05:01:01 for HLA class II (6.23%). The total allelic ambiguities by NGS were estimated to be minimal and considerably decreased compared with those by Sanger sequencing. The Japanese population had the most similar allele distribution to Koreans, followed by the Chinese population. Frequency data of 11 HLA loci in Koreans can provide essential data for population genetics and disease association studies.
韩国人群中包括DQA1和DPA1在内的HLA基因型分布数据有限。我们旨在通过基于二代测序（NGS）的HLA分型方法，调查339名韩国受试者中11个HLA基因座的等位基因和单倍型频率。使用两种不同的基于NGS的HLA分型试剂盒，对339例来自无血缘关系健康受试者的样本进行HLA - A、- B、- C、- DRB1、- DRB3、- DRB4、- DRB5、- DQB1、- DQA1、- DPB1和- DPA1基因分型（166例使用NGSgo - MX11 - 3试剂盒[荷兰GenDx公司]检测，173例使用AllType NGS 11基因座扩增试剂盒[美国One Lambda公司]检测）。使用PyPop软件估计等位基因和单倍型频率以及基因座之间的连锁不平衡。此外，进行主成分分析以比较韩国人与其他人群的等位基因分布。共确定了214个HLA等位基因（97个I类等位基因和117个II类等位基因）。每个基因座最常见的等位基因分别为A24:02:01（24.78%）、B15:01:01（10.18%）、C01:02:01（18.44%）、DRB104:05:01（9.59%）、DRB302:02:01（13.72%）、DRB401:03:01（25.81%）、DRB501:01:01（9.0%）、DQA101:02:01（16.96%）、DQB103:01:01（14.31%）、DPA101:03:01（44.4%）和DPB105:01:01（35.1%）。I类HLA最常见的单倍型是A33:03:01 - C03:02:02 - B58:01:01（5.01%），II类HLA最常见的单倍型是DRB104:05:01 - DQA103:03:01 - DQB104:01:01 - DPA102:02:02 - DPB1*05:01:01（6.23%）。NGS检测的总等位基因模糊度估计最低，与桑格测序相比显著降低。日本人群的等位基因分布与韩国人最相似，其次是中国人群。韩国人11个HLA基因座的频率数据可为群体遗传学和疾病关联研究提供重要数据。
