中华骨髓库造血干细胞捐献志愿者HLA-A、-B、-C、-DRB1、-DQB1高分辨单体型频率初步分析

Analysis of HLA-A,-B,-C,-DRB1,-DQB1 high-resolution haplotype frequencies in Chinese Marrow Donor Program registry

目的分析中华骨髓库造血干细胞捐献者HLA-A、-B、-C、-DRB1、-DQB15位点在高分辨基因分型水平上的单体型频率及连锁不平衡特征。方法根据718名中华骨髓库捐献者HLA5位点高分辨分型数据,运用Arle-quin3.1软件以最大似然法分析单体型频率。结果双座位连锁不平衡分析显示,HLA-C与HLA-B、HLA-DRB1与HLA-DQB1呈现较为显著的连锁不平衡;多位点单体型频率分析结果显示,最常见的2、3、4、5位点单体型分别为:A*0207-B*4601(7.34%)、Cw*0102-B*4601(8.71%)、B*1302-DRB1*0701(6.19%)、DRB1*0901-DQB1*0303(14.27%)、A*3001-B*1302-DRB1*0701(5.36%)、A*0207-B*4601-Cw*0102(7.06%)、A*3001-Cw*0602-B*1302-DRB1*0701(5.36%)、Cw*0602-B*1302-DRB1*0701-DQB1*0202(6.12%)、A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0202(5.29%)。结论本研究提供了中华骨髓库718名捐献者HLA5位点高分辨单体型频率遗传学数据,将为临床寻找HLA匹配的无关供者、法医学鉴定、HLA与疾病相关研究等提供分子遗传学参考。

Objective To analyze HLA-A, -B, -C, -DRB1 and DQB1 high-reselution haplotype frequencies in Chinese Marrow Donor Program （CMDP） registry. Methods High-resolution genotypings at HLA-A, -B, -C, -DRB1 and DQB1 loci from718 donors were extracted from CMDP registry, and the haplotype frequencies were estimated using Arlequin software. Results Linkage Disequilibrium analysis between two alleles at different locus indicated that Cw-B and DRBI- DQBI exhibit the strongest association. The most common two, three, four and five-locus haplotypes were as follows：A^＊ 0207-B^＊ 4601（7.34%）、Cw^＊ 0102-B^＊ 4601（8.71%）、B^＊ 1302-DRB1^＊ 0701（6.19%）、DRB1^＊0901-DQB1^＊0303（14.27%）、A^＊ 3001-B^＊ 1302-DRB1^＊0701（5.36%）、A^＊ 0207.B^＊ 4601-Cw^＊ 0102（7.06%）、A^＊ 3001-Gw^＊ 0602-B^＊ 1302-DRB1^＊ 0701（5.36%）、Cw^＊ 0602.B^＊ 1302.DRB1 ^＊0701.DQB^1＊ 0202（6.12%）、A^＊ 3001-Cw^＊ 0602-B^＊ 1302-DRB1^＊ 0701-DQB1^＊ 0202（5.29%）, respectively. Conclusion The high-resolution haplotype data at HLA-A, -Cw, - B, -DRBI and DQBI loci in CMDP 718 marrow donors will be helpful for HLA matching in transplantation, as well as for other medical and anthropologic applications in Chinese population.