4082名上海骨髓库汉族无关供者HLA-A、B、DRB1高分辨等位基因及单体型多态性研究  

Polymorphism analysis of HLA-A,-B,-DRB1 alleles and haplotypes at high-resolution level in 4 082 Han unrelated donors from marrow donor program registry of Shanghai

作　　者：杨剑豪[1] 刘嬿[1] 郑皆炜[1] 谢军华[1] 孙瑛[1] 姜跃琴[1] 唐晴钧 杜可明[1] 

机构地区：[1]上海市血液中心,上海200051

出　　处：《中国输血杂志》2012年第12期1262-1267,共6页Chinese Journal of Blood Transfusion

摘　　要：目的了解上海地区汉族人群HLA-A、B、DRB1在高分辨分型水平上的等位基因及单体型频率分布特征。方法采用PCR-测序分型技术(Sequence-based typing,SBT)对4 082名随机、无血缘关系、健康的中华骨髓库上海分库汉族造血干细胞捐献者进行HLA-A、B、DRB1高分辨基因分型,利用计数法和最大似然性原理方法分别计算HLA-A、B、DRB1等位基因及单体型频率。结果 4 082例样本中,共观察到204个HLA等位基因,其中频率>0.1的HLA-A、B、DRB1等位基因分别有A*11∶01、A*24∶02、A*02∶01、B*46∶01、DRB1*09∶01、DRB1*15∶01。841条A-B单体型中,70条单体型呈现显著的连锁不平衡(ALD>0,HF≥3.67×10-4,χ2>3.84),8条表现为强连锁不平衡(RLD>0.40),17条单体型的频率高于0.01;1 027条B-DRB1单体型中,99条单体型呈现显著的连锁不平衡(ALD>0,HF≥3.67×10-4,χ2>3.84),12条表现为强连锁不平衡(RLD>0.40),12条单体型的频率高于0.01;3 344条A-B-DRB1单体型中,681条单体型是"可靠的"(频率≥3.67×10-4),单体型频率高于0.001有135条。结论获得上海地区汉族人群HLA-A、B、DRB1高分辨等位基因频率和单体型分布数据及相关遗传参数,为临床移植供者的选择、中国人群CWD表的制订、骨髓库最适库容的评估及人类遗传学研究提供参考数据。Objective To analyze the distribution of HI_A-A,B, and DRB1 high-resolution alleles and haplotype fre- quencies in Shanghai Han population. Methods Polymerase-chain-reaction （PCR） sequence-based-typing （SBT） meth- ods were used to genotypo HI.A-A,-B, and -DRB1 alleles of 4 082 randomly selected, unrelated and healthy Han people in Shanghai branch of China Marrow Donor Program （CMDP） registry, and haplotype frequencies were estimated using count- ing and maximum-likelihood method. Results A total of 204 HLA alleles were observed and the most frequent alleles（ 〉 0. 1 ） were A ＊ 11 ： 01 ,A ＊ 24：02 ,A ＊ 02： 01, B ＊ 46： 01, DRB1 ＊ 09： 01, and DRB1 ＊ 15： 01. Among the 841 HLA-A/B two loci haplotypes, 17 had a frequency over 0. 01,70 showed significant positive linkage disequilibrium （ ALD 〉 0, HF ≥ 3.67 × 10 -4 ,X2 〉 3. 84）. Moreover, 12 of the 1 027 HLA-B/DRB1 haplotypes identified had a frequency over 0. 01,99 showed sig- nificant positive linkage disequilibrium （ALD 〉 0, HF ≥3.67 × 10-4, X2 〉 3.84 ）. In addition, 681 of the 3 344 HLA-A-B- DRB1 haplotypes identified had a frequency over 3.67 × 10 -4,135 had a frequency over 0. 001. Conclusion The HI_A-A, B and DRB1 allele frequencies and haplotype structure of the Shanghai Han population has their own characteristics. The re- suits of the study provides useful information for transplant donor selection,formulation of the Chinese Han population CWD alleles, estimation of optimal bone marrow registry size and general human genetics studies.

关 键 词：HLA-A B DRB1 高分辨基因分型 等位基因频率 单体型频率 

分 类 号：R457.11[医药卫生—治疗学]