论文部分内容阅读
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 understand the allele and haplotype distribution of HLA-A, B and DRB1 in high-resolution typing of Han nationality in Shanghai. Methods A total of 4 082 randomized, unrelated and healthy Han Chinese hematopoietic stem cell donors from China Marrow Bank Shanghai Branch were enrolled in this study. The high-resolution HLA-A, B and DRB1 genes were analyzed by PCR-Sequencing-based typing (SBT) The frequencies of alleles and haplotypes of HLA-A, B and DRB1 were calculated by counting, counting and maximum likelihood respectively. Results A total of 204 HLA alleles were observed in 4 082 samples. The alleles of HLA-A, B and DRB1 with frequency> 0.1 were A * 11:01, A * 24:02 and A * 02: 70 haplotypes showed significant linkage disequilibrium (ALD> 0, HF≥3.67 × 10 -11) in the haplotypes AB01, B * 46:01, DRB1 * 09:01 and DRB1 * 4, χ2> 3.84). Eight of them displayed strong linkage disequilibrium (RLD> 0.40). The frequencies of 17 haplotypes were higher than 0.01. Among 1027 B-DRB1 haplotypes, 99 haplotypes showed significant (ALD> 0, HF≥3.67 × 10-4, χ2> 3.84), 12 showed strong linkage disequilibrium (RLD> 0.40), and the frequencies of 12 haplotypes were higher than 0.01; 3 344 Of the AB-DRB1 haplotypes, 681 haplotypes were “reliable” (frequency ≥3.67 × 10-4) and haplotype frequencies were higher than 0.001 with 135. Conclusion The HLA-A, B, DRB1 high-resolution allele frequency and haplotype distribution data and related genetic parameters were obtained from Han population of Shanghai. The data were of clinical transplanted donors, CWD of Chinese population, Assessment and human genetics research provide reference data.