一个HLA-A抗原三联体家庭的分子遗传学研究

Molecular genetics analysis of a Chinese family carrying triple HLA-A antigen

目的 研究江苏省骨髓库供者SZHD1及其 4名家庭成员的HLA A抗原HLA三联体表型的分子遗传学基础。方法 使用标准微量淋巴细胞毒试验和特异性单克隆抗体 ,测定淋巴细胞HLA血清学抗原特异性。使用PCR SSP方法作HLA基因分型 ,并进一步采用分子克隆和DNA序列方法分析测定相应的基因结构。结果 供者SZHD1的淋巴细胞带有HLA A2、A11.2和A2 4等 3个抗原。分子克隆和DNA序列分析表明相应等位基因为HLA A 0 2 0 6、A 110 2和A 2 4 0 2 0 10 1。家系调查表明该供者的 1条单体型为HLA A 2 4 0 2 0 10 1,A 110 2 ;B 38;DRB1 15。同一条单体型带有 2个表达的HLA A等位基因 ,该单体型按孟德尔定律分离 ,稳定地传递了 3代。供者的父亲、哥哥、妹妹、及其孩子也带有该单体型。结论 供者SZHD1及其 4名家庭成员的 1条HLA单体型上 ,带有 2个表达的HLA A等位基因 ,该单体型稳定地遗传 ,表现出HLA遗传多态性的一种新形式。HLA A座位表达 3种抗原的家庭为世界上首次报告。

Objective A rare HLA phenotype carrying three HLA-A antigens, A2, A11.2 and A24, was identified in a potential bone marrow donor SZHD1. Methods To determine molecular basis of this phenotype the HLA-A gene fragments from this donor and his family members were cloned and sequenced. Results Sequencing analysis indicated that the donor carries an unusual HLA haplotype, A*1102, A*24020101; B*38; DRB1*15. Conclusions Other four family members were found to carry this haplotype, which as a Mendelian gene was segregated and stably transmitted through three generations. This is a first example of a family carrying triple HLA-A antigens to the best of our knowledge.