父源HLA单倍型染色体A位点基因重组一家系

A Recombination Event Occurring between HLA-A and-A loci from Father′s HLA Haplotype Chromosome

本研究探讨父源HLA单倍型染色体A位点基因座间的重组。采集患者及其父母和两个姐姐静脉血标本,用PCR-SSP进行HLA-Ⅰ、Ⅱ类低分辨基因分型,PCR-SSBT进行HLA-A、B、DR位点高分辨基因分型。结果表明,HLA高分辨基因分型证实患者的2条单倍型分别为A*3001-B*1302-DRB1*0701和A*3001-B*5601-DRB1*1454;其父亲的2条单倍型为A*3001-B*1302-DRB1*0701和A*1101-B*5601-DRB1*1454。遗传家系分析显示患者所携有的A*3001-B*1302-DRB1*0701单倍体是源自母亲的一条染色单体,而A*3001-B*5601-DRB1*1454则源自父亲的另一条染色单体,可患者的A位点为3001,而B、DR位点一致。这表明,父亲的2条染色单体在减数分裂时A基因座间发生了交换,重组后的单倍型又完整地遗传给了患者。该家系HLA低分辩和高分辨分型结果和遗传分析表明,子1是亲生;亲子鉴定也证明,子1和父亲、母亲具有亲缘关系;进一步遗传分析证实,子1HLA-A位点发生父源染色体基因重组。结论:本家系为国内首次发现父源HLA单倍型染色体A位点发生重组的家系,这为更深入研究HLA重组机制提供了依据。

This study was aimed investigate the recombination event occurring between HLA-A and-A loci discovered from father′s HLA haplotype chromosome in a family.Peripheral blood samples were collected from a family.HLA classⅠ（-A,-B,and-Cw） and Ⅱ（-DRB1 and-DQB1） alleles were amplified and typed by both low and high resolution PCR with sequence-specific primers（PCR-SSP）and sequence-based typing（SBT）.The results showed that 2 haplotypes of the patient were A＊3001-B＊1302-DRB1＊0701 and A＊3001-B＊5601-DRB1＊1454 respectively,those of her father were A＊3001-B＊1302-DRB1＊0701 and A＊1101-B＊5601-DRB1＊1454.Family analysis demonstrated that the patient′s A＊3001-B＊1302-DRB1＊0701 came from her mather and A＊1101-B＊5601-DRB1＊1454 came from her father,but the A of patient was A＊3001 and B,DR were the same to her father.This showed that the chromosome exchange and recombination event of father′s 2 haplotypes occurring between HLA-A and-A loci at meiosis.And recombinated haploid chromosome was completely inherited to his dauther 1.HLA typing and Paternity testing demonstrated that father was the natural father,and the recombination event occurring between HLA-A and-A loci of the daughter 1 with father′s HLA haplotype chromosome.It is concluded that the HLA-A/A of father′s HLA haplotype chromosome recombination event occurring between HLA-A an-A loci has been found in a family in China,which helps further study on the mechanisms of HLA recombination.