目的:分析一个在父母双方的HLA-A/C基因座之间发生重组的中国家系。
方法:选择2022年2月因“再生障碍性贫血”计划进行造血干细胞移植的患者作为研究对象。收集患者外周血样本,他的父母和兄弟。通过使用基于序列的分型和序列特异性寡核苷酸进行HLA-A/C/B/DRB1/DQB1高分辨率分型。通过谱系分析鉴定重组。通过系谱分析鉴定每个个体的HLA单倍型。通过短串联重复分析确定亲子关系的可能性。HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1是通过下一代基于高通量序列的分型来确定的。通过家族研究分析重组位点。
结果:通过短串联重复分析证实了家庭的高亲子关系可能性。在父系传播的单倍型中,HLA-A*24:02A*33:03/C*14:03之间发现了重组,而HLA-A*01:01A*03:01/C*08:02在母体传播的单倍型中发现,在先证者中产生了两种新的HLA单倍型。
结论:发现一例罕见的父系和母系HLA-A/C位点同时重组,这可能有助于进一步研究HLA重组的机制。
OBJECTIVE: To analyze a Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents.
METHODS: A patient who was planning to undergo hematopoietic stem cell transplantation due to \"aplastic anemia\" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA-A/C/B/DRB1/DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study.
RESULTS: The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA-A*24:02 A*33:03/C*14:03 in the paternally transmitted haplotype, whilst HLA-A*01:01 A*03:01/C*08:02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband.
CONCLUSIONS: A rare case with simultaneous recombination of the paternal and maternal HLA-A/C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.