罕见父源母源HLA-A/C基因座位间同时重组一个家系的遗传学研究  

Genetic study of a rare Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents

作　　者：王天菊[1] 王满妮[1] 齐珺[1] 李昱辉 武君华[1] 尚利侠 陈乐 Wang Tianju;Wang Manni;Qi Jun;Li Yuhui;Wu Junhua;Shang Lixia;Chen Le(HLA Typing Laboratory,Shaanxi Provincial Blood Center,Xi′an,Shaanxi 710061,China)

机构地区：[1]陕西省血液中心HLA组织配型实验室,西安710061

出　　处：《中华医学遗传学杂志》2024年第7期853-857,共5页Chinese Journal of Medical Genetics

基　　金：陕西省重点研发计划(2022SF-098);西安市卫生健康委员会研究基金(2022yb06)。

摘　　要：目的探讨1个家系中父源和母源人类白细胞抗原单体型HLA-A/C基因座之间的重组情况。方法选取2022年2月因"再生障碍性贫血"拟接受造血干细胞移植的1例患者作为研究对象。采集患者及其父母和胞兄的外周血样,分别采用测序和聚合酶链反应-序列特异性寡核苷酸探针技术对HLA-A/C/B/DRB1/DQB1位点进行高分辨基因分型,通过家系分析确定个体的HLA单体型。通过检测短串联重复序列位点确定家系成员之间的亲缘关系,再用二代测序技术对HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1等11个位点进行高分辨分型,再次确认HLA的重组位点。结果短串联重复序列位点结果证实家系成员之间存在亲缘关系。父源HLA单体型HLA-A*24:02 A*33:03/C*14:03之间发生重组,母源HLA单体型HLA-A*01:01 A*03:01/C*08:02之间发生重组,产生的新单体型被完整地遗传给子代。结论发现并证实了1个陕西汉族人群父源和母源HLA-A/C基因座位间同时发生重组的家系,为深入研究HLA的重组机制提供依据。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.Conclusion 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.

关 键 词：人类白细胞抗原 单体型 基因重组 

分 类 号：R457.7[医药卫生—治疗学]