一个罕见HLA-C等位基因间重组家系的遗传背景研究
일개한견HLA-C등위기인간중조가계적유전배경연구
The genetic study on a rare inter-allelic recombination of HLA-C locus in a Chinese Han family
  • 万方数据
    中华检验医学杂志 중화검험의학잡지
    CHINESE JOURNAL OF LABORATORY MEDICINE
    2011年 7期 586-590 ,共5页

    邹红岩%羊婷婷%李桢

    추홍암%양정정%리정

    HLA-C抗原%等位基因%系谱%重组,遗传 HLA-C抗原%等位基因%繫譜%重組,遺傳
    HLA-C항원%등위기인%계보%중조,유전
    HLA-C antigens%Alleles%Pedigree%Recombination,genetic
    目的 研究HLA-C等位基因座位上的交换重组,探讨HLA新等位基因产生的分子遗传背景.方法 采集拟进行造血干细胞移植的1例慢性粒细胞白血病患者、患者父母以及2名哥哥的静脉血,采用AlleleSEQR HLA 测序分型试剂进行HLA-A、C、B、DRB1和DQB1共5个位点的高分辨基因分型;再采用Protrans S4 HLA单倍体测序技术分离2个HLA-C等位基因,以确定序列异常的1个C等位基因;进一步采用分子克隆和测序方法进行患者及父母HLA-C等位基因的全长单倍体序列分析.按遗传规律分析该家系的HLA 5个位点的连锁单倍型,同时将HLA-C等位基因全长序列经IMGT/HLA Database中的"BLAST"程序进行序列的对比,以确定C等位基因重组发生的精确位置.结果 经HLA测序及遗传家系分析,该家系中父亲的2条HLA连锁单倍型分别为a:A*0207-C*010201-B*550201-DRB1*090102-DQB1*030302与b:A*240201-C*120202-B*5201-DRB1*1502-DQB1*0601;母亲的分别为:c:A*300101-C*060201-B*130201-DRB1*0405-DQB1*0401与d:A*110101-C*070201-B*4001-DRB1*080302-DQB1*0601.患者的2名哥哥均分别正常遗传了父母的2条单倍体a、d及b、c.患者的2条单倍体分别为母源单倍体c及父源重组单倍体a/b,其中A*240201来自父亲的1条染色单体b,而B*550201-DRB1*090102-DQB1*030302则来自父亲的另1条染色单体a.对比患者携带的C未知新等位基因与父亲的1对C*010201 、C*120202等位基因的全长单倍体序列,推断父亲的2条染色单体在减数分裂时,由于HLA-C等位基因的第273位至330位碱基区域之间发生了交换,重组后形成新的C等位基因及单倍型并遗传给了患者.该C新等位基因的全长序列已递交GenBank,并被世界卫生组织HLA因子命名委员会正式命名为C*0121.结论 本研究发现了1个罕见的中国汉族人群HLA-C基因座位上的基因重组家系,阐明了HLA-C*0121新等位基因及单倍型的产生来源,为更深入研究基因重组及HLA多态性形成机制提供了理论依据.
    목적 연구HLA-C등위기인좌위상적교환중조,탐토HLA신등위기인산생적분자유전배경.방법 채집의진행조혈간세포이식적1례만성립세포백혈병환자、환자부모이급2명가가적정맥혈,채용AlleleSEQR HLA 측서분형시제진행HLA-A、C、B、DRB1화DQB1공5개위점적고분변기인분형;재채용Protrans S4 HLA단배체측서기술분리2개HLA-C등위기인,이학정서렬이상적1개C등위기인;진일보채용분자극륭화측서방법진행환자급부모HLA-C등위기인적전장단배체서렬분석.안유전규률분석해가계적HLA 5개위점적련쇄단배형,동시장HLA-C등위기인전장서렬경IMGT/HLA Database중적"BLAST"정서진행서렬적대비,이학정C등위기인중조발생적정학위치.결과 경HLA측서급유전가계분석,해가계중부친적2조HLA련쇄단배형분별위a:A*0207-C*010201-B*550201-DRB1*090102-DQB1*030302여b:A*240201-C*120202-B*5201-DRB1*1502-DQB1*0601;모친적분별위:c:A*300101-C*060201-B*130201-DRB1*0405-DQB1*0401여d:A*110101-C*070201-B*4001-DRB1*080302-DQB1*0601.환자적2명가가균분별정상유전료부모적2조단배체a、d급b、c.환자적2조단배체분별위모원단배체c급부원중조단배체a/b,기중A*240201래자부친적1조염색단체b,이B*550201-DRB1*090102-DQB1*030302칙래자부친적령1조염색단체a.대비환자휴대적C미지신등위기인여부친적1대C*010201 、C*120202등위기인적전장단배체서렬,추단부친적2조염색단체재감수분렬시,유우HLA-C등위기인적제273위지330위감기구역지간발생료교환,중조후형성신적C등위기인급단배형병유전급료환자.해C신등위기인적전장서렬이체교GenBank,병피세계위생조직HLA인자명명위원회정식명명위C*0121.결론 본연구발현료1개한견적중국한족인군HLA-C기인좌위상적기인중조가계,천명료HLA-C*0121신등위기인급단배형적산생래원,위경심입연구기인중조급HLA다태성형성궤제제공료이론의거.
    Objective To study the inter-allelic recombination event occurring in the HLA-C locus in a family of Chinese Han nationality, and to evaluate the molecular genetic background of the new HLA allele.Methods Peripheral blood samples were collected from a Chinese leukemia woman patient, as well as her healthy parents and two brothers.HLA-A, C, B, DRB1 and DQB1 alleles were typed by high-resolution PCR-sequence-based typing (SBT) method using Atria Genetic AlleleSEQR HLA SBT kits.The Protrans S4 HLA-C single allele-specific sequencing strategy was used to separate the two HLA-C alleles and to determine novelty of the allele.The full length sequences of HLA-C alleles of the patient and her parents were further analyzed using cloning and haplotype sequencing method. The HLA five loci linked haplotypes and the recombination site were analyzed by family study, meanwhile the full length sequences of the five HLA-C alleles were compared with the IMGT/HLA database by the program "BLAST".Results The two haplotypes of the father and mother were a:A*0207-C*010201-B*550201-DRB1*090102-DRQ1*030302 and b:A*240201-C*120202-B*5201-DRB1*1502-DRQ1*0601, c:A*300101-C*060201-B*130201-DRB1*0405-DRQ1*0401 and d:A*110101-C*070201-B*4001-DRB1*080302-DRQ1*0601,respectively.The two brothers inherited their parent′s haplotypes a, d and b, c respectively.The two haplotypes of the patient were the maternal c and paternal recombinant a/b haplotype.The recombinant a/b haplotype A*240201-C*new-B*550201-DRB1*090102-DRQ1*030302, A*240201 came from the paternal haplotype b,while B*550201-DRB1*090102-DRQ1*030302 came from the other paternal haplotype a.When comparing the full length sequences of the HLA-C new allele with the father′s allele C*010201 and C*120202, it could deduce that the recombinant a/b haplotype derived from a recombination event occurring between the paternal chromosome 6 during meiosis.The crossover site was between genomic nt273 and nt330 of HLA-C alleles, which created a HLA-C new allele and the fifth haplotype of the family, and inherited it to the patient.The full length sequences of the new allele had been submitted to Genbank, and officially named C*0121 by WHO nomenclature committee.Conclusion This study demonstrates a rare inter-allelic recombination event occurring in the HLA-C locus within a Chinese Han family and illustrates the process of novel allele and haplotype, and provides direct theory for further studying the mechanisms of gene recombination and HLA polymorphism.
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