3个HLA-A新等位基因的序列分析及确认  

Sequences Analysis and Identification of Three New HLA-A Alleles

作　　者：尚利侠 齐珺[1] 武君华[1] 陈乐 王满妮[1] 王小芳[1] 房婕[1] 王天菊[1] SHANG Li-xia;QI Jun;WU Jun-hua(Shaanxi Blood Center,Xi'an 710061)

机构地区：[1]陕西省血液中心,西安710061

出　　处：《临床输血与检验》2021年第6期728-732,共5页Journal of Clinical Transfusion and Laboratory Medicine

基　　金：西安市科技计划项目(No.20YXYJ0009);西安市科技计划项目(No.201805095YX3SF29);中国造血干细胞捐献者资料库(CMDP)资助。

摘　　要：目的确认3个HLA新等位基因,并分析其核苷酸和氨基酸序列。方法应用DNA测序分型技术(Sanger测序)对2018年中国造血干细胞捐献者资料库入库样本A/B/C/DRB1/DQB1位点进行常规检测,采用二代测序(Next Generation Sequence,NGS)方法对Sanger测序检测到A位点无匹配结果的3个样本进行测序确认,所得序列与已知同源性最高的等位基因序列进行比对,分析其核苷酸序列的差异。结果样本1与其同源性最高的A^(*)02:07:01相比,第3外显子520碱基发生G>A变异,导致第174位密码子GCC>ACC,氨基酸由丙氨酸(Ala)变成苏氨酸(Thr);样本2与其同源性最高的A^(*)02:06:01相比,第4外显子641碱基发生C>T变异,导致第214位密码子ACT>ATT,氨基酸由苏氨酸(Thr)变成异亮氨酸(Ile);样本3与其同源性最高的A^(*)02:01:01相比,第4外显子652碱基发生G>C变异,导致第218位密码子GTC>CTC,氨基酸由缬氨酸(Val)变成亮氨酸(Leu)。结论3个等位基因均为HLA-A新等位基因,被世界卫生组织HLA因子命名委员会分别正式命名为:HLA-A^(*)02:897、HLA-A^(*)02:898、HLA-A^(*)02:899。Objective To identify three novel alleles of HLA-A,analyze their nucleotide and amino acid sequences.M e t hods Three novel alleles were initially detected by DNA sequencing typing(Sanger sequencing),then the sample sequenced by Next Generation Sequence(NGS)to confirm the mutation allele and locus.Results The first new allele sequence was different from that A^(*)02:07:01 at the position 520(G>A)in exon 3,which results in an amino acid change from Ala to Thr at codon 174.The second new allele sequence was different from that A^(*)02:06:01 at the position 641(C>T)in exon 4,which results in an amino acid change from Thr to Ile at codon 214.The third new allele sequence was different from that A^(*)02:01:01 at the position 652(G>C)in exon 4,which results in an amino acid change from Val to Leu at codon 218.Conclusion All three alleles were new HLA-A alleles which have been designated as:HLA-A^(*)02:897,HLA-A^(*)02:898,HLA-A^(*)02:899 by the Word Health Organization(WHO)HLA Nomenclature Committee.

关 键 词：HLA等位基因 碱基变异 二代测序 

分 类 号：R394[医药卫生—医学遗传学]