DNA 序列分析鉴定HLA新等位基因B^＊0740

Identification of a novel HLA allele (B*0740) by sequencing-based typing

目的确认一个中国人群中的新HLA等位基因.方法应用单倍型特异性分离(haplotype-specific extraction,HSE)技术和DNA序列分析技术鉴定HLA-B*的新等位基因.结果被检标本HLA-B位点有一个等位基因的核苷酸序列与任何已知的HLA等位基因均不同,与同源性最高的B*0705相比,在exon3区域中的605位碱基由A>T,引起编码178位的氨基酸由赖氨酸(K)变成甲硫氨酸(M).血清学分型表明新等位基因的免疫学表型仍为HLA-B7.家系分析提示,HLA- B*0740基因来源于其母亲.结论该等位基因序列为HLA-B位点的一个新等位基因,于2005年2月由WHO HLA因子命名委员会正式命名为HLA-B*0740.

Objective To identify a novel HLA-B allele variant from a donor of Chinese Marrow Donor Program （CMDP）. Methods Haplotype-Specific Extraction （HSE） and DNA sequencing were used to identify the sequence of potential novel HLA-B allele variant. HLA serological typing as well as family genetic investigation were Derformed for the new HLA allele. Results The HLA-B exons 2, 3, and 4 nucleotide sequence of the novel allele were different from all other known alleles. It had one nucleotide substitution at position 605 from A to T （codon 178 AAG-〉 ATG）, resulting in an amino acid change from lysine（K） to methionine（M） in comparison to the most homologous allele B 0705. However, serologic specificity remained B7 based on serological HLA typing. Family genetic analysis indicated that the novel HLA-B allele of the donor was inherited from his mother. Conclusion A novel HLA allele was confirmed by the sequencing based typing （SBT） and it was officially designated as HLA-B^＊ 0740 by WHO Nomenclature Committee for Factors of the HLA System in February, 2005.