新等位基因HLA-A*24:233与HLA*-A26:89的分析确认

Identification of novel HLA alleles: HLA-A*24:233 and HLA-A*26:89

背景:分子生物学新技术的发展和大量应用加快了中国发现HLA新等位基因的步伐。新等位基因的发现不仅给HLA家族增加了新成员,同时也为研究民族或地区的优势基因或消失基因(不适合客观环境的基因)找到了突破点。目的:确认2个新的HLA等位基因,并分析其核苷酸序列。方法:应用PCR-SBT、GSSP测序基因分型技术对两份中华骨髓库供者样本进行HLA高分辨分型,发现2个样本HLA-A位点均为异常基因,与已知同源性最高的等位基因型进行序列比对,分析核苷酸序列的差异。结果与结论:2个样本HLA-A位点与目前已知的相应HLA-A等位基因序列均不一致,样本1与其同源性最高的A*24:02:01的差异表现在第3外显子区域中的第360位碱基由G>C,导致第96位密码子由谷氨酰胺变为组氨酸,样本2与其同源性最高的A*26:01:01比较差异表现在第2外显子区域中第97位碱基由T>C,导致编码的第9位密码子由酪氨酸变为组氨酸。结果表明两个样本为HLA-A位点的新等位基因,已提交GenB ank进行注册,并已被WHO HLA因子命名委员会正式命名为HLA-A*24:233与HLA-A*26:89。

BACKGROUND: The discovery of novel HLA alleles is accelerated by development of molecular biology and applications of numerous new technologies. These new findings not only rich HLA family, but also find a breakthrough point for the study of genetic superiority or disappearance of national gene.OBJECTIVE: To identify two novel HLA-A alleles and to analysis their nucleotide sequences.METHODS: The two samples from two volunteers of Chinese Marrow Donor Program were detected using PCR-SBT and GSSP methods. The HLA-A locus in the two samples were both abnormal genes, and the nucleotide sequence differences were analyzed.RESULTS AND CONCLUSION: The sequences of the samples were different from all alleles in the HLA databases. Sample 1 was found to be different from the closet matching allele A*24:02:01 in one nucleotide substitutions, 360 G > C in exon 3, resulting in amino acid changed from glutamine to histidine at codon 96; and sample 2 differed from A*26:01:01 in one nucleotide substitution, 97 T > C in exon 2, resulting in amino acid changed from tyrosine to histidine at codon 9. The novel alleles were identified and assigned the name HLA-A*24:233 and HLA-A*26:89 officially by the WHO Nomenclature Committee.