HLA新等位基因B＊5827核苷酸序列的分析

Sequence analysis of a novel human leukocyte antigen allele B＊ 5827

目的确认人类白细胞抗原（human leukocyte antigen，HLA）新等位基因B＊5827并分析其核苷酸序列。方法用聚合酶链反应-序列特异性寡核苷酸探针对1份HLA分型反应异常的血样进行基因分型，并用基因克隆测序技术正反向测定DNA序列。结果测序结果显示HLA-B位点有1个与已知HLA等位基因序列均不同的新等位基因，该等位基因与HLA-B＊5820序列同源性最高。但在第3外显子存在8个碱基的差异，分别为nt 290（G〉C）、nt 346（T〉A）、nt 390（A〉C）、nt 404（G〉C）、nt 413（C〉G）、nt 471（A〉G）、nt 486（A〉G）和nt 487（C〉A）。碱基的不同导致了氨基酸不同nt 97（ser〉arg）、nt 115（phe〉tyr）、nt 130（ser〉arg）、nt 157（thr〉ala）和nt 162（thr〉glu），其中nt 404和nt 413是同义突变。结论该等位基因为HLA新等位基因，基因序列已提交至GenBank数据库，提交号为GU071234，于2010年1月被世界卫生组织HLA因子命名委员会正式命名为HLA-B＊5827。

Objective To investigate the molecular basis for a novel human leukocyte antigen（HLA） allele B ＊ 5827. Methods DNA from the proband was analyzed by polymerase chain reaction-sequence specific oligonucleotide （PCR SSO） typing. The amplified product was sequenced bidirectionally. Results Abnormal HLA-B locus was observed and its nucleotide sequence was different from the known HLA-B allele sequences, with highest homology to HLA-B ＊ 5820 allele. It differs from HLA-B ＊ 5820 by 8 nucleotide substitutions in exon 3, i. e. , nt 290 （G〉C）, nt 346 （T〉A）, nt 390 （A〉C）, nt 404 （G〉C）, nt 413 （C〉G）, nt 471 （A〉G）, nt 486 （A〉G） and nt 487 （C〉A）, resulting in an amino acid change from ser〉arg at nt 97, phe〉tyr at nt 115, ser〉arg at nt 130, thr〉ala at nt 157 and thr〉glu at nt 162. Nucleotide differences of nt 404（G〉C） and nt 413（C〉G） did not change amino acid. Conclusion The sequences of the novel allele have been submitted to GenBank （access No. GU071234）. A novel HLA class I allele B ＊ 5827 has been officially assigned by the WHO HLA Nomenclature Committee in Jan 2010.