HLA-B＊2736等位基因的序列分析  

Identifying and sequence analysis of HLA-B＊2736

作　　者：李桢[1] 邹红岩[1] 邵超鹏[1] 唐斯[1] 王大明[1] 程良红[1] 

机构地区：[1]广东省深圳市血液中心,深圳518035

出　　处：《遗传》2007年第11期1367-1372,共6页Hereditas（Beijing)

摘　　要：使用FLOW-SSO、PCR-SSP以及测序等分型技术,发现一个与HLA-B*270401基因相关的未知基因。设计基因特异性引物单独扩增B*27基因的外显子2-5,包括内含子2-4,并进行双向测序,分析与B*270401基因序列的差异。该基因的扩增产物为1815bp。与B*270401相比在外显子3和4共有10个碱基的改变,从而使相应氨基酸发生错义或同义突变。碱基634A→C(密码子130丝氨酸→精氨酸);670A→T(密码子142苏氨酸→丝氨酸);683G→T(密码子146色氨酸→亮氨酸);698A→T(密码子151谷氨酸→缬氨酸);774G→C(密码子176谷氨酸→天冬氨酸);776C→A(密码子177苏氨酸→赖氨酸);781C→G(密码子179谷氨酰胺→谷氨酸);789G→T(密码子181丙氨酸同义突变);1438C→T(密码子206甘氨酸同义突变);1449G→C(密码子210甘氨酸→丙氨酸)。在IMGT/HLA数据库中B*27组只有3个基因(B*270502/2706/2732)提交了内含子序列。该未知基因的内含子2序列与B*2706相同,显示了与B*27组基因的同源性,但其同源性在内含子3、4均未得到支持,与B*27组基因相比,内含子3的第106个碱基C→G,碱基168缺失,碱基179G→A,碱基536G→A;内含子4中碱基82T→C。但其内含子3、4序列却与B*070201完全相同。该基因序列已提交GenBank,编号为被DQ915176,被WHO确认为HLA-B*2736等位基因。An unknown HLA-B allele which was similar to HLA-B＊270401 was detected by FLOW-SSO, PCR-SSP and heterozygous sequence-based typing （SBT） in Chinese Han individual. Its anomalous patterns suggested the possible presence of new allele. Amplifying exon 2-5（include intron 2-4） of the HLA-B＊27 allele separately by using allele-specific primers and sequencing in both directions. Identifying the difference between the novel B＊27 allele and B＊270401. The sequence of novel B＊27 from exon 2 to partial exon 5 is 1 815 bp. There are 10 nt changes from B＊270401 in exon 3-4, at nt634where A→C（codonl30 AGC→CGC, 130 S→R）; nt670 where A→T （codon142 ACC→TCC, 142 T→S）; nt683 where G→T （codon146 TGG→TrG, 146 W→L）; nt698 where A→T （codonl51 GAG→GTG, 151 E→V）; nt774 where G→C （codon176 GAG→GAC, 176 E→D）; nt776 where C→A （codon177 ACG→AAG, 177 T→K）; nt781 where C→G （codon179 CAG→GAG, 179Q→E）; nt789 where G→T （codonl81 GCG→GCT） resulting no coding change; nt1438 where C→T （codon206 GGC→GGT） resulting no coding change; nt1449 where G→C （codon210 GGG→GCG, 210G→A）. In IMGT/HLA database, only three alleles （B＊2705021270612732） have sequences of introns. The same sequence in intron 2 showed homology between the novel HLA-B＊27 allele and B＊2706, but their homology could not be supported in intron 3-4 Comparing the sequence of the novel B＊27 allele in intron 3 and 4 with B＊27 group, it showed there are three mutations at ntl06 C→G, nt179 G→A, nt536 G→A and one deletion at nt168 in intron 3 and one mutations at nt82 T→C in intron 4, but the sequence of the novel B＊27 allele in intron 3 and 4 was all the same to B＊070201. The sequence was submitted to Gen- Bank and the accession number was DQ915176. The allele has been confirmed as an extension of B＊2736 by the WHO Nomenclature committee in November 2006.

关 键 词：人类白细胞抗原 基因 序列 外显子 内含子 

分 类 号：R392[医药卫生—免疫学] Q987[医药卫生—基础医学]