α-1,3-N-乙酰半乳糖胺基转移酶等位基因467C＞T和539G＞C变异导致A2亚型

为了研究中国汉族人群ABO血型系统中A2亚型的分子遗传背景，发现并鉴定新的ABO等位基因，采用血型血清学方法鉴定5例ABO血型疑难样本，PCR扩增ABO基因转录调控序列和全编码序列，PCR产物经割胶纯化后直接测序，并对含有变异位点的扩增片段进行单倍体序列分析。结果表明：5例疑难样本分别鉴定为A2或A2B亚型；进一步研究发现，1例A2B和1例A2样本分别含有A201和A205等位基因，另3例A2B样本中发现一个新的A2等位基因。该等位基因与A101相比，差异在外显子7的467C〉T和539G〉C变异，导致多肽链P156L和R180P的替换。结论：首次发现467C〉T和539G〉C组合的A2等位基因，中国汉族人群中A2亚型具有遗传多态性。

Variants 467C＞T and 539G＞C of the α-1,3-N-acetylgalactosaminyltransferase Allele Responsible for A2 Subgroup

The purpose of this study was to investigate the molecular genetic basis of A_2 subgroup and identify the novel alleles at ABO locus in Chinese Han population. All seven exons and their flanking sequences, enhancer and promoter in the ABO gene of five samples from individuals with serological discrepancies were amplified by polymerase chain reaction (PCR); the PCR products were screened by directly sequencing; the haplotypes of exon 6 and 7 were analyzed by TOPO cloning sequencing. The results showed that five samples were identified as A_2 or A_2B subgroup by serological technology. The A_ 201 and A_ 205 alleles were confirmed in one A_2B individual and one A_2 individual, respectively. A novel A_2 variant allele was identified in three A_2B individuals. The two nucleotide acid alterations (467C>T and 539G>C) at the exon 7 resulting in two amino acid substitutions (P156L and R180P) in this novel allele were observed, when compared with A_ 101 allele. It is concluded that the polymorphism of A_2 allele is found to be relatively variable in Chinese population, and a novel A_ 208 allele responsible for A_2 subgroup is firstly reported.