ABO血型系统中Aw基因分子遗传背景的研究与分析

Molecular genetics of Aw alleles in ABO blood group

目的:研究一个含有Aw亚型中国汉族家系的ABO基因的遗传机制。方法:对1例血型血清学鉴定为Aw亚型的样本及有关家系,采用PCR-SSP扩增、DNA测序方法,以A101一致序列进行比对,对其ABO等位基因的第6外显子、第6内含子及第7外显子进行基因克隆和单倍体测序分析。结果:血清学为Aw型样本中ABO基因序列与ABO*A101相比有两个位点发生了突变467C>T,543G>T),文献中未见报道,为一个新的A等(位基因,该样本的家系5人中,2人带有这个新变异的A等位基因。结论:543位突变倒致编码ABO糖基转移酶的156位氨基酸由脯氨酸(Pro)变为亮氨酸Leu),大大降低了酶活性;这个位点对转移酶的活性(是至关重要的。

AIM: To study the ABO alleles molecular genetic mechanism in a Chinese family of which some individuals are suspected as Aw subgroup.METHODS: ABO genes of an individual diagnosed as having variant Aw subgroup by serological tests and the family were amplified by polymerase chain reaction sequence specific primers (PCR SSP) and sequenced with DNA, and compared with A101 consensus sequence, the gene cloning and haplotype sequence of last two exons (exon 6 and 7) and intron 6 of ABO alleles were performed.RESULTS: Compared with ABO* A101, there were two sites with mutation (467C >T, 543G >T) in ABO gene sequence of serological Aw type sample,and it was a new A allele,which had never been reported. In the Aw family with five members, two were demonstrated to carry this novel A variant allele.CONCLUSION: The mutation at 543 site, where G is replaced by T, results in amino acid at 156 site with glycosyltransferase encoded by ABO changes from proline (Pro) to leucine (Leu), and the activity is greatly decreased. It indicates that this site is critical to the activity of the glycosyltransferases.