一个中国汉族ABO血型B亚型家系中发现新的B等位基因  

Identification of a novel B variant allele in a Chinese Han individual with B subgroup

作　　者：喻琼[1] 吴国光[1] 梁延连[1] 邓志辉[1] 苏宇清[1] 

机构地区：[1]广东省深圳市血液中心深圳市输血医学研究所,518035

出　　处：《中华医学遗传学杂志》2005年第2期129-133,共5页Chinese Journal of Medical Genetics

基　　金：广东省医学科研基金课题(2001641);深圳市科技局资助(200304217)~~

摘　　要：目的　研究中国汉族人群ABO血型中B亚型的分子遗传背景,发现并鉴定ABO新等位基因。方法　随机选择10个正常的B型志愿捐血者样本作对照,对6例血型血清学鉴定为B亚型的样本,采用序列特异性引物-聚合酶链反应方法、ABO基因第6及第7外显子PCR产物直接测序,进行基因定型;并对B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　2例血清学为Bx、BW的B亚型样本中,发现一个新的B等位基因。该等位基因与B1 0 1 等位基因相比,差异仅在第7外显子nt6 95位T>C突变。进一步对其中一个Bx 血型的个体进行家系调查,结果该家系的11人中,7人带有该新B等位基因。而其余的4例B亚型样本及10例对照样本,ABO基因的第6、7外显子未发现新的点突变。结论　首次发现6 95 T>C变异的新B等位基因,该等位基因nt6 95位由T转变为C,2 32位氨基酸由亮氨酸转变为脯氨酸,可导致糖基转移酶活性的降低,表明ABO基因的第2 32位氨基酸对决定糖基转移酶活性至关重要。Objective To study the molecular genetic background of B subtype in Chinese Han population and identify novel allele at the ABO locus. Methods Ten samples from randomly selected blood donors of normal B phenotype used as controls, and six samples from individuals diagnosed as B subgroup by serological tests were genotyped by sequence specific primer-polymerase chain reaction and direct DNA sequencing at the exons 6 and 7 of ABO gene. The exons 6 and 7 and the intervening intron 6 of the B allele from each B subgroup sample were analyzed by cloning and haplotype-sequencing. Results A novel B variant allele was identified in two individuals whose blood samples were diagnosed as belonging to B x subgroup and Bw subgroup respectively, the novel B allele being different from the allele B 101 by single 695T>C missense mutation in exon 7. A family with the individual possessed Bx subgroup was studied. Among 22 family members tested, seven family members were found to carry the novel B variant allele. No novel point mutation at the exons 6 and 7 of ABO gene were detected in the ten control samples and the other four samples with B subgroup. Conclusion The present authors define this allele as a novel B variant allele. The mutation of this novel allele, in which the nucleotide alters from T to C at position of 695 in exon 7 and hence results in an amino acid change from Leu to Pro, is expected to diminish the enzyme's activity. It indicates that the alteration of amino acid at the position of 232 is critical to the activity of glycosyltransferases.

关 键 词：ABO血型 B亚型 聚合酶链反应方法 第7外显子 ABO基因 序列特异性引物 中国汉族人群 新等位基因 血清学鉴定 PCR产物 第6外显子 遗传背景 直接测序 基因定型 测序分析 基因克隆 家系调查 Bx血型 首次发现 氨基酸 酶活性 

分 类 号：Q987[生物学—遗传学]