ABO^(*)B.01 等位基因 c.3G>C 突变所致亚型的鉴定与分子生物学机制研究  

Identification and molecular biological mechanism study of subtypes caused by ABO^(*)B.01 allele

作　　者：张钰 蔡杰[1] 凌亚亭 张璐[1] 李萌[2] 傅强[1] 何成涛[1] ZHANG Yu;CAI Jie;LING Yating;ZHANG Lu;LI Meng;FU Qiang;HE Chengtao(Nanjing Red Cross Blood Center,Nanjing 210003,China;Children’s Hospital of Nanjing Medical University,Nanjing 211112,China)

机构地区：[1]南京红十字血液中心,江苏南京210003 [2]南京医科大学附属儿童医院输血科,江苏南京211112

出　　处：《中国输血杂志》2025年第2期274-279,共6页Chinese Journal of Blood Transfusion

基　　金：2021年度南京市医学科技发展项目(YKK21172)。

摘　　要：目的对1例血型血清学检测正反定型不符的标本进行基因分型,并对其进行家系调查分析及分子生物学机制研究。方法采用血型血清学方法鉴定先证者及其家系成员ABO血型;采用Sanger和单分子实时测序法(single molecule real-time sequencing,SMRT)对先证者及其家系标本进行ABO基因的1~7外显子测序分析;采用DeepTMHMM对突变前后的蛋白质进行跨膜区预测与分析。结果先证者及其母亲为Bw表型,其外公为ABw表型,其他家系成员血型结果正反定型相符;ABO基因测序结果显示先证者及其母亲、外公的B基因第1外显子存在c.3 G>C新变异,导致翻译起始位点后移;DeepTMHMM分析结果显示翻译起始位点后移改变了蛋白拓扑结构。结论ABO基因第1外显子c.3 G>C突变导致翻译起始位点后移,使得蛋白拓扑结构从α-跨膜区变为球形信号肽,降低了酶的活性,产生Bw血清学表型。Objective To study on the genotyping of a sample with inconsistent forward and reverse serological tests,and to conduct a pedigree investigation and molecular biological mechanism study.Methods The ABO blood group of the proband and his family members were identified using blood group serological method.The ABO gene exon 1-7 of samples of the proband and his family were sequenced by Sanger and single molecule real-time sequencing(SMRT).DeepTMHMM was used to predict and analyze the transmembrane region of proteins before and after mutation.Results The proband and his mother have the Bw phenotype,while his maternal grandfather has ABw phenotype.The blood group results of forward and reverse typing of other family members were consistent.ABO gene sequencing results showed that there was B new mutation of c.3 G>C in exon 1 of ABO gene in the proband,his mother and grandfather,leading to a shift in translation start site.DeepTMHMM analysis indicated that the shift in the translation start site altered the protein topology.Conclusion The c.3 G>C mutation in the first exon of the ABO gene leads to a shift in the translation start site,altering the protein topology from anα-transmembrane region to a spherical signaling peptide,reducing enzyme activity and resulting in the Bw serological phenotype.

关 键 词：Bw亚型 家系调查 DNA测序 蛋白跨膜区 

分 类 号：R457.1[医药卫生—治疗学]