现代医药卫生2025，Vol.41Issue(8)：1809-1813,5.DOI:10.3969/j.issn.1009-5519.2025.08.007
1种ABO等位基因新突变组合鉴定及蛋白结构分析
Identification of new ABO allele mutation combinations and analysis of protein structure
摘要
Abstract
Objective To analyze the serological and molecular biological characteristics of a new ABO allele mutation combination specimen,and to explore its genetic molecular mechanism by combining a three-dimensional structure model of the protein.Methods The laboratory used conventional serological methods to determine the ABO blood type of a proband and family members who were voluntary blood donors in October 2023.ABO genotyping was performed using Sanger sequencing,and the entire ABO gene,including flanking regulatory regions,was analyzed using PacBio third-generation long-read single-molecule real-time sequen-cing.Wild-type and mutant glycosyltransferase(GTA)three-dimensional molecular models were constructed using DynaMut,and the effects of mutations on enzyme function and protein stability were predicted using PROVEAN and PolyPhen2.Results The serum test results for both the proband and her father were AweakB,with genotyping results of Ax24/B101.ABO gene testing results compared with the ABO*A1.01 sequence:Both samples exhibit the following mutations:297A>G,467C>T,526C>G,657C>T,703G>A,796C>A,803G>C,838C>T,and 903G>A.This mutation combination genotype had not yet been identified in the ISBT database;third-generation sequencing resulted in ABO*A3.new/ABO*B.01,leading to the ami-no acid substitution p.Leu280Phe(L280F).GTA three-dimensional molecular modeling suggested that the L280F mutation reduced the number of hydrogen bonds and water-mediated hydrogen bonds in the protein structure,corresponding increased in the number of weak hydrogen bonds and weak water-mediated hydrogen bonds,and changed in interatomic interactions that affect the stability of the protein structure.Conclusion A new allele mutation combination of 467C>T and 838C>T is found in exon 7 of ABO.This missense mutation causes amino acid substitution to affect the change of enzyme activity,resulting in weak expression of A anti-gen and stable inheritance.关键词
ABO基因/抗原弱表达/基因测序/3D分子模型Key words
ABO allele/Weak expression of antigen/Gene sequencing/3D molecular model分类
医药卫生引用本文复制引用
杨红梅,马思飞,邹昕,钱程,徐立..1种ABO等位基因新突变组合鉴定及蛋白结构分析[J].现代医药卫生,2025,41(8):1809-1813,5.基金项目
江苏省常州市科技局项目(CJ20245046 （）
CJ20241124) （）
江苏省常州市中心血站科研基金项目(XZ202403). （XZ202403）
