导致中国人 Ax 表型的两个新型 a 等位基因的分子遗传分析。

IF 2.6 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Journal of the Formosan Medical Association Pub Date : 2024-09-09 DOI:10.1016/j.jfma.2024.09.002
Hang Lei,Jiaming Li,Can Lou,Hui Zhang,Yuqing Shen,Naizhu Su,Xuefeng Wang,Xiaohong Cai,Yeling Lu
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引用次数: 0

摘要

背景ABO基因突变可能导致ABO糖基转移酶(GT)功能障碍,从而导致弱ABO表型。材料与方法通过血清学研究和 ABO 基因的直接 DNA 测序进行 ABO 表型和基因分型。通过三维模型、蛋白质结构变化预测和体外表达检测评估了突变的作用。结果血清学结果显示受试者 RJ23 和 RJ52 均为 Ax 表型。根据基因分析,确定了新型 A 等位基因 Avar-1 和 Avar-2。Avar-1和Avar-2都含有重组杂合等位基因,特别是A2.05和O.01.02。这些等位基因在各自外显子中的位置分别为 c.106G > T、c.189C > T、c.220C > T 和 c.1009A > G。值得注意的是,这两个等位基因的交叉区域互不相同。体外表达研究表明,GTA 突变体阻碍了 H 抗原向 A 抗原的转化,而突变体并不影响 Western bolt 中 GTA 的产生。结论发现了 Avar-1 和 Avar-2 等位基因,它们可通过改变 GTA 的局部构象和降低其稳定性而导致 Ax 表型。
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Molecular genetic analysis of two novel a allele to cause Ax phenotype in Chinese.
BACKGROUND Mutations of ABO gene may cause the dysfunction of ABO glycosyltransferase (GT) that can result in weak ABO phenotypes. Here, we identified two novel weak ABO subgroup alleles and explored the mechanism that caused Ax phenotype. MATERIALS AND METHODS The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the mutations was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. RESULTS The results of serological showed the subject RJ23 and RJ52 both were Ax phenotypes. The novel A alleles, Avar-1 and Avar-2 were identified according to the gene analysis. Both Avar-1 and Avar-2 harbored recombinant heterozygous alleles, specifically A2.05 and O.01.02. These alleles showcased substitutions at positions c.106G > T, c.189C > T, c.220C > T, and c.1009A > G in their respective exons. It is worth noting that the crossing-over regions of these two alleles differed from each other. In vitro expression study showed that GTA mutant impaired H to A antigen conversion, and the mutant did not affect the production of GTA though the Western bolt. In silico analysis showed that GTA mutant may change the local conformation and the stability of GT. CONCLUSIONS The Avar-1 and Avar-2 alleles were identified, which could cause the Ax phenotype through changing the local conformation and reducing stability of the GTA.
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来源期刊
CiteScore
6.50
自引率
6.20%
发文量
381
审稿时长
57 days
期刊介绍: Journal of the Formosan Medical Association (JFMA), published continuously since 1902, is an open access international general medical journal of the Formosan Medical Association based in Taipei, Taiwan. It is indexed in Current Contents/ Clinical Medicine, Medline, ciSearch, CAB Abstracts, Embase, SIIC Data Bases, Research Alert, BIOSIS, Biological Abstracts, Scopus and ScienceDirect. As a general medical journal, research related to clinical practice and research in all fields of medicine and related disciplines are considered for publication. Article types considered include perspectives, reviews, original papers, case reports, brief communications, correspondence and letters to the editor.
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