通过全外显子组测序发现基因变异与中国藏族人群室间隔缺损相关。
Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing.
作者信息
Zhang Xiaohui, Zhen Da, Li Xuemei, Yi Faling, Zhang Zhanhao, Yang Wei, Li Xuguang, Sheng Yemeng, Liu Xiaoli, Jin Tianbo, He Yongjun
机构信息
Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, People's Republic of China.
Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, People's Republic of China.
出版信息
Pharmgenomics Pers Med. 2023 Apr 27;16:389-400. doi: 10.2147/PGPM.S404438. eCollection 2023.
BACKGROUND
Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients in the Chinese Tibetan population, and to provide a theoretical basis for the genetic mechanism of VSD.
METHODS
Peripheral venous blood was collected from 20 VSD subjects, and whole-genome DNA was extracted. High-throughput sequencing was performed on qualified DNA samples using whole-exome sequencing (WES) technology. After filtering, detecting, and annotating qualified data, single nucleotide variations (SNVs) and insertion-deletion (InDel) markers were analyzed, and data processing software such as GATK, SIFT, Polyphen, and MutationTaster were used for comparative evaluation and prediction of pathogenic deleterious variants associated with VSD.
RESULTS
A total of 4793 variant loci, including 4168 SNVs, 557 InDels and 68 unknown loci and 2566 variant genes were obtained from 20 VSD subjects through bioinformatics analysis. According to the screening of the prediction software and database, the occurrence of VSD was predicted to be associated with five inherited pathogenic gene mutations, all of which were missense mutations, including (c.1396C >A:p.Gln466Lys), (c.235C >T:p.Arg79Cys), (c.629G >A:p.Arg210Gln), (c.1138G >A:p.Gly380Arg), (c.1363C >T:p.Arg455Trp).
CONCLUSION
This study demonstrated that gene variants were potentially associated with VSD in Chinese Tibetan population.
背景
室间隔缺损（VSD）是儿童中最常见的先天性心脏异常，在成人中是第二常见的。本研究旨在探索中国藏族人群VSD患者中潜在的致病基因，为VSD的遗传机制提供理论依据。
方法
收集20例VSD受试者的外周静脉血，提取全基因组DNA。使用全外显子测序（WES）技术对合格的DNA样本进行高通量测序。对合格数据进行过滤、检测和注释后，分析单核苷酸变异（SNV）和插入缺失（InDel）标记，并使用GATK、SIFT、Polyphen和MutationTaster等数据处理软件对与VSD相关的致病性有害变异进行比较评估和预测。
结果
通过生物信息学分析，从20例VSD受试者中获得了总共4793个变异位点，包括4168个SNV、557个InDel和68个未知位点以及2566个变异基因。根据预测软件和数据库的筛选，预测VSD的发生与五个遗传性致病基因突变有关，所有这些都是错义突变，包括（c.1396C>A:p.Gln466Lys）、（c.235C>T:p.Arg79Cys）、（c.629G>A:p.Arg210Gln）、（c.1138G>A:p.Gly380Arg）、（c.1363C>T:p.Arg455Trp）。
结论
本研究表明，在中国藏族人群中，基因变异可能与VSD有关。
Zotero 插件