Targeted next-generation sequencing (NGS) of nine candidate genes with custom AmpliSeq in patients and a cardiomyopathy risk group
Targeted next-generation sequencing (NGS) of nine candidate genes with custom AmpliSeq in patients and a cardiomyopathy risk group
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DOI：
10.1016/j.cca.2015.04.014
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发表时间：
2015-06-15
影响因子：
5
通讯作者：
Baranov, Vladislav S.
中科院分区：
文献类型：
--
作者：
Glotov, Andrey S.;Kazakov, Sergey V.;Baranov, Vladislav S.
背景：肥厚型心肌病是一种常见的遗传性心脏病。预防和早期诊断这种疾病是非常重要的。由于大量的致病基因和高突变率参与了这种疾病的发病机制，传统的早期诊断方法是无效的。方法：我们开发了一个自定义的AmpliSeq面板，用于ACTC 1，MYBPC 3，MYH 7，MYL 2，MYL 3，TNN 13，TNNT 2，TPM 1和CASQ 2的编码序列的NGS测序。对学生队列（病史中有或无心肌病风险）和心肌病患者进行遗传分析。对于统计和生物信息学分析，使用Polyphen2、SIFT、SnpSift和PLINK软件。为了选择心肌病患者和高风险组学生的遗传标记物，我们应用了四种添加剂models.Results：我们的AmpliSeq自定义面板使我们能够有效地探索靶序列。基于评分分析，我们检测到MYBPC3和C4SQ2基因中的三个替换以及MYBPC3、MYH7和CASQ2基因中的六个位点之间的组合，这些基因与我们的队列中的心肌病风险有关。我们还检测到的TNNT2基因，可以被认为是对cardiomyopathy.Conclusion的保护取代：我们使用NGS与AmpliSeq库和离子PGM测序开发改善的预测信息，为患者的心肌病的风险。(C)2015爱思唯尔B.V.保留所有权利。
Background: Hypertrophic cardiomyopathy is a common genetic cardiac disease. Prevention and early diagnosis of this disease are very important. Because of the large number of causative genes and the high rate of mutations involved in the pathogenesis of this disease, traditional methods of early diagnosis are ineffective.Methods: We developed a custom AmpliSeq panel for NGS sequencing of the coding sequences of ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNN13, TNNT2, TPM1, and CASQ2. A genetic analysis of student cohorts (with and without cardiomyopathy risk in their medical histories) and patients with cardiomyopathies was performed. For the statistical and bioinformatics analysis, Polyphen2, SIFT, SnpSift and PLINK software were used. To select genetic markers in the patients with cardiomyopathy and in the students of the high risk group, four additive models were applied.Results: Our AmpliSeq custom panel allowed us to efficiently explore targeted sequences. Based on the score analysis, we detected three substitutions in the MYBPC3 and C4SQ2 genes and six combinations between loci in the MYBPC3, MYH7 and CASQ2 genes that were responsible for cardiomyopathy risk in our cohorts. We also detected substitutions in the TNNT2 gene that can be considered as protective against cardiomyopathy.Conclusion: We used NGS with AmpliSeq libraries and Ion PGM sequencing to develop improved predictive information for patients at risk of cardiomyopathy. (C) 2015 Elsevier B.V. All rights reserved.