Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort
Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort
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DOI：
10.1016/j.neurobiolaging.2015.11.030
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发表时间：
2016-03-01
影响因子：
4.2
通讯作者：
Sobue, Gen
中科院分区：
文献类型：
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作者：
Nakamura, Ryoichi;Sone, Jun;Sobue, Gen
我们调查了日本ALS患者中28个已知肌萎缩侧索硬化（ALS）相关基因变异的频率和贡献。我们设计了一个多重的，聚合酶链反应为基础的引物面板扩增的编码区的28 ALS相关基因和测序的DNA样本从257日本ALS患者使用离子激流PGM测序仪。我们还进行了外显子组测序，并使用Illumina HiSeq 2000平台在另外251名ALS患者中鉴定了28个基因的变体。我们确定了已知的ALS致病变异体，并预测了新的非同义变异体的功能特性。通过桑格测序证实这些变体。39例家族性ALS患者中有19例（48.7%）和469例散发性ALS患者中有14例（3.0%）发现了已知的致病变异。32例散发性ALS患者（6.8%）携带1或2种可能有害的ALS相关基因的新非同义变体。这项研究报告了日本ALS患者的第一次广泛的遗传筛查。这些发现有助于为此类患者制定遗传筛查和咨询策略。(C)2016 Elsevier Inc. All rights reserved.
We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients. (C) 2016 Elsevier Inc. All rights reserved.