Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing

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• 作者：Iris E. Jansen ; Hui Ye ; Sasja Heetveld ; Marie C. Lechler ; Helen Michels…
• 关键词：Parkinson’s disease ; Genomics ; Whole ; exome sequencing ; Loss ; of ; function ; Rare variants ; Functional screening ; Mitochondria ; Parkin ; α ; synuclein ; Animal model
• 刊名：Genome Biology
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：18
• 期：1
• 全文大小：8082KB
• 刊物主题：Animal Genetics and Genomics; Human Genetics; Plant Genetics & Genomics; Microbial Genetics and Genomics; Bioinformatics; Evolutionary Biology;
• 出版者：BioMed Central
• ISSN：1474-760X
• 卷排序：18

文摘

BackgroundWhole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson’s disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models.