Authors
Iris E Jansen, Hui Ye, Sasja Heetveld, Marie C Lechler, Helen Michels, Renée I Seinstra, Steven J Lubbe, Valérie Drouet, Suzanne Lesage, Elisa Majounie, J Raphael Gibbs, Mike A Nalls, Mina Ryten, Juan A Botia, Jana Vandrovcova, Javier Simon-Sanchez, Melissa Castillo-Lizardo, Patrizia Rizzu, Cornelis Blauwendraat, Amit K Chouhan, Yarong Li, Puja Yogi, Najaf Amin, Cornelia M van Duijn, Huw R Morris, Alexis Brice, Andrew B Singleton, Della C David, Ellen A Nollen, Shushant Jain, Joshua M Shulman, Peter Heutink
Publication date
2017/12
Journal
Genome biology
Volume
18
Pages
1-26
Publisher
BioMed Central
Description
Background
Whole-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.
Results
Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore …
Scholar articles
IE Jansen, H Ye, S Heetveld, MC Lechler, H Michels… - Genome biology, 2017