Whole-exome sequencing of 228 patients with sporadic Parkinson's disease

Sandor, Cynthia, Honti, Frantisek, Haerty, Wilfried ORCID: https://orcid.org/0000-0003-0111-191X, Szewczyk-Krolikowski, Konrad, Tomlinson, Paul, Evetts, Sam, Millin, Stephanie, Keane, Thomas, McCarthy, Shane A., Durbin, Richard, Talbot, Kevin, Hu, Michele, Webber, Caleb, Ponting, Chris P. and Wade-Martins, Richard (2017) Whole-exome sequencing of 228 patients with sporadic Parkinson's disease. Scientific Reports, 7. ISSN 2045-2322

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Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting 1% of the population over 65 years characterized clinically by both motor and non-motor symptoms accompanied by the preferential loss of dopamine neurons in the substantia nigra pars compacta. Here, we sequenced the exomes of 244 Parkinson's patients selected from the Oxford Parkinson's Disease Centre Discovery Cohort and, after quality control, 228 exomes were available for analyses. The PD patient exomes were compared to 884 control exomes selected from the UK10K datasets. No single non-synonymous (NS) single nucleotide variant (SNV) nor any gene carrying a higher burden of NS SNVs was significantly associated with PD status after multiple-testing correction. However, significant enrichments of genes whose proteins have roles in the extracellular matrix were amongst the top 300 genes with the most significantly associated NS SNVs, while regions associated with PD by a recent Genome Wide Association (GWA) study were enriched in genes containing PD-associated NS SNVs. By examining genes within GWA regions possessing rare PD-associated SNVs, we identified RAD51B. The protein-product of RAD51B interacts with that of its paralogue RAD51, which is associated with congenital mirror movements phenotypes, a phenotype also comorbid with PD.

Item Type: Article
Additional Information: Funding Information: The work was funded by the Monument Trust Discovery Award from Parkinson's UK. The OPDC Discovery Cohort is further supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, and the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). Publisher Copyright: © The Author(s) 2017.
Uncontrolled Keywords: general ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
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Depositing User: LivePure Connector
Date Deposited: 15 Sep 2022 14:30
Last Modified: 19 Apr 2023 01:13
URI: https://ueaeprints.uea.ac.uk/id/eprint/88324
DOI: 10.1038/srep41188

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