Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes
Lobón, Irene (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
Solís-Moruno, Manuel (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Juan, David (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
Muhaisen, Ashraf (Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia)
Abascal, Federico (Wellcome Trust Sanger Institute (Regne Unit))
Esteller-Cucala, Paula (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
García Perez, Raquel (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
Martí, Maria Josep (Universitat de Barcelona. Departament de Neurologia)
Tolosa, Eduardo (Universitat de Barcelona. Departament de Neurologia)
Ávila, Jesús (Centro de Biología Molecular Severo Ochoa)
Rahbari, Raheleh (Wellcome Trust Sanger Institute (Regne Unit))
Marques-Bonet, Tomas 1975- (Institut Català de Paleontologia Miquel Crusafont)
Casals, Ferran (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Soriano García, Eduardo (Institució Catalana de Recerca i Estudis Avançats)

Date:	2022
Abstract:	The role of somatic mutations in complex diseases, including neurodevelopmental and neurodegenerative disorders, is becoming increasingly clear. However, to date, no study has shown their relation to Parkinson disease's phenotype. To explore the relevance of embryonic somatic mutations in sporadic Parkinson disease, we performed whole-exome sequencing in blood and four brain regions of ten patients. We identified 59 candidate somatic single nucleotide variants (sSNVs) through sensitive calling and a careful filtering strategy (COSMOS). We validated 27 of them with amplicon-based ultra-deep sequencing, with a 70% validation rate for the highest-confidence variants. The identified sSNVs are in genes with synaptic functions that are co-expressed with genes previously associated with Parkinson disease. Most of the sSNVs were only called in blood but were also found in the brain tissues with ultra-deep amplicon sequencing, demonstrating the strength of multi-tissue sampling designs.
Grants:	Ministerio de Economía y Competitividad SAF2016-76340R Agencia Estatal de Investigación PID2019-106764RB-C21 Agencia Estatal de Investigación RTI 2018-096824-B-C22 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-702 Ministerio de Economía y Competitividad MDM-2014-0370-16-3 Agència de Gestió d'Ajuts Universitaris i de Recerca FI_B00122
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Parkinson disease ; Somatic mutations ; Brain mosaicism ; Neurodegenaration ; Somatic genome alteration
Published in:	Frontiers in Aging, Vol. 3 (April 2022) , art. 851039, ISSN 2673-6217

DOI: 10.3389/fragi.2022.851039
PMID: 35821807

14 p, 1.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Institut Català de Paleontologia Miquel Crusafont (ICP)
Articles > Research articles
Articles > Published articles