Frontiers in Aging (Apr 2022)
Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes
- Irene Lobon,
- Manuel Solís-Moruno,
- Manuel Solís-Moruno,
- David Juan,
- Ashraf Muhaisen,
- Ashraf Muhaisen,
- Federico Abascal,
- Paula Esteller-Cucala,
- Raquel García-Pérez,
- Maria Josep Martí,
- Maria Josep Martí,
- Eduardo Tolosa,
- Eduardo Tolosa,
- Jesús Ávila,
- Jesús Ávila,
- Raheleh Rahbari,
- Tomas Marques-Bonet,
- Tomas Marques-Bonet,
- Tomas Marques-Bonet,
- Tomas Marques-Bonet,
- Ferran Casals,
- Ferran Casals,
- Eduardo Soriano,
- Eduardo Soriano
Affiliations
- Irene Lobon
- Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain
- Manuel Solís-Moruno
- Genomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
- Manuel Solís-Moruno
- Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain
- David Juan
- Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain
- Ashraf Muhaisen
- Department of Cell Biology, Physiology and Immunology and Institute of Neurosciences, Universitat de Barcelona (UB), Barcelona, Spain
- Ashraf Muhaisen
- Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Federico Abascal
- Cancer, Ageing, and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United Kingdom
- Paula Esteller-Cucala
- Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain
- Raquel García-Pérez
- Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain
- Maria Josep Martí
- Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Maria Josep Martí
- Department of Neurology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain
- Eduardo Tolosa
- Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Eduardo Tolosa
- Department of Neurology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain
- Jesús Ávila
- Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Jesús Ávila
- Centro de Biología Molecular Severo Ochoa, Madrid, Spain
- Raheleh Rahbari
- Cancer, Ageing, and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United Kingdom
- Tomas Marques-Bonet
- Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain
- Tomas Marques-Bonet
- Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain
- Tomas Marques-Bonet
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
- Tomas Marques-Bonet
- 0Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Barcelona, Spain
- Ferran Casals
- Genomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
- Ferran Casals
- 1Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
- Eduardo Soriano
- Department of Cell Biology, Physiology and Immunology and Institute of Neurosciences, Universitat de Barcelona (UB), Barcelona, Spain
- Eduardo Soriano
- Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- DOI
- https://doi.org/10.3389/fragi.2022.851039
- Journal volume & issue
-
Vol. 3
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.
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