Somatic mutations detected in Parkinson disease could affect genes with a role in synaptic and neuronal processes

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• dc.contributor.author Lobon Garcia, Irene
• dc.contributor.author Solís Moruno, Manuel, 1993-
• dc.contributor.author Juan, David
• dc.contributor.author Muhaisen, Ashraf
• dc.contributor.author Abascal, Federico
• dc.contributor.author Esteller Cucala, Paula
• dc.contributor.author García Pérez, Raquel, 1989-
• dc.contributor.author Martí, Maria José
• dc.contributor.author Tolosa, Eduard
• dc.contributor.author Ávila, Jesús
• dc.contributor.author Rahbari, Raheleh
• dc.contributor.author Marquès i Bonet, Tomàs, 1975-
• dc.contributor.author Casals López, Ferran
• dc.contributor.author Soriano, Eduardo
• dc.date.accessioned 2023-07-07T06:51:18Z
• dc.date.available 2023-07-07T06:51:18Z
• dc.date.issued 2022
• dc.description.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.
• dc.description.sponsorship This work was supported by the grants from the Spanish MINECO and MICIN (SAF2016-76340R and PID2019-106764RB-C21, Excellence Unit María de Maeztu/Institute of Neurosciences), CIBERNED (ISCIII), and by the “Fundación Reina Sofía” (Exome Project) awarded to ES, by RTI 2018-096824-B-C22 grant from Agencia estatal de Investigación- Spanish Ministry of Science, Innovation and Universities co-financed by FEDER, and by Direcció General de Recerca, Generalitat de Catalunya (2017SGR-702) to FC, MS-M is supported by the Ministerio de Economía y Competitividad, Spain (Maria de Maetzu grant MDM-2014-0370-16-3). PE-C was supported by a Formació de Personal Investigador fellowship from Generalitat de Catalunya (FI_B00122). RR is funded by Cancer Research UK (C66259/A27114).
• dc.format.mimetype application/pdf
• dc.identifier.citation Lobon I, Solís-Moruno M, Juan D, Muhaisen A, Abascal F, Esteller-Cucala P, García-Pérez R, Martí MJ, Tolosa E, Ávila J, Rahbari R, Marques-Bonet T, Casals F, Soriano E. Somatic mutations detected in Parkinson disease could affect genes with a role in synaptic and neuronal processes. Front Aging. 2022 Apr 28;3:851039. DOI: 10.3389/fragi.2022.851039
• dc.identifier.doi http://dx.doi.org/10.3389/fragi.2022.851039
• dc.identifier.issn 2673-6217
• dc.identifier.uri http://hdl.handle.net/10230/57494
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Aging. 2022 Apr 28;3:851039
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-76340R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106764RB-C21
• dc.rights © 2022 Lobon, Solís-Moruno, Juan, Muhaisen, Abascal, Esteller-Cucala, García-Pérez, Martí, Tolosa, Ávila, Rahbari, Marques-Bonet, Casals and Soriano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Parkinson disease
• dc.subject.keyword Brain mosaicism
• dc.subject.keyword Neurodegenaration
• dc.subject.keyword Somatic genome alteration
• dc.subject.keyword Somatic mutations
• dc.title Somatic mutations detected in Parkinson disease could affect genes with a role in synaptic and neuronal processes
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion