Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes
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 P...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Aging |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fragi.2022.851039/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Irene Lobon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T06:37:56Z |
| format | Article |
| id | doaj.art-011c1e8d4d8244819e098b74be025789 |
| institution | Directory Open Access Journal |
| issn | 2673-6217 |
| language | English |
| last_indexed | 2024-04-14T06:37:56Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging |
| spelling | doaj.art-011c1e8d4d8244819e098b74be0257892022-12-22T02:07:25ZengFrontiers Media S.A.Frontiers in Aging2673-62172022-04-01310.3389/fragi.2022.851039851039Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal ProcessesIrene Lobon0Manuel Solís-Moruno1Manuel Solís-Moruno2David Juan3Ashraf Muhaisen4Ashraf Muhaisen5Federico Abascal6Paula Esteller-Cucala7Raquel García-Pérez8Maria Josep Martí9Maria Josep Martí10Eduardo Tolosa11Eduardo Tolosa12Jesús Ávila13Jesús Ávila14Raheleh Rahbari15Tomas Marques-Bonet16Tomas Marques-Bonet17Tomas Marques-Bonet18Tomas Marques-Bonet19Ferran Casals20Ferran Casals21Eduardo Soriano22Eduardo Soriano23Institute of Evolutionary Biology (UPF-CSIC), Barcelona, SpainGenomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, SpainInstitute of Evolutionary Biology (UPF-CSIC), Barcelona, SpainInstitute of Evolutionary Biology (UPF-CSIC), Barcelona, SpainDepartment of Cell Biology, Physiology and Immunology and Institute of Neurosciences, Universitat de Barcelona (UB), Barcelona, SpainCentre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, SpainCancer, Ageing, and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United KingdomInstitute of Evolutionary Biology (UPF-CSIC), Barcelona, SpainInstitute of Evolutionary Biology (UPF-CSIC), Barcelona, SpainCentre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, SpainDepartment of Neurology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, SpainCentre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, SpainDepartment of Neurology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, SpainCentre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, SpainCentro de Biología Molecular Severo Ochoa, Madrid, SpainCancer, Ageing, and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United KingdomInstitute of Evolutionary Biology (UPF-CSIC), Barcelona, SpainCatalan Institution of Research and Advanced Studies (ICREA), Barcelona, SpainCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain0Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Barcelona, SpainGenomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain1Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, SpainDepartment of Cell Biology, Physiology and Immunology and Institute of Neurosciences, Universitat de Barcelona (UB), Barcelona, SpainCentre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, SpainThe 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.https://www.frontiersin.org/articles/10.3389/fragi.2022.851039/fullParkinson diseasesomatic mutationsbrain mosaicismneurodegenarationsomatic genome alteration |
| spellingShingle | 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 Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes Frontiers in Aging Parkinson disease somatic mutations brain mosaicism neurodegenaration somatic genome alteration |
| title | Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes |
| title_full | Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes |
| title_fullStr | Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes |
| title_full_unstemmed | Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes |
| title_short | Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes |
| title_sort | somatic mutations detected in parkinson disease could affect genes with a role in synaptic and neuronal processes |
| topic | Parkinson disease somatic mutations brain mosaicism neurodegenaration somatic genome alteration |
| url | https://www.frontiersin.org/articles/10.3389/fragi.2022.851039/full |
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