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 spora...
| Autores: | , , , , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:264820 |
| Acesso em linha: | https://ddd.uab.cat/record/264820 https://dx.doi.org/urn:doi:10.3389/fragi.2022.851039 |
| Access Level: | acceso abierto |
| Palavra-chave: | Parkinson disease Somatic mutations Brain mosaicism Neurodegenaration Somatic genome alteration |
| Resumo: | 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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