Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes
Abstrak
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.
Topik & Kata Kunci
Penulis (24)
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
Akses Cepat
- Tahun Terbit
- 2022
- Sumber Database
- DOAJ
- DOI
- 10.3389/fragi.2022.851039
- Akses
- Open Access ✓