Frequency and signature of somatic variants in 1461 human brain exomes.
Genet Med
; 21(4): 904-912, 2019 04.
Article
de En
| MEDLINE
| ID: mdl-30214067
ABSTRACT
PURPOSE:
To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders.METHODS:
In this study we developed a pipeline to identify somatic variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum. Identified somatic variants were validated by targeted amplicon sequencing and/or PyroMark® Q24.RESULTS:
We observed somatic coding variants present in >10% of sampled cells in at least 1% of brains. The mutational signature of the detected variants showed a predominance of C>T variants most consistent with arising from DNA mismatch repair, occurred frequently in genes that are highly expressed within the central nervous system, and with a minimum somatic mutation rate of 4.25 × 10-10 per base pair per individual.CONCLUSION:
These findings provide proof-of-principle that deleterious somatic variants can affect sizeable brain regions in at least 1% of the population, and thus have the potential to contribute to the pathogenesis of common neurodegenerative diseases.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Encéphale
/
Réparation de mésappariement de l'ADN
/
Exome
/
Maladies génétiques congénitales
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Genet Med
Sujet du journal:
GENETICA MEDICA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Royaume-Uni