ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Frequency and signature of somatic variants in 1461 human brain exomes.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Probability and Neurodegeneration: Alzheimer's Disease and Huntington's Disease.Brain sciences · 2025Article
- Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
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- The genetic landscape of early-onset Alzheimer's disease in China.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A microglia clonal inflammatory disorder in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.Acta neuropathologica · 2024Article
- Neuropathologically-directed profiling ofbioRxiv : the preprint server for biology · 2024Article
- In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease.International journal of molecular sciences · 2024Review
- Phylovar: toward scalable phylogeny-aware inference of single-nucleotide variations from single-cell DNA sequencing data.Bioinformatics (Oxford, England) · 2022Article
- Tracing brain genotoxic stress in Parkinson's disease with a novel single-cell genetic sensor.Science advances · 2022Article
- Genomic frontiers in congenital heart disease.Nature reviews. Cardiology · 2022Review
- Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.Cellular and molecular life sciences : CMLS · 2021Review
- Brain Somatic Mutation in Aging and Alzheimer's Disease.Annual review of genomics and human genetics · 2021Review
- Review
- The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing.Nature neuroscience · 2021Article
- Somatic TARDBP variants as a cause of semantic dementia.Brain : a journal of neurology · 2020Article
- The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues.Genome medicine · 2020Article
- Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation.Nature communications · 2019Article
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 1 country.
Funding
Abstract
purposeTo systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders.
methodsIn 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.
resultsWe 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
conclusionThese 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.
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