Frequency and signature of somatic variants in 1461 human brain exomes

Year: 2018

Type: article

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.

Source: Genetics in Medicine

DOI: 10.1038/s41436-018-0274-3

Authors: Wei Wei, Michael J. Keogh, Juvid Aryaman, Zoe Golder, Peter J. Kullar, Ian Wilson, Kevin Talbot, Martin R. Turner, Chris-Anne McKenzie, Claire Troakes, Johannes Attems, Colin Smith, Safa Al Sarraj, Chris M. Morris, Olaf Ansorge, Nick S. Jones, James W. Ironside, Patrick F. Chinnery

Institutions: University of Cambridge, Imperial College London, Newcastle University, John Radcliffe Hospital, University of Oxford, Western General Hospital, University of Edinburgh, King's College London, MRC Mitochondrial Biology Unit

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,122

Funders: Wellcome Trust, National Institute for Health and Care Research, Motor Neurone Disease Association, University of Cambridge, Cambridge University Hospitals, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council

OpenAlex ID: W2889954697