| Literature DB >> 29217584 |
Michael A Lodato1,2,3, Rachel E Rodin1,2,3,4, Craig L Bohrson5, Michael E Coulter1,2,3,4, Alison R Barton5, Minseok Kwon5, Maxwell A Sherman5, Carl M Vitzthum5, Lovelace J Luquette5, Chandri N Yandava6, Pengwei Yang6, Thomas W Chittenden6,7,8, Nicole E Hatem1,2,3, Steven C Ryu1,2,3, Mollie B Woodworth1,2,3, Peter J Park9,10, Christopher A Walsh11,2,3.
Abstract
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age-which we term genosenium-shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.Entities:
Mesh：
Year: 2017 PMID： 29217584 PMCID： PMC5831169 DOI： 10.1126/science.aao4426
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728