PT - JOURNAL ARTICLE AU - Michael A. Lodato AU - Rachel E. Rodin AU - Craig L. Bohrson AU - Michael E. Coulter AU - Alison R. Barton AU - Minseok Kwon AU - Maxwell A. Sherman AU - Carl M. Vitzthum AU - Lovelace J. Luquette AU - Chandri Yandava AU - Pengwei Yang AU - Thomas W. Chittenden AU - Nicole E. Hatem AU - Steven C. Ryu AU - Mollie B. Woodworth AU - Peter J. Park AU - Christopher A. Walsh TI - Aging and neurodegeneration are associated with increased mutations in single human neurons AID - 10.1101/221960 DP - 2017 Jan 01 TA - bioRxiv PG - 221960 4099 - http://biorxiv.org/content/early/2017/11/21/221960.short 4100 - http://biorxiv.org/content/early/2017/11/21/221960.full AB - 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 fifteen normal individuals (aged 4 months to 82 years) as well as nine 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.One-Sentence Summary Somatic single-nucleotide variants accumulate in human neurons in aging with regional specificity and in progeroid diseases.