@article{a439c26f0a294a95af598caae07b146a,
title = "The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing",
abstract = "We characterize the landscape of somatic mutations—mutations occurring after fertilization—in the human brain using ultra-deep (~250×) whole-genome sequencing of prefrontal cortex from 59 donors with autism spectrum disorder (ASD) and 15 control donors. We observe a mean of 26 somatic single-nucleotide variants per brain present in ≥4% of cells, with enrichment of mutations in coding and putative regulatory regions. Our analysis reveals that the first cell division after fertilization produces ~3.4 mutations, followed by 2–3 mutations in subsequent generations. This suggests that a typical individual possesses ~80 somatic single-nucleotide variants present in ≥2% of cells—comparable to the number of de novo germline mutations per generation—with about half of individuals having at least one potentially function-altering somatic mutation somewhere in the cortex. ASD brains show an excess of somatic mutations in neural enhancer sequences compared with controls, suggesting that mosaic enhancer mutations may contribute to ASD risk.",
author = "{Brain Somatic Mosaicism Network} and Rodin, {Rachel E.} and Yanmei Dou and Minseok Kwon and Sherman, {Maxwell A.} and D{\textquoteright}Gama, {Alissa M.} and Doan, {Ryan N.} and Rento, {Lariza M.} and Girskis, {Kelly M.} and Bohrson, {Craig L.} and Kim, {Sonia N.} and Ajay Nadig and Luquette, {Lovelace J.} and Gulhan, {Doga C.} and Walsh, {Christopher A.} and Javier Ganz and Woodworth, {Mollie B.} and Pengpeng Li and Rodin, {Rachel E.} and Hill, {Robert S.} and Sara Bizzotto and Zinan Zhou and Lee, {Eunjung A.} and Barton, {Alison R.} and D{\textquoteright}Gama, {Alissa M.} and Alon Galor and Bohrson, {Craig L.} and Daniel Kwon and Gulhan, {Doga C.} and Lim, {Elaine T.} and Cortes, {Isidro Ciriano} and Luquette, {Lovelace J.} and Sherman, {Maxwell A.} and Coulter, {Michael E.} and Lodato, {Michael A.} and Park, {Peter J.} and Monroy, {Rebeca B.} and Kim, {Sonia N.} and Yanmei Dou and Andrew Chess and Attila Guly{\'a}s-Kov{\'a}cs and Chaggai Rosenbluh and Schahram Akbarian and {Ben Langmead}, Langmead and Jeremy Thorpe and Jonathan Pevsner and Soonweng Cho and Jaffe, {Andrew E.} and Apua Paquola and Weinberger, {Daniel R.} and Shin, {Jooheon H.}",
note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = feb,
day = "1",
doi = "10.1038/s41593-020-00765-6",
language = "English (US)",
volume = "24",
pages = "176--185",
journal = "Nature neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "2",
}