Lim, Elaine T.Uddin, MohammedDe Rubeis, SilviaChan, YingleongKamumbu, Anne S.Zhang, XiaochangD'Gama, AlissaKim, SoniaHill, RobertGoldberg, Arthur P.Poultney, ChristopherMinshew, Nancy J.Kushima, ItaruAleksic, BrankoOzaki, NorioParellada, MaraArango, CelsoPenzol, Maria J.Carracedo, AngelKolevzon, AlexanderHultman, Christina M.Weiss, Lauren A.Fromer, MenachemChiocchetti, Andreas G.Freitag, Christine M.Church, GeorgeScherer, Stephen W.Buxbaum, Joseph D.Walsh, Christopher2018-02-262017Lim, E. T., M. Uddin, S. De Rubeis, Y. Chan, A. S. Kamumbu, X. Zhang, A. D'Gama, et al. 2017. “Rates, Distribution, and Implications of Post-zygotic Mosaic Mutations in Autism Spectrum Disorder.” Nature neuroscience 20 (9): 1217-1224. doi:10.1038/nn.4598. http://dx.doi.org/10.1038/nn.4598.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34869010We systematically analyzed post-zygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed re-sequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, with 83.3% of these PZMs not discovered in previous studies. Damaging, non-synonymous PZMs within critical exons of prenatally-expressed genes were more common in ASD probands than controls (P<1×10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P=5.4×10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU, SMARCA4) known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.en-USJournal Article2018-02-2610.1038/nn.4598