Rates, Distribution, and Implications of Post-zygotic Mosaic Mutations in Autism Spectrum Disorder

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Rates, Distribution, and Implications of Post-zygotic Mosaic Mutations in Autism Spectrum Disorder

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Title: Rates, Distribution, and Implications of Post-zygotic Mosaic Mutations in Autism Spectrum Disorder
Author: Lim, Elaine T.; Uddin, Mohammed; De Rubeis, Silvia; Chan, Yingleong; Kamumbu, Anne S.; Zhang, Xiaochang; D'Gama, Alissa; Kim, Sonia N.; Hill, Robert Sean; Goldberg, Arthur P.; Poultney, Christopher; Minshew, Nancy J.; Kushima, Itaru; Aleksic, Branko; Ozaki, Norio; Parellada, Mara; Arango, Celso; Penzol, Maria J.; Carracedo, Angel; Kolevzon, Alexander; Hultman, Christina M.; Weiss, Lauren A.; Fromer, Menachem; Chiocchetti, Andreas G.; Freitag, Christine M.; Church, George M.; Scherer, Stephen W.; Buxbaum, Joseph D.; Walsh, Christopher A.

Note: Order does not necessarily reflect citation order of authors.

Citation: Lim, 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.
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Abstract: We 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sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed re-sequencing using multiple independent technologies.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.
Published Version: doi:10.1038/nn.4598
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672813/pdf/
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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34869010
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