Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Lim, Elaine T, Uddin, Mohammed, De Rubeis, Silvia, Chan, Yingleong, Kamumbu, Anne S, Zhang, Xiaochang, D'Gama, Alissa M, 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 and Anney, Richard 2017. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nature Neuroscience 20 (9) , pp. 1217-1224. 10.1038/nn.4598

[img]
Preview
PDF - Accepted Post-Print Version
Download (990kB) | Preview

Abstract

We systematically analyzed postzygotic 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sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous 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 and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Richard Anney is a member of the Autism Sequencing Consortium
Publisher: Nature Research
ISSN: 1097-6256
Date of First Compliant Deposit: 4 January 2019
Date of Acceptance: 20 May 2017
Last Modified: 20 Oct 2019 04:12
URI: http://orca.cf.ac.uk/id/eprint/118087

Citation Data

Cited 49 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics