Dataset Information

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

ABSTRACT: Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or disrupt splicing. We estimate that recurrent disruptive mutations in six genes-CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1-may contribute to 1% of sporadic ASDs. Our data support associations between specific genes and reciprocal subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicate the importance of a ?-catenin-chromatin-remodeling network to ASD etiology.

SUBMITTER: O'Roak BJ

PROVIDER: S-EPMC3528801 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

O'Roak Brian J BJ Vives Laura L Fu Wenqing W Egertson Jarrett D JD Stanaway Ian B IB Phelps Ian G IG Carvill Gemma G Kumar Akash A Lee Choli C Ankenman Katy K Munson Jeff J Hiatt Joseph B JB Turner Emily H EH Levy Roie R O'Day Diana R DR Krumm Niklas N Coe Bradley P BP Martin Beth K BK Borenstein Elhanan E Nickerson Deborah A DA Mefford Heather C HC Doherty Dan D Akey Joshua M JM Bernier Raphael R Eichler Evan E EE Shendure Jay J

Science (New York, N.Y.) 20121115 6114

Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or disrupt splicin ...[more]

PMID: 23160955

Dataset Information

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

Publications

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy.
| S-EPMC5886262 | biostudies-literature

Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma.
| S-EPMC3862727 | biostudies-literature

Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.
| S-EPMC3115696 | biostudies-literature

Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.
| S-EPMC7530681 | biostudies-literature

Targeted next-generation sequencing in children with intellectual disabilities, autism spectrum disorders and multiple congenital abnormalities
2019-08-31 | E-MTAB-8041 | biostudies-arrayexpress

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
| S-EPMC5501701 | biostudies-literature

The autism sequencing consortium: large-scale, high-throughput sequencing in autism spectrum disorders.
| S-EPMC3863639 | biostudies-literature

Novel recurrently mutated genes in African American colon cancers.
| S-EPMC4313860 | biostudies-other

Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene.
| S-EPMC4755142 | biostudies-literature