Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neuron. 2012 Apr 26;74(2):285-99. doi: 10.1016/j.neuron.2012.04.009.

De novo gene disruptions in children on the autistic spectrum.

Author information

  • 1Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.

Abstract

Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.

Copyright © 2012 Elsevier Inc. All rights reserved.

Comment in

PMID:
22542183
[PubMed - indexed for MEDLINE]
PMCID:
PMC3619976
Free PMC Article

Images from this publication.See all images (1)Free text

Figure 1
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk