domingo, 8 de febrero de 2015

Whole-genome sequencing of quartet families with autism spectrum di... - PubMed - NCBI

Whole-genome sequencing of quartet families with autism spectrum di... - PubMed - NCBI



 2015 Feb;21(2):185-91. doi: 10.1038/nm.3792. Epub 2015 Jan 26.

Whole-genome sequencing of quartet families with autism spectrum disorder.

Abstract

Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for hundreds of susceptibility loci. Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics.

PMID:
 
25621899
 
[PubMed - in process]

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