@article {308634,
	title = {Whole-genome sequencing of quartet families with autism spectrum disorder.},
	journal = {Nat Med},
	volume = {21},
	year = {2015},
	note = {http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3792.html},
	month = {2015 Feb},
	pages = {185-91},
	abstract = {<p>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.</p>},
	keywords = {Adult, Child, Child Development Disorders, Pervasive, Female, Genetic Predisposition to Disease, Humans, Male, Parents, Sequence Analysis, DNA, Siblings},
	issn = {1546-170X},
	doi = {10.1038/nm.3792},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25621899},
	author = {Yuen, Ryan K C and Thiruvahindrapuram, Bhooma and Merico, Daniele and Walker, Susan and Tammimies, Kristiina and Hoang, Ny and Chrysler, Christina and Nalpathamkalam, Thomas and Pellecchia, Giovanna and Liu, Yi and Gazzellone, Matthew J and D{\textquoteright}Abate, Lia and Deneault, Eric and Howe, Jennifer L and Liu, Richard S C and Thompson, Ann and Zarrei, Mehdi and Uddin, Mohammed and Marshall, Christian R and Ring, Robert H and Zwaigenbaum, Lonnie and Ray, Peter N and Weksberg, Rosanna and Carter, Melissa T and Fernandez, Bridget A and Roberts, Wendy and Szatmari, Peter and Scherer, Stephen W}
}
