wholegenome sequencing of quartet families with autism spectrum disorder autism spectrum disorder asd is genetically heterogeneous with evidence for hundreds of susceptibility loci previous microarray and exomesequencing studies have examined portions of the genome in simplex families parents and one asdaffected child having presumed sporadic forms of the disorder we used wholegenome sequencing wgs of 85 quartet families parents and two asdaffected 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 singlenucleotide and structural variations in genes previously reported to be associated with asd or other neurodevelopmental disorders we found that some 694 of the affected siblings carried different asdrelevant 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 nongenic susceptibility variants in research and in clinical diagnostics