RESEARCH Rare deleterious mutation r o J D

Full list of author information is available at the end of the articleBackground Autism spectrum disorders (ASDs) are defined by per-sistent deficits in social communication and social inter-action and restricted repetitive patterns of behavior, interests or activities [1]. These syndromes are common in the population, with a prevalence of approximately 1 % [2], and demonstrate both considerable phenotypic and extensive genetic heterogeneity [3]. High-through-put sequencing approaches have provided substantial insight into the genomic architecture of ASDs. For example, multiple analyses of whole-exome sequencing data demonstrate an over-representation of de novo, loss-of-function mutations in brain-expressed genes in affected individuals and point to half a dozen new ASD genes [3-6]. These have been identified based on the clustering of mutations in the same gene in unrelated individuals, providing strong evidence for association [3]. However, a large number of compelling, rare, d