The Genetic Landscapes of Autism Spectrum Disorders

Abstract

The autism spectrum disorders (ASD) are characterized by impairments in social interaction and stereotyped behaviors. For the majority of individuals with ASD, the causes of the disorder remain unknown; however, in up to 25% of cases, a genetic cause can be identified. Chromosomal rearrangements as well as rare and de novo copy-number variants are present in ∼10–20% of individuals with ASD, compared with 1–2% in the general population and/or unaffected siblings. Rare and de novo coding-sequence mutations affecting neuronal genes have also been identified in ∼5–10% of individuals with ASD. Common variants such as single-nucleotide polymorphisms seem to contribute to ASD susceptibility, but, taken individually, their effects appear to be small. Despite a heterogeneous genetic landscape, the genes implicated thus far—which are involved in chromatin remodeling, metabolism, mRNA translation, and synaptic function—seem to converge in common pathways affecting neuronal and synaptic homeostasis. Animal models developed to study these genes should lead to a better understanding of the diversity of the genetic landscapes of ASD.