The Genetic Landscapes of Autism Spectrum Disorders

• Published in: Annual review of genomics and human genetics 2013-01, Vol.14 (1), p.191-213
• Main Authors: Huguet, Guillaume, Ey, Elodie, Bourgeron, Thomas
• Format: Article
• Language: English
• Subjects: animal models; Animals; Brain - physiology; Child Development Disorders, Pervasive - genetics; Cognitive science; copy-number variant; de novo mutation; DNA Copy Number Variations; Genetic Predisposition to Disease; Genetics; Human genetics; Humans; Life Sciences; Mutation; Neuroscience; Polymorphism, Single Nucleotide; synapse
• ISSN: 1527-8204; 1545-293X; 1527-8204
• DOI: 10.1146/annurev-genom-091212-153431

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.