title: Copy-number variation in the pathogenesis of autism spectrum disorder.
abstract: Autism spectrum disorder is a neurodevelopmental disorder present in 1% of the population, characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Approximately 10% of the autism spectrum disorder population is thought to have large chromosomal rearrangements. Copy-number variations (CNV) alter the genome structure either by duplication or deletion of a chromosomal region. The association between CNV and autism susceptibility has become more apparent through the use of methods based on comparative genomic hybridization in screening CNV. The nature of the high CNV rate in the human genome is partly explained by non-allelic homologous recombination between flanking repeated sequences derived from multiple copies of transposons or mobile genetic elements. There are hotspots for CNV in the human genome, such as 16p11.2 and 22q11.2. Genes involved in CNV are supposed to have copy-number dose-dependent effects on the behavior of affected individuals. Animal models give insight into the possible interactions between core genetic loci and additional factors contributing to the phenotypes of each individual. If affected genes code for cellular signaling molecules, reducing the dosage in the intracellular signaling pathway may result in the malfunction of the nervous system. The genetic background of autism spectrum disorder is highly heterogenic and most common or rare CNV do not lead to autism spectrum disorders in the majority of cases, but may occasionally increase the risk of developing an autism spectrum disorder.
authors.affiliation: National Institute for Physiological Sciences, Tokyo, Japan; Restart Postdoctoral Fellowship of Japan Society for the Promotion of Science, Tokyo, Japan; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Shishido
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D056915:DNA Copy Number Variations; D006801:Humans; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics
keywords: autism spectrum disorders; copy‐number variation; de novo mutation; schizophrenia; signal transduction