Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders
Item Type:Journal Article
Citation:Pinto, D., Delaby, E., Merico, D., (...), Betancur, C., Scherer, StephenW., Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders, American Journal of Human Genetics, 94, 5, 2014, 77 694
Pinto-2014-Convergence of Genes and Cellular P.pdf (Accepted for publication (author's copy) - Peer Reviewed) 961.1Kb
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10−5) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10−15, ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Type of material:Journal Article
Series/Report no:American Journal of Human Genetics
Availability:Full text available