  Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder
(NDD) that is caused by genetic, epigenetic, and environmental factors. Recent
advances in genomic analysis have uncovered numerous candidate genes with
common and/or rare mutations that increase susceptibility to ASD. In addition,
there is increasing evidence that copy number variations (CNVs), single
nucleotide polymorphisms (SNPs), and unusual de novo variants negatively affect
neurodevelopment pathways in various ways. The overall rate of copy number
variants found in patients with autism is 10%-20%, of which 3%-7% can be
detected cytogenetically. Although the role of submicroscopic CNVs in ASD has
been studied recently, their association with genomic loci and genes has not
been properly studied. In this review, we focus on 47 ASD-associated CNV
regions and their related genes. Here, we identify 1,632 protein-coding genes
and long non-coding RNAs (lncRNAs) within these regions. Among them, 552 are
significantly expressed in the brain. Using a list of ASD-associated genes from
SFARI, we detect 17 regions containing at least one known ASD-associated
protein-coding genes. Of the remaining 30 regions, we identify 24 regions
containing at least one protein-coding genes with brain-enriched expression and
nervous system phenotype in mouse mutant and one lncRNAs with both
brain-enriched expression and upregulation in iPSC to neuron differentiation.
Our analyses highlight the diversity of genetic lesions of CNV regions that
contribute to ASD and provide new genetic evidence that lncRNA genes may
contribute to etiology of ASD. In addition, the discovered CNVs will be a
valuable resource for diagnostic facilities, therapeutic strategies, and
research in terms of variation priority.
