Discovery and Validation of Copy Number Variants in Autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, stereotyped repetitive behaviors, and defective communication. Twin studies indicate that more than 90% of ASD cases are the result of genetic variation. One sort of genetic variation is copy number variants (CNVs), which are duplications and deletions in the genome; rare CNVs (<1% frequency) have been associated with neurodevelopmental disorders including autism spectrum disorders, intellectual disability, schizophrenia, and epilepsy. We hypothesize that recurrent rare CNVs contribute to the etiology of autism. To address this hypothesis, we previously identified 1,340 gene-rich regions for recurrent CNVs (hotspots) ranging in size from >5 kbp to 5 Mbp, and also several recurrent variants in 1,834 cases of autism using array comparative genomic hybridization. Of particular interest, we identified 220 smaller CNVs (<20 kbp) involving neurologically relevant genes. To validate these hotspot regions of the genome, a series of both traditional polymerase chain reaction (PCR) and real time quantitative (qPCR) will be performed. The purpose of this experiment is to validate array-CGH results using an orthogonal method, determine the inheritance of the variant and also compare the frequency of the identified variants in individuals with autism compared to neurologically-normal individuals.