Role of Copy-Number Variations in Non-Coding Regions of Autism Spectrum Disorders

Abstract

Autism Spectrum Disorders have a strong genetic basis. So far, only a small fraction of affected individuals has been linked to a certain genetic risk factor. Previous genetic studies focused on analyses of the protein-coding regions in the genomes of Autism Spectrum Disorder affected individuals whereas the relationship between the non-coding regions and Autism Spectrum Disorder development was largely unexplored. Copy-number variants, a type of genomic rearrangements, has been suggested to contribute significantly to phenotypic diversity and disease susceptibility in many neurodevelopmental disorders. In this study, I assessed the copy-number variations recorded in SFARI Gene, an on-going database that collects copy-number variations reported in the published scientific literature. I systematically evaluated the effect of copy-number variations in the non-coding regions of Autism Spectrum Disorder genomes. By combining the chromosomal interaction information and the expression quantitative trait loci data, I found that Autism Spectrum Disorder specific copy-number variations were enriched in the non-coding regions, especially in the enhancer regions. In addition, I identified 19 novel functional cis-regulatory enhancers in Autism Spectrum Disorders.