Autism spectrum disorders (ASD’s) are neurological conditions characterized by impairment in the ability to communicate, form relationships, and respond appropriately to the environment. With a worldwide incidence of 1:250-1:500, autism is common, and studies have suggested that the prevalence of autism may now be 10 times what it was 10 years ago. Twin studies suggest that autism has a large genetic component. However, few potential autism-susceptibility genes have been identified and known genes likely account for only a small percentage of cases. Recently published work has shown that genomic copy number changes (i.e., deletions and duplications) are surprisingly prevalent in the human population and often cause disease. Our preliminary data indicate that there are rare de novo copy number changes as well as inherited autosomal deletions in individuals with ASD. This project will identify genomic copy number changes in probands of families with ASD enrolled at Children’s Hospital Boston and the Autism Consortium, determine if the identified changes are rare or common by comparison with databases of known changes and analysis of controls, and determine if changes occur at a higher than expected rate among individuals with ASD. Our second hypothesis is that genes that are deleted or duplicated in some individuals with ASD, may show point mutations in other individuals with ASD; we will test this hypothesis by sequencing genes that are in regions duplicated or deleted in some individuals with ASD in additional individuals with ASD without copy number changes for that gene, to determine whether some patients without deletions or duplications carry point mutations. Finally, homozygosity mapping of consanguineous Middle Eastern pedigrees in our lab has identified loci linked to ASD, so we will also sequence candidate genes (chosen from loci identified by homozygosity mapping of consanguineous Middle Eastern pedigrees) in individuals with ASD enrolled as part of this study.
