The genetic predisposition to autism is likely to be conferred by multiple genes and gene variants. As there is a strong familial component to autism, even the unaffected siblings of autistic children may to carry multiple vulnerability genes that are also carried by their autistic siblings. It is hypothesized that unaffected siblings may therefore have additional, protective genetic variants, which confer resistance to the development of autism, and which are missing in their autism-affected siblings. Previous research from the Persico laboratory has identified two gene loci as candidate protective genes in unaffected siblings of children with autism. In the present study, these researchers will use DNA sequencing to characterize genetic variation at these loci. Next, they will determine the functional consequences of the expression of these protective gene variants using in vitro techniques. Identification and characterization of protective gene variants will be a powerful strategy in identifying therapeutic targets which may prevent the negative effects of the vulnerability genes.