Autism spectrum disorders (ASD) are largely genetic in origin and occur either sporadically (simplex) or in a familial (multiplex) pattern. This project is intended to address the genetic basis of ASD through a high-throughput, candidate-gene sequencing approach. For these experiments, the Simons Simplex Collection (SSC) will be utilized as the sample population. The SSC is the largest high-quality set of ASD families assembled so far, and it is specifically designed to compensate for the shortcomings of existing ASD family populations by ensuring comprehensive and consistent clinical analyses. More importantly, it is a collection of simplex families, and as a result the proportion of cases of autism due to spontaneous mutation-as opposed to inheritance-is maximized. This study will yield significant insight into the molecular basis of autistic spectrum disorders, which are largely genetic in origin, highly prevalent among all populations, and difficult to diagnose and classify. This work will lead to advances in molecular screening of ASD among young children, which will in turn result in improved diagnoses and more precisely targeted treatment regimes.