Although there is strong evidence of a genetic contribution to the cause of autism spectrum disorders (ASD), the isolation of specific causative genetic defects has been difficult. This project will use existing DNA and clinical data from the Autism Genetic Resource Exchange (AGRE) and National Institute of Mental Health (NIMH) repositories to search for ASD susceptibility genes. Genotype analysis, mapping of single nucleotide polymorphisms (changes in a single DNA codon), and linkage studies will be used to identify candidate genes. Post-mortem human tissue, neuronal cultures, and mouse models will then be used to assess whether associated alleles in different locations on the chromosome (haplotypes) functionally alter autism candidate genes. These experiments are expected to identify ASD-associated alleles for multiple genes, and the mouse models that are generated for some of the associated haplotypes can be used as future models for developmental, behavioral, and toxicological experiments.