Autism is a complex developmental disorder manifested by severe social, language and cognitive impairments. Autism is considered to be a part of a spectrum of genetically related disorders. This broader phenotype, the autism spectrum disorders (ASD), includes autism, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), and Asperger's Disorder. Heritability estimates in autism exceed 90%, and therefore, genetic linkage studies have been a major focus of research in ASD. In spite of this, a clear genetic cause for autism has been elusive. It has been hypothesized that there are ways to subdivide the autism spectrum disorder group through behavioral and physical phenotyping of the children and their families. By doing this, we may be able to identify more homogeneous groups that will increase our power to detect the associated genetic factors. We believe that we can identify genes and gene pathways that lead to the ASD phenotype and that we might be able to subdivide the patients into diagnostic categories based on their phenotypic features. In addition, we believe that we can subdivide patients into categories based on differences in their gene expression profiles in lymphocytes from peripheral blood. These studies could lead to a biologically based diagnosis of ASD and to an improved understanding of and possible novel interventions in the disease process. A variety of approaches will be used in these studies including transmission disequilibrium testing (TDT), affected sib pair (ASP) analysis, genome-wide scans and novel Bayesian algorithms (which utilize all data both from phenotypic analysis and from expression arrays).
