The Reiter laboratory utilizes the genetic tools available in Drosophila melanogaster (fruit flies) to study genes related to autism, specifically the protein targets of the ubiquitin ligase E6-AP (gene name UBE3A). Mutations in the UBE3A gene cause a mental retardation disorder known as Angelman syndrome. Recently it has been shown that duplication of the genomic region containing this gene could be the underlying cause in as many as 3% of all cases of inherited autism. This project will use fruit flies to identify genes regulated at the protein level by E6-AP. Several techniques will be used to generate artificially high levels of Drosophila UBE3A (Dube3a) protein. The investigators will then use protein sequencing (proteomics) to identify those proteins affected by changes in the levels of Dube3a protein. Upon validation, proteins that appear to change their expression in this analysis will be considered as new autism genes. In a separate collaboration, these potential autism genes will then be analyzed as susceptibility factors in families where autism appears to be inherited.