Novel Web-based, High-throughput Drosophila Computational Tool used to Investigate the role of UBE3A in Autism Spectrum Disorders. Ryan Turner¹, Rami R. Ajjuri², Larry Reiter³, Janis M. O'Donnell². 1) Computer-Based Honors Program, University of Alabama, Tuscaloosa, AL; 2) Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama; 3) Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee.

   Autism Spectrum Disorders (ASDs) affect 1 in 88 American children. This cluster of related disorders includes behavioral and developmental defects. Current evidence indicates strong genetic components. Among these are duplications or deletions in human UBE3A. In humans, UBE3A encodes E3 ubiquitin-protein ligase which functions in the degradation of specific proteins via the ubiquitin-proteosome pathway. However, the protein is also predicted to be a transcriptional co-activator for other genes, a feature that complicates genetic analysis of these disorders. Dube3a, the Drosophila homolog, has been used by our lab to model the molecular basis for neurodysfunction as seen in human ASD. To define networks of genes that respond to changes in UBE3a expression, whole genome expression profiling was conducted, comparing the wild-type expression profile to Dube3a null mutant, an over-expressed wild-type transgene, and a transgenic mutant gene with a loss of the ligase function but retention of the co-activator function. We report here the expression profile analysis conducted to identify the following: 1) genes altered in patterns correlating with the over-expression and loss-of-function lines; 2) potential transcription factor binding site (TFBS) clusters of these genes to detect prospective transcriptional co-activators; 3) gene ontology subsets with relevant neuronal function. These candidate genes were then queried for human homologs. A high-throughput computational program was created to access multiple online databases and facilitate this analysis. Additionally, behavioral assays have been conducted to model aberrant behaviors and will be employed to validate candidate genes resulting from the microarray analysis. Together, these analyses will provide potential target genes involved in various domains of Autism Spectrum Disorders.