The high and potentially increasing prevalence of Autism Spectrum Disorder (ASD) is taking a significant emotional and economic toll on patients, their families and Canadian society. Although progress has been made in identifying genes associated with ASD, the underlying mechanism of this disorder remains unknown. Recently, several exome-sequencing studies of thousands of patients and their families have been completed yielding hundreds of genes loosely linked to ASD. It is as of yet unknown how these multiple genes give rise to the disease. Traditional, slow throughput methods testing individual gene variants at one time are untenable when 4 to 30 variants need to be tested for tens to hundreds of genes. For this project, Ms. Post will use bioinformatics and high-throughput biological systems to screen for gene mutations most likely to provide strong phenotypes in secondary slower throughput assays. This strategy will allow rapid categorization of large numbers of mutations of individual ASD-associated genes into smaller subsets that all produce the same phenotypes. This strategy will both provide insight to underlying molecular pathways mediating pathophysiology, and allow reduction of the number of variants to focus on by selecting representative mutations that produce the strongest phenotypes within their group. These representative gene mutants will then be tested in lower throughput model systems that more accurately examine their effect on neuronal and neural circuit development. Such a combination of high and low throughput pipelines is our best hope at rapidly identifying the causes of ASD.