2014 International Meeting for Autism Research

May 14 - 17, 2014

Exome sequencing has led to robust identification of genes associated with Autism Spectrum Disorder (ASD), thus offering an unprecedented opportunity to investigate its neuropathology. However, the large number of genes affecting risk and their numerous biological functions challenge conventional genetic methodologies. To overcome this hurdle we integrate recent ASD gene discoveries with genome-wide analysis of gene expression and regulation in the developing human brain to highlight common biological mechanisms leading to ASD. We will present: 1) Gene-discovery from exome sequencing of the Simons Simplex Collection and where these genes converge in their expression in the developing human brain; 2) A novel approach to integrating exome and expression data to greatly accelerate gene discovery; 3) A map of the gene network regulated by CHD8, a chromatin modifier with the best evidence of ASD-associated via loss of function mutations; and 4) Development of zebrafish models to assess hypotheses of neuropathology in vivo. Through integration of psychiatry, neuroscience, genetics, and statistics we present a strategy that uses the genes discovered by exome sequencing to illuminate features of the developmental neuropathology that underlie ASD.