Haiyuan Yu, Bernie Devlin and Kathryn Roeder aim to develop an experimentally and computationally integrated interactome perturbation screening pipeline and additional analytical methods to study the functional impact of de novo missense mutations in autism.

Joseph Dougherty will assess the functional consequences of mutations in untranslated regions (UTRs), furthering our understanding of the risk burden of noncoding variants in ASD. This project is part of a number of linked projects within the SSC-ASC Whole-Genome Sequencing Consortium.

Joseph Gleeson proposes to measure gonadal mosaicism for the presence of ASD-causative mutations. He also plans to use this information to stratify males into those with baseline risk and those with high risk of fathering a child with ASD.

Studying the development of the human midfetal prefrontal cortex (PFC) is integral to understanding the pathophysiology of ASD. Nenad Sestan aims to generate a multispecies comprehensive tissue-level and single-cell profile of the midfetal PFC to identify pertinent gene regulatory pathways and candidate genes. The function of identified ASD-relevant pathways will then be assessed in CRISPR-based targeted deletion/insertion mouse lines.

The SSC-ASC Whole-Genome Sequencing Consortium has been established to discover de novo and inherited genomic variation that increase risk for ASD. In project one of four linked projects, Stephan Sanders will reprocess existing whole-genome sequencing data from thousands of ASD families using a common standardized pipeline to identify noncoding variants associated with ASD.

Michael Talkowski will assess the mutational spectrum of structural variation associated with autism risk, as part of a linked number of projects within the SSC-ASC Whole-Genome Sequencing Consortium.