Stephen Scherer will study the effects of mutations in the PTCHD1-AS long noncoding RNA gene, a candidate ASD risk gene, using induced pluripotent stem cells and mouse models. Results from these studies are expected to provide new insights into molecular and physiological events underlying ASD pathogenesis.

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.

Ellen Hoffman and Ted Abel aim to compare findings from high-throughput behavior-based screens in zebrafish models of ASD risk genes to mouse behavioral phenotypes in order to elucidate the cellular and circuit-level effects of drug candidates that suppress ASD-relevant behaviors in both systems. The results are expected to identify novel pharmacological targets for further evaluation in ASDs.

Hongjun Song will assess whether m⁶A methylation — the most prevalent RNA modification in mammals — regulates the expression of autism risk genes. He will do this by generating a genome-wide map of m⁶A tags in several neural cell types relevant for autism. He will also investigate the potential functional impact of m⁶A tagging on mRNA stability and protein translation of ASD risk genes in both stem cells and animal models.

Caroline Robertson’s laboratory aims to develop a neurophysiological marker of autism that reflects reductions in GABAergic action in the autistic brain. Such a marker will help shed light on the neurobiology of autism and aid in the development of pharmacological interventions.

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.

A seven-laboratory consortium, headed by Kurt Haas, has established a platform to measure the impact of large numbers of ASD missense variants on protein function in multiple model systems, making best use of rapid high-throughput screening assays and slower high-sensitivity assays to examine the effects of these mutations on vertebrate neuronal development.

Dulac aims to identify neurons activated during fever episodes and reveal how they may modulate neural circuits governing social interactions in mice. She also plans to study behavioral changes in autism mouse models during febrile periods.

Bernie Devlin and Kathryn Roeder will develop statistical methods that help to identify noncoding variants contributing to autism, as part of a linked number of projects within the SSC-ASC Whole-Genome Sequencing Consortium.

The NeuroDev study seeks to expand knowledge of the genetic architecture of etiologically related neurodevelopmental disorders — particularly ASDs, intellectual disability and ADHD — in Africa through large-scale sample collection, analysis and participant follow-up. Over the next four years (2018–2022), Elise Robinson, in collaboration with Charles Newton, Kirsty Donald and Amina Abubakar, will develop the initial NeuroDev collection of genotyping and exome-sequencing data of 1,800 children with neurodevelopmental disorders in South Africa and Kenya, 1,800 ancestry matched child controls and 1,900 parents. All NeuroDev materials and results will be made available as a resource for the scientific community.