SFARI | Topic: Genetics

Impact and mechanisms of paternal gonadal mosaicism on risk for autism

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.

Gene regulatory control of prefrontal cortex development and evolution

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.

SSC-ASC Whole-Genome Sequencing Consortium (project 1): Association testing

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.

Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk.

SSC-ASC Whole-Genome Sequencing Consortium (project 3): Discovery and functional characterization of structural variation in autism

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.

Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations.

Case-control meta-analysis of blood DNA methylation and autism spectrum disorder.

SSC-ASC Whole-Genome Sequencing Consortium (project 2): Development of statistical methods

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.

GeNets: A unified web platform for network-based genomic analyses.

NeuroDev: Genetic characterization of neurodevelopmental disorders in African populations

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.