Project Description

Challenge

Autism spectrum disorder often runs in families. For example, identical twins of people with ASD have roughly a 60 percent chance of having it as well while siblings have a 20 percent chance. This statistic points to genetic risk factors. But which gene variants increase susceptibility to ASD? Moreover, how do genes influence the brain development and behaviour of children with autism?

Project Summary

As part of the network’s “ASD Demonstration Project,” researchers and partners used state-of-the-art genome-sequencing technologies to delve deeper into these questions. Project investigators also compared children diagnosed with ASD to their siblings to see how genetic differences and similarities line up with developmental trajectories. In preparing to do so, they helped to spearhead the creation of an international biorepository.

Result

By comparing the genomes of families affected by ASD to control participants, they uncovered new associations between particular genetic variations, autism and its symptoms. Many of these alterations are rare or “de novo” (not inherited but instead appearing for the first time in the person with ASD). Such findings have potential clinical utility i.e. they may pave the way for earlier diagnostic testing using a combination of behavioural and genetic biomarkers. They allow for more informative genetic counselling about recurrence risk, which is highly valued by many families. They could also lead to new targets for pharmaceutical interventions and new, individualized therapies that would minimize the impact of a genetic vulnerability on a child’s life.

Team

Investigators

Project Leaders

Lonnie Zwaigenbaum, University of Alberta
Stephen Scherer, University of Toronto

Co-Investigators

Peter Szatmari, McMaster University
Eric Fombonne, McGill University
Michael Brudno, University of Toronto
Sal Carbonetto, McGill University
Anne Marie Craig, University of British Columbia
Krista L. Hyde, McGill University
Alan Evans, McGill University
Evdokia Anagnostou, University of Toronto
Geoff Hall, McMaster University
Susan Bryson, Dalhousie University
Isabel Smith, Dalhousie University
Wendy Roberts, University of Toronto
Jessica Brian, University of Toronto
Joanne Volden, University of Alberta
Pat Mirenda, University of British Columbia
Anthony Bailey, Warneford Hospital
Tracy Vaillancourt, University of Ottawa
Fiona Miller, University of Toronto
David Nicholas, University of Calgary
Bridget Fernandez, Memorial University

Collaborators

Andrew Paterson, The Hospital for Sick Children, Toronto
John Vincent, Centre for Addiction and Mental Health
David Stellwagen, McGill University Health Centre
Margot Taylor, Holland-Bloorview Kids Rehabilitation Hospital, The Hospital for Sick Children, University of Toronto
Larry Tuff, McMaster Children’s Hospital, Hamilton Health Sciences
Eric Duku, McMaster University
Marc Woodbury-Smith, McMaster University
Mandi Steinman, Montreal Children’s Hospital
Keith Goulden, Glenrose Rehabilitation Hospital
Margaret Clarke, Child Development Centre, Calgary
Charlotte Waddell, Simon Fraser University
Veronica Smith, University of Alberta

Partners

Applied Biosystems
Illumina Inc.
DNA Genotek Inc.
NIH Autism Sequencing Consortium
Ontario Research Fund GL2 grant for autism genomics
Women and Children’s Health Research Institute
Sinneave Family Foundation
Autism Speaks Canada
Autism Research Training Program