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First autism study to apply whole genome sequencing

While it is known that autism spectrum disorder has a genetic basis, the underlying factors (genes) of this lifelong developmental condition are still only partially understood.

An international research team led by The Hospital for Sick Children (SickKids) is the first to determine the entire DNA code, a process called whole genome sequencing, and provide a definitive look at the wide-ranging genetic variation associated with autism, including both inherited as well as spontaneous or de novo, genetic alterations.

The million-dollar pilot study, published in the July 11 online edition of American Journal of Human Genetics, is a collaboration among SickKids and BGI, Duke University and Autism Speaks. The team completed whole genome sequencing on 32 unrelated Canadian individuals with autism and their families.

“Whole genome sequencing offers the ultimate tool to advance the understanding of the genetic architecture of autism,” says Dr. Stephen Scherer, Senior Scientist and Director of the Centre for Applied Genomics at SickKids. “The fact that we found notable genetic variants in 50 per cent of families who were examined using the new breakthrough technology reflects our ability to examine regions of the genome and inherited genetic variants missed in other approaches.”

Researchers detected genetic risk variants relevant to clinical manifestations in 50 per cent of the participants. This is a promising finding, as current diagnostic technology has only been able to determine a genetic etiology in about 20 per cent of autism patients tested.

“Our results provide evidence that whole genome sequencing may help in identifying and clinically assessing autistic children and their families,” explains Dr. Peter Szatmari, Chief, Child & Youth Mental Health Collaborative at SickKids and the Centre for Addition and Mental Health, as well as Director of the Division of Child and Adolescent Psychiatry at the University of Toronto.  “As more individuals with autism are studied and more genetic variants are discovered and characterized, the diagnostic yield and clinical utility will also increase.”

The study identified both de novo, X-linked and other inherited mutations in four previously unrecognized genes, nine genes previously linked to autism and eight candidate autism risk genes. Some families had a combination of mutations.

"From diagnosis to treatment to prevention, whole genome sequencing efforts like these hold the potential to fundamentally transform the future of medical care for people with autism," says Dr. Rob Ring, Chief Scientific Officer at Autism Speaks and co-author of the study.

“In the future, results from whole genome sequencing could highlight potential molecular targets for pharmacological intervention, and pave the way for individualized therapy in autism. It could also allow for earlier diagnosis of autism, particularly among siblings of children with autism where recurrence is approximately 18 per cent,” says Scherer, who is also Director of the McLaughlin Centre at the University of Toronto.  

This work was supported by Autism Speaks, Autism Speaks Canada, Autism Genetic Resource Exchange (AGRE), National Institutes of Health (NIH), National Science and Technology Ministry Project -973 program, National Science and Technology Ministry Project -863 program, National Natural Science Foundation of China-Major Program,  the Shenzhen Municipal Government of China,  Enterprise Key Laboratory Supported by Guangdong Province, Shenzhen Key Laboratory of Gene Bank for National Life Science (National Gene Bank Project of China), NeuroDevNet, the Canadian Institutes for Advanced Research, the University of Toronto McLaughlin Centre, Genome Canada/ Ontario Genomics Institute, the Ontario Brain Institute, the Government of Ontario, the Canadian Institutes of Health Research (CIHR) and SickKids Foundation.

About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.

About Peter Gilgan Centre for Research and Learning
The Peter Gilgan Centre for Research and Learning will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The facility will physically connect SickKids science, discovery and learning activities to its clinical operations.  Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Gilgan Centre will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. The Peter Gilgan Centre for Research and Learning is funded by a grant from the Canada Foundation for Innovation, the Government of Ontario, philanthropist Peter Gilgan and community support for the ongoing fundraising campaign. For more information, please visit www.sickkidsfoundation.com/bepartofit.

For more information, please contact: 

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca

Caitlin McNamee-Lamb
The Hospital for Sick Children
Phone: 416-813-7654 ext. 201436
email: caitlin.mcnamee-lamb@sickkids.ca 

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