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About SickKids

May 26, 2014

SickKids researchers make great strides towards cracking the autism code

Scientists create a new “genetic formula” that helps to predict effects of genetic mutations in autism

TORONTO –Recent advances in genome sequencing technology have facilitated rapid identification of genetic alterations in genes associated with Autism Spectrum Disorder (ASD). The universal challenge in the field of genetics has been to determine whether these mutations will result in autism.

In a study to be published in the May 25th advanced online edition Nature Genetics, researchers at The Hospital for Sick Children (SickKids) and University of Toronto have essentially unraveled the autism code, by creating a “genetic formula” that will enable clinicians to identify genetic mutations that have the highest and lowest likelihood of causing ASD. 

ASD, which has recently been reported to affect one in every 68 children, is a neurodevelopmental disorder characterized by impairments in social interaction and communication, as well as repetitive and restrictive behaviors. It is well established that genetics has a major role in the development of autism, which in itself represents a collection of clinically similar disorders.

“There has been incredible progress finding genetic answers, but these are often accompanied by puzzling clinical observations. Previous research has revealed many conundrums such as mutation carriers who do not exhibit symptoms of autism,” says Dr. Stephen Scherer, principal author of the study and senior scientist and director of The Centre for Applied Genomics at SickKids and the University of Toronto McLaughlin Centre. “In our new study we’ve finally discovered a unifying set of characteristics in the DNA that we can weave into a ‘genetic formula’ that helps us calculate which genetic mutations have the highest probability of causing autism, and equally important, which alterations do not have a role.”

Dr. Stephen Scherer, here at his lab’s Next-Generation DNA sequencer, closes in on roots of autism
Dr. Stephen Scherer, here at his lab’s Next-Generation DNA sequencer, closes in on roots of autism. (Photo courtesy of Genome Canada and OGI)

Dr. Mohammed Uddin, a postdoctoral fellow on Scherer’s team determined that the key to solving the enigma of the autism mutation code, resides in recognizing small segments (called exons) of genes that are both “highly conserved” in human evolution and “turned on”  during early brain development.

“The timing of this gene activation is an important finding. The fact that these genes could be turned on prenatally, gives us a clue as to when autism could start to develop,” says Scherer.  

Metaphorically, genes are often compared to an orchestra, with the most important exons representing instruments like the violin that crescendo (turn on, or express) at critical times in the developmental symphony.

The Toronto team identified almost four thousand such brain exons in more than seventeen hundred different genes. In addition, the one hundred or so known autism susceptibility genes already used for diagnostic testing were further validated by the new approach, as were genes involved in other neurodevelopmental conditions such as intellectual disability, which is often a feature of ASD.

Scherer predicts that  many of the novel genes discovered by his group that bear these newly defined unique characteristics, will eventually be proven by other means to be involved in autism or intellectual disability, or other related medical conditions associated with brain development or cognition.

“This groundbreaking work will have immediate impact on efforts to develop more accurate genetic diagnostic tests aimed at improving earlier detection and clinical decisions to begin intervention” says Dr. Robert Ring, Chief Scientific Officer of Autism Speaks. “Improvements in our understanding of mechanisms involved in brain expression of disease mutations will also help to reveal new biological space worth targeting for the development of medicines that benefit individuals with autism and related neurodevelopmental disorders.”

This research was supported by grants from the University of Toronto McLaughlin Centre, NeuroDevNet, Genome Canada and the Ontario Genomics Institute, the Canadian Institutes for Health Research (CIHR), the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the government of Ontario, the Ontario Brain Institute, Autism Speaks and SickKids Foundation.

This research has been developed in close collaboration with the Industry Partnerships and Commercialization Office at SickKids. The technology mentioned above is available for licensing.

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.


For more information, please contact:

Caitlin McNamee-Lamb
The Hospital for Sick Children
416-813-7654, ext. 201436

Matet Nebres
The Hospital for Sick Children