New Genetic Findings Expected to Accelerate Autism Testing and Development of Treatments

Results of International Autism Genome Project – Phase 2 are unveiled
Posted June 11, 2010

Canadian and international scientists have uncovered key changes in DNA in individuals with autism. The Phase 2 results of the multinational Autism Genome Project Consortium, published in the June 9 advance online edition of Nature, substantiate the importance of genes as susceptibility factors in autism spectrum disorders.

This study is the largest of its kind, involving 1,500 families and more than 120 scientists and clinicians from across North America and Europe. The team was led by Professor Stephen Scherer, corresponding author of the study, director of the McLaughlin Centre at the University of Toronto, senior scientist at The Hospital for Sick Children (SickKids) and director of its Centre for Applied Genomics, and Dr. Peter Szatmari, co-principal investigator, director of the Offord Centre for Child Studies and professor at McMaster University. Dr. Dalila Pinto, post-doctoral research fellow at SickKids, was lead author.

Using microarrays (or gene-chip technology) in the highest-resolution testing to date, researchers investigated individuals with autism spectrum disorders (ASDs). ASDs, diagnosed in one in 110 children, are a group of neurodevelopmental conditions resulting in challenges connected to communication, social understanding and behaviour.

The researchers reported that individuals with ASDs tended to carry more insertions and deletions affecting their genes – called copy number variants (CNV) – than did people in the control group. Some of these CNVs appeared to be inherited, while others are considered new, because they are found only in offspring with autism and not in the parents. Dozens of new “autism risk genes” were discovered, including some that might be helpful in early diagnosis.

“We now know several of the genes involved in autism and for the first time, we are able to tie many of these genes into the same biological pathways involved in brain function,” said Scherer. “Knowing these autism genes are linked, we can begin to develop therapies to target the common pathways involved.”

Szatmari added, “This study will lead to a paradigm shift when it comes our understanding of the root causes of autism and indeed other neurodevelopmental disorders. Previously it was believed that autistic individuals share common genetic variations in a few genes.This research points to the fact that genetic variations are actually rare, meaning individuals with autism are genetically quite unique. But as we discover more and more of these variants, the number
of cases of ASD we can explain increases substantially. ”

According to Pinto, “Another surprising discovery was the significant overlap between autism susceptibility genes and those genes that were previously thought to be implicated in intellectual disability. This suggests that at least some genetic risk factors are shared at the pathway level by different mental
health disorders and developmental disabilities, providing insights into possible common pathogenic mechanisms.”

The study found that for about 10 per cent of the families studied, there are some genetic clues that may assist in the early diagnosis of autism or related
complications. The Canadian researchers say the next goal is to set up mechanisms and processes so that all families who are interested can have access to this testing.

“Guided by these massive genomic data sets, we can start to see the forest through the trees, offering answers and hope for families with autism,” said

The Autism Genome Project consists of 120 scientists from more than 50 institutions representing 12 countries who formed a first-of-its-kind autism genetics consortium. The project began in 2002, when researchers from around the world came together to share their samples, data and expertise to facilitate the identification of autism susceptibility genes.

The funding to the Canadian team which provided leadership in the identification and analysis of these genes came from public and private partners including major awards and support from Genome Canada through the Ontario Genomics Institute, the McLaughlin Centre, the Canadian Institutes of Health Research, the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the Ministry of Research and Innovation, the Ontario Innovation Trust, the Catherine and Maxwell Meighen Foundation, the Premier’s Summit Award in Medical Research, Autism Speaks, The Centre for Applied Genomics, the Chedoke Health Corporation, the Mayberry Family Fund, the Hamilton Health Sciences Foundation and SickKids Foundation.

Pinto was supported by fellowships of the Netherlands Organization for Scientific Research and the Royal Netherlands Academy of Arts and Sciences.

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