Canadian scientists lead international autism genome discoveries

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Autism-causing genes

Researchers at The Hospital for Sick Children (SickKids) and the Offord Centre for Child Studies have led an international consortium in the discovery of a previously unidentified chromosomal region containing autism-causing genes. Their findings, part of the largest genome scan ever attempted in autism research, have just been published online in the prestigious journal Nature Genetics.

Working with 137 researchers from eight other countries, the scientists analyzed DNA from about 1,600 families worldwide to zero in on a special group of neurons and the genes affecting their development and function. In particular, they implicate neurexin 1, a member of a family of genes believed to be important in neuronal contact and communication.

All the scientists involved in the project are members of a first-of-its-kind autism genetics consortium called the Autism Genome Project (AGP). The AGP began in 2002 when researchers from around the world decided to come together and share their samples, data, and expertise to facilitate the identification of autism susceptibility genes. The first phase of the effort involved the assembly of the largest autism DNA collection ever and a genome linkage scan.

The Canadian team, led by Dr. Stephen Scherer of SickKids and Dr. Peter Szatmari of the Offord Centre for Child Studies, has played a lead role from the beginning. It was Dr. Scherer who first co-discovered the existence of common genetic variants in the general population that could be involved with autism and other common disorders. These copy number variations (CNVs) are what the AGP scientists were looking for in their DNA scans of autistic individuals.

Dr. Szatmari led the committee to decide the phenotypes to be used in analysis, and was instrumental in drafting the memorandum of agreement among the consortium members, who represent 50 different institutions. They include a dozen other Canadian scientists from five institutions and four provinces.

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"We first used genome scanning technology to test genetic markers in autistic children and find regions in the genome linking to autism susceptibility genes," said Dr. Scherer, a senior corresponding author of the study, senior scientist in Genetics and Genomic Biology at SickKids and professor of Molecular and Medical Genetics at the University of Toronto. "By combining this with cutting edge CNV analysis we were able to reveal, for the first time, the genetic architecture underlying autism susceptibility."

Using this unprecedented statistical power, the scientists were able to implicate a previously unidentified region of chromosome 11, and neurexin 1, among other regions and genes in the genome. The neurexin finding in particular highlights a special group of neurons, called glutamate neurons, and the genes affecting their development and function, suggesting they play a critical role in autism spectrum disorders.

"The clinical implications of this discovery are unprecedented," said Dr. Szatmari, director of the Offord Centre for Child Studies, Professor, Vice-Chair of Research, Head of Division of Child Psychiatry at McMaster University. "Not only have we found which haystack the needle is in, we now know where in the haystack that needle is located. This is a major breakthrough in our efforts to better understand the disorder and improve diagnosis and treatment for patients and their families."

Autism is a complex developmental disorder affecting roughly one in 165 children, making it the most common form of any neurological disorder or severe developmental disability of childhood. Those affected exhibit severe impairments in reciprocal social interaction and communication, and a preference for repetitive, stereotyped behaviours.

"As a parent of a child with autism, I am very excited about this news. Our son, Jaden was already two-and-a-half years old when he was diagnosed and began his ABA program," said, Mr. Mike Lake, MP for Edmonton-Mill Woods-Beaumont and active member of the Edmonton Autism Society. "This research will lead the way to earlier diagnosis and treatment, which is crucial for achieving the best possible results for these kids."

"Canadians should be extremely proud of the leadership role our researchers have taken on this project and on other autism-related projects. This is an incredibly important day for families affected by autism, not only in Canada, but around the world."

The launch of a $26.7 million dollar second phase of the project, building on the success of the linkage and CNV scan, is being announced today.

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