The Journal of Young Investigators: An Undergraduate, Peer-Reviewed Science Journal

08 March 2007 - An international consortium led by Canadian researchers at the Hospital for Sick Children and the Offord Centre for Child Studies has discovered a previously unidentified chromosomal region containing autism-causing genes. Their findings, part of the largest genomic scan ever attempted in autism research, have just been published online in the 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, the findings implicate neurexin 1, a member of a family of genes believed to be important in neuronal contact and communication.

All the scientists involved are members of the Autism Genome Project (AGP), which is a genetics consortium established in 2002 to facilitate the identification of autism susceptibility genes. The first phase of that effort involved the assembly of the largest autism DNA collection ever and a genome linkage scan.
AGP scientists looked for common genetic variants known as copy number variations (CNVs), large DNA segments present at variable copy number, in their DNA scans of these autistic individuals. These regions of variation are thought to potentially contribute to autism susceptibility.

“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 Stephen Scherer, a senior corresponding author of the study at the Hospital for Sick Children and co-discoverer of CNVs in 2004. “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 from such a large sample size, 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 co-author Dr. Szatmari, director of the Offord Centre of Child studies at McMaster University. “Not only have we found which haystack the needle is in, we now know where in the haystack the needle is located. This is a major breakthrough in our efforts to 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 behaviors.

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