Consortium tackles the genetic basis of autism

The first results from a scan of the world's largest collection of DNA samples from families affected by autism point to two new genetic links that may predispose people to the disorder. The findings were published online this week in Nature Genetics.

The five-year study was led by the Autism Genome Project, an international consortium involving scientists from 50 institutions in 19 countries. The first phase of the project was supported by the not-for-profit Autism Speaks charity and the US National Institutes of Health.

The group shared DNA samples, data and expertise in a co-ordinated effort to identify autism-susceptibility genes. It carried out a two-fold analysis, initially assessing the frequency of alterations in copy number of different segments of the genome.

They found an unexpectedly high percentage of the families - seven to 12 per cent, depending on how the analysis was done - in which all affected individuals share possibly detrimental chromosomal abnormalities.

Two female siblings had deletions of the gene encoding the protein neurexin 1, which interacts with neuroligins, a family of proteins that have been implicated in some cases of autism.

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.

Finally, the authors carried out a linkage analysis of these families, searching for regions of the genome that might be shared by the individuals with ASD. One particular region on chromosome 11 - 11p12-p13 - was identified, which has not previously been reported to harbour genes that affect risk of developing autism.

"This large-scale study reveals that autism is an extremely diverse condition," Dr Daniel Geschwind, director of a neurogenetics program at UCLA, one of the study's 13 research centres, said. "Our findings suggest that autism has numerous genetic origins, rather than a single or few major causes."

Phase two of the project, which will build on the success of the linkage scan, is being launched next week. It represents a US$14.5 million investment over three years by Autism Speaks, the UK Medical Research Council (MRC), the Health Research Board of Ireland (HRB), Genome Canada, the Canadian Institutes for Health Research (CIHR), Southwest Autism Research and Resource Center (SARRC), and the Hilibrand Foundation. Professor Tony Monaco from the University of Oxford's Wellcome Trust Centre for Human Genetics led the funding bid.