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Stephen Scherer, director of the Centre for Applied Genomics, Hospital for Sick Children, is pictured in a handout photo. A Canadian-led international research team has identified several new genetic mutations that appear to be linked to autism spectrum disorder, using a method that looks at the entire DNA code of affected individuals.Handout

Efforts to trace the hidden factors underlying autism have received a potent boost from a Canadian-led study that combed through the whole genomes of autistic individuals and their families.

The findings, which include variations in four genes not previously linked to autism, are expected to improve prospects for early detection of autism in children and help guide the search for effective treatments.

"For the first time, we can really look at inherited variants," said Stephen Scherer, director of the Centre for Applied Genomics at the Toronto Hospital for Sick Children.

Along with Dr. Scherer, more than three dozen authors were involved in the international study, published online on Thursday by the American Journal of Human Genetics. Participating institutions included Duke University, BGI-Shenzhen, a major sequencing centre in China, and the advocacy organization Autism Speaks.

The million-dollar pilot study is an initial step toward a larger international effort to decode the entire DNA sequences of 10,000 families who are coping with autism over the next five years, including about 1,000 in Canada.

Researchers have long known that genes must play a crucial role in many cases of autism spectrum disorder (ASD), a broad range of syndromes characterized by problems with communication and social development. While the overall incidence of ASD in the general population is just over 1 per cent, the odds that the sibling of an autistic child will also appear in the spectrum of syndromes jump to 18 per cent. Yet most autistic individuals do not carry any of the gene variants already linked to ASD, meaning that dozens, if not hundreds, of gene combinations that could trigger it remain unknown. Typically, only one in five individuals with ASD can be linked to a specific genetic risk factor.

For the study, the group sequenced the whole genomes of 32 Canadians with full blown autism as well as those of their parents and some other family members. They found specific genetic variants – changes in individual genes – linked to ASD in about half of the families. Some of the variants occurred spontaneously while others were inherited. In at least one case, researchers were able to determine that a sibling who was not previously thought to have ASD was in fact on the spectrum and carried a relevant gene.

One goal of the study is to help identify young children who are likely to have ASD. Currently, the average age for diagnosis of ASD in Canada is about four and a half. Earlier diagnosis and intervention have been shown to improve outcomes and help families prepare to care for their autistic children.

"If there's a family history or a suspicion, we can do a genome sequencing to prioritize kids and get them into programs much earlier," Dr. Scherer said. With information gleaned from whole genome sequencing, families found to have specific gene variants that are linked to ASD might also be fast-tracked for drug trials that target the effects of those anomalies.

The study is the largest to date to apply whole-genome sequencing to autism and "a nice proof of principle" that dramatic improvements in genetic technologies will translate into clinical benefits, said Jonathan Sebat, director of the Beyster Center for Molecular Genomics of Psychiatric Diseases at the University of California, San Diego, which published a smaller whole-genome study last December.

In recent years, "the genetics of autism has just been blown wide open," Dr. Sebat added, with DNA sequencing making it possible not only to link genes to the risk of developing ASD but illuminating the precise biological causes of autism, currently thought to involve a breakdown in the formation and maintenance of connections between brain cells.

"Whole-genome sequencing is really the direction where we anticipate the field going, not just for research but clinically in the upcoming years," said Eric Morrow, a geneticist and child psychiatrist at Brown University in Rhode Island, who called the new work "exciting."