June 9, 2010
By Megan Ogilvie,
A Toronto-led consortium of international researchers has described the clearest picture yet of how genetics influences autism, the developmental disorder that affects an estimated one in 110 children.
The findings reveal the majority of families with individuals diagnosed with autism have their own unique form of the disorder, that the particular changes in their DNA are not shared by other affected families.
Scientists involved in the project say it has led to a paradigm shift in how they understand autism spectrum disorder.
It had been thought common genetic changes in only a few genes triggered autism.
But now, they say, the genetic alterations that lead to autism are rare, shared by few individuals with the disorder.
The scientists also identified new biochemical and brain development pathways affected in autism, which give drug makers new targets for creating therapies.
Almost immediately, the research will help to diagnose individuals with an autism spectrum disorder earlier in life – perhaps in the first 12 or 18 months, before behavioural symptoms arise.
And knowing each family affected by autism is unique suggests one day doctors will be able to prescribe individualized treatment and therapy for their patients with an autism spectrum disorder.
"We're really starting to see the forest through the trees," said Stephen Scherer, the study's senior corresponding author, a senior scientist at the Hospital for Sick Children and director of the hospital's Centre for Applied Genomics.
"As we start to parse out these different forms of autism, we can use the information in a more personalized way for each family to give them the best tools for the decisions they need to make."
The study, the largest of its kind and involving more than 120 scientists from across North America and Europe, was published online Wednesday in the journal Nature.
The Autism Genome Project Consortium is a global effort to find the genetic roots of autism. Autism spectrum disorder can cause a range of symptoms in children, including repetitive behaviours and impaired language development and social interaction. The disorder affects four times as many boys as girls.
To home in on the genetic underpinnings of autism, the scientists collected DNA samples from 1,500 families. Using microarray technology, they scanned the entire genome of close to 1,000 individuals with autism and about 1,200 people without the diagnosis, looking for copy number variants.
Copy number variants, or CNVs, are long stretches of genetic material that either have missing or extra DNA.
The study found people with an autism spectrum disorder carry a greater number of CNVs than healthy individuals. Those CNVs can either be inherited from parents or arise spontaneously during development.
The study – the second phase of the consortium's work – pinpointed about 100 genes related to autism. Scherer said these account for about 10 to 15 per cent of cases of autism.
The research also found an overlap between the newly identified autism susceptibility genes and genes known to be associated with intellectual disability.
"No one had tested that before because they didn't have the data," said Scherer.
Dr. Peter Szatmari, who shared the leading role with Scherer and is director of the Offord Centre for Child Studies in Hamilton, said the research will help families affected by autism.
"Giving families an understanding is really, really important," Szatmari said. "After you tell them the child has a diagnosis of ASD, the next thing they want to know is what caused it. Ten years ago, all we could say is that it was genetic. But we couldn't point to any genes or any mechanisms with any clarity, so that left a lot of families unsatisfied.
"Now we can say we know a number of the genes, there are lot of them – way more than we thought – but they appear to have this common function and we know what that is now and we're working toward real advances."
Geraldine Dawson, chief science officer of the U.S. branch of Autism Speaks, that country's largest autism science and advocacy organization, said the most immediate clinical application of the findings will be in earlier diagnosis.
"By screening for rare mutations in children at risk for autism, such as infant siblings of children with autism, we may be able to identify those infants who have a higher likelihood of developing the condition," said Dawson, who is also a professor in the department of psychiatry at the University of North Carolina Chapel Hill. "The strategy would be to monitor these infants' development more closely and begin intervention as soon as symptoms are apparent."