Scientists have unveiled results of the largest study of the genetics of autism, involving DNA from almost 1,200 affected families worldwide. Two key clues have already been isolated.
Discoveries in two areas of the genome -- a region on chromosome 11 suspected of having links to autism, and aberrations in a brain-development gene called neurexin 1 -- could spur more targeted research, the experts noted.
"That's the real promise here," said Autism Genome Project co-researcher Dr. Stephen Scherer, director of the Center for Applied Genomics at The Hospital for Sick Children in Toronto. "When you identify certain genes, you can then develop genetic tests -- in some cases prenatal and in some cases postnatal -- because early diagnosis is crucial here."
Genetic discoveries can also further research toward a cure for autism, Scherer said.
"When we have this type of knowledge, we can actually think about designing better therapies based on what we know is not happening properly in the [brain] cell. We can try and design things to make it work better," he explained.
The Autism Genome Project was funded by the U.S.
National Institutes of Health and the nonprofit advocacy group Autism Speaks. Its findings were published in the Feb. 18 online edition of Nature Genetics.
Autism remains a real health crisis, with the U.S. Centers for Disease Control and Prevention announcing recently that one in every 150 American 8-year-olds now have some form of autistic spectrum disorder. That number is higher than prior estimates, and the debate rages as to just why the disease might be becoming more prevalent.
Experts agree that autism's causes remain cloaked in mystery, although prior research has pointed to a strong genetic component. For example, "there's about 90 percent concordance [of autism] between identical twins -- that's a significant genetic contribution," Scherer said.
So, the Autism Genome Project, which took five years to complete, sought to probe much deeper into the DNA driving the disorder. The project involved more than 120 scientists working at 50 institutions in 19 countries. They painstakingly sought out almost 1,200 families worldwide in which at least two members were affected by autism. The scientists then collected DNA samples from family members and analyzed these samples in the most advanced and standardized manner, looking for genomic "commonalities."
Those efforts have met with real success.
"First, we found several regions of the genome, particularly one region on chromosome 11, that seem to be very highly associated with the development of autism," said Scherer, who is also professor of medicine at the University of Toronto. While prior research had suggested chromosome 11 as a potential hotspot for autism-linked DNA, this study greatly strengthens that view, he said.
The researchers also used cutting-edge technologies to seek out what are known as "copy number variations" -- genes that appear not in pairs (as most genes passed down from mom and dad are), but as just a single copy, or as three or more copies.
"We found several regions of the genome -- sometimes the same region popping up in unrelated individuals -- with 3 or more copies," Scherer said. "We didn't see these in the individuals' parents, so that implies that these regions are harboring susceptibility genes for autism."
One gene in particular, called neurexin 1, appeared in some cases in just one copy. "In one family, both of the children who were autistic actually had that piece missing," Scherer said. "That's kind of a smoking gun that the gene is implicated."
It makes intuitive sense that dysfunctional neurexin 1 might play some role in autistic disorders, another expert said.
The neurexin 1 protein and its kin, "are very important in determining how properly the brain is wired up from one nerve cell to another, and in the chemical transmission of information from one nerve cell to another," said Dr. Bradley Peterson, a professor of child psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute, in New York City.
Peterson, who was not involved in the project, said genes that effect early neural growth could be key to autistic disorders, since "the genetic and the non-genetic contributions to autism, by definition, have to exert their effect very early in brain development, either in utero or in the first months or couple of years of life."
Still, he and Scherer both stressed that the new study only points to potential leads for future research. Because of the study's particular methodology, no one finding reached statistical significance, Peterson said. "This is all very strong evidence, and a very good set of leads, but we can't yet say that we have proved the involvement of these regions in autism," he said.
Scherer said that, except in very rare instances, there isn't likely to be a single gene responsible for autism. Instead, a variety of genetic abnormalities may work on each other during development to create some level of autism. And experts don't discount the potential role of environmental stresses on that mix, either.
"Remember, autism is actually a grab bag of different developmental disorders. And what we show here is that many genes can be involved, and also these copy number variants," Scherer said. "And could it be that environment is contributing? Absolutely."
One thing is for sure, however: Autism research holds more promise now than ever before, the experts said.
"Anybody that's working out here can use this information now, and it really provides a great path forward as to how we need to do our experiments over the next five years or so," Scherer said. "We've now got all these new candidate genes --- the neurexins, the various copy number variants -- and we can tackle the problem in a much more focused and organ ized way."
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