Posted on 02/18/2007 4:36:19 PM PST by Choose Ye This Day
SUNDAY, Feb. 18 (HealthDay News) -- The largest study of the genetics of autism ever conducted, involving DNA from almost 1,200 affected families worldwide, has already yielded two important clues to the poorly understood disorder, scientists say.
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."
autism ping
As the grandmother of a child who was diagnosed as autistic as a little boy, and having seen this "autistic" boy grow into a 17 year-old-math genius, I am highly skeptical of this research.
It seems this type of research always leads to a genetic test in utero and we know the solution for that problem. Don't even suggest it. I also have a niece with Down's. There is no sweeter person in the world.
I would rather they stop right now that to come to the conclusion to which I think they will come.
Seems a bit too general to me. Granted, pinpointing anything in the genome is difficult; I just don't know why they chose now to announce this bit of news. Sounds like a justification for additional funding.
While genes may indeed be a contributing factor, it's hard to have an epidemic that is rooted in genetics.
University of Medicine and Dentistry in New Jersey came out with an article today that claims to identify those at risk of Autism with a urine test. It tests for missing proteins. I'll be posting that article shortly.
It's no longer simple Mendelian genetics.
Global variation in copy number in the human genome
You might have to register for Nature, but it is free. P.S. I could only copy the first line of your list, Incorrigible.
My granddaughter, (the sister of my grandson with "autism") is expecting a baby boy in May. I'm concerned about the baby's vaccines, etc.
With the exception of multi-dose vials of the annual flu vaccines, thimerosal has been removed from the pediatric vaccines as those now come in unit doses.
I know. I actually worked for the lead sponsor of this legislation in a state that was the leader in removing thimerisol from vaccines. Thanks for trying to calm my concerns. I still don't want the baby bombarded with lots of vaccines. However, I don't have a vote.
Do you know if she (the mother) has a auto-immune disease? Like Multiple Sclerosis, Lupis, Thyroid problems, etc? My wife is convinced that we are missing an epidemic in auto-immune disease in mothers.
Not that I know but this is an interesting hypothesis.
Thx for pinging.
Even if the mercury has been eliminated from vaccines, most of them still contain aluminum, a known neurotoxin.
Imagine that...it wasn't the MMR after all.
This does nothing to rule out MMR or any other environmental factor. Such factors could more dramatically affect individuals with a certain genetic predisposition.
All this says is, we still don't know, but we're getting a tiny bit closer.
I guess the sarcasm of mmy original post was missed; outside of naturopaths and chiropractors with mail order degrees, the idea that the MMR vaccine causes autism carries no scientific weight at all.
*sigh*
Oh yeah. Genetics cause epidemics.
I caught the sarcasm. I just don't happen to agree. I rule nothing out.
Question: Are ALL Aspergers of high intelligence?
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