Search for Autism Clues Gets Complex
One clue was a region of mouse brains that looked like a cut-and-paste job. Other hints came from methodically trolling through the human genes. And now scientists hope they’ve picked up the scent for identifying genes that set up some babies to develop autism.
Nobody can declare a clear victory yet. A proposed autism gene that captured headlines in November, for example, will have to be confirmed by further research before it’s widely accepted.
But gene hunters say the search has been heating up in the last few years, with more investigators, sophisticated tools and techniques being brought to bear, and a run of tantalizing results.
Once they start finding genes--nobody knows how many might be involved--researchers hope to acquire clues into the roots of the dimly understood disorder.
Autism usually appears by age 3, mostly in boys. Affected children have trouble communicating and interacting with others. In severe cases they may become aggressive or injure themselves.
Scientists hope finding genes can answer several questions:
* What exactly goes wrong in the brain to cause autism?
* Are there targets for drugs to treat or prevent it, even before birth?
* Do symptoms result from a single event in the brain, or from a process that could be interrupted?
* Could people destined to develop autism be recognized at birth, before symptoms appear, allowing for early intervention?
The hunt for autism genes is complicated. It’s not a case of a single flawed gene causing a disease, as in Huntington’s or cystic fibrosis. Rather, autism appears to be brought on by unknown environmental influences coupled with a dimly understood combination of genes that make people vulnerable.
That’s the case with some other conditions, such as diabetes, heart disease and schizophrenia. And it makes these “susceptibility genes” much harder to find.
When a person inherits a disease-promoting version of such a gene, it only tips the scale toward illness rather than causing it outright; a link between a gene and a disease can be difficult to demonstrate.
But autism also offers an advantage for gene hunters: The genetic effect on susceptibility is strong. The rate of autism in the general population is about two-tenths of a percent or less, but for siblings of an autism patient it jumps to around 3%. And for an identical twin of an autism patient, someone who shares all the patient’s genes, the rate is 60% or more.
That powerful genetic influence lured investigators into the autism gene hunt around the mid-1990s, giving hope for quick success.
“I thought this would be an easy find. I really did,” said Susan Santangelo of the Tufts School of Medicine and Harvard School of Public Health.
As she and others looked for the genes, however, they came to believe that this inherited influence was split among more genes than expected, leaving no gene with an easily traceable influence.
Nowadays the “wild optimism” of the mid-’90s has given way to a more realistic appreciation of the challenge, says Gerard Schellenberg, a research professor at the University of Washington. But he and some others say autism could be the next common psychiatric disorder, after Alzheimer’s, to yield susceptibility genes.
There are encouraging results from a variety of approaches.
One is to scan all the human chromosomes, the rodlike structures that hold genes, for locations that show evidence of harboring an autism gene. A half-dozen of these scans have been done for autism, and while results have not been uniform, researchers say at least two locations show promise.
Scientists also are pursuing clues from some accidents of nature. Researchers at UC Irvine recently found that a girl with the condition had been born without a chunk of chromosome 15. So genes found in that chunk become candidates for study.
Information on autism:
https://www.ninds.nih.gov/health_and_medical/pubs/autism.htm
Autism Genetic Resource Exchange:
https://www.agre.org
National Alliance for Autism Research: https://www.naar.org
Autism Society of America:
https://www.autism-society.org
