Little glitches in the DNA of people with autism suggest that the disease might be caused by as many as 100 different genes, researchers reported on Thursday.
The study is one of several new reports on autism in recent months, which have shown the disease is far more common and more complex than many experts had believed.
“These findings certainly complicate the search for genes contributing to autism. These are rare changes, dispersed across the genome, and they tell us that autism may be the final common path for many different genetic abnormalities,” said Dr. Thomas Insel, director of the National Institute for Mental Health, which helped fund the study.
The small changes are not what people usually think of as genetic mutations but are called copy number variations — extra copies or missing stretches of DNA.
For instance, one child with Asperger syndrome was missing DNA from a stretch of 27 genes.
The findings suggest that autism spectrum disorder may involve 100 or more genes, the researchers report in Friday’s issue of the journal Science.
Experts know autism has a genetic cause, and in February the U.S. Centers for Disease Control and Prevention reported it affects about one in every 150 children.
For the study, Dr. Jonathan Sebat of the Cold Spring Harbor Laboratory in New York and colleagues across the United States, in Finland and in Britain looked at the DNA of people in 264 families.
“We performed whole-genome scans on all parents, patients and unaffected children,” the researchers wrote. New technology to sequence genes rapidly, as well as several published sequences of the human genome, have helped scientists do this in recent years.
Not a family affair
Usually, tests of DNA of people with diseases show that everyone in a family who has the disorder carries the same mutation or pattern of mutations.
But that’s not the case here. The researchers found numerous spontaneous mutations in 14 of 195 people with autism spectrum disorders compared to two of 196 unaffected people.
And of the 14 autism patients with mutations, only two had relatives with autism.
“Our results show conclusively that these tiny glitches are frequent in autism, occurring in at least 10 percent of cases, and primarily in the sporadic form of the disease, which accounts for 90 percent of affected individuals,” Sebat said in a statement.
Dr. Jeffrey Lieberman, chairman of the department of psychiatry at Columbia University Medical Center in New York, said such work does not answer one overwhelming question about autism: What causes these genetic changes in the first place?
Some advocacy groups believe an environmental factor, such as mercury, must be damaging the genes to cause autism.
“For example, if you expose cells to radiation, you can produce similar types of effects,” Lieberman, who was not involved in the study, said in a telephone interview.
“But these types of copy number variations do not (necessarily) implicate an environmental agent.”
Autism is marked by a variety of difficulties in social interaction and behavior, and range from the awkwardness of Asperger syndrome to severely debilitating repetitive behaviors and an inability to speak.
The recent studies suggest that these important abilities are scattered throughout the human genome, and that small changes anywhere can have broad effects, Lieberman said.
“This is just one piece of information that is going to add to the evolving story but more is needed,” he said.