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Girls May Be More Resistant to Autism Than Boys: Study
Date:6/8/2011

By Jenifer Goodwin
HealthDay Reporter

WEDNESDAY, June 8 (HealthDay News) -- Girls may be more resistant to the spontaneous genetic mishaps that explain some cases of autism in families with no history of the disorder, two new studies suggest.

Everyone carries a certain number of duplications or deletions of one or more sections of DNA, something known as copy number variants, explained Dr. Christian Schaaf, an assistant professor in the department of molecular and human genetics at the Baylor College of Medicine, who wrote an accompanying editorial. If you accumulate enough of them, and the duplications and deletions occur on certain important areas of the chromosomes, those variants may lead to autism and other conditions.

In the studies, published in the June 9 issue of Neuron, researchers searched copy number variants in genetic samples from more than 1,000 families with an autistic child who were recruited as part of the Simons Simplex Collection project.

Autism spectrum disorders are neurodevelopmental conditions marked by impaired social interaction and communication, unusual interests, repetitive behaviors and, in some cases, intellectual disability.

In cases where only one child in a family is affected, it has been difficult to pinpoint new copy number variants. Researchers believed that was because the available technology did not allow them to view the genetic material at a high enough resolution to see what had gone wrong, Schaaf said.

The new studies made use of newer, high resolution array analysis to seek out copy number variants that differed between the child with autism and the parents and siblings without autism.

"Before, it was like looking at the map of the United States. There was good enough resolution to tell the states and the big cities," Schaaf explained. "Now, the resolution is so much higher, you can look at individual streets."

They were searching such "streets" for the genetic mutations that lead to autism spectrum disorder in "simplex" cases -- those in which only one sibling is diagnosed with the disorder -- which researchers have long thought may be different from those that lead to multiplex cases. "Multiplex" means that more than one child in a family has the disorder and that the condition seems to be inherited.

In simplex cases, it's thought that new variants -- known to scientists as "de novo" variants -- arise spontaneously when the child is conceived and are to blame for the autism disorder, as opposed to variants that are passed from one generation to the next.

The presumption was that by using a higher resolution technology, researchers would turn up more copy number variants, said Andy Shih, vice president of scientific affairs for Autism Speaks.

But researchers didn't find a remarkable increase. In the study, led by researchers at Cold Spring Harbor Laboratory in New York, researchers found de novo events in 8 percent of children with an autism spectrum disorder, compared to 2 percent of the unaffected siblings.

That's relatively consistent with other work in which the range is anywhere from 7 to 20 percent, said Schaaf said, who added that the studies did confirm that children with autism carry de novo copy number variants at a higher frequency than their parents and unaffected siblings.

The researchers also made some intriguing discoveries. In this study and a second one led by scientists at Yale University, researchers found that children with autism were more likely to have copy number duplications on an area of Chromosome 7 known as 7q11.23.

Prior research has shown that deletions on 7q11.23 is associated with Williams or Williams-Beuren Syndrome, a rare disorder in which children are hypersocial and have no inhibitions about talking to strangers, as well as cardiovascular disease and developmental delays.

"That's really interesting," Schaaf said. "It appears when you're missing a little bit, you are too social, and when you have too much, you are anti-social."

In addition, it's been well-documented that boys are at least four times more likely to have autism than girls, and the new research hints at why this may be.

The study led by the Cold Spring Harbor Laboratory researchers found that girls with autism are more likely to have detectable de novo "events," that is, larger copy number variants and more genes involved in the deletions or duplications.

This suggests that it takes more, genetically speaking, to cause girls to have autism.

"It seems to take more hits or more damage to the genome to lead to autism in girls than in boys," Shih said. "That may start to explain some of the sex biases, that boys are more vulnerable genetically."

Interestingly, Schaaf added, most of the autistic kids in the Simons Simplex Collection were relatively high-functioning, Schaaf said. Among high-functioning autistic people, there's an even greater gender difference, he noted.

Still, much is unknown, including what might make boys more susceptible, Schaaf added.

In addition, the research does little to explain the vast majority of autism cases. Prior research has shown that about 5 percent to 7 percent of autism cases can be explained by a single gene disorder. Another 5 percent seems to be caused by metabolic conditions that affect brain function.

De novo copy number variants explain anywhere from 7 percent to 20 percent of autism cases with no known cause. But for the other 70-plus percent, there is no genetic explanation.

"It doesn't mean we'll [never] know the risk factors for the other 70 percent. Some could be environmental, some could be other genetic mechanism not yet discovered or that our current technology doesn't allow us to identify," Shih said.

It seems, he added, that "we are fast approaching the limitation of this particular technology."

More information

Find out more about autism spectrum disorders at the U.S. Centers for Disease Control and Prevention.

SOURCES: Christian P. Schaaf, M.D., Ph.D., assistant professor, department of molecular and human genetics, Baylor College of Medicine, Houston; Andy Shih, Ph.D., vice president, scientific affairs, Autism Speaks; June 9, 2011, Neuron


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