Scientists Link Gene Abnormality to Autism

A rare chromosome abnormality increases the risk of developing autism by about 100 times, a new study finds.

Researchers at Massachusetts General Hospital in Boston found that a tiny segment of chromosome 16 is missing or duplicated in about 1 percent of children with autism. Autism experts hope the finding could someday lead to the development of a genetic test that will help parents determine their risk of having a child with autism.

"By identifying more of these underlying causes of the disorder, eventually what will happen is a biotech company or academic researcher will be able to put a lot of these genes on micro array chips -- a mechanism by which you can simultaneously look at many different genes -- so we can screen for the risk of having an autistic child," said Dr. Peter Hotez, professor and chairman of the department of microbiology, immunology and tropical medicine at George Washington University.

Using data collected from the Autism Genetic Resource Exchange, researchers analyzed the genetic tests of 751 families with one or more autistic children. They found that five of the people with autism had an area on chromosome 16 that was missing genetic information -- a phenomenon known as a deletion.

In all five of these cases, the parents of the child with autism did not have the deletion, suggesting that the abnormality was not inherited but rather occurred spontaneously.

To confirm this finding, researchers examined nearly 1,000 patients at Children's Hospital Boston, about half of whom had been diagnosed with autism or a similar developmental delay disorder. Among those who were diagnosed with such a disorder, five had the same deletion. Moreover, four children were found to have a separate abnormality at the same region of the chromosome -- specifically, a duplication of these genes.

Researchers did not find these abnormalities in any of the patients they studied who did not have autism or a similar disorder, further reinforcing the idea that these genetic abnormalities were specific to those with such disorders.

Missing Genes Linked to Brain Function

The human genome is a vast compendium of information; scientists currently estimate that it comprises at least 20,000 separate genes -- the bits of genetic information that spell the language of the human blueprint.

This figure dwarfs the random deletions the researchers found on chromosome 16 -- a total loss of about 25 genes. But because many of these genes are associated with brain function, brain development, behavior and other factors, doctors believe these few genes could be key in the development of autism.

"The study … supports the general notion that large, spontaneous deletions and duplications contribute to the molecular causes of autism," Evan Eichler, associate professor of genome sciences at the University of Washington, wrote in the study's editorial.

And as rare as these particular deletions appear to be, they seem to dramatically affect the chances of developing autism for the few who have these abnormalities. Researchers found that only about one in 10,000 normal people have the abnormality on chromosome 16, while one in 100 people with autism do -- suggesting that the deletion on chromosome 16 raises autism risk by roughly 100 times.

Mark Daly, senior author of the study and assistant professor of medicine at Massachusetts General Hospital, said that while this abnormality does not mean a person is definitely going to develop autism, it appears to raise the risk substantially.

"As with just about every genetic mutation, not everyone who inherits the mutation gets a specific or conclusive diagnosis of autism," Daly explained. "This speaks to the fact that genetics never works in deterministic fashion -- it's a product of many genes in the genome acting simultaneously, plus external and environmental factors playing a role."

This study is not the first to draw a link between abnormalities on chromosome 16 and autism. Researchers at the University of Chicago led by Dr. Edwin Cook, associate professor of psychiatry and pediatrics, first made this association in a study published in the Dec. 21, 2007, issue of the journal Human Molecular Genetics.

"[This study] doesn't change that we already know that autism is more genetic than environmental, but it does contribute to our specific knowledge of what specific variants on what specific genes may contribute [to autism]," Cook explained. "These studies represent the incremental work necessary to explain the complex nature of the estimated 90 percent causation of autism attributed to genetics."

However, researchers for this latest study also found that this so-called "hot spot" in the human genome for spontaneous deletion and duplication on chromosome 16 is also likely to be associated with clinical manifestations beyond autism. Other disorders associated with this chromosome abnormality include mental retardation and multiple congenital abnormalities.

"New technologies that are allowing geneticists to study very small deletions and duplications in the genome are finding out that this kind of variation is the cause of some diseases and disorders," said Geraldine Dawson, chief science officer of the autism advocacy group Autism Speaks.

"Genetics will now begin to examine the genes that are located in this region of chromosome 16 … If we can isolate the specific genes in this region of chromosome 16 that [are] related to autism, this will be an important step toward understanding the biological basis of the disorder, which is necessary for developing medical treatments."