Decoding Autism: Study finds DNA clues to developmental disorders

New results from the largest study of its kind direct the search for autism-influencing genes to a previously overlooked DNA segment and highlight the role of a crucial chemical-messenger system in creating brains susceptible to autism.

Genetic analyses of 1,168 families, each containing two or more persons with autism or a related condition, indicate that as-yet-unidentified genes on part of chromosome 11 often contribute to the developmental disorders. A group of more than 120 scientists in 19 countries report the findings online and in the March Nature Genetics. Previous studies of fewer people with autism (SN: 10/21/06, p. 259: Autism’s DNA Trail: Gene variant tied to developmental disorder) had identified a potential autism gene but missed the genetic link to chromosome 11.

That DNA location and several others linked to autism in the new study harbor genes for proteins that shuttle glutamate among brain cells. That chemical messenger stimulates neural activity and influences brain development.

Report coauthors Bernie Devlin of the University of Pittsburgh and Stephen W. Scherer of the University of Toronto and others now plan to look for links between variants of glutamate-related genes and autism in the families.

“It is likely that a number of autism genes will be identified in the next couple of years,” says psychiatrist and study coauthor Joachim Hallmayer of Stanford University.

The new data reveal autism-linked chromosome alterations in 7 to 12 percent of the families, depending on whether the disorder was defined narrowly or broadly. These DNA modifications included deletions and repeated short sequences.

In one family, for instance, only individuals with autism displayed a particular deletion on a chromosome 2 gene known as neurexin 1. Other studies have indicated that neurexin 1 fosters glutamate’s movement from one brain cell to another.

Boys display autism and other developmental disruptions of language and social relations far more often than girls do. Consequently, earlier genetic studies of autism had focused on boys. In the new study, more than one-third of the families included girls diagnosed with these disorders.

When the analysis included families with affected girls, the evidence linking genes on chromosome 11 and in other DNA areas to autism became much stronger than when only affected boys were considered.

Neuroscientist Matthew Belmonte of Cornell University regards the new chromosome 11 finding as “especially interesting.” Much evidence had already indicated that females who develop autism have, on average, more of the known genetic and environmental risks for the disorder than males do, he notes. So, males seem more susceptible to autism.

The chromosome 11 region identified in the new study deserves scrutiny for genes that contribute to autism, particularly in girls, Belmonte says.

The autism-related deletion in the neurexin 1 gene, although limited to one family in the new study, should be explored in further investigations, he adds. Increasing evidence suggests that variations in a family of genes that includes neurexin 1 disturb the delicate balance between substances that amplify and quell neural activity as the brain grows. Belmonte suggests that the resulting neural imbalance may trigger patterns of brain development that foster autism.