Chemical changes to DNA called methylation appear to play a role in autism, according to researchers at City of Hope and George Washington University Medical Center in Washington, D.C. The research, published in the August issue of the Federation of American Societies for Experimental Biology Journal, also found a new gene that appears to be linked to the disorder.

Gerd Pfeifer, right, and his former postdoctoral fellow, Tibor Rauch. (Photo by Paula Myers)

Gerd P. Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology, collaborated with George Washington University’s AnhThu Nguyen, a graduate student and the study’s lead author, and Valerie W. Hu, Ph.D., professor of biochemistry and molecular biology and senior author on the study. The team studied DNA within certain immune system cells, called lymphoblastoid cells, taken from autism patients, and compared it to DNA from the patients’ identical twins and other siblings who did not have autism. Specifically, they looked for differences in methylation patterns between those who had autism and those who did not.

Cells use methylation to control gene activity. Methylation amounts to adding knobs or caps to the surface of DNA that can stop cells from reading and translating parts of the genetic code. It has been implicated in diseases from cancer to diabetes.

This type of gene control falls under the title of epigenetics, a rapidly growing field of study that examines changes to DNA and chromosomes that can be inherited but that are not a part of the actual genetic code. Pfeifer is a renowned expert in epigenetics and, in particular, finding methylation patterns associated with cancer and other diseases.

The researchers found many genes previously linked to autism were methylated differently in the two groups, suggesting that epigenetic gene control plays a role in the disorder.

According to Pfeifer, chair of the Department of Cancer Biology at City of Hope, the study results further suggest that widespread disruption of gene control mechanisms contributes to autism.

“The genes with differing methylation between autistic and nonautistic people have a broad array of functions,” he explained. “The changes in their methylation lead to changes in gene expression and could throw the entire system out of balance.” That imbalance could lead to autism.

The researchers also found methylation differences in a gene called retinoic acid-related orphan receptor alpha, or RORA.

“This is the first time RORA has been linked to autism,” Pfeifer said.

RORA and another gene, called BCL2, which also showed altered methylation, appeared to be less active in autistic patients. This direct link between altered methylation and lowered gene activity leads the researchers to believe that lymphoblastoid cells might serve as an effective laboratory model to study autism, a complex disorder with no current model in the lab. This, in turn, could help researchers find drugs or other therapies to counter the epigenetic changes that may lead to autism as well as ways to diagnose the disorder.

Tibor Rauch, Ph.D., formerly a postdoctoral fellow in Pfeifer’s lab, also contributed to the study, which was supported by grants from Autism Speaks and the National Institutes of Health.