Removable methyl groups on specific genes of autistic individuals that led to gene silencing identified

The George Washington University Medical CenterApr 22 2010

A new study by researchers at The George Washington University School of Medicine and Health Sciences' Department of Biochemistry and Molecular Biology raises hope that autism may be more easily diagnosed and that its effects may be more reversible than previously thought. Researchers have identified potentially removable chemical tags (called "methyl groups") on specific genes of autistic individuals that led to gene silencing. They also observed these changes in cells derived from blood, opening the way to molecular screening for autism using a blood test.

Valerie Hu, Ph.D., professor of Biochemistry and Molecular Biology, with a GW graduate student and collaborators from the City of Hope, have identified chemical changes in DNA taken from cells of identical twins and sibling pairs, in which only one of the twins or siblings was diagnosed with autism. The researchers compared the genes that showed changes in DNA tagging (called "methylation") with a list of genes that showed different levels of expression (or gene "activity") from these same individuals. The amount of protein produced by two genes that appear on both lists in the cerebellum and frontal cortex of autistic and control subjects was studied, and the researchers found that both proteins, as predicted by the observed increase in DNA tagging, were reduced in the autistic brain.

These outcomes suggest that blocking the chemical tagging of these genes with drugs that prevent the methylation process may reverse symptoms of autism if the specific genes can be targeted, and demonstrate the feasibility of using more easily accessible cells from blood (or other non-brain tissues) for diagnostic screening.

"As the mother of a now 22-year-old son with an autism spectrum disorder, I hope that our studies, as well as those of others, will lead to therapies that are designed to address specific deficiencies that are caused by autism, thus improving the lives of affected individuals," said Dr. Hu. "Since autism is very diverse in the array of symptoms present in any given individual, it is first necessary to be able to identify specific deficits in each individual in order to design and then prescribe the best treatment."

The research is highlighted in the study, titled "Global Methylation Profiling of Lymphoblastoid Cell Lines Reveals Epigenetic Contributions to Autism Spectrum Disorders and a Novel Autism Candidate Gene, RORA, Whose Protein Product is Reduced in Autistic Brains," was recently published in the Federation of American Societies for Experimental Biology (FASEB) Journal.

"For far too long, autism research has been side-tracked by the cranky notion that it's caused by the MMR vaccine," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "Studies like this, which define genetic and epigenetic changes in discrete subgroups of the autism spectrum, offer real hope that effective treatments and accurate diagnosis are closer at hand."