Autism may arise from a mixture of sources that include a few genes and epigenetics

Sep 8 2004

Autism, a serious developmental disorder in children, may arise from a mixture of sources that include a few genes and alterations in the factors that regulate genes (epigenetics) that may be inherited or occur as a new event, said researchers from Baylor College of Medicine.

“This new model represents a new kind of complexity in understanding this puzzling disease,” said Dr. Arthur Beaudet, senior author on the paper and chair of the BCM department of molecular and human genetics. It could also explain the difficulty in identifying genes that cause autism. The report appears online in the American Journal of Medical Genetics.

Autism usually appears by age 3. The result of a neurological disorder, it affects the child’s ability to interact and communicate with other people on both a verbal and non-verbal level.

Beaudet and his colleagues theorize that only a few genes – one of them the cause of Angelman syndrome – are involved. However, the factors acting on these genes are complex, resulting in a puzzle that is difficult to unravel.

There are currently two schools of thought on the cause of autism. One group thinks that 10 or more genes may be involved. Another thinks only a few may cause the disease.

The fact that genes are involved is obvious. Studies of twins showed that identical twins, who share the same DNA, are much more likely to share the diagnosis of autism than fraternal twins, whose DNA is different.

Based on a series of experiments, Beaudet and his colleagues theorize that epigenetic and genetic factors can cause autism by abnormal alterations in the regulation of two or more principal genes. The gene for Angelman syndrome is the strongest candidate known for one of these genes. This defective regulation that may or may not include a mutation in the genes themselves may occur through inheritance or arise newly in the person with the disorder.

In some cases of autism, duplications of DNA in the area of the Angelman gene that were inherited from the mother resulted in the disease. However, children who inherited the same kind of duplication from the father did not have the disease. In a study of brain tissue from 17 people with autism, Beaudet and his colleagues found one in which a control region of the gene implicated in Angelman syndrome had acquired a chemical change called DNA methylation.

Beaudet said that his model is consistent with data about the disease and presents fresh perspectives on autism. He hopes researchers will challenge and test it in the laboratory and clinic.

“We believe that this model is highly likely to apply to some small fraction of autism cases, but more importantly and more speculatively, we propose that it will explain the majority of cases of autism.

Others who participated in the research include Drs. Yong-hui Jiang, Trilochan Sahoo, Dani Bercovich, Jan Bressler, Catherine D. Kashork, Qian Liu, Lisa G. Shaffer and David W. Stockton of BCM, Dr. Richard S. Spielmanof the University of Pennsylvania School of Medicine and Drs. Roger E. Stevenson, Ron C. Michaelis, and Richard J. Schroer of the Greenwood Genetic Center in Greenwood, South Carolina.