Researchers discover important genetic flaw in family affected by schizophrenia

Work published in Journal of Medical Genetics indicates break may lead to an understanding of an important piece of the puzzle

Researchers at the University of Alberta have discovered a genetic flaw in a family suffering with schizophrenia that may help to explain an important biochemical process implicated in the onset of the disease.
Studying a British mother and daughter, the researchers discovered that both were found to have a “break” in a large gene on human chromosome 14, due to a rearranged chromosome.

The broken gene is a member of a family of similar genes affecting brain development and function. The genes in this group are involved in behaviour, memory and regulating day/night cycles.

“The fact that these genes–important in brain development and behaviour–are broken, cuts off important functions of the corresponding protein, particularly the ability to bind to DNA. Binding to DNA is an important way proteins can control the expression of other genes,” says Professor Diane Cox, Chair of the Medical Genetics Department. “We believe this gene has all the features expected for a gene contributing to mental illness in this family.”

Under the supervision of Dr. Cox, the work was conducted by PhD graduate student, Deepak Kamnasaran, and is published in the May issue of the Journal of Medical Genetics, entitled Disruption of the neuronal PAS3 gene in a family affected with schizophrenia.

Dr. Cox points out that schizophrenia is a complex disease and many genes are likely associated with its cause and development. “Our work isn’t the whole story, but it helps us put in place a key piece of the puzzle that we can further explore.”

The authors include: Dr. Kamnasaran (former University of Alberta graduate student, now a postdoctoral fellows at The Hospital for Sick Children, Toronto); Dr. Walter Muir (psychiatrist, Royal Edinburgh Hospital); Professor Malcolm Ferguson-Smith (Centre for Veterinary Science, Cambridge); and Dr. Cox (Medical Genetics, University of Alberta).

Funding for the work was provided by the March of Dimes (USA) and studentships to Dr. Kamnasaran from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research.

Schizophrenia is a biochemical brain disorder characterized by delusions, disordered thinking, hallucinations and a lack of motivation and energy. One in every 100 people in Canada is affected; it usually strikes between the ages of 15 and 25.

The U of A in Edmonton, Alberta is one of Canada’s premier teaching and research universities serving more than 33,000 students with 6,000 faculty and staff. It continues to lead the country with the most 3M Teaching Fellows, Canada’s only national award recognizing teaching excellence.