New genetic mutations that are not inherited from one’s parents appear to happen more frequently in people with schizophrenia than might normally be expected in healthy individuals said a team of scientists led by Dr Guy A Rouleau from the University of Montreal in Canada. The team hopes their discovery, which includes genes not linked to schizophrenia before, will provide a list of genes for researching how the disease develops, and also lead to new treatments.
Rouleau and colleagues found the new or de novo mutations, that is genetic errors present in a person that are not present in their biological parents, when they examined about 20,000 genes in the “exomes” of 14 patients with schizophrenia and their unaffected parents. They write about their discovery in this week’s issue of Nature Genetics.
It can be very expensive to analyze the genetic code of all the genes in a human being, the “genome”, so many scientists looking for new genes behind diseases have settled on a more cost-effective method, they analyze just the “exome”, that part of the genome that expresses the genes responsible for making proteins and developing the individual as he or she grows from a fertilized egg. The exome is thought to represent less than 2% of the total genome.
The researchers note in their paper that:
“We identified 15 de novo mutations (DNMs) in eight probands [patients], which is significantly more than expected considering the previously reported DNM rate. In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance.”
Rouleau, who is also Director of the Centre Hospitalier Universitaire Sainte-Justine Research Center in Montreal, told the press their discovery that de novo mutations appear to occur more frequently in people with schizophrenia may explain the high worldwide incidence of the disease.
“Our results not only open the door to a better understanding of schizophrenia. They also give us valuable information about the molecular mechanisms involved in human brain development and function,” said Rouleau.
Simon Girard, a student at the University of Montreal Hospital Research Centre, where Rouleau also does research, carried out the main experiments behind the discovery. He explained that:
“Because the mutations are located in many different genes, we can now start to establish genetic networks that would define how these gene mutations predispose to schizophrenia.”
“Most of the genes identified in this study have not been previously linked to schizophrenia, thereby providing new potential therapeutic targets,” he added.
In 2006, Rouleau proposed that de novo mutations might play a big part in autism, schizophrenia, and other diseases that arise from factors affecting brain development.
Schizophrenia is a major mental disorder with a wide range of symptoms including disorganized speech and thinking, paranoid delusions, hallucinations, and deterioration of emotional responsiveness and social behaviours.
The World Health Organization (WHO) estimates there are 24 million people with schizophrenia worldwide, and more than 50% of them are not getting the treatment they need.
Much of the funding for the study came from Genome Canada and Génome Québec, with additional support from the Canadian Institutes of Health Research (CIHR) and the Brain and Behavior Research Foundation (formerly NARSAD, the National Alliance for Research on Schizophrenia and Depression) and the University of Montreal.
“Increased exonic de novo mutation rate in individuals with schizophrenia.”
Simon L Girard, Julie Gauthier, Anne Noreau, Lan Xiong, and others.
Nature Genetics, Published online: 10 July 2011 | doi:10.1038/ng.886.
Additional source : University of Montreal.
Written by: Catharine Paddock, PhD