Yeast mutations offer window into human disease
Different combinations of genetic mutations may give rise to diverse human traits, including complex diseases such as schizophrenia, say scientists at the University of Toronto and McGill University in Montreal.
Drs. Brenda Andrews and Charles Boone of U of T and Howard Bussey of McGill used simple yeast cells to demonstrate that there are many different combinations of genetic mutations that can lead to cell death or reduced cell fitness. The research team will now focus on mapping gene interactions for those yeast genes that are similar to human genes. Their study appears in the Feb. 6 issue of the journal Science.
The researchers crossed a yeast strain carrying a mutation in a particular gene of interest with a collection or “array” of other yeast strains to determine which gene pairs were lethal. The team studied more than 4,000 of these interactions involving gene pairs and was able to provide a large scale “genetic interaction network” that provokes new ideas about how genes interact to produce different traits.
For example, the researchers determined that genes arrange themselves in “neighbourhoods” or small networks. A gene is more likely to interact with its “neighbour,” they discovered, than with more distant genes. Each yeast gene has on average about 30 of these interactions over the life of a cell, many more than had been predicted by previous experiments. By understanding the composition of these genetic “neighbourhoods,” it is possible to predict which genes will interact and which traits will result when two genes combine.
“Constructing these networks will help human geneticists to focus their research on the culprits of disease,” says Andrews, chair of U of Ts medical genetics and microbiology department. “If we can begin to construct these kinds of networks in an intelligent way, we might directly accelerate the discovery of those genes that are lethal when combined.”
The study has sparked interest among other researchers in developing techniques for mapping the genetic “neighbourhoods” of more complex organisms.
“Because our global genetic network studies map out how cells work, these studies have implications that may help us in understanding the foundation of complex inherited diseases, such as glaucoma, type II diabetes and schizophrenia,” says Bussey, a professor in McGills biology department.
The studys lead authors are Amy Hin Yan Tong, a U of T graduate student in the molecular and medical genetics department, and Guillaume Lesage, a post-doctoral student at McGill. The international team included researchers at Harvard Medical School, Cornell University, the University of Pennsylvania, the University of California, the Institute of Biochemistry in Zurich, Switzerland, MRC Laboratory in Cambridge, England, and Memorial Sloan-Kettering Cancer Center in New York.
The study received funding from the Canadian Institutes of Health Research, the Canadian Foundation for Innovation and Genome Canada through the Ontario Genomics Institute and Genome Quebec.
NOTE: A photo of researcher Tong with robotics equipment used in the research may be obtained from Elaine Smith at U of T.
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