Fast Breaking Comment by Charles Boone

Charles Boone answers a few questions about this month's fast breaking paper in the field of Molecular Biology & Genetics.

From •>>December 2004

Field: Molecular Biology & Genetics
Article Title: Global mapping of the yeast genetic interaction network
Authors: Tong, AHY;Lesage, G;Bader, GD;Ding, HM;Xu, H;Xin, XF;Young, J;Berriz, GF;Brost, RL;Chang, M;Chen, YQ;Cheng, X;Chua, G;Friesen, H;Goldberg, DS;Haynes, J;Humphries, C;He, G;Hussein, S;Ke, LZ;Krogan, N;Li, ZJ;Levinson, JN;Lu, H;Menard, P;Munyana, C;Parsons, AB;Ryan, O;Tonikian, R;Roberts, T;Sdicu, AM;Shapiro, J;Sheikh, B;Suter, B;Wong, SL;Zhang, LV;Zhu, HW;Burd, CG;Munro, S;Sander, C;Rine, J;Greenblatt, J;Peter, M;Bretscher, A;Bell, G;Roth, FP;Brown, GW;Andrews, B;Bussey, H;Boone, C
Journal: SCIENCE
Volume: 303
Page: 808-813
Year: FEB 6 2004
* Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada.
* Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada.
* Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada.
* McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
* Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA.
* Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
* Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
* Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
* Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
* Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
* MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
* ETH Honggerberg, Inst Biochem, CH-8093 Zurich, Switzerland.

Why do you think your paper is highly cited?

“Our paper provides the first large-scale view of genetic interactions in eukaryotic cells.”

The paper is highly cited because it contains a compendium of synthetic lethal genetic interaction data, which provides the first view of the topology of genetic interaction networks. We found that synthetic genetic interactions are very common, suggesting that digenic interactions may underlie many inherited phenotypes associated with individuals in an outbred population.

Does it describe a new discovery or a new methodology that's useful to others?

Our paper provides the first large-scale view of genetic interactions in eukaryotic cells. It exploits a new method called Synthetic Genetic Array (SGA) analysis and the collection of yeast deletion mutants to automate yeast genetics. We demonstrate that synthetic lethal genetic interactions tend to occur amongst functionally related genes and thus can be used to define gene function. More specifically, genes that show similar patterns of genetic interactions may encode components of the same pathway or complex.

Could you summarize the significance of your paper in layman's terms?

The comprehensive identification of genetic interactions will create a wiring diagram of functional relationships amongst all the components of the cell.

How did you become involved in this research?

We have used yeast genetics to explore conserved biological processes in our laboratories for many years. We were inspired to undertake a large-scale genetic interaction project by other functional genomics approaches applied to yeast cells, e.g., visualization of global gene expression changes by microarray analysis, large-scale mapping of protein-protein interactions by two-hybrid analysis, and the construction and phenotypic profiling of a complete set of gene deletion mutants.

Professor Charles Boone
Banting and Best Department of Medical Research
and Department of Medical Genetics and Microbiology
University of Toronto
Toronto, Ontario, Canada

ESI Special Topics, December 2004
Citing URL - http://www.esi-topics.com/fbp/2004/december04-CharlesBoone.html