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Science 294 (5550): 2364-2368

Copyright © 2001 by the American Association for the Advancement of Science

Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants

Amy Hin Yan Tong,12 Marie Evangelista,3 Ainslie B. Parsons,12 Hong Xu,12 Gary D. Bader,45 Nicholas Pagé,6 Mark Robinson,1 Sasan Raghibizadeh,7 Christopher W. V. Hogue,45 Howard Bussey,6 Brenda Andrews,2* Mike Tyers,25* Charles Boone123*

In Saccharomyces cerevisiae, more than 80% of the ~6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of ~4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

1 Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada M5G 1L6.
2 Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON, Canada M5S 1A8.
3 Biology Department, Queens University, Kingston ON, Canada K7L 3N6.
4 Department of Biochemistry, University of Toronto, Toronto ON, Canada M5S 1A8.
5 Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto ON, Canada M5G 1X5.
6 Department of Biology, McGill University, Montreal PQ, Canada H3A 1B1.
7 Virtek Engineering Sciences, Inc. (VESI), 1 Bedford Road, Toronto ON, Canada M5R 2J7.
*   To whom correspondence should be addressed. E-mail: brenda.andrews{at}utoronto.ca, tyers{at}mshri.on.ca, and charlie.boone{at}utoronto.ca

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Pandora, a PAthway and Network DiscOveRy Approach based on common biological evidence.
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The Genetic Landscape of a Cell.
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Science 327, 425-431
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Cytoplasmic protein quality control degradation mediated by parallel actions of the E3 ubiquitin ligases Ubr1 and San1.
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Systems cell biology of the mitotic spindle.
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Integrating high-throughput genetic interaction mapping and high-content screening to explore yeast spindle morphogenesis.
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