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Science 14 December 2001:
Vol. 294. no. 5550, pp. 2364 - 2368
DOI: 10.1126/science.1065810
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Reports

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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P.-J. Kim, D.-Y. Lee, T. Y. Kim, K. H. Lee, H. Jeong, S. Y. Lee, and S. Park (2007)
PNAS 104, 13638-13642
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Analysis of Transcriptional Activation at a Distance in Saccharomyces cerevisiae.
K. C. Dobi and F. Winston (2007)
Mol. Cell. Biol. 27, 5575-5586
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Interaction of the Endocytic Scaffold Protein Pan1 with the Type I Myosins Contributes to the Late Stages of Endocytosis.
S. L. Barker, L. Lee, B. D. Pierce, L. Maldonado-Baez, D. G. Drubin, and B. Wendland (2007)
Mol. Biol. Cell 18, 2893-2903
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Coevolution of robustness, epistasis, and recombination favors asexual reproduction.
T. MacCarthy and A. Bergman (2007)
PNAS 104, 12801-12806
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BUB1 mediation of caspase-independent mitotic death determines cell fate.
Y. Niikura, A. Dixit, R. Scott, G. Perkins, and K. Kitagawa (2007)
J. Cell Biol. 178, 283-296
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Sequential and Distinct Roles of the Cadherin Domain-containing Protein Axl2p in Cell Polarization in Yeast Cell Cycle.
X.-D. Gao, L. M. Sperber, S. A. Kane, Z. Tong, A. H. Y. Tong, C. Boone, and E. Bi (2007)
Mol. Biol. Cell 18, 2542-2560
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