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Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants
Abstract
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.
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“Synthetic genetic interaction screens in yeast123,124 have demonstrated that thousands of combinations of individually viable mutations can jointly be lethal, and similar examples have been documented in Drosophila melanogaster and Caenorhabditis elegans125,126.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [123]
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- The following supplementary material is available on Science Online at www.sciencemag.org/cgi/content/full/294/5550/2364/DC1: supplementary table 1 a table of the deletion mutants used to create the double-mutant arrays shown in Fig. 2A by SGA analysis; supplementary table 2 a table of the 4672 unique deletion mutants assembled for large-scale SGA analysis; supplementary notes a description of the materials and methods for SGA analysis and bioinformatic analysis (yeast strains will be provided upon request); supplementary table 3 a table summarizing all the synthetic lethal/fitness interactions; supplementary table 4 a table of 523 gene deletions within the array that often appeared to be synthetically lethal with a wild-type control strain; supplementary table 5 a table of the overlap of the genetic interactions presented in Fig. 3 and the published genetic interactions assembled at MIPS (Munich Information Center for Protein Sequences) and YPD; supplementary fig. 1 a figure of the protein-protein interactions corresponding to genes within the genetic-interaction network shown in Fig. 3; supplementary table 6 a table of the gene deletions that are linked to the query gene and appeared to be synthetically lethal; supplementary fig. 2 a figure that shows two-dimensional clustering analysis of synthetic lethal interactions; supplementary table 7 a table that shows an analysis of the false-positives for the BIM1 and SGS1 screens as a comparison of the list of gene deletions that were scored as positive by SGA analysis to the list of gene deletions that were ultimately confirmed to be synthetically lethal by tetrad analysis; and supplementary table 8 a table of the synthetic genetic interactions and their BIND identification numbers.
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Metadata
- Authors
- Tong, A. H. Y., Evangelista, M., Parsons, A. B., Xu, H., Bader, G. D., Pagé, N., Robinson, M., Raghibizadeh, S., Hogue, C. W. V., Bussey, H., Andrews, B., Tyers, M., & Boone, C.
- Affiliations
- University of Toronto (CA)
- Queen's University (CA)
- Mount Sinai Hospital (CA)
- McGill University (CA)
- Virtek Engineering Sciences, Inc. (VESI), 1 Bedford Road, Toronto ON, Canada M5R 2J7.
- Corresponding author
- Andrews, Brenda
- Tyers, Mike
- Boone, Charles
- ORCID
- Venue
- Science
- Published
- 2001-12-14
- Volume
- 294
- Issue
- 5550
- Pages
- 2364-2368
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2127073167
- Cited by
- 2,138
- References
- 23
- Citations by year
- 2026: 24 · 2025: 39 · 2024: 51 · 2023: 51 · 2022: 49 · 2021: 67 · 2020: 71 · 2019: 63 · 2018: 65 · 2017: 105 · 2016: 73 · 2015: 96 · 2014: 115 · 2013: 101 · 2012: 107
- FWCI
- 27.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- synthetic genetic array, yeast deletion mutants, genetic interactions, cytoskeletal organization, non-essential genes, Saccharomyces cerevisiae
- MeSH terms
- Carrier Proteins, Crosses, Genetic, Cytoskeletal Proteins, Cytoskeleton, DNA Repair, DNA Helicases, DNA, Fungal, Endodeoxyribonucleases, Fungal Proteins, Genes, Fungal, Genetic Markers, Genetic Techniques, Microfilament Proteins, Microtubule Proteins, Mitosis, Recombination, Genetic, Robotics, Saccharomyces cerevisiae, Genome, Fungal, Cell Polarity, Gene Deletion, Cell Cycle Proteins, Computational Biology, Genes, Essential, Saccharomyces cerevisiae Proteins, Databases, Genetic, Flap Endonucleases, RecQ Helicases
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