Systematic genetic analysis with ordered arrays of yeast deletion mutants.
In Saccharomyces cerevisiae, more than 80% of the approximately 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 approximately 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.
Tong
A H
AH
Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada M5G 1L6.
Evangelista
M
M
Parsons
A B
AB
Xu
H
H
Bader
G D
GD
Pagé
N
N
Robinson
M
M
Raghibizadeh
S
S
Hogue
C W
CW
Bussey
H
H
Andrews
B
B
Tyers
M
M
Boone
C
C
D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity; D019295:Computational Biology; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology; D004260:DNA Repair; D004271:DNA, Fungal / Q000096:biosynthesis; D030541:Databases, Genetic; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000502:physiology; D045585:Flap Endonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D020043:Genes, Essential; D005800:Genes, Fungal / Q000502:physiology*; D005819:Genetic Markers; D005821:Genetic Techniques; D016681:Genome, Fungal; D008840:Microfilament Proteins; D008868:Microtubule Proteins / Q000235:genetics / Q000502:physiology; D008938:Mitosis; D053484:RecQ Helicases; D011995:Recombination, Genetic; D012371:Robotics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology
C119683:BIM1 protein, S cerevisiae; C106463:BNR1 protein, S cerevisiae; C105191:Bni1 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D005819:Genetic Markers; D008840:Microfilament Proteins; D008868:Microtubule Proteins; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; D045585:Flap Endonucleases; C468323:RAD27 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases