Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants

TLDR

In *Saccharomyces cerevisiae*, over 80 % of the ~6,200 predicted genes are nonessential, indicating a genome buffered against phenotypic effects of genetic perturbation. The authors developed synthetic genetic array (SGA) analysis to systematically evaluate gene function by crossing a query mutation with an array of ~4,700 deletion mutants. SGA constructs double mutants by meiotic crossing; inviable progeny reveal functional relationships, and the approach is intended to generate a global map of gene function. Applying SGA to cytoskeletal, DNA repair, and uncharacterized genes identified 291 interactions among 204 genes.

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.