Synthetic Genetic Array Analysis in <I>Saccharomyces cerevisiae</I>

TLDR

Synthetic lethality arises when two mutations together kill the organism, and screens for such interactions have been widely used to identify genes that buffer each other or share essential pathways. The authors developed Synthetic Genetic Array (SGA) analysis to systematically construct double mutants and globally analyze synthetic lethal interactions in *Saccharomyces cerevisiae*. In a typical SGA screen, a query mutation is crossed to an ordered array of ~5,000 viable gene deletions (~80 % of yeast genes) so that meiotic progeny carrying both mutations are scored for fitness defects, automating genetic analysis and enabling adaptation to screens such as suppression or dosage lethality.

Abstract

Synthetic lethality occurs when the combination of two mutations leads to an inviable organism. Screens for synthetic lethal genetic interactions have been used extensively to identify genes whose products buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed Synthetic Genetic Array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic lethal genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of approx 5000 viable gene deletion mutants (representing ∼80% of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different screens, including genetic suppression, plasmid shuffling, dosage lethality, or suppression.