Figure 1

Flowchart of the synthetic genetic array-based method for identifying CFTR-ΔF508 modifier genes. The (a) Matα yor1ΔF haploid strain, which presents an intermediate level of oligomycin sensitivity between that of Yor1 null mutants and wild-type Yor1, is robotically crossed with a collection of (b) Mata haploid strains that are deleted for every single yeast gene. Then sporulation of the resulting diploids is induced and the haploid double mutants are robotically selected and (c) their level of resistance to oligomycin assessed. An increased (yor1ΔF, geneYΔ double mutant) or decreased (yor1ΔF, geneZΔ double mutant) resistance to oligomycin indicates genetic interaction between yor1ΔF and the corresponding gene deletion, thereby highlighting yor1ΔF modifier genes. These yeast genes reveal potential human modifier genes of CFTR-ΔF508, which then require further validation in human cells expressing CFTR-ΔF508.