Epistasis and cryptic QTL identified using modified bulk segregant analysis of copper resistance in budding yeast.

The contributions of genetic interactions to natural trait variation are challenging to estimate experimentally, as current approaches for detecting epistasis are often underpowered. Powerful mapping approaches such as bulk segregant analysis, wherein individuals with extreme phenotypes are pooled for genotyping, obscure epistasis by averaging over genotype combinations. To accurately characterize and quantify epistasis underlying natural trait variation, we have engineered strains of the budding yeast to enable crosses where one parent's chromosome is fixed while the rest of the chromosomes segregate.

High-Throughput Live Imaging of Microcolonies to Measure Heterogeneity in Growth and Gene Expression.

Precise measurements of between- and within-strain heterogeneity in microbial growth rates are essential for understanding genetic and environmental inputs into stress tolerance, pathogenicity, and other key components of fitness. This manuscript describes a microscope-based assay that tracks approximately 10 Saccharomyces cerevisiae microcolonies per experiment. After automated time-lapse imaging of yeast immobilized in a multiwell plate, microcolony growth rates are easily analyzed with custom image-analysis software.