title: A noncomplementation screen for quantitative trait alleles in saccharomyces cerevisiae.
abstract: Both linkage and linkage disequilibrium mapping provide well-defined approaches to mapping quantitative trait alleles. However, alleles of small effect are particularly difficult to refine to individual genes and causative mutations. Quantitative noncomplementation provides a means of directly testing individual genes for quantitative trait alleles in a fixed genetic background. Here, we implement a genome-wide noncomplementation screen for quantitative trait alleles that affect colony color or size by using the yeast deletion collection. As proof of principle, we find a previously known allele of CYS4 that affects colony color and a novel allele of CTT1 that affects resistance to hydrogen peroxide. To screen nearly 4700 genes in nine diverse yeast strains, we developed a high-throughput robotic plating assay to quantify colony color and size. Although we found hundreds of candidate alleles, reciprocal hemizygosity analysis of a select subset revealed that many of the candidates were false positives, in part the result of background-dependent haploinsufficiency or second-site mutations within the yeast deletion collection. Our results highlight the difficulty of identifying small-effect alleles but support the use of noncomplementation as a rapid means of identifying quantitative trait alleles of large effect.
authors.affiliation: Department of Genetics, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Juyoung
authors.initials: J
authors.lastname: Huh
authors.forename: Linda
authors.initials: L
authors.lastname: Riles
authors.forename: Alejandro
authors.initials: A
authors.lastname: Reyes
authors.forename: Justin C
authors.initials: JC
authors.lastname: Fay
mesh_terms: D000483:Alleles; D002374:Catalase / Q000235:genetics; D003541:Cystathionine beta-Synthase / Q000235:genetics; D005816:Genetic Complementation Test; D057898:Hemizygote; D009154:Mutation; D010641:Phenotype; D040641:Quantitative Trait Loci; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D002374:Catalase; D003541:Cystathionine beta-Synthase