title: Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
abstract: Complex traits typically involve the contribution of multiple gene variants. In this study, we took advantage of a high-density genotyping analysis of the BY (S288c) and RM strains of Saccharomyces cerevisiae and of 123 derived spore progeny to identify the genetic loci that underlie a complex DNA repair sensitivity phenotype. This was accomplished by screening hybrid yeast progeny for sensitivity to a variety of DNA damaging agents. Both the BY and RM strains are resistant to the ultraviolet light-mimetic agent 4-nitroquinoline 1-oxide (4-NQO); however, hybrid progeny from a BYxRM cross displayed varying sensitivities to the drug. We mapped a major quantitative trait locus (QTL), RAD5, and identified the exact polymorphism within this locus responsible for 4-NQO sensitivity. By using a backcrossing strategy along with array-assisted bulk segregant analysis, we identified one other locus, MKT1, and a QTL on Chromosome VII that also link to the hybrid 4-NQO-sensitive phenotype but confer more minor effects. This work suggests an additive model for sensitivity to 4-NQO and provides a strategy for mapping both major and minor QTL that confer background-specific phenotypes. It also provides tools for understanding the effect of genetic background on sensitivity to genotoxic agents.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Demogines
authors.forename: Erin
authors.initials: E
authors.lastname: Smith
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
authors.forename: Eric
authors.initials: E
authors.lastname: Alani
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000187:drug effects / Q000235:genetics; D003433:Crosses, Genetic; D004249:DNA Damage / Q000187:drug effects; D004265:DNA Helicases; D004260:DNA Repair / Q000187:drug effects*; D008040:Genetic Linkage; D016681:Genome, Fungal; D008826:Microbial Sensitivity Tests; D009153:Mutagens / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D019655:Quantitative Trait, Heritable; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013172:Spores, Fungal / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: C092218:MKT1 protein, S cerevisiae; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D015112:4-Nitroquinoline-1-oxide; D000251:Adenosine Triphosphatases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases