identification and dissection of a complex dna repair sensitivity phenotype in bakers yeast识别和解剖复杂的dna修复敏感的表型在面包酵母.pdfVIP

Identification and Dissection of a Complex DNA Repair Sensitivity Phenotype in Baker’s Yeast 1 2,3¤ 2,3 1 Ann Demogines , Erin Smith , Leonid Kruglyak , Eric Alani * 1 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America, 2 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America, 3 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America 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 BY 6RM 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