Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.

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 r...

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Main Authors: Ann Demogines, Erin Smith, Leonid Kruglyak, Eric Alani
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-07-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC2440805?pdf=render
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author Ann Demogines
Erin Smith
Leonid Kruglyak
Eric Alani
author_facet Ann Demogines
Erin Smith
Leonid Kruglyak
Eric Alani
author_sort Ann Demogines
collection DOAJ
description 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.
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spelling doaj.art-dd26f7efef3646c2b73c56ad63ea65fd2022-12-22T01:11:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-07-0147e100012310.1371/journal.pgen.1000123Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.Ann DemoginesErin SmithLeonid KruglyakEric AlaniComplex 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.http://europepmc.org/articles/PMC2440805?pdf=render
spellingShingle Ann Demogines
Erin Smith
Leonid Kruglyak
Eric Alani
Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
PLoS Genetics
title Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
title_full Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
title_fullStr Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
title_full_unstemmed Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
title_short Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.
title_sort identification and dissection of a complex dna repair sensitivity phenotype in baker s yeast
url http://europepmc.org/articles/PMC2440805?pdf=render
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