The genetic architecture in Saccharomyces cerevisiae that contributes to variation in drug response to the antifungals benomyl and ketoconazole.
FEMS Yeast Res
; 17(3)2017 05 01.
Article
em En
| MEDLINE
| ID: mdl-28472279
ABSTRACT
The genetic basis of variation in drug response was investigated in individual Saccharomyces cerevisiae strains that exhibited different susceptibility to two antifungal agents benomyl and ketoconazole. Following dose-response screening of 25 strains, 4 were selected on the basis of resistance or sensitivity relative to the standard laboratory strain BY. UWOPS87-2421 and L-1374 were respectively resistant and sensitive to benomyl; DBVPG6044 and Y12 were respectively resistant and sensitive to ketoconazole. We used advanced intercross lines and next generation sequencing-bulk segregant analysis to characterise the quantitative trait loci (QTL) underpinning drug responses after drug selection. Drug response was controlled by multiple QTL, ranging from a minimum of 5 to a maximum of 60 loci, almost all of which were not the primary drug target. For each drug, the resistant and the sensitive strain exhibited a number of shared loci, but also had strain-specific QTL. In our analysis, it was possible to estimate genetic effect of QTL, and a number of those shared between resistant and sensitive strains exhibited variable effect on the response phenotype. Thus, drug responses arise as a result of different genetic architectures, depending on the genetic background of the individual strain in question.
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MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Benomilo
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Farmacorresistência Fúngica
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Locos de Características Quantitativas
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Cetoconazol
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Antifúngicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article