ArticlePLoS genetics2014
Genetic basis of haloperidol resistance in Saccharomyces cerevisiae is complex and dose dependent.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
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- Independently evolved pollution resistance in four killifish populations is largely explained by few variants of large effect.Evolutionary applications · 2024Article
- Genome instability footprint under rapamycin and hydroxyurea treatments.PLoS genetics · 2023Article
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- Silver(I) Coordination Polymers: Photocatalytic Properties and Enhanced Treatment Activity of Haloperidol on Children Tic Disorder by Regulating Neurotransmitter Content.Journal of fluorescence · 2020Article
- Pooled analysis of radiation hybrids identifies loci for growth and drug action in mammalian cells.Genome research · 2020Article
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- Genomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding Yeast.Antimicrobial agents and chemotherapy · 2019Article
- The Genetic Basis of Mutation Rate Variation in Yeast.Genetics · 2019Article
- Resolving the Complex Genetic Basis of Phenotypic Variation and Variability of Cellular Growth.Genetics · 2017Article
- Identification of Nitrogen Consumption Genetic Variants in Yeast Through QTL Mapping and Bulk Segregant RNA-Seq Analyses.G3 (Bethesda, Md.) · 2017Article
- Population perspectives on functional genomic variation in yeast.Briefings in functional genomics · 2016Review
- The complex genetic and molecular basis of a model quantitative trait.Molecular biology of the cell · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain) and RM11_1a (a vineyard strain), to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance.
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