Genetic Basis of Haloperidol Resistance in Is Complex and Dose Dependent

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Variation in response to a drug can be determined by many factors. In the model organism baker's yeast, many studies of chemical resistance traits have uncovered a complex genetic basis of such resistance. However, an in-depth study of how drug dose alters the effects of underlying genetic factors is lacking. Here, we employed linkage analysis to map the specific genetic loci underlying response to haloperidol, a small molecule therapeutic drug, using a large panel of segregants from a cross between two genetically divergent yeast strains BY (a laboratory strain) and RM (a vineyard strain). We found that loci associated with haloperidol resistance are dose-dependent. We also showed that variants in the oxysterol-binding-protein-like domain of the gene SWH1 underlie the major locus detected at all doses of haloperidol. Genetic interactions among genes SWH1, MKT1, and IRA2 in the RM background contribute to the differential response at high concentrations of haloperidol.

Vyšlo v časopise: Genetic Basis of Haloperidol Resistance in Is Complex and Dose Dependent. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004894
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004894

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