Pharmacogenomics: candidate gene identification, functional validation and mechanisms.
Pharmacogenetics is the study of the role of inheritance in variation in drug response phenotypes. Those phenotypes can range from life-threatening adverse drugs reactions at one end of the spectrum to equally serious lack of therapeutic efficacy at the other. Over the past half century, pharmacogenetics has--like all of medical genetics--evolved from a discipline with a focus on monogenetic traits to become pharmacogenomics, with a genome-wide perspective. This article will briefly review recent examples of the application of genome-wide techniques to clinical pharmacogenomic studies and to pharmacogenomic model systems that vary from cell line-based model systems to yeast gene deletion libraries. Functional validation of candidate genes and the use of genome-wide techniques to gain mechanistic insights will be emphasized for the establishment of biological plausibility and as essential follow-up steps after the identification of candidate genes.
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics and Medicine, Mayo Medical School-Mayo Clinic, Rochester, MN 55905, USA.
Liewei
L
Wang
Richard M
RM
Weinshilboum
D020869:Gene Expression Profiling; D018390:Gene Targeting; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods / Q000592:standards