This article appears in the following Human Molecular Genetics issue: Association Studies [View the issue table of contents]
Pharmacogenomics: candidate gene identification, functional validation and mechanisms
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics and Medicine, Mayo Medical School-Mayo Clinic, Rochester, MN 55905, USA
* To whom correspondence should be addressed at: Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA Tel: +1 5072842246; Fax: +1 5072844455; Email: weinshilboum.richard{at}mayo.edu
Received August 15, 2008; Accepted August 28, 2008
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.