Pharmacogenetic studies are frequently jump-started by isolated observations of unexpected drug responses or anecdotal accounts of esoteric epidemiological findings, but they ultimately involve in-depth studies at all levels of gene action from the genotypic properties of the gene itself to its phenotypic effects in individuals and populations. The essence of pharmacogenetics lies in the application of the principles of pharmacology and genetics to variation of human drug response, but the expertise and technical know-how available in other fields, biochemistry, toxicology, epidemiology, and computational biology, are usually called upon to attain a comprehensive understanding of the root causes of phar-macogenetic traits. And while the discussion here centers on the investigation of human subjects, studies of knockout, transgenic animals and other eukaryotic models can often provide new insight into the biological basis of pharmacoge-netic traits as well as the mechanisms that underpin them. Study designs that exclude such systems may thus sacrifice an invaluable alternative to the strategy and tactics of human pharmacogenetic investigations.
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