Database analysis and gene discovery in pharmacogenetics

The global genome research effort has resulted in the creation of extensive DNA and protein sequence databases that are a valuable resource for the id entification of new genes and polymorphic variants of enzymes of pharmacoge netic interest. Previously undescribed members of gene families with novel functions and substrate specificities can be identified by database searchi ng and sequence alignment strategies. Since the expressed sequence tag (EST ) database contains sequences from many individuals, it can be searched for evidence of polymorphisms that can significantly influence enzyme function . The different approaches to these forms of analysis are reviewed and illu strated with examples from the glutathione transferase gene family.