Pharmacogeneticists have traditionally relied on phenotypic criteria to analyze individual responsiveness to exogenous chemicals. For genes expressed in accessible tissues, such as peripheral blood cells and skin, the analytical difficulties are not as formidable as for traits whose expression is specific to less accessible tissues such as the liver, skeletal muscle, adrenal, and heart. Investigators have made rapid strides toward the delineation of the structure and organization of human genes and of the pathways by which cells regulate gene expression through the use of recombinant DNA techniques. Since their introduction and widespread adoption about two decades ago, molecular genetic studies have produced a prodigious amount of new information about hereditary susceptibilities to exogenous substances, and profound insights into their underlying mechanisms.
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