chapter  24
22 Pages


WithRichard F. Wintle, Katherine A. Siminovitch

Advances in recombinant DNA technologies and the sequence data provided by the human genome project have provided an unprecedented opportunity to characterize the molecular pathophysiology of disease. It is now evident that the majority of human diseases arise as a result of the interplay between environmental factors and genetic background. Genetic and environmental interactions play an essential role not only in disease predisposition, but also in the modulation of disease characteristics (such as age at onset and expression of various subphenotypes), therapeutic responsiveness, and outcome. Recently, the elucidation of these complex interactions has been greatly facilitated by the completion of the human genome project and publication of the full genome sequence, currently estimated to encompass about 22,000 protein coding genes (1). The major challenge now facing medical science is to exploit this genetic information so as to identify the sets of genes responsible for specific illnesses and thereby unravel the molecular processes coupling such genetic determinants to expression and persistence of disease (2). Such knowledge will allow for definition of molecular biomarkers for use in diagnosis and prediction of disease risk, prognosis and drug

responsiveness, andwill thereby enable ‘‘individualized’’medical carewherein both diagnosis and therapy are predicated on the individual’s profile of susceptibility gene variants. Thus, definition of the full complement of susceptibility alleles involved in common diseases will pave the way for earlier, more precise diagnosis and for developing the pharmacogenomic knowledge required to optimize drug therapy (3).