Genomics: implications for toxicology

The primary goal of the Environmental Genome Project (EGP) is the identific ation of human polymorphisms indicative of susceptibility to specific envir onmental agents. Despite evidence for a substantial genetic contribution to disease variation in the population. progress towards identifying specific genes has been slow. To date, most of the advances in our understanding of human diseases has come from genetic analyses of monogenic diseases that a ffect a relatively small portion of the population. The principal strategy of the EGP involves resequencing DNA samples from populations representativ e of the US racial and ethnic groups to develop a database of variations. P olymorphisms in specific genes may also be detected by gene-expression prof iling. The identification of polymorphisms by resequencing is straightforwa rd, and can be accomplished with minimal difficulty. Gene-expression profil ing is still problematic; however, determining the functional significance of the allelic variations will be a monumental challenge involving sophisti cated proteomics and population-based and animal model studies. These studi es will change radically the practice of public health and clinical medicin e, and the approach to the development of pharmaceuticals. (C) 2001 Elsevie r science B.V. All rights: reserved.