Putting the search for genes in perspective

Abstract

The sequencing of the human genome has been heralded by both the mass media and scientists as a breakthrough that will allow the detection of individuals at increased risk for common diseases and the tailoring of drugs to an individual's genetic profile in order to prevent disease. Sequencing is likely to benefit those at risk of developing rare diseases in which inherited mutations in a single gene play a major causal role. In the vast majority of people with common diseases, however, genotypes at many different loci, as well as environmental exposures, must be simultaneously present before disease appears. Elucidating the genes involved will prove elusive. In addition to the large number, different combinations account for a particular disease. Most of the genotypes that contribute to the constellation of necessary genes are uncommon and will be difficult to find. Common genotypes may confer susceptibility but will be weak predictors of disease. Because of the difficulty of discovering genes for common diseases, designing therapies will also prove difficult. More attention to environmental risk factors for particular diseases will have greater yield than a genetic search, but this too will be difficult because of environmental-genetic and other interactions. The search for risk factors for particular diseases neglects the political and social milieu in which individuals swim or sink and in which all diseases occur.