Search for complex disease genes: Achievements and failures

Abstract

In this paper current methods of mapping complex disease genes are reviewed. Outlined are the rationale of these methods, fields of their application, their strong and weak points. The progress in genetic mapping of human diseases has been mainly concerned with the Mendelian diseases. Achievements in identification and mapping of complex disease genes have been less impressive. A substantial progress has been reached in development of statistical methods of complex disease mapping. However, most of them are still based on the implicit assumption that there is a gene with a significant effect. They are effective in cases when a disease is due to mutations in structural genes or in their genetic neighborhood. Statistical methods are capable of isolating the effect of the major gene from the effects of genetic background and environmental noise, and localizing it. However, these methods fail when several genes of equal effect are involved. What hinders the progress in mapping of complex disease gene is not the drawbacks of the methods themselves, but underdevelopment of the general concept of genetic anatomy of complex traits.