COMPARATIVE GENOME ANALYSIS-A NOVEL STRATEGY TO STUDY THE GENETICS OF HOST-PARASITE INTERACTION*

Parasitologists traditionally have focused on the investigation of parameters associated with the life cycle, physiology, and biochemistry of parasites as important modulators of the pathogenesis of infectious diseases. It has become increasingly clear, however, that variability in the host's physiological, biochemical, and immunological constitution is equally important in understanding the infectious process and the hostparasite relationship. Indisputably, environmental conditions influence the host's susceptibility to parasitic disease to some degree, but a major part of a host's responsiveness to parasites is an intricate function of its specific genetic make-up. Although the analysis of the contribution of host genes to disease susceptibility is still in its infancy, it is obvious that the modulation of host susceptibility to infection by the genetic background is both profound and complex. Recent complex segregation analyses of disease susceptibility in families living in endemic areas of leprosy (Abel and Demenais, 1988), schistosomiasis (Abel et al., 1991), and malaria (Abel et al., 1992) have shown clearly that susceptibility to these diseases is under the control of major genes. Thus, the rigorous statistical analysis of susceptibility variation in endemic populations gives strong support for a crucial role of host genes in the pathogenesis and mechanism of infectious disease. The study of genetic factors that control susceptibility to infectious disease in humans is difficult because such susceptibility genes only predispose to disease. Genetic studies therefore rely on the identification of patients affected with a clearly defined clinical phenotype of infectious disease. In practice, the identification of such cases and appropriate controls for genetic studies are tedious or may not be possible. For this reason, investigators turned early on to animal models for the study of genetic susceptibility to in