The problem of polygenic disease

Most diseases have a genetic component. In those caused by a mutation at a single locus and with a clear phenotype (Mendelian disorders) the molecular genetics approach is relatively simple. The identification and cloning of the mutated gene leads to a complete analysis of the underlying molecular pathology and usually explains variation in incidence and severity. However, most adult diseases are not of this type. Coronary heart disease, cancer, diabetes, arthritis and mental illness all have a genetic component but are rarely inherited in a Mendelian fashion. Multifactorial diseases have both genetic and environmental components which contribute in different proportions in a given patient or family. The genes involved may exert additive effects, or act synergistically. Other cases of the same disease may be entirely environmental in their causation. Molecular genetics facilitates investigation of the number of genes involved in cases of multifactorial disease, their relative weight in different families and in the community, and the nature of their interaction. One particularly powerful approach is to study a large family in which simple Mendelian segregation occurs for a disease which is more often complex or sporadic.