EDITORIAL Dissecting Complex Genetic Diseases: Promises and Perils

Advances in molecular techniques and technology have unravelled many of the secrets of diseases caused by single gene defects. In particular, the race to complete the sequencing of the human genome has exponentially accelerated the rate at which disease causing genes are being identified. However, this success has been largely confined to diseases where the defect is due to mutations in a single gene. The challenge for genetics in the new millennium, however, lies in the dissection of complex genetic diseases. These are diseases that have a genetic predisposition but are influenced by the interplay of multiple genes and/or the environment. Many of these diseases are thought to be inherited because they tend to run in families; however, they do not show the same pedigree patterns typical of Mendelian disorders. Examples of such diseases include coronary artery disease, diabetes mellitus and asthma. The genetic contribution in these diseases consists of susceptibility genes, which act in concert to increase an individual’s risk to disease, but may not result in disease in the absence of abetting genetic or environmental triggers. In contrast to the situation in single-gene defects, most susceptibility genes exert only a minor individual effect on the disease itself. Nevertheless, since multifactorial diseases are much more prevalent than single-gene diseases, the minor effects of susceptibility genes on common diseases are the focus of increasing attention in genetics research. Two complementary analytical methods, linkage analysis and association (linkage disequilibrium) mapping have been used t