Some of these variants lead to disease, although purely genetically determined diseases caused by a single gene are rare. The mutations in these diseases, like cystic fibrosis and muscular dystrophy, are necessary and sufficient for the disease. Far more common are the complex multi-factorial diseases, in which genetic susceptibility rather than genetic determinism, plays a role. Multiple variants or a combination of variants and environmental insult leads to disease. This category includes not only diseases that run in families, such as diabetes, cancer, and cardiovascular disease, but also a wide range of other diseases, such as birth defects, mental illness, and infectious diseases.
Variants can increase susceptibility or can provide protection.
For example, a protective variant in the chemokine receptor gene absolutely eliminates HIV infectivity. Most genetically based diseases arise from a variety of mutations. Cystic fibrosis, for example, a genetically determined disease, derives from one of many different variant alleles. Willard warned of the impending shortage of medical geneticists, emphasizing that all physicians will need some training to become more knowledgeable about genetics.