Human Genome Sequence Variation and the Inherited Basis of Common Disease

Abstract

A central goal in medical research is to understand how variation in DNA sequence, environment and behavior combine to cause common human diseases. To date, most progress has been limited to rare conditions in which mutation of a single gene is both necessary and sufficient to cause disease. In common diseases, in contrast, multiple genes combine with environmental influences, meaning that the contribution of any single gene variant is probabilistic rather than deterministic. Where gene effects are partial, rather than complete, their effects can only be demonstrated by measuring frequencies of variants in collections of patients and controls much larger than a single family.