Many loci are characterized by a number of relatively common alleles that allow members of a naturally occurring population to be categorized into sharply distinct phenotypes. Genetic polymorphism is defined as the occurrence of multiple alleles at a locus, where at least two alleles appear with frequencies greater than 1 percent. By convention, then, polymorphic loci are those at which at least 2 percent of the population is heterozygous. However, because many polymorphic loci are characterized by a large number of different alleles, the proportion of heterozygote at some loci is much greater. Again by convention, alleles with frequencies of less than 1 percent are called rare variants. As discussed further, most (but not all) deleterious mutations that lead to genetic disease are of this latter, rare class.
Over the years, a large number of different human enzymes and other proteins have been screened for electrophoretic variants in different populations. Of all loci tested, about one third have been found to exhibit detectable polymorphism in at least one major ethnic or racial group and often in all major population groups (Haris, 1980; Cavalli-Sforza and Bodmer, 1971).
The widespread occurrence of genetic polymorphism implies that any individual is likely to be heterozygous at many different gene loci. What is the proportion of loci in a given individual at whom there will be two different alleles, each specifying a structurally distinct form of the gene product? It has been estimated from surveys of many enzymes that any individual is likely to be heterozygous at approximately 6 percent of enzyme-encoding loci. Correcting for the lack of detection of electrophoretically silent mutations, one can estimate that any individual is likely to be heterozygous for alleles determining structurally different polypeptides at approximately 12 to 18 percent of all loci. This figure is sometimes called the average heterozygosity, and it underscores the striking degree of biochemical individuality that exists within the human species.