Gene polymorphism

A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population.^[1] In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic.^[2]

Gene polymorphisms can occur in any region of the genome. The majority of polymorphisms are silent, meaning they do not alter the function or expression of a gene.^[3] Some polymorphisms are visible. For example, in dogs the E locus can have any of five different alleles, known as E, E^m, E^g, E^h, and e.^[4] Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats.^[5]

A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein; this abnormality may cause or be associated with disease. For example, a polymorphic variant of the gene encoding the enzyme CYP4A11, in which thymidine replaces cytosine at the gene's nucleotide 8590 position encodes a CYP4A11 protein that substitutes phenylalanine with serine at the protein's amino acid position 434.^[6] This variant protein has reduced enzyme activity in metabolizing arachidonic acid to the blood pressure-regulating eicosanoid, 20-hydroxyeicosatetraenoic acid. A study has shown that humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of hypertension, ischemic stroke, and coronary artery disease.^[6]

Most notably, the genes coding for the major histocompatibility complex (MHC) are in fact the most polymorphic genes known. MHC molecules are involved in the immune system and interact with T-cells. There are more than 32,000 different alleles of human MHC class I and II genes, and it has been estimated that there are 200 variants at the HLA-B HLA-DRB1 loci alone.^[7]

Some polymorphism may be maintained by balancing selection.