Skin/hair/eye pigmentation with variations

Iris color was one of the first human traits used in the study of Mendelian inheritance in humans. Davenport and Davenport (1907) suggested, and this opinion was long taught in schools as a guide for beginners in genetics, thatbrown eye color always dominates over blue, with two blue-eyed parents always producing a blue-eyed child, never one with brown eyes. As with many physical traits, this simplistic model does not take into account the fact that, as is commonly known, eye color is inherited as a polygenic, not a monogenic, trait . The earlier view that blue is a simple recessive trait has been repeatedly proven wrong by the observation of brown-eyed offspring from two blue-eyed parents. Blue-eyed offspring from 2 brown-eyed parents are a more common result.

Gedde-Dahl et al (1982) found positive lod scores between the brown eye color BEY1 (later described as central brown eye color) and the Colton (CO; 110450, which maps to chromosome 7) and Kidd (JK; 111000, which maps to chromosome 18 (Eiberg 1997) blood types. Another phenotype, green eye color (GEY; see 601800), was mapped to chromosome 19 by linkage to Sekretor (SE; 182100) and Lutheran (LU; 111150). A gene for brown hair color segregated with GEY (maximum lod score = 5.6 ) (see Eiberg et al. 1996).

Skin/hair/eye pigmentation and gene variations (acronym: SHEP) is a genetic classification system that relates different phenotypes (SHEP 1- SHEP 11) to detectable and known polymorphisms in different genes. Associated are genes that have been shown to (co-)determine the pigment system of skin, hair and iris.

The pigmentation of hair, eyes and skin is among the most visible examples of human phenotypic variation, with a wide normal range that is, and very obviously, subject to considerable geographic stratification. Thus, pigmentation in human tissues is due to the number, type, and cellular distribution of melanosomes (subcellular compartments formed by melanocytes that synthesize and store the light-absorbing polymer melanin) (Sulem et al. 2007).

The variation in pigmentation between individuals is thought to be due to biochemical differences that affect the number of melanosomes produced, the type of melanin synthesized (either black-brown eumelanin or red-yellow pheomelanin), and the size and shape of melanosomes. The number of melanocytes is not the same even in different regions of the body. It varies between 1000-2000/mm2skin surface.

Undoubtedly, the absorption of ultraviolet radiation (UVR) is the most important physiological function of melanocytes. This protective function involves all systems of the skin, especially the highly proliferative epithelia that phagocytose the pigment (pigment transfer) and place it around their nucleus in a polar cap-like manner, the melanocytes themselves, collagen and elastic fiber systems(actinic elastosis), and the dermal vascular systems. This protective function must be balanced against the lower amount of UV radiation available for the synthesis of vitamin D3.

It is generally believed that the geographic distribution of human skin color reflects an adaptation to latitude-dependent UV radiation, with individuals tending to have lighter pigmentation with increasing distance from the equator (Relethford, 1997).

The greatest variation in human eye and hair color is found in people of European ancestry, while most other human populations are fixed to brown eyes and black hair (Sulem et al. 2007). Studies cited by Stokowski et al. (2007) suggest that the genetic factors influencing lighter pigmentation in Europeans differ significantly from the mechanisms responsible for lighter pigmentation in East Asians (Relethford, 1997; Norton et al. 2006; Myles et al. 2007).

Given the direct relationship between skin color and UV exposure, it has long been postulated that skin pigmentation is a trait under strong selection pressure (Stokowski et al. 2007). Pigment mutants in model organisms and human genodermatoses with pigmentary abnormalities have been the main source for the discovery of genes that are partly responsible for skin color. In mice, more than 100 pigmentation genes have now been identified. Mutations in 18 genes are currently associated with human albinism (see Albinism below).

Sulem et al. (2007) conducted a genome-wide association study (GWAS) in 2,986 healthy Icelanders to find variants associated with hair and eye pigmentation, skin sun sensitivity, and freckles. The most strongly associated SNPs were then tested for replication in a second sample of 2,718 Icelanders and a sample of 1,214 healthy Dutch. Sulem et al. (2007) found an association of the A allele of a single nucleotide polymorphism (SNP), rs1540771, on chromosome 6p25.3 between the IRF4 and SEC5L1 genes (615329), with the presence of freckles in Icelandic and Dutch population samples. Secondary associations of this allele were found with brown rather than blond hair and with sun sensitivity of the skin. The frequency of rs1540771 is approximately 50% in European populations, but only 30% and 5% in East Asian and Nigerian populations, respectively.

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