User:Countercanter/Sandbox

Extension
The Extension locus is occupied by the Melanocortin-1-receptor (Mc1r) gene, which encodes the eponymous protein. The MC1R protein straddles the membrane of pigment cells (melanocytes). MC1R picks up a chemical called alpha-melanocyte-stimulating hormone (α-MSH), which is produced by the body, from outside the cell. When MC1R comes into contact with α-MSH, a complex reaction is triggered inside the cell, and the melanocyte begins to produce black-brown pigment (eumelanin). Without the stimulation of α-MSH, the melanocyte produces red-yellow pigment (pheomelanin) by default.

Various mutations in the human Mc1r gene result in red hair, blond hair, fair skin, and susceptibility to sundamaged skin and melanoma. Polymorphisms of Mc1r also lead to light or red coats in mice, cattle, and dogs, among others. The Extension locus was first suggested to have a role in horse coat color determination in 1974 by Stefan Adalsteinsson. Researchers at Uppsala University, Sweden, identified a missense mutation in the Mc1r gene that resulted in a loss-of-function of the MC1R protein. Without the ability to produce a functional MC1R protein, eumelanin production could not be initiated in the melanocyte, resulting in coats devoid of true black pigment. Since horses with only one copy of the defective gene were normal, the mutation was labeled e or sometimes Ee. A single copy of the wildtype allele, which encodes a fully-functional MC1R protein, is protective against the loss-of-function. The normal or wildtype allele is labeled E, or sometimes E+ or EE.

Phenotypes

 * e/e (Ee/Ee) homozygous recessive. Visually, the horse may be any color in the "red" family: chestnut, palomino, cremello, red dun, gold champagne, gray, and so on. Paired with an e/e mate, such horses will only ever produce red-family coat colors. At birth, the skin may be pink and the eyes blue, but these traits disappear after a few days and the eyes and skin of adult red coated horses are unaffected by this allele. No health defects are associated with the e allele.
 * E/E (+/+, E+/E+, EE/EE) wildtype, homozygous dominant. Visually, the horse may be black, seal brown, bay, buckskin, perlino or smoky cream, bay dun or grullo, silver bay or silver black, gray or many other colors. Such a horse will always pass on a functional copy of the Mc1r gene to its offspring, and will never produce offspring with the e/e genotype.
 * E/e (+/e, E+/Ee, EE/Ee) wildtype, heterozygous. Visually, the horse may also be black, seal brown, bay, buckskin, perlino or smoky cream, bay dun, grullo, silver bay, silver black, amber champagne, gray, and so on. A recent study that compared horse genotypes to their coat color phenotypes did find a statistically significant connection that suggested that lighter bay shades were heterozygous for the Extension mutation (E/e) and darker bay shades were homozygous wildtype (E/E).