In other species: ass (donkey) , Przewalski's horse

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601621 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: no

Key variant known: yes

Year key variant first reported: 2016

Species-specific description: "Dun is a wild-type coat color in horses characterized by pigment dilution with a striking pattern of dark areas termed primitive markings." (Imsland et al., 2016). These primitive markings were discussed at some length by Darwin (1859) (chap 5, pp. 163-167).

Inheritance: By studying the results of matings in Icelandic toelter horses, Adalsteinsson (1978) concluded that "a dominant dilution gene, D, converts bay to yellow dun with dark mane and tail, chestnut to yellow dun and dun mane and tail, and black to blue dun (mouse, grullo". In contrast, "The palomino gene, c cr . . . is hypostatic to black and blue dun. In heterozygous form, c cr converts bay to buckskin, and chestnut and sorrel to palomino, and results in blue-eyed white when homozygous."

Mapping: Imsland et al. (2016) "mapped the Dun locus to a region on horse chromosome 8 (chr. 8: 18,061,745–18,482,196) using microsatellite markers and then fine-mapped the locus with a 27-SNP panel to a 200-kb region containing only one gene, TBX3"

Molecular basis: Imsland et al. (2016) showed that "pigment dilution in Dun horses is due to radially asymmetric deposition of pigment in the growing hair caused by localized expression of the T-box 3 (TBX3) transcription factor in hair follicles, which in turn determines the distribution of hair follicle melanocytes." In contrast, "Most domestic horses are non-dun, a more intensely pigmented phenotype caused by regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs" (Imsland et al., 2016). These same authors "identified two different alleles (non-dun1 and non-dun2) causing non-dun color. non-dun2 is a recently derived allele, whereas the Dun and non-dun1 alleles are found in ancient horse DNA, demonstrating that this polymorphism predates horse domestication" and concluded "These findings uncover a new developmental role for T-box genes and new aspects of hair follicle biology and pigmentation". To summarise, the three alleles are: D = the fully-functional (wild-type or ancestral) TBX3 sequence nd1 (associated with markings) = differs from the wild-type allele by a SNP downstream of the wild-type TBX3 sequence (located 1067bp downstream of the start of the larger nd2 deletion described below), with allele nd1 = T compared with the wild-type D allele = G); an ancient variant nd2 (not associated with markings) = a 1609bp deletion (18 227 267–18 227 279; EquCab2) downstream of the wild-type TBX3 sequence plus an 8bp deletion 11 bases upstream of the larger deletion; a recent variant As explained by Imsland et al (2016), both nd1 and nd2 are "regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs", resulting in "a more intensely pigmented phenotype".

Associated gene: