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

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601621 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2016

Species-specific symbol: D, d1, d2

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). Primitive markings usually appear as a dorsal stripe and bars on the legs. 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 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)". Imsland et al. (2016) described three alleles at the D locus: D for dilution, d1 (non-dun1) for no dilution but primitive markings, and d2 (non-dun2) for no dilution and no primitive markings. D and d1 have dominant modes of inheritance. The d2 allele is recessive and most prevalent among the  common horse breeds. D and d1 are considered ancestral forms of the gene as there were present in horses prior to domestication.

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: Following mapping, the candidate region was DNA sequenced leading to the discovery of a pair of insertions associated with the D and d1 alleles (Imsland et al., 2016). The D allele appears as an 8 bp insertion followed downstream by a 1609 bp insertion. The d1 allele (no dilution but showing primitive markings) appears as an 8 bp insertion followed downstream by a 1610 bp insertion. The d2 allele (described as having no dilution and no primitive markings) is represented in the reference sequence, EquCab 3.0. 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." Furthermore, both d1 and d2 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”. 

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene: