OMIA:001972-9796 : Coat colour, dun in Equus caballus
In other species: ass
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 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".
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|TBX3||T-box 3||Equus caballus||8||NC_009151.3 (20646967..20661149)||TBX3||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1028||Non-dun||TBX3||nd1||regulatory||Naturally occurring variant||EquCab2.0||8||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 in the nd2 entry), with allele nd1 = T compared with the wild-type D allele = G); an ancient variant||2016||26691985|
|1029||Non-dun||TBX3||nd2||regulatory||Naturally occurring variant||EquCab2.0||8||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||2016||26691985|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2021||Cieslak, J., Brooks, S.A., Wodas, L., Mantaj, W., Borowska, A., Sliwowska, J.H., Ziarniak, K., Mackowski, M. :|
|Genetic background of the Polish primitive horse (Konik) coat color variation-new insight into dun dilution phenotypic effect. J Hered 112:436-442, 2021. Pubmed reference: 34432873 . DOI: 10.1093/jhered/esab034.|
|2019||Mackowski, M., Wodas, L., Brooks, S.A., Cieslak, J. :|
|TBX3 and ASIP genotypes reveal discrepancies in officially recorded coat colors of Hucul horses. Animal :1-6, 2019. Pubmed reference: 30614426 . DOI: 10.1017/S1751731118003506.|
|2016||Imsland, F., McGowan, K., Rubin, C.J., Henegar, C., Sundström, E., Berglund, J., Schwochow, D., Gustafson, U., Imsland, P., Lindblad-Toh, K., Lindgren, G., Mikko, S., Millon, L., Wade, C., Schubert, M., Orlando, L., Penedo, M.C., Barsh, G.S., Andersson, L. :|
|Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses. Nat Genet 48:152-8, 2016. Pubmed reference: 26691985 . DOI: 10.1038/ng.3475.|
|1978||Adalsteinsson, S. :|
|Inheritance of yellow dun and blue dun in the Icelandic toelter horse. Journal of Heredity 69:146-148, 1978. Pubmed reference: 731005 .|
|1859||Darwin, C.R. :|
|On the Origin of Species by Means of Natural Selection John Murray, London :, 1859.|
- Changed by Frank Nicholas on 22 Dec 2015
- Created by Frank Nicholas on 22 Dec 2015
- Changed by Frank Nicholas on 06 Aug 2016
- Changed by Frank Nicholas on 12 Feb 2019