OMIA 001972-9796 : Coat colour, dun in Equus caballus

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".

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Non-dun TBX3 nd1 regulatory EquCab2 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
Non-dun TBX3 nd2 regulatory EquCab2 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

References


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.
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.

Edit History


  • Created by Frank Nicholas on 22 Dec 2015
  • Changed by Frank Nicholas on 22 Dec 2015
  • Changed by Frank Nicholas on 06 Aug 2016
  • Changed by Frank Nicholas on 12 Feb 2019