OMIA 001199-9913 : Coat colour, extension in Bos taurus

In other species: , coyote , dog , red fox , American black bear , domestic cat , jaguar , ass , horse , pig , Arabian camel , reindeer , goat , sheep , rabbit , domestic guinea pig , domestic yak , alpaca , gray squirrel , woolly mammoth , rock pocket mouse , oldfield mouse , lesser earless lizard , Geoffroy's cat , Kodkod , jaguarundi , Colocolo , little striped whiptail , water buffalo , Arctic fox

Possibly relevant human trait(s) and/or gene(s) (MIM number): 266300

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 1995

Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; also known as MC1R). This receptor controls the level of tyrosinase within melanocytes. Tyrosinase is the limiting enzyme involved in synthesis of melanins: high levels of tyrosinase result in the production of eumelanin (dark colour, e.g. brown or black), while low levels result in the production of phaeomelanin (light colour, e.g. red or yellow). When melanocyte-stimulating hormone (MSH) binds to its receptor, the level of tyrosinase is increased, leading to production of eumelanin. The wild-type allele at the extension locus corresponds to a functional MSHR, and hence to dark pigmentation in the presence of MSH.

Species-specific name: Black/red coat colour; Haplotype HBR; Haplotype HHR

Species-specific symbol: MC1-R, MSH; HBR; HHR

Inheritance: As summarised by Lawlor et al. (2014), "Dominant inheritance of black over red hair color was suggested by Barrington and Pearson (1906), and later proven through a designed experiment by Lloyd-Jones and Evvard (1916) at Iowa State University".

Mapping: Klungland et al. (1995) reported close linkage (theta = 0.08) between the classic bovine E locus and RFLPs in the bovine MSHR gene.

Molecular basis: By cloning and sequencing the most likely comparative candidate gene (based on similar phenotypes in mice), Klungland et al. (1995) obtained molecular evidence for three alleles at the MSHR locus in Norwegian and Icelandic cattle. The wild-type allele (E+) encodes the normal functional receptor for MSH. The E^D allele contains a missense mutation, changing the 99th amino acid from leucine to proline (p.Leu99Pro). The resultant MSHR molecule is constitutively expressed, i.e. it is expressed without the need for MSH binding. This results in continuously high levels of tyrosinase, and hence production of eumelanin (black coat colour). The e allele contains a single base deletion (a frameshift mutation; c.772delG; p.Tyr155X) which gives rise to a non-functional receptor, and hence to low levels of tyrosinase, resulting in production of phaeomelanin (red coat colour). Because one copy of the E^D allele is sufficient to produce functional MSHR molecules and hence to produce black coat colour, this allele is dominant, while the e allele is recessive. Thus black is dominant to red. As expected, the coat colour associated with wild-type (E+) allele varies, depending, among other things, on the level of MSH produced.

Joerg et al. (1996) extended these results by showing that red coat colour in Friesians is due to the same deletion (c.772delG; p.Tyr155X) in the MSHR gene, which is now known as MC1R.

Prevalence: In a project involving the whole-genome sequencing (WGS) of 43 Fleckvieh cattle with average coverage 7.46X (range 4.17X to 24.98X), Jansen et al. (2013) showed that all but one of the animals was homozygous for the recessive red (deletion; c.772delG; p.Tyr155X) allele, consistent with the typical red and white colour of this breed. The other animal was heterozygous for the recessive red allele and the wild-type allele, but was also red and white.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MC1R melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) Bos taurus 18 NC_037345.1 (14705093..14706843) MC1R Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Angus Holstein-Friesian Icelandic Dominant black MC1R E^D missense UMD3.1 18 g.14757910T>C c.296T>C p.L99P rs109688013 1995 8535072 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Angus Fleckvieh Red Friesian Recessive red MC1R e deletion, small (<=20) UMD3.1 18 g.14757924delG c.310delG p.Gly104ValfsX53 rs110710422 1995 8535072 Variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)

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.
2016 Niemi, M., Sajantila, A., Vilkki, J. :
Temporal variation in coat colour (genotypes) supports major changes in the Nordic cattle population after Iron Age. Anim Genet 47:495-8, 2016. Pubmed reference: 27297978. DOI: 10.1111/age.12445.
2014 Lawlor, T.J., VanRaden, P.M., Null, D., Levisee, J., Dorhorst, B. :
Using haplotypes to unravel the inheritance of Holstein coat color. Proceedings, 10th World Congress of Genetics Applied to Livestock Production, Vancouver :Comm. 289, 2014.
2013 Druet, T., Pérez-Pardal, L., Charlier, C., Gautier, M. :
Identification of large selective sweeps associated with major genes in cattle. Anim Genet 44:758-62, 2013. Pubmed reference: 23859468. DOI: 10.1111/age.12073.
Jansen, S., Aigner, B., Pausch, H., Wysocki, M., Eck, S., Benet-Pagès, A., Graf, E., Wieland, T., Strom, T.M., Meitinger, T., Fries, R. :
Assessment of the genomic variation in a cattle population by re-sequencing of key animals at low to medium coverage. BMC Genomics 14:446, 2013. Pubmed reference: 23826801. DOI: 10.1186/1471-2164-14-446.
Schmutz, S.M., Dreger, D.L. :
Interaction of MC1R and PMEL alleles on solid coat colors in Highland cattle. Anim Genet 44:9-13, 2013. Pubmed reference: 22524257. DOI: 10.1111/j.1365-2052.2012.02361.x.
Switonski, M., Mankowska, M., Salamon, S. :
Family of melanocortin receptor (MCR) genes in mammals-mutations, polymorphisms and phenotypic effects. J Appl Genet 54:461-72, 2013. Pubmed reference: 23996627. DOI: 10.1007/s13353-013-0163-z.
2008 Mohanty, T.R., Seo, K.S., Park, K.M., Choi, T.J., Choe, H.S., Baik, D.H., Hwang, I.H. :
Molecular variation in pigmentation genes contributing to coat colour in native Korean Hanwoo cattle. Anim Genet 39:550-3, 2008. Pubmed reference: 18557975. DOI: 10.1111/j.1365-2052.2008.01746.x.
2003 Klungland, H., Vage, D.I. :
Pigmentary switches in domestic animal species Annals of the New York Academy of Sciences 994:331-8, 2003. Pubmed reference: 12851333.
2002 Graphodatskaya, D., Joerg, H., Stranzinger, G. :
Molecular and pharmacological characterisation of the MSH-R alleles in Swiss cattle breeds Journal of Receptor & Signal Transduction Research 22:421-430, 2002.
Maudet, C., Taberlet, P. :
Holstein's milk detection in cheeses inferred from melanocortin receptor 1 (MC1R) gene polymorphism Journal of Dairy Science 85:707-715, 2002. Pubmed reference: 12018414. DOI: 10.3168/jds.S0022-0302(02)74127-1.
2001 Kriegesmann, B., Dierkes, B., Leeb, T., Jansen, S., Brenig, B. :
Two breed-specific bovine MC1-R alleles in Brown Swiss and Saler breeds Journal of Dairy Science 84:1768-1771, 2001. Pubmed reference: 11467827. DOI: 10.3168/jds.S0022-0302(01)74612-7.
2000 Graphodatskaya, D., Joerg, H., Stranzinger, G. :
Polymorphism in the MSHR gene of different cattle breeds Veterinarni Medicina 45:290-295, 2000.
Kantanen, J., Olsaker, I., Brusgaard, K., Eythorsdottir, E., Holm, LE., Lien, S., Danell, B., Adalsteinsson, S. :
Frequencies of genes for coat colour and horns in Nordic cattle breeds. Genet Sel Evol 32:561-76, 2000. Pubmed reference: 14736370. DOI: 10.1051/gse:2000137.
Rouzaud, F., Martin, J., Gallet, P.F., Delourme, D., Goulemot-Leger, V., Amigues, Y., Menissier, F., Leveziel, H., Julien, R., Oulmouden, A. :
A first genotyping assay of French cattle breeds based on a new allele of the extension gene encoding the melanocortin-1 receptor (Mc1r) Genetics Selection Evolution 32:511-520, 2000.
1999 Klungland, H., Roed, K.H., Nesbo, C.L., Jakobsen, K.S., Vage, D.I. :
The melanocyte-stimulating hormone receptor (MC1-R) gene as a tool in evolutionary studies of Artiodactyles Hereditas 131:39-46, 1999. Pubmed reference: 10628296.
Klungland, H., Vage, D.I. :
Presence of the dominant extension allele E-D in red and mosaic cattle Pigment Cell Research 12:391-393, 1999. Pubmed reference: 10614579.
1996 Joerg, H., Fries, H.R., Meijerink, E., Stranzinger, G.F. :
Red coat color in Holstein cattle is associated with a deletion in the MSHR gene Mammalian Genome 7:317-318, 1996. Pubmed reference: 8661706.
Werth, L.A., Hawkins, G.A., Eggen, A., Petit, E., Elduque, C., Kreigesmann, B., Bishop, M.D. :
Rapid communication - melanocyte stimulating hormone receptor (MC1R) maps to bovine chromosome 18 Journal of Animal Science 74:262, 1996. Pubmed reference: 8778108.
1995 Adalsteinsson, S., Bjarnadottir, S., Vage, D.I., Jonmundsson, J.V. :
Brown coat color in icelandic cattle produced by the loci extension and agouti Journal of Heredity 86:395-398, 1995. Pubmed reference: 7560875.
Klungland, H., Vage, D.I., Gomezraya, L., Adalsteinsson, S., Lien, S. :
The role of melanocyte-stimulating hormone (msh) receptor in bovine coat color determination Mammalian Genome 6:636-639, 1995. Pubmed reference: 8535072.
1916 Lloyd-Jones, O., Evvard, J. :
Inheritance of color and horns in blue gray cattle. Iowa State College Research Bulletin No. 30 :, 1916.
1906 Barrington, A., Pearson, K. :
On the inheritance of coat color in cattle. Biometrika 4:427-464, 1906.

Edit History


  • Created by Mohammad Shariflou on 10 Nov 2006
  • Changed by Frank Nicholas on 02 Dec 2011
  • Changed by Frank Nicholas on 09 Dec 2011
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