OMIA 001199-9940 : Coat colour, extension in Ovis aries

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

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

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 1999

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: Dominant black

Mapping: To "assess the feasibility of performing GWAS for a dominant trait for which the genetic basis was already known", Kijas et al. (2013) conducted a GWAS on "42 Manchega and Rasa Aragonesa sheep that segregate solid black or white coat pigmentation", each genotyped with the ovine SNP50 SNP chip (yielding 49,034 informative SNPs). The test was successful: the strongest association for this pigmentation trait was with the SNP nearest to MC1R, alleles at which (p.M73K and p.D121N; see Molecular section) had previously been shown, by Calco et al. (2006), to segregate perfectly with this trait in this breed.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the supposition that dominant black in sheep is an allele at the extension (E) locus, that in other species is encoded by the MC1R gene), Våge et al. (1999) "identified a Met-->Lys mutation in position 73 (M73K) together with a Asp --> Asn change at position 121 (D121N) showing complete cosegregation with dominant black coat color in a family lineage".

Deng et al. (2009) identified two novel alleles in Black-boned, Nanping indigenous and Romney Marsh sheep, namely p.A12G and p.G144C, with a "significant" effect on coat colour.

Fontanesi et al. (2010) identified a missense allele (c.199C>T; p.R67C) in Valle del Belice sheep. The authors proposed that this variant "represents the e allele at the ovine Extension series that was, so far, not completely recognized in sheep by classical genetic studies".

Hepp et al. (2012) reported the same two variants originally identified by Våge et al. (1999) (namely p.M73K and p.D121N) in Brazilian Creole sheep, and noted "The dominant allele (E(D): p.73K, and p.121N) was found only in colored animals, whereas the recessive allele (E⁺: p.73M, and p.121D) was homozygous only in white individuals."

Rochus et al. (2019) reported two new missense likely causal variants, namely c.452G>A and c.785C>T.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MC1R melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) Ovis aries 14 NC_040265.1 (15487155..15488108) MC1R 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
Valle del Belice Recessive pheomelanism MC1R e missense c.199C>T p.R67C 2010 Reference not in PubMed; see OMIA 001199-9940 for reference details
Corriedale Dala Damara Merino Dominant black MC1R E^D missense c.218T>A p.D121N 1999 9892731 c.218T>A obtained from Fontanesi et al. (2010); breeds obtained from Rochus et al. (2019)
Massese Dominant black MC1R E^D missense c.361G>A p.M73K 1999 9892731 c.361G>A obtained from Fontanesi et al. (2010); breed obtained from Ruchus et al. (2019)
Gotland Gute Värmland Dominant black MC1R missense c.452G>A 2019 31475378
Gute Helsinge Klövsjö Texel Värmland Dominant black MC1R missense c.785C>T 2019 31475378

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 Rochus, C.M., Westberg Sunesson, K., Jonas, E., Mikko, S., Johansson, A.M., Rochus, C.M., Westberg Sunesson, K., Jonas, E., Mikko, S., Johansson, A.M. :
Mutations in ASIP and MC1R: dominant black and recessive black alleles segregate in native Swedish sheep populations. Anim Genet 50:712-717, 2019. Pubmed reference: 31475378. DOI: 10.1111/age.12837.
2016 Hepp, D., Gonçalves, G.L., Moreira, G.R., de Freitas, T.R. :
Epistatic Interaction of the Melanocortin 1 Receptor and Agouti Signaling Protein Genes Modulates Wool Color in the Brazilian Creole Sheep. J Hered 107:544-52, 2016. Pubmed reference: 27288530. DOI: 10.1093/jhered/esw037.
Mahmoud, A.H., Mashaly, A.M., Al-Anazi, K.M., Rady, A.M., Saleh, A.A. :
Allelic variation of Melanocortin-1 Receptor (MC1R) locus in Saudi indigenous sheep exhibiting different color coats. Asian-Australas J Anim Sci :, 2016. Pubmed reference: 27492350. DOI: 10.5713/ajas.16.0138.
Muniz, M.M.M., Caetano, A.R., McManus, C., Cavalcant, L.C.G., Façanha, D.A.E., Leite, J.H.G.M., Paiva, S.R. :
Application of genomic data to assist a community-based breeding program: A preliminary study of coat color genetics in Morada Nova sheep Animal 190:89-93, 2016. DOI: 10.1016/j.livsci.2016.06.006.
2013 Kijas, J.W., Serrano, M., McCulloch, R., Li, Y., Salces Ortiz, J., Calvo, J.H., Pérez-Guzmán, M.D. :
Genomewide association for a dominant pigmentation gene in sheep. J Anim Breed Genet 130:468-75, 2013. Pubmed reference: 24236609. DOI: 10.1111/jbg.12048.
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.
Yang, G.L., Fu, D.L., Lang, X., Wang, Y.T., Cheng, S.R., Fang, S.L., Luo, Y.Z. :
Mutations in MC1R gene determine black coat color phenotype in Chinese sheep. ScientificWorldJournal 2013:675382, 2013. Pubmed reference: 24082855. DOI: 10.1155/2013/675382.
2012 Hepp, D., Gonçalves, G.L., Moreira, G.R., Freitas, T.R., Martins, C.T., Weimer, T.A., Passos, D.T. :
Identification of the e allele at the Extension locus (MC1R) in Brazilian Creole sheep and its role in wool color variation. Genet Mol Res 11:2997-3006, 2012. Pubmed reference: 22653672. DOI: 10.4238/2012.May.22.5.
2011 Fontanesi, L., Beretti, F., Dall'Olio, S., Portolano, B., Matassino, D., Russo, V. :
A melanocortin 1 receptor (MC1R) gene polymorphism is useful for authentication of Massese sheep dairy products. J Dairy Res 78:122-8, 2011. Pubmed reference: 21214968. DOI: 10.1017/S0022029910000890.
Fontanesi, L., Dall'Olio, S., Beretti, F., Portolano, B., Russo, V. :
Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes. Animal 5:8-17, 2011. Pubmed reference: 22440696. DOI: 10.1017/S1751731110001382.
2010 Fontanesi, L., Beretti, F., Riggio, V., Dall'Olio, S., Calascibetta, D., Russo, V., Portolano, B. :
Sequence characterization of the melanocortin 1 receptor (MC1R) gene in sheep with different coat colours and identification of the putative e allele at the ovine Extension locus. Small Ruminant Research 91:200-207, 2010.
2009 Deng, WD., Shu, W., Yang, SL., Shi, XW., Mao, HM. :
Pigmentation in Black-boned sheep (Ovis aries): association with polymorphism of the MC1R gene. Mol Biol Rep 36:431-436, 2009. Pubmed reference: 18075782. DOI: 10.1007/s11033-007-9197-9.
2008 Loehr, J., Worley, K., Moe, J., Carey, J., Coltman, D.W. :
MC1R variants correlate with thinhorn sheep colour cline but not individual colour. Canadian Journal of Zoology 86:147-150, 2008.
2006 Calvo, J.H., Bouzada, J.A., Jurado, J.J., Serrano, M. :
Genetic substructure of the Spanish Manchega sheep breed. Small Rumin. Res. 64:116–125, 2006.
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.
Våge, D.I., Fleet, M.R., Ponz, R., Olsen, R.T., Monteagudo, L.V., Tejedor, M.T., Arruga, M.V., Gagliardi, R., Postiglioni, A., Nattrass, G.S., Klungland, H. :
Mapping and characterization of the dominant black colour locus in sheep. Pigment Cell Res 16:693-7, 2003. Pubmed reference: 14629728.
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.
Vage, D.I., Klungland, H., Lu, D., Cone, R.D. :
Molecular and pharmacological characterization of dominant black coat color in sheep Mammalian Genome 10:39-43, 1999. Pubmed reference: 9892731.

Edit History


  • Created by Frank Nicholas on 15 Nov 2005
  • Changed by Frank Nicholas on 08 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 15 Sep 2012
  • Changed by Frank Nicholas on 25 Nov 2013
  • Changed by Frank Nicholas on 18 Sep 2019