OMIA 001199-9986 : Coat colour, extension in Oryctolagus cuniculus
In other species: cattle , dog , horse , red fox , pig , sheep , jaguar , jaguarundi , American black bear , woolly mammoth , domestic cat , 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 , Colocolo , ass , Arabian camel , Mongolian gerbil , raccoon dog , fallow deer , zebu , lorises , antarctic fur seal
Category: Pigmentation phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2006
Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; now 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. As explained by Schneider et al. (PLoS Genet 10(2): e1004892; 2015), "The most common causes of melanism (black coat) mutations are gain-of-function alterations in MC1R, or loss-of function alterations in ASIP, which encodes Agouti signaling protein, a paracrine signaling molecule that inhibits MC1R signaling". Mutations in MC1R have been associated with white colouring in several species.
Species-specific description: See Robinson (1958, pp. 248-251)
Molecular basis: Fontanesi et al. (2006) reported that the recessive (red) e allele is "a 30-nucleotide in-frame deletion (c.304_333del30)"; and "a 6-nucleotide in-frame deletion (c.280_285del6) . . . may be allele E(D) or allele E(S) [dominant black]".
Fontanesi et al. (2010) showed that allele eJ (Extension Japanese allele) is determined by a 6 bp in-frame deletion flanked by a G>A transition in 5' (c.124G>A;125_130del6) in the MC1R gene. In homozygous eJ/eJ rabbits, this allele is expressed in skin areas with black hair, whereas it is not expressed in skin with red hair areas (Fontanesi et al., 2010). [Based on wording provided by Luca Fontanesi to FN]
By using the CRISPR/Cas9 system, Xiao et al. (2019) bred rabbits with a light yellow coat colour by creating deletions in the MC1R gene. These rabbits are genetically-modified organiams (GMO).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MC1R||melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor)||Oryctolagus cuniculus||-||no genomic information (-..-)||MC1R||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|
|448||Dominant black or Steel||MC1R||E(D) or E(S)||deletion, small (<=20)||Naturally occurring variant||c.280_285del||2006||16978179|
|630||Red/fawn/yellow||MC1R||e||deletion, gross (>20)||Naturally occurring variant||c.304_333del30||2006||16978179|
|1160||Japanese brindling||MC1R||eJ||complex rearrangement||Naturally occurring variant||c.[124G>A;125_130del6]||"6 bp-in frame deletion flanked by a G > A transition in 5' (c.[124G>A;125_130del6]) that was present in all animals with Japanese brindling coat colour and pattern." (Fontanesi et al., 2010)||2010||20594318|
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||Dorożyńska, K., Maj, D. :|
|Rabbits - their domestication and molecular genetics of hair coat development and quality. Anim Genet 52:10-20, 2021. Pubmed reference: 33216407. DOI: 10.1111/age.13024.|
|Jia, X., Ding, P., Chen, S., Zhao, S., Wang, J., Lai, S. :|
|Analysis of MC1R, MITF, TYR, TYRP1, and MLPH genes polymorphism in four rabbit breeds with different coat colors. Animals (Basel) 11:, 2021. Pubmed reference: 33466315. DOI: 10.3390/ani11010081.|
|2019||Xiao, N., Li, H., Shafique, L., Zhao, S., Su, X., Zhang, Y., Cui, K., Liu, Q., Shi, D. :|
|A novel pale-yellow coat color of rabbits generated via MC1R mutation with CRISPR/Cas9 System. Front Genet 10:875, 2019. Pubmed reference: 31620174. DOI: 10.3389/fgene.2019.00875.|
|2010||Fontanesi, L., Scotti, E., Colombo, M., Beretti, F., Forestier, L., Dall'Olio, S., Deretz, S., Russo, V., Allen, D., Oulmouden, A. :|
|A composite six bp in-frame deletion in the melanocortin 1 receptor (MC1R) gene is associated with the Japanese brindling coat colour in rabbits (Oryctolagus cuniculus). BMC Genet 11:59, 2010. Pubmed reference: 20594318. DOI: 10.1186/1471-2156-11-59.|
|2007||Fontanesi, L., Tazzoli, M., Russo, V. :|
|Non-invasive and simple methods for sampling DNA for PCR analysis of melanocortin 1 receptor (MC1R) gene mutations: a technical note. World Rabbit Science 15:121-126, 2007.|
|2006||Fontanesi, L., Tazzoli, M., Beretti, F., Russo, V. :|
|Mutations in the melanocortin 1 receptor (MC1R) gene are associated with coat colours in the domestic rabbit (Oryctolagus cuniculus). Anim Genet 37:489-93, 2006. Pubmed reference: 16978179. DOI: 10.1111/j.1365-2052.2006.01494.x.|
|1958||Robinson, R. :|
|Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.|
|1924||Castle, W.E. :|
|Genetics of the Japanese rabbit Journal of Genetics 14:225-229, 1924.|
|Punnett, RC. :|
|On the "Japanese" rabbit Journal of Genetics 14:230-240, 1924.|
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