Hostname: page-component-745bb68f8f-d8cs5 Total loading time: 0 Render date: 2025-01-13T23:28:39.879Z Has data issue: false hasContentIssue false
  • English
  • Français

Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes

Published online by Cambridge University Press:  01 July 2010

L. Fontanesi ,
S. Dall’Olio ,
F. Beretti ,
B. Portolano  and
V. Russo
L. Fontanesi*
Affiliation:
DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, Via F.lli Rosselli 107, 42100 Reggio Emilia, Italy
S. Dall’Olio
Affiliation:
DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, Via F.lli Rosselli 107, 42100 Reggio Emilia, Italy
F. Beretti
Affiliation:
DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, Via F.lli Rosselli 107, 42100 Reggio Emilia, Italy Department of S.En.Fi.Mi.Zo., Sezione di Produzioni Animali, University of Palermo, Viale delle Scienze – Parco d’Orleans, 90128 Palermo, Italy
B. Portolano
Affiliation:
Department of S.En.Fi.Mi.Zo., Sezione di Produzioni Animali, University of Palermo, Viale delle Scienze – Parco d’Orleans, 90128 Palermo, Italy
V. Russo
Affiliation:
DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, Via F.lli Rosselli 107, 42100 Reggio Emilia, Italy
*
†E-mail: luca.fontanesi@unibo.it
Get access

Abstract

Massese is an Italian dairy sheep breed characterized by animals with black skin and horns and black or apparent grey hairs. Owing to the presence of these two coat colour types, this breed can be considered an interesting model to evaluate the effects of coat colour gene polymorphisms on this phenotypic trait. Two main loci have been already shown to affect coat colour in sheep: Agouti and Extension coding for the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes, respectively. The Agouti locus is affected by a large duplication including the ASIP gene that may determine the Agouti white and tan allele (AWt). Other disrupting or partially inactivating mutations have been identified in exon 2 (a deletion of 5 bp, D5; and a deletion of 9 bp, D9) and in exon 4 (g.5172T>A, p.C126S) of the ASIP gene. Three missense mutations in the sheep MC1R gene cause the dominant black ED allele (p.M73K and p.D121N) and the putative recessive e allele (p.R67C). Here, we analysed these ASIP and MC1R mutations in 161 Massese sheep collected from four flocks. The presence of one duplicated copy allele including the ASIP gene was associated with grey coat colour (P = 9.4E-30). Almost all animals with a duplicated copy allele (37 out of 41) showed uniform apparent grey hair and almost all animals without a duplicated allele (117 out of 120) were completely black. Different forms of duplicated alleles were identified in Massese sheep including, in almost all cases, copies with exon 2 disrupting or partially inactivating mutations making these alleles different from the AWt allele. A few exceptions were observed in the association between ASIP polymorphisms and coat colour: three grey sheep did not carry any duplicated copy allele and four black animals carried a duplicated copy allele. Of the latter four sheep, two carried the ED allele of the MC1R gene that may be the cause of their black coat colour. The coat colour of all other black animals may be determined by non-functional ASIP alleles (non-agouti alleles, Aa) and in a few cases by the EDExtension allele. At least three frequent ASIP haplotypes ([D5:g.5172T], [N:g.5172A] and [D5:g.5172A]) were detected (organized into six different diplotypes). In conclusion, the results indicated that coat colours in the Massese sheep breed are mainly derived by combining ASIP and MC1R mutations.

Keywords

coat coloursheepASIPMC1Rmutations
Type
Full Paper
Information
animal , Volume 5 , Issue 1 , January 2011 , pp. 8 - 17
Copyright
Copyright © The Animal Consortium 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adalsteinsson, S 1970. Colour inheritance in Icelandic sheep and relation between colour, fertility, and fertilization. Journal of Agricultural Research in Iceland 2, 3–135.Google Scholar
Adalsteinsson, S 1975. Depressed fertility in Icelandic sheep caused by a single colour gene. Annales de Génétique et de Sélection Animal 7, 445–447.Google Scholar
Bennett, DC, Lamoreux, ML 2003. The color loci of mice – a genetic century. Pigment and Cell Research 16, 333–344.CrossRefGoogle ScholarPubMed
Berryere, TG, Kerns, JA, Barsh, GS, Schmutz, SM 2005. Association of an Agouti allele with fawn or sable coat color in domestic dogs. Mammalian Genome 16, 262–272.CrossRefGoogle ScholarPubMed
Bultman, SJ, Michaud, EJ, Woychik, RP 1992. Molecular characterization of the mouse agouti locus. Cell 71, 1195–1204.CrossRefGoogle ScholarPubMed
Cooper, GM, Nickerson, DA, Eichler, EE 2007. Mutational and selective effects on copy-number variants in the human genome. Nature Genetics 39, S22–S29.Google Scholar
Dawson, M, Moore, RC, Bishop, SC 2008. Progress and limits of PrP gene selection policy. Veterinary Research 39, 25.Google Scholar
Eizirik, E, Yuhki, N, Johnson, WE, Menotti-Raymond, M, Hannah, SS, O’Brien, SJ 2003. Molecular genetics and evolution of melanism in the cat family. Current Biology 13, 448–453.CrossRefGoogle ScholarPubMed
Everts, RE, Rothuizen, J, van Oost, BA 2000. Identification of a premature stop codon in the melanocyte-stimulating hormone receptor gene (MC1R) in Labrador and Golden retrievers with yellow coat colour. Animal Genetics 31, 194–199.CrossRefGoogle ScholarPubMed
Fontanesi, L, Tazzoli, M, Beretti, F, Russo, V 2006. Mutations in the melanocortin 1 receptor (MC1R) gene are associated with coat colours in the domestic rabbit (Oryctolagus cuniculus). Animal Genetics 37, 489–493.CrossRefGoogle ScholarPubMed
Fontanesi, L, Beretti, F, Riggio, V, Dall’Olio, S, Gómez González, E, Finocchiaro, R, Davoli, R, Russo, V, Portolano, B 2009a. Missense and nonsense mutations in melanocortin 1 receptor (MC1R) gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences. BMC Genetics 10, 47.CrossRefGoogle ScholarPubMed
Fontanesi, L, Beretti, F, Riggio, V, Gómez González, E, Dall’Olio, S, Davoli, R, Russo, V, Portolano, B 2009b. Copy number variation and missense mutations of the agouti signaling protein (ASIP) gene in goat breeds with different coat colours. Cytogenetic and Genome Research 126, 333–347.CrossRefGoogle Scholar
Fontanesi, L, Beretti, F, Riggio, V, Dall’Olio, S, Calascibetta, D, Russo, V, Portolano, B 2010a. Sequence characterization of the melanocortin 1 receptor (MC1R) gene in sheep with different coat colour and identification of the putative e allele at the ovine Extension locus. Small Ruminant Research 91, 200–207.Google Scholar
Fontanesi, L, Forestier, L, Allain, D, Scotti, E, Beretti, F, Deretz-Picoulet, S, Pecchioli, E, Vernesi, C, Robinson, TJ, Malaney, JL, Russo, V, Oulmouden, A 2010b. Characterization of the rabbit agouti signaling protein (ASIP) gene: transcripts and phylogenetic analyses and identification of the causative mutation of the nonagouti black coat colour. Genomics 95, 166–175.CrossRefGoogle ScholarPubMed
Franci, O, Pugliese, C, Acciaioli, A, Parisi, G, Lucifero, M 1999. Application of two models to the lactation curve of Massese ewes. Small Ruminant Research 31, 91–96.Google Scholar
Girardot, M, Guibert, S, Laforet, M-P, Gallard, Y, Larroque, H, Oulmouden, A 2006. The insertion of a full-length Bos taurus LINE element is responsible for a transcriptional deregulation of the Normanne Agouti gene. Pigment Cell Research 19, 346–355.CrossRefGoogle Scholar
Gratten, J, Beraldi, D, Lowder, BV, McRae, AF, Visscher, PM, Pemberton, JM, Slate, J 2007. Compelling evidence that a single nucleotide substitution in TYRP1 is responsible for coat-colour polymorphism in a free-living population of Soay sheep. Proceedings of the Royal Society B Biological Sciences 274, 619–626.CrossRefGoogle Scholar
Gratten, J, Pilkington, JG, Brown, EA, Beraldi, D, Pemberton, JM, Slate, J 2010. The genetic basis of recessive self-colour pattern in a wild sheep population. Heredity 104, 206–214.CrossRefGoogle Scholar
Hunter, N 2007. Scrapie: uncertainties, biology and molecular approaches. Biochimica et Biophysica Acta 1772, 619–628.Google Scholar
Joerg, H, Fries, HR, Meijerink, E, Stranzinger, GF 1996. Red coat color in Holstein cattle is associated with a deletion in the MSHR gene. Mammalian Genome 7, 317–318.CrossRefGoogle ScholarPubMed
Kanetsky, PA, Swoyer, J, Panossian, S, Holmes, R, Guerry, D, Rebbeck, TR 2002. A polymorphism in the agouti signaling protein gene is associated with human pigmentation. American Journal of Human Genetics 70, 770–775.Google Scholar
Kerns, JA, Newton, J, Berryere, TG, Rubin, EM, Cheng, JF, Schmutz, SM, Barsh, GS 2004. Characterization of the dog Agouti gene and a nonagouti mutation in German Shepherd dogs. Mammalian Genome 15, 798–808.Google Scholar
Kiefer, LL, Ittoop, ORR, Bunce, K, Truesdale, AT, Willard, DH, Nichols, JS, Blanchard, SG, Mountjoy, K, Chen, W-J, Wilkison, WO 1997. Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to melanocortin receptors. Biochemistry 36, 2084–2090.CrossRefGoogle ScholarPubMed
Kijas, JMH, Moller, M, Plastow, G, Andersson, L 2001. A frameshift mutation in MC1R and a high frequency of somatic reversions cause black spotting in pigs. Genetics 158, 779–785.CrossRefGoogle Scholar
Kijas, JMH, Wales, R, Törnsten, A, Chardon, P, Moller, M, Andersson, L 1998. Melanocortin receptor 1 (MC1R) mutations and coat color in pigs. Genetics 150, 1177–1185.Google Scholar
Klungland, H, Våge, DI, Gomez-Raya, L, Adalsteinsson, S, Lien, S 1995. The role of melanocyte-stimulating hormone (MSH) receptor in bovine coat color determination. Mammalian Genome 6, 636–639.CrossRefGoogle ScholarPubMed
Kuramoto, T, Nomato, T, Sugimura, T, Ushijima, T 2001. Cloning of the rat agouti gene and identification of the rat nonagouti mutation. Mammalian Genome 12, 469–471.CrossRefGoogle ScholarPubMed
Lu, D, Willard, D, Patel, IR, Kadwell, S, Overton, L, Kost, T, Luther, M, Chen, W, Woychik, RP, Wilkison, WO, Cone, RD 1994. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371, 799–802.CrossRefGoogle ScholarPubMed
Marklund, L, Johansson Moller, M, Sandberg, K, Andersson, L 1996. A missense mutation in the gene for melanocyte-stimulating hormone receptor (MC1R) is associated with the chestnut coat color in horses. Mammalian Genome 7, 895–899.CrossRefGoogle ScholarPubMed
McNulty, JC, Jackson, PJ, Thompson, DA, Chai, B, Gantz, I, Barsh, GS, Dawson, PE, Millhauser, GL 2005. Structure of the agouti signalling protein. Journal of Molecular Biology 346, 1059–1070.CrossRefGoogle Scholar
Miltenberger, RJ, Wakumatsu, K, Ito, S, Woychik, RP, Russell, LB, Michaud, EJ 2002. Molecular and phenotypic analysis of 25 recessive, homozygous-viable alleles at the mouse agouti locus. Genetics 160, 659–674.Google Scholar
Newton, JM, Wilkie, AL, He, L, Jordan, SA, Metallinos, DL, Holmes, NG, Jackson, IJ, Barsh, GS 2000. Melanocortin 1 receptor variation in the domestic dog. Mammalian Genome 11, 24–30.Google Scholar
Norris, BJ, Whan, VA 2008. A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep. Genome Research 18, 1282–1293.CrossRefGoogle ScholarPubMed
Ollmann, MM, Lamoreux, ML, Wilson, BD, Barsh, GS 1998. Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo. Genes and Development 12, 316–330.CrossRefGoogle ScholarPubMed
Peterschmitt, M, Grain, F, Arnaud, B, Deléage, G, Lambert, V 2009. Mutation in the melanocortin 1 receptor is associated with amber colour in the Norwegian Forest Cat. Animal Genetics 40, 547–552.Google Scholar
Rieder, S, Taourit, S, Mariat, D, Langlois, B, Guerin, G 2001. Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mammalian Genome 12, 450–455.Google Scholar
Robbins, LS, Nadeau, JH, Johnson, KR, Kelly, MA, Roselli-Rehfuss, L, Baack, E, Mountjoy, KG, Cone, RD 1993. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72, 827–834.Google Scholar
Rouzaud, F, Martin, J, Gallet, PF, Delourme, D, Goulemot-Leger, V, Amigues, Y, Ménissier, F, Levéziel, H, Julien, R, Oulmouden, A 2000. 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.CrossRefGoogle ScholarPubMed
Royo, LJ, Alvarez, I, Arranz, JJ, Fernández, I, Rodríguez, A, Pérez-Pardal, L, Goyache, F 2008. Differences in the expression of the ASIP gene are involved in the recessive black coat colour pattern in sheep: evidence from the rare Xalda sheep breed. Animal Genetics 39, 290–293.Google Scholar
Russo, V, Fontanesi, L, Scotti, E, Tazzoli, M, Dall’Olio, S, Davoli, R 2007. Analysis of melanocortin 1 receptor (MC1R) gene polymorphisms in some cattle breeds: their usefulness and application for breed traceability and authentication of Parmigiano Reggiano cheese. Italian Journal of Animal Science 6, 257–272.Google Scholar
Sawalha, RM, Bell, L, Brotherstone, S, White, I, Wilson, AJ, Villanueva, B 2009. Scrapie-resistant sheep show certain coat colour characteristics. Genetics Research 91, 39–46.Google Scholar
Searle, AG 1968. Comparative genetics of coat colour in mammals. Logos Press, London.Google Scholar
Smit, MA, Shay, T, Beever, JE, Notter, DR, Cockett, NE 2002. Identification of an agouti-like locus in sheep. Animal Genetics 33, 383–385.Google Scholar
Sponenberg, DP 1997. Genetics of colour and hair texture. In The genetics of sheep (ed. L Piperand and A Ruvinsky), pp. 51–86. CAB International, Wallingford, UK.Google Scholar
Stephens, M, Smith, NJ, Donnelly, P 2001. A new statistical method for haplotype reconstruction from population data. American Journal of Human Genetics 68, 978–989.Google Scholar
Våge, DI, Fleet, MR, Ponz, R, Olsen, RT, Monteagudo, LV, Tejedor, MT, Arruga, MV, Gagliardi, R, Postiglioni, A, Nattrass, GS, Klungland, H 2003. Mapping and characterization of the dominant black colour locus in sheep. Pigment and Cell Research 16, 693–697.Google Scholar
Våge, DI, Klungland, H, Lu, D, Cone, RD 1999. Molecular and pharmacological characterization of dominant black coat color in sheep. Mammalian Genome 10, 39–43.Google ScholarPubMed
Våge, DI, Lu, D, Klungland, H, Lien, S, Adalsteinsson, S, Cone, RD 1997. A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes. Nature Genetics 15, 311–315.Google Scholar
Valverde, P, Healy, E, Jackson, I, Rees, JL, Thody, AJ 1995. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nature Genetics 11, 328–330.Google Scholar
Vascellari, M, Aufiero, GM, Nonno, R, Agrimi, U, Vaccari, G, Basilicata, L, Falcaro, C, Mancin, M, Marcon, S, Mutinelli, F 2005. Diagnosis and PrP genotype target of scrapie in clinically healthy sheep of Massese breed in the framework of a scrapie eradication programme. Archives of Virology 150, 1959–1976.CrossRefGoogle ScholarPubMed