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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.

Fontanesi L, Beretti F, Riggio V, Dall'Olio S, González EG, Finocchiaro R, Davoli R, Russo V, Portolano B - BMC Genet. (2009)

Bottom Line: The Extension locus encodes the melanocortin 1 receptor (MC1R) whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals.However, its frequency was only 33%, despite the fact that these animals are completely red.However, they are probably not the only factors.

View Article: PubMed Central - HTML - PubMed

Affiliation: DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, 42100 Reggio Emilia, Italy. luca.fontanesi@unibo.it

ABSTRACT

Background: Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R) whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals.

Results: The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F1 goats and the parental animals). Five single nucleotide polymorphisms (SNPs) were identified: one nonsense mutation (p.Q225X), three missense mutations (p.A81V, p.F250V, and p.C267W), and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour.

Conclusion: According to the results obtained in the investigated goat breeds, MC1R mutations may determine eumelanic and pheomelanic phenotypes. However, they are probably not the only factors. In particular, the surprising not complete association of the nonsense mutation (p.Q225X) with red coat colour raises a few hypotheses on the determination of pheomelanic phenotypes in goats that should be further investigated.

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2D structure of the deduced goat MC1R amino acid sequence with the identified amino acid changes indicated. Mutations affecting coat colour in other mammals are reported (modified from Majerus and Mundy [52])
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Figure 3: 2D structure of the deduced goat MC1R amino acid sequence with the identified amino acid changes indicated. Mutations affecting coat colour in other mammals are reported (modified from Majerus and Mundy [52])

Mentions: Alignments of the deduced goat protein regions around the polymorphic sites with the corresponding MC1R amino acid positions available in other species are reported in Figure 2. Figure 3 reports their positions in the 2D protein structure together with amino acid changes associated with different coat or feather colours in several mammalian or avian species. All three amino acid substitutions are in highly conserved positions across species. Estimation of the likelihood of these non-synonymous (amino-acid changing) coding SNPs to cause a putative functional impact on the protein was evaluated using the cSNP analysis tool of PANTHER (Protein ANalysis THrough Evolutionary Relationships) classification system [31,32], which calculates the subPSEC (substitution position-specific evolutionary conservation) and probability (Pdeleterious) scores based on an alignment of evolutionarily related proteins [31,33] (see Methods section). PANTHER analysis indicated that all these amino acid substitutions may have functional impacts. The p.A81V residue change is located in the second transmembrane-domain, where many mutations affect MC1R activity in several other species. The subPSEC and Pdeleterious scores for this substitution were -6.96288 and 0.98135, respectively. The p.F250V substitution, located in the sixth transmembrane domain, had subPSEC = -5.99812 and Pdeleterious = 0.95249. The p.C267W amino acid variation interested a position in the third extracellular loop, that is one of the most conserved domains of this receptor (Figure 2), resulting in a subPSEC of -5.19272 with Pdeleterious of 0.89959.


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.

Fontanesi L, Beretti F, Riggio V, Dall'Olio S, González EG, Finocchiaro R, Davoli R, Russo V, Portolano B - BMC Genet. (2009)

2D structure of the deduced goat MC1R amino acid sequence with the identified amino acid changes indicated. Mutations affecting coat colour in other mammals are reported (modified from Majerus and Mundy [52])
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2748843&req=5

Figure 3: 2D structure of the deduced goat MC1R amino acid sequence with the identified amino acid changes indicated. Mutations affecting coat colour in other mammals are reported (modified from Majerus and Mundy [52])
Mentions: Alignments of the deduced goat protein regions around the polymorphic sites with the corresponding MC1R amino acid positions available in other species are reported in Figure 2. Figure 3 reports their positions in the 2D protein structure together with amino acid changes associated with different coat or feather colours in several mammalian or avian species. All three amino acid substitutions are in highly conserved positions across species. Estimation of the likelihood of these non-synonymous (amino-acid changing) coding SNPs to cause a putative functional impact on the protein was evaluated using the cSNP analysis tool of PANTHER (Protein ANalysis THrough Evolutionary Relationships) classification system [31,32], which calculates the subPSEC (substitution position-specific evolutionary conservation) and probability (Pdeleterious) scores based on an alignment of evolutionarily related proteins [31,33] (see Methods section). PANTHER analysis indicated that all these amino acid substitutions may have functional impacts. The p.A81V residue change is located in the second transmembrane-domain, where many mutations affect MC1R activity in several other species. The subPSEC and Pdeleterious scores for this substitution were -6.96288 and 0.98135, respectively. The p.F250V substitution, located in the sixth transmembrane domain, had subPSEC = -5.99812 and Pdeleterious = 0.95249. The p.C267W amino acid variation interested a position in the third extracellular loop, that is one of the most conserved domains of this receptor (Figure 2), resulting in a subPSEC of -5.19272 with Pdeleterious of 0.89959.

Bottom Line: The Extension locus encodes the melanocortin 1 receptor (MC1R) whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals.However, its frequency was only 33%, despite the fact that these animals are completely red.However, they are probably not the only factors.

View Article: PubMed Central - HTML - PubMed

Affiliation: DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, 42100 Reggio Emilia, Italy. luca.fontanesi@unibo.it

ABSTRACT

Background: Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R) whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals.

Results: The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F1 goats and the parental animals). Five single nucleotide polymorphisms (SNPs) were identified: one nonsense mutation (p.Q225X), three missense mutations (p.A81V, p.F250V, and p.C267W), and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour.

Conclusion: According to the results obtained in the investigated goat breeds, MC1R mutations may determine eumelanic and pheomelanic phenotypes. However, they are probably not the only factors. In particular, the surprising not complete association of the nonsense mutation (p.Q225X) with red coat colour raises a few hypotheses on the determination of pheomelanic phenotypes in goats that should be further investigated.

Show MeSH
Related in: MedlinePlus