Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-23T03:06:45.308Z Has data issue: false hasContentIssue false
  • English
  • Français

Three novel mutations in ASIP associated with black fibre in alpacas (Vicugna pacos)

Published online by Cambridge University Press:  05 January 2011

N. L. FEELEY ,
S. BOTTOMLEY  and
K. A. MUNYARD
N. L. FEELEY
Affiliation:
WABRI, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
S. BOTTOMLEY
Affiliation:
WABRI, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
K. A. MUNYARD*
Affiliation:
WABRI, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
*
*To whom all correspondence should be addressed. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

The coding region of the alpaca Agouti signalling protein (ASIP) gene was sequenced. It was determined to be 402 nucleotides long and code for a protein that is 133 amino acids long. Eight mutations were identified in a sample of 15 alpaca, five in the coding region and three in the introns flanking the exons. In silico analysis showed that three of the five mutations in the coding sequence, c.325_381del57, c.292C>T and c.353G>A are probable loss-of-function mutations. The three mutations were strongly associated with black fibre colour, with 0·90 of black alpacas in the current study having two copies of one or another of the mutations. However, not all black animals displayed the putative ‘aa’ genotype, and almost half of the non-black animals did display that genotype. Contributing factors such as regulatory region mutations, interactions of ASIP with melanocortin-1 receptor (MC1R) and α-melanocyte stimulating hormone (α-MSH), the effect of dilution genes and subjective phenotype assignment are discussed. These mutations will allow alpaca breeders to select for or against black, but they do not explain all black phenotypes in this species.

Type
Animals
Information
The Journal of Agricultural Science , Volume 149 , Issue 4 , August 2011 , pp. 529 - 538
Copyright
Copyright © Cambridge University Press 2011

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

REFERENCES

Bendtsen, J. D., Nielsen, H., von Heijne, G. & Brunak, S. (2004). Improved prediction of signal peptides: SignalP 3.0. Journal of Molecular Biology 340, 783–795.CrossRefGoogle ScholarPubMed
Berryere, T. G., Schmutz, S. M., Schimpf, R. J., Cowan, C. M. & Potter, J. (2003). TYRP1 is associated with dun coat colour in Dexter cattle or how now brown cow? Animal Genetics 34, 169–175.CrossRefGoogle ScholarPubMed
Bolin, I. (1998). Rituals of Respect: The Secret of Survival in the High Peruvian Andes. Austin, TX: University of Texas Press.Google Scholar
Buscà, R. & Ballotti, R. (2000). Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Research 13, 60–69.CrossRefGoogle ScholarPubMed
Capriotti, E., Fariselli, P. & Casadio, R. (2005). I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Research 33 (Suppl. 2), W306–W310.CrossRefGoogle ScholarPubMed
Chen, Y., Duhl, D. M. J. & Barsh, G. S. (1996). Opposite orientations of an inverted duplication and allelic variation at the mouse agouti locus. Genetics 144, 265–277.CrossRefGoogle ScholarPubMed
Cook, D., Brooks, S., Bellone, R. & Bailey, E. (2008). Missense mutation in exon 2 of SLC36A1 responsible for champagne dilution in horses. PLoS Genetics 4, e1000195. doi:10.1371/journal.pgen.1000195CrossRefGoogle ScholarPubMed
Cransberg, R. & Munyard, K. A. (2009) Polymorphisms detected in the tyrosinase and MATP (SLC45A2) genes did not explain coat colour dilution in a sample of alpaca (Vicugna pacos). In Matching Genetics and Environment: A New Look at an Old Topic. Proceedings of the 18th Conference of the Association for the Advancement of Animal Breeding and Genetics, Barossa Valley, South Australia, Australia, 28 Sept – 1 Oct 2009 (Ed. Alex Safari, B. P. B. R.), pp. 520–523. South Australia: Association for the Advancement of Animal Breeding and Genetics.Google Scholar
Dinulescu, D. M. & Cone, R. D. (2000). Agouti and agouti-related protein: analogies and contrasts. Journal of Biological Chemistry 275, 6695–6698.CrossRefGoogle ScholarPubMed
Edgar, R. C. (2004). MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Research 32, 1792–1797.CrossRefGoogle ScholarPubMed
Feeley, N. L. & Munyard, K. A. (2009). Characterisation of the melanocortin-1 receptor gene in alpaca and identification of possible markers associated with phenotypic variations in colour. Animal Production Science 49, 675–681.CrossRefGoogle Scholar
Fontanesi, L., Beretti, F., Riggio, V., Gomez Gonzalez, E., Dall'Olio, S., Davoli, R., Russo, V. & Portolano, B. (2009). Copy number variation and missense mutations of the agouti signaling protein (ASIP) gene in goat breeds with different coat colors. Cytogenetic and Genome Research 126, 333–337.CrossRefGoogle ScholarPubMed
Fontanesi, L., Beretti, F., Riggio, V., Dall'Olio, S., Calascibetta, D., Russo, V. & Portolano, B. (2010). 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.CrossRefGoogle Scholar
Furumura, M., Sakai, C., Abdel-Malek, Z., Barsh, G. S. & Hearing, V. J. (1996). The interaction of agouti signal protein and melanocyte stimulating hormone to regulate melanin formation in mammals. Pigment Cell Research 9, 191–203.CrossRefGoogle ScholarPubMed
Graphodatskaya, D., Joerg, H. & Stranzinger, G. (2002). Molecular and pharmacological characterisation of the MSH-R alleles in Swiss cattle breeds. Journal of Receptor and Signal Transduction Research 22, 421–430.CrossRefGoogle ScholarPubMed
Gratten, J., Beraldi, D., Lowder, B. V., McRae, A. F., Visscher, P. M., Pemberton, J. M. & 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, J. G., Brown, E. A., Beraldi, D., Pemberton, J. M. & Slate, J. (2010). The genetic basis of recessive self-colour pattern in a wild sheep population. Heredity 104, 206–214.CrossRefGoogle Scholar
Hearing, V. J. (2005). Biogenesis of pigment granules: a sensitive way to regulate melanocyte function. Journal of Dermatological Science 37, 3–14.CrossRefGoogle ScholarPubMed
Henikoff, S. & Henikoff, J. G. (1992). Amino acid substitution matrices from protein blocks. Proceedings of the National Academy of Sciences of the USA 89, 10915–10919.CrossRefGoogle ScholarPubMed
Hiragaki, T., Inoue-Murayama, M., Miwa, M., Fujiwara, A., Mizutani, M., Minvielle, F. & Ito, S. I. (2008). Recessive black is allelic to the yellow plumage locus in Japanese quail and associated with a frameshift deletion in the ASIP gene. Genetics 178, 771–775.CrossRefGoogle Scholar
Hoekstra, H. E. (2006). Genetics, development and evolution of adaptive pigmentation in vertebrates. Heredity 97, 222–234.CrossRefGoogle ScholarPubMed
Hoekstra, H. E., Hirschmann, R. J., Bundey, R. A., Insel, P. A. & Crossland, J. P. (2006). A single amino acid mutation contributes to adaptive beach mouse color pattern. Science 313, 101–104.CrossRefGoogle ScholarPubMed
Huang, L. T., Gromiha, M. M. & Ho, S. Y. (2007). iPTREE-STAB: interpretable decision tree based method for predicting protein stability changes upon mutations. Bioinformatics 23, 1292–1293.CrossRefGoogle ScholarPubMed
Hustad, C. M., Perry, W. L., Siracusa, L. D., Rasberry, C., Cobb, L., Cattanach, B. M., Kovatch, R., Copeland, N. G. & Jenkins, N. A. (1995). Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus. Genetics 140, 255–265.CrossRefGoogle ScholarPubMed
Ito, S., Wakamatsu, K. & Ozeki, H. (2000). Chemical analysis of melanins and its application to the study of the regulation of melanogenesis. Pigment Cell Research 13 (Suppl. 8), 103–109.CrossRefGoogle Scholar
Jackson, I. J., Budd, P., Horn, J. M., Johnson, R., Raymond, S. & Steel, K. (1994). Genetics and molecular biology of mouse pigmentation. Pigment Cell Research 7, 73–80.CrossRefGoogle ScholarPubMed
Kall, L., Krogh, A. & Sonnhammer, E. L. (2007). Advantages of combined transmembrane topology and signal peptide prediction – the Phobius web server. Nucleic Acids Research 35 (Web Server issue), W429–W432.CrossRefGoogle ScholarPubMed
Kerns, J. A., Olivier, M., Lust, G. & Barsh, G. S. (2003). Exclusion of melanocortin-1 receptor (Mclr) and Agouti as candidates for dominant black in dogs. The Journal of Heredity 94, 75–79.Google Scholar
Kerns, J. A., Newton, J., Berryere, T. G., Rubin, E. M., Cheng, J. F., Schmutz, S. M. & Barsh, G. S. (2004). Characterization of the dog Agouti gene and a nonagoutimutation in German Shepherd Dogs. Mammalian Genome 15, 798–808.CrossRefGoogle Scholar
Kumar, P., Henikoff, S. & Ng, P. C. (2009). Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nature Protocols 4, 1073–1081.CrossRefGoogle ScholarPubMed
Le Pape, E., Wakamatsu, K., Ito, S., Wolber, R. & Hearing, V. J. (2008). Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor. Pigment Cell and Melanoma Research 21, 477–486.CrossRefGoogle ScholarPubMed
Lin, H.-H. & Tseng, L.-Y. (2010). DBCP: a web server for disulfide bonding connectivity pattern prediction without the prior knowledge of the bonding state of cysteines. Nucleic Acids Research 38 (Suppl. 2), W503–W507.CrossRefGoogle ScholarPubMed
McGregor, B. A. (2006). Production, attributes and relative value of alpaca fleeces in southern Australia and implications for industry development. Small Ruminant Research 61, 93–111.CrossRefGoogle Scholar
McNulty, J. C., Jackson, P. J., Thompson, D. A., Chai, B., Gantz, I., Barsh, G. S., Dawson, P. E. & Millhauser, G. L. (2005). Structures of the agouti signaling protein. Journal of Molecular Biology 346, 1059–1070.CrossRefGoogle ScholarPubMed
Miltenberger, R. J., Wakamatsu, K., Ito, S., Woychik, R. P., Russell, L. B. & Michaud, E. J. (2002). Molecular and phenotypic analysis of 25 recessive, homozygous-viable alleles at the mouse agouti locus. Genetics 160, 659–674.CrossRefGoogle ScholarPubMed
Newton, R. A., Smit, S. E., Barnes, C. C., Pedley, J., Parsons, P. G. & Sturm, R. A. (2005). Activation of the cAMP pathway by variant human MC1R alleles expressed in HEK and in melanoma cells. Peptides 26, 1818–1824.CrossRefGoogle ScholarPubMed
Ng, P. C. & Henikoff, S. (2006). Predicting the effects of amino acid substitutions on protein function. Annual Review of Genomics and Human Genetics 7, 61–80.CrossRefGoogle ScholarPubMed
Norris, B. J. & Whan, V. A. (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
Oyehaug, L., Plahte, E., Vage, D. I. & Omholt, S. W. (2002). The regulatory basis of melanogenic switching. Journal of Theoretical Biology 215, 449–468.CrossRefGoogle ScholarPubMed
Perry, W. L., Hustad, C. M., Swing, D. A., Jenkins, N. A. & Copeland, N. G. (1995). A transgenic mouse assay for agouti protein activity. Genetics 140, 267–274.CrossRefGoogle ScholarPubMed
Powell, A. J., Moss, M. J., Tree, L. T., Roeder, B. L., Carleton, C. L., Campbell, E. & Kooyman, D. L. (2008). Characterization of the effect of Melanocortin 1 Receptor, a member of the hair color genetic locus, in alpaca (Lama pacos) fleece color differentiation. Small Ruminant Research 79, 183–187.CrossRefGoogle Scholar
Ramensky, V., Bork, P. & Sunyaev, S. (2002). Human non-synonymous SNPs: server and survey. Nucleic Acids Research 30, 3894–3900.CrossRefGoogle ScholarPubMed
Rees, J. L. (2003). Genetics of hair and skin color. Annual Review of Genetics 37, 67–90.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Rouzaud, F. & Hearing, V. J. (2005). Regulatory elements of the melanocortin 1 receptor. Peptides 26, 1858–1870.CrossRefGoogle ScholarPubMed
Rouzaud, F., Martin, J., Gallet, P. F., Delourme, D., Goulemot-Leger, V., Amigues, Y., Menissier, F., Leveziel, 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, L. J., Alvarez, I., Arranz, J. J., Fernandez, I., Rodriguez, A., Perez-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.CrossRefGoogle Scholar
Schmutz, S. M., Berryere, T. G. & Goldfinch, A. D. (2002). TYRP1 and MC1R genotypes and their effects on coat color in dogs. Mammalian Genome 13, 380–387.CrossRefGoogle ScholarPubMed
Scott, M. C., Wakamatsu, K., Ito, S., Kadekaro, A. L., Kobayashi, N., Groden, J., Kavanagh, R., Takakuwa, T., Virador, V., Hearing, V. J. & Abdel-Malek, Z. A. (2002). Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation. Journal of Cell Science 115, 2349–2355.CrossRefGoogle ScholarPubMed
Siracusa, L. D. (1994). The agouti gene: turned on to yellow. Trends in Genetics 10, 423–428.CrossRefGoogle Scholar
Sponenberg, P. (2001). Some educated guesses on color genetics of alpacas. Alpaca Registry Journal 6, 4–15.Google Scholar
Sturm, R. A., Teasdale, R. D. & Box, N. F. (2001). Human pigmentation genes: identification, structure and consequences of polymorphic variation. Genetics 277, 49–62.Google ScholarPubMed
Thiruvenkadan, A. K., Kandasamy, N. & Panneerselvam, S. (2008). Coat colour inheritance in horses. Livestock Science 117, 109–129.CrossRefGoogle Scholar
Tully, G. (2007). Genotype versus phenotype: human pigmentation. Forensic Science International: Genetics 1, 105–110.CrossRefGoogle ScholarPubMed
Waterhouse, A. M., Procter, J. B., Martin, D. M., Clamp, M. & Barton, G. J. (2009). Jalview Version 2 – a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191.CrossRefGoogle ScholarPubMed
Willard, D. H., Bodnar, W., Harris, C., Kiefer, L., Nichols, J. S., Blanchard, S., Hoffman, C., Moyer, M., Burkhart, W., Weiel, J., Luther, M. A., Wilkinson, W. O. & Rocque, W. J. (1995). Agouti structure and function: characterization of a potent alpha-melanocyte stimulating hormone receptor antagonist. Biochemistry 34, 12341–12346.CrossRefGoogle ScholarPubMed
Yu, B. & Millhauser, G. L. (2007). Chemical disulfide mapping identifies an inhibitor cystine knot in the agouti signaling protein. FEBS Letters 581, 5561–5565.CrossRefGoogle ScholarPubMed
Supplementary material: File

Munyard Supplementary Material

Munyard Supplementary Table Explanation

Download Munyard Supplementary Material(File)
File 12 KB
Supplementary material: PDF

Munyard Supplementary Material

Munyard Supplementary Table

Download Munyard Supplementary Material(PDF)
PDF 43.6 KB