OMIA 000201-9940 : Coat colour, agouti in Ovis aries

In other species: horse , cattle , meadow voles , red fox , pig , domestic cat , rabbit , dog , gray wolf , coyote , goat , Eurasian water mole , Northern mole vole , North American deer mouse , alpaca , leopard , Asiatic golden cat , leopard cat , ass , impala , Colocolo , Kodkod , Geoffroy's cat , Arabian camel

Possibly relevant human trait(s) and/or gene(s) (MIM number): 611742

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2008

Cross-species summary: This locus, ASIP, encodes the agouti signalling protein, a peptide antagonist of the melanocyte-stimulating hormone receptor (MC1R), which is the product of the extension locus.

Species-specific name: black sheep

Inheritance: Davenport (1905) reported autosomal recessive inheritance of black sheep.

Mapping: Utilising comparative deduction from Adalsteinsson (1983) and Adalsteinsson et al. (1987) that recessive black in sheep is likely to be due to an allele at the agouti (ASIP) locus, and comparative-mapping evidence that the ovine agouti locus should be on chromosome OAR13, Parsons et al. (1999) reported linkage between microsatellite markers on OAR13 and recessive self-colour in Australian Merinos.

By genotyping each of 588 Soay sheep with 251 microsatellites and 4 allozyme markers, Beraldi et al. (2006) linkage-mapped a "coat pattern" (wild-type: lighter belly and rump; self: uniform, more intense colour) locus to the region of chromosome OAR13 that includes the ASIP gene.

Molecular basis: Using the comparative candidate-gene strategy (reinforced by mapping results described above), Norris and Whan (2008) showed that the economically important white coat colour in sheep is due to a 190kb tandem duplication encompassing the ASIP gene, the neighbouring AHCY gene and the promoter for a third gene ITCH. This duplicated promoter is so placed as to cause ubiquitous expression of the ASIP gene immediately downstream from it, resulting in the white phenotype. Black sheep are homozygous for a single copy of ASIP with a non-functional promoter.

Building on the mapping results of Beraldi et al. (2006) in Soay sheep, Gratten et al. (2010) sequenced the ASIP gene in Soay sheep segregating for wild-type and self-colour coat pattern (see mapping results above). They identified two mutations "likely to influence the function of the Agouti protein", namely "A 5-bp deletion, g.100-104delAGGAA (hereafter referred to as D5), was present in exon 2. This is a frameshift mutation that introduces a premature stop codon at amino acid position 64, resulting in a mature peptide that lacks the functionally important cysteine-signalling domain"; and "(g.5172T → A) is a non-synonymous mutation that is predicted to cause a cysteine to serine substitution at codon 126 within the signalling domain of the protein." They also reported a synonymous SNP (g.5051G → C). All three mutations had been reported previously in other breeds, by Smit et al. (2002) and Norris and Whan (2008). Gratten et al. reported that "All six self-type sheep were homozygous for a putatively non-functional haplotype comprising D5, g.5051C and g.5172A, whereas wild-type sheep were either homozygous for a functional haplotype containing the non-deleted allele at g.100–104 (referred to as N5), g.5051G and g.5172T (N=4), or were heterozygous at all three positions (N=2)."

By conducting a GWAS on 99 Finnsheep phenotyped for coat colour and pattern, and each genotyped with the Illumina ovine SNP50K BeadChip (yielding 47,303 informative SNPs), Li et al. (2013) identified SNP s66432.1 in the ASIP gene as showing the strongest association with white vs non-white, with the A allele of this SNP being strongly associated with (dominant) white and the G allele with (recessive) non-white in a segregation analysis.

Breed: Merino.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ASIP agouti signaling protein Ovis aries 13 NC_019470.2 (63051795..63128668) ASIP 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 required column headers

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
Coat colour, agouti ASIP insertion, gross (>20) a 190kb tandem duplication encompassing the ASIP gene, the neighbouring AHCY gene and the promoter for a third gene ITCH 2008 18493018

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.
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.
2013 Feulner, P.G., Gratten, J., Kijas, J.W., Visscher, P.M., Pemberton, J.M., Slate, J. :
Introgression and the fate of domesticated genes in a wild mammal population. Mol Ecol :, 2013. Pubmed reference: 23786437. DOI: 10.1111/mec.12378.
Li, M.H., Tiirikka, T., Kantanen, J. :
A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries). Heredity (Edinb) :, 2013. Pubmed reference: 24022497. DOI: 10.1038/hdy.2013.83.
2012 Barrett, R.D. :
Bad coat, ripped genes: cryptic selection on coat colour varies with ontogeny in Soay sheep. Mol Ecol 21:2833-5, 2012. Pubmed reference: 22676073. DOI: 10.1111/j.1365-294X.2012.05560.x.
Gratten, J., Pilkington, J.G., Brown, E.A., Clutton-Brock, T.H., Pemberton, J.M., Slate, J. :
Selection and microevolution of coat pattern are cryptic in a wild population of sheep. Mol Ecol 21:2977-90, 2012. Pubmed reference: 22432567. DOI: 10.1111/j.1365-294X.2012.05536.x.
2011 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 Gratten, J., Pilkington, JG., Brown, EA., Beraldi, D., Pemberton, JM., Slate, J. :
The genetic basis of recessive self-colour pattern in a wild sheep population. Heredity 104:206-14, 2010. Pubmed reference: 19672282. DOI: 10.1038/hdy.2009.105.
Henshall, JM., Whan, VA., Norris, BJ. :
Reconstructing CNV genotypes using segregation analysis: combining pedigree information with CNV assay. Genet Sel Evol 42:34, 2010. Pubmed reference: 20701809. DOI: 10.1186/1297-9686-42-34.
2008 Norris, BJ., Whan, VA. :
A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep. Genome Res 10.1101/gr.072090.10:, 2008. Pubmed reference: 18493018. DOI: 10.1101/gr.072090.107.
Renieri, C., Valbonesi, A., La Manna, V., Antonini, M., Lauvergne, J.J. :
Inheritance of coat colour in Merino sheep. Small Ruminant Research 74:23-29, 2008.
Royo, L.J., Alvarez, I., Arranz, J.J., Fernández, I., Rodríguez, A., Pérez-Pardal, L., Goyache, F. :
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. Anim Genet 39:290-3, 2008. Pubmed reference: 18384465. DOI: 10.1111/j.1365-2052.2008.01712.x.
2006 Beraldi, D., McRae, AF., Gratten, J., Slate, J., Visscher, PM., Pemberton, JM. :
Development of a linkage map and mapping of phenotypic polymorphisms in a free-living population of Soay sheep (Ovis aries). Genetics 173:1521-37, 2006. Pubmed reference: 16868121. DOI: 10.1534/genetics.106.057141.
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.
2002 Smit, M.A., Shay, T.L., Beever, J.E., Notter, D.R., Cockett, N.E. :
Identification of an agouti-like locus in sheep Animal Genetics 33:383-385, 2002. Pubmed reference: 12354151.
1999 Parsons, Y.M., Fleet, M.R., Cooper, D.W. :
Isolation of the ovine Agouti coding sequence Pigment Cell Research 12:394-397, 1999. Pubmed reference: 10614580.
Parsons, Y.M., Fleet, M.R., Cooper, D.W. :
The Agouti gene: a positional candidate for recessive self-colour pigmentation in Australian Merino sheep Australian Journal of Agricultural Research 50:1099-1103, 1999.
1987 Adalsteinsson, S., Hersteinsson, P., Gunnarsson, E. :
Fox colors in relation to colors in mice and sheep Journal of Heredity 78:235-237, 1987. Pubmed reference: 3624844.
1983 Adalsteinsson, S. :
Inheritance of colours, fur characteristics and skin quality traits in North European sheep breeds: a review. Livetsock Production Science 10:555-567, 1983.
1970 Adalsteinsson, S. :
Colour inheritance in Icelandic sheep and relationship between colour, fertility and fertilisation Journal of Agricultural Research in Iceland 2:3-135, 1970.
1969 Brooker, M.G., Dolling, C.H.S. :
Pigmentation of sheep. II. The inheritance of colour patterns in black Merinos Australian Journal of Agricultural Research 20:387-394, 1969.
1965 Hayman, R.H., Cooper, D.W. :
The frequency of pigmented sheep in the Australian Merino Wool Technology and Sheep Breeding 12:81-85, 1965.
1957 Warwick, B.L., Berry, R,O., Davis, S.P. :
Inheritance of recessive black in sheep. Journal of Heredity 48:254–258, 1957.
1905 Davenport, C.B. :
The origin of black sheep in the flock Science 22:674-5, 1905. Pubmed reference: 17797580. DOI: 10.1126/science.22.569.674.
1880 Darwin, C.R. :
Black sheep Nature 23:193, 1880.

Edit History


  • Created by Frank Nicholas on 24 May 2008
  • Changed by Frank Nicholas on 12 Sep 2011
  • Changed by Frank Nicholas on 14 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 27 Feb 2013
  • Changed by Frank Nicholas on 20 Sep 2013
  • Changed by Frank Nicholas on 01 Oct 2015