OMIA 000201-9925 : Coat colour, agouti in Capra hircus

In other species: horse , cattle , meadow voles , red fox , pig , sheep , domestic cat , rabbit , dog , gray wolf , coyote , Eurasian water mole , Northern mole vole , North American deer mouse , alpaca , leopard , Asiatic golden cat , leopard cat , ass , impala , Colocolo , Kodkod , Arabian camel , Mongolian gerbil , domestic guinea pig , Western roe deer

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

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2009

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. 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".

Inheritance: Adalsteinsson et al. (1994) that there are "10 alleles at the Agouti locus [in goats], with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A(wt)), black mask (A(blm)), bezoar (A(bz)), badgerface (A(b)), grey (A(g)), lightbelly (A(lb)), swiss markings (A(sm)), lateral stripes (A(ls)), mahogany (A(mh)), red cheek (A(rc)), and nonagouti (Aa)."

Molecular basis: Fontanesi et al. (2009) "confirmed the presence of CNV [copy number variation] affecting a region of less that 100 kb including the ASIP and AHCY genes. In Girgentana and Saanen breeds, this CNV might cause the AWt allele, as already suggested for a similar structural mutation in sheep affecting the ASIP and AHCY genes, providing evidence for a recurrent interspecies CNV."

Henkel et al. (2019) "confirmed the previously reported [by Fontanesi et al., 2009] triplication and revealed the exact boundaries of the triplication [for the A^Wt allele]. It spans 154,677 bp of the reference genome sequence and comprises the entire coding sequence of the ASIP, AHCY and ITCH genes. The individual copies are arranged in tandem in a head to tail orientation." These same authors also identified the molecular basis of three other alleles, summarising their results for the four alleles as: "Analysis of . . . selective sweeps revealed four different CNVs associated with the white or tan (AWt), Swiss markings (Asm), badgerface (Ab), and the newly proposed peacock (Apc) allele. RNA-seq analyses on skin samples from goats with the different CNV alleles suggest that the identified structural variants lead to an altered expression of ASIP between eumelanistic and pheomelanistic body areas."

Breeds: Appenzell, Bezoar, Chamois Colored, Girgentana, Grisons Striped, Peacock, Saanen, St. Gallen Booted, Toggenburg.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ASIP agouti signaling protein Capra hircus 13 NC_030820.1 (63228709..63249542) 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 second, third etc relevant column headers.

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.

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
Peacock Peacock ASIP A^pc repeat variation "The ASIP allele in Peacock goats, which we propose to term “peacock” (A^pc), has a quadruplication of the same ~45 kb region having five copies in the A^b allele. It is additionally flanked by triplicated segments of 27,996 bp and 41,807 bp on the left and right side of the quadruplicated sequence (Fig 3, S4 Fig, S5 Table). The central part of the A^pc allele has exactly the same breakpoints as the A^b allele suggesting a common origin of A^b and A^pc." (Henkel et al., 2019) "63'158'171-63'203'851: 4 copies (corresponds to the CNV in the Ab allele)" (Table S5; Henkel et al., 2019) 200922: Marius picked this g. entry up as requiring attention: "g.63130175_63245658 (3 copies)". Because this will take time to sort out, I have removed it from the g. field for the time being. 2019 31841508
Bezoar Wild type or Bezaur ASIP A^bz wild type (i.e. normal) "The goat genome reference sequence is derived from a San Clemente goat, which has a similar coat color pattern as bezoars. The genome reference therefore supposedly represents the wildtype allele at the ASIP locus, termed “bezoar” (Abz) [8]. Bezoars and all other Swiss goat breeds did not show any CNVs at the ASIP locus." (Henkel et al., 2019) 2019 31841508
Appenzell Girgentana Saanen White or tan ASIP A^Wt repeat variation ARS1 13 "CNV [copy number variation] affecting a region of less that 100 kb including the ASIP and AHCY genes" (Fontanesi et al., 2009)."spans 154,677 bp ofthe reference genome sequence and comprises the entire coding sequence ofthe ASIP, AHCYand ITCH genes. The individual copies are arranged in tandem in a head to tail orientation." (Henkel et al., 2019) 200922: moved the g. entry to here (g.63,226,824-63,381,501 (3 copies)) until it can be standardised 2009 20016133
Grisons Striped Toggenburg Swiss markings ASIP A^sm repeat variation ARS1 13 "8 tandem copies of a 13,433 bp sequence from the 5’-flanking region of ASIP" (Henkel et al., 2019) 200922: moved g. entry to here (g.63,129,198-63,142,631 (8 copies)) until it can be fixed 2019 31841508
Chamois Colored St. Gallen Booted Badgerface ASIP A^b repeat variation ARS1 13 "a five-fold amplification of45,680 bp located ~61 kb downstream ofthe Asm amplification" (Henkel et al., 2019) 200922: move the g. entry to here (g.63,158,171-63,203,851 (5 copies)), until it can be fixed 2019 31841508

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.
2019 Henkel, J., Saif, R., Jagannathan, V., Schmocker, C., Zeindler, F., Bangerter, E., Herren, U., Posantzis, D., Bulut, Z., Ammann, P., Drögemüller, C., Flury, C., Leeb, T. :
Selection signatures in goats reveal copy number variants underlying breed-defining coat color phenotypes. PLoS Genet 15:e1008536, 2019. Pubmed reference: 31841508. DOI: 10.1371/journal.pgen.1008536.
2017 Martin, P.M., Palhière, I., Ricard, A., Tosser-Klopp, G., Rupp, R. :
Correction: Genome Wide Association Study Identifies New Loci Associated with Undesired Coat Color Phenotypes in Saanen Goats. PLoS One 12:e0186029, 2017. Pubmed reference: 28982168. DOI: 10.1371/journal.pone.0186029.
2016 Martin, P.M., Palhière, I., Ricard, A., Tosser-Klopp, G., Rupp, R. :
Genome Wide Association Study Identifies New Loci Associated with Undesired Coat Color Phenotypes in Saanen Goats. PLoS One 11:e0152426, 2016. Pubmed reference: 27030980. DOI: 10.1371/journal.pone.0152426.
2013 Adefenwa, M.A., Peters, S.O., Agaviezor, B.O., Wheto, M., Adekoya, K.O., Okpeku, M., Oboh, B., Williams, G.O., Adebambo, O.A., Singh, M., Thomas, B., De Donato, M., Imumorin, I.G. :
Identification of single nucleotide polymorphisms in the agouti signaling protein (ASIP) gene in some goat breeds in tropical and temperate climates. Mol Biol Rep 40:4447-57, 2013. Pubmed reference: 23661018. DOI: 10.1007/s11033-013-2535-1.
2011 Badaoui, B., D'Andrea, M., Pilla, F., Capote, J., Zidi, A., Jordana, J., Ferrando, A., Delgado, J.V., Martínez, A., Vidal, O., Amills, M. :
Polymorphism of the goat agouti signaling protein gene and its relationship with coat color in Italian and Spanish breeds. Biochem Genet 49:523-32, 2011. Pubmed reference: 21373989. DOI: 10.1007/s10528-011-9427-7.
2010 Li, X.L., Zhao, J.W., Tang, C.J., Zhou, R.Y., Zheng, G., Li, L.H., Guo, X.L. :
Sequencing of part of the goat agouti gene and SNP identification. Biochem Genet 48:152-6, 2010. Pubmed reference: 20094847. DOI: 10.1007/s10528-009-9307-6.
2009 Fontanesi, L., Beretti, F., Riggio, V., Gómez González, E., Dall'Olio, S., Davoli, R., Russo, V., Portolano, B. :
Copy number variation and missense mutations of the agouti signaling protein (ASIP) gene in goat breeds with different coat colors. Cytogenet Genome Res 126:333-47, 2009. Pubmed reference: 20016133. DOI: 10.1159/000268089.
2008 Tang, C.J., Zhou, R.Y., Li, X.L., Zhao, J.W., Li, L.H., Feng, F.J., Li, D.F., Wang, J.T., Guo, X.L., Keng, J.F. :
Variation of 423G>T in the Agouti gene exon 4 in indigenous chinese goat breeds. Biochem Genet 46:770-80, 2008. Pubmed reference: 18792776. DOI: 10.1007/s10528-008-9192-4.
1994 Adalsteinsson, S., Sponenberg, D.P., Alexieva, S., Russel, A.J.F. :
Inheritance of goat coat colors Journal of Heredity 85:267-272, 1994. Pubmed reference: 7930499.

Edit History


  • Created by Frank Nicholas on 10 Sep 2011
  • Changed by Frank Nicholas on 10 Sep 2011
  • Changed by Frank Nicholas on 17 Oct 2011
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