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 , llama , oldfield mouse
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 611742 (trait) , 600201 (gene)
Links to MONDO diseases: No links.
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) hypothesized 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 (a)."
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 A^Wt 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 (A^Wt), Swiss markings (A^sm), badgerface (A^b), and the newly proposed peacock allele (A^pc). 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."
Henkel et al. (2021): "4 different color varieties of Valais goats were known. Besides Blackneck animals … the brown and white Copperneck goat, the white Capra Sempione, and the greyish Grüenochte comprised the historic Valais goats. The brown pigmentation of Copperneck goats had previously been traced back to an introgression of a mutant TYRP1 allele from Toggenburg goats [OMIA 001249-9925]. In the present study, we identified additional introgression events of distinct ASIP alleles causing the remaining 2 rare coat color patterns within the Valais Blackneck goat breed. We identified the introgression of the AWt allele from Appenzell or Saanen goats in white Capra Sempione goats. Similarly, introgression of the A^pc allele from Peacock goats resulted in the greyish Grüenochte phenotype."
Breeds: Appenzell (Goat) (VBO_0000724), Bezoar (Goat) (VBO_0000733), Chamois Coloured (Goat) (VBO_0000747), Girgentana, Italy (Goat) (VBO_0009647), Grisons Striped (Goat) (VBO_0000771), Peacock Goat (Goat) (VBO_0000818), Saanen (Goat) (VBO_0000827), St Gallen Booted Goat (Goat) (VBO_0000839), Toggenburg (Goat) (VBO_0000846), Valais Blackneck (Goat) (VBO_0000849), Valais Capra Sempione, Valais Copperneck, Valais Grüenochte.
|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|
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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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1199||Peacock Goat (Goat) Valais Grüenochte||Peacock||ASIP||A^pc||repeat variation||Naturally occurring variant||13||"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|
|1200||Bezoar (Goat) Valais Blackneck (Goat) Valais Copperneck||Wild type or Bezaur||ASIP||A^bz||reference sequence allele||Naturally occurring variant||13||"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) . Bezoars and all other Swiss goat breeds did not show any CNVs at the ASIP locus." (Henkel et al., 2019)||2019||31841508|
|1196||Appenzell (Goat) Girgentana, Italy (Goat) Saanen (Goat)||White or tan||ASIP||A^Wt||repeat variation||Naturally occurring variant||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|
|1197||Grisons Striped (Goat) Toggenburg (Goat)||Swiss markings||ASIP||A^sm||repeat variation||Naturally occurring variant||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|
|1198||Chamois Coloured (Goat) St Gallen Booted Goat (Goat)||Badgerface||ASIP||A^b||repeat variation||Naturally occurring variant||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|
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.
|2022||Guo, J., Sun, X., Mao, A., Liu, H., Zhan, S., Li, L., Zhong, T., Wang, L., Cao, J., Liu, G.E., Zhang, H. :|
|A 13.42-kb tandem duplication at the ASIP locus is strongly associated with the depigmentation phenotype of non-classic Swiss markings in goats. BMC Genomics 23:437, 2022. Pubmed reference: 35698044 . DOI: 10.1186/s12864-022-08672-9.|
|Signer-Hasler, H., Henkel, J., Bangerter, E., Bulut, Z. :|
|Runs of homozygosity in Swiss goats reveal genetic changes associated with domestication and modern selection. Genet Sel Evol 54:6, 2022. Pubmed reference: 35073837 . DOI: 10.1186/s12711-022-00695-w.|
|2021||Henkel, J., Dubacher, A., Bangerter, E., Herren, U., Ammann, P., Drögemüller, C., Flury, C., Leeb, T. :|
|Introgression of ASIP and TYRP1 alleles explains coat color variation in Valais goats. J Hered 112:452-457, 2021. Pubmed reference: 34050662 . DOI: 10.1093/jhered/esab024.|
|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 .|
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