OMIA 000201-9615 : Coat colour, agouti in Canis lupus familiaris

In other species: horse , cattle , meadow voles , red fox , pig , sheep , domestic cat , rabbit , 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 , Mongolian gerbil

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: 2004

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.

Mapping: Kerns et al. (2004) mapped the canine Agouti/ASIP gene to "the mid-distal region of CFA24".

Using genotype data from the Affymetrix Canine Array v2.0 100K SNP chip, Dreger et al. (2013) conducted a GWAS on "130 black-and-tan and saddle tan cases and 596 non-pattern controls", which confirmed the ASIP locus on chromosome CFA24 as being responsible for the black-and-tan and saddle tan phenotypes.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on knowledge that the Agouti locus is actually the ASIP gene in many species), Kerns et al. (2004) were the first to characterise the ASIP gene in dogs. The reported "a missense alteration in exon 4, C427T, predicted to cause an Arg-to-Cys substitution at codon 96 (R96C)" and concluded tentatively that "the R96C mutation is the biochemical cause for recessive black".

Berryere et al. (2005) "identified an Agouti allele with two [adjacent] missense alterations, A82S and R83H, which was present (heterozygous or homozygous) in 41 dogs (22 breeds) with a fawn or sable coat, but was absent from 16 dogs (8 breeds) with a black-and-tan or tricolor phenotype"

Dreger and Schmutz (2011) "characterize[d] a mutation consisting of a short interspersed nuclear element (SINE) insertion in intron 1 of ASIP that allows for the differentiation of the a(w) wolf sable and a(t) black-and-tan alleles. The SINE insertion is present in dogs with the a(t) and a alleles but absent from dogs with the a(w) and a(y) alleles. Dogs with the saddle tan phenotype were all a(t)/a(t). Schnauzers were all a(w)/a(w)."

Ciampolini et al. (2013) reported "a short interspersed element and a poly(A) stretch inserted within the promoter region of the ASIP in the Boxer . . . [and] that both insertions are also present in brindle and fawn animals of the Boxer and Great Dane breeds."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ASIP agouti signaling protein Canis lupus familiaris 24 NC_006606.3 (23338757..23393913) 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
Coat colour, agouti ASIP insertion, gross (>20) "a short interspersed element and a poly(A) stretch inserted within the promoter region of the ASIP" 2013 22524303
Fawn or sable ASIP missense c.244G>T; 248G>A p.A82S and p.R83H 2005 15965787
Coat colour, agouti ASIP insertion, gross (>20) CanFam3.1 24 g.23365298ins239 "a short interspersed nuclear element (SINE) insertion in intron 1 of ASIP that allows for the differentiation of the a(w) wolf sable and a(t) black-and-tan alleles" 2011 21846741 Genomic location and description kindly provided by Professor Claire wade in August 2018.
German Shepherd Dog Recessive black ASIP missense CanFam3.1 24 g.23393552C>T c.286C>T p.R96C 2004 15520882 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2013 Ciampolini, R., Cecchi, F., Spaterna, A., Bramante, A., Bardet, S.M., Oulmouden, A. :
Characterization of different 5'-untranslated exons of the ASIP gene in black-and-tan Doberman Pinscher and brindle Boxer dogs. Anim Genet 44:114-7, 2013. Pubmed reference: 22524303. DOI: 10.1111/j.1365-2052.2012.02364.x.
Dreger, D.L., Parker, H.G., Ostrander, E.A., Schmutz, S.M. :
Identification of a mutation that is associated with the saddle tan and black-and-tan phenotypes in Basset Hounds and Pembroke Welsh Corgis. J Hered 104:399-406, 2013. Pubmed reference: 23519866. DOI: 10.1093/jhered/est012.
2012 Dreger, D.L., Schmutz, S.M. :
A case of canine chimerism diagnosed using coat color tests. Mol Cell Probes 26:253-5, 2012. Pubmed reference: 22433982. DOI: 10.1016/j.mcp.2012.03.004.
2011 Dreger, D.L., Schmutz, S.M. :
A SINE Insertion Causes the Black-and-Tan and Saddle Tan Phenotypes in Domestic Dogs. J Hered :S11-8, 2011. Pubmed reference: 21846741. DOI: 10.1093/jhered/esr042.
Oguro-Okano, M., Honda, M., Yamazaki, K., Okano, K. :
Mutations in the melanocortin 1 receptor, β-defensin103 and agouti signaling protein genes, and their association with coat color phenotypes in Akita-inu dogs. J Vet Med Sci 73:853-8, 2011. Pubmed reference: 21321476.
2007 Schmutz, SM., Berryere, TG., Barta, JL., Reddick, KD., Schmutz, JK. :
Agouti sequence polymorphisms in coyotes, wolves and dogs suggest hybridization. J Hered 98:351-5, 2007. Pubmed reference: 17630272. DOI: 10.1093/jhered/esm036.
2005 Berryere, TG., Kerns, JA., Barsh, GS., Schmutz, SM. :
Association of an Agouti allele with fawn or sable coat color in domestic dogs. Mamm Genome 16:262-72, 2005. Pubmed reference: 15965787. DOI: 10.1007/s00335-004-2445-6.
2004 Kerns, JA., Newton, J., Berryere, TG., Rubin, EM., Cheng, JF., Schmutz, SM., Barsh, GS. :
Characterization of the dog Agouti gene and a nonagoutimutation in German Shepherd Dogs. Mamm Genome 15:798-808, 2004. Pubmed reference: 15520882. DOI: 10.1007/s00335-004-2377-1.
2003 Kerns, JA., Olivier, M., Lust, G., Barsh, GS. :
Exclusion of melanocortin-1 receptor (mc1r) and agouti as candidates for dominant black in dogs. J Hered 94:75-9, 2003. Pubmed reference: 12692166.

Edit History


  • Created by Frank Nicholas on 20 Nov 2010
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 22 Sep 2012
  • Changed by Frank Nicholas on 13 May 2013
  • Changed by Frank Nicholas on 17 Jun 2013
  • Changed by Frank Nicholas on 13 Jul 2017