OMIA 000201-9986 : Coat colour, agouti in Oryctolagus cuniculus

In other species: horse , cattle , meadow voles , red fox , pig , sheep , domestic cat , 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 , 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: 2010

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: As summarised by Robinson (1958), classic inheritance studies established the existence of three alleles at this locus, namely agouti (A), tan (also known as black and tan) (a^t) and self or non-agouti (a).

Molecular basis: Fontanesi et al. (2010) "identified the causative mutation (an insertion in exon 2) of the black nonagouti allele", namely "c.5_6insA mutation (which causes a frameshift and a predicted truncated protein of only 21 amino acids".

Letko et al. (2020) identified a likely causal variant for the a^t allele, namely "an approximately 11 kb deletion (NC_013672.1:g.5,455,408_5,466,123del" in the ASIP gene. The authors noted that the "deletion is located in the region of the hair cycle‐specific ASIP promoter and thus in a region homologous to the site of the retroviral insertion causing the at allele in mice."

Prevalence: Letko et al. (2020) "genotyped 49 rabbits with different coat colours . . . . Out of 19 black and tan rabbits analysed, 17 carried the deletion in a homozygous state. The remaining two black and tan rabbits were heterozygous for the deletion but also heterozygous for the single base insertion, causing recessive black and thus presumably compound heterozygous a^t/a. As the a allele is recessive to a^t, rabbits with an a^t/a genotype are phenotypically black and tan. None of the 30 rabbits that were not black and tan carried the deletion in a homozygous state."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ASIP agouti signaling protein Oryctolagus cuniculus 4 NC_013672.1 (5554164..5435027) 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
Black (non-agouti) ASIP a insertion, small (<=20) c.5_6insA Letko et al. (2020): NM_001122939.1:c.5_6insA 2010 20004240
Black and tan ASIP a^t deletion, gross (>20) OryCun2.0 4 g.5,455,408_5,466,123del Letko et al. (2020): NC_013672.1:g.5,455,408_5,466,123del 2020 31729778

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.
2020 Letko, A., Ammann, B., Jagannathan, V., Henkel, J., Leuthard, F., Schelling, C., Carneiro, M., Drögemüller, C., Leeb, T. :
A deletion spanning the promoter and first exon of the hair cycle-specific ASIP transcript isoform in black and tan rabbits. Anim Genet 51:137-140, 2020. Pubmed reference: 31729778. DOI: 10.1111/age.12881.
2019 Sakuma, Y., Matsunami, M., Takada, T., Suzuki, H. :
Multiple Conserved Elements Structuring Inverted Repeats in the Mammalian Coat Color-Related Gene <i>Asip</i>. Zoolog Sci 36:23-30, 2019. Pubmed reference: 31116535. DOI: 10.2108/zs180081.
2010 Fontanesi, L., Forestier, L., Allain, D., Scotti, E., Beretti, F., Deretz-Picoulet, S., Pecchioli, E., Vernesi, C., Robinson, TJ., Malaney, JL., Russo, V., Oulmouden, A. :
Characterization of the rabbit agouti signaling protein (ASIP) gene: transcripts and phylogenetic analyses and identification of the causative mutation of the nonagouti black coat colour. Genomics 95:166-75, 2010. Pubmed reference: 20004240. DOI: 10.1016/j.ygeno.2009.11.003.
1958 Robinson, R. :
Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.
1953 Cleffmann, G. :
[Studies on the coat markings of wild rabbits; a contribution to the mechanism of the agouti factor.] Z Indukt Abstamm Vererbungsl 85:137-62, 1953. Pubmed reference: 13091004.

Edit History


  • Created by Frank Nicholas on 09 Jul 2010
  • Changed by Frank Nicholas on 08 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 17 Jun 2013
  • Changed by Frank Nicholas on 19 Nov 2019
  • Changed by Frank Nicholas on 13 Apr 2020