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 , 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: 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."
Breeds: Alaska (Rabbit) (VBO_0001227), Blauer Wiener (Rabbit) (VBO_0001234), California (Rabbit) (VBO_0001239), Champagne-Silberkaninchen, Germany (Rabbit) (VBO_0013836), Checkered Giant, Checkered Small, Coloured dwarf, Dutch (Rabbit) (VBO_0001245), English Spot (Rabbit) (VBO_0001246), Fairly Pearly, Giant Grey, Havanna (Rabbit) (VBO_0001256), Lop, Lop dwarf, Marburger Feh (Rabbit) (VBO_0001262), Mini Silver, New Zealand White (Rabbit) (VBO_0001269), Rex (Rabbit) (VBO_0001272), Rheinische Schecken (Rabbit) (VBO_0001275), Russian (Rabbit) (VBO_0001276), Silver (Rabbit) (VBO_0001280), Thüringer (Rabbit) (VBO_0001283), Weisse Wiener (Rabbit) (VBO_0001285), White Hotot (Rabbit) (VBO_0001288).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ASIP||agouti signaling protein||Oryctolagus cuniculus||4||NC_067377.1 (13285285..13089975)||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|
|567||New Zealand White (Rabbit)||Black (non-agouti)||ASIP||a||insertion, small (<=20)||Naturally occurring variant||4||c.5_6insA||Letko et al. (2020): NM_001122939.1:c.5_6insA||2010||20004240|
|1134||Black and tan||ASIP||a^t||deletion, gross (>20)||Naturally occurring variant||OryCun2.0||4||g.5455408_5466123del||Letko et al. (2020): NC_013672.1:g.5,455,408_5,466,123del||2020||31729778|
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 Asip. 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 .|
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