OMIA:002549-9685 : Coat colour and pattern, charcoal, ASIP-related in Felis catus
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 600201 (gene) , 611742 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal incomplete dominant
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2014
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".
Species-specific description: Gershony et al. (2014): "The Bengal cat breed consists of hybrid animals originally developed from crosses between the domestic cat (Felis silvestris catus) and the Asian leopard cat (Prionailurus bengalensis) ... . An unusual pelage type involving a darker face ‘mask’ and a dark dorsal stripe, commonly referred to as a ‘cape’, is unique to the breed. This ‘charcoal’ pattern does not produce a fully melanistic cat (see OMIA000201-9685 : Coat colour, agouti in Felis catus) but bestows darker and more extended markings ... , suggesting unusual interactions between melanism and patterning genes in the hybrid cats."
Molecular basis: By sequencing a prime comparative candidate locus (ASIP) in Bengal cats, Asian leopard cats and domestic cats, Gershony et al. (2014) showed that the charcoal coat colouration/pattern in Bengal cats is strongly associated with compound heterozygosity for an ASIP haplotype from the euptilura form of Asian leopard cat (called A^Pbe) and the feline non-agouti allele a (ASIP:c.123-124del; Eizirik et al., 2003; see OMIA 000201-9685) from domestic cats.
The A^Pbe haplotype, considered by Gershony et al. (2014) to be the wild-type ASIP allele in euptilura Asian leopard cats, differs from the feline agouti (A) "by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4.” The authors do not know which of these leopard cat variants would independently cause the phenotype. The four missense variants (c.41G>C, p.(Cys14Ser); c.142T>C, p.(Ser48Pro); c.251A>G, p.(Gln84Arg) and c.302A>G, p.Asp101Gly), and possibly the 42-bp deletion in intron 4, have been proposed to be used as associated markers.
However, the association between the compound heterozygote A^Pbe/a (ASIP:c.[41G>C;142T>C;251A>G;302A>G];[123-124del]) and charcoal phenotype is not complete. Gershony et al. (2014): "Fifty-six of 64 charcoal Bengals were heterozygous at ASIP, with one domestic cat non-agouti haplotype (a) and one leopard cat haplotype (A^Pbe). Eight Bengals, submitted as charcoal in colouration, had different haplotype combinations. ... Eight of 78 Bengal cats submitted as non-charcoal were homozygous or heterozygous for the leopard cat ASIP haplotype (A^Pbe) and the wild-type domestic haplotype (A)."
Additional variants were identified to contribute to a unique haplotype for ASIP exon 2 (c.41G>C, c.110-111GG>AA and c.127A>G) termed A2. "Twenty-four non-charcoal Bengals and one Savannah carried the A2 haplotype with either the domestic cat wild-type agouti (A) or non-agouti (a) haplotypes. ... The A2 haplotype was not detected in the wild felids; therefore, its origin is unknown.”
Gershony et al. (2014) conclude that “the allelic relationships of ASIP-A^Pbe with ASIP-A and ASIP-a are not fully understood, and more systematic studies are needed”, and that “other interesting phenotypes may occur when the hybrid cats have agouti haplotypes from different species. … Other wild felid-specific variants will likely affect tabby patterning … as well as other aspects of colouration and morphological variation, each potentially affecting the accuracy of genetic tests.”
Breed: Bengal (Cat) (VBO_0100040).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ASIP||agouti signaling protein||Felis catus||A3||NC_058370.1 (24990144..24826711)||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|
|1452||Bengal (Cat)||Coat colour and pattern, charcoal||ASIP||missense||Naturally occurring variant||Felis_catus_9.0||A3||c.251A>G||p.(Q84R)||variant contributes to A^Pbe haplotype associated with charcoal colour/pattern (in exon 4, not present in Felis_catus_9.0)||2014||25143047|
|1453||Bengal (Cat)||Coat colour and pattern, charcoal||ASIP||missense||Naturally occurring variant||Felis_catus_9.0||A3||c.302A>G||p.(D101G)||variant contributes to A^Pbe haplotype associated with charcoal colour/pattern (in exon 4, not present in Felis_catus_9.0)||2014||25143047|
|1450||Bengal (Cat)||Coat colour and pattern, charcoal||ASIP||missense||Naturally occurring variant||Felis_catus_9.0||A3||g.25086548A>G||c.142T>C||p.(S48P)||NM_001009190.1; NP_001009190.1; variant contributes to A^Pbe haplotype associated with charcoal colour/pattern||2014||25143047|
|1451||Bengal (Cat)||Coat colour and pattern, charcoal||ASIP||missense||Naturally occurring variant||Felis_catus_9.0||A3||g.25086649C>G||c.41G>C||p.(C14S)||NM_001009190.1; NP_001009190.1; variant contributes to A^Pbe haplotype associated with charcoal colour/pattern||2014||25143047|
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.
|2014||Gershony, L.C., Penedo, M.C., Davis, B.W., Murphy, W.J., Helps, C.R., Lyons, L.A. :|
|Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed. Anim Genet 45:893-897, 2014. Pubmed reference: 25143047 . DOI: 10.1111/age.12206.|
|2003||Eizirik, E., Yuhki, N., Johnson, W.E., Menotti-Raymond, M., Hannah, S.S., O'Brien, S.J. :|
|Molecular genetics and evolution of melanism in the cat family Current Biology 13:448-53, 2003. Pubmed reference: 12620197 .|
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