OMIA 000202-9685 : Coat colour, albinism in Felis catus

In other species: goldfish , grass carp , rainbow trout , Japanese medaka , axolotl , African clawed frog , dark-spotted frog , Japanese wrinkled frog , Tufted capuchin , grivet , Bornean orangutan , dog , American black bear , brown bear , raccoon , domestic ferret , lion , Sumatran tiger , humpback whale , ass , pig , hippopotamus , cattle , sheep , hares , rabbit , golden hamster , North American deer mouse , Mongolian gerbil , meadow voles , domestic guinea pig , nutria , gray short-tailed opossum , northern pocket gopher , Arizona pocket mouse , rufous rat-kangaroo , turkey vulture , eastern chipmunk , Campbell's desert hamster , water buffalo , western chorus frog , American mink , Rice frog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 203100

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Congenital lack of pigment in all parts of the body. Due to a non-functional form of the enzyme tyrosinase. Also known as Oculocutaneous albinism (OCA)

Species-specific name: congenital inherited strabismus and spontaneous nystagmus

Species-specific symbol: CISSN

Inheritance: As reported by Lyons et al. (2005), "The locus was originally designated the color locus (C). Breeding data from cats suggested an allelic series with at least three alleles, C > c^b > c^s (Robinson 1991). . . . The C allele is completely dominant with normal colour presentation. The Burmese phenotypic variant, c^b c^b, results in a temperature-sensitive gradient of greatest pigmentation at the points and less on the torso. The well-known Siamese ‘pointed’ phenotype is c^s c^s; the fur is pigmented only at the extremities, the torso colouration is very light to white, and the lack of pigmentation produces blue eye colour. One cat breed, the Tonkinese, is heterozygous (c^b c^s) and has an intermediate colour gradient phenotype to Burmese and Siamese. Several cat breeds are fixed for the albinism alleles. These include Burmese and Singapura for the c^b allele, and Siamese, Birman, and Himalayan (pointed Persians) for the c^s allele."

Yu et al. (2019) extended this allelic relationship by including the mocha allele, c^m: "The new color variant adds to the allelic series for TYR (C > c^b = c^s > c, c^2 ) and is recessive to full color (C); however, interactions with the c^b and c^s alleles are unclear due to the temperature-sensitivity of the alleles."

Mapping: O'Brien et al. (1986) linkage mapped feline albinism to the gene for beta haemoglobin (HBB). Since the tyrosinase gene (TYR) was known to be linked to HBB in mice, this provided additional strong evidence for TYR as the most likely comparative positional candidate gene for feline albinism.

Molecular basis: In a landmark study, and based on TYR being a very likely comparative positional candidate gene (see above), Lyons et al. (2005) confirmed what had long been suspected, namely that the trademark Burmese and Siamese coat colours are due to mutations in the tyrosinase (TYR) gene. The Burmese phenotype is due to a 715G>T transversion in exon 1, resulting in a G227W amino-acid substitution; and the Siamese phenotype is due to a 940G>A transition in exon 2, resulting in a G302R amino-acid substitution. Two months later, Schmidt-Küntzel et al. (2005) independently reported the same results. (Lyons et al. (2005): accepted 20 January 2005; Schmidt-Küntzel et al. (2005): accepted 21 March 2005)

The following year, Imes et al. (2006) discovered a causal mutation for complete albinism: "a cytosine deletion in TYR at position 975 in exon 2, which causes a frame shift resulting in a premature stop codon nine residues downstream from the mutation."

Abitbol et al. (2017) reported a different TYR albino mutation in a domestic shorthair cat, namely c.1204C>T; p.R402*

Yu et al. (2019) reported that a "novel coloration named 'mocha' has been identified in the Burmese cat breed from Thailand" and that "Sanger sequencing for genomic DNA revealed NC_018732.3:chromosome D1:45 898 609_45 898 771dup in exon 2 and intron 2 of TYR. Transcription analysis using cDNA detected c.820_936delinsAATCTC (p.I274_L312delinsNL), which caused a 111-bp (37 amino acid) deletion in the reading frame of TYR. The identified variant was concordant with the phenotype and segregated with TYR variants in a pedigree of 12 Burmese cats."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TYR tyrosinase Felis catus D1 NC_018732.3 (45908743..45803122) TYR 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, complete albinism TYR c deletion, small (<=20) D1 "a cytosine deletion in TYR at position 975 in exon 2" 2006 16573534
Siamese Siamese coat colour TYR c^s missense D1 c. 940G>A p.G302R 2005 15771720
Albinism TYR c^2 nonsense (stop-gain) Felis_catus_6.2 D1 g.46311692C>T c.1204C>T p.R402* 2017 27634063 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Burmese Burmese coat colour TYR c^b missense Felis_catus_6.2 D1 g.46406472G>T c.679G>T p.G227W 2005 15771720 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Burmese Mocha TYR c^m duplication Felis_catus_9.0 D1 g.45898609-45898771dup c.820_936delinsAATCTC p.I274_L312delinsNL Yu et al. (2019): "Sanger sequencing for genomic DNA revealed NC_018732.3:chromosome D1:45 898 609_45 898 771dup in exon 2 and intron 2 of TYR. Transcription analysis using cDNA detected c.820_936delinsAATCTC (p.I274_L312delinsNL), which caused a 111‐bp (37 amino acid) deletion in the reading frame of TYR." 2019 30716167

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.
2019 Yu, Y., Grahn, R.A., Lyons, L.A. :
Mocha tyrosinase variant: a new flavour of cat coat coloration. Anim Genet :, 2019. Pubmed reference: 30716167. DOI: 10.1111/age.12765.
2017 Abitbol, M., Bossé, P., Grimard, B., Martignat, L., Tiret, L. :
Allelic heterogeneity of albinism in the domestic cat. Anim Genet 48:127-128, 2017. Pubmed reference: 27634063. DOI: 10.1111/age.12503.
2006 Imes, DL., Geary, LA., Grahn, RA., Lyons, LA. :
Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation. Anim Genet 37:175-8, 2006. Pubmed reference: 16573534. DOI: 10.1111/j.1365-2052.2005.01409.x.
2005 Kaas, JH. :
Serendipity and the Siamese cat: the discovery that genes for coat and eye pigment affect the brain. ILAR J 46:357-63, 2005. Pubmed reference: 16179744.
Lyons, LA., Imes, DL., Rah, HC., Grahn, RA. :
Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus). Anim Genet 36:119-26, 2005. Pubmed reference: 15771720. DOI: 10.1111/j.1365-2052.2005.01253.x.
Schmidt-Küntzel, A., Eizirik, E., O'Brien, S.J., Menotti-Raymond, M. :
Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. J Hered 96:289-301, 2005. Pubmed reference: 15858157. DOI: 10.1093/jhered/esi066.
2000 Christensen, A.C. :
Cats as an aid to teaching genetics. Genetics 155:999-1004, 2000. Pubmed reference: 10880464.
Schmolesky, M.T., Wang, Y.C., Creel, D.J., Leventhal, A.G. :
Abnormal retinotopic organization of the dorsal lateral geniculate nucleus of the tyrosinase-negative albino cat Journal of Comparative Neurology 427:209-219, 2000. Pubmed reference: 11054689.
1992 Berman, N.E.J., Grant, S. :
Topographic Organization, Number, and Laminar Distribution of Callosal Cells Connecting Visual Cortical Area-17 and Area-18 of Normally Pigmented and Siamese Cats Visual Neuroscience 9:1-19, 1992. Pubmed reference: 1378754.
1991 Robinson, R. :
Colour and cat inheritance. In "Genetics for cat breeders", Pergamon Press, Oxford. :113-114, 1991.
1990 Garraghty, P.E., Schall, J.D., Kaas, J.H. :
Normal Somatotopy in SI of a Tyrosinase-Negative Albino Cat Brain Research 536:315-317, 1990. Pubmed reference: 2085758.
Yin, T.C.T., Carney, L.H., Joris, P.X. :
Interaural Time Sensitivity in the Inferior Colliculus of the Albino Cat Journal of Comparative Neurology 295:438-448, 1990. Pubmed reference: 2351762. DOI: 10.1002/cne.902950308.
1986 O'Brien, S.J., Haskins, M.E., Winkler, C.A., Nash, W.G., Patterson, D.F. :
Chromosomal mapping of beta-globin and albino loci in the domestic cat. A conserved mammalian chromosome map Journal of Heredity 77:374-378, 1986. Pubmed reference: 3559163.
1985 Leventhal, A.G., Vitek, D.J., Creel, D.J. :
Abnormal visual pathways in normally pigmented cats that are heterozygous for albinism Science 229:1395-1397, 1985. Pubmed reference: 3929383.
Leventhal, AG., Creel, DJ. :
Retinal projections and functional architecture of cortical areas 17 and 18 in the tyrosinase-negative albino cat. J Neurosci 5:795-807, 1985. Pubmed reference: 2983049.
1984 Conlee, JW., Parks, TN., Romero, C., Creel, DJ. :
Auditory brainstem anomalies in albino cats: II. Neuronal atrophy in the superior olive. J Comp Neurol 225:141-8, 1984. Pubmed reference: 6725637. DOI: 10.1002/cne.902250115.
1983 Creel, D., Conlee, J.W., Parks, T.N. :
Auditory brainstem anomalies in albino cats. I. Evoked potential studies. Brain Res 260:1-9, 1983. Pubmed reference: 6824946.
1982 Creel, D., Hendrickson, AE., Leventhal, AG. :
Retinal projections in tyrosinase-negative albino cats. J Neurosci 2:907-11, 1982. Pubmed reference: 6808091.
1981 Turner, P., Robinson, R., Dyte, C.E. :
Blue-eyed albino - a new albino allele in the domestic cat Genetica 56:71-73, 1981.
1971 Creel, D.J. :
Visual system anomaly associated with albinism in the cat. Nature 231:465-6, 1971. Pubmed reference: 4931610.
1963 Todd, N.B. :
Independent assortment of Manx and three coat colour mutants in the domestic cat Journal of Heredity 54:266-272, 1963. Pubmed reference: 14098315.
1931 Bamber, R.C., Herdman, E.C. :
Two new colour-types in cats Nature 127:558 only, 1931. DOI: 10.1038/127558c0.
1930 Iljin, N.A., Iljin, V.N. :
Temperature effects on the colour of the Siamese cat Journal of Heredity 21:309-318, 1930.
1924 Tjebbes. K. :
Crosses with Siamese cats Journal of Genetics 14:355-366, 1924.

Edit History


  • Created by Frank Nicholas on 12 Nov 2010
  • Changed by Frank Nicholas on 15 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
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  • Changed by Frank Nicholas on 08 Feb 2019