In other species: Japanese medaka , dark-spotted frog , Japanese wrinkled frog , Tufted capuchin , Rhesus monkey , hamadryas baboon , dog , red fox , domestic ferret , lion , humpback whale , ass (donkey) , pig , red deer , American bison , taurine cattle , rabbit , golden hamster , Mongolian gerbil , domestic guinea pig , Japanese ratsnake , water buffalo , four-striped grass mouse , ocelot gecko , American mink , Japanese raccoon dog , Rice frog

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 203100 (trait) , 606952 (trait) , 606933 (gene)

Links to MONDO diseases: No links.

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 most parts of the body. Due to a non-functional form of the enzyme tyrosinase. Also known as Oculocutaneous albinism (OCA), Acromelanism and as the Himalayan coat-colour pattern

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."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene: