Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610046 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Disease-related: no

Key variant known: yes

Year key variant first reported: 2012

Species-specific symbol: Ta

Inheritance: Classical segregation studies by Robinson and others suggested that the tabby locus has four alleles that exist in a dominance hierarchy, namely non-tabby (unpatterned agouti, also called Abyssinian or ticked) T^a; spotted tabby T^s; mackerel tabby T^M; blotched tabby t^b. Subsequently, as described in the Mapping section of this page, three loci have been implicated and mapped.

Mapping: By examining the segregation of pairs of tabby alleles in three pedigrees, Eizirik et al. (2010) showed that at least three loci are involved in determining the tabby pattern. A gene (not then identified) in a 5Mb region of cat chromosome FCAA1 accounts for the two main tabby alleles, namely mackerel (T^a) and blotched (t^b). Eizirik et al. (2010) suggested calling this locus the tabby locus. They also show that the T^a allele maps to a 3.8Mb region, now called the Ticked locus, on cat chromosome FCAB1, thereby refining the mapping result of Lyons et al. (2006); see Coat Colour, Ticked (OMIA 001484-9685). The spotted phenotype appears to be due to the action of one or more modifying loci, as yet unmapped.

Molecular basis: By conducting an association analysis with SNPs in the 5MB candidate region of the Tabby locus on chromosome FCAA1 (see Mapping section above), Kaelin et al. (2012) narrowed the hunt down to a 244kb region containing three coding sequences, one of which had not been described previously in the cat. Sequencing cats of various tabby phenotypes revealed a range of causal mutations in the "new" gene, which the authors named Transmembrane Aminopeptidase Q (Taqpep). They named its peptide product Tabulin, to reflect its key role in tabby phenotypes. Using a slightly different nomenclature for tabby alleles, Kaelin et al. (2012) reported that "most blotched cats carried a nonsense mutation, W841X . . . in exon 17 of the third gene [i.e. Taqpep]. We subsequently identified two additional variants in the same gene, S59X and D228N . . . . This gene [Taqpep] is expressed in developing felid skin, and its loss of function causes a loss of color pattern periodicity without obvious effects on other organ systems. . . . In feral cats, we observed homozygosity or compound heterozygosity for the Ta^b S59X or W841X alleles in 58 out of 58 (58/58) blotched animals [Ta^b/Ta^b], with no phenotypic distinction among the different genotypic classes, compared to 51/51 mackerel cats [Ta^M/Ta^M or Ta^M/Ta^b] that carried 0 or 1 Ta^b alleles . . . A third Ta^b allele, D228N, was found to cosegregate with the blotched phenotype in a research colony ...The T139N allele is associated (P = 0.0017, Fisher’s exact test) with an atypical swirled pattern but is incompletely penetrant". In summary, Kaelin et al. (2012) reported three blotched tabby (Ta^b) alleles, namely S59X, D228N and W841X, in the gene named Transmembrane Aminopeptidase Q (Taqpep). Jackson (2013) provides a very informative summary of the results of Kaelin et al. (2012). The gene name "Taqpep" has been replaced by laeverin with symbol LVRN.

Associated gene: