In other species: dog , taurine cattle , sheep , Asiatic golden cat

Categories: Limbs / fins / digit / tail phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601397 (gene) , 615709 (trait) , 182940 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Also called brachyury

Species-specific name: Manx tailllessness

Species-specific symbol: MX

History: The taillessness of Manx cats was mentioned in both volumes of Darwin's (1968) "The Variation of Animals and Plants under Domestication". The vol. II entry cites data from a Dr Wilson, which (intriguingly) is not consistent with autosomal dominance and lethal recessiveness: "The Manx cat is tailless and has long hind legs; Dr. Wilson crossed a male Manx with common cats, and, out of twenty-three kittens, seventeen were destitute of tails; but when the female Manx was crossed by common male cats all the kittens had tails, though they were generally short and imperfect." The reliability of these data are uncertain. Nine years after the rediscovery of Mendelism, Bateson (1909) listed Manx taillessness as a Mendelian trait, citing Anthony (1899; Bull. Soc. Anthr., Paris), Hind (1899), Kennel (1901) and Davenport (1905). In describing the variation in the number of vertebrae affected, Todd (1964; J. Hered) cited Anthony (1899; Bull. Soc. Anthr.), Kennel (1901), Schwangart and Grau (1931) and Tacke (1936).

Inheritance: In a report arising from his undergraduate honours project, Todd (1961) documented substantial evidence consistent with Manx tailllessness being an autosomal dominant trait that is lethal when homozygous. The data came from his own observations, and those of Dr Wilson (as quoted by Darwin (1868), Anthony (1899; Bull. Soc. Anthr.), Kennel (1901) and Davenport (1905). Two years later, it appears that Todd (1963) had become aware of earlier evidence published by Suomalainen (1956).

Mapping: After identifying the four causal mutants in the T gene (now called TBXT; see Molecular basis section), Buckingham et al. (2013) conducted a linkage analysis between the T gene and the short-tail trait, and showed zero recombination.

Molecular basis: Following the comparative candidate gene strategy, based on similar phenotypes in mice and dogs known to be due to mutations in the T gene (now called TBXT) that encodes Brachyury (a transcription factor which regulates notochord differentiation), Buckingham et al. (2013) characterised and "sequenced the T gene in several independent lineages of Manx cats from both the US and the Isle of Man and identified three 1-bp deletions [c.998delT; c.1169delC; c.1199delC] and one duplication/deletion [c.998_1014dup17delGCC], each predicted to cause a frameshift that leads to premature termination and truncation of the carboxy terminal end of the Brachyury protein". Buckingham et al. (2013) went on to report "No evidence suggested that the presence of a specific mutant allele of T determined the extent of tail length reduction in the Manx cat . . . no cats were homozygous or compound heterozygous for mutations in T, supporting complete absence of Brachyury results in early embryonic lethality. Genotyping of three fetal cats that died late in gestation found that in all three instances, these individuals were heterozygous for mutant T alleles."

Clinical features: As summarised by Buckingham et al. (2013), "The variable tail length of the Manx recapitulates that of tail variation in mice and can be categorized into four specific tail-length phenotypes. These range from absence of the tail (anury) (i.e., rumpy), a minimal tail (i.e., rumpy-riser) that is apparent only by palpation, a short tail (i.e., stumpy), to a full tail (i.e., longie) . . . (Howell and Siegel 1963; Robinson 1993; Todd 1963). The length of the tail is proportional to the number of caudal vertebrae, with complete absence of caudal vertebrae found only in cats with the rumpy phenotype."

Breeds: American Bobtail (Cat) (VBO_0100003), Manx (Cat) (VBO_0100156), Pixiebob (Cat) (VBO_0100191).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: