Polydactyly

 

Gene: SHH, LMBR1 genes

Transmission: Autosomal dominant

For a genetic disease that is autosomal dominant, the animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.

Mutation: within ZRS (ZPA Regulatory Sequence) region of the LMBR1 gene, upstream of the SHH gene

Mutation UK1: Substitution, ZPA; g.169533066 C>G, c.257 G>C, chromosome A2

Mutation Hw: Substitution, ZPA; g.169532844 T>C, c.479 A>G, chromosome A2

Mutation UK2: Substitution, ZPA; g.169532842 T>A, c.481 A>T, chromosome A2

Medical system: Skeletal

Breeds: Many breeds, Domestic Shorthair, Highland Lynx, Maine Coon, Pixie-bob

Age of onset of symptoms: polydactyly is evident at birth.

Polydactyly refers to more than the usual number of toes.  The cat normally has 5 toes (digits) on each of its front paws and 4 toes on each of its back paws.  Additional digits can occur, usually on the front paws, to give an animal known as a mitten cat or a Hemingway cat.  Polydactyly cats were historically found on the east coast of North America and the west coast of England and were felt to bring good luck to sailors on sailing ships.  Polydactyly is an autosomal dominant trait that shows incomplete penetrance.  It has been associated with natural mutations within the ZRS (ZPA regulatory Sequence) region found within the LMBR1 gene.  The ZRS is found 1 MB upstream of the SHH gene, which codes for a signalling protein involved in normal modelling of the digits.  These mutations cause excessive and ectopic expression of the SHH gene (and protein), resulting in the formation of the additional digits.

 

References:

OMIA link: [0810-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Hamelin A, Conchou F, Fusellier M, et al. (2020) Genetic heterogeneity of polydactyly in Maine Coon cats.  J Feline Med Surg (Epub)  [pubmed/32067556]

Hamelin A, Begon D, Conchou F, et al. (2016) Clinical characterization of polydactyly in Main Coon cats.  J Feline medicine and surgery 19(4):382-393  [pubmed/26862149]

Lange A, Nemeschkal HL, Muller GB. (2014) Biased Polyphenism in Polydactylous Cats Carrying a Single Point Mutation: The Hemingway Model for Digit Novelty. Evolutionary Biology 41(2):262-275. [https://link.springer.com/article/10.1007%2Fs11692-013-9267-y]

Lettice LA, Hill AE, Devenney PS, Hill RE. (2008) Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly.  Human Molecular Genetics 17(7):978-985. [pubmed/18156157]