Skeletal Atavism

Gene: SHOX

Transmission: Autosomal recessive (pseudoautosomal region, sex chromosomes)

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Mutation Del-l : Deletion, SHOX and CRLF2 genes; 160-180 kb, pseudoautosomal region chrs.X/Y.

Mutation Del-2 : Deletion, CRLF2 gene, 3’ to SHOX gene; 60-80 kb, pseudoautosomal region chrs.X/Y.

Medical system: Skeletal

Breeds: Shetland Poney

Age of onset of symptoms: At birth or several months after birth.

A genetic disease now referred to as Skeletal Atavism has been reported in the Shetland Pony breed of horses for over 60 years. The phenotype involves an abnormal development in the forelimb whereby the ulna is retained as a separate bone and not fused with the radius. In a similar fashion in the hindlimb, the fibula is retained as a separate bone and is not fused with the tibia. Since these modifications to the ulna and the fibula reflect the ancestral form of the primitive horse (as represented in the fossil record), the phenotype is referred to as a skeletal “atavism,” where atavism refers to “ancestral form”. In addition, the phenotype involves a shortening of the humerus, femur, and tibia bones. Affected foals show clinical signs including shorter-than-normal legs, angular deviations of the legs, worsening locomotion with marked lameness, pain, and hoof rotation. These anomalies can be observed at or soon after birth, and usually result in euthanasia of the affected animal. Molecular studies identified two deletions, Del-1 and Del-2, found in the pseudoautosomal region of the X and Y chromosomes that are predicted to deregulate the expression of the SHOX gene. The SHOX gene (Short stature HOmeobox gene X) codes for a transcription factor involved in normal skeletal development of the limbs during early embryo development. Further studies of the skeletal atavism cases showed that the phenotype could be the result of homozygote Del-1, homozygote Del-2, or double heterozygote Del-1/Del-2 genotypes. In a study of 94 normal Swedish Shetland Ponies, the overall combined carrier rate for these mutations was measured to be 11.7%. Availability of DNA tests will allow breeders to eliminate this genetic disease and eventually these mutations from their animals, via selective breeding practices.

References:

Lien OMIA: [2013-9796]

Rafati N, Andersson LS, Mikko S, et al. (2016). Large deletions at the SHOX locus in the pseudoautosomal region are associated with skeletal atavism in Shetland Ponies. G3 (Bethesda) 6(7):2213‑2223. [pm/27207956]

Tyson R, Graham JP, Colahan PT, Berry CR. (2004) Skeletal atavism in a miniature horse. Vet Radiol Ultrasound 45:315-7. [pm/15373256]

Shamis LD, Auer J. (1985) Complete ulnas and fibulas in a pony foal. J Am Vet Med Assoc 186:802-4. [pm/3997641]

Contributed by: Anne-Li Loiselle and Océanne Michaud, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation, DWS)