Categories: Skeleton phene (incl. short stature & teeth) , Limbs / fins / digit / tail phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 312865 (gene) , 249700 (trait) , 127300 (trait) , 300582 (trait)

Single-gene trait/disorder: yes

Mode of inheritance: Recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2016

Cross-species summary: Atavism is a general term for the reappearance of one or more traits that are known to have occurred in remote ancestors, usually from an ancestral species. The term "skeletal atavism" has been applied to horses with abnormal development of ulna and fibula that somewhat resembles the reduction in size of both bones and their fusion to radius and tibula, respectively, in ancestral equids.

History: Affected Shetland ponies were reported in 1958 in the UK, Netherlands and Sweden. This trait is referred to as an atavism because ancestral species appeared to normally exhibit this condition, according to fossil records (reviewed in Rafati et al., 2016). [IT thanks Miranda Slingerland, working under the guidance of Professor Ernie Bailey, for contributions to this entry in April 2022]

Mapping: Rafati et al. (2016) "performed whole genome resequencing of six SA [skeletal atavism] cases and a pool of control horses and use this data to show that skeletal atavism is associated with two, partially overlapping, large deletions on sequence scaffolds not assigned to any chromosome in the EquCab2.0 genome assembly". These "two partially overlapping large deletions [are] in the pseudoautosomal region (PAR) of chromosome X/Y"

Molecular basis: The deletions mentioned in the Mapping section were named Del-1 and Del-2 (Rafati et al., 2016), and the authors reported that "One of the identified deletions removes the entire coding region of the short stature homeobox (SHOX) gene [Del-1] and both deletions remove parts of the cytokine receptor-like factor 2 (CRLF2) gene located downstream of SHOX." The same authors then "sequenced bacterial artificial chromosome (BAC) clones by single-molecule real-time (SMRT) sequencing technology. This considerably improved the assembly and enabled size estimations of the two deletions to 160-180 kb [Del-1] and 60-80 kb [Del-2], respectively. Complete association between the presence of these deletions and disease status was verified in eight other affected horses. .... We did not observe any obvious phenotypic difference between Del-1/Del-1 and Del-1/Del-2 individuals."

Clinical features: As reported by Rafati et al. (2016), "Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure, impaired movements, and affected foals are usually euthanized."

Prevalence: When testing a random set of 94 Shetland ponies in Sweden, the allele frequencies of disease associated deletions Del1 and Del2 were 0.0479 and 0.0106, respectively (Rafati et al., 2016)

Breed: Shetland Pony (Horse) (VBO_0001066).
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: