Interdigital hyperplasia (ROR2-related)

Gene: ROR2

Transmission: Multifactorial.  Heritability estimates of between 0.3 and 0.4.

Mutation: Substitution, ROR2 gene: c.25T>A, p.(Trp9Arg), exon1, Chr.8.

Medical system: Cutaneous, limbs

Breed: Holstein

Age of onset of symptoms: Variable, in the adult animal.

Foot diseases are a common concern for dairy cattle due lameness and resulting to production and economic losses.  The causes of foot diseases in cattle are multifactorial.  Interdigital hyperplasia is one form of foot disease that is suspected to have a genetic component contributing to its incidence.   Interdigital hyperplasia can present initially as a small painless dermal protrusion between the digits but can progresses to a large tumor like mass involving inflammation, necrosis and lameness and resulting in the eventual culling of the affected animal.  A molecular analysis was performed on 91 cows from a herd of Holstein dairy cows that showed a high prevalence of interdigital hyperplasia, and a mutation within the ROR2 gene was identified. The ROR2 gene codes for a growth factor receptor known to be involved in bone and cartilage growth particularly within the digits. In the study, animals that were carriers of the ROR2 mutation had an increased incidence of interdigital hyperplasia compared to animals that were clear for the mutation, indicating an association with the disease. However, animals that were clear for the mutation could still suffer from interdigital hyperplasia, suggesting that additional factors were also contributing to the incidence of the disease.  A large survey of 3093 samples revealed a carrier frequency of the ROR2 mutation of 20.1%.  The relevance of the ROR2 mutation in interdigital hyperplasia must now be validated in additional studies.

References:

OMIA link: [2223-9913]

Križanac AM, Reimer C, Heise J, et al. (2025) Sequence-based genome-wide association study and fine-mapping in German Holstein reveal new quantitative trait loci for health traits. J Dairy Sci 108:7310-7328.  [pm/40349760]

Zhang X, Swalve HH, Pijl R, et al. (2019) Interdigital hyperplasia in Holstein Cattle is associated with a missense mutation in the signal peptide region of the tyrosine-protein kinase transmembrane receptor gene. Front Genet 10:1157. [pm/31798639]

With contributions by: Camille Daigneault and Kaitlyn Lewis, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).