OMIA 002223-9913 : Interdigital hyperplasia in Bos taurus

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: Bovine interdigital hyperplasia

Species-specific symbol: BIH

Inheritance: This disorder is multifactorial. As summarised by Zhang et al. (2019), "Bovine interdigital hyperplasia (IH) is a typical disease of the foot with varying prevalence depending on age, breed, and environmental factors resulting in different degrees of lameness. In studies based on assessments of claw health status at time of hoof trimming and applying genetic-statistical models to analyze this data, IH consistently exhibits high estimates of heritability in the range of 0.30–0.40."

Mapping: A GWAS on 91 Holsteins, each genotyped with the BovineSNP50 BeadChip, yielding 45,232 informative SNPs, enabled Zhang et al. (2019) to identify a QTL for this disorder on chromosome BTA8, marked by two SNPs, one "in intron 5 and [the other] downstream of the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene . . . [which] plays a key role in ossification of the distal limbs and is associated with brachydactylies in humans".

Markers: Sequencing of the positional and functional candidate gene ROR2 enabled Zhang et al. (2019) to identify a missense variant (NC_037335.1:g.85,905,534T>A, ARS-UCD1.2; ENSBTAP00000053765.2:p.Trp9Arg; rs377953295) significantly associated with the disorder, accounting for 32.2% of the variance in type A IH (at least one hind leg affected) and 20.1% of the variance in type B IH (both hind legs affected). The authors also reported that "Quantification of ROR2 mRNA and ROR2 protein showed that the variant resulted in a significant suppression of ROR2 expression in homozygous affected compared to wild type and carrier cows."

Clinical features: Zhang et al. (2019): "Normally IH begins with a small and painless protrusion of the interdigital skin which sometimes can already be diagnosed at calf age. In the final stage clinical signs of IH are firm tumor like masses found in the interdigital space with skin lesions that can result in deep necrosis and phlegmonous inflammations."

Breed: Holstein.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ROR2 receptor tyrosine kinase-like orphan receptor 2 Bos taurus 8 NC_037335.1 (85905274..86141520) ROR2 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Holstein Interdigital hyperplasia ROR2 missense ARS-UCD1.2 8 g.85,905,534T>A p.(Trp9Arg) Zhang et al. (2019): "NC_037335.1:g.85,905,534T>A, ARS-UCD1.2; ENSBTAP00000053765.2:p.Trp9Arg; rs377953295" rs377953295 2019 31798639

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2019 Zhang, X., Swalve, H.H., Pijl, R., Rosner, F., Wensch-Dorendorf, M., Brenig, B. :
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, 2019. Pubmed reference: 31798639. DOI: 10.3389/fgene.2019.01157.
1952 Götze, R. :
Praktische Hinweise zur Erkennung der Erbgesundheit und Erbfruchtbarkeit aus dem Erscheinungsbild des Zuchtbullen Tierärztl. Umsch. 7:466-474, 1952.

Edit History


  • Created by Frank Nicholas on 18 Jan 2020
  • Changed by Frank Nicholas on 18 Jan 2020
  • Changed by Frank Nicholas on 19 Jan 2020