OMIA:002223-9913 : Interdigital hyperplasia in Bos taurus (taurine cattle)
Categories: Limbs / fins / digit / tail phene
Links to MONDO diseases: No links.
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."
Have human generated variants been created, e.g. through genetic engineering and gene editing
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."
Holstein (black and white) (Cattle) (VBO_0000237).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|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 (85905286..86141522)||ROR2||Homologene, Ensembl , NCBI gene|
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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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1139||Holstein (black and white) (Cattle)||Interdigital hyperplasia||ROR2||missense||Naturally occurring variant||ARS-UCD1.2||8||g.85905534T>A||c.25T>A||p.(W9R)||ENSBTAT00000061589.3:c.25T>A ENSBTAP00000053765.2:p.Trp9Arg||rs377953295||rs377953295||2019||31798639|
Cite this entry
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.
|2023||Schneider, H., Heise, J., Tetens, J., Thaller, G., Wellmann, R., Bennewitz, J. :|
|Genomic dominance variance analysis of health and milk production traits in German Holstein cattle. J Anim Breed Genet , 2023. Pubmed reference: 36872841. DOI: 10.1111/jbg.12765.|
|Sousa Junior, L.P.B., Pinto, L.F.B., Cruz, V.A.R., Junior, G.A.O., Oliveira, H.R., Chud, T.S., Pedrosa, V.B., Miglior, F., Schenkel, F.S., Brito, L.F. :|
|Genome-wide association and functional genomic analyses for various hoof health traits in North American Holstein cattle. J Dairy Sci , 2023. Pubmed reference: 37939841. DOI: 10.3168/jds.2023-23806.|
|2022||Schneider, H., Segelke, D., Tetens, J., Thaller, G., Bennewitz, J. :|
|A genomic assessment of the correlation between milk production traits and claw and udder health traits in Holstein dairy cattle. J Dairy Sci , 2022. Pubmed reference: 36460501. DOI: 10.3168/jds.2022-22312.|
|Sölzer, N., May, K., Yin, T., König, S. :|
|Genomic analyses of claw disorders in Holstein cows: Genetic parameters, trait associations, and genome-wide associations considering interactions of SNP and heat stress. J Dairy Sci 105:8218-8236, 2022. Pubmed reference: 36028345. DOI: 10.3168/jds.2022-22087.|
|2021||Butty, A.M., Chud, T.C.S., Cardoso, D.F., Lopes, L.S.F., Miglior, F., Schenkel, F.S., Cánovas, A., Häfliger, I.M., Drögemüller, C., Stothard, P., Malchiodi, F., Baes, C.F. :|
|Genome-wide association study between copy number variants and hoof health traits in Holstein dairy cattle. J Dairy Sci 104(7):8050-8061, 2021. Pubmed reference: 33896633. DOI: 10.3168/jds.2020-19879.|
|Capion, N., Raundal, P., Foldager, L., Thomsen, P.T. :|
|Status of claw recordings and claw health in Danish dairy cattle from 2013 to 2017. Vet J :105749, 2021. Pubmed reference: 34537342. DOI: 10.1016/j.tvjl.2021.105749.|
|2019||Sánchez-Molano, E., Bay, V., Smith, R.F., Oikonomou, G., Banos, G. :|
|Quantitative trait loci mapping for lameness associated phenotypes in Holstein-Friesian dairy cattle. Front Genet 10:926, 2019. Pubmed reference: 31636655. DOI: 10.3389/fgene.2019.00926.|
|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.|
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