Categories: Limbs / fins / digit / tail phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 602337 (gene) , 113000 (trait) , 268310 (trait)

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Disease-related: 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 (black and white) (Cattle) (VBO_0000237).
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: