Computed Tomographic Measures of Funnel-Shaped Lumbar Vertebral Canal and Articular Process Dysplasia Malformations Differ Between German Shepherd and Belgian Malinois Military Working Dogs

Dragicevich, Constance; Jones, Jeryl C.; Bridges, William C.; Dunn, Heather

doi:10.3389/fvets.2020.00275

Cited by 1 publication

(1 citation statement)

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“…A precise, systematic and, ultimately, ontological collection of the phenes (deep phenotyping) becomes increasingly important as the number of known hereditary disorders very rapidly increases, along with an awareness that different genetic variants are responsible for confounding phenotypes. While this has already been well established in human medicine, the characterization of atypical clinical cases in animals is also of pivotal importance to veterinary medicine and science [32].…”

Section: Discussionmentioning

confidence: 99%

PRKG2 Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism

Garces

Turba²,

Muracchini

et al. 2021

Genes

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Dwarfism phenotypes occur in many species and may be caused by genetic or environmental factors. In this study, we investigated a family of nine Dogo Argentino dogs, in which two dogs were affected by disproportionate dwarfism. Radiographs of an affected dog revealed a decreased level of endochondral ossification in its growth plates, and a premature closure of the distal ulnar physes. The pedigree of the dogs presented evidence of monogenic autosomal recessive inheritance; combined linkage and homozygosity mapping assigned the most likely position of a potential genetic defect to 34 genome segments, totaling 125 Mb. The genome of an affected dog was sequenced and compared to 795 control genomes. The prioritization of private variants revealed a clear top candidate variant for the observed dwarfism. This variant, PRKG2:XM_022413533.1:c.1634 + 1G>T, affects the splice donor site and is therefore predicted to disrupt the function of the PKRG2 gene encoding protein, kinase cGMP-dependent type 2, a known regulator of chondrocyte differentiation. The genotypes of the PRKG2 variant were perfectly associated with the phenotype in the studied family of dogs. PRKG2 loss-of-function variants were previously reported to cause disproportionate dwarfism in humans, cattle, mice, and rats. Together with the comparative data from other species, our data strongly suggest PRKG2:c.1634+1G>T to be a candidate causative variant for the observed dwarfism phenotype in Dogo Argentino dogs.

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Section: Discussionmentioning

confidence: 99%