PRKG2 Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism

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 endochondra...

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Bibliographic Details
Published in:Genes
Main Authors: Gabriela Rudd Garces, Maria Elena Turba, Myriam Muracchini, Alessia Diana, Vidhya Jagannathan, Fabio Gentilini, Tosso Leeb
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2021
Subjects:
Canis lupus familiaris
linkage analysis
homozygosity mapping
whole genome sequencing
bone
growth
Genetics
QH426-470
Argentino
Canis lupus
Online Access:https://doi.org/10.3390/genes12101489
https://doaj.org/article/9ed0930d757f44c296ef175c0d9b6201
Description
Summary: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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