<i>PRKG2</i> 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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MDPI AG
2021-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/10/1489 |
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| author | Gabriela Rudd Garces Maria Elena Turba Myriam Muracchini Alessia Diana Vidhya Jagannathan Fabio Gentilini Tosso Leeb |
| author_facet | Gabriela Rudd Garces Maria Elena Turba Myriam Muracchini Alessia Diana Vidhya Jagannathan Fabio Gentilini Tosso Leeb |
| author_sort | Gabriela Rudd Garces |
| collection | DOAJ |
| description | 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, <i>PRKG2</i>:XM_022413533.1:c.1634+1G>T, affects the splice donor site and is therefore predicted to disrupt the function of the <i>PKRG2</i> gene encoding protein, kinase cGMP-dependent type 2, a known regulator of chondrocyte differentiation. The genotypes of the <i>PRKG2</i> variant were perfectly associated with the phenotype in the studied family of dogs. <i>PRKG2</i> 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 <i>PRKG2</i>:c.1634+1G>T to be a candidate causative variant for the observed dwarfism phenotype in Dogo Argentino dogs. |
| first_indexed | 2024-03-10T06:32:57Z |
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| id | doaj.art-9ed0930d757f44c296ef175c0d9b6201 |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T06:32:57Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-9ed0930d757f44c296ef175c0d9b62012023-11-22T18:20:42ZengMDPI AGGenes2073-44252021-09-011210148910.3390/genes12101489<i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate DwarfismGabriela Rudd Garces0Maria Elena Turba1Myriam Muracchini2Alessia Diana3Vidhya Jagannathan4Fabio Gentilini5Tosso Leeb6Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandGenefast Srl, 47100 Forlì, ItalyLupo Alberto Veterinary Clinic, 40038 Vergato, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, ItalyInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandDepartment of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, ItalyInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandDwarfism 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, <i>PRKG2</i>:XM_022413533.1:c.1634+1G>T, affects the splice donor site and is therefore predicted to disrupt the function of the <i>PKRG2</i> gene encoding protein, kinase cGMP-dependent type 2, a known regulator of chondrocyte differentiation. The genotypes of the <i>PRKG2</i> variant were perfectly associated with the phenotype in the studied family of dogs. <i>PRKG2</i> 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 <i>PRKG2</i>:c.1634+1G>T to be a candidate causative variant for the observed dwarfism phenotype in Dogo Argentino dogs.https://www.mdpi.com/2073-4425/12/10/1489<i>Canis lupus familiaris</i>linkage analysishomozygosity mappingwhole genome sequencingbonegrowth |
| spellingShingle | Gabriela Rudd Garces Maria Elena Turba Myriam Muracchini Alessia Diana Vidhya Jagannathan Fabio Gentilini Tosso Leeb <i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism Genes <i>Canis lupus familiaris</i> linkage analysis homozygosity mapping whole genome sequencing bone growth |
| title | <i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism |
| title_full | <i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism |
| title_fullStr | <i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism |
| title_full_unstemmed | <i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism |
| title_short | <i>PRKG2</i> Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism |
| title_sort | i prkg2 i splice site variant in dogo argentino dogs with disproportionate dwarfism |
| topic | <i>Canis lupus familiaris</i> linkage analysis homozygosity mapping whole genome sequencing bone growth |
| url | https://www.mdpi.com/2073-4425/12/10/1489 |
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