Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy
Pug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflam...
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MDPI AG
2023-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/2/385 |
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| author | Gustaf Brander Cecilia Rohdin Matteo Bianchi Kerstin Bergvall Göran Andersson Ingrid Ljungvall Karin Hultin Jäderlund Jens Häggström Åke Hedhammar Kerstin Lindblad-Toh Katarina Tengvall |
| author_facet | Gustaf Brander Cecilia Rohdin Matteo Bianchi Kerstin Bergvall Göran Andersson Ingrid Ljungvall Karin Hultin Jäderlund Jens Häggström Åke Hedhammar Kerstin Lindblad-Toh Katarina Tengvall |
| author_sort | Gustaf Brander |
| collection | DOAJ |
| description | Pug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflammation have been described. PDM has a late onset and affects more male than female dogs. The breed-specific presentation of the disorder suggests that genetic risk factors are involved in the disease development. To perform a genome-wide search for PDM-associated loci, we applied a Bayesian model adapted for mapping complex traits (BayesR) and a cross-population extended haplotype homozygosity test (XP-EHH) in 51 affected and 38 control pugs. Nineteen associated loci (harboring 67 genes in total, including 34 potential candidate genes) and three candidate regions under selection (with four genes within or next to the signal) were identified. The multiple candidate genes identified have implicated functions in bone homeostasis, fibrotic scar tissue, inflammatory responses, or the formation, regulation, and differentiation of cartilage, suggesting the potential relevance of these processes to the pathogenesis of PDM. |
| first_indexed | 2024-03-11T08:46:57Z |
| format | Article |
| id | doaj.art-701c7925dd0d45f9b3aff9bc07d9fea6 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T08:46:57Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-701c7925dd0d45f9b3aff9bc07d9fea62023-11-16T20:42:13ZengMDPI AGGenes2073-44252023-02-0114238510.3390/genes14020385Multiple Genetic Loci Associated with Pug Dog Thoracolumbar MyelopathyGustaf Brander0Cecilia Rohdin1Matteo Bianchi2Kerstin Bergvall3Göran Andersson4Ingrid Ljungvall5Karin Hultin Jäderlund6Jens Häggström7Åke Hedhammar8Kerstin Lindblad-Toh9Katarina Tengvall10Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, SwedenDepartment of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, SwedenScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, SwedenDepartment of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, SwedenDepartment of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 750 07 Uppsala, SwedenDepartment of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, SwedenDepartment of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, N-1432 Ås, NorwayDepartment of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, SwedenDepartment of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, SwedenScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, SwedenScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, SwedenPug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflammation have been described. PDM has a late onset and affects more male than female dogs. The breed-specific presentation of the disorder suggests that genetic risk factors are involved in the disease development. To perform a genome-wide search for PDM-associated loci, we applied a Bayesian model adapted for mapping complex traits (BayesR) and a cross-population extended haplotype homozygosity test (XP-EHH) in 51 affected and 38 control pugs. Nineteen associated loci (harboring 67 genes in total, including 34 potential candidate genes) and three candidate regions under selection (with four genes within or next to the signal) were identified. The multiple candidate genes identified have implicated functions in bone homeostasis, fibrotic scar tissue, inflammatory responses, or the formation, regulation, and differentiation of cartilage, suggesting the potential relevance of these processes to the pathogenesis of PDM.https://www.mdpi.com/2073-4425/14/2/385pugmyelopathyGWASdog geneticsBayesRbayesian |
| spellingShingle | Gustaf Brander Cecilia Rohdin Matteo Bianchi Kerstin Bergvall Göran Andersson Ingrid Ljungvall Karin Hultin Jäderlund Jens Häggström Åke Hedhammar Kerstin Lindblad-Toh Katarina Tengvall Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy Genes pug myelopathy GWAS dog genetics BayesR bayesian |
| title | Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy |
| title_full | Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy |
| title_fullStr | Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy |
| title_full_unstemmed | Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy |
| title_short | Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy |
| title_sort | multiple genetic loci associated with pug dog thoracolumbar myelopathy |
| topic | pug myelopathy GWAS dog genetics BayesR bayesian |
| url | https://www.mdpi.com/2073-4425/14/2/385 |
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