Research article - Peer-reviewed, 2023
Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy
Brander, Gustaf; Rohdin, Cecilia; Bianchi, Matteo; Bergvall, Kerstin; Andersson, Goran; Ljungvall, Ingrid; Jaderlund, Karin Hultin; Haggstrom, Jens; Hedhammar, Ake; Lindblad-Toh, Kerstin; Tengvall, KatarinaAbstract
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.Keywords
pug; myelopathy; GWAS; dog genetics; BayesR; bayesian; selection; XP-EHH; bone homeostasis; cartilage; inflammatory response; fibrotic scar tissuePublished in
Genes2023, volume: 14, number: 2, article number: 385
Publisher: MDPI
Authors' information
Brander, Gustaf
Uppsala University
Brander, Gustaf
Broad Institute
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Bianchi, Matteo
Uppsala University
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Jaderlund, Karin Hultin
Norwegian University of Life Sciences
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Lindblad-Toh, Kerstin
Uppsala University
Lindblad-Toh, Kerstin
Broad Institute
Tengvall, Katarina
Uppsala University
UKÄ Subject classification
Genetics
Publication Identifiers
DOI: https://doi.org/10.3390/genes14020385
URI (permanent link to this page)
https://res.slu.se/id/publ/121670