| 1. |
- Andersson, Linda, et al.
(författare)
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Exploration of body weight in 115 000 young adult dogs of 72 breeds
- 2023
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- High body weight (BW), due to large size or excess body fat, has been associated with developmental and metabolic alterations, and degenerative diseases in dogs. Study objectives were to determine mean BW in young adult dogs of different breeds, including changes over a 10-year period. Body weight data from the official Swedish hip dysplasia screening program were used, including data from dogs screened at 1-2.5 years of age, in breeds with >= 15 individual observations/year during 2007-2016. Mean BW per breed and sex was established from 114 568 dogs representing 72 breeds. Estimates of breed BW showed significant change in 33 (45%) breeds over the 10-year period. Body weight increased in five breeds (2-14% change) and decreased in 26 breeds (1-8% change). In two breeds, BW increased in male and decreased in female dogs. This observational study provides extensive breed BW data on young adult dogs. The change in breed BW, noted in almost half of the breeds, could be due to changes either in size or in body fat mass. In certain breeds, the change in BW over time might have an impact on overall health. Studies with simultaneous evaluation of BW and body condition over time are warranted.
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| 2. |
- Axelsson, Erik, et al.
(författare)
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The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels
- 2021
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.
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| 3. |
- Bianchi, Matteo, et al.
(författare)
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Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs
- 2020
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Ingår i: BMC Genomics. - : BMC. - 1471-2164. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed.Results: By employing genome-wide association followed by fine-mapping (top variant p-value=5.7x10(-6)), integrated with whole-genome resequencing and copy number variation analysis, we detected a similar to 8.9 kbp deletion strongly associated (p-value=0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail.Conclusions: Our results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.
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| 4. |
- Brander, Gustaf, et al.
(författare)
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Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy
- 2023
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Engdahl, Karolina, et al.
(författare)
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Demography and disorders of English Cocker Spaniels under primary veterinary care in the UK
- 2023
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Ingår i: Canine Medicine and Genetics. - 2662-9380. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS.ResultsEnglish Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25–8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12–17.35). The annual proportional birth rate was relatively stable between 2.97–3.51% from 2005–2016. The most common specific diagnoses were periodontal disease (n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31–22.62), otitis externa (n = 234, 10.09%, 95% CI: 8.87–11.32), obesity (n = 229, 9.88%, 95% CI: 8.66–11.09), anal sac impaction (n = 187, 8.07%, 95% CI: 6.96–9.18), diarrhoea (n = 113, 4.87%, 95% CI: 4.00–5.75), and aggression (n = 93, 4.01%, 95% CI: 3.21–4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) (P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) (P = 0.010). The median age at death was 11.44 years (IQR 9.46–13.47) and the most common grouped causes of death were neoplasia (n = 10, 9.26%, 95% CI: 3.79–14.73), mass-associated disorders (n = 9, 8.33%, 95% CI: 4.45–15.08), and collapse (n = 8, 7.41%, 95% CI: 3.80–13.94).ConclusionsPeriodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS.
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| 6. |
- Hedhammar, Åke
(författare)
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Swedish Experiences From 60 Years of Screening and Breeding Programs for Hip Dysplasia-Research, Success, and Challenges
- 2020
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 7
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Forskningsöversikt (refereegranskat)abstract
- A screening program for hip dysplasia (HD) was introduced in Sweden during the 1950s for German shepherd dogs, before for a few breeds and now any breed. Degree of canine HD was originally graded 1-4 (slight, mild, moderate, and severe) and used in Swedish screening program up to year 2000 and was thereafter replaced by letters A-E with A and B for no signs/near normal, C for mild, D for moderate, and E for severe HD. Final scoring is based on "the worst" side. In Sweden, 70% of all dogs are registered by the Swedish Kennel Club, and in relevant breeds, almost all breeding stock and 30-50% of all dogs are screened for HD. By an extensive database of all dogs registered since 1976 and mandatory identification by microchip, all results can be linked to dogs well-defined by identity and ancestral background. An implementation of structured screening and genetic health programs resulted in markedly decreased prevalence of HD already during the 1980s. The programs are based on open registries and on positive as well as negative results for identified individuals linked to their ancestral background. The successful decrease in moderate and severe HDs is illustrated for seven common breeds. However, there is also the challenge of a further decrease when already almost all breeding is performed with unaffected breeding stock. Handling that and the increased relative prevalence of less severe grades of HD (grade C) calls for breed-specific breeding strategies, taking into account the prevalence and clinical significance in each breed. Further decrease might rather be achieved by using estimated breeding values and genomic selection instead of more extensive and costly screening procedures. For the public perception of HD, the value of a clear distinction between grades D and E as a good predictor of the clinical entity vs. grade C as a tool to refine the selection criteria for breeding stock is indicated.
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| 7. |
- Kieler, Ida Nordang, et al.
(författare)
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Genome wide association study in Swedish Labrador retrievers identifies genetic loci associated with hip dysplasia and body weight
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome wide association studies (GWAS) have been utilized to identify genetic risk loci associated with both simple and complex inherited disorders. Here, we performed a GWAS in Labrador retrievers to identify genetic loci associated with hip dysplasia and body weight. Hip dysplasia scores were available for 209 genotyped dogs. We identified a significantly associated locus for hip dysplasia on chromosome 24, with three equally associated SNPs (p = 4.3 x 10-7) in complete linkage disequilibrium located within NDRG3, a gene which in humans has been shown to be differentially expressed in osteoarthritic joint cartilage. Body weight, available for 85 female dogs, was used as phenotype for a second analysis. We identified two significantly associated loci on chromosome 10 (p = 4.5 x 10-7) and chromosome 31 (p = 2.5 x 10-6). The most associated SNPs within these loci were located within the introns of the PRKCE and CADM2 genes, respectively. PRKCE has been shown to play a role in regulation of adipogenesis whilst CADM2 has been associated with body weight in multiple human GWAS. In summary, we identified credible candidate loci explaining part of the genetic inheritance for hip dysplasia and body weight in Labrador retrievers with strong candidate genes in each locus previously implicated in the phenotypes investigated.
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| 8. |
- Lingaas, Frode, et al.
(författare)
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Bayesian mixed model analysis uncovered 21 risk loci for chronic kidney disease in boxer dogs
- 2023
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Author summaryChronic kidney disease (CKD) is described as a set of heterogeneous disorders affecting kidney structure and function. CKD is common in dogs and has been diagnosed in nearly all breeds. In this study, we identified 21 genetic regions associated with CKD in a boxer population and investigated the relevant genes and putative regulatory variants in these regions. Studies of canine CKD may help to better understand the pathology of kidney disease in both dogs and humans, and shows an important potential for early identification of high-risk individuals. Chronic kidney disease (CKD) affects 10% of the human population, with only a small fraction genetically defined. CKD is also common in dogs and has been diagnosed in nearly all breeds, but its genetic basis remains unclear. Here, we performed a Bayesian mixed model genome-wide association analysis for canine CKD in a boxer population of 117 canine cases and 137 controls, and identified 21 genetic regions associated with the disease. At the top markers from each CKD region, the cases carried an average of 20.2 risk alleles, significantly higher than controls (15.6 risk alleles). An ANOVA test showed that the 21 CKD regions together explained 57% of CKD phenotypic variation in the population. Based on whole genome sequencing data of 20 boxers, we identified 5,206 variants in LD with the top 50 BayesR markers. Following comparative analysis with human regulatory data, 17 putative regulatory variants were identified and tested with electrophoretic mobility shift assays. In total four variants, three intronic variants from the MAGI2 and GALNT18 genes, and one variant in an intergenic region on chr28, showed alternative binding ability for the risk and protective alleles in kidney cell lines. Many genes from the 21 CKD regions, RELN, MAGI2, FGFR2 and others, have been implicated in human kidney development or disease. The results from this study provide new information that may enlighten the etiology of CKD in both dogs and humans.
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| 9. |
- Tengvall, Katarina, 1980-, et al.
(författare)
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Bayesian model and selection signature analyses reveal risk factors for canine atopic dermatitis
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus (Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated.
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| 10. |
- Tengvall, Katarina, 1980-, et al.
(författare)
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Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin
- 2020
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Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 72:5, s. 315-323
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Tidskriftsartikel (refereegranskat)abstract
- Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.
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| 11. |
- Wang, Chao, et al.
(författare)
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A novel canine reference genome resolves genomic architecture and uncovers transcript complexity
- 2021
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- We present GSD_1.0, a high-quality domestic dog reference genome with chromosome length scaffolds and contiguity increased 55-fold over CanFam3.1. Annotation with generated and existing long and short read RNA-seq, miRNA-seq and ATAC-seq, revealed that 32.1% of lifted over CanFam3.1 gaps harboured previously hidden functional elements, including promoters, genes and miRNAs in GSD_1.0. A catalogue of canine "dark" regions was made to facilitate mapping rescue. Alignment in these regions is difficult, but we demonstrate that they harbour trait-associated variation. Key genomic regions were completed, including the Dog Leucocyte Antigen (DLA), T Cell Receptor (TCR) and 366 COSMIC cancer genes. 10x linked-read sequencing of 27 dogs (19 breeds) uncovered 22.1 million SNPs, indels and larger structural variants. Subsequent intersection with protein coding genes showed that 1.4% of these could directly influence gene products, and so provide a source of normal or aberrant phenotypic modifications. Here, the authors report an improved de novo reference genome for the domestic dog based on a female German Shepherd named Mischka. The new genome increases contiguity 55-fold over the previous dog assembly and uncovers functional elements that were not previously identifiable.
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