| 1. |
- Axelsson, Erik, et al.
(author)
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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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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:9
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Ljungvall, Ingrid, et al.
(author)
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A Questionnaire Survey on Long-Term Outcomes in Cats Breed-Screened for Feline Cardiomyopathy
- 2022
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In: Animals. - : MDPI AG. - 2076-2615. ; 12
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Journal article (peer-reviewed)abstract
- Simple Summary Feline cardiomyopathy (FCM) is a serious, potentially fatal disease in cats. There is an international screening program that aims to identify pedigree cats affected with FCM, as the disease is believed to be inherited in some cat families. Using a self-reporting questionnaire, this study explored the long-term outcomes of cats breed-screened for FCM. We found that approximately 9.3% of the cats developed FCM at some time-point of which approximately 50% were diagnosed within the screening program and 50% of these cats at the first breed-screen occasion. For cats that did develop FCM, there was a significantly higher risk for a cardiac related death and also a shorter time to all-cause mortality, compared to cats that did not develop FCM. Frequency and types of non-cardiac disease were similar in all screen classification groups. The large proportion of cats that did develop FCM later in life, despite normal previous screen results, underscores the value of repeated breed-screenings later in life to identify cats that develop FCM. Feline cardiomyopathy (FCM) is an important contributor to feline morbidity and mortality. This explorative follow-up questionnaire study was aimed at investigating the long-term outcome in cats breed-screened for FCM (BS-FCM) in three Nordic countries. Records of cats with >= 1 BS-FCM between 2004-2015 were included. Of the 1113 included cats, 104/1113 (9.3%) had developed FCM at some time-point. Fifty-nine of the 104 (56.7%) FCM cats were diagnosed within the screening program (Screen(FCM)), and 33/59 (55.9%) of these were diagnosed at the first BS-FCM. Screen(FCM) cats or with an owner-reported FCM diagnosis at a later time-point had a higher risk of cardiac-related death compared to cats that never developed FCM. A shorter lifespan was found in Screen(FCM) cats compared to those with normal screen results (p < 0.001). Times to all-cause mortality were shorter (p < 0.001) in cats that developed FCM at any time-point compared to those that did not. Non-cardiac morbidities were similar in all screen classification groups. The large proportion of cats that developed FCM at a later time-point underscores the need for repeated screenings later in life. Cats that developed FCM at any time-point had a shorter lifespan, with a similar proportion and in line with the nature of non-cardiac morbidities, compared to those without FCM.
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| 4. |
- Tidholm, Anna, et al.
(author)
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Prognostic value of selected one-, two-and three-dimensional and Doppler echocardiographic methods to assess severity in dogs with myxomatous mitral valve disease
- 2022
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In: Journal of Veterinary Cardiology. - : Elsevier BV. - 1760-2734 .- 1875-0834. ; 39, s. 89-101
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Journal article (peer-reviewed)abstract
- Introduction: Although challenging, predicting outcomes in dogs with myxomatous mitral valve disease (MMVD) is of importance to owners and veterinar-ians. Our aim was to compare the prognostic value of selected one-, two-, and three-dimensional and Doppler echocardiographic methods to predict cardiac-re-lated and all-cause mortality in MMVD dogs. We hypothesize that three-dimensional methods would better predict prognosis than one-and two-dimensional methods.Animals: One-hundred thirty-eight privately-owned dogs with MMVD. Materials and methods: Cox proportional Hazard analyses and Kaplan-Meier curves were used to investigate the predictive value of 14 variables; left atrial (LA) volume indexed to body weight (BW) measured by real-time three-dimensional echocardio-graphy (RT3DE) and calculated using Simpson's modified method of discs (SMOD) and the area-length method; LA diameter in short-axis and long-axis to aortic in short-axis ratio, effective regurgitant orifice area indexed to body surface area measured in RT3DE en face view and calculated using four-chamber (4Ch) and two-chamber views alone or in combination; percentage increase in left ventricular end-diastolic and systolic internal diameters; fractional shortening; E wave velo -city; regurgitant jet area/LA area. Results: All 14 variables were significantly predictive of cardiac-related mortality, and 11 were predictive of all-cause mortality. The prognosis was best predicted by LA volume/BW estimated by SMOD or RT3DE, consistently showing the highest pre-dictive value in all analyses.Conclusions: Left atrial volume calculated by SMOD showed a similar predictive va-lue compared to RT3DE. Performing SMOD from apical 4Ch images should be consid-ered an alternative to RT3DE for echocardiographic examinations where prognostication of disease outcome is sought. 2021 Elsevier B.V. All rights reserved.
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| 5. |
- Dubbelboer, Ilse R, et al.
(author)
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Gastrointestinal mucus in dog : Physiological characteristics, composition, and structural properties
- 2022
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 173, s. 92-102
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Journal article (peer-reviewed)abstract
- Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from the epithelium. Our aim was to characterize the composition and structure of mucus throughout the various GI segments in dog.Mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum), and large intestine (cecum, proximal and distal colon) from dogs. Composition was determined by multi-omics. Structural properties were investigated using cryoSEM and rheology.GI mucus contained 74-95% water and maintained a pH around 6.5. The proteome was similar across the different GI segments. The highest abundant secreted gel-forming mucin in the gastric mucus was mucin 5AC, whether mucin 2 had highest abundance in the intestinal mucus. Lipid and metabolite abundance was generally higher in the jejunal mucus than the colonic mucus. CryoSEM microscopy revealed smaller pore size in small intestinal mucus, which increased in the large intestine. All mucus samples showed shear-thinning behavior and characteristics of gel-like structure.In conclusion, the mucus is a highly viscous and hydrated material. These data provide an important baseline for future studies on human and canine intestinal diseases and the dog model in drug absorption.
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| 6. |
- Hanås, Sofia, et al.
(author)
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Cardiac troponin I in healthy Norwegian Forest Cat, Birman and domestic shorthair cats, and in cats with hypertrophic cardiomyopathy.
- 2022
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In: Journal of feline medicine and surgery. - : Sage Publications. - 1098-612X .- 1532-2750. ; 24:10, s. e370-e379
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables.METHODS: Cardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE.RESULTS: In healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats (P = 0.014) and in neutered male cats than in intact females (P = 0.032). Cardiac TnI was positively associated with HR (P <0.0001). In cats with HCM, cTnI concentration was positively associated with left ventricular wall thickness and with left atrial-to-aortic root ratio (all P ⩽0.010). Cats with HCM had higher cTnI concentrations than healthy cats, and cTnI concentrations were higher in cats with HCM and LAE than in those with HCM without LAE (all P = 0.0003).CONCLUSIONS AND RELEVANCE: Breed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM.
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| 7. |
- Höglund, Katja, et al.
(author)
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The chromogranin A-derived peptides catestatin and vasostatin in dogs with myxomatous mitral valve disease
- 2020
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In: Acta Veterinaria Scandinavica. - : BMC. - 0044-605X .- 1751-0147. ; 62:1
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Journal article (peer-reviewed)abstract
- Background The protein chromogranin A (CgA) is stored and co-released with catecholamines from the stimulated adrenal glands. Increased plasma concentrations of CgA have been shown in people with heart disease. The aim of the study was to investigate whether plasma concentrations of the CgA-derived biologically active peptides catestatin and vasostatin were associated with the severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between these blood variables and dog characteristics, echocardiographic variables, heart rate (HR), blood pressure (BP) and plasma N-terminal-proBNP (NT-proBNP) concentration. Sixty-seven privately owned dogs with or without MMVD were included. The dogs underwent physical examination, blood pressure measurement, blood sample collection, and echocardiographic examination. Plasma concentrations of catestatin and vasostatin were analyzed using radioimmunoassay. Results Catestatin concentration decreased with increasing left atrial and ventricular size (R-2 <= 0.09, P <= 0.019), and increased with increasing systolic and diastolic blood pressures (R-2 <= 0.08, P <= 0.038). Regression analyses showed no significant associations for vasostatin. No differences in plasma concentrations of catestatin or vasostatin were found between the disease severity groups used in the study. Conclusions In the present dog population, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes, both of which are known to increase with increasing severity of MMVD. Furthermore, the catestatin concentration showed weak positive associations with blood pressure.
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| 8. |
- Mäkeläinen, Suvi, et al.
(author)
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Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs
- 2020
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In: Genes. - : MDPI. - 2073-4425. ; 11:9
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Journal article (peer-reviewed)abstract
- In golden retriever dogs, a 1 bp deletion in the canineTTC8gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans,TTC8is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited 10 affected dogs to the study. The progression of PRA for two of the dogs was followed for 2 years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-lengthTTC8transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.
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| 9. |
- Rohdin, Cecilia, et al.
(author)
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Thoracolumbar meningeal fibrosis in pugs
- 2020
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In: Journal of Veterinary Internal Medicine. - : WILEY. - 0891-6640 .- 1939-1676. ; 34:2, s. 797-807
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Journal article (peer-reviewed)abstract
- Background Thoracolumbar myelopathies associated with spinal cord and vertebral column lesions, with a similar clinical phenotype, but different underlying etiologies, occur in pugs. Objectives To further characterize the clinical and neuropathological characteristics of pugs with longstanding thoracolumbar myelopathy. Animals Thirty client-owned pure-bred pugs with a history of more than a month of ataxia and paresis of the pelvic limbs, suggesting a myelopathy localized to the thoracolumbar spinal cord, were included in the study. Methods Prospective clinicopathological study. Included pugs underwent a complete neurological examination and gross and histopathologic postmortem studies with focus on the spinal cord. Computed tomography (n = 18), magnetic resonance imaging (n = 17), and cerebrospinal fluid analysis (n = 27) were performed before or immediately after death. Results Twenty male and 10 female pugs had a median age at clinical onset of 84 months (interquartile range, 66-96). Affected pugs presented with a progressive clinical course and 80% were incontinent. There was circumferential meningeal fibrosis with concomitant focal, malacic, destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs. Vertebral lesions accompanied the focal spinal cord lesion, and there was lympho-histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs. Conclusions and Clinical Importance Meningeal fibrosis with associated focal spinal cord destruction and neighboring vertebral column lesions were common findings in pugs with long-standing thoracolumbar myelopathy.
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| 10. |
- Wang, Chao, et al.
(author)
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A novel canine reference genome resolves genomic architecture and uncovers transcript complexity
- 2021
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Journal article (peer-reviewed)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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