OP1 Severity-dependent gene expression in canine myxomatous mitral valve disease

2020 ◽  
Author(s):  
Greg Markby ◽  
Vicky Macrae ◽  
Kim Summers ◽  
Brendan Corcoran
Keyword(s):  
Gene Expression ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Valve Disease

scholarly journals Comparative transcriptomic profiling of myxomatous mitral valve disease in the cavalier King Charles spaniel

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
G. R. Markby ◽  
V. E. Macrae ◽  
B. M. Corcoran ◽  
K. M. Summers
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Expression Patterns ◽  
Valve Disease ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Transcriptomic Profiling ◽  
Cavalier King Charles Spaniel

Abstract Background Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the cavalier King Charles spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs. Results Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

scholarly journals Transcriptomic profiling of peripheral blood nucleated cells in dogs with and without clinical signs of chronic mitral valve disease

2014 ◽  
Vol 58 (1) ◽  
pp. 135-140
Author(s):  
Magdalena Garncarz ◽  
Magdalena Hulanicka ◽  
Marta Parzeniecka-Jaworska ◽  
Jacek Garncarz ◽  
Michał Jank
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Mitral Valve ◽  
Peripheral Blood ◽  
Mitral Valve Disease ◽  
Clinical Signs ◽  
Valve Disease ◽  
Non Invasive ◽  
The Status ◽  
Healthy Dogs

Abstract The aim of the study was to demonstrate differences in the gene expression of signalling pathways between healthy dogs and dogs with chronic mitral valve disease in different heart failure groups. Blood samples were collected from 49 dogs of various breeds between 1.4 and 15.2 years of age. Isolated RNA samples were analysed for quality and integrity and the gene expression profile was determined. The study demonstrated that nucleated cells from peripheral blood can be used to assess the status of heart failure in dogs. Furthermore, significant differences in the expression of the genes were noticed between healthy dogs and dogs with clinical signs of chronic mitral valve disease. This is a preliminary non-invasive study showing the feasibility of genetic testing from peripheral blood nucleated cells, which at the same time has made it possible to set the future directions of genetic studies in clinical cases of canine chronic mitral valve disease.

scholarly journals Correlation between peripheral blood cell transcriptomic profile and clinical parameters of chronic mitral valve disease in Dachshunds

2016 ◽  
Vol 19 (4) ◽  
pp. 849-857 ◽  
Author(s):  
M. Garncarz ◽  
M. Hulanicka ◽  
H. Maciejewski ◽  
M. Parzeniecka-Jaworska ◽  
M. Jank
Keyword(s):  
Gene Expression ◽  
Heart Disease ◽  
Mitral Valve ◽  
Peripheral Blood ◽  
Mitral Valve Disease ◽  
Expression Profiles ◽  
Valve Disease ◽  
Microarray Data Analysis ◽  
Future Research ◽  
Tissue Samples

Abstract Studies identifying specific pathologically expressed genes have been performed on diseased myocardial tissue samples, however less invasive studies on gene expression of peripheral blood mononucleated cells give promising results. This study assessed transcriptomic data that may be used to evaluate Dachshunds with chronic mitral valve disease. Dachshunds with different stages of heart disease were compared to a control, healthy group. Microarray data analysis revealed clusters of patients with similar expression profiles. The clusters were compared to the clinical classification scheme. Unsupervised classification of the studied groups showed three clusters. Clinical and laboratory parameters of patients from the cluster 1 were in accordance with those found in patients without heart disease. Data obtained from patients from the cluster 3 were typical of advanced heart failure patients. Comparison of the cluster 1 and 3 groups revealed 1133 differentially expressed probes, 7 significantly regulated process pathways and 2 significantly regulated Ariadne Metabolic Pathways. This study may serve as a guideline for directing future research on gene expression in chronic mitral valve disease.

scholarly journals Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel

2020 ◽  
Author(s):  
Brendan Corcoran ◽  
Greg Markby ◽  
Vicky Macrae ◽  
Kim Summers
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Expression Patterns ◽  
Valve Disease ◽  
Gene Expression Patterns ◽  
Transcriptomic Profiling ◽  
Cavalier King Charles Spaniel ◽  
The Impact

Abstract Background. All dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in CKCS diseased mitral valves compared to valves from non-CKCS dogs. Results. Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, CKCS diseased valves and diseased valves from other breeds; the latter were more similar to the normal valves than were the CKCS valves. CKCS valve gene expression patterns were quite different from those in the other dogs, both affected and normal. Patterns in all diseased valves (CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS valves compared to normal) and MEF2C pathway activation (CKCS valves compared to non-CKCS) had the strongest association with the gene changes. A large number of DEGs in the CKCSs were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion. Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

scholarly journals Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel

2020 ◽  
Author(s):  
Greg Markby ◽  
Vicky Macrae ◽  
Brendan Corcoran ◽  
Kim Summers
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Expression Patterns ◽  
Valve Disease ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Transcriptomic Profiling ◽  
Cavalier King Charles Spaniel

Abstract Background. Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs. Results. Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion. Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

scholarly journals Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel

2020 ◽  
Author(s):  
Greg Markby ◽  
Vicky Macrae ◽  
Brendan Corcoran ◽  
Kim Summers
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Expression Patterns ◽  
Valve Disease ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Transcriptomic Profiling ◽  
Cavalier King Charles Spaniel

Abstract Background. Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs. Results. Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion. Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

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