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 ◽  
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 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):  
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 Toxoplasma infection alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease

2021 ◽  
Author(s):  
Graham L. Cromar ◽  
Jonathan Epp ◽  
Ana Popovic ◽  
Yusing Gu ◽  
Violet Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Low Grade ◽  
Cocaine Exposure ◽  
Multiple Testing Correction ◽  
The Impact

ABSTRACTToxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.

scholarly journals Expression of placental regulatory genes is associated with fetal growth

2017 ◽  
Vol 45 (7) ◽  
Author(s):  
Maya A. Deyssenroth ◽  
Qian Li ◽  
Marina Lacasaña ◽  
Yoko Nomura ◽  
Carmen Marsit ◽  
...  
Keyword(s):  
Gene Expression ◽  
Birth Weight ◽  
Fetal Growth ◽  
Gestational Age ◽  
Expression Patterns ◽  
Regulatory Genes ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Metabolic Functions

AbstractThe placenta is the principal organ regulating respiratory, nutritional, endocrine and metabolic functions on behalf of the developing fetus. Changes in gene expression patterns of placenta-specific genes may influence fetal growth. We profiled the expression of 17 genes related to placenta functioning in term placentas (n=677) to identify genes differentially expressed across birth weight categories [small (SGA), appropriate (AGA) and large (LGA) for gestational age].

171 THE EFFECT OF TRICHOSTATIN A ON THE DEVELOPMENT AND THE GLOBAL GENE EXPRESSION PATTERNS IN MOUSE EMBRYOS DEVELOPING IN VITRO

2008 ◽  
Vol 20 (1) ◽  
pp. 165
Author(s):  
X. S. Cui ◽  
X. Y. Li ◽  
T. Kim ◽  
N.-H. Kim
Keyword(s):  
Gene Expression ◽  
Trichostatin A ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Mouse Embryos ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Cell Stage

Trichostatin A (TSA) is an inhibitor of histone deacetylase and is able to alter gene expression patterns by interfering with the removal of acetyl groups from histones. The aim of this study was to determine the effect of TSA treatment on the development and gene expression patterns of mouse zygotes developing in vitro. The addition of 100 nm TSA to the culture medium did not affect the cleavage of mouse embryos (TSA treatment, 148/150 (99%) v. control, 107/107 (100%)); however, embryos that were treated with TSA arrested at the 2-cell stage (145/148, 98%). We estimated the number of nuclei in control and TSA-treated embryos by propidium iodide staining, taking into account the presence of any cells with two or more nuclei. At 62–63 h post-hCG stimulation, control zygotes had developed to the 4-cell stage and exhibited one nucleus in each blastomere, indicative of normal development. In contrast, we observed tetraploid nuclei in at least one blastomere in 20.8% (11/53) of the embryos that had been treated with TSA. At 28–29 h post-hCG stimulation (metaphase of the 1-cell stage), there was no difference in the mitotic index (as determined by analyzing the microtubule configuration) in the TSA group compared to the control group. At the 2-cell stage, however, we did not observe mitotic spindles and metaphase chromatin in embryos in the TSA treatment group compared to the controls. Interestingly, when embryos were cultured in TSA-free medium from 35 h post-hCG stimulation (S- or early G2-phase of the 2-cell stage) onward, almost all of them (47/50) developed to the blastocyst stage. In contrast, when embryos were cultured in TSA-free medium from 42 h post-hCG stimulation (middle G2-phase of the 2-cell stage) onward, they did not develop to the 4-cell stage. We used Illumina microarray technology to analyze the gene expression profiles in control and TSA-treated late 2-cell-stage embryos. Applied Biosystems Expression System software was used to extract assay signals and assay signal-to-noise ratio values from the microarray images. Our data showed that 897 genes were significantly (P < 0.05; 2-sample t-test) up- or down-regulated by TSA treatment compared to controls. Analysis using the PANTHER classification system (https://panther.appliedbiosystems.com) revealed that the 575 genes that were differentially expressed in the TSA group compared to the control were classified as being associated with putative biological processes or molecular function. Overall, in terms of putative biological processes, more nucleoside, nucleotide, and nucleic acid metabolism, protein metabolism and modification, signal transduction, developmental process, and cell cycle genes were differentially expressed between the TSA and control groups. In terms of putative molecular function, more nucleic acid-binding transcription factor and transferase genes were differentially expressed between the groups. The results collectively suggest that inhibition of histone acetylation in mouse embryos affects gene expression profiles at the time of zygotic genome activation, and this subsequently affects further development.

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 Beyond Field Effect: Analysis of Shrunken Centroids in Normal Esophageal Epithelia Detects Concomitant Esophageal Adenocarcinoma

2007 ◽  
Vol 1 ◽  
pp. BBI.S311 ◽  
Author(s):  
Florin M. Selaru ◽  
Suna Wang ◽  
Jing Yin ◽  
Karsten Schulmann ◽  
Yan Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Neoplastic Progression ◽  
Esophageal Epithelium

Background and Aims Because of the extremely low neoplastic progression rate in Barrett's esophagus, it is difficult to diagnose patients with concomitant adenocarcinoma early in their disease course. If biomarkers existed in normal squamous esophageal epithelium to identify patients with concomitant esophageal adenocarcinoma, potential applications would be far-reaching. The aim of the current study was to identify global gene expression patterns in normal esophageal epithelium capable of revealing simultaneous esophageal adenocarcinoma, even located remotely in the esophagus. Methods Tissues comprised normal esophageal epithelia from 9 patients with esophageal adenocarcinoma, 8 patients lacking esophageal adenocarcinoma or Barrett's, and 6 patients with Barrett's esophagus alone. cDNA microarrays were performed, and pattern recognition in each of these subgroups was achieved using shrunken nearest centroid predictors. Results Our method accurately discriminated normal esophageal epithelia of 8/8 patients without esophageal adenocarcinoma or Barrett's esophagus and of 6/6 patients with Barrett's esophagus alone from normal esophageal epithelia of 9/9 patients with Barrett's esophagus and concomitant esophageal adenocarcinoma. Moreover, we identified genes differentially expressed between the above subgroups. Thus, based on their corresponding normal esophageal epithelia alone, our method accurately diagnosed patients who had concomitant esophageal adenocarcinoma. Conclusions These global gene expression patterns, along with individual genes culled from them, represent potential biomarkers for the early diagnosis of esophageal adenocarcinoma from normal esophageal epithelia. Genes discovered in normal esophagus that are differentially expressed in patients with vs. without esophageal adenocarcinoma merit further pursuit in molecular genetic, functional, and therapeutic interventional studies.

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