Analysis of the Progeny of Sibling Matings Reveals Regulatory Variation Impacting the Transcriptome of Immune Cells in Commercial Chickens

Freem, Lucy; Summers, Kim M.; Gheyas, Almas; Psifidi, Androniki; Boulton, Kay; MacCallum, Amanda; Harne, Rakhi; O’Dell, Jenny; Bush, Stephen J.; Hume, David

doi:10.3389/fgene.2019.01032

Cited by 9 publications

(9 citation statements)

References 88 publications

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“…In this analysis we reviewed all clusters with at least 5 nodes (probesets with expression patterns correlated at r ≥ 0.9). As we have seen in other studies [ 29 , 30 ] there was considerable individual dog-specific variation and many clusters were driven by high expression of a subset of genes in a single or small number of individuals, independent of disease status. These clusters were not analysed further.…”

Section: Resultssupporting

confidence: 72%

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

et al. 2020

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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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Section: Resultssupporting

confidence: 72%

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

et al. 2020

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show abstract

“…7,247 genes making 20,612 edges were included in the analysis. As we have seen in other studies [29,30] there was considerable individual dog-specific variation and many clusters were driven by high expression of a subset of genes in a single or small number of individuals, independent of disease status.…”

Section: Network Analysis Of Samplessupporting

confidence: 71%

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

Corcoran

Markby

MacRae

et al. 2020

Preprint

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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.

show abstract

“…In this analysis we reviewed all clusters with at least 5 nodes (probesets with expression patterns correlated at r ≥ 0.9). As we have seen in other studies [29,30] there was considerable individual dog-speci c variation and many clusters were driven by high expression of a subset of genes in a single or small number of individuals, independent of disease status. These clusters were not analysed further.…”

Section: Network Analysis Of Samplessupporting

confidence: 70%

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

Markby

MacRae

Corcoran

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Analysis of the Progeny of Sibling Matings Reveals Regulatory Variation Impacting the Transcriptome of Immune Cells in Commercial Chickens

Cited by 9 publications

References 88 publications

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

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

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

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

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