Genetics and genomics of myxomatous mitral valve disease in dogs
As a result of its unique evolutionary history, the modern dog (Canis lupus familiaris) has a simplified genetic landscape that makes it a strong model for investigating the genetic basis of breed specific traits and diseases. This thesis applies genomic methodologies to a complex disease, myxomatou...
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ftunivsydney:oai:ses.library.usyd.edu.au:2123/27483 2023-05-15T15:51:00+02:00 Genetics and genomics of myxomatous mitral valve disease in dogs O'Brien, Mitchell John 2022 application/pdf https://hdl.handle.net/2123/27483 en eng The University of Sydney Faculty of Science, School of Life and Environmental Sciences https://hdl.handle.net/2123/27483 The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission. genetics genomics canine dog complex trait disease Thesis Doctor of Philosophy 2022 ftunivsydney 2022-05-30T13:35:20Z As a result of its unique evolutionary history, the modern dog (Canis lupus familiaris) has a simplified genetic landscape that makes it a strong model for investigating the genetic basis of breed specific traits and diseases. This thesis applies genomic methodologies to a complex disease, myxomatous mitral valve disease (MMVD), with the primary aim of improving our understanding of its genetic basis. MMVD is an acquired disease of the dog that causes valvular dysfunction and may result in the development of congestive heart failure (CHF). In dogs, MMVD is the most frequent cause of cardiovascular morbidity and mortality, and despite a thorough understanding of the clinical aspects, the genetic mechanisms that drive disease onset and progression are uncertain. Current MMVD research supports a polygenic mode of inheritance and exemplifies the difficulty in identifying disease risk variants in complex traits. In this thesis, genomic workflows are used to investigate MMVD in an Australian population of Cavalier King Charles Spaniels (CKCS), a breed disproportionately affected by the trait. I first assessed the strength of MMVD phenotypes for use in comparative genomic studies. Then, through bioinformatic approaches, I investigated the genetic landscape of the disease in this breed. Using genomic tools developed for the dog and a combined approach of objective phenotyping, I was able to thoroughly explore the genetics and genomics of MMVD in the CKCS using different types of genomic analyses. In doing so, I was able to demonstrate the utility of pedigreed breeds in the investigation of complex traits and the versatility of genomic datasets. Throughout this thesis MMVD associated loci, candidate genes and putative functional variants are reported. Thesis Canis lupus The University of Sydney: Sydney eScholarship Repository Cavalier ENVELOPE(-69.462,-69.462,-67.825,-67.825) |
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The University of Sydney: Sydney eScholarship Repository |
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English |
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genetics genomics canine dog complex trait disease |
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genetics genomics canine dog complex trait disease O'Brien, Mitchell John Genetics and genomics of myxomatous mitral valve disease in dogs |
topic_facet |
genetics genomics canine dog complex trait disease |
description |
As a result of its unique evolutionary history, the modern dog (Canis lupus familiaris) has a simplified genetic landscape that makes it a strong model for investigating the genetic basis of breed specific traits and diseases. This thesis applies genomic methodologies to a complex disease, myxomatous mitral valve disease (MMVD), with the primary aim of improving our understanding of its genetic basis. MMVD is an acquired disease of the dog that causes valvular dysfunction and may result in the development of congestive heart failure (CHF). In dogs, MMVD is the most frequent cause of cardiovascular morbidity and mortality, and despite a thorough understanding of the clinical aspects, the genetic mechanisms that drive disease onset and progression are uncertain. Current MMVD research supports a polygenic mode of inheritance and exemplifies the difficulty in identifying disease risk variants in complex traits. In this thesis, genomic workflows are used to investigate MMVD in an Australian population of Cavalier King Charles Spaniels (CKCS), a breed disproportionately affected by the trait. I first assessed the strength of MMVD phenotypes for use in comparative genomic studies. Then, through bioinformatic approaches, I investigated the genetic landscape of the disease in this breed. Using genomic tools developed for the dog and a combined approach of objective phenotyping, I was able to thoroughly explore the genetics and genomics of MMVD in the CKCS using different types of genomic analyses. In doing so, I was able to demonstrate the utility of pedigreed breeds in the investigation of complex traits and the versatility of genomic datasets. Throughout this thesis MMVD associated loci, candidate genes and putative functional variants are reported. |
format |
Thesis |
author |
O'Brien, Mitchell John |
author_facet |
O'Brien, Mitchell John |
author_sort |
O'Brien, Mitchell John |
title |
Genetics and genomics of myxomatous mitral valve disease in dogs |
title_short |
Genetics and genomics of myxomatous mitral valve disease in dogs |
title_full |
Genetics and genomics of myxomatous mitral valve disease in dogs |
title_fullStr |
Genetics and genomics of myxomatous mitral valve disease in dogs |
title_full_unstemmed |
Genetics and genomics of myxomatous mitral valve disease in dogs |
title_sort |
genetics and genomics of myxomatous mitral valve disease in dogs |
publisher |
The University of Sydney |
publishDate |
2022 |
url |
https://hdl.handle.net/2123/27483 |
long_lat |
ENVELOPE(-69.462,-69.462,-67.825,-67.825) |
geographic |
Cavalier |
geographic_facet |
Cavalier |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_relation |
https://hdl.handle.net/2123/27483 |
op_rights |
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission. |
_version_ |
1766386039821172736 |