Molecular genetic studies of canine inherited diseases including SAMS, neuronal ceroid lipofuscinosis and dilated cardiomyopathy
Dissertation supervisor: Dr. Gary S. Johnson. Includes vita. The genome of Canis lupus familiaris, the domestic dog, is an ideal tool for the study of inherited diseases. Its genome is uniquely suited for the mapping of genes that cause disease, and its reference genome has been published since 2008...
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| Format: | Thesis |
| Language: | English |
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University of Missouri--Columbia
2016
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| Online Access: | https://hdl.handle.net/10355/56525 https://doi.org/10.32469/10355/56525 |
| Summary: | Dissertation supervisor: Dr. Gary S. Johnson. Includes vita. The genome of Canis lupus familiaris, the domestic dog, is an ideal tool for the study of inherited diseases. Its genome is uniquely suited for the mapping of genes that cause disease, and its reference genome has been published since 2008. Dogs and humans share many of the same diseases, making them an ideal model for the study of comparative genetics. The identification of disease-causing genes in dogs has relevance to human health. We here describe the identification of causal mutations for three different canine diseases in orthologs of genes with orthologous human diseases. We used Next Generation Sequencing in order to generate Whole Genome Sequences for 145 dogs from 69 different breeds with various inherited canine diseases, most of which were suspected to be inherited recessively. We here report the discovery of the causes of; Spinocerebellar Ataxia with Myokymia and Seizures in Russell-Group Terriers, Neuronal Ceroid Lipofuscinosis in Golden Retrievers and Dilated Cardiomyopathy in Standard Schnauzers. While all three were identified via whole genome sequencing, different methodologies and techniques were used to discover and validate the findings. We discuss the importance of these studies and suggest future studies for the projects as well as possible other means of discovering potential canine disease models via Whole Genome Sequencing. Summaries of these three findings are provided in the next three paragraphs. Juvenile-onset spinocerebellar ataxia has been recognized in Jack Russell Terriers and related Russell group terriers (RGTs) for over 40 years. Ataxia occurs with varying combinations of myokymia, seizures and other signs, thus more than one form of the disease has been suspected. Our objective was to identify the mutation causing the spinocerebellar ataxia associated with myokymia and/or seizures and distinguish the phenotype from other ataxias seen in the RGTs. We collected DNA samples from 16 RGTs with signs of ... |
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