The domestic dog, Canis familiaris, with over 450 naturally-occurring hereditary
diseases, serves as a valuable model organism for study of the genetics underlying many
human hereditary diseases. Approximately half of the diseases that afflict the dog are
clinically very similar to various human hereditary diseases. Several cardiac diseases are
in this category. Our laboratory is interested in cardiac diseases because they are
common causes of death in the human and are also a widespread problem in many
breeds of dog. The specific focus of my work is on understanding the genetics of dilated
cardiomyopathy (DCM).
DCM is a disease characterized by enlargement of the left ventricle leading to an
inability of the heart to pump sufficient blood to the body. It is one of the most common
cardiac diseases in the dog and has a high mortality. The Great Dane is the second most
commonly affected breed. It is seen in many families of Great Danes, and this suggests
that DCM has a genetic component. The mode of inheritance of DCM in the Great Dane
is currently unknown, although studies have reported both autosomal recessive and
autosomal dominant transmission. Many different genes cause DCM, indicating the complexity of the disease.
These typically produce proteins that are involved in the sarcomere or cytoskeletal
components, leading to problems with contraction or cardiac cell integrity.
In order to identify causative or susceptibility genes for DCM in the Great Dane,
a whole-genome linkage screen was conducted in a family of Great Danes. One
candidate gene, gamma-sarcoglycan (SGCG), was identified through linkage and
sequenced in affected and unaffected dogs. Sequencing data revealed no mutations in the
coding regions of SGCG, most likely excluding it as a candidate gene for DCM.
Continued evaluation of this gene and others, both in sequence content and additional
properties such as epigenetic effects, protein structure, and interaction with other genes
will increase understanding of DCM in both the dog and the human.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2515 |
| Date | 15 May 2009 |
| Creators | Herbst, Stephanie Michelle |
| Contributors | Murphy, Keith E. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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