Defense Date

2006

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Dr. Peter O'Connell

Abstract

The study of telomere and telomerase biology holds substantial promise in uncovering the molecular process of aging and the treatment of cancers. Studies have shown that telomere shortening is directly linked to cellular aging and that telomerase expression is found in over 85% of human cancers, including 95% of all advanced malignancies. Development of effective model systems to elucidate the molecular mechanisms underlying the role of telomeres and telomerase in the processes aging and cancer is of particular importance. While inbred strains of mice have provided a wealth of information for a variety of pathways and diseases, the mouse model poses a challenge for the study of telomere biology due to their extremely large telomere sizes. The telomerase knockout mouse suffers no adverse effect for at least 6 generations, making studies of telomere shortening-associated pathology in single generations of animal very difficult. For this reason, the identification of new vertebrate models for the study of telomeres and telomerase biology is critical. The chicken, Gallus gallus, has been an important model system for the study of embryology and development for decades. The chicken has three classes of telomeres, characterized and differentiated by their size. Class I ranging from 0.5 to 10 kb in size, Class II ranging between 10 to 40 kb in size, and Class Ill ranging between 40 kb to 2 Mb in size. The class I and II chicken telomeres are close enough in size to those of humans, which range between 4 and 15 kb, to allow for chicken studies to elucidate information valuable to the understanding of the molecular process in humans. The chicken telomerase genes have been cloned and characterized, providing a foundation for unlimited study of telomere biology in the chicken. Additional models, including many different fish species, will also hold promise as telomere models for aging and cancer. The development of an additional model of telomere biogenesis and telomerase regulation should provide important insights into the molecular processes surrounding both the development of cancer and organismal aging.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008

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