DOI
https://doi.org/10.25772/TX13-S780
Defense Date
2016
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology and Biophysics
First Advisor
Dr. Raj R. Rao
Second Advisor
Dr. Shilpa Iyer
Third Advisor
Dr. Liya Qiao
Fourth Advisor
Dr. Edward Lesnefsky
Abstract
Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts reprogrammed to induced pluripotent stem cells maintain the same level of mutation burden seen in the original patient cell line. Mutation burden was maintained through several passages and spontaneous differentiation. This cell based model could be useful for future pathogenesis studies, or therapeutic drug screenings in a patient and tissue specific manner.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-2-2016
Included in
Bioinformatics Commons, Biophysics Commons, Cellular and Molecular Physiology Commons, Disease Modeling Commons, Genetics Commons, Musculoskeletal Diseases Commons, Nervous System Diseases Commons