Date of Graduation
8-2011
Document Type
Thesis (MS)
Program Affiliation
Biomathematics and Biostatistics
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Shoudan Liang, Ph.D
Committee Member
Thomas J. Goka, Ph.D
Committee Member
Yuan Ji, Ph.D
Committee Member
Peter Mueller, Ph.D
Committee Member
R. Allen White, Ph.D
Abstract
Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible loss of gene function. In our genome wide analysis of human genes, results suggested that 22% of the genes in cancer were predicted to be methylation-prone; in cancer these genes are generally down-regulated and function in the development process. In summary, our investigation validated our hypothesis and showed that these widespread genomic elements in cancer are highly associated with promoter DNA methylation and may further participate in influencing epigenetic regulation.
Keywords
Epigenetics, DNA Methylation, Positional Weight Matrices, CpG Islands