The activity of polymerase ã (pol ã) is complicated. To understand how its kinetics values affect the final function of the pol ã, I created a stochastic model of pol ã replication on the single nucleotide incorporation level. Using this model, I analyzed replication pauses of both wild-type and pathogenic mutated pol ã and discovered that the pausing time is proportional to the number of disassociations occurring in each forward step of the pol ã, and studied mitochondrial toxicity caused by nucleoside analogs in antiretroviral treatment.
To enrich the yield of rare disease alleles, a probability-based approach, SampleSeq, has been developed to select samples for a targeted resequencing experiment that outperforms over sampling based on genotypes at associated SNPs from GWAS data. To detect somatic mutations, novel algorithms have been developed to detect base substitution and loss of heterozygosity, using next-generation sequencing data for normal-tumor sample pairs.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03082012-105109 |
| Date | 14 March 2012 |
| Creators | Song, Zhuo |
| Contributors | Chun Li, Todd I. Edwards, Ellen H. Fanning, William S. Bush, David C. Samuels, C. William Wester |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03082012-105109/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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