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The ability to metabolise drugs and achieve positive therapeutic outcomes is dependent on both genetic and environmental factors. The focus of this study was to determine the distribution and frequency of clinically relevant DME alleles and to assess the impact of these DME alleles on therapeutic outcomes in a cohort of 50 HIV-TB co-infected Zulu participants. PCR-RFLP was used to generate a genotypic profile of CYPIA2, 2C9, 2C19, 2E1, 3A4, MDR-1 and NAT-2. The distributions of the allelic frequencies were as follows. The CYPIA2 (A) - 50.7%, CYP2C9*2 — 100% and *3 — 56.2%, CYP2C19*2 — 35.4%, CYP2E1 (C2) — 28.4%, CYP3A4*1B (G) — 58.2%, MDR-1 (C3435T) - 16% and NAT-2 slow acetylators — 6.5%. Seventy-three percent of participants had prolonged TB therapy. Within this group, 82.9% of patient displayed wild type and 17.2% variant allele for CYP2E1 gene (p= 0.04) profile. In addition, all the slow acetylators in this study had prolonged TB therapy. In the MDR-1 gene, 87.5% showed wild type allele and 12.5% displayed the variant allele. Unsuccessful TB outcomes were also noted in 22% of this study population. In this group the variant allele was found to be dominant in CYPIA2, CYP3A4 and NAT-2, the opposite was seen in CYP2E1 and MDR-1. It was also interesting to note a similar genetic profile in the group that showed successful TB therapy outcomes. All participants had positive ARV treatment outcomes despite DME genotypic variations. However, 26% of all study participants experienced liver enzyme abnormalities. These findings concur with other studies regarding the ethnic distribution of DME alleles and evidence of an association between ART and TB therapeutic outcomes and DME genotype variation was inconclusive. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2007.

Two studies were conducted on gene mapping analysis. For the first study, genetic simulation experiments were conducted to address the effects of marker density, method of mapping analysis, and gaps in a marker map on the efficiency of QTL detection and the accuracy of QTL parameter estimation. The simulated genome consisted of seven chromosomes with seven or eight segregating QTL affecting the simulated quantitative trait. A set of six randomly segregating QTL outside the test region was consistently used to represent 40% of phenotypic variation. An individual QTL or a linkage block of two QTL on a target chromosome contributed 10% of phenotypic variation. The marker map was either dense (with markers every 4 cM) or sparse (with markers every 20 cM). The gap in the marker map was either 32 cM or 56 cM. Interval mapping and composite interval mapping were used to map QTL on the target chromosome. A dense map provided more power of QTL detection, better accuracy of QTL parameter estimation, and higher false-positive error rates for the target chromosome than a sparse map. Composite interval mapping provided more power of QTL detection, better accuracy of QTL parameter estimation, and lower false-positive error rates than interval mapping. Presence of a large gap in a marker map affected QTL detection and QTL parameter estimation for a QTL inside or near the gap. The use of a dense map with composite interval mapping was the most efficient combination tested in this study. For the second study, a mixed factorial regression model for interval mapping was developed for conducting QTL-by-environment interaction analysis and for providing inferences about QTL that are applicable beyond the environments used in the experiments. Genetic simulation was used to test the model for the power of detecting QTL-by-environment interaction and identifying the types of such interaction as crossover or non-crossover, and for the accuracy of estimating QTL parameters. The model prov

Thesis (Ph.D.)--University of Melbourne, Dept. of Zoology, 2007. / Typescript. Includes bibliographical references (leaves 218-237).

Thesis (M. Agr. Sc.)--University of Adelaide, 1966. / At foot of title page: Joint Coconut Research Scheme, Yandina, British Solomon Islands. Includes bibliographical references (p. 111-119).

Thesis (Ph.D.)--University of Western Australia, 2006.

Thesis--Auburn University, 2005. / Abstract. Vita. Includes bibliographic references (p.66-78).

Thesis (Ph. D.)--Biology, Georgia Institute of Technology, 2005. / Hay, Mark, Committee Chair ; Dusenbery, David, Committee Member ; Kubanek, Julia, Committee Member ; Paffenhofer, Gustav-Adolf, Committee Member ; Yen, Jeannette, Committee Member. Includes bibliographical references.

Thesis (M.S.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on August 13, 2009) Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 124-141).