Thesis (Ph.D.) -- University of Rhode Island, 2007 / Typescript. Includes bibliographical references (leaves 250-294).

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 100-125) Also available online.

Thesis (Ph. D.)--University of Texas at El Paso, 2009. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Thesis (M.S.)--University of Michigan, 1997. / Includes bibliographical references.

Thesis (Ph. D.)--Duke University, 2008. / Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1997. / Includes bibliographical references.

Thesis (M.Med.Sc.) - University of Queensland, 2002. / Includes bibliography.

Thesis (Ph. D.)--Washington State University, May 2007. / Includes bibliographical references.

Genome wide association studies (GWAS) have transformed the study of the heritability of complex diseases such as type 2 diabetes (T2D), with the current tally of established risk loci close to ninety. Each of these loci has the potential to offer novel insights into the biology of this disease, and opportunities for clinical exploitation. However, the complexity of T2D has often frustrated efforts to achieve these functional and translational advances. This thesis aims to delve into the functional characterisation of two known susceptibility loci, KLF14 and ADCY5, and describe findings relevant to disease pathology. KLF14 and ADCY5 are two loci associated with T2D predisposition working through disparate mechanisms. Variants at the maternally imprinted KLF14 locus are associated with measures of insulin resistance and expression data has implicated KLF14 as a master regulator of genes in adipose tissue. In contrast, variation at the ADCY5 locus is associated with impaired beta cell function, high fasting glucose, and low birth weight suggesting ADCY5 is having an effect on insulin secretion. In this thesis, ENU mouse models of these two genes are investigated functionally to elucidate more about the pathology of common human variation at these loci. A mouse model was derived with an ENU point mutation at Adcy5 Y1064C. Phenotyping of this model revealed improved oral glucose tolerance, and secretion studies from isolated islet cells demonstrated impaired glucagon secretion from mice homozygous for the Y1064C mutation in the presence of adrenaline. These results suggest that Adcy5 is involved in glucagon regulation in the alpha cell. The Adcy5 Y1064C confers a protective effect against hyperglycaemia in mouse indicating that the T2D risk allele at the ADCY5 locus in humans may have the opposite direction of effect. A mouse model containing the ENU point mutation Klf14 R238L predicted to be disruptive to KLF14 protein function showed no significant difference in body weight, measures of insulin resistance, or blood cholesterol. However, expression of several genes associated in trans with variation near KLF14 in humans was changed in adipose tissue and skeletal muscle when the R238L mutation was inherited maternally compared to mice which had inherited the mutation paternally or carried two wild type alleles. This result suggests a mechanism by which Klf14 is regulating genes across metabolic tissues.

Thesis (MSc (Biomedical Technology))--Cape Peninsula University of Technology, 2016. / The early detection of individuals who are at risk of developing type 2 diabetes mellitus (T2DM) would decrease the morbidity and mortality associated with this disease. DNA methylation, the most widely studied epigenetic mechanism, offers unique opportunities in this regard. Aberrant DNA methylation is associated with disease pathogenesis and is observed during the asymptomatic stage of disease. DNA methylation has therefore attracted increasing attention as a potential biomarker for identifying individuals who have an increased risk of developing T2DM. The identification of high risk biomarkers for T2DM could facilitate risk stratification and lifestyle interventions, which could ultimately lead to better ways to prevent, manage and control the T2DM epidemic that is rampant worldwide. The aim of the study was to investigate global DNA methylation as a potential risk factor for T2DM by studying the association between the global DNA methylation levels and hyperglycaemic states. A cross-sectional, quantitative study design, involving 564 individuals of mixed ancestry descent, residing in Bellville South, South Africa was used. Participants were classified as normal, pre-diabetic (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)) or diabetic (screen detected diabetic and known diabetics) according to WHO criteria of 1998. DNA was extracted from whole blood using the salt extraction method. The percentage global DNA methylation was measured by an enzyme-linked immunosorbent assay (ELISA). The association between global DNA methylation and hyperglycaemia, as well as other biochemical markers of T2DM was tested in a robust linear regression analysis adjusted for age, gender and smoking.