published_or_final_version / Medicine / Master / Master of Philosophy

Bibliography: leaves 126-147 / xiv, 147 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Summary: Aims to develop reliable procedures for determining the genetic status of embryos derived by IVF procedures prior to implantation. Prenatal diagnosis allows pregnancy to be established using only acceptable embryos / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1994

The increasing transparence of the human genome has profound implications for how we understand health and illness and perceive our biological and social relatedness to others. Presymptomatic testing for adult onset conditions, in particular, creates the novel situation in which some individuals know in advance of impending illness while others learn that they have escaped such a fate. How families at risk for one adult onset condition — Huntington Disease (HD) — communicate about such information is the topic of this dissertation. HD is often described as a 'genetic time bomb'. It is an autosomal dominant neuropsychiatric disorder characterized by mid-life onset, involuntary movements, cognitive impairment, and depression. There is no effective prevention or cure but with the advent of predictive testing in 1987 it became possible for at risk individuals to learn if they had inherited the mutation associated with HL\ Empirical studies on predictive testing for HD focus primarily on the individual psychological impacts of the test; few studies consider how families understand and attempt to manage genetic information in their everyday lives. This dissertation begins to address these lacunae by examining the stories that test candidates and their families tell about hereditary risk and predictive testing. These stories derive from a prospectively designed study which includes 102 in-depth, at-home interviews conducted in the pre and post-results period with 16 test candidates and 33 family members. Focusing on three narrative 'moments', the dissertation explores how study participants storied their experiences of: 1) learning about the family history of HD, 2) deciding to request the predictive test and, 3) making sense of an informative result. Drawing upon a social constructionist approach, the analysis emphasizes the processual nature of predictive testing as well as the significance of interpersonal communication in producing and reproducing the social realities in which genetic information acquires a particular salience. Given the recent proliferation of genetic tests as well as the absence of an adequate popular discourse on embodied risk, the research underscores lay actors' abilities to reframe existing clinical schema in order to interpret and manage hereditary risk in an intersubjectively meaningful way.

The increasing transparence of the human genome has profound implications for how we understand health and illness and perceive our biological and social relatedness to others. Presymptomatic testing for adult onset conditions, in particular, creates the novel situation in which some individuals know in advance of impending illness while others learn that they have escaped such a fate. How families at risk for one adult onset condition — Huntington Disease (HD) — communicate about such information is the topic of this dissertation. HD is often described as a 'genetic time bomb'. It is an autosomal dominant neuropsychiatric disorder characterized by mid-life onset, involuntary movements, cognitive impairment, and depression. There is no effective prevention or cure but with the advent of predictive testing in 1987 it became possible for at risk individuals to learn if they had inherited the mutation associated with HL\ Empirical studies on predictive testing for HD focus primarily on the individual psychological impacts of the test; few studies consider how families understand and attempt to manage genetic information in their everyday lives. This dissertation begins to address these lacunae by examining the stories that test candidates and their families tell about hereditary risk and predictive testing. These stories derive from a prospectively designed study which includes 102 in-depth, at-home interviews conducted in the pre and post-results period with 16 test candidates and 33 family members. Focusing on three narrative 'moments', the dissertation explores how study participants storied their experiences of: 1) learning about the family history of HD, 2) deciding to request the predictive test and, 3) making sense of an informative result. Drawing upon a social constructionist approach, the analysis emphasizes the processual nature of predictive testing as well as the significance of interpersonal communication in producing and reproducing the social realities in which genetic information acquires a particular salience. Given the recent proliferation of genetic tests as well as the absence of an adequate popular discourse on embodied risk, the research underscores lay actors' abilities to reframe existing clinical schema in order to interpret and manage hereditary risk in an intersubjectively meaningful way. / Arts, Faculty of / Anthropology, Department of / Graduate

Indiana University-Purdue University Indianapolis (IUPUI) / Human induced pluripotent stem (iPS) cells have the unique ability to differentiate into 200 or so somatic cell types that make up the adult human being. The use of human iPS cells to study development and disease is a highly exciting and interdependent field that holds great promise in understanding and elucidating mechanisms behind cellular differentiation with future applications in drug screening and cell replacement studies for complex and currently incurable cellular degenerative disorders. The recent advent of iPS cell technology allows for the generation of patient-specific cell lines that enable us to model the progression of a disease phenotype in a human in vitro model. Differentiation of iPS cells toward the affected cell type provides an unlimited source of diseased cells for examination, and to further study the developmental progression of the disease in vitro, also called the “disease-in-a-dish” model. In this study, efforts were undertaken to recapitulate the differentiation of distinct retinal cell affected in two highly prevalent retinal diseases, Usher syndrome and glaucoma. Using a line of Type III Usher Syndrome patient derived iPS cells efforts were undertaken to develop such an approach as an effective in vitro model for studies of Usher Syndrome, the most commonly inherited disorder affecting both vision and hearing. Using existing lines of iPS cells, studies were also aimed at differentiation and characterization of the more complex retinal cell types, retinal ganglion cells (RGCs) and astrocytes, the cell types affected in glaucoma, a severe neurodegenerative disease of the retina leading to eventual irreversible blindness. Using a previously described protocol, the iPS cells were directed to differentiate toward a retinal fate through a step-wise process that proceeds through all of the major stages of neuroretinal development. The differentiation process was monitored for a period of 70 days for the differentiation of retinal cell types and 150 days for astrocyte development. The different stages of differentiation and the individually derived somatic cell types were characterized by the expression of developmentally associated transcription factors specific to each cell type. Further approaches were undertaken to characterize the morphological differences between RGCs and other neuroretinal cell types derived in the process. The results of this study successfully demonstrated that Usher syndrome patient derived iPS cells differentiated to the affected photoreceptors of Usher syndrome along with other mature retinal cell types, chronologically analogous to the development of the cell types in a mature human retina. This study also established a robust method for the in vitro derivation of RGCs and astrocytes from human iPS cells and provided novel methodologies and evidence to characterize these individual somatic cell types. Overall, this study provides a unique insight into the application of human pluripotent stem cell biology by establishing a novel platform for future studies of in vitro disease modeling of the retinal degenerative diseases: Usher syndrome and glaucoma. In downstream applications of this study, the disease relevant cell types derived from human iPS cells can be used as tools to further study disease progression, drug screening and cell replacement strategies.