<p>The goal of this thesis is to algorithmically identify candidate modifiers for <i>retinitis pigmentosa</i> (RP) to help improve therapy and predictions for this genetic disorder that may lead to a complete loss of vision. A current research by (Chow et al., 2016) focused on the genetic contributors to RP by trying to recognize a correlation between genetic modifiers and phenotypic variation in female <i>Drosophila melanogaster</i>, or fruit flies. In comparison to the genome-wide association analysis carried out in Chow et al.’s research, this study proposes using a K-Means clustering algorithm on RNA expression data to better understand which genes best exhibit characteristics of the RP degenerative model. Validating this algorithm’s effectiveness in identifying suspected genes takes priority over their classification.</p><p>This study investigates the linear relationship between <i>Drosophila </i>eye size and genetic expression to gather statistically significant, strongly correlated genes from the clusters with abnormally high or low eye sizes. The clustering algorithm is implemented in the R scripting language, and supplemental information details the steps of this computational process. Running the mean eye size and genetic expression data of 18,140 female <i>Drosophila</i> genes and 171 strains through the proposed algorithm in its four variations helped identify 140 suspected candidate modifiers for retinal degeneration. Although none of the top candidate genes found in this study matched Chow’s candidates, they were all statistically significant and strongly correlated, with several showing links to RP. These results may continue to improve as more of the 140 suspected genes are annotated using identical or comparative approaches.</p>

The variety of middle-class speakers in St. John’s conforms to some degree to mainland Canadian-English pronunciation norms, but in complex and distinctive ways (Clarke, 1985, 1991, 2010; D’Arcy, 2005; Hollett, 2006). One as yet unresolved question is whether speakers of this variety participate in the Canadian Shift (cf. Clarke, 2012; Chambers, 2012), a chain shift of the lax front vowels that has been confirmed for many different regions of Canada (e.g. Roeder and Gardner, 2013, for Thunder Bay and Toronto, Sadlier-Brown and Tamminga, 2008, for Halifax and Vancouver). While acoustic phonetic analyses of St. John’s English are rare, some claims have been made that urban St. John’s speakers do not participate in the shift, based on two or six speakers (Labov, Ash & Boberg, 2006; Boberg 2010). Other researchers with larger data sets suggest that younger St. John’s speakers participate in mainland Canadians innovations to different degrees than mainlanders (e.g. Hollett, 2006). The Canadian Shift has not been uniformly defined, but agreement exists that with the low-back merger in place, BATH/TRAP retracts and consequently DRESS lowers. Clarke et al. (1995), unlike Labov et al. (2006), assert that KIT is subsequently lowered. Boberg (2005, 2010), however, emphasizes retraction of KIT and DRESS and suggests unrelated parallel shifts instead. In this PhD thesis, I demonstrate the presence of the Canadian Shift in St. John’s, NL, conforming to Clarke et al.’s (1995) original proposal. In my stratified randomly-sampled data (approx. 10,000 vowels, 34 interviewees, stratified as to age, gender, socioeconomic status, and “local-ness”), results from Euclidean distance measures, correlation coefficients, and linear, as well as logistic, mixed-effects regression show that (1) young St. John’s speakers clearly participate in the shift; and that (2) age has the strongest and a linear effect. Continuous modeling of age yields even more significant results for participation in a classic chain shift (6% decrease in lowering per added year). My findings also confirm that the change seems to have entered the system via formal styles (cf. Clarke, 1991, 2010, for TRAP in St. John’s). Traditionally, the linguistic homogeneity on a phonetic level of the Canadian middle class has been explained by Canada’s settlement and migration patterns of the North American Loyalists from Ontario to the west (cf. Chambers, 2009). Newfoundland’s settlement is distinct, in that the British and the Irish were the only two relevant sources. If settlement were the only crucial reason for a shared pronunciation of Canada’s middle class from Vancouver to St. John’s, the Canadian Shift should be absent in the latter region. I suggest three reasons for middle-class St. John’s’ participation in the Canadian Shift: 1) Newfoundland’s 300-year-old rural-urban divide as a result of its isolation, through which British/Irish features are attributed to rural und lower social class speakers; 2) the development of the oil industry since the 1990’s, through which social networks changed according to the perception of social distance/closeness; and 3) the importance of the linguistic marketplace, which is high in St. John’s due to 1) and 2).:List of Tables viii List of Figures x 0 Prologue – Variationist Sociolinguistics 1 1 Introduction 27 2 English-speaking Canada and its Vowel Shifts 31 3 Newfoundland and its Englishes 77 4 Data and Methodology 107 5 Analysis and Discussion 243 6 Conclusion 363 Bibliography 375 Appendices 409 A Interview Questionnaire 409 B Normality Tests per Speaker and Age Group 423 C Vowel Plot of Median Formant Values 433 D Results for the Assumptions of T-tests 435 E Results from Decision Trees and Optimal Binning 439 F Results from Regression Analyses 449 G Résumé 457 H Deutsche Zusammenfassung der Dissertation 461 I Eidestattliche Erklärung zur Eigenständigkeit 469