Les objectifs de cette thèse étaient d'explorer les mécanismes moléculaires et les bases génétiques impliquées dans la survie des huîtres Crassostrea gigas à des maladies infectieuses, en considérant deux souches de Vibrio pathogènes pour l'huître (V. splendidus LGP32 et V. aestuarianus LPi 02/41) qui ont été associées aux phénomènes de mortalités massives d'huîtres en France. Par l'approche transcriptomique de « Digital Gene Expression », nous avons identifié des composants génétiques d'une réponse efficace à des infections par des Vibrio virulents. La capacité de survie des huîtres se traduit par l'expression basale d'une combinaison de 14 gènes hémocytaires, une signature de survie, et par l'induction de différentes fonctions cellulaires au cours de la réponse immunitaire. Une analyse transcriptomique détaillée au niveau individuel a révélé un extraordinaire polymorphisme d'expression basale des gènes, incluant des cas où chez certaines huîtres des transcrits sont absents. Afin de comprendre ce polymorphisme, nous nous sommes intéressés à la caractérisation d'une nouvelle famille de peptides antimicrobiens (PAMs), les big défensines (Cg-BigDef). Nous avons montré que Cg-BigDef est une famille de PAMs composée de trois membres et diversifiée en termes de séquences, d'organisation génomique et de régulation de l'expression des gènes. Les Cg-BigDefs sont codées par des gènes distincts dont l'expression est régulée suivant différents modes en réponse à une infection. Chose intéressante, certaines huîtres n'expriment pas simultanément les trois formes de Cg-BigDef ou dans certains cas, n'en expriment aucune. Nous avons démontré que l'absence d'expression basale de Cg-BigDef est liée à l'absence de gène correspondant dans le génome des huîtres. C'est la première mise en évidence chez un invertébré de variation de présence/absence (PAV) de gènes, un phénomène qui pourrait contribuer à une susceptibilité accrue aux maladies infectieuses. / The objectives of this thesis were to explore the molecular mechanisms and genetic bases involved in Crassostrea gigas oyster survival to infectious diseases, considering two Vibrio strains (V. splendidus LGP32 and V. aestuarianus LPi 02/41) pathogenic for oysters which have been shown to be involved in C. gigas mass mortalities in France. By the Digital Gene Expression transcriptomic approach, we have identified some genetic components implicated in a successful response and survival to virulent Vibrio infections. Oyster survival capacity is reflected by the basal expression of a selected combination of hemocyte genes, a 14-gene survival signature, and by the induction of some cellular functions during the oyster immune response. A detailed transcriptomic analysis at individual level revealed an extraordinary interindividual polymorphism in basal gene expression, including cases where some transcripts are fully absent. In order to understand this striking variability in gene expression, we have focused on the characterization of a novel family of antimicrobial peptides (AMP) in C. gigas oysters, the big defensins (Cg-BigDef). We have shown that Cg-BigDef is an AMP family, composed of three members, and diversified in terms of sequences but also in terms of genomic organization and regulation of gene expression. Each Cg-BigDef form is encoded by a distinct gene that follows different patterns of gene regulation upon Vibrio infection. Interestingly, some oysters were shown do not express simultaneously the three Cg-BigDef forms or any Cg-BigDef. We demonstrated that the absence of Cg-BigDef basal gene expression is likely due to the absence of the Cg-bigdef gene in oyster genome. This is the first evidence in an invertebrate of a presence/absence variation (PAV) of genes, a phenomenon that could be associated to a susceptibility to infectious diseases.

Thesis (MA (Psychology))--Stellenbosch University, 2008. / South Africa’s violence and injury death rates pandemic are steadily growing. Global estimates reported by the World Health Organisation (2000) have revealed that there is an increase in worldwide deaths. Approximately 5 million people die as a result of injuries each year and hundreds of thousands more are left physically or psychologically scarred (World Health Organisation, 2000). There are alarmingly high incidences of violence, crime and injury deaths in South Africa and the impact of these injury fatalities is imposing an immense burden on government, communities, families and even individuals. The burden of fatal injury mortalities has not fallen evenly. In South Africa, low socio-economic communities have borne the brunt of this epidemic. This study presents a focus on mortality and injury patterns and emerging problem areas for children and youth in a peri-urban setting. The aim of this study was to provide an overview of the fatal injury mortality and suicide data of children and youth in the Stellenbosch district, in order to develop a comprehensive understanding of the problem areas of injury deaths such as the main causes and consequences and age, sex, race and other pertinent comparisons. The study also aimed to consider the impact and relationship between alcohol abuse and youth injury deaths. Mortuary data were compiled from 591 children and youth cases for the period 2001-2005 in the Stellenbosch district using the National Injury Mortality Surveillance System data form. The present study highlighted several key findings. Transport-related deaths were indicated as a serious cause for concern among both children and youth in peri-urban settings. The importance of specific road safety awareness initiatives within peri-urban areas and among specific age groups were also indicated. Violence-related deaths were determined to be a leading cause of death among the older age groups in the youth category, with sharp force objects being the leading external cause of violent deaths. This highlighted an additional key finding reporting that sharp force objects death are a more serious cause for concern than firearm deaths in peri-urban areas, which challenges previous urban data. vi Burns and drowning were indicated as pertinent cause of unintentional deaths among both children and youth within peri-urban areas. This was suggested to be due to the high use of paraffin enabled heating systems in house in peri-urban areas and the lack of safety surrounding materials such as matches in the home. In addition, suffocation deaths among infants were also identified as a concern. Furthermore, the link between alcohol abuse among the youth age group was indicated by a key finding that alcohol is a prominent risk factor for fatal injury mortalities among youth. However more studies are needed to explore the effects and risks of other substances on youth fatal injury deaths. Several implications of the research findings are identified for health care professionals, policy developers, government departments and non-government organisations to consider in reducing the mortality rates of children and youth. These implications are critical in informing preventative interventions and initiatives aimed at enhancing safety to children and youth living in peri-urban areas within South Africa. vii