Genetic Variants Contributing to Frontotemporal Dementia with Parkinsonism

Frontotemporal dementia with parkinsonism (FTDP) is a neurodegenerative disease characterized by disturbances in cognition, language, and personality, which also has features of parkinsonism. This disease is associated with multiple genes including two located close together on chromosome 17: MAPT and GRN. Human and medical genetics can be used to identify the genes that contribute to the risk of this disease. Earlier work in the Chase lab had identified a large Mennonite kindred (MEN-1) where parkinsonism and dementia were found in five members of a nuclear family. These symptoms parallel those seen in FTDP and all of the affected members share a novel GRN DNA variant that does not appear to be pathological. My research sought to understand whether these individuals share a common haplotype - a set of closely linked variants in the region of the MAPT and GRN genes - that might contribute to the phenotypes seen in the MEN-1 kindred. Whole-exome sequencing was used to characterize two additional members of the nuclear family. This data was analyzed using a pipeline in GeneStack, and the resulting variant call files, together with the previously gathered whole genome sequences, are currently being used to assess shared haplotypes using the SHAPEIT2 program at the Oxford Phasing Server

Understanding the multiple roles for the state in HIV vaccine research

Kenya has a rich and controversial history of HIV vaccine-related research and incidents between researchers, participants and authorities have highlighted pertinent and endemic ethical, legal, social and political issues. The role of the state during these events and in wider vaccine research is unexamined and misunderstood; yet, the state is a deeply involved and dominant party.My thesis provides a coherent explanation of the role of the state in vaccine research and links recurrent ethical issues to the multiple and competing interests the state has in this activity. I develop multiple roles for the state as a Facilitator, Guardian, Participant, Regulator, Researcher and Sponsor based on a common understanding of the key parties in biomedical ethics. These roles explain the complex state participation and are developed and shaped by crucial influential factors in the environment surrounding HIV vaccine research.Le Kenya a une histoire riche et controversée à l'égard de la recherche relative au vaccin contre le VIH. En effet, plusieurs incident et conflits entre les chercheurs, les participants et les autorités mettent en évidence les difficultés éthiques, légales, sociales et politiques de la recherche d'un vaccin. Le rôle de l'Etat au cours de ces évènements et en ce qui a trait a la recherche de vaccin en général est non examine et mal compris, et pourtant, l'Etat est une partie profondément impliquée et dominante.Ma thèse propose une explication cohérente du rôle de l'E tat dans la recherche d'un vaccin et relie les difficultés éthiques récurrentes aux multiplies intérêts concurrents que l'Etat détient a l'egard de cette activité. En se basant sur une compréhension commune des principales parties impliquées en éthique biomédicale, je développe de multiples rôles pour l'Etat en tant que facilitateur, gardien, participant, régulateur, chercheur et mémé commanditaire de l'activité. Ces rôles, expliquant la participant complexe de l'Etat sont façonnes par des facteurs cruciaux et influents provenant de l'environnement qui entoure la recherche d'un vaccin contre le VIH. En effet, l'implémentation de ces rôles créé un environnement propice aux conflits et aux difficultés éthiques