The University of Manitoba in Partial Fulfilment of the Requirements of The

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The University of Manitoba in Partial Fulfilment of the Requirements of The A Palaeopathological and Immunogenetic Assessment of Archaeological Canadian Inuit Populations By Morgan Campbell L. A Thesis submitted to the Faculty of Graduate Studies of The University of Manitoba In partial fulfilment of the requirements of the degree of Doctor of Philosophy Department of Anthropology University of Manitoba Winnipeg Copyright © 2013 Morgan L. Campbell i Abstract For centuries there has been a disparity in the health of Canadian Aboriginal populations and the colonizers who came to inhabit their territories. In contemporary times, this disparity is translated into a number of growing health concerns that appear at higher rates in circumpolar populations than in many other Canadian communities. Tuberculosis rates in Arctic and circumpolar communities, particularly those with a high Inuit demographic, remain more than 20 times higher than in any other population demographic. Understanding the factors that contribute to the continued prevalence and high incidence of TB in the Arcticcompared to the remainder of Canadian populations demonstrate requires a longitudinal analysis of a number of factors related to overall health. This dissertation explores this disparity through the examination of the immunogenetics and palaeopathology of an archaeological Inuit population. This archaeological cohort was assessed using palaeopathological techniques of to establish the disease burden experienced by the Inuit in the pre‐contact and early contact period. The palaeopathologicual inventory also established individuals with possible TB pathologies as candidates for further molecular analysis. Molecular analyses focused on the establishment of Inuit ancestry and the examination of the presence of four polymorphic sites in the promoter regions of IL‐6, IL‐10, TNFα and IFNγ. Polymorphisms for the Th2 cytokines IL‐6 and IL‐10 are associated with the down regulation of Th1 cytokines activated to combat TB infection, while the Th1 cytokines TNFα and IFNγ are essential for the effective immune response against TB infection. These analyses resulted in the establishment of genotypes and phenotypes detected utilising a novel molecular method and protocols developed specifically for this research. Osteological observations indicated an increase in risk of disease in early contact populations, particularly those associated with infectious disease or the co‐infection of multiple conditions compared to the pre‐contact cohort. In contrast pre‐mortem tooth loss decreased with contact, and degenerative pathologies maintained a relatively balanced presence. TB pathologies were observed in both pre‐contact and contact groups, with an increased level of pathologies observed in contact individuals. Molecular results suggest immunogenetic profiles similar to First Nations groups, with only a single cytokine SNP exhibiting a unique phenotype in comparison. Immunogenetic profiles suggest Inuit have maintained a Th2 immune response for many generations, and this remains unchanged with contact. ii Acknowledgements While ultimately this dissertation is the product of my doctoral research, it is the result of a great deal of emotional, academic and financial support and encouragement. I acknowledge that without that support this thesis would not represent what it does today, the penultimate ending to my graduate career. I therefore wish to acknowledge a number of individuals who helped along the way. Primary support came from my co‐advisors, Dr. Linda Larcombe and Dr. Rob Hoppa, who pushed when needed and allowed me my quiet times to reflect and, usually, rewrite. Thank you for your support and the chance to explore my anthropological knowledge. To Dr. Larcombe, gratitude for teaching me the basics of molecular research (from the anthropological perspective) and providing the opportunity to expand on previous research ideas. Additionally, thanks to my committee members Drs. Stacie Burke and Paul Hackett for help with the overall thesis. The Canadian Museum of Civilization at Gatineau, Quebec opened its collections section and provided a work space during my initial research. Concomitantly, I wish to express heartfelt gratitude to the Inuit Heritage Trust for extending permission to me to examine the archaeological remains of their ancestors. I hope that a continued respectful working relationship with First Nations, Métis and Inuit communities can lead to greater future discoveries about our shared and individual histories. While conducting the molecular analysis portion of my research I had the honour of exploiting the expertise of the Paleo‐DNA Laboratory staff at Lakehead University, particularly Stephen Fratpietro and Ryan Lehto who shared a lab and answered all my questions, sometimes multiple times. Thank you for, what seems like your infinite, patience, while I learned the intricacies of analyzing ancient DNA. With gratitude I acknowledge that funding was provided by the Social Sciences and Humanities Research Council, Canada Research Chairs Program, National Sanitarium Association, University of Manitoba Graduate Fellowship Program and the Faculty of Arts. The greatest support I could receive, came from family and friends, who encouraged me from the beginning, reminded me that there was a light at the end of the tunnel (and that it was getting ever closer) and now, constantly tell me I will find a job doing what I love the most. Thank you to Momma and Da, my brother Curtis and my best friend Amanda Coughlin, without you I may have taken over the bakery! iii Table of Contents Abstract ............................................................................................................................................... ii Acknowledgements ............................................................................................................................ iii Table of Contents .................................................................................................................................iv List of Tables ..................................................................................................................................viii List of Figures ...................................................................................................................................... ix Chapter 1 Introduction ......................................................................................................................... 1 Chapter 2 Pathological Conditions and Health Status in the New World: Pre‐contact to Contemporary Populations ............................................................................................................. 8 Health in the New World prior to contact ................................................................................. 10 Inuit Health .................................................................................................................................... 15 Contact ......................................................................................................................................... 17 Arctic Contact and the Impact on the Inuit Environment ....................................................... 19 New World Tuberculosis ................................................................................................................ 25 Chapter 3 Human Immunogenetic Diversity Present and Past .................................................. 29 The Human Immune System........................................................................................................... 29 Innate Immune System ............................................................................................................... 32 Adaptive Immune System ........................................................................................................... 34 Th1 vs. Th2 ..................................................................................................................................... 35 Cytokines ................................................................................................................................... 37 Immunity and Tuberculosis ............................................................................................................ 38 Population‐based immunological variation ............................................................................. 41 Cytokine Polymorphisms and Disease ............................................................................................ 48 Analysis of Cytokine Gene Polymorphisms .......................................................................... 49 Canadian Aboriginal and Inuit Specific Immune Diversity ............................................................... 53 Ancient DNA and Anthropology ......................................................................................................... 54 Mitochondrial DNA ..................................................................................................................... 59 Haplogroups ............................................................................................................................ 61 Nuclear DNA ................................................................................................................................ 68 Sex Determination .................................................................................................................. 69 iv Analysis of Microbial DNA .....................................................................................................
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