Doctoral Dissertation Research: Genetic Adaptation to Disease: Tuberculosis Susceptibility in Native South Americans

University Of New Mexico, Albuquerque NM

Investigators

Abstract

Biological anthropologists have long been interested in the question of population differences in disease susceptibility, but Native American communities have historically been underrepresented in research on host-pathogen co-evolution. Given that a longstanding, unresolved controversy in paleopathology concerns the origin of New World tuberculosis, inclusion of these groups is of utmost importance to the understanding of the evolution of this disease and its historical and current impact on native communities. Tuberculosis incidence in Native American populations since European contact has been high, and extreme susceptibility of Native Americans was traditionally considered evidence against pre-Columbian tuberculosis, but recent studies confirm presence of the disease in the New World prior to European contact. Thus, susceptibility of Native American groups must be examined as a potential adaptive mechanism to other environmental factors. Mounting evidence from research performed on other world populations indicates that a complex interplay of host genetics and the environment play an important role in determining tuberculosis susceptibility. In Asian, African and European populations studied to date, for example multiple genes are involved in susceptibility, and these genes differ by population. This dissertation examines the role of host genetics and environmental factors in tuberculosis susceptibility in the Ache of Paraguay. Candidate genes associated with tuberculosis in other populations (vitamin D receptor, natural resistance-associated macrophage protein, and mannose binding lectin) will be analyzed for linkage to tuberculosis. The scientific merit of this project is that it is the first large-scale study of Native Americans to incorporate extensive pedigree, demographic and epidemiological data to examine genetic and environmental causes of tuberculosis susceptibility. The longitudinal nature of the data set will allow examination of the underlying genetic causes of the high case rates in Native American populations relative to European ones. At a broader level, this project can serve as a model for examining susceptibility to TB in other Native American groups in that similar loci may be involved. The research proposed here can add to the growing body of information on the co-evolution of human populations and their pathogens by identifying loci that are involved in TB susceptibility in an as yet unexamined Native American group. The broader impact of this research can be divided into two stages. At an individual level, a graduate student, and an undergraduate assistant will be trained. At the level of the population, there may be health and economic consequences for Ache and perhaps other native South American communities, who have been underrepresented in this type of research. Disease susceptibility in native communities is more than a biological question: high rates of disease lead to social disruption and loss of economic productivity. Information about genetic vs. environmental causes of disease susceptibility may be key for future public health strategies.