Dissertation Research: Tempo and Mode of HLA Evolution in the Americas

欧洲传染病传入美洲，导致土著居民灾难性的死亡。 虽然这场悲剧在整个美洲都很普遍，但它可以从北方亚利桑那州的一个讲尤曼语的部落Havasupai的历史中得到例证。 哈瓦苏派人居住在大峡谷的一个偏远的峡谷，生活在相对孤立的地方。 在1897年至1905年期间，哈瓦苏派遭受了一系列流感和麻疹的流行，只有四分之一的人口幸存下来。 以前的研究表明，这些流行病导致选择的个人谁是杂合在两个主要组织相容性复合体（MHC）基因，这是免疫防御病原体的关键组成部分。为了确定是否在Havasupai的MHC基因的变异模式是选择病原体抗性的结果，我们打算进行全基因组的微卫星位点调查，它们是高度可变的标记，不受自然选择的影响。 因为这些标记不受选择的影响，它们的变化模式将只反映哈瓦苏派的人口统计学历史。 我们将检查分布在所有22个常染色体上的106个位点，其中3个与MHC基因相关，15对相互关联。 遗传模式、群体变异和连锁对之间的关联将决定性地确定自然选择是否对在该代表性群体的MHC基因处观察到的变异负责。 这项研究有望深入了解与欧洲人对美洲的殖民化有关的美洲原住民人口下降的遗传后果。

The introduction of European infectious diseases to the Americas resulted in a catastrophic loss of life among the indigenous populations. While this tragedy was widespread throughout the Americas, it can be exemplified by the history of the Havasupai, a Yuman-speaking tribe of northern Arizona. The Havasupai inhabit a remote side canyon of the Grand Canyon and live in relative isolation. Between 1897 and 1905, the Havasupai suffered serial epidemics of introduced influenza and measles; only one-quarter of the population survived. Previous research suggests that these epidemics resulted in selection for individuals who were heterozygous at two major histocompatibility complex (MHC) genes, which are critical components of immunological defense against pathogens.To determine whether the pattern of variation at MHC genes in the Havasupai is the result of selection for pathogen resistance, we intend to perform a genome-wide survey of microsatellite loci, which are highly mutable markers that are not subject to natural selection. Because these markers are not subject to selection, their pattern of variation will reflect only the demographic history of the Havasupai. We will examine 106 loci spread over all 22 autosomes, three of which are linked to the MHC genes and 15 pairs are linked to one another. The patterns of inheritance, population variation, and association between linked pairs will determine conclusively if natural selection is responsible for the variation observed at the MHC genes of this representative population. This research promises to yield insight into the genetic consequences of the Native American population declines associated with colonization of the Americas by Europeans.