High Risk: Admixture/migrant based study approach to evaluate oxygen transport in Andean high altitude natives

这是一项探索性研究项目，旨在调查安第斯山脉高海拔原住民群体的独特生理特征。一个持久的问题是，特征(如大肺容量)在多大程度上是遗传的，是自然选择的结果，还是发育的，是终身暴露于HA的结果。以前的许多研究都有这样的目标，即在这方面将遗传效应与发育效应分开，但取得的成功各不相同。在本研究中，我们将应用一种新的方法，牢记这一基本目标。这种方法可以被称为混合/移民研究设计，因为它利用了安第斯山脉的两个基本现实。首先，目前的大多数安第斯人都是欧洲人和美洲印第安人的混血后裔。其次，目前的人口不仅居住在高海拔地区，而且作为最近移民到海平面附近的大城市中心。如果将匹配的高原和低地出生的受试者组进行比较，这可能会让我们更好地了解终身高原暴露如何影响生理。此外，如果估计群体中每个个体的混合率，那么我们可能更好地理解遗传学和自然选择是如何影响生理学的。通过量化这两种影响，我们可以明确地测试基因和环境相互作用产生给定特征的想法。与秘鲁利马的卡耶塔诺大学合作，我们将在利马(海平面)和秘鲁塞罗德帕斯科(4300米)测量至少25名低地出生的受试者的肺功能和最大耗氧量(VO2max)。在塞罗德帕斯科，我们将对至少25名出生在高原的受试者进行同样的测量。血液样本将被用来根据为此目的开发的一组信息遗传标记来确定混合率。这项研究应该提供关于这一有希望的新方法的可行性的关键信息。

This is an exploratory research project to investigate the unique physiological characteristics of high altitude native populations in the Andes. An enduring question is the extent to which characteristics (such as large lung volume) are genetic, as the result of natural selection, or developmental, as the result of lifelong exposure to HA. Many previous studies have had the goal to partition genetic from developmental effects in this regard, but with varying success. In the present study we will apply a novel approach with this basic goal in mind. The approach might be termed an admixture/migrant study design because it takes advantage of two fundamental realities in the Andes. First, the majority of current Andeans are the admixed descendents of both European and Amerindian populations. Second, current populations reside not only at high altitude, but also as recent migrants to large urban centers near sea-level. If matched groups of highland and lowland born subjects are compared, this may allow us to better understand how lifelong altitude exposure affects physiology. Further, if admixture rates are estimated for each individual within a group, then we may better understand how genetics and natural selection have affected physiology. By quantifying both effects, we can explicitly test the idea that gene and environment interact to produce a given characteristic. In collaboration with the Universidad Cayetano, Lima, Peru, we will measure pulmonary function and maximal oxygen consumption (VO2max) in at least 25 lowland born subjects in Lima (sea level) and also at Cerro de Pasco, Peru (4,300 m). In Cerro de Pasco, we will perform the same measurements on at least 25 highland born subjects. A blood sample will be used to determine admixture rate based on a panel of informative genetic markers developed for this purpose. This study should provide crucial information regarding the feasibility of this promising new approach.