POPULATION GENETICS OF MOBILE ELEMENTS

该项目的总体目标是研究Alu逆转录酶在人类群体中的变异。Alu元素约占人类基因组的5%，其中许多元素在人类中是多态的(存在或不存在)。它们的独特性质使其非常适合于遗传变异和进化史的研究：因为每个元素只插入基因组一次，所以可以明确地确定极性和血统身份。然而，到目前为止，只有少数这些多态被识别和分析，而且它们在人类群体中的变异仍然知之甚少。在这个项目中，我们将在全球400个个体的样本中识别125个新的多态Alu多态。我们将开发新的统计方法，充分利用这些多态的特性。本项目中开发的数据和主题将充分利用这些多态的特性。这个项目开发的数据和方法将使我们能够检验一系列关于现代人类起源和古代人类人口规模的假设。人类种群规模的轨迹对导致复杂疾病易感性的等位基因的分布具有重要影响。对于10个Alu多态的子集，将使用位于Alu插入20kb内的单核苷酸和微卫星多态来构建单倍型。这将使我们能够估计Alu元素的插入时间，比较不同历史群体中的连锁不平衡模式，并研究在良好控制的环境中连锁不平衡的行为。这些项目将有助于我们理解人类基因进化及其影响复杂人类疾病背后的遗传变异性的方式。

The overall goal of this project is to study variation in Alu retroposons in human populations. Alu elements compose approximately 5% of the human genome, and many of them are polymorphic (present or absent) in humans. Their unique properties make them ideally suited to studies of genetic variation and evolutionary history: because each element is inserted into the genome only once, polarity and identify by descent can be determined unambiguously. To date, however, only a handful of these polymorphisms have been identified and analyzed, and their variation in human populations remains poorly understood. In this project, we will identify 125 new polymorphic Alu polymorphisms in a worldwide sample of 400 individuals. We will develop new statistical methods that fully exploit the properties of these polymorphisms. The data and themes developed in this project will fully exploit the properties of these polymorphisms. The data and methods developed in this project will permit us to test a series of hypotheses about modern human origins and ancient human population sizes. The trajectory of human population size has important implications for the distribution of alleles that contribute to susceptibility to complex diseases. For a subset of 10 Alu polymorphisms, haplotypes will be constructed using single nucleotide and microsatellite polymorphisms located within 20 kb of the Alu insert. This will permit us to estimate the time of insertion of Alu elements, compare linkages disequilibrium patterns in populations with different histories, and study the behavior of linkage disequilibrium in well-controlled settings. These project will contribute to our understanding of human genetic evolution and the ways in which it influences the genetic variability that underlies complex human diseases.