POPULATION GENETICS OF MOBILE ELEMENTS

该项目的总体目标是研究人群中Alu逆转录子的变异。Alu元素约占人类基因组的5%，其中许多在人类中是多态性的（存在或不存在）。它们独特的特性使它们非常适合研究遗传变异和进化历史：因为每个元素只插入基因组一次，极性和血统鉴定可以明确确定。然而，到目前为止，只有少数这些多态性被识别和分析，它们在人类群体中的变化仍然知之甚少。在这个项目中，我们将在全球400个个体的样本中确定125个新的多态Alu多态性。我们将开发新的统计方法，充分利用这些多态性的特性。在这个项目中开发的数据和主题将充分利用这些多态性的特性。在这个项目中开发的数据和方法将使我们能够测试一系列关于现代人类起源和古代人类人口规模的假设。人类种群大小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意义。对于10个Alu多态性的子集，将使用位于Alu插入物20kb内的单核苷酸和微卫星多态性构建单倍型。这将使我们能够估计Alu元素插入的时间，比较具有不同历史的种群中的连杆不平衡模式，并研究在良好控制环境下连杆不平衡的行为。这些项目将有助于我们了解人类遗传进化及其影响构成复杂人类疾病基础的遗传变异的方式。

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.