POPULATION GENETICS OF MOBILE ELEMENTS

该项目的总体目标是研究人类群体中Alu逆转录酶的变异。Alu元件约占人类基因组的5%，其中许多在人类中具有多态性（存在或不存在）。它们独特的性质使它们非常适合研究遗传变异和进化历史：因为每个元件只插入基因组一次，所以可以明确地确定极性和血统。然而，迄今为止，只有少数这些多态性已被确定和分析，其在人群中的变化仍然知之甚少。在这个项目中，我们将确定125个新的多态性Alu多态性在全球400个个体的样本。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属性。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。人类人口规模的变化轨迹对等位基因的分布有重要影响，而等位基因的分布又导致了对复杂疾病的易感性。对于10个Alu多态性的子集，将使用位于Alu插入片段20 kb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插入的Alu元素的时间，比较不同的历史群体中的连锁不平衡模式，并研究在良好的控制设置的连锁不平衡的行为。这些项目将有助于我们了解人类遗传进化及其影响遗传变异的方式，这些遗传变异是复杂的人类疾病的基础。

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.