Pilot HGDP: Contribution of Alu repeats to Human Genomic Diversity

在基因组中插入移动的元件是研究人类基因组多样性的一类新的核标记。 Alu家族的移动的元件占人类基因组的5%。 最近整合的Alu亚家族的大多数成员仅限于人类基因组，而不存在于非人灵长类动物中。 这些重复单位中的许多最近才插入人类基因组中，以至于它们对于在特定染色体位置存在或不存在Alu元件是多态的。 Alu插入多态性为人类进化研究提供了两个重要的优势。 首先，一个Alu元件的存在代表了血统上的同一性，因为两个不同的年轻Alu重复序列在同一染色体位置独立整合的概率是可以忽略的。 第二，每个Alu插入多态性的祖先状态是已知的元素，这可以用来根树的人口关系的情况下。 在这个项目中，我们将确定与几个多态性Alu元件相关的人类基因组多样性，并开发由多态性Alu插入和相邻微卫星位点组成的单倍型系统。在每个单倍型中使用Alu重复序列和微卫星导致相同的血统（Alu插入）标记与一类具有高突变率的标记（微卫星）的组合，为人类的早期辐射以及最近的进化史提供基因组记忆。

The insertion of mobile elements into the genome represents a new class of nuclear markers for the study of human genomic diversity. The Alu family of mobile elements comprise 5% of the human genome. Most members of the recently integrated Alu subfamilies are restricted to the human genome and absent from nonhuman primates. Many of these repeat units have inserted so recently within the human genome that they are polymorphic for the presence or absence of an Alu element at a particular chromosomal location. Alu insertion polymorphisms offer two important advantages over other nuclear based polymorphisms for human evolution studies. First, the presence of an Alu element represents identity by descent, since the probability that two different young Alu repeats would integrate independently in the same chromosomal location is negligible. Second, the ancestral state of each Alu insertion polymorphism is known to be the absence of the element, which can be used to root trees of population relationships. In this project we will determine the human genomic diversity associated with several polymorphic Alu elements and develop haplotyping systems composed of polymorphic Alu insertions and adjacent microsatellite loci. Using both Alu repeats and microsatellites in each haplotype results in the combination of an identical by descent (Alu insertion) marker, with a class of marker that has a high mutation rate (microsatellites) providing a genomic memory for both early radiations of humans as well as recent evolutionary history.