RECONSTRUCTING GENETIC ANCESTRY BLOCKS IN ADMIXED INDIVIDUALS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近混合祖先的个体的染色体类似于染色体片段或祖先块的马赛克，每个染色体片段或祖先块来自特定的祖先群体。我们考虑了在混合个体中沿着染色体推断祖先的问题，从而描绘出祖先块。使用一个简单的种群模型，我们可以推断出每个个体的基因流动历史。与现有的基于隐马尔可夫模型的方法相比，我们提出的马尔可夫隐马尔可夫模型(MHMM)具有考虑祖先种群中存在的背景连锁不平衡(LD)的优势。当有两个以上的祖先群体时，我们允许每个祖先群体在不同的历史时期混杂在一起。我们使用模拟来说明推断祖先的准确性以及对背景LD建模的重要性；如果不考虑标记之间的背景LD，可能会误导我们对土著人口中的混合祖先做出错误的推断。MHMM使得通过使用任何高密度单核苷酸多态小组来识别特定祖先的基因组块成为可能。我们方法的一个应用是执行混合作图，而不需要对特殊的血统信息标记面板进行基因分型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A chromosome in an individual of recently admixed ancestry resembles a mosaic of chromosomal segments, or ancestry blocks, each derived from a particular ancestral population. We consider the problem of inferring ancestry along the chromosomes in an admixed individual and thereby delineating the ancestry blocks. Using a simple population model, we infer gene-flow history in each individual. Compared with existing methods, which are based on a hidden Markov model, the Markovhidden Markov model (MHMM) we propose has the advantage of accounting for the background linkage disequilibrium (LD) that exists in ancestral populations. When there are more than two ancestral groups, we allow each ancestral population to admix at a different time in history. We use simulations to illustrate the accuracy of the inferred ancestry as well as the importance of modeling the background LD; not accounting for background LD between markers may mislead us to false inferences about mixed ancestry in an indigenous population. The MHMM makes it possible to identify genomic blocks of a particular ancestry by use of any high-density single-nucleotidepolymorphism panel. One application of our method is to perform admixture mapping without genotyping special ancestry-informativemarker panels.