RECONSTRUCTING GENETIC ANCESTRY BLOCKS IN ADMIXED INDIVIDUALS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 最近混合祖先的个体中的染色体类似于染色体片段或祖先块的镶嵌，每个染色体片段都源自特定的祖先群体。我们考虑沿着混合个体的染色体推断祖先并从而描绘祖先块的问题。使用简单的群体模型，我们推断每个个体的基因流历史。与基于隐马尔可夫模型的现有方法相比，我们提出的马尔可夫隐马尔可夫模型（MHMM）具有考虑祖先群体中存在的背景连锁不平衡（LD）的优点。当有两个以上的祖先群体时，我们允许每个祖先群体在历史的不同时间混合。我们使用模拟来说明推断血统的准确性以及对背景 LD 进行建模的重要性；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血统做出错误的推断。 MHMM 使得通过使用任何高密度单核苷酸多态性组来识别特定祖先的基因组块成为可能。我们的方法的一种应用是执行混合作图，而无需对特殊的祖先信息标记组进行基因分型。

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.