The Population Genetics of Divergence

分歧的群体遗传学

• 批准号: 8640190
• 负责人: Emanuel Hey
• 金额: $ 22.03万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8640190
• 关键词: Address; Admixture; Affect; Africa; African; Applications Grants; Budgets; Collaborations; Complex; DNA Resequencing; Data; Data Set; Development; Disease; Event; Gene Exchanges; Gene Frequency; Genealogy; Genes; Genetic; Genetic Drift; Genetic Recombination; Genetic Variation; Genome; Genomics; Goals; Haplotypes; Human; Human Genetics; Knowledge; Left; Link; Medical; Medical Genetics; Methodology; Methods; Modeling; Mutation; Pattern; Population; Population Genetics; Population Sizes; Portraits; Probability; Process; Recording of previous events; Research; Research Personnel; Sampling; Single Nucleotide Polymorphism; Speed; Staging; Technology; Text; Time; Trees; Work; base; computer program; design; human disease; method development; migration; novel strategies; tool

The propose research will address a great challenge of modern human genetics which is to understand the recent evolutionary history of our species. This is important not only as key basic knowledge, but also for many medical genetic questions, such as when and where have mutations occurred that contribute to diseases. The backdrop for medical questions like these is the demographic history of human populations, which includes our history of population sizes, population founding events, migrations and admixture, and population size changes. Two new methods for estimating the demographic history of a species will be developed. Both of these have been designed to address three major challenges that limit current methods. First, methods that are intended to study the history of gene exchange must include recombination as part of the model because of the strong interaction affect that recombination and gene exchange have on patterns of genetic variation. Second, methods must be able to handle large, complex demographic models with human populations. This is especially true for histories with gene exchange. Third, methods must be able to handle very large data sets with speed and without introducing biases. One new method will provide estimates of the Allele Frequency Spectrum (AFS) for pairs of linked single-nucleotide- polymorphisms (SNPs). By including recombination for pairs of SNPs, the 2 SNP AFS is far larger and holds much more information on gene exchange than the conventional single SNP-based AFS. The second new method will be a new genealogy sampling approach that uses a greatly reduced representation of genealogies (gene trees). This method does not give up any information, and yet unlike most current genealogy samplers will be able to be used for models with recombination and for large data sets. The third goal is to apply these methods to the study of human demographic history among African populations. African populations have ancient and complex genetic histories that include all of the major demographic processes considered here. Both methods will be applied to a large high-quality population genomic data set that currently includes 33 genomes from 7 populations, including three hunter-gatherer populations. The goal is an accurate and rich multi- population portrait of human history in Africa.

这项研究将解决现代人类遗传学的一个巨大挑战，即了解最近的 我们物种的进化史。这不仅是重要的关键基础知识，而且对于许多医学遗传学也很重要。 问题，例如何时何地发生导致疾病的突变。医疗背景 诸如此类的问题是人类人口的人口历史，其中包括我们的人口规模历史， 人口创建事件、迁移和混合以及人口规模变化。 将开发两种估计物种人口历史的新方法。这两个都已经 旨在解决限制当前方法的三大挑战。首先，研究的方法 基因交换的历史必须包括重组作为模型的一部分，因为强烈的相互作用会影响重组 重组和基因交换影响遗传变异的模式。其次，方法必须能够处理大的、 复杂的人口统计模型与人口。对于基因交换的历史尤其如此。第三， 方法必须能够快速处理非常大的数据集并且不会引入偏差。 一种新方法将提供对相连的单核苷酸对的等位基因频谱（AFS）的估计 多态性（SNP）。通过包括 SNP 对的重组，2 个 SNP AFS 变得更大并且容纳更多 与传统的基于单 SNP 的 AFS 相比，基因交换信息更丰富。 第二种新方法将是一种新的谱系抽样方法，该方法使用大大减少的表示 家谱（基因树）。这种方法不会放弃任何信息，但与大多数当前的家谱不同 采样器将能够用于具有重组的模型和大型数据集。 第三个目标是将这些方法应用于非洲人口的人类人口史研究。非洲人 人口具有古老而复杂的遗传历史，其中包括所考虑的所有主要人口过程 这里。这两种方法都将应用于大型高质量群体基因组数据集，目前包括 33 来自 7 个种群的基因组，其中包括三个狩猎采集种群。目标是准确且丰富的多 非洲人类历史的人口肖像。