COALESCENT THEORY AND ANALYSIS OF DNA POLYMORPHISM

DNA多态性的聚结理论与分析

• 批准号: 2188273
• 负责人: Yun-Xin Fu
• 金额: $ 10.45万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2188273
• 关键词: DNA; chromosome movement; computer program /software; computer system design /evaluation; gene frequency; genetic polymorphism; human population genetics; mathematical model; nucleic acid sequence; nucleotides; statistics /biometry; DNA; chromosome movement; computer program /software; computer system design /evaluation; gene frequency; genetic polymorphism; human population genetics; mathematical model; nucleic acid sequence; nucleotides; statistics /biometry

The goal of this research project is to develop the coalescent theory to the level so that power of the information of DNA polymorphism, the ultimate resolution of genetic variation, can be fully realized. The theory has wide applications ranging from studying mutation rate to the estimation of the time to the common ancestor of our human beings. Specific aims include: a. to develop the theory of coalescent for the frequencies of segregating types. We propose to derive analytically the mean,, variances and covariances of the frequencies of segregating types under models, from the classic which assumes no recombination and equal rates of mutations for all sites to more realistic model that allows both recombination and unequal rates of mutations at different sites of sequences. The theory will make the application of the theory of coalescent highly efficient. b. to develop highly efficient statistical methods for estimating theta. We propose a framework, which will utilize both the phylogenetic information and the frequencies of segregating types, to estimate the crucial parameter theta=4Nemu. c. to develop powerful statistical method for testing the hypotheses concerned about theta. We propose to develop statistical tests for the assumptions underlying the coalescent theory, including the assumption of neutrality of mutations, by utilizing the information contained in frequencies of segregating types. d. to develop a visual method for identifying the main causes of genetic variations at DNA sequences. We propose to use graphical comparison of the observed frequencies of segregating types with the expected frequencies of segregating types under different assumptions, including selection, population subdivision. e. to estimate the time to common ancestor and determine the pattern and speed of population growth. We propose a maximum likelihood method for estimating the time to the most recent common ancestor of the individuals in a sample. This likelihood method also allows one to analyze the pattern and speed of changes in the effective population size.

该研究项目的目的是将合并理论发展为 这样的水平使DNA多态性信息的力量， 遗传变异的最终分辨率可以完全实现。 这 理论具有广泛的应用，从研究突变率到 估计我们人类共同祖先的时间。 具体目的包括： 一个。 开发出频率的融合理论 隔离类型。 我们建议通过分析得出平均值 隔离类型的频率的差异和协方差 模型，来自没有重组和相等速率的经典 所有站点的突变，以更现实的模型 不同地点的重组和突变的不等速率 序列。 该理论将使理论的应用 合并高效。 b。 开发高效的统计方法来估计theta。 我们提出了一个框架，该框架将同时利用系统发育 信息和隔离类型的频率，以估计 关键参数theta = 4nemu。 c。 开发强大的统计方法来检验假设 担心theta。 我们建议开发针对 合并理论为基础的假设，包括假设 通过利用所包含的信息的中立性 分离类型的频率。 d。 开发一种视觉方法来识别遗传的主要原因 DNA序列的变化。 我们建议使用的图形比较 观察到的隔离类型的频率与预期 不同假设下的分离类型的频率，包括 选择，人口细分。 e。 估算共同祖先的时间并确定模式和 人口增长的速度。 我们提出了一种最大似然方法 将时间估计到个人的最新共同祖先 在样本中。 这种可能性方法还允许一个人分析 有效人口规模的变化的模式和速度。