NUMERICAL ANALYSIS OF HUMAN MOLECULAR POLYMORPHISMS

人类分子多态性的数值分析

• 批准号: 6571534
• 负责人: MARCUS W FELDMAN
• 金额: $ 28.24万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6571534
• 关键词: biochemical evolution; computer assisted sequence analysis; gene expression; gene mutation; genetic disorder; genetic polymorphism; genotype; haploidy; human data; human genetic material tag; human population genetics; human tissue; linkage disequilibriums; mathematical model; mitochondrial DNA; model design /development; nucleic acid repetitive sequence; sex chromosomes; statistics /biometry

Two areas of research in human molecular population genetics are proposed. The first entails statistical and mathematical analysis of molecular variability in samples taken from a worldwide array of population. The molecular variation includes polymorphisms in short tandemly repeated DNA, also called microsatellites, and single nucleotide polymorphisms on the autosomes and X and Y chromosomes. Single nucleotide variation in microsatellite data whose values reflect the history of population expansion or contraction. Genealogical approaches will also be developed to analyze Y-chromosomal and mtDNA haplotypes, giving estimates of the rates of population growth as well as the time since the most recent common ancestral haplotype. Estimates obtained from microsatellite data and single nucleotide variation will be compared. Linkage disequilibrium in haplotypes will be used to estimate the amount of migration. Data from wild ancestors of cultivated wheat, barley, and chickens will be compared with data from domesticated varieties to give estimates of the time of human cultivation of these important species. In the second area of research, we will investigate measures of disease association, population stratification, and admixture using case-control studies. We will use a statistical method to determine from multi-locus genotypes whether a case-control sample is subject to population stratification. We will also derive statistical tests of association, based on case-control studies, that can be used when the population is stratified, and investigate the power of these tests. Using multi-locus genotypes and likelihood analysis, we will develop a method to identify the population(s) of origin from individuals of unknown ancestry.

提出了人分子种群遗传学的两个研究领域。第一个需要对来自全球人口阵列的样品中分子变异性的统计和数学分析。分子变异包括短串联重复的DNA中的多态性，也称为微卫星，以及常染色体和X和Y染色体上的单核苷酸多态性。微卫星数据中的单核苷酸变化，其值反映了种群扩张或收缩的历史。还将开发族谱方法来分析Y染色体和mtDNA单倍型，从而估计人口增长率以及自最近常见的祖先单倍型以来的时间。将比较从微卫星数据和单核苷酸变异的估计值。单倍型的连锁不平衡将用于估计迁移量。将将耕种小麦，大麦和鸡的野生祖先的数据与驯化品种的数据进行比较，以估计这些重要物种的人类培养时间。在第二个研究领域，我们将使用病例对照研究研究疾病关联，种群分层和混合的测量。我们将使用一种统计方法来从多级别基因型中确定病例对照样本是否受人群分层的影响。我们还将基于病例对照研究得出统计结合测试，该研究可以在分层时使用，并研究这些测试的功能。使用多基因级基因型和似然分析，我们将开发一种方法来识别未知祖先个体的起源人群。