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.

提出了人类分子群体遗传学的两个研究领域。第一个需要对从世界范围内的人口中提取的样本的分子变异性进行统计和数学分析。分子变异包括短串联重复DNA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异，其值反映了种群扩张或收缩的历史。还将开发系谱学方法来分析Y染色体和mtDNA单倍型，估计人口增长率以及最近的共同祖先单倍型的时间。将比较从微卫星数据和单核苷酸变异获得的估计值。单倍型的连锁不平衡将用于估计迁移量。从栽培小麦，大麦和鸡的野生祖先的数据将与驯化品种的数据进行比较，以估计人类种植这些重要物种的时间。在研究的第二个领域，我们将采用病例对照研究调查疾病关联、人群分层和混合的措施。我们将使用统计学方法从多位点基因型中确定病例对照样本是否受人群分层的影响。我们还将根据病例对照研究得出相关性的统计检验，当人群分层时可以使用，并研究这些检验的功效。使用多位点基因型和似然分析，我们将开发一种方法来识别来自未知祖先的个体的起源群体。