NUMERICAL ANALYSIS OF HUMAN MOLECULAR POLYMORPHISMS

提出了人类分子群体遗传学的两个研究领域。第一种方法需要统计和数学分析从世界各地的人群中提取的样本的分子变异性。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染色体和Y染色体上的单核苷酸多态性。微卫星数据的单核苷酸变异，其值反映种群扩张或收缩的历史。系谱学方法也将被用于分析y染色体和mtDNA单倍型，给出人口增长率的估计，以及从最近的共同祖先单倍型开始的时间。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被用来估计迁移的数量。将把来自栽培小麦、大麦和鸡的野生祖先的数据与来自驯化品种的数据进行比较，以估计人类栽培这些重要物种的时间。在第二个研究领域，我们将使用病例对照研究调查疾病关联、人口分层和混合的措施。我们将使用统计方法从多位点基因型中确定病例对照样本是否受群体分层影响。我们还将基于病例对照研究得出关联的统计检验，可用于人群分层，并调查这些检验的有效性。利用多位点基因型和似然分析，我们将开发一种从未知祖先个体中识别起源群体的方法。

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.