NUMERICAL ANALYSIS OF HUMAN MOLECULAR POLYMORPHISMS

提出了人类分子群体遗传学研究的两个领域。第一个需要对从世界各地的人群中采集的样本进行分子可变性的统计和数学分析。分子变异包括短串联重复DNA的多态，也称为微卫星，常染色体以及X和Y染色体上的单核苷酸多态。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。还将开发系谱方法来分析Y染色体和mtDNA单倍型，估计人口增长率以及距离最近的共同祖先单倍型以来的时间。我们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量。来自栽培小麦、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，以估计这些重要物种的人类栽培时间。在第二个研究领域，我们将使用病例对照研究来调查疾病关联、人口分层和混合的措施。我们将使用统计学方法从多基因座基因型别中确定病例对照样本是否受到人群分层的影响。我们还将在病例对照研究的基础上，得出可在人口分层时使用的关联性统计检验，并调查这些检验的力量。利用多位点基因分型和似然分析，我们将开发一种从未知血统的个体中识别起源群体(S)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.