LINKAGE DISEQUILIBRIUM AND HUMAN GENETIC STUDIES

连锁不平衡是一个不断变化的方面， 群体和微区域沿着基因组，反映了积累的 来自许多来源的影响，如重组，人口，历史， 选择，遗传漂变，突变，染色体区域（端粒到 着丝粒）效应等。连锁的静态观察 一个群体中一个位点的不平衡不能充分代表 人类基因组中变异组织的动态方面。 本方案项目建议对以下方面进行系统评价： 连锁不平衡在各种人群中的代表 代表不同染色体区域的基因座的物种多样性 的基因组。该研究将涉及不同的数据收集 20个常染色体基因座的标记类型， 和一个很长的区域（一个兆）在三个相当不同的 人口，理论和统计研究，以制定改进的 分析方法，计算机模拟作为评估的辅助手段， 各种方法和数据分析。的独特数据集 将导致和改进的分析方法将允许表征 连锁不平衡的系统特征归因于效应 群体和染色体区域以及特异质特征。 由此概述了连锁不平衡的性质和程度 应该为广泛的实践提供更好的指导方针， 临床和基础研究人员应用连锁不平衡 追求，特别是疾病相关基因的地图位置的细化。

Linkage disequilibrium is a continuously changing aspect of each population and micro-locale along the genome that reflects the accumulated influences from many sources such as recombination, population, history, selection, genetic drift, mutation, chromosomal region (telomeric to centromeric) effects, etc. The static observation of linkage disequilibrium at one locus in one population cannot adequately represent this dynamic aspect of the organization of variation in the human genome. This Program Project proposes to carry out a systematic evaluation of linkage disequilibrium in a variety of human populations representing the diversity of the species for loci representing diverse chromosomal regions of the genome. The research will involve data collections for different types of markers at twenty autosomal loci in each of twenty populations, and one very long region (one megabase) in three quite diverse populations, theoretical and statistical studies to develop improved analytic approaches, computer simulations as an aid to evaluation of various methodologies and analyses of the data. The unique dataset that will result and the improved analytic methods will allow characterization of systematic features of linkage disequilibrium attributable to effects of population and chromosomal region as well as idiosyncratic features. The resulting overview of the nature and extent of linkage disequilibrium should provide greatly improved guidelines for the wide range of practical applications of linkage disequilibrium that clinical and basic researchers pursue, especially the refining of map locations of disease related genes.