LINKAGE ANALYSIS AND MULTIPLE LOCI

连锁分析和多位点

• 批准号: 3173924
• 负责人: DAVID T BISHOP
• 金额: $ 12.66万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3173924
• 关键词: computer simulation; genetic mapping; genetic markers; genetic models; hereditary hemochromatosis; linkage mapping; mathematical model

This research is designed to investigate the efficient localization and ordering of major genes through linkage analysis. Although new gene mapping methods and programs have emerged, significant capabilities are still lacking and many of the statistical concepts are dated. Gene mapping can be divided into two phases: 1) initial assignment of a gene to a chromosomal region, and 2) assignment of gene order and map distance of the disease locus to all of the markers. The issues of significance and efficiency are different for these phases. In the first phase, we are testing for linkage between the disease locus and well-spaced highly polymorphic markers. Three locus evaluation of expected LOD scores and actual LOD scores are sufficient. We will investigate significance levels of the three locus analysis for testing linkage on saturated maps. For fine mapping we will compute expected LOD scores and LOD scores for gene order with multiple loci. We will also establish significance levels for comparison of orders. The preliminary LOD scores sufficient to justify a switch in strategy from localization to establishing order will be described. As the set of tools for calculating expected LOD scores and LOD scores are investigated, a knowledge-based expert system will be developed which will integrate these tools with the appropriate databases and rules. The system will be an automated tool assisting in designing the experiments, evaluating data from the experiments, and redesigning the experiment in light of the preliminary results. Thus, the large number of linkage experiments carried out in the near future can be performed efficiently.

本研究旨在调查有效的本地化和 通过连锁分析对主要基因进行排序。 虽然是新基因 绘图方法和程序已经出现，重要的能力正在 仍然缺乏，并且许多统计概念已经过时。 基因图谱 可以分为两个阶段：1）将基因初始分配给 染色体区域，以及 2) 基因顺序分配和图谱距离 所有标记的疾病位点。 问题的重要性和 这些阶段的效率是不同的。 在第一阶段，我们是 测试疾病位点和间隔良好的高度之间的联系 多态性标记。 预期 LOD 分数的三个位点评估和 实际的 LOD 分数就足够了。 我们将调查显着性水平 用于测试饱和图上连锁的三基因座分析。 为了 精细映射我们将计算基因的预期 LOD 分数和 LOD 分数 具有多个基因座的顺序。 我们还将建立显着性水平 订单比较。 初步的 LOD 分数足以证明 战略从本土化转向建立秩序 描述的。 作为计算预期 LOD 分数和 LOD 的工具集 调查分数，将开发基于知识的专家系统 它将这些工具与适当的数据库和规则集成。 该系统将是一个自动化工具，协助设计 实验、评估实验数据并重新设计 根据初步结果进行实验。 因此，大量的 近期可以进行连锁实验 高效。