LINKAGE ANALYSIS AND MULTIPLE LOCI

连锁分析和多位点

• 批准号: 3173926
• 负责人: DAVID T BISHOP
• 金额: $ 12.88万
• 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/3173926
• 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.

这项研究旨在调查有效的本地化和 通过连锁分析对主效基因进行排序。虽然新基因 地图绘制方法和程序已经出现，重要的功能是 仍然缺乏，许多统计概念已经过时。基因作图 可分为两个阶段：1)将基因初始分配给 染色体区域；2)基因序列和作图距离的分配 所有标记物上的疾病轨迹。意义重大的问题和 这些阶段的效率是不同的。在第一阶段，我们是 检测致病基因座与高度间隔的连锁性 多态标记。预期LOD得分的三个轨迹评估和 实际的LOD分数就足够了。我们将调查重要性级别 对饱和图谱进行连锁检验的三个基因座分析。为 精细作图我们将计算预期的LOD分数和基因的LOD分数 订购具有多个位置的订单。我们还将为以下内容建立重要级别 订单的比较。初步的LOD分数足以证明 从本地化到建立秩序的战略转换将是 描述。作为计算预期LOD分数和LOD的工具集 对成绩进行调查，将开发基于知识的专家系统 它将把这些工具与适当的数据库和规则结合起来。 该系统将成为一个自动化工具，帮助设计 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 在不久的将来进行的链接实验可以进行 效率很高。