ANALYTIC CONSTRUCTION AND EVALUATION OF MEIOTIC INDEX MAPS

减数分裂指数图的分析构建和评估

• 批准号: 3843228
• 负责人: KENNETH H BUETOW
• 金额: --
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3843228
• 关键词: chromosomes; computer assisted sequence analysis; computer human interaction; computer program /software; computer simulation; evaluation /testing; genetic mapping; heterozygote; human genetic material tag; information systems; mathematical model; meiosis; statistics /biometry

Meiotic gene maps have proven to be valuable tools in the field of human genetic research. These maps provide significant insights into human disease, genetic diversity, and chromosome/gene structure. The meiotic maps play a crucial role in integrating the information obtained from physical mapping techniques with the study of genetic disorders of unknown molecular etiology. The construction of multilocus human genetic maps has become common place due to the ubiquity of user-friendly computer analysis programs. Recently, efforts have been focused on the construction on high resolution linkage maps. In these maps, the target interlocus map distances are 5 cMs or less. While theoretically these methods should have similar analytic characteristics, practical differences in the nature of the data and the statistical problem may result in unexpected outcomes. This is particularly true with respect to the influence of aberrant observations. Uncertainty of data validity has resulted in the construction of meiotic maps of unknown integrity. Preliminary studies have shown that genotyping errors can lead to gross inflation of map distances and derivation of incorrect gene orders. There are currently no widely accepted methods for the identification/correction of genotype misclassification. It is the primary goal of this research to construct a high integrity, fine structure, meiotic map of each human chromosome. However, to address the above questions, amp construction will proceed simultaneously with development of statistical tools that allow the assessment of map quality and integrity. In SPECIFIC AIM I the analytic methods used in the construction of fine structure genetic maps will be extended. The primary focus of these efforts will be the development of statistical diagnostic methods for the evaluation of mapping outcomes. In SPECIFIC AIM II, the information garnered above will be applied to the DNA polymorphism data collected in PROJECTS 3 and 4 to construct a high resolution meiotic map of each human chromosome. Map construction will be conducted in a two tiered manner. First, a high heterozygosity 10 cM resolution index map of PCR detectable markers will be constructed. Next, crossover minimization techniques will be used to integrate additional points to achieve a 2.5 cM minimum density index map. These techniques will also be applied to obtain likely locations for a large number of gene loci.

减数分裂基因图谱已被证明是人类研究领域中有价值的工具 基因研究。这些地图提供了对人类的重要洞察 疾病、遗传多样性和染色体/基因结构。减数分裂 地图在整合从获取的信息方面起着至关重要的作用 物理作图技术与未知遗传性疾病的研究 分子病因学。多位点人类遗传图谱的构建 由于用户友好的计算机分析无处不在，成为常见的地方 程序。最近，高铁的建设工作一直在集中进行。 分辨率链接图。在这些映射中，目标轨迹间映射 距离为5厘米或更短。虽然从理论上讲这些方法应该有 相似的分析特征，不同的实际性质 数据和统计问题可能会导致意想不到的结果。 就异常的影响而言，这一点尤其正确 观察。数据有效性的不确定性导致了 构建完整性未知的减数分裂图谱。初步研究 已经表明，基因分型错误会导致MAP的严重膨胀 不正确基因序列的距离和派生。目前没有 被广泛接受的鉴定/纠正基因的方法 分类错误。 本研究的首要目标是构建一个高诚信、精细化的 每条人类染色体的结构、减数分裂图谱。然而，为了解决 以上问题，功放建设将同步进行。 开发能够评估地图质量的统计工具 和正直。在具体目标I中使用的分析方法 推广构建精细结构遗传图谱。初级阶段 这些努力的重点将是发展统计诊断 测绘成果评价方法。在特定的AIM II中， 以上收集的信息将应用于DNA多态数据 在项目3和4中收集，以构建高分辨率的减数分裂图 每条人类染色体。地图构建将分两个层次进行 举止。首先，建立了高杂合度10 cM分辨率的聚合酶链式反应指标图 将构建可检测的标记。接下来，交叉最小化 将使用技术来积分额外的点数，以实现2.5厘米 最小密度指数图。这些技术也将被应用于获得 大量基因座的可能位置。