ANALYTIC CONSTRUCTION AND EVALUATION OF MEIOTIC INDEX MAPS

减数分裂基因图谱已被证明是人类基因组学领域中有价值的工具。 基因研究 这些地图提供了重要的见解，人类 疾病、遗传多样性和染色体/基因结构。 减数分裂 地图在整合信息方面发挥着至关重要的作用， 物理绘图技术与未知遗传疾病的研究 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， 程序. 近年来，我国重点建设了 分辨率连锁图。 在这些图谱中，靶基因座间图谱 距离是5厘米或更少。虽然理论上这些方法应该有 相似的分析特征，实际性质的差异， 数据和统计问题可能会导致意想不到的结果。 这是特别真实的关于异常的影响， 意见。 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地图的严重膨胀， 距离和不正确的基因顺序的推导。 目前没有 用于鉴定/校正基因型的广泛接受的方法 分类错误 构建一个完整性高、质量好、 结构，每个人类染色体的减数分裂图。 然而，为了解决 上述问题，amp建设将同时进行， 开发统计工具，以便评估地图质量 和正直 在具体目标I中， 精细结构遗传图谱的构建将得到推广。 主 这些努力的重点将是发展统计诊断 评估绘图结果的方法。 在具体目标II中， 上述信息将应用于DNA多态性数据 收集在项目3和4中，以构建高分辨率的减数分裂图， 每个人类染色体 地图构建将在两个层次中进行 方式 首先，利用PCR技术构建了高杂合度10 cM分辨率的索引图， 将构建可检测标记。 其次，交叉最小化 技术将用于整合额外的点，以实现2.5 cM 最小密度指数图 这些技术也将用于获得 大量基因位点的可能位置。

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.