IBD MAPPING & PATTERN OF HUMAN MEIOTIC RECOMBINATION

此次更新申请的重点是DNA序列变异。我们的目标是继续 [开发一种称为直接IBD作图的作图方法，并研究减数分裂的模式， 在人体内的重组。改变的重组与不分离有关， 非整倍体。 I首先，直接IBD作图是一种允许鉴定共享的基因组区域的方法， 没有标记基因分型的相关个体之间的差异。共享的大DNA片段 相关个体之间序列相同（可能代表IBD DNA片段）， 基因组错配扫描的过程中得到了丰富。然后将所选择的DNA片段 通过杂交映射到基因组DNA微阵列上。在过去的几年里，我们 优化了步骤，并为直接IBD映射创建了必要的资源。接下来，我们将验证 通过绘制CEPH家族中个体之间共享的IBD区域的程序， 简化各种步骤，使直接IBD作图成为高通量作图的工具。 第二，受IBD直接作图工作的刺激，我们已经开始表征 人类减数分裂重组的模式。在这次更新申请中，我们将扩大 该项目旨在描述人类重组率的变化并绘制遗传决定因素 这种变化。 本提案的目的如下：1.开发直接IBD绘图， 不需要基因分型的血统同一性作图方法。2.表征自然 人类重组率的变化。3.绘制自然变异的遗传决定因素 人类的重组率。 我们希望这项研究的结果将提供一个强大的映射方法， 比目前的方法更有效。它还将使我们深入了解人类减数分裂的模式， 重组是一个关键过程，有助于遗传多样性和不分离的风险。

The focus of this renewal application is DNA sequence variation. Our goal is to continue to [develop a mapping method known as direct IBD mapping and to study the pattern of meiotic Irecombination in humans. Altered recombination is associated with non-disjunction, the major cause Iof aneuploidy. I First, direct IBD mapping is a method that allows identification of genomic regions shared between related individuals without marker-by-marker genotyping. Large DNA segments shared identical in sequence (likely representing IBD DNA fragments) between related individuals are enriched in a procedure known as genomic mismatch scanning. The selected DNA fragments are then mapped by hybridization onto a genomic DNA microarray. In the last several years, we have optimized the steps and created the necessary resources for direct IBD mapping. Next, we will validate the procedure by mapping the IBD regions shared between individuals in CEPH families and will streamline various steps so that direct IBD mapping can become a tool for high-throughput mapping. Second, stimulated by the work on direct IBD mapping, we have begun to characterize the pattern of meiotic recombination in humans. In this renewal application, we will expand the scope of the project to characterize the variation in human recombination rates and map the genetic determinants of this variation. This proposal has the following aims: 1. Develop direct IBD mapping, a high-resolution identity-by-descent mapping method that does not require genotyping. 2. Characterize natural variation in recombination rate in humans. 3. Map the genetic determinants of natural variation in total recombination rate in humans. We expect the results from this study will provide a robust mapping method that is more efficient than current methods. It will also give insights into the pattern of human meiotic recombination, a key process that contributes to genetic diversity and to risk of non-disjunction.