HIGH DENSITY GENETIC MAP OF XQ25-XQ28

该项目的主要目标是开发高密度遗传图谱 人类X染色体的选定区域， 物理图谱，并利用这些图谱研究连锁不平衡， 三个不同的群体。 根据在这里进行的大量工作， 华盛顿大学基因组中心和其他地方，>80%的X 染色体被高质量的酵母人工染色体（YAC）覆盖 重叠群 我们建议利用这一宝贵的本地资源， 专门知识，开发基因图谱，标记约100 kb 此外，使用单核苷酸多态性作为标记， 通过半自动寡核苷酸连接测定（奥拉）进行基因分型。 的 双等位基因标记的使用是至关重要的， 因为高信息量和有用的简单串联重复序列 多态性（STRP）标记似乎具有高突变率， 不利于不平衡作图。 选择的区域包括Xq25和Xq26之间的20 Mb X染色体。 XQ28 这些区域包含许多疾病基因位点，包括 其中一些是当地人感兴趣的。 增加了大约200个基因 这些地区的标志物将帮助国内外的许多研究人员 寻找他们感兴趣的基因。 一旦形成， 将确定这些标记的频率，并将其用于 基因型大约100名男性在每个三个群体，包括 那些CEPH谱系，在芬兰的一个孤立的人口，和一个 在撒丁岛也有类似的孤立人群。 这些单倍型 将对个体进行分析，以研究连锁不平衡， 人口历史和染色体定位。 如果成功，本提案中制定的方法将 适用于人类基因组的任何区域。 此外，链接 获得的不平衡数据将揭示几个重要的 群体遗传学中的问题和指导疾病基因定位工作 基于人口或不平衡研究。

The primary goals of this project are to develop high-density genetic maps of selected regions of the human X chromosome based on well characterized physical maps and to use these maps to study linkage disequilibrium in three distinct populations. Based on extensive work performed here at the Washington University Genome Center and elsewhere, >80% of the X chromosome is covered by high quality yeast artificial chromosome (YAC) contigs. We propose to utilize this invaluable local resource and expertise to develop genetic maps with markers placed approximately 100 kb apart, using as markers single nucleotide polymorphisms that can be genotyped by the semi-automated oligonucleotide ligation assay (OLA). The use of diallelic markers, which are less mutable, is of crucial importance because the highly informative and useful simple tandem repeat polymorphism (STRP) markers appear to have a high mutation rate which make them disadvantageous for disequilibrium mapping. The regions selected comprised of 20 Mb of the X chromosome between Xq25 and Xq28. These regions contain numerous disease gene loci, including several that are of local interest. The addition of some 200 genetic markers in these regions will aid numerous investigators here and abroad in their search for their genes of interest. Once developed, the allele frequencies of these markers will be determined and they will be used to genotype approximately 100 males in each of three populations, including those of the CEPH pedigree, an isolated population in Finland, and a similarly isolated population in Sardinia. The haplotypes of these individuals will be analyzed to study linkage disequilibrium in terms of population history and chromosomal location. If successful, the approaches developed in this proposal will be applicable to any region of the human genome. Furthermore, the linkage disequilibrium data obtained will shed light on several important questions in population genetics and guide disease gene mapping efforts based on population or disequilibrium studies.