LINKAGE MAPPING HUMAN TELOMERES AND CENTROMERES

本研究的目的是：（1）确定 来自个体端粒附近DNA的多态性位点 人类染色体，并将其用于连锁研究， 关闭遗传图谱，2）确定并放置在 为单个人类着丝粒绘制多态性基因座的连锁图， 为遗传学和遗传学提供有用的染色体参考点， 物理映射 人类端粒特异性和着丝粒特异性酵母人工 染色体（YAC）克隆以及用于着丝粒的其他探针 并且候选端粒邻近序列将被提供为 合作者的起始材料。 染色体定位 端粒和着丝粒探针将通过4 与端粒特异性和着丝粒特异性杂交 序列，并通过遗传连锁分析。 我们计划从着丝粒和端粒构建文库 YAC克隆，筛选它们的多态性探针， 对40个CEPH参考家系进行基因分型，并整合 利用连锁分析程序将标记插入我们的遗传图谱 CRI-MAP包。 此外，我们还将对现有的 着丝粒特异性探针和现有的端粒邻近探针 并利用着丝粒基因型数据 由我们的合作者提供，使我们能够将这些 将先前识别的RFLP插入图谱中。 对于任何端粒RFLP 它不与基因图谱（一个由所有其他人 标准应跨越染色体），YAC步行实验 将努力将物理端连接起来， 染色体和基因图谱 这项拟议中的研究直到最近才变得可行， 将定义基因图谱的边界， 物理和基因图谱。 我们还将开发高效的 数据管理系统，用于跟踪内部资源和数据 我们的实验室，用于与其他实验室的通信，以及 为现有的国家资源提供大型数据集， 数据库。

The goals of this research proposal are 1) to identify polymorphic loci from DNA adjacent to telomeres of individual human chromosomes, and to use them in linkage studies to attempt closure of the genetic maps, and 2) to identify and place on the linkage maps polymorphic loci for individual human centromeres, providing useful chromosome reference points for both genetic and physical mapping. Human telomere-specific and centromere-specific Yeast Artificial Chromosome (YAC) clones as well as other probes for centromeres and candidate telomere adjacent sequences will be provided as starting materials by collaborators. Chromosomal localization of the telomere and centromere probes will be determined by 4 hybridization to telomere-specific and centromere-specific sequences, and by genetic linkage analysis. We plan to construct libraries from the centromere and telomere YAC clones, screen them for probes that reveal polymorphism, genotype the 40 CEPH reference pedigrees, and integrate the markers into our genetic maps using the linkage analysis program package CRI-MAP. In addition, we will genotype existing centromere-specific probes and existing telomere adjacent probes on reference pedigrees and make use of centromeric genotypic data provided by our collaborators, enabling us to incorporate these previously identified RFLPs into the maps. For any telomere RFLP that does not link to the genetic map (a map that by all other criteria should span the chromosome), YAC walking experiments will be conducted in an effort to link the physical end of chromosome with the genetic map. The proposed research, which has only recently become feasible, will define the boundaries of genetic maps and facilitate merging of physical and genetic maps. We will also develop efficient data management systems for tracking of resources and data within our laboratory, for communication with other laboratories, and for contributing large data sets to established national resource databases.