CONSTRUCTION OF A FRAMEWORK MAP OF CHROMOSOME 18

提出了一种构建染色体遗传连锁图谱的策略 18.地图将由高度多态的索引标记组成 (杂合度&GT；0.7)间隔不超过10-15厘米且跨越 染色体的全部估计遗传长度。连锁图 将由我们实验室开发的新标记物组成，包括 索引和常规(het&lt；0.7)标记，以及其他标记 由科学界报道。我们估计另有35人 索引标记是完成该项目所必需的。一种策略是 提出分离和鉴定这些标记并确定 它们相对于现有18号染色体标记的图谱位置和顺序。 所有新标记都将以STS格式进行表征。穿过 协作、新标记和现有标记将使用以下工具进行物理映射 减少辐射的细胞杂交体、体细胞标测面板、脉冲场凝胶 电泳图，并指定为YAC重叠群。战略以实现 也不分青红皂白地在整个染色体上丰富索引标记 作为识别离散基因座或染色体亚群标记的策略 对区域进行了描述。作为开发索引的次要优先事项 标记，我们将分离、鉴定和遗传图谱较少 信息性标记并开始构建高分辨率 连锁图。将制定标准以优化最终效用 框架图的。标记物之间的最佳关系 我们将探索杂合度和间隔间距，我们将评估 完成遗传图谱的标准。我们将继续 调查常见错误对遗传的影响 链接图，对这些错误的更正将被合并到 18号染色体连锁数据分析。18号染色体资源和 作为拟议研究的一部分而产生的信息将 可立即提供给研究界。

A strategy is presented to develop a genetic linkage map of chromosome 18. The map will consist of highly polymorphic index markers (heterozygosity > 0.7) spaced not more than 10-15 cM apart and spanning the full estimated genetic length of the chromosome. The linkage map will be composed of new markers developed in our laboratory, including both index and conventional (het < 0.7) markers, and other markers reported by the scientific community. we estimate that an additional 35 index markers are required to complete the project. A strategy is presented to isolate and characterize these markers and to determine their map location and order relative to existing chromosome 18 markers. All new markers will be characterized in the STS format. Through collaboration, new and existing markers will be physically mapped using radiation-reduced cell hybrids, somatic mapping panels, pulse-field gel electrophoresis mapping, and assignment to YAC contigs. Strategies to enrich for index markers indiscriminately across the chromosome as well as strategies to identify markers at discrete loci or chromosomal sub- regions are described. As a priority secondary to development of index markers, we will isolate, characterize, and genetically map less informative markers and begin the construction of a high resolution linkage map. Criteria will be developed to optimize the ultimate utility of the framework map. The optimal relationship between marker heterozygosity and interval spacing will be explored and we will assess the criteria for completion of the genetic map. we will continue to investigate the effects of commonly occurring errors on the genetic linkage map, and corrections for these errors will be incorporated into analysis of the chromosome 18 linkage data. Chromosome 18 resources and information generated as a part of the proposed research will be made immediately available to the research community.