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.
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