HIGH RESOLUTION GENETIC MAPPING: STRATEGY-BASED APPROACH

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The overall objective of this study is to develop a resource for high resolution mapping, initially for markers on chromosomes 17 and X; and subsequently, for other chromosomes. The resource will be developed by identifying meiotic fragments that are defined by crossovers in 60 CEPH families. The meiotic mapping panel will greatly improve the efficiency and reliability of genetic mapping. The potential resolution of the CEPH resource is about 0.01 cM for autosomes and 0.02 cM for chromosome X. In order to develop the mapping panel resource most efficiently, it will be necessary to modify and extend existing computer programs that are currently used for haplotyping and quality control of CEPH marker data. The current density of markers for chromosomes 17 and X is sufficient to identify nearly all crossovers unambiguously using these simple algorithms. The position of each crossover will be validated by duplicate typing of the nearest flanking markers. Additional meioses will be screened for recombinants between tightly linked loci that cannot be ordered by other means. Selective typing of additional markers will be done in a directed effort to close the gap surrounding each crossover. This strategy will improve resolution and, at the same time, refine the localization of the new marker. Computer algorithms for translating genetic data into a physical mapping representation will be developed as a simple means of combining and comparing the results of genetic and physical mapping studies.