The goal of this program project is to produce detailed physical and genetic maps of polymorphic markers for human chromosomes 2 and 3. The current maps of chromosomes 2 and 3 only have a limited number of markers and there are several large gaps on both the physical and genetic maps. The physical map generated by the program project will be based on radiation reduction hybrids and the genetic map a result of analyzing CEPH family DNA. The genetic markers generated will all be PCR based and consist of highly polymorphic markers such as found with simple di-, tri-, and tetranucleotide repeats and in the poly A tract of L1 sequences as well as transcribed sequences specific for these chromosomes. In addition the program will devise a method for globally mapping each chromosome with Line elements and correlating this map to the genetic and radiation hybrid map. To accomplish these goals, the program consists of 4 projects and a core for linkage studies as well as an administrative core. These highly interdependent projects will result in the placement of 600 highly useful markers on chromosomes 2 and 3 over the grant period. The markers are termed highly useful since they will be highly polymorphic, be based on PCR and available to all investigators, and be mapped on both physical and genetic maps. The physical map generated will be complete at the 2 cM level and in many regions 1 cM distances will be achieved. The physical map of each chromosome will have approximately 1 marker per megabase. This framework panel of markers and cell reagents will be used to direct the isolation of ordered clones for chromosomes 2 and 3 and will be especially useful for closure on these chromosomes. The polymorphic markers will be immediately applicable for identifying markers adjacent to disease loci.
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