Dr. Lander and colleagues propose to construct key mapping resources needed to take full advantage of the rat as a system for the study of the genetic basis of physiology and disease. Specifically, they will: Construct a rat genetic map consisting of 6,000 simple sequence length polymorphism (SSLPs) genotyped using two F2 intercrosses; Characterize the allele sizes of the SSLPs in 48 important rat strains used in genetic and physiological studies -- thereby identifying the markers that are informative for any particular cross. Genotype about 1,000 SSLPs in (SHR X BN) recombinant inbred (R1) strains. Identify a screening set for initial genome scans, consisting of 400 evenly spaced, highly polymorphic, and extremely robust markers. Ensure rapid distribution of data through electronic databases and servers. Ensure convenient and affordable access to PCR primers for the SSLPs, through a distribution arrangement with Research Genetics, Inc. Anchor the genetic map in the cytogenetic map, by using FISH mapping. Construct a rat genomic library in yeast artificial chromosomes (YACs), providing 7-fold coverage with average insert size of at least 800kb. Construct a rat genomic library in bacterial artificial chromosomes (BACs), providing 7-fold coverage with average insert size of about 130kb. Construct two panels of radiation hybrid (RH) cell lines, a high connectivity panel containing large fragments, and a high resolution panel containing small fragments allowing rapid genomic localization of sequences even when a polymorphism is not available. Genotype the high connectivity RH panel for about 1000 well-spaced loci. Ensure availability of the YAC library, BAC library, and RH panels through a distribution arrangement with Research Genetics, Inc.
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