This application by Stephen N. Thibodeau entitled """"""""Localization of susceptibility loci in prostate cancer"""""""" seeks funding to support a three-part study to identify genes responsible for prostate cancer predisposition. The study proposes a genome-wide search by microsatellite polymorphism in families with three or four members affected by prostate cancer. These families have been ascertained from the Mayo Clinic Registry of Radical Prostatectomy, comprising approximately 5,500 men who were treated with radical prostatectomy since 1967. As a result of initial evaluation of this registry, 60 kindreds with three or more living affected men (200 sib pairs) have been identified so far as potential subjects for this study. Initial screening by full genome analysis using markers separated by approximately 10 centimorgans will be conducted. Data will be analyzed by both conventional parametric linkage analysis and by affected sib pair approaches. Regions of the genome harboring known or suspected candidate genes for familial prostate cancer or those regions showing elevated LOH in prostate tumor progression (as determined in preliminary studies by the applicant and by other published studies) will be targeted first. Regions identified as potential candidates will be evaluated more closely by refined linkage mapping using additional markers from the region, by physical mapping, and by positional cloning within the regions of interest. Candidate genes within these regions will ultimately be evaluated using conventional approaches for candidate gene analysis.
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