Genetic linkage analysis of X-ray hypersensitivity in the LEC mutant rat

The LEC rat has been reported to exhibit X-ray hyper sensitivity and defici ency in DNA double-strand break (DSB) repair. The present study was perform ed to map the locus responsible for this phenotype, the xhs (X-ray hypersen sitivity), as the first step in identifying the responsible gene. Analysis of the progeny of (BN x LEC)F-1 x LEC backcrosses indicated that the X-ray hypersensitive phenotype was controlled by multiple genetic loci in contras t to the results reported previously. Quantitative trait loci (QTL) linkage analysis revealed two responsible loci located on Chromosomes (Chr) 4 and 1. QTL on Chr 4 exhibited very strong linkage to the X-ray hypersensitive p henotype, while QTL on Chr 1 showed weak linkage. The Rad52 locus, mutation of which results in hypersensitivity to ionizing radiation and impairment of DNA DSB repair in yeast, was reported to be located on the synteneic reg ions of mouse Chr 6 and human Chr 12. However, mapping of the rat Rad52 loc us indicated that it was located 23 cM distal to the QTL on Chr 4. Furtherm ore, none of the radiosensitivity-related loci mapped previously in the rat chromosome were identical to the QTL on Chrs 4 and 1 in the LEC rat. Thus, it seems that X-ray hypersensitivity in the LEC rat is caused by mutation( s) in as-yet-undefined genes.