Identification of a Locus for Susceptibility to Renal Cell Carcinoma in the Long-Evans Cinnamon Rat

Abstract

The Long-Evans Cinnamon (LEC) mutant rat shows higher incidence of renal cell carcinomas induced by a treatment with the chemical carcinogen N-diethylnitrosamine, as compared to the normal control rat. We performed the first genome-wide scan for genes responsible for susceptibility to chemically induced renal cell carcinoma in an F₂ intercross obtained by mating the LEC and Fischer-344 (F344) rats. The genotype of 71 (F344 × LEC) F₂ progenies was determined with the use of 338 simple sequence length polymorphisms (SSLPs) spread over the genome. The F₂ rats which carried renal cell carcinoma were shown to possess the incidence of homozygosity of the LEC allele which is higher than that of the other genotypes at SSLP markers on chromosome 5 (χ² = 17.5 for D5Rat21). Our linkage analysis has led to the revelation of a novel gene that influences susceptibility to renal cell carcinoma on rat chromosome 5.