Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs

Canine hereditary multifocal renal cystadenocarcinoma and nodular dermatofi brosis (RCND) is a rare, naturally occurring inherited cancer syndrome obse rved in dogs. Genetic linkage analysis of an RCND-informative pedigree has identified a linkage group flanking RCND (CHP14-C05.377-C05.414-FH2383-C05. 771-[RCND-CPH18]-C02608-GLUT4-TP53-ZuBeCa6-AHT141-FH2140-FH2594) thus local izing the disease to a small region of canine chromosome 5. The closest mar ker, C02608, is linked to RCND with a recombination fraction (0) of 0.016, supported by a logarithm of odds score of 16.7. C02608 and the adjacent lin ked markers map to a region of the canine genome corresponding to portions of human chromosomes Ip and 17p. A combination of linkage analysis and dire ct sequencing eliminate several likely candidate genes, including tuberous sclerosis 1 and 2 genes (TSC1 and TSC2) and the tumor suppressor gene TP53. These data suggest that RCND may be caused by a previously unidentified tu mor suppressor gene and highlight the potential for canine genetics in the study of human disease predisposition.