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

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Abstract
Canine hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) is a rare, naturally occurring inherited cancer syndrome observed in dogs. Genetic linkage analysis of an RCND-informative pedigree has identified a linkage group flankingRCND(CHP14-C05.377-C05.414-FH2383-C05.771-[RCND-CPH18]-C02608-GLUT4-TP53-ZuBeCa6-AHT141-FH2140-FH2594) thus localizing the disease to a small region of canine chromosome 5. The closest marker, C02608, is linked toRCNDwith a recombination fraction (θ) of 0.016, supported by a logarithm of odds score of 16.7. C02608 and the adjacent linked markers map to a region of the canine genome corresponding to portions of human chromosomes 1p and 17p. A combination of linkage analysis and direct sequencing eliminate several likely candidate genes, including tuberous sclerosis 1 and 2 genes (TSC1andTSC2) and the tumor suppressor geneTP53.These data suggest that RCND may be caused by a previously unidentified tumor suppressor gene and highlight the potential for canine genetics in the study of human disease predisposition.