Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs.
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 flanking RCND (CHP14-C05.377-C05.414-FH2383-C05. 771-[RCND-CPH18]-C02608-GLUT4-TP53-ZuBe Ca6-AHT141-FH2140-FH2594) thus localizing the disease to a small region of canine chromosome 5. The closest marker, C02608, is linked to RCND with a recombination fraction (theta) 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 (TSC1 and TSC2) and the tumor suppressor gene TP53. 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.
Jónasdóttir
T J
TJ
Norwegian School of Veterinary Science, Department of Morphology, Genetics, and Aquatic Biology, Section of Genetics, Oslo. tora.jonasdottir@veths.no
Mellersh
C S
CS
Moe
L
L
Heggebø
R
R
Gamlem
H
H
Ostrander
E A
EA
Lingaas
F
F
D000818:Animals; D003536:Cystadenocarcinoma / Q000235:genetics / Q000662:veterinary*; D004285:Dogs; D005260:Female; D016158:Genes, p53; D008040:Genetic Linkage; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000662:veterinary*; D008297:Male; D010375:Pedigree; D011506:Proteins / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins
D011506:Proteins; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins