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Genetic Mapping
and Analysis
of a
Canine Hereditary
Renal Cancer Syndrome
Frode Lingaas*, Kenine E. Comstock*b, Ewen F. Kirknessc, Anita Sorensena, Tone Aarskauga,
Christophe Hittef, Michael L. Nickersond, Lars Moea, Laura S. Schmidtg, Rachael
Thomash, Matthew Breene, Francis Galibertf, Berton Zbard and Elaine A. Ostrander
aNorwegian School of Veterinary Science, P.O. Box 8146 N-0033 Oslo,
Norway; bClinical and Human Biology Divisions, Fred Hutchinson Cancer Research Center, P.O. Box 190224, D4-100,
Seattle, WA 98109-1024 USA; cThe Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850
USA; dLaboratory of Immunobiology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702 USA;
eDept. of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh,
NC 27606 USA; fUMR 6061 CNRS, Genetique et Developpement, Faculte de Medecine, 35043 Rennes Cedex, France; gBasic
Research Program, SAIC-Frederick, Inc., National Cancer Institute Frederick, Frederick, MD, 21702 USA; hOncology
Research, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU United Kingdom
We
have proposed previously that mapping cancer susceptibility genes in the domestic dog can circumvent many of the difficulties
associated with mapping human cancer susceptibility genes. To this end we describe
our progress toward the localization of a gene for a rare canine kidney cancer syndrome termed Herditary Multifocal Renal
Cystadenocarcinoma and Nodular Dermatofibrosis (RCND). RCND is a rare, naturally
occurring syndrome characterized by bilateral, multifocal tumors in kidneys and numerous firm nodules in the skin consisting
of dense collagen fibers, that was originally described in German Shepherds. We
previously mapped RCND to canine chromosome 5 (CFA5) with a highly significant Lod score of 16.7 (theta=0.016). We have now narrowed the RCND interval, following selection and RH mapping of canine genes from the 1x
canine genome sequence, to a small portion of CFA5 that corresponds to human chromosome 17p11.2. Using comparative genomics, we evaluated potential candidate genes in the region and undertaken mutation
screening in those considered most likely. This work underscores the emerging
power of canine genomics to aid in the pursuit of genes causing mammalian disease. Towards
that end, we present data on a likely candidate gene.
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