Human Molecular Genetics Advance Access published online on October 7, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg336
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Norwegian School of Veterinary Science, P.O. Box 8146 N-0033 Oslo, Norway
* To whom correspondence should be addressed. E-mail: eostrand{at}fhcrc.org.
Hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) is a naturally occurring canine kidney cancer syndrome that was originally described in German Shepherd dogs. The disease is characterized by bilateral, multifocal tumors in the kidneys, uterine leiomyomas and nodules in the skin consisting of dense collagen fibers. We previously mapped RCND to canine chromosome 5 (CFA5) with a highly significant Lod score of 16.7 (theta = 0.016). We have since narrowed the RCND interval following selection and RH mapping of canine genes from the 1.3x canine genome sequence. These sequences also allowed for the isolation of gene-associated BACs and the characterization of new microsatellite markers. Ordering of newly defined markers and genes with regard to recombinants localizes RCND to a small chromosomal region that overlaps the human Birt-Hogg-Dubé locus, suggesting the same gene may be responsible for both the dog and the phenotypically-similar human disease. We herein describe a disease-associated mutation in exon 7 of canine BHD that leads to the mutation of a highly conserved amino acid of the encoded protein. The absence of recombinants between the disease locus and the mutation in U.S. and Norwegian dogs separated by several generations is consistent with this mutation being the disease-causing mutation. Strong evidence is provided that the RCND mutation may have a homozygous lethal effect (P < 0.01).
Article
A Mutation in the Canine BHD Gene is Associated with Hereditary Multifocal Renal Cystadenocarcinoma and Nodular Dermatofibrosis in the German Shepherd Dog
2 Clinical and Human Biology Divisions, Fred Hutchinson Cancer Research Center, P.O. Box 19024, D4-100, Seattle, WA 98109-1024 USA
3 The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850 USA
4 UMR 6061 CNRS, Génétique et Développement, Faculté de Médecine, 35043 Rennes Cédex, France
5 Laboratory of Immunobiology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702 USA
6 Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute Frederick, Frederick, MD, 21702 USA
7 Oncology Research, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU United Kingdom
8 Dept. of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606 USA
9 Clinical and Human Biology Divisions, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D4-100, P.O. Box 19024, Seattle, WA 98109-1024, USA
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Kim, D. Turner, J. Nelson, I. Dobrinski, M. McEntee, and A. J Travis Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog Reproduction, December 1, 2008; 136(6): 823 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Gardiner and T. R. Spraker Generalized Nodular Dermatofibrosis in the Absence of Renal Neoplasia in an Australian Cattle Dog Vet. Pathol., November 1, 2008; 45(6): 901 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Woodward, C. Ricketts, P. Killick, S. Gad, M.R. Morris, F. Kavalier, S. V. Hodgson, S. Giraud, B. Bressac-de Paillerets, C. Chapman, et al. Familial Non-VHL Clear Cell (Conventional) Renal Cell Carcinoma: Clinical Features, Segregation Analysis, and Mutation Analysis of FLCN Clin. Cancer Res., September 15, 2008; 14(18): 5925 - 5930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J R Toro, M-H Wei, G M Glenn, M Weinreich, O Toure, C Vocke, M Turner, P Choyke, M J Merino, P A Pinto, et al. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports J. Med. Genet., June 1, 2008; 45(6): 321 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baba, M. Furihata, S.-B. Hong, L. Tessarollo, D. C. Haines, E. Southon, V. Patel, P. Igarashi, W. G. Alvord, R. Leighty, et al. Kidney-Targeted Birt-Hogg-Dube Gene Inactivation in a Mouse Model: Erk1/2 and Akt-mTOR Activation, Cell Hyperproliferation, and Polycystic Kidneys J Natl Cancer Inst, January 16, 2008; 100(2): 140 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cadieu and E. A. Ostrander Canine Genetics Offers New Mechanisms for the Study of Human Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2181 - 2183. [Full Text] [PDF]
|
|
|
|
 |
|
 M. van Slegtenhorst, D. Khabibullin, T. R. Hartman, E. Nicolas, W. D. Kruger, and E. P. Henske The Birt-Hogg-Dube and Tuberous Sclerosis Complex Homologs Have Opposing Roles in Amino Acid Homeostasis in Schizosaccharomyces pombe J. Biol. Chem., August 24, 2007; 282(34): 24583 - 24590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Toro, S. E. Pautler, L. Stewart, G. M. Glenn, M. Weinreich, O. Toure, M.-H. Wei, L. S. Schmidt, L. Davis, B. Zbar, et al. Lung Cysts, Spontaneous Pneumothorax, and Genetic Associations in 89 Families with Birt-Hogg-Dube Syndrome Am. J. Respir. Crit. Care Med., May 15, 2007; 175(10): 1044 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. McCaw, A. S. Chan, A. L. Stegner, B. Mooney, J. N. Bryan, S. E. Turnquist, C. J. Henry, H. Alexander, and S. Alexander Proteomics of Canine Lymphoma Identifies Potential Cancer-Specific Protein Markers Clin. Cancer Res., April 15, 2007; 13(8): 2496 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Kukekova, J. Nelson, R. W. Kuchtey, J. K. Lowe, J. L. Johnson, E. A. Ostrander, G. D. Aguirre, and G. M. Acland Linkage Mapping of Canine Rod Cone Dysplasia Type 2 (rcd2) to CFA7, the Canine Orthologue of Human 1q32. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 1210 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. M. Thomson, E. Kennerly, N. Olby, J. R. Mickelson, D. E. Hoffmann, P. J. Dickinson, G. Gibson, and M. Breen Microarray Analysis of Differentially Expressed Genes of Primary Tumors in the Canine Central Nervous System Vet. Pathol., September 1, 2005; 42(5): 550 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Aguirre-Hernandez and D. R. Sargan Evaluation of Candidate Genes in the Absence of Positional Information: A Poor Bet on a Blind Dog! J. Hered., September 1, 2005; 96(5): 475 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Graham, M. Nolasco, B. Peterlin, and C. K. Garcia Nonsense Mutations in Folliculin Presenting as Isolated Familial Spontaneous Pneumothorax in Adults Am. J. Respir. Crit. Care Med., July 1, 2005; 172(1): 39 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Richard, R. Lidereau, S. Giraud, and on behalf of the French inherited kidney tumours c The growing family of hereditary renal cell carcinoma Nephrol. Dial. Transplant., December 1, 2004; 19(12): 2954 - 2958. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Okimoto, J. Sakurai, T. Kobayashi, H. Mitani, Y. Hirayama, M. L. Nickerson, M. B. Warren, B. Zbar, L. S. Schmidt, and O. Hino A germ-line insertion in the Birt-Hogg-Dube (BHD) gene gives rise to the Nihon rat model of inherited renal cancer PNAS, February 17, 2004; 101(7): 2023 - 2027. [Abstract] [Full Text] [PDF]
|
|