Journal Article

A mutation in the canine <i>BHD</i> gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog

Frode Lingaas, Kenine E. Comstock, Ewen F. Kirkness, Anita Sørensen, Tone Aarskaug, Christophe Hitte, Michael L. Nickerson, Lars Moe, Laura S. Schmidt, Rachael Thomas, Matthew Breen, Francis Galibert, Berton Zbar and Elaine A. Ostrander

in Human Molecular Genetics

Volume 12, issue 23, pages 3043-3053
Published in print December 2003 | ISSN: 0964-6906
Published online December 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg336
A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog

Show Summary Details

Preview

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 (𝛉=0.016). We have since narrowed the RCND interval following selection and RH mapping of canine genes from the 1.3× 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 US 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).

Journal Article.  6994 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.