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 1.3 x 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).

Three outbreaks of Legionnaires' disease were reported in the Fredrikstad/Sarpsborg community, Norway, in 2005 and 2008 caused by the L. pneumophila ST15 and ST462 strains determined by sequence based typing. In this retrospective study, we suggest that the aeration ponds, a part of the biological treatment plant at Borregaard Ind. Ltd., are the main amplifiers and primary disseminators of the outbreak L. pneumophila strains. This result is supported by the finding that the ST15 and ST462 strains were not able to survive in air scrubber liquid media more than two days of incubation at the scrubber's operating conditions during the 2005 and 2008 outbreaks. In 2008, >10¹⁰ CFU/L of L. pneumophila ST462 were detected in the aeration ponds. ST15 and ST462 were also detected in the river Glomma in 2005 and 2008, respectively, downstream of the wastewater outlet from the treatment plant (10⁵CFU/L). These findings strongly suggest that the presence of L. pneumophila in the river is due to the release of wastewater from the industrial aeration ponds, demonstrating that the river Glomma may be an additional disseminator of L. pneumophila during the outbreaks. This work emphasizes the need for preventive actions against the release of wastewater containing human pathogens to the environment.