Genome-Wide Analysis Identifies Germ-Line Risk Factors Associated with Canine Mammary Tumours.

Canine mammary tumours (CMT) are the most common neoplasia in unspayed female dogs. CMTs are suitable naturally occurring models for human breast cancer and share many characteristics, indicating that the genetic causes could also be shared. We have performed a genome-wide association study (GWAS) in English Springer Spaniel dogs and identified a genome-wide significant locus on chromosome 11 (praw = 5.6x10-7, pperm = 0.019). The most associated haplotype spans a 446 kb region overlapping the CDK5RAP2 gene. The CDK5RAP2 protein has a function in cell cycle regulation and could potentially have an impact on response to chemotherapy treatment. Two additional loci, both on chromosome 27, were nominally associated (praw = 1.97x10-5 and praw = 8.30x10-6). The three loci explain 28.1±10.0% of the phenotypic variation seen in the cohort, whereas the top ten associated regions account for 38.2±10.8% of the risk. Furthermore, the ten GWAS loci and regions with reduced genetic variability are significantly enriched for snoRNAs and tumour-associated antigen genes, suggesting a role for these genes in CMT development. We have identified several candidate genes associated with canine mammary tumours, including CDK5RAP2. Our findings enable further comparative studies to investigate the genes and pathways in human breast cancer patients.

Large outbreak of mumps virus genotype G among vaccinated students in Norway, 2015 to 2016.

From 6 September 2015-May 2016, a large mumps outbreak occurred among vaccinated students in Norway. A case was defined as a person presenting with a clinical mumps infection, notified between 1 September 2015 and 30 June 2016. Confirmed cases had positive laboratory confirmation and probable cases had an epidemiological link; PCR-positive specimens were genotyped. A total of 232 cases were notified (230 confirmed) with median age of 23 years (range 4-81) and 61% were male. Of 68 (30%) confirmed cases that were genotyped, 66 were genotype G and associated with the outbreak. Cases that had received two doses of the measles-mumps-rubella (MMR) vaccine had reduced risk of hospitalisation (adjusted relative risk (aRR): 0.14; 95%CI: 0.03-0.57), mumps-related orchitis (aRR: 0.21; 95% CI: 0.08-0.55) and severe outcome (aRR: 0.25; 95% CI: 0.10-0.62) compared with those unvaccinated. A third dose of the vaccine was offered to approximately 1,300 fully vaccinated close contacts and subsequently reported cases decreased. This large outbreak, occurring among predominately vaccinated students, suggests the current genotype A vaccine offers suboptimal protection against mumps genotype G. We recommend maintaining high vaccination coverage and offering the vaccine to all unvaccinated individuals.

The ESR1 gene is associated with risk for canine mammary tumours.

BACKGROUND: The limited within-breed genetic heterogeneity and an enrichment of disease-predisposing alleles have made the dog a very suitable model for the identification of genes associated with risk for specific diseases. Canine mammary cancer is an example of such a disease. However, the underlying inherited risk factors for canine mammary tumours (CMTs) are still largely unknown. In this study, 52 single nucleotide polymorphisms (SNPs) in ten human cancer-associated genes were genotyped in two different datasets in order to identify genes/alleles associated with the development of CMTs. The first dataset consisted of English Springer Spaniel (ESS) CMT cases and controls. ESS is a dog breed known to be at increased risk of developing CMTs. In the second dataset, dogs from breeds known to have a high frequency of CMTs were compared to dogs from breeds with a lower occurrence of these tumours. RESULTS: We found significant associations to CMT for SNPs and haplotypes in the estrogen receptor 1 (ESR1) gene in the ESS material (best PBonf = 0.021). A large number of SNPs, among them several SNPs in ESR1, showed significantly different allele frequencies between the high and low risk breed groups (best PBonf = 8.8E-32, best PBPerm = 0.076). CONCLUSIONS: The identification of CMT-associated SNPs in ESR1 in two independent datasets suggests that this gene might be involved in CMT development. These findings also support that CMT may serve as a good model for human breast cancer research.

Litter size at birth in purebred dogs--a retrospective study of 224 breeds.

Despite the long history of purebred dogs and the large number of existing breeds, few studies of canine litter size based upon a large number of breeds exist. Previous studies are either old or include only one or a few selected breeds. The aim of this large-scale retrospective study was to estimate the mean litter size in a large population of purebred dogs and to describe some factors that might influence the litter size. A total of 10,810 litters of 224 breeds registered in the Norwegian Kennel Club from 2006 to 2007 were included in the study. The overall mean litter size at birth was 5.4 (± 0.025). A generalized linear mixed model with a random intercept for breed revealed that the litter size was significantly influenced by the size of the breed, the method of mating and the age of the bitch. A significant interaction between breed size and age was detected, in that the expected number of puppies born decreased more for older bitches of large breeds. Mean litter size increased with breed size, from 3.5 (± 0.04) puppies in miniature breeds to 7.1 (± 0.13) puppies in giant breeds. No effect on litter size was found for the season of birth or the parity of the bitch. The large number of breeds and the detail of the registered information on the litters in this study are unique. In conclusion, the size of the breed, the age of the bitch and the method of mating were found to influence litter size in purebred dogs when controlling for breed, with the size of the breed as the strongest determinant.