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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.

Simultaneous canine mammary tumours (CMTs) are frequently reported in the literature, but few studies have addressed their biological relationship in detail or performed statistical assessments. In this study, 269 canine mammary gland tumours from 216 dogs were categorized using an extended histopathological classification, where semiquantitative and binomial scales enumerated morphological parameters of the tumours. The classification facilitated a statistical study of the biological relationship between simultaneous within-dog tumours. Seventy-seven percent of the dogs had single tumours and 23% had simultaneous tumours. Sixty-one percent of the neoplasias were benign, with complex adenoma as the most frequent diagnosis and 39% were malignant, with complex carcinoma as the most common malignancy. Simultaneous tumours within dogs more often had equal diagnoses and neoplastic level (benign or malignant) than would be expected by chance alone, as compared with random pairs of single tumours from different dogs. This statistically supported finding indicated the presence of a biological relationship between simultaneous tumours., (© 2015 John Wiley & Sons Ltd.)

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.

Background: Copy number aberrations frequently occur during the development of many cancers. Such events affect dosage of involved genes and may cause further genomic instability and progression of cancer. In this survey, canine SNP microarrays were used to study 117 canine mammary tumours from 69 dogs., Results: We found a high occurrence of copy number aberrations in canine mammary tumours, losses being more frequent than gains. Increased frequency of aberrations and loss of heterozygosity were positively correlated with increased malignancy in terms of histopathological diagnosis. One of the most highly recurrently amplified regions harbored the MYC gene. PTEN was located to a frequently lost region and also homozygously deleted in five tumours. Thus, deregulation of these genes due to copy number aberrations appears to be an important event in canine mammary tumour development. Other potential contributors to canine mammary tumour pathogenesis are COL9A3, INPP5A, CYP2E1 and RB1. The present study also shows that a more detailed analysis of chromosomal aberrations associated with histopathological parameters may aid in identifying specific genes associated with canine mammary tumour progression., Conclusions: The high frequency of copy number aberrations is a prominent feature of canine mammary tumours as seen in other canine and human cancers. Our findings share several features with corresponding studies in human breast tumours and strengthen the dog as a suitable model organism for this disease.

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.

Canine perinatal mortality is known to be relatively high. However, the literature on perinatal mortality in dogs is still sparse and often refers to a single or only a few breeds. The aim of this large-scale observational study was to describe the perinatal mortality in purebred dogs of various breeds at both puppy and litter level. In addition, the influence of breed, breed size, litter size, age of the bitch, litter number and season for whelping on the risk of perinatal mortality at litter level was studied and the mean litter size at eight days and eight wks after birth was calculated. A retrospective cohort study was performed by studying 10,810 litters of 224 breeds registered in the Norwegian Kennel Club in 2006 and 2007. Perinatal mortality was defined as the sum of stillborn puppies and puppies that died during the first wk after birth (early neonatal mortality) and was present in 24.6% of the litters. Eight percent of the puppies died before eight days after birth, with 4.3% as stillbirth and 3.7% as early neonatal mortality. For most breeds the perinatal mortality was low, but for some breeds a higher perinatal mortality was found. The mean litter size at eight days and eight wks after birth was 4.97 (±0.02) and 4.92 (±0.02) puppies, respectively. Of all puppies born, only 1% died during the period from eight days to eight wks after birth. Random effects logistic regression analysis indicated that increasing litter size and age of the bitch were associated with an increased risk of stillbirth, early neonatal mortality and total perinatal mortality at the litter level (P < 0.001). The random breed effect was significant for all outcomes. Litter number also had a significant effect on stillbirth, early neonatal mortality and total perinatal mortality at the litter level, with the highest risk of perinatal mortality found in the first litter (P < 0.001). Further, the risk of early neonatal mortality was doubled in litters with stillborn puppies. No significant effect of whelping season on perinatal mortality at litter level was found. An interaction existed between the age of the bitch and litter number and the risk of stillbirth was three times as high (odds ratio = 3.00) in litters from bitches having their first litter after the age of six y. Breed was a more important determinant of perinatal mortality in litters than breed size. However, more than 90% of the variation in perinatal mortality was found at the individual litter level and efforts to minimize puppy mortality should be targeted at the management of the individual litter rather than at the breed level., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The incidence of canine mammary tumours (CMTs) differs significantly between breeds, strongly supporting an influence of genetic risk factors. We aimed at identifying germline genetic variations in mammary tumour-associated genes in dogs and survey whether these might alter the encoded proteins. We sequenced 11 genes (BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EGFR, ESR1, HER2, PTEN, STK11 and TP53) and screened for genetic variations. Sixty-four single nucleotide polymorphisms (SNPs) were identified. Nine of the coding SNPs were non-synonymous, of which four were located in gene regions conserved across four species. Three of the non-synonymous SNPs might be damaging according to PolyPhen predictions. One of the indels identified has previously been associated with CMTs. Because of the founder effects, genetic drift and inbreeding in many dog breeds the allele frequencies of the genes studied are likely to vary significantly between breeds and contribute to the considerable difference in genetic risk associated with cancer., (© 2011 Blackwell Publishing Ltd.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)