A recurrent de novo missense mutation in COL1A1 causes osteogenesis imperfecta type II and preterm delivery in Normande cattle.

BACKGROUND: Nine male and eight female calves born to a Normande artificial insemination bull named "Ly" were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality. RESULTS: Using Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes. CONCLUSIONS: In conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.

Cutaneous and systemic granulomatous disease associated with hairy vetch toxicosis in a French Holstein dairy herd.

This report describes an outbreak of hairy vetch toxicosis afflicting a herd of cattle with a fatal cutaneous and systemic granulomatous disease. It highlights how this condition remains poorly recognized by cattle production professionals in Europe and the need for communication about vetch-associated diseases.

Cet article décrit une épidémie de toxicose due à la vesce velue touchant un troupeau de bovins se manifestant par une maladie granulomateuse systémique et cutanée fatale. Ceci illustre comment cette atteinte reste peu connue par les professionnels de l'élevage en Europe et le besoin de communiquer sur les maladies associées à la vesce velue.

Este artículo describe un brote de toxicosis de veza vellosa (Vicia villosa) que afectó a un rebaño de ganado con una enfermedad granulomatosa cutánea y sistémica mortal. Destaca cómo esta condición sigue siendo poco reconocida por los profesionales de la producción ganadera en Europa y la necesidad de comunicación sobre las enfermedades asociadas al consumo de veza.

Este relato descreve um surto de intoxicação por ervilhaca peluda em um rebanho de gado com uma doença granulomatosa cutânea e sistêmica. Destaca-se como essa enfermidade continua pouco reconhecida pelos profissionais de bovinocultura na Europa, e a necessidade de comunicação sobre doenças associadas à ervilhaca.

Surveillance of Extended-Spectrum ß-Lactamase-, Cephalosporinase- and Carbapenemase-Producing Gram-Negative Bacteria in Raw Milk Filters and Healthy Dairy Cattle in Three Farms in Île-de-France, France.

The aim of this work was to test a surveillance protocol able to detect extended-spectrum ß-lactamase (ESBL)-, cephalosporinase (AmpC)- and carbapenemase (CP)-producing gram-negative bacteria in three conveniently chosen dairy farms with known prior occurrences of ESBL- and CP-producing strains. The protocol was applied monthly for a year. At each visit, 10 healthy lactating dairy cows were rectally swabbed, and raw milk filters (RMFs) were sampled in two of the three farms. Bacterial isolation was based on a first screening step with MacConkey agar supplemented with 1 mg/L cefotaxime and commercial carbapenem-supplemented media. We failed to detect CP-producing strains but showed that ESBL-Escherichia strains, found in one farm only (13 strains), were closely associated with multi-drug resistance (12 out of 13). The limited number of conveniently selected farms and the fact that RMFs could not be retrieved from one of them limit the validity of our findings. Still, our results illustrate that ESBL-status changes monthly based on fecal swabs and negative herds should be qualified as "unsuspected" as proposed by previous authors. Although surveillance of farm statuses based on RMF analysis could theoretically allow for a better sensitivity than individual swabs, we failed to illustrate it as both farms where RMFs could be retrieved were constantly negative. Determination of CP herd-level status based on RMFs and our surveillance protocol was hindered by the presence of intrinsically resistant bacteria or strains cumulating multiple non-CP resistance mechanisms which means our protocol is not specific enough for routine monitoring of CP in dairy farms.

Meloxicam administration in the management of postoperative pain and inflammation associated with caesarean section in beef heifers: Evaluation of reproductive parameters.

Post-operative pain and inflammation are normal physiological reactions to caesarean section. Their management in cattle have rarely been investigated. This surgical procedure negatively affects reproductive function with, for example, a reduction in fertility resulting in an increase in calving interval. In this multicenter clinical trial, the objective was to evaluate the impact on reproductive performance of meloxicam injected before caesarean section to manage post-operative pain and inflammation. Meloxicam is a non-steroidal anti-inflammatory drug. One hundred and twenty-seven Charolais heifers (n = 127) were recruited from 47 farms in six French veterinary practices in the Burgundy region. The heifers underwent a non-elective standardized caesarean section operation. Heifers were randomly assigned to one of two groups: meloxicam (n = 66), intravenous meloxicam injection before surgery, or control (n = 61). Reproductive performance and health information were recorded from the time of the caesarean section to the next calving or to culling. In our study, meloxicam administration before caesarean section had no effect on the incidence of retained placenta (18.2% of treated vs 25.0% of control cows, p = 0.35). The pregnancy rate was higher in treated than in control cows (83.1% vs 67.8%, p = 0.04 after multivariate analysis) and a survival analysis showed that the median calving interval was 35 days shorter in the meloxicam (t50% = 417 days) compared to the control group (t50% = 452 days, p = 0.05). A trend was also observed for culling rate to be lower in treated (4.7%) compared to control cows (13.3%, p = 0.09). In conclusion, this study suggests that there is a beneficial effect of meloxicam administration before caesarean section on reproductive performance in Charolais heifers.