Genetic defects that occur naturally in livestock species provide valuable models for investigating the molecular mechanisms underlying rare human diseases. Livestock breeds are subject to the regular emergence of recessive genetic defects due to genetic drift and recent inbreeding. At the same time, their large population sizes provide easy access to case and control individuals and to massive amounts of pedigree, genomic and phenotypic information recorded for management and selection purposes. In this study, we investigated a lethal form of recessive chondrodysplasia observed in 21 stillborn calves of the Aubrac beef cattle breed. Detailed examinations of three affected calves revealed proximal limb shortening, epiphyseal calcific deposits, and other pathological signs consistent with human rhizomelic chondrodysplasia punctata, a rare peroxisomal disorder caused by recessive variants in one of five genes (AGPS, FAR1, GNPAT, PEX5, and PEX7). Using homozygosity mapping, whole genome sequencing of two affected individuals, and filtering for variants found in 1867 control genomes, we reduced the list of candidate variants to a single deep intronic substitution in GNPAT (NC_037355.1:g.4039268G > A on chromosome 28 of the ARS-UCD1.2 bovine genome assembly). For verification, we performed large-scale genotyping of this variant using a custom SNP array and found a perfect genotype–phenotype correlation in 21 cases and 26 of their parents, and a complete absence of homozygotes in 1195 unaffected Aubrac controls. The g.4039268A allele segregated at a frequency of 2.6

To support farmers in their decisions related to Q fever, a dedicated economic assessment tool is developed. The present work describes the calculator, its economic rationale, and the supporting assumptions. The calculator integrates a yearly compartmental model to represent population dynamism and the main interactions between disorders linked to Q fever, especially reproductive disorders (abortion, retained foetal membranes, purulent vaginal discharge and endometritis, extra services, and calving–conception delays). The effects of the nontangible cost of the disease on human health, the welfare of the animals, and the workload of farmers were not integrated into the model. The model shows high-level sensitivity to the prevalence of Q fever in the herd prevaccination and to the costs of abortion and extra days of calving–conception intervals. Breakeven points, i.e., cost values that allow us to achieve positive vaccination benefits, are also reported. For herds with moderate or high prevalence rates of Q fever prevaccination (>30%), a vaccination benefit is observed. The vaccine should be considered a type of insurance in herds with low prevalence rates of Q fever prevaccination (≤20%). The calculator was developed to aid decision-making at the farm level, and no conclusion can be extrapolated as a generic trend based on the present work.

The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasizes the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analyzing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include: studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers’ willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organization of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

BACKGROUND:Dairy cattle breeds are populations of limited effective size, subject to recurrent outbreaks of recessive defects that are commonly studied using positional cloning. However, this strategy, based on the observation of animals with characteristic features, may overlook a number of conditions, such as immune or metabolic genetic disorders, which may be confused with pathologies of environmental etiology. RESULTS:We present a data mining framework specifically designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. CONCLUSIONS:The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

Coxiellosis or Q fever is an infectious zoonotic disease caused by the bacterium Coxiella burnetii. A systematic review using bibliographic research was carried out, and the focus was the relationship between C. burnetii infection and reproductive disorders in cattle [abortion/stillbirth/perinatal morality/weak calves (ASPW complex); retained foetal membranes (RFMs); metritis/endometritis; and infertility/sub-fertility]. The bibliographical search yielded 443 results from databases, but only 61 were deemed eligible. For each disorder, summary tables were prepared, and a scientific evidence score was calculated for each study based on four criteria to help assess the level of evidence for the impact of C. burnetii on the reproductive disorders assessed: type of publication (peer-reviewed or other); type of study (case–control/cohort or other); type of C. burnetii test (direct or indirect); and comparative statistical analysis (yes or no). In addition, summary tables also included information on the study population, country, authors and year of publication, key findings and an assessment of the evidence for an association. For the ASPW complex, RFMs, metritis/endometritis and infertility/sub-fertility, 43, 9, 8 and 19 studies provided data, respectively. On a scale of four, nearly 50% of all study citations had evidence scores of three or four. For ASPW, RFMs and infertility/sub-fertility, there is a significant body of evidence to support a deleterious role for Q fever. In contrast, for metritis/endometritis, the evidence is unclear. It is concluded that there is a substantial need for further research, particularly involving larger animal populations in more controlled settings. To provide more consistency, it is recommended that authors follow more precise definitions of reproductive parameters and more robust diagnostic methodologies.

This paper presents the work and research to be conducted to place health and welfare at the heart of the agroecological transition of livestock systems. It highlights the need to consider health in a broader perspective than today and the question of positive emotional experiences in terms of welfare. The positive interactions between health and welfare as well as the possible tensions between these two dimensions are discussed. The joint improvement of animal health and welfare raises questions at different scales. At the animal level, the trade-offs between the physiological functions of production, reproduction and immunity, the role of the microbiota as well as the psycho-neuro-endocrine mechanisms that link mental state and health need to be explored. At the farm level, it would be appropriate to consider the expertise of breeders and to assess the effect of changes in practices on their well-being at work. On production chain and territory levels strategies to improve animal health and welfare while preserving economic viability are to be studied, such as the possibility of labeling, consumers' willingness to pay, the consequences of the phenotypic heterogeneity of animals for the processing of products and the spatial distribution of farms. On the citizens level, a challenge is to better link their concerns regarding animal welfare and health. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

Cet article présente les travaux et les recherches à conduire pour placer la santé et le bien-être au cœur de la transition agroécologique des systèmes d’élevage. Il souligne la nécessité de considérer la santé dans une perspective plus large qu’aujourd’hui et la question des expériences émotionnelles positives en matière de bien-être. Les interactions positives entre santé et bien-être mais aussi les tensions possibles entre ces deux dimensions sont discutées. L'amélioration conjointe de la santé et du bien-être des animaux pose des questions à différentes échelles. Au niveau de l'animal, sont à explorer les compromis entre les fonctions physiologiques de production, de reproduction et d'immunité, le rôle du microbiote ainsi que les mécanismes psycho-neuro-endocriniens qui relient l'état mental et la santé. Au niveau de l'exploitation, il conviendrait de considérer l’expertise des éleveurs et d’évaluer l’effet des changements de pratiques sur leur bien-être au travail. Au niveau de la filière de production comme du territoire, les stratégies pour améliorer la santé et le bien-être des animaux tout en préservant la viabilité économique sont à étudier, comme la possibilité d’étiquetage et de labellisation des produits, le consentement à payer des consommateurs, les conséquences de l'hétérogénéité phénotypique des animaux pour la transformation des produits et la répartition spatiale des exploitations. Au niveau des citoyens, un défi consiste à mieux relier leurs préoccupations en matière de bien-être des animaux et de santé. Ces nombreuses questions plaident en faveur d'une approche interdisciplinaire et transdisciplinaire sur de nombreux sujets, associant l’ensemble des acteurs, y compris les décideurs publics, dans une démarche de recherche participative.

The objective of this study was to apply and preliminarily evaluate a High-Resolution Melting (HRM) analysis technique coupled with qPCR, that allows the simultaneous detection of 10 different ruminant abortogenic pathogens, for investigating abortions in sheep and goats throughout Greece. A total of 264 ovine and caprine vaginal swabs were obtained the week following the abortion from aborted females and analyzed using a commercially available kit (ID Gene™ Ruminant Abortion Multiplex HRM, Innovative Diagnostics). Results indicated a high prevalence of Coxiella burnetii and Chlamydophila spp., which were detected in 48.9% and 42.4% of the vaginal swabs, respectively. Results for these most commonly detected pathogens were compared with those of a well-established commercial qPCR kit, with near-perfect agreement. Toxoplasma gondii, Salmonella spp., Brucella spp., Anaplasma phagocytophilum, Campylobacter fetus, and Neospora caninum were also identified, the two latter reported for the first time in the country in small ruminants. Mixed infections occurred in 35.6% of the animals examined. This technique allows for the simultaneous detection of many abortogenic pathogens in an accurate and cost-effective assay. Detection of uncommon or not previously reported pathogens in various cases indicates that their role in ovine and caprine abortions may be underestimated.

Abstract 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.

Q fever is a disease caused by Coxiella burnetii that affects many animal species and humans. In ruminants, the disease is responsible for several reproductive disorders (such as abortions, stillbirths, premature births, weak offspring, retained foetal membranes and infertility). An inactivated vaccine based on a phase I antigen of C. burnetii is available for cattle, goats and sheep. This review aims to summarise the scientific literature regarding the efficacy and safety of this vaccine to control the infection in these three domestic ruminant species. Forty-five publications and one experimental veterinary thesis reporting on experimental studies, case reports, mathematical modelling and intervention studies were selected according to the PRISMA guidelines. Although some studies lack control groups or statistical analyses, for all three species, published data show that vaccination often results in a reduction in abortions and an improvement in reproductive performance in comparison with absence of vaccination. There is also evidence, including in infected herds and animals, that vaccination is associated with a reduction in bacterial shedding, both in intensity and duration in comparison with absence of vaccination. For these reasons, in case of human outbreaks, vaccination is one of the pillars of control measures. Vaccination is generally well tolerated, despite the rare occurrence of mild, transient side-effects, such as hyperthermia and reduction in milk yield.

Precision Livestock Farming (PLF) describes the combined use of sensor technology, the related algorithms, interfaces, and applications in animal husbandry. PLF technology is used in all animal production systems and most extensively described in dairy farming. PLF is developing rapidly and is moving beyond health alarms towards an integrated decision-making system. It includes animal sensor and production data but also external data. Various applications have been proposed or are available commercially, only a part of which has been evaluated scientifically; the actual impact on animal health, production and welfare therefore remains largely unknown. Although some technology has been widely implemented (e.g., estrus detection and calving detection), other systems are adopted more slowly. PLF offers opportunities for the dairy sector through early disease detection, capturing animal-related information more objectively and consistently, predicting risks for animal health and welfare, increasing the efficiency of animal production and objectively determining animal affective states. Risks of increasing PLF usage include the dependency on the technology, changes in the human-animal relationship and changes in the public perception of dairy farming. Veterinarians will be highly affected by PLF in their professional life; they nevertheless must adapt to this and play an active role in further development of technology.