HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Studying the Contribution of P-Glycoproteins in Anthelmintic Resistance in the Nematode Model Caenorhabditis elegans
No full textInternational audienceInfection of grazing ruminants by helminth parasites alters animal welfare and leads to massive economic losses. Combatting these parasites relies on the use of powerful anthelmintic (AH) drugs, such as Ivermectin (IVM). However, the effectiveness of these drugs is being compromised by the development of drug resistance among the parasite population. Resistance to IVM involves complex and polygenic mechanisms. In particular, by generating an IVM resistant Caenorhabditis elegans strain through step-wise selection pressure (IVR10), we showed that these worms overexpress genes encoding P-Glycoproteins (PGPs), which belong to the ATP-binding cassette drug transporter family. Using the CRISPR-Cas9 genome editing technique, we engineered IVR10 strains deleted individually for six of the most overexpressed pgp genes. We then studied how the lack of each pgp affected IVM susceptibility. We compared IVM efficacy across wild-type, IVR10, and the various IVR10 knock-out strains using development and motility phenotypes. Interestingly, only pgp-9 deletion significantly increased susceptibility to IVM, suggesting its crucial and unique role in IVM resistance. Following this discovery, using a novel IVM fluorescent probe, we quantified the drug distribution within the nematode, to clarify the relationship between PGP-9 and IVM resistance. We observed that IVM resistance was associated with lower drug accumulation in the worms, consistent with an increased drug efflux rate, while pgp-9 knock-out in IVR10 restored drug levels similar to those in the sensitive strain. In summary, pgp-9 deletion increased IVM sensitivity by preventing drug efflux in the resistant IVR10 strain. These findings advance our understanding of IVM resistance mechanisms, and identify PGP-9 as a promising target to improve IVM-based treatments and prevent future resistance development.Acknowledgements: This work is supported by grant N° ANR-21-CES35-004 “Fluo-RES” from the Agence Nationale de la Recherche
A genome-wide study of ruminants uncovers two endogenous retrovirus families recently active in goats
No full textInternational audienceAbstractBackground: Endogenous retroviruses (ERV) are traces of ancestral retroviral germline infections that constitute a significant portion of mammalian genomes and are classified as LTR-retrotransposons. The exploration of their dynamics and evolutionary history in ruminants remains limited, highlighting the need for a comprehensive and thorough investigation of the ERV landscape in the genomes of cattle, sheep and goat.Results: Through a de novo bioinformatic analysis, we characterized 24 Class I and II ERV families across four reference assemblies of domestic and wild sheep and goats, and one assembly of cattle. Among these families, 13 are represented by consensus sequences identified in the five analyzed species, while eight are exclusive to small ruminants and three to cattle. The similarity-based approach used to search for the presence of these families in other ruminant species revealed multiple endogenization events over the last 40 million years and distinct evolutionary dynamics among species. The ERV annotation resulted in a high-resolution dataset of 100,534 ERV insertions across the five genomes, representing between 0.5 and 1% of their genomes. Solo-LTRs account for 83.2% of the annotated insertions demonstrating that most of the ERVs are relics of past events. Two Class II families showed higher abundance and copy conservation in small ruminants. One of them is closely related to circulating exogenous retroviruses and is represented by 22 copies sharing identical LTRs and 12 with complete coding capacities in the domestic goat.Conclusions: Our results suggest the presence of two ERV families with recent transpositional activity in ruminant genomes, particularly in the domestic goat, illustrating distinct evolutionary dynamics among the analyzed species. This work highlights the ongoing influence of ERVs on genomic landscapes and call for further investigation of their evolutionary trajectories in these genomes
Sequence‐Based Multi Ancestry Association Study Reveals the Polygenic Architecture of Varroa destructor Resistance in the Honeybee Apis mellifera
No full textInternational audienceHoneybees, Apis mellifera , have experienced the full impacts of globalisation, including the recent invasion by the parasitic mite Varroa destructor , now one of the main causes of colony losses worldwide. The strong selection pressure it exerts has led some colonies to develop defence strategies conferring some degree of resistance to the parasite. Assuming these traits are partly heritable, selective breeding of naturally resistant bees could be a sustainable strategy for fighting infestations. To characterise the genetic determinism of varroa resistance, we conducted the largest genome wide association study performed to date on whole genome sequencing of more than 1500 colonies on multiple phenotypes linked to varroa resistance of honeybees. To take into account some genetic diversity of honeybees, colonies belonging to different ancestries representing the main honeybee subspecies in Western Europe were included and analysed both as separate populations and combined in a meta‐analysis. The results show that varroa resistance is substantially heritable and polygenic: while 60 significant associations were identified, none explain a substantial part of the trait genetic variance. Overall our study highlights that genomic selection for varroa resistance is promising but that it will not be based on managing a few strong effect mutations and rather use approaches that leverage the genome wide diversity of honeybee populations. From a broader perspective, these results point the way towards understanding the genetic adaptation of eusocial insects to parasite load
YAPP
No full textyapp is a program that includes a set of utilities to work on high density genetic data in pedigrees. It is similar to other existing softwares such as LINKPHASE, FIMPUTE, AlphaPhase ... . I developed it for my own research to have a tool that is opensource and that I can tweak to my own needs.If you find it useful for you, drop me a note (e.g. on twitter @BertrandServin). If you want to contribute ideas or code, you are welcome if you know python :)yapp and its utilities implement some models and methods that have been invented by other people. If you use yapp it is important that you acknowledge their work by citing the appropriate references. These will depend on the way you use the software, see the documentation
Guidance on the planning and reporting of experimental design and analysis
No full textEditorialInternational audienc
MoSBReal : un dispositif pour l’enregistrement et le suivi automatisé des postures de la truie allaitante
No full textInternational audienceWe developed an automatic monitoring system, called MoSBReal, to record the postures of lactating sows kept in crates. The system consists of a Raspberry Pi, protected in a waterproof box, connected to two closed-circuit television (CCTV) cameras to monitor two sows at the same time. The system is easy to install inside a building on a pig farm and to use. The system can be controlled using a smartphone with a direct wireless connection, which does not require Wi-Fi. It can be used for example to set up the camera and check the angle of view. The system uses a convolutional neural network (CNN) to estimate sow postures from the CCTV images at a rate of one estimate every 30 s. A total of eight postures were considered: standing, sitting, kneeling, lying sternal, and lying on right or left side and with the udder exposed or not. The CNN was trained with 89,399 images of 164 different sows and evaluated with 40,206 images of 60 different sows not included in the training set. Using this evaluation procedure, we assessed the capacity of the method to estimate posture from sows never seen by the neural network as it is the case in practice. The overall precision of the prediction and recall were both equal to 92%. The system was installed on 10 farms and used for 10 months on each with no notable difficulties
Effects of the Maximum Recommended Levels of Fumonisins in the EU on Oxylipin Profiles in the Liver and Brain of Chickens
No full textInternational audienceThis study aimed to assess the effects of a diet containing 20.8 mg FB1 + FB2/kg over four and nine days on oxylipin (OL) profiles in the liver and brain of chickens. A total of 96 OLs, derived from seven polyunsaturated fatty acids (PUFAs) via the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (P450), and non-enzymatic pathways, were measured using HPLC-MS/MS. In the liver, a significant increase in epoxide P450-derived OLs was detected by day 4, with smaller but notable increases in COX- and LOX-derived OLs by day 9. These alterations were independent of whether the parent PUFA was ω6 or ω3. However, OLs derived from 18-carbon (C18) PUFAs, such as linoleic acid and alpha-linolenic acid, showed greater increases compared to those derived from C20 or C22 PUFAs. The diol/epoxide ratios in the liver decreased at four and nine days, suggesting that fumonisins did not induce an inflammatory response. In the brain, at four days, the most discriminative OLs were derived from ω3-PUFAs, including docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid, via the LOX pathway. By nine days, several OLs derived from arachidonic acid, spanning all enzymatic pathways, became discriminative. In general, the diol/epoxide ratios in the brain were decreased at 4 days and then returned to the initial levels. Taken together, these results show strong effects of fumonisins on OLs in the liver and brain that are both specific and distinct
La santé animale au prisme des sciences sociales : pratiques, défis et enjeux des approches interdisciplinaires
No full textInternational audienceDiverses recherches impliquant les sciences sociales ont été développées depuis une quinzaine d’années dans le domaine de la santé animale. L’objectif de cet ouvrage est, sur la base d’approches réflexives et d’études de cas, de livrer un panorama des recherches interdisciplinaires conduites sur des questions de santé animale dans l’espace de la recherche francophone et de livrer une analyse critique de cette trajectoire afin de lui donner un nouvel élan pour la décennie à venir. La première partie regroupe des travaux qui trouvent leur source dans des questionnements propres aux sciences sociales, dans le but d’éclairer des enjeux d’intérêt pour les sciences vétérinaires. Il y est notamment question des pratiques, des savoirs et des formes d’organisation relatives à la santé animale. La seconde partie regroupe un ensemble de travaux co-construits avec des porteurs d’enjeux, menés sur la base d’approches participatives, dans un objectif opérationnel de changement de pratiques ou d’amélioration des dispositifs de gestion et de surveillance des maladies animales. La dernière partie fait la place à des réflexions sur la place des approches interdisciplinaires dans l’action publique, la formation, l’expertise, et se conclut par un bilan critique et réflexif sur la recherche interdisciplinaire en santé animale. Les propos sont illustrés par des exemples concrets d’études portant sur diverses maladies infectieuses animales au Nord et au Sud, pouvant pour certaines d’entre elles affecter l’Homme
Combining genomics and semen microbiome increases the accuracy of predicting bull prolificacy
No full textInternational audienceCommercial livestock producers need to prioritize genetic progress for health and efficiency traits to address productivity, welfare, and environmental concerns but face challenges due to limited pedigree information in extensive multi‐sire breeding scenarios. Utilizing pooled DNA for genotyping and integrating seminal microbiome information into genomic models could enhance predictions of male fertility traits, thus addressing complexities in reproductive performance and inbreeding effects. Using the Angus Australia database comprising genotypes and pedigree data for 78,555 animals, we simulated percentage of normal sperm (PNS) and prolificacy of sires, resulting in 713 sires and 27,557 progeny in the final dataset. Publicly available microbiome data from 45 bulls was used to simulate data for the 713 sires. By incorporating both genomic and microbiome information our models were able to explain a larger proportion of phenotypic variation in both PNS (0.94) and prolificacy (0.56) compared to models using a single data source (e.g., 0.36 and 0.41, respectively, using only genomic information). Additionally, models containing both genomic and microbiome data revealed larger phenotypic differences between animals in the top and bottom quartile of predictions, indicating potential for improved productivity and sustainability in livestock farming systems. Inbreeding depression was observed to affect fertility traits, which makes the incorporation of microbiome information on the prediction of fertility traits even more actionable. Crucially, our inferences demonstrate the potential of the semen microbiome to contribute to the improvement of fertility traits in cattle and pave the way for the development of targeted microbiome interventions to improve reproductive performance in livestock
Évaluation de la variabilité de la concentration en Immunoglobulines G1 (IgG1) du colostrum de brebis de race Lacaune
No full textColostrum in ewes is a key determinant of lamb survival and health, as it provides both nutritional supply and passive immune transfer through immunoglobulins (mainly IgG1), leukocytes, and nonspecific antimicrobial factors. In lambs, early and adequate intake of high-quality colostrum conditions immune protection and future performance. Data regarding the variability of IgG concentration in colostrum from dairy sheep breeds are scarse, as most studies have been conducted in meat breeds. In this study, colostrum samples were collected at lambing (T0) from 98 multiparous Lacaune ewes, and at T0+6 hours and T0+12 hours (n = 34), then analyzed by radial immunodiffusion (RID, reference method) and digital refractometry. The mean IgG concentration of first milking colostrum (T0) was 35.2 ± 18.4 g/L, with a more than twofold decrease already observed at T0+6h. The correlation between IgG concentration measured by RID and mean Brix index was high (r = 0.781; p < 2.2e-16). Fat content was low (57.6 +/- 27.9 g/L) and showed a positive linear effect on Brix measurement. No significant influence of the investigated potential sources of variation (parity, litter size, genetic line, genetic index for milk yield, milk yield at first recording, change in body condition score during gestation) could be demonstrated.Le colostrum des brebis est un élément clé pour la survie et la santé des agneaux, puisqu’il assure à la fois l’apport nutritionnel et le transfert de l’immunité passive grâce aux immunoglobulines (principalement IgG1), aux leucocytes et aux facteurs antimicrobiens non spécifiques. Chez l’agneau, la consommation précoce et suffisante de colostrum de bonne qualité conditionne la protection immunitaire et les performances futures. Les données relatives à la variabilité de la concentration en IgG du colostrum de brebis de races laitières sont quasi-inexistantes, la plupart des études ayant été menées en races allaitantes. Dans cette étude, des échantillons de colostrum ont été collectés à la mise bas (T0) chez 96 brebis Lacaune multipares et à T0+6 heures et T0+12 heures (n=34), puis analysés par immunodiffusion radiale (IDR, méthode de référence) et par réfractométrie digitale. La concentration moyenne en IgG des colostrums de première traite (T0) était de 35.2 +/-18.4 g/L, avec une réduction de plus de moitié dès T0+6h. La corrélation entre la concentration en IgG mesurée par IDR et l’indice Brix moyen était élevée (r = 0,781 ; p < 2,2e-16). La teneur en matière grasse était faible (57.6 +/- 27.9 g/L) et influençait positivement et linéairement la mesure Brix. Aucune influence significative des facteurs de variation potentiels investigués (rang de lactation, taille de portée, lignée génétique, index génétique de production laitière, production laitière au première contrôle, évolution de la note d’état corporel au cours de la gestation), n’a pu être mise en évidence