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Recently, we evidenced that the Manech Tête Rousse (MTR) deficient homozygous haplotype 2 (MTRDHH2) was likely to harbor a recessive lethal variant in ovine. In the present study, we fine mapped this region by analyzing the whole genome sequence of five MTRDHH2 heterozygous carriers compared to 95 sequences of non-carrier animals from MTR and others ovine breeds. We successfully identified a single base pair duplication in theSLC33A1gene, resulting in a frameshift leading to a premature stop codon (p.Arg246Alafs*3). SLC33A1 acts as a transmembrane transporter of acetyl-Coenzyme A, essential for cellular metabolism. In order to assess for the lethal phenotype in homozygous MTR sheep, we generated at-risk matings by artificial insemination (AI) between rams and ewes heterozygous for theSLC33A1variant namedSLC33A1_dupG. Gestation status was checked 15 days post-AI by a molecular test from blood expression of the interferon Tau-stimulatedMX1gene, and by ultrasonography performed between 45 days and 60 days post-AI. Based on ultrasonography, the AI success was reduced by 12% compared to safe matings suggesting embryonic/fetal losses further confirmed by the molecular test based onMX1differential expression. Forty-nine lambs were born from at-risk matings with a mortality rate of 34.7% observed before weaning. HomozygousSLC33A1_dupG lambs contributed to 47% of this mortality occurring mainly in the first five days after lambing with no obvious clinical signs. Thus, an appropriate management ofSLC33A1_dupG (allele frequency of 0.04) in the MTR selection scheme should increase the overall fertility and lamb survival.

Recessive deleterious variants are known to segregate in livestock populations as in human, and some may cause lethality when homozygous. By scanning the genome of 6,845 Manech Tête Rousse dairy sheep using phased 50k SNP genotypes and pedigree data, we searched for deficiency in homozygous haplotype (DHH). Five Manech Tête Rousse deficient homozygous haplotypes (MTRDHH1 to 5) were identified with a homozygous deficiency ranging from 84% to 100%. These haplotypes are located on OAR1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5) and OAR20 (MTRDHH1), and have frequencies ranging from 7.8% to 16.6%. When comparing at-risk mating between DHH carriers to safe mating between non-carriers, two DHH (MTRDHH1 and 2) showed significant effects on decreasing artificial insemination success and/or increasing stillbirth rate. We particularly investigated the MTRDHH1 haplotype highly increasing stillbirth rate, and we identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in theMMUTgene (methylmalonyl-CoA mutase) by using a whole genome sequencing (WGS) approach. We generated homozygous lambs for theMMUTmutation by oriented mating, and most of them died within the first 24h after birth without any obvious clinical defect. RT-qPCR and western blotting performed on post-mortem liver and kidney biological samples showed a decreased expression ofMMUTmRNA in the liver and absence of a full-length MMUT protein in mutated homozygous lambs. In parallel, MTRDHH4 and MTRDHH5 showed partial association with variants inRXFP2andASIPgenes, respectively, already known to control horned/polled and coat color phenotypes in sheep, two morphological traits accounting in the MTR breed standard. Further investigations are needed to identified the supposed recessive deleterious variant hosted by MTRDHH2 and MTRDHH3. Anyway, an appropriate management of these haplotypes/variants in the MTR dairy sheep selection program should increase the overall fertility and lamb survival.Author SummaryIn this article, we used reverse genetics screen in ovine using large genotype data available in the framework of genomic selection program in Manech Tête Rousse dairy sheep. We identified five genomic regions with a highly significant deficit in homozygous animal. These regions are thus supposed to host recessive deleterious mutations. In one of these genomic regions, we identified a nonsense mutation inMMUTthat alters the functioning of this essential gene of cell metabolism, causing perinatal mortality of homozygous lambs. In this work, we also identified other regions possibly associated with morphological appearance part of the breed standard such as polledness and coat color. Increasing knowledge in these genomic regions will help the future genetic management of the Manech Tête Rousse breed, particularly to reduce lamb mortality.

Les filières et systèmes d’élevage ont considérablement évolué au cours du XXe siècle. La recherche en génétique animale et la mise en place des programmes d’amélioration génétique ont joué un rôle important dans cette évolution. Aujourd’hui, le modèle dominant, caractérisé par une utilisation intensive d’intrants, une très grande spécialisation des systèmes et la recherche de coûts de production toujours plus bas, est remis en cause. Un objectif désormais largement partagé est de contribuer à l’émergence de systèmes alimentaires durables, équitables, sains et respectueux de l’environnement. L’agroécologie est un moyen pour atteindre cet objectif et guider la nécessaire transition des systèmes d’élevage, à laquelle la génétique animale doit contribuer. Des exemples de contributions passées, actuelles et potentielles sont présentés et positionnés selon cinq principes d’agroécologie proposés pour guider l’évolution des systèmes d’élevage. La plupart, telles que la sélection d’animaux résistants à différentes maladies infectieuses ou valorisant de façon plus efficace leur alimentation, correspondent à des niveaux de transition agroécologique faible, dans la mesure où elles ne remettent pas en cause les fondements, les composantes ou la conception générale des systèmes. De nouvelles contributions, visant une transition forte, fondée sur une reconception en profondeur des systèmes d’élevage, sont à développer à l’avenir.

In a context of climate change, identifying the genes underlying adaptations to extreme environments is essential. Small ruminants are adapted to a wide variety of habitats and thus, are promising study models. Here, we considered 17 goat and 25 sheep local Mediterranean breeds, in Italy, France and Spain. We proposed, and empirically tested a new methodology to highlight selection signatures in relation to the environments. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original geographical cradle, including transhumant pastoral areas. For both species, the cradles were arranged along latitudinal gradient of aridity and altitude. Then we used the programs PCAdapt and LFMM. Considering cradles, instead of current GPS coordinates, markedly improved the sensitivity of the LFMM analyses. All the results combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles. Some of these genes, have been found implicated in lipid metabolism (SUCLG2, BMP2), hypoxia/heat stress (UBE2R2/UBAP2), lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). For the intergenic region between PCDH9 and KLH1, as well as NBEA, identified in both species, the adaptive role could be strong. We found for RXFP2, associated with sheep horn development, and MSRB3 and SLC26A4, both associated with hearing of sheep, a strong association with the environment gradient. We conclude that our new methodology, which considers breeds in their historical, environmental and anthropological context, provides novel and essential information on local breeds and their unique adaptations.

IntroductionDrug-resistant parasites threaten livestock production. Breeding more resistant hosts could be a sustainable control strategy. Environmental variation may however alter the expression of genetic potential and directional selection toward host resistance could initiate an arms race between the host and its parasites.Methods and ResultsWe created sheep lines with high or low resistance to Haemonchus contortus. We first exposed both lines to chronic stress or to the infection by another parasite Trichostrongylus colubriformis, to test for genotype-by-environment and genotype-by-parasite species interactions respectively. Overall, between-line divergence remained significant across environmental perturbations. But we found that the impact of chronic stress on H. contortus infection varied among families and that divergence was reduced during infection by T. colubriformis. Second, we quantified genomic and transcriptomic differences in H. contortus worms collected from both lines to identify components of an arms race. We found no evidence of genetic differentiation between worms from each line. But survival to more resistant hosts was associated with enhanced expression of cuticle collagen coding genes.DiscussionBreeding for resistance hence remains a sustainable strategy that requires to anticipate the effects of environmental perturbations and to monitor worm populations.

International audience; Feeding costs represent one of the highest expenditures in animal production systems. Breeding efficient animals that express their growth potential while eating less is therefore a major objective for breeders. We estimated the genetic parameters for feed intake, feed efficiency traits (residual feed intake (RFI) and feed conversion ratio (FCR)), growth and body composition traits in the Romane meat sheep breed. In these traits, selection responses to single-generation divergent selection on RFI were evaluated. From 2009 to 2016, a total of 951 male lambs were tested for 8 weeks starting from 3 months of age. They were weighed at the beginning and at the end of the testing period. Backfat thickness and muscle depth were recorded at the end of the testing period through ultrasound measurements. Feed intake was continuously recorded over the testing period using the automatic concentrate feeders. The heritability of RFI was estimated at 0.45 ± 0.08, which was higher than the heritability of FCR (0.30 ± 0.08). No significant genetic correlations were observed between RFI and growth traits. A favourable low negative genetic correlation was estimated between RFI and muscle depth (−0.30 ± 0.15), though additional data are needed to confirm these results. The selection of low RFI sires based on their breeding values led to the production of lambs eating significantly less concentrate (3% decrease in the average daily feed intake), but with the same growth as lambs from sires selected based on high RFI breeding values. We concluded that in meat sheep, RFI is a heritable trait that is genetically independent of postweaning growth and body composition traits. A one-generation divergent selection based on RFI breeding values highlighted that substantial gains in feeding costs can be expected in selection schemes for meat sheep breeds.

La résistance génétique des petits ruminants aux infestations par les nématodes gastro-intestinaux (strongles) peut être sélectionnée puisqu’elle est mesurable indirectement par le comptage d’oeufs dans les fèces, héritable et génétiquement peu ou pas corrélée aux autres critères de sélection. La mise en place d’une telle sélection dans les schémas nécessitera la création de plateformes permettant de faire face au nombre de mesures à réaliser et imposera le suivi de l’évolution de la communauté de nématodes afin de prévenir un contournement potentiel de la résistance de l’hôte par les parasites. La meilleure pratique pour éviter ce contournement est de considérer la résistance génétique comme un levier d’action à intégrer à d’autres stratégies (la nutrition, la gestion des prairies et les traitements anthelminthiques)., The resistance of small ruminants to gastro-intestinal nematode infection can be included into a genetic selection program. This resistance can be measured by faecal nematode egg counts. This trait is heritable and only lightly correlated to other selected traits. Faecal egg counts should be measured on a large number of small ruminants in order to be included in selection schemes and this requires the services of a phenotyping platform. The evolution of the nematode community under the selection pressure due to an increase in host resistance should be controlled in order to prevent a putative adaptation of nematodes. In order to avoid adaptation of the parasites, an integrated strategy should be implemented and genetic selection for resistance to nematodes should be associated with the use of anthelmintics, as well as an adequate fulfillment of nutritional needs of small ruminants and adequate management of pastures to reduce infection risk.

We recently demonstrated that the Lacaune deficient homozygous haplotype 6 (LDHH6) potentially hosts a recessive perinatal lethal mutation in Lacaune dairy sheep mapped on OAR3. In the present study, we have analyzed the whole-genome sequences of two Lacaune ram heterozygous carriers of LDHH6. After variant calling and filtering against the variants of 86 non-carrier rams, we have identified a single nucleotide variant (SNV) in the two LDHH6 carriers whose variant allele induced a premature stop codon (p.Glu111*) in the Coiled-Coil Domain Containing 65 (CCDC65) gene. CCDC65 is involved in the assembly of the nexin-dynein regulatory complex for the formation of microtubules in ciliated cells. In order to identify the phenotype in homozygous sheep, we generated at-risk matings (n = 17) between rams and ewes heterozygous for the candidate variant in CCDC65. A total of 16 lambs were born alive with five genotyped as homozygous carriers. The homozygous lambs suffered from respiratory problems, and four of them died within the first month of life. At necropsy, we observed a broad hepatization of lung lobes possibly induced by infectious pneumonia. The management of this lethal recessive allele (frequency of 0.06) through reasoned mating in the Lacaune sheep selection schemes could reduce lamb mortality by 2%.

International audience; Breeding strategies based on feed efficiency are now implemented in most animal species using residual feed intake (RFI) criteria. Although relevant, the correlated responses of feeding behaviour traits resulting from such selection on RFI are poorly documented. We report the estimated feeding behaviour at three time levels (visit, meal and day) and genetic parameters between the feeding behaviour traits and their links with RFI and its components. Feed intake, feeding duration at three time levels (per visit, meal and day), feeding rate, number of visits and time‐between‐visits were estimated for 951 Romane lambs fed via automatic concentrate feeders. Heritability estimates of feeding behaviour traits ranged from 0.19 to 0.54 with higher estimates for the day level than the visit level. Daily feed intake was not genetically linked to feed intake at the visit level, whereas feeding duration between visit and day levels was moderately correlated (Rg = +0.41 ± 0.12). RFI was not significantly correlated with feeding rate, but was positively linked to feed intake and feeding duration at the day level (+0.73 ± 0.09 and +0.41 ± 0.13, respectively) and negatively at the visit level (−0.33 ± 0.14 and −0.22 ± 0.17, respectively). Selecting animals with lower RFI values might modify their feeding behaviour by increasing feed intake and feeding duration at the visit level but decrease the number of visits per day (+0.51 ± 0.14).

National audience; Selecting efficient animals is a major concern for livestock production, not only for economic but also for agro-environmental purposes. The selection of efficient animals leads to a decrease of feed intakes and limits pollutant emissions (greenhouse gases and nitrogen). In meat sheep, we demonstrated that Residual Feed Intake (CR) is a heritable selection criteria (h²=0.41) which is genetically correlated to average daily feed intake (rg=+0.73) under a concentrated diet. We setup a divergent selection experiment on CR (under a concentrated diet) in the Romane breed in order to 1) have a better understanding of biological processes underlying feed efficiency and 2) to evaluate the consequences of the genetic divergence on feed efficiency over a panel of traits (growth, fattening, muscular development,…), also when animals are fed with forages. After two generations of selection, the divergence is marked since it reaches 1.9 genetic standard deviations. Efficient animals (CR-) under a concentrated diet also have a lower daily feed intake with a forage-based diet (103 g less) than less efficient animals (CR+) while displaying similar growth. Significant differences between CR- and CR+ animals were also described at the level of the rumen microbiota.; La sélection d’animaux efficaces est un enjeu majeur pour les filières animales, que ce soit pour des raisons économiques, mais aussi agro-environnementales. En effet, sélectionner des animaux efficaces permet de limiter les quantités ingérées et les émissions de polluants (gaz à effet de serre et résidus azotés). Chez les ovins allaitants, nous avons montré que la consommation résiduelle (CR) est un critère de sélection héritable (h²=0,41) corrélé génétiquement à la quantité de concentré ingérée par jour (rg=+0,73). La mise en place de lignées divergentes sur la CR (mesurée avec une alimentation concentrée) en race Romane permet 1) de mieux comprendre les mécanismes biologiques impliqués dans l’efficacité alimentaire et 2) d’évaluer les conséquences de la sélection génétique de ce critère d’efficacité alimentaire sur une diversité d’autres caractères (croissance, engraissement, développement musculaire, …) mais aussi lorsque les animaux ont une ration fourragère. Après deux générations de sélection, la divergence est marquée puisqu’elle s’élève à 1,9 écart-type génétique. Nous avons montré que les animaux efficaces (CR-) avec une ration concentrée mangent également moins de fourrage (103 g en moins par jour par animal) que les animaux peu efficaces (CR+) tout en ayant des niveaux de croissance équivalents. Des différences significatives entre CR- et CR+ se retrouvent au niveau du microbiote ruminal

Background One of the approaches to detect genetics variants affecting fitness traits is to identify their surrounding genomic signatures of past selection. With established methods for detecting selection signatures and the current and future availability of large datasets, such studies should have the power to not only detect these signatures but also to infer their selective histories. Domesticated animals offer a powerful model for these approaches as they adapted rapidly to environmental and human-mediated constraints in a relatively short time. We investigated this question by studying a large dataset of 542 individuals from 27 domestic sheep populations raised in France, genotyped for more than 500,000 SNPs. Results Population structure analysis revealed that this set of populations harbour a large part of European sheep diversity in a small geographical area, offering a powerful model for the study of adaptation. Identification of extreme SNP and haplotype frequency differences between populations listed 126 genomic regions likely affected by selection. These signatures revealed selection at loci commonly identified as selection targets in many species (“selection hotspots”) including ABCG2, LCORL/NCAPG, MSTN, and coat colour genes such as ASIP, MC1R, MITF, and TYRP1. For one of these regions (ABCG2, LCORL/NCAPG), we could propose a historical scenario leading to the introgression of an adaptive allele into a new genetic background. Among selection signatures, we found clear evidence for parallel selection events in different genetic backgrounds, most likely for different mutations. We confirmed this allelic heterogeneity in one case by resequencing the MC1R gene in three black-faced breeds. Conclusions Our study illustrates how dense genetic data in multiple populations allows the deciphering of evolutionary history of populations and of their adaptive mutations. Electronic supplementary material The online version of this article (10.1186/s12864-018-4447-x) contains supplementary material, which is available to authorized users.

Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and data sets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified ∼50,000 crossover hotspots on the genome, and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting interindividual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly two other loci of smaller effects including the KCNJ15 and FSHR genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two data sets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for interindividual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism.

Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and datasets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified about 50,000 crossover hotspots on the genome and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting inter-individual variation in recombination rate in Lacaune, including theRNF212andHEI10genes and possibly 2 other loci of smaller effects including theKCNJ15andFSHRgenes. Finally, we compared our results to those obtained previously in a distantly related population of domestic sheep, the Soay. This comparison revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome and that the two datasets can be combined to create more precise male meiotic recombination maps in sheep. Despite their similar recombination maps, we show that Soay and Lacaune males exhibit different heritabilities and QTL effects for inter-individual variation in genome-wide recombination rates.

Sheep was one of the first domesticated livestock species in the Anatolia region of contemporary Iran and eventually spread world-wide. Previous studies have shown that French sheep populations likely harbour a large part of European domesticated sheep diversity in a relatively small geographical region, offering a powerful model for the study of adaptation. We studied the diversity of 27 French sheep populations by genotyping 542 individuals for more than 500 000 SNPs. We found that French sheep breeds were divided into two main groups, corresponding to northern and southern origins and additionally we identified admixture events between northern and southern populations. The genetic diversity of domesticated animals results from adaptation of populations to constraints imposed by farmers and environmental conditions. We identified 126 genomic regions likely affected by selection. In many cases, we found evidence for parallel selection events in different genetic backgrounds, most likely for different mutations. Some of these regions harbour genes potentially involved in morphological traits (SOCS2, NCAPG/LCORL, MSRB3), coat colour (MC1R) and adaptation to environmental conditions (ADAMTS9). Closer inspection of two of these regions clarified their evolutionary history: at the LCORL/NCAPG locus we found evidence for introgression of an adaptive allele from a southern population into northern populations and by resequencing MC1R in some breeds we confirmed different mutations in this gene are responsible for the same phenotypic trait. Our study illustrates how dense genetic data in multiple populations allows the deciphering of evolutionary history of populations and of their adaptive mutations.

L’agro-écologie utilise les processus naturels et les ressources locales plutôt que des intrants chimiques pour assurer la production tout en limitant l’impact environnemental de l’agriculture. A cette fin, des innovations en génétique sont nécessaires pour disposer d’animaux productifs et adaptés à des contextes locaux variés. Pour toute filière d’élevage, réorienter les programmes de sélection actuels semble plus utile que développer des programmes spécifiques qui peineront à être efficaces en termes de coûts et de progrès génétiques attendus. Améliorer la robustesse des animaux vise à promouvoir leurs capacités d’adaptation en intégrant de nombreux critères de sélection, en particulier de reproduction, santé, et d’adaptation à des ressources alimentaires peu digestibles et au changement climatique. Cela amène à considérer les interactions génotype-environnement dans la prédiction des valeurs génétiques et à évaluer les performances des animaux dans des systèmes à bas intrants pour sélectionner ceux qui sont adaptés à des conditions limitantes. La standardisation tant des animaux que des conditions d’élevage paraît antinomique avec les principes de l’agro-écologie prônant une adaptation des animaux aux ressources et contraintes locales dans des systèmes peu artificialisés et très liés à leur environnement physique. Il n’y a donc pas UN animal type agro-écologique, mais DES animaux aux profils variés permettant de répondre aux attentes de l’agro-écologie. Face à la diversité des milieux et des systèmes d’élevage, il faut conserver une diversité génétique importante intra-race, mais aussi préserver la diversité génétique entre races. Cela nécessite une caractérisation phénotypique et génétique des races locales. Enfin, il s’agit de favoriser l'appropriation par les éleveurs et les techniciens d’élevage des outils et des ressources génétiques disponibles pour répondre à leurs besoins., Agroecology uses natural processes and local resources rather than chemical inputs to ensure production while limiting the environmental footprint of agriculture. In this context, breeding innovations are necessary to obtain animals that are both productive and adapted to a broad range of local contexts. Whatever the animal sector, reorienting current breeding programmes seems to be more useful than developing programmes dedicated to agroecological systems that will struggle to be really effective in terms of costs and expected genetic progress. Breeding for robustness aims to promote individual adaptive capacities by considering various selection criteria including reproduction, health, and adaptation to rough feed resources, warm climate or fluctuating environmental conditions. It leads considering genotype-environment interactions in the prediction of breeding values. Animal performance should be evaluated in low-input systems in order to select those animals adapted to limiting conditions. Standardization of both animals and breeding conditions appears contradictory to the agroecological paradigm that calls for an adaptation of animals to local opportunities and constraints in weakly artificialized systems tied to their physical environment. There is thus not a single agroecological animal type, but animals with various profiles that meet the expectations of agroecology. As well as supporting the value of within-breed diversity, we must preserve between-breed diversity to maintain numerous options for adaptation to a variety of production environments and contexts. This may involve to phenotypically and genetically characterize local breeds. Last but not least, improved assimilation by farmers and farm technicians of available genetic resources and breeding tools is necessary.

Threatened populations that have undergone a strong reduction of their size are subsequently more likely to reproduce under inbred conditions. The adverse effects of such matings on the fitness of the progeny have long been known. Unlike natural populations for which detailed records of genealogy are scarce, domestic and captive populations can benefit from available pedigree data. In this regard, the Merino population from Rambouillet, which has been maintained at small size since its arrival at the Bergerie Nationale de Rambouillet, is a valuable model to study the effects of a small population size associated with a closed registry system on genome structure and genetic diversity. This study showed that, despite a low genetic diversity and a strong structure of the genome, the population management, aiming to minimize matings between the most closely related animals was an adequate breeding policy: the population is not structured into family groups. Furthermore inbreeding depression is low. This project should help to assess the evolutionary potential of the flock. In the long term, it should contribute to the development of recommendations on the management of endangered populations where inbreeding and genetic drift are inevitable, due to their small size.

Gastrointestinal nematodes are one of the main health issues in sheep breeding. To identify loci affecting the resistance to Haemonchus contortus, a genome scan was carried out using 1,275 Romane × Martinik Black Belly backcross lambs. The entire population was challenged with Haemonchus contortus in 2 consecutive experimental infections, and fecal egg counts (FEC) and packed cell volumes were measured. A subgroup of 332 lambs with extreme FEC was necropsied to determine the total worm burden, length of female worms, sex ratio in the worm population, abomasal pH, and serum and mucosal G immunoglobulins (IgG) responses. Pepsinogen concentration was measured in another subset of 229 lambs. For QTL detection, 160 microsatellite markers were used as well as the Illumina OvineSNP50 BeadChip that provided 42,469 SNP markers after quality control. Linkage, association, and joint linkage and association analyses were performed with the QTLMAP software. Linkage disequilibrium (LD) was estimated within each pure breed, and association analyses were carried out either considering or not the breed origin of the haplotypes. Four QTL regions on sheep chromosomes (OAR)5, 12, 13, and 21 were identified as key players among many other QTL with small to moderate effects. A QTL on OAR21 affecting pepsinogen concentration exactly matched the pepsinogen (PGA5) locus. A 10-Mbp region affecting FEC after the 1st and 2nd infections was found on OAR12. The SNP markers outperformed microsatellites in the linkage analysis. Taking advantage of the LD helped to refine the locations of the QTL mapped on OAR5 and 13.

Quantitative trait loci (QTL) mapping for susceptibility to a Salmonella Abortusovis vaccinal strain was performed using an experimental design involving 30 Romane sheep sire families (1216 progenies). Nine QTL corresponding to bacterial load, weight variations and antibody response criteria were mapped on eight chromosomes, including the major histocompatibility complex area on chromosome 20. Surprisingly, none was found to be significant in the SLC11A1 region (formerly NRAMP1) that has been shown to influence Salmonella susceptibility in other species.

Although susceptibility to scrapie is largely controlled by the PrP gene, the role of other genes that affect scrapie resistance in sheep is now confirmed. Following the detection of quantitative trait loci (QTL) on chromosomes 6 and 18 in a half-sib family with an ARQ/VRQ susceptible PrP genotype, the whole pedigree of a naturally infected flock was investigated to confirm these QTL regions in different PrP genotypes. The present study has allowed us to confirm the QTL on chromosome 18, and to demonstrate the QTL effects in several PrP genotypes.

A mathematical approach was developed to model and optimize simultaneous selection on 2 traits, a quantitative trait with underlying polygenic variation and a monogenic trait (e.g., resistance to a disease). A deterministic model allows global optimization of the selection scheme to maximize the frequency of the desired genotype for the monogenic trait, while minimizing the loss of genetic progress on the polygenic trait. An additive QTL or gene was considered. Breeding programs with overlapping generations, different selection strategies for males and females, and assortative mating were modeled. A genetic algorithm was used to solve this optimization problem. This modeling approach may easily be adapted to a variety of underlying genetic models and selection schemes. This model was applied to an example where selection on the Prp gene for scrapie resistance was introduced as an additional selection criterion in an already existing dairy sheep selection scheme.

In this study, the potential association of PrP genotypes with health and productive traits was investigated. Data were recorded on animals of the INRA 401 breed from the Bourges-La Sapinière INRA experimental farm. The population consisted of 30 rams and 852 ewes, which produced 1310 lambs. The animals were categorized into three PrP genotype classes: ARR homozygous, ARR heterozygous, and animals without any ARR allele. Two analyses differing in the approach considered were carried out. Firstly, the potential association of the PrP genotype with disease (Salmonella resistance) and production (wool and carcass) traits was studied. The data used included 1042, 1043 and 1013 genotyped animals for the Salmonella resistance, wool and carcass traits, respectively. The different traits were analyzed using an animal model, where the PrP genotype effect was included as a fixed effect. Association analyses do not indicate any evidence of an effect of PrP genotypes on traits studied in this breed. Secondly, a quantitative trait loci (QTL) detection approach using the PRNP gene as a marker was applied on ovine chromosome 13. Interval mapping was used. Evidence for one QTL affecting mean fiber diameter was found at 25 cM from the PRNP gene. However, a linkage between PRNP and this QTL does not imply unfavorable linkage disequilibrium for PRNP selection purposes.

Le néologisme « agro-écologie » est apparu dans la littérature dans les années 30, d’abord pour désigner une discipline scientifique au carrefour de l’écologie et de l’agronomie, puis à partir des années 70 un ensemble de pratiques et un mouvement social en réaction à l’intensification de l’agriculture (Wezel et al., 2009). Francis et al. (2003) ont encore élargi cette définition en considérant l’ensemble des dimensions environnementales et socio-économiques à l’échelle des filières. Dans son acception scientifique, qui est l’angle choisi dans cette étude, l’agro-écologie se définit comme l’application des concepts et principes de l’écologie à la conception et à la gestion d’agroécosystèmes durables. La question du bouclage des cycles pour limiter les intrants et les pollutions par une meilleure réutilisation des sorties des différents ateliers est au coeur de ces problématiques. On vise également un recours accru à des régulations biologiques et écologiques que l’on cherche à piloter au mieux des attendus de l’élevage. Ceci implique de prendre en compte la diversité biologique à tous ses niveaux d'organisation, de comprendre et d’utiliser les capacités adaptatives des animaux et les interactions biotiques dans les agroécosystèmes, en considérant les systèmes de culture ou les systèmes d'élevage comme des écosystèmes particuliers (Dumont et al. 2013). Ainsi, l’agro-écologie s’inscrit-elle dans un mouvement de fond autour du « Comment produire autrement ? » dans des systèmes de production dont on cherche à concilier les performances techniques, environnementales, économiques et sociales. Lancé le 18 décembre 2012, le Projet Agro-Ecologique pour la France (PAEF) vise à conjuguer l’ensemble de ces performances tant au niveau de l'exploitation qu’au niveau collectif (territoires, filières, etc.). Il s’agit d’engager une évolution des systèmes de production, qui remette l’agronomie au coeur des pratiques, pour combiner ces différentes performances. La Loi n° 2014-1170 du 13 octobre 2014 dite Loi d'avenir pour l'agriculture, l'alimentation et la forêt en donne la définition suivante : « Les politiques publiques visent à promouvoir et à pérenniser les systèmes de production agro-écologiques, dont le mode de production biologique, qui combinent performance économique, sociale, notamment au travers d’un haut niveau de protection sociale, environnementale et sanitaire. Ces systèmes privilégient l'autonomie des exploitations agricoles et l'amélioration de leur compétitivité, en maintenant ou en augmentant la rentabilité économique, en améliorant la valeur ajoutée des productions et en réduisant la consommation d'énergie, d'eau, d'engrais, de produits phytopharmaceutiques et de médicaments vétérinaires, en particulier les antibiotiques. Ils sont fondés sur les interactions biologiques et l'utilisation des services écosystémiques et des potentiels offerts par les ressources naturelles, en particulier les ressources en eau, la biodiversité, la photosynthèse, les sols et l'air, en maintenant leur capacité de renouvellement du point de vue qualitatif et quantitatif. Ils contribuent à l'atténuation et à l'adaptation aux effets du changement climatique.

In this study, the potential association of PrP genotypes with ewe reproductive traits and lamb growth traits was investigated. Data were included on ewes and lambs of the INRA 401 breed from the Bourges-La Sapiniere INRA experimental farm. This breed was chosen because of good breeding (prolificacy and maternal abilities) and carcass qualities, and the large number of available animals with performance records and PrP genotypes. Ewes were categorized into 3 PrP genotype classes: ARR homozygous, ARR heterozygous, and animals without any ARR haplotype. Two analyses differing in the traits considered were carried out. Firstly, the potential association of the PrP genotype of ewes with their reproduction traits (fertility, litter size, and ovulation rate) was studied. The data included 801, 779, and 587 genotyped ewes for fertility, litter size, and ovulation rate, respectively. Secondly, the association of the PrP genotype of the ewes with growth traits of their lambs (birth weight, ADG between 10 and 30 d of age) was investigated. The data included 3,749 and 3,512 lambs for birth weight and ADG, respectively. The different traits were analyzed using an animal model, where the PrP genotype effect was included as a fixed effect. The reproductive traits were modeled under a probit or a threshold approach. The results of this study indicate no evidence of an association between PrP genotypes and reproductive and growth traits. It is unlikely that selection for scrapie resistance will have an effect on the reproductive or performance traits studied in the INRA 401 breed.

In this study the potential association of PrP genotypes with meat traits has been investigated. The data included young rams from individual testing stations of three breeds: Ile de France, Préalpes du Sud and Blanc du Massif Central. These breeds were chosen due to their large number of available animals (with performance records and PrP genotypes) and their differential ARR haplotype frequency. Two analyses differing in the PrP genotype classes considered were carried out. Firstly, animals were categorized into three classes: ARR homozygous, ARR heterozygous, and animals without the ARR haplotype. The data for this analysis included 725, 534 and 832 animals for Ile de France, Préalpes du Sud and Blanc du Massif Central breeds, respectively. Secondly, as the two predominant haplotypes in these breeds are ARR and AR- (and AR- includes ARQ and ARH haplotypes), the effect of substituting 1 or 2 ARR haplotypes for AR- haplotypes was studied. These comparisons involved three genotype classes: ARR homozygous, ARR/AR-, and AR-homozygous. The data for this analysis included 532, 509 and 620 animals of Ile de France, Préalpes du Sud and Blanc du Massif Central breeds, respectively. Meat traits were analysed using an animal model (where the PrP genotype was included as a fixed effect) and they included growth rate, ultrasonic fat depth, and ultrasonic muscle depth. The results of this study indicate no evidence of association between PrP genotypes and the meat traits studied in these sheep breeds.

Gastrointestinal (GI) integrity and function are regulated by nutrition and growth factors. The discovery of ghrelin, a natural growth hormone (GH) secretagogue produced by the gastrointestinal (GI) tract, is a potential link between diet and growth signals. The aim of this study was to evaluate macronutrient effect on ghrelin expression and secretion in addition to some possible function in intestinal trophic status. Wistar rats were fed a high-carbohydrate, high-protein (HP), high-fat or standard (St) diet. Animals received the same daily food volume and caloric intake. After 7 days, animals were fasted for 24 h and blood and tissue samples were obtained just before feeding or at 2 or 6 h after feeding. Fasting high-protein-fed rats had higher ghrelin plasma levels than with rats fed the high-carbohydrate, high-fat or standard diets. Two-hours after refeeding, ghrelin plasma levels had decreased in all groups with a slight recovery at 6 h after refeeding, except in the high-protein group. Ghrelin plasma levels in rats fed with the high-protein diet correlated negatively with their GH and insulin-like growth factor 1 (IGF-1) plasma concentrations which were also the lowest among the study groups. In conclusion, ghrelin secretion was nutritionally manipulated because a protein-enriched diet increased its levels.

A chromosome region involved in scrapie incubation time was identified on sheep chromosome 18 (OAR18). Since OAR18 (and OAR7) share conserved chromosome segments with human chromosomes HSA14 and HSA15, a dense map of type I markers was constructed by FISH mapping of bacterial artificial chromosomes containing genes located on these human chromosomes. In this study, we used the complete human sequence information (gene positions in megabases, Mb) to locate approximately one gene every 2 Mb on HSA15 (19 genes mapped between 19.51 and 66.02 Mb) and on HSA14 (11 genes between 73.24 and 102.62 Mb). Combined with previous work carried out in cattle and goats, our results made it possible to refine the comparative map between ruminants and humans for these two highly rearranged chromosomes (10 segments on HSA15 and 7 on HSA14). Furthermore, we identified relatively short intervals containing evolutionary breakpoints, which is a prerequisite to position them precisely. This work is also the first step in the cloning of the region involved in scrapie incubation period in sheep.

International audience; Background: Haemonchosis is a parasitic disease that causes severe economic losses in sheep industry. In recent years, the increasing resistance of the parasite to anthelmintics has raised the need for alternative control strategies. Genetic selection is a promising alternative but its efficacy depends on the availability of genetic variation and on the occurrence of favourable genetic correlations between the traits included in the breeding goal. The objective of this study was twofold. First, to estimate both the heritability of and the genetic correlations between growth traits and parasite resistance traits, using bivariate linear mixed animal models, from the phenotypes and genotypes of 1004 backcross lambs (considered as a single population), which underwent two subsequent experimental infestations protocols with Haemonchus contortus. Second, to compare the precision of the estimates when using two different relationship matrices: including pedigree information only or including also SNP (single nucleotide polymorphism) information.Results: Heritabilities were low for average daily gain before infestation (0.10 to 0.15) and average daily gain during the first infestation (0.11 to 0.16), moderate for faecal egg counts during the first infestation (0.21 to 0.38) and faecal egg counts during the second infestation (0.48 to 0.55). Genetic correlations between both growth traits and faecal egg count during the naive infestation were equal to zero but the genetic correlation between faecal egg count during the second infestation and growth was positive in a Haemonchus contortus free environment and negative in a contaminated environment. The standard errors of the estimates obtained by including SNP information were smaller than those obtained by including pedigree information only.Conclusions: The genetic parameters estimates suggest that growth performance can be selected for independently of selection on resistance to naive infestation. Selection for increased growth in a non-contaminated environment could lead to more susceptible animals with long-term exposure to the infestation but it could be possible to select for increased growth in a contaminated environment while also increasing resistance to the long-term exposure to the parasite. The use of molecular information increases the precision of the estimates.

International audience; Gastrointestinal nematode infections are one of the main health/economic issues in sheep industries, worldwide. Indicator traits for resistance such as faecal egg count (FEC) are commonly used in genomic studies; however, published results are inconsistent among breeds. Meta (or joint)-analysis is a tool for aggregating information from multiple independent studies. The aim of this study was to identify loci underlying variation in FEC, as an indicator of nematode resistance, in a joint analysis using data from three populations (Scottish Blackface, Sarda × Lacaune and Martinik Black-Belly × Romane), genotyped with the ovine 50k SNP chip. The trait analysed was the average animal effect for Strongyles and Nematodirus FEC data. Analyses were performed with regional heritability mapping (RHM), fitting polygenic effects with either the whole genomic relationship matrix or matrices excluding the chromosome being interrogated. Across-population genomic covariances were set to zero. After quality control, 4123 animals and 38 991 SNPs were available for the analysis. RHM identified genome-wide significant regions on OAR4, 12, 14, 19 and 20, with the latter being the most significant. The OAR20 region is close to the major histocompatibility complex, which has often been proposed as a functional candidate for nematode resistance. This region was significant only in the Sarda × Lacaune population. Several other regions, on OAR1, 3, 4, 5, 7, 12, 19, 20 and 24, were significant at the suggestive level.

International audience

International audience; Genomic prediction utilizes single nucleotide polymorphism (SNP) chip data to predict animal genetic merit. It has the advantage of potentially capturing the effects of the majority of loci that contribute to genetic variation in a trait, even when the effects of the individual loci are very small. To implement genomic prediction, marker effects are estimated with a training set, including individuals with marker genotypes and trait phenotypes; subsequently, genomic estimated breeding values (GEBV) for any genotyped individual in the population can be calculated using the estimated marker effects. In this study, we aimed to: (i) evaluate the potential of genomic prediction to predict GEBV for nematode resistance traits and BW in sheep, within and across populations; (ii) evaluate the accuracy of these predictions through within-population cross-validation; and (iii) explore the impact of population structure on the accuracy of prediction. Four data sets comprising 752 lambs from a Scottish Blackface population, 2371 from a Sarda×Lacaune backcross population, 1000 from a Martinik Black-Belly×Romane backcross population and 64 from a British Texel population were used in this study. Traits available for the analysis were faecal egg count for Nematodirus and Strongyles and BW at different ages or as average effect, depending on the population. Moreover, immunoglobulin A was also available for the Scottish Blackface population. Results show that GEBV had moderate to good within-population predictive accuracy, whereas across-population predictions had accuracies close to zero. This can be explained by our finding that in most cases the accuracy estimates were mostly because of additive genetic relatedness between animals, rather than linkage disequilibrium between SNP and quantitative trait loci. Therefore, our results suggest that genomic prediction for nematode resistance and BW may be of value in closely related animals, but that with the current SNP chip genomic predictions are unlikely to work across breeds.

This study reports a functional characterization of a limited segment (QTL) of sheep chromosome 12 associated with resistance to the abomasal nematode Haemonchus contortus. The first objective was to validate the identified QTL through the comparison of genetically susceptible (N) and resistant (R) sheep produced from Martinik × Romane back-cross sheep. The R and N genotype groups were then experimentally infected with 10 000 H. contortus larvae and measured for FEC (every three days from 18 to 30 days post-challenge), haematocrit, worm burden and fertility. Significant differences in FEC and haematocrit drop were found between R and N sheep. In addition, the female worms recovered from R sheep were less fecund. The second step of the characterization was to investigate functional mechanisms associated with the QTL, thanks to a gene expression analysis performed on the abomasal mucosa and the abomasal lymph node. The gene expression level of a candidate gene lying within the QTL region (PAPP-A2) was measured. In addition, putative interactions between the chromosome segment under study and the top ten differentially expressed genes between resistant MBB and susceptible RMN sheep highlighted in a previous microarray experiment were investigated. We found an induction of Th-2 related cytokine genes expression in the abomasal mucosa of R sheep. Down-regulation of the PAPP-A2 gene expression was observed between naïve and challenged sheep although no differential expression was recorded between challenged R and N sheep. The genotyping of this limited region should contribute to the ability to predict the intrinsic resistance level of sheep.

Chantier qualité GA; This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome-wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half-sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti-Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti-L3, and IgE anti-ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants.

National audience; The sustainability of tropical and extensive temperate farming systems is the key for a balance between the environment (soil, fauna and flora) and animal and plant productions. The restoration or preservation of such a trophic and ecological balance requires the implementation of innovative techniques. It is vain to avoid constraints in animal rearing and wiser to choose animals for their adaptations to these constraints. In this context, gastrointestinal strongyle infections are a major constraint in small ruminants, particularly in the humid tropics. In recent years, the strategy of pest eradication has evolved to a more logical manipulation of hostparasite equilibrium in grazed systems by implementation of various actions. The genetic resistance of small ruminants to gastrointestinal strongyle infections is part of this new approach and plays a major role. The objective of this review was to highlight the contributions of quantitative genetics and genomics to the understanding and exploitation of the differences between individuals for resistance to gastrointestinal strongyle infections. Local breeds are found, in most cases, to be the most resistant and more productive in their environment. Genetic variability exploitable in selection is known in sheep as in goats with a similar genetic control. However, the underlying biological mechanisms are more basic and less efficient in goats. The genomic information accumulates but remains difficult to exploit by professionals.; La durabilité des systèmes d'élevage tropicaux et tempérés extensifs est à rechercher dans l'équilibre entre le milieu et les productions, animales et végétales. Ainsi, il est judicieux de choisir les animaux pour leur adaptation aux contraintes du milieu, plutôt que de chercher à les en soustraire. Dans ce contexte, les strongyloses gastro-intestinales représentent une contrainte pathologique majeure des petits ruminants, particulièrement en zone tropicale humide. Depuis quelques années, la stratégie d'éradication des parasites a évolué vers une logique de manipulation des équilibres hôtes-parasites dans les systèmes pâturés par combinaison de diverses stratégies. La résistance génétique aux strongles gastro-intestinaux s'inscrit dans cette nouvelle démarche et y tient un rôle majeur. L'objectif de cette synthèse est de souligner les apports de la génétique et de la génomique à la compréhension et à l'exploitation de différences entre individus pour la résistance aux strongyloses gastro-intestinales. Les races locales se révèlent dans la plupart des cas les plus résistantes et les plus productives dans leur milieu. Que ce soit chez des races de milieu tropical ou tempéré, une variabilité génétique intra-race a pu être observée chez les ovins et les caprins. Des critères de résistance exploitables en sélection sont connus chez les ovins comme chez les caprins avec un contrôle génétique comparable. Enfin, la composante immunitaire (complexe majeur d'histocompatibilité notamment) de la résistance est clairement impliquée dans les mécanismes. Cependant, du fait de comportements alimentaires différents, les mécanismes sous-jacents pourraient être plus simples et moins efficients chez les caprins. L'information génomique s'accumule mais reste encore difficilement valorisable par les professionnels.

SUMMARY In the past, several studies have been performed to look for genes affecting traits of interest using microsatellite markers in sheep. Even if numerous chromosomal regions have been detected, few genes and causal mutations have been identified. The recent availability of high density SNP chip in sheep is a technological revolution for genomic researches and breeding selection. Firstly, genomic research in small ruminants will be boosted towards the identification of causative mutations underlying large genetic effects on sustainability traits, or the identification of very closely linked genetic markers that allow selecting genes in ovine breeding programmes. Secondly, such new molecular tools allow considering a new type of selection: the genomic selection. The principle of this selection is to use marker effects (without any information about the underlying genes) estimated within a part of the population which is phenotyped and genotyped (called the training population) and applying these effects to the rest of the genotyped population. However, the genomic selection might not always be a profitable strategy in sheep.

National audience

Diffusion du document : ID 787; absent

Agricultural Research ServiceWorld Organisation for Animal Health; absent

Susceptibility to scrapie is mainly controlled by point mutations at the PRNP locus. However, additional quantitative trait loci (QTL) have been identified across the genome including a region in OAR18. The gene which encodes the inducible form of the cytoplasmic Hsp90 chaperone (HSP90AA1) maps within this region and seems to be associated with the resistance/susceptibility to scrapie in sheep. Here, we have analyzed several polymorphisms which were previously described in the ovine HSP90AA1 5' flanking region and in intron 10 in two naturally scrapie infected Romanov sheep populations. First, we have studied 58 ARQ/VRQ animals pertaining to the sire family where the QTL influencing scrapie incubation period in OAR18 was detected. We have found a significant association between polymorphisms localized at -660 and -528 in the HSP90AA1 5' flanking region and the scrapie incubation period. These two polymorphisms have also been studied in a second sample constituted by 62 VRQ/ VRQ sheep showing an extreme incubation period. Results are concordant with the first dataset. Finally, we have studied the HSP90AA1 expression in scrapie and control animals (N=41) with different HSP90AA1 genotypes by real time PCR on blood samples. The HSP90AA1 expression rate was equivalent in CC -600AA-528 and CG-600AG-528 scrapie resistant animals (ARR/ARR) and was higher in their CC-600AA-528 than in their CG-600AG-528 scrapie susceptible counterparts (VRQ/VRQ). Our results support the hypothesis that the ovine HSP90AA1 gene acts as a modulator of scrapie susceptibility, contributing to the observed differences in the incubation period of scrapie infected animals with the same PRNP genotype. © Cell Stress Society International 2009.