Advanced survival models for risk-factor analysis in scrapie

Because of the confounding effects of long incubation duration and flock management, accurate epidemiological studies of scrapie outbreaks are difficult to carry out. In this study, 641 Manech red-faced sheep from six scrapie-affected field flocks in Pyrénées Atlantiques, France, were monitored for clinical scrapie over a 6–9 year period. Over this period, 170 scrapie clinical cases were recorded and half of the culled animals were submitted for post-mortem transmissible spongiform encephalopathy diagnosis to assess their infectious status. Collected data were analysed using a ‘mixture cure model’ approach, which allowed for the discriminating effect of PrP genotype and flock origin on incidence and incubation period. Simulations were performed to evaluate the applicability of such a statistical model to the collected data. As expected, ARR heterozygote sheep were less at risk of becoming infected than ARQ/ARQ individuals and had a greater age at clinical onset. Conversely, when compared with ARQ/ARQ, the VRQ haplotype was associated with an increased infection risk, but not a shorter incubation period. Considering the flock effect, we observed that a high incidence rate was not associated with shorter incubation periods and that the incubation period could be significantly different in flocks harbouring similar infection risks. These results strongly support the conclusion that other parameters, such as the nature of the agent or flock management, could interfere with epidemiological dynamics of the infection in scrapie-affected flocks

La sélection génétique d'ovins résistants aux strongles gastro-intestinaux en France : mythe ou réalité ?

National audienc

Asymptomatic

Protozoan parasites of the Cryptosporidium genus cause severe cryptosporidiosis in newborn lambs. However, asymptomatic infections also occur frequently in lambs and ewes. In sheep, the most commonly detected Cryptosporidium species are C. ubiquitum, C. xiaoi and C. parvum. Due to a lack of relevant information about such infections in France, we investigated the situation on five dairy sheep farms in the Pyrénées-Atlantiques Department in south-western France in December 2017. Individual fecal samples were collected from 79 female lambs (5–17 days old) and their mothers (72 ewes). Oocysts were screened using Heine staining before and after Bailenger concentrations. Cryptosporidium species identification and genotyping were performed using real-time PCR and gp60 gene sequencing. No cases of clinical cryptosporidiosis were observed in the 79 lambs. Microscopically, Cryptosporidium spp. oocysts were observed in only one lamb on one farm (prevalence 1.3%) and one ewe on another farm (prevalence 1.4%). By contrast, Cryptosporidium spp. DNA was detected in 17 ewes (prevalence ranging from 10.5% to 50% depending on the farm) and in 36 lambs (prevalence ranging from 0% to 77.8% depending on the farm). Only zoonotic Cryptosporidium parvum IId and IIa genotypes were identified when genotyping was possible. Cryptosporidium ubiquitum and C. xiaoi were detected on one and three farms, respectively. We conclude that healthy young lambs and their mothers during the peripartum period could be a source of environmental contamination with oocysts

Unfavorable genetic correlations between fecal egg count and milk production traits in the French blond-faced Manech dairy sheep breed

International audienceBackgroundGenetic selection has proven to be a successful strategy for the sustainable control of gastrointestinal parasitism in sheep. However, little is known on the relationship between resistance to parasites and production traits in dairy breeds. In this study, we estimated the heritabilities and genetic correlations for resistance to parasites and milk production traits in the blond-faced Manech breed. The resistance to parasites of 951 rams from the selection scheme was measured through fecal egg counts (FEC) at 30 days post-infection under experimental conditions. Six milk production traits [milk yield (MY), fat yield (FY), protein yield (PY), fat content (FC), protein content (PC) and somatic cell score (LSCS)], were used in this study and were collected on 140,127 dairy ewes in first lactation, as part of the official milk recording. These ewes were related to the 951 rams (65% of the ewes were daughters of the rams).ResultsFecal egg counts at the end of the first and second infections were moderately heritable (0.19 and 0.37, respectively) and highly correlated (0.93). Heritabilities were moderate for milk yields (ranging from 0.24 to 0.29 for MY, FY and PY) and high for FC (0.35) and PC (0.48). MY was negatively correlated with FC and PC (− 0.39 and − 0.45, respectively). FEC at the end of the second infection were positively correlated with MY, FY and PY (0.28, 0.29 and 0.24, respectively with standard errors of ~ 0.10). These slightly unfavorable correlations indicate that the animals with a high production potential are genetically more susceptible to gastrointestinal parasite infections. A low negative correlation (− 0.17) was also found between FEC after the second infection and LSCS, which suggests that there is a small genetic antagonism between resistance to gastrointestinal parasites and resistance to mastitis, which is another important health trait in dairy sheep. ConclusionsOur results indicate an unfavorable but low genetic relationship between resistance to gastrointestinal parasites and milk production traits in the blond-faced Manech breed. These results will help the breeders’ association make decisions about how to include resistance to parasites in the selection objective

Le programme français d'éradication de la tremblante du cheptel ovin fondé sur l'utilisation de la génétique

National audienceStudies carried out since 1993 on scrapie infected flocks, have allowed to describe the frequency of susceptible alleles of the PrP gene in French dairy sheep breeds, to verify the greater risk of susceptible animals, and to test the selection feasibility and efficiency based on PrP genotyping. The idea of using a genetic strategy to eradicate scrapie in infected flocks was born as a result. Since 2002, the programme to eradicate scrapie in French sheep livestock, implemented by the Ministry of Agriculture, is rooted in a genetic strategy based on the genotyping of the PrP gene : its objective is aimed both at eradicating scrapie in infected flocks and reinforcing the resistance of the entire national flock. The fact that it was launched within the framework of the livestock selection organisation, defined in 1966 by a French law, is obviously a key point to explain its efficient and rapid implementation from the starting year. Moreover, it illustrates the mobilisation of all the people in charge of the sheep breeding programmes in France : the jointed evolutions observed for the ARR allelic frequency, the genetic merit for production traits and the maintenance of criteria describing the genetic variability are evidence of a good application of the objectives defined for the breeding programmes. The national supervision, carried out by INRA, the Institut de l’Elevage and France UPRa selection, will set out, in the next years, to reach all the objectives of this national programme, particularly by supplying scrapie infected flocks with resistant sheep, managing the genetic variability of the selection flocks and diffusing resistant germplasm towards the commercial flocks. This plan is based on the following crucial points : resistance of ARR/ARR is universal to natural infections and ARR/ARR sheep are not healthy carriers. It will be necessary to always check these crucial points and include any new scientific knowledge in the breeding programmes.Les travaux conduits en ovins laitiers dès 1993 dans des élevages ovins atteints de tremblante ont permis de connaître la fréquence des allèles sensibles du gène PrP selon les races considérées, vérifier le risque accru de tremblante pour ces génotypes, et tester la faisabilité d’une sélection sur le gène PrP et son efficacité sur le risque de tremblante dans les troupeaux. Ils ont ainsi contribué à l’émergence de l’outil génétique pour éradiquer la tremblante dans les élevages atteints. Depuis 2002, le programme d’éradication de la tremblante mis en place en France par le Ministère de l’Agriculture, est fondé sur le génotypage du gène PrP : il vise à éradiquer à court et moyen terme la tremblante dans les élevages atteints, tout en renforçant la résistance génétique à moyen et long terme de l’ensemble du cheptel national, compte tenu des délais de renouvellement des cheptels femelles. Avoir choisi d’asseoir le programme national de sélection sur le dispositif existant d’amélioration génétique du cheptel national, organisé dans le cadre de la loi de l’Elevage de 1966, est manifestement un point clé pour expliquer la mise en oeuvre rapide et efficace du programme dès la première année, confirmant la mobilisation massive de tous les maîtres d’oeuvre des schémas de sélection des ovins en France : les évolutions conjointes constatées pour les fréquences alléliques en faveur de l’allèle ARR, les index de sélection pour les caractères de production et les indicateurs de gestion de la variabilité génétique sont une bonne illustration de l’application des objectifs assignés aux programmes de sélection. L’encadrement national, conduit par l’INRA, l’Institut de l’Elevage et France UPRa Sélection (Unité de Promotion et de sélection de Race), s’attachera, dans les prochaines années, à vérifier et à aider à la mise en oeuvre des quatre objectifs du programme national de sélection, en particulier la fourniture de reproducteurs résistants pour les élevages atteints, la gestion de la variabilité génétique dans les noyaux de sélection et la diffusion vers les élevages de production. Ce programme repose sur les points clés d’universalité de la résistance génétique à la tremblante en situation de contamination naturelle et d’absence de porteurs sains, qu’il faudra en permanence continuer de valider

Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability

Abstract Background Recessive deleterious variants are known to segregate in livestock populations, as in humans, and some may be lethal in the homozygous state. Results We used phased 50 k single nucleotide polymorphism (SNP) genotypes and pedigree data to scan the genome of 6845 Manech Tête Rousse dairy sheep to search for deficiency in homozygous haplotypes (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 Ovis aries chromosome (OAR)1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5), and OAR20 (MTRDHH1), and have carrier frequencies ranging from 7.8 to 16.6%. When comparing at-risk matings between DHH carriers to safe matings between non-carriers, two DHH (MTRDHH1 and 2) were linked with decreased insemination success and/or increased stillbirth incidence. We investigated the MTRDHH1 haplotype, which substantially increased stillbirth rate, and identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in the methylmalonyl-CoA mutase (MMUT) gene by using a whole-genome sequencing approach. We generated homozygous lambs for the MMUT mutation by at-risk mating between heterozygous carriers, and most of them died within the first 24 h after birth without any obvious clinical symptoms. Reverse transcriptase-qPCR and western blotting on post-mortem liver and kidney biological samples showed a decreased expression of MMUT mRNA in the liver and absence of a full-length MMUT protein in the mutant homozygous lambs. Conclusions We identified five homozygous deficient haplotypes that are likely to harbor five independent deleterious recessive variants in sheep. One of these was detected in the MMUT gene, which is associated with lamb lethality in the homozygous state. A specific management of these haplotypes/variants in the MTR dairy sheep selection program would help enhance the overall fertility and lamb survival

Additional file 1 of Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability

Additional file 1: Figure S1. Distribution of genotyped animals over time. The bar charts represent the number of genotyped animals according to sex and year of birth. The genomic selection in MTR dairy sheep was implemented in 2017