[Show abstract][Hide abstract] ABSTRACT: Although susceptibility to scrapie is largely controlled by the PRNP gene, we have searched for additional genomic regions that affect scrapie incubation time in sheep, using two half-sib families with a susceptible PRNP genotype and naturally infected by scrapie. Quantitative trait loci were detected on OAR6 and OAR18.
[Show abstract][Hide abstract] ABSTRACT: The cytogenetic study of 413 Romanov sheep (170 males and 243 females) revealed the presence of a rare fragile site located on chromosome 8 in some cells from 149 animals (86 females and 63 males). The frequency of cells expressing fragility varied from 1 to 40% in different animals. Family studies showed that the fragile site has a Mendelian codominant mode of inheritance, and that the viability of homozygous and heterorygous carrier embryos is similar to that of normal embryos.
Zytogenetische Untersuchungen einer Herde von 413 Romanov-Schafen (170 männliche und 243 weibliche Tiere) haben die Anwesenheit einer seltenen Schnittstelle auf dem Chromosom 8 gezeigt. Diese war in einigen Zellen von 149 Tieren (86 weibliche und 63 männliche) vorhanden. Die Frequenz der Zellen, die diese Fragilität aufweisen, variierte rwischen 1 und 40% in den verschiedenen Tieren. Familienanalysen haben gezeigt, daβ sich die Schnittstelle nach Mendel in kodominanter Weise vererbt und daβ die Lebensfähigkeit der homozygoten und heterozygoten Embryonen zu derjenigen normaler Tiere ähnlich ist.
No preview · Article · Oct 2007 · Reproduction in Domestic Animals
[Show abstract][Hide abstract] ABSTRACT: Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.
[Show abstract][Hide abstract] ABSTRACT: Presence of scrapie infectivity in the placenta suggests the possibility of increased transmission of scrapie during the lambing season. This hypothesis was explored here using a mathematical model of scrapie transmission dynamics which has previously been successfully used to study several scrapie outbreaks in Scottish sheep flocks. It was applied here to the Langlade experimental sheep flock (INRA Toulouse, France), in which a natural scrapie epidemic started in 1993. Extensive data were available, including pedigree, scrapie histopathological diagnoses and PrP genotypes. Detailed simulations of the scrapie outbreak reveal that the observed patterns of seasonality in incidence can not be accounted for by seasonality in demography alone and provide strong support for the hypothesis of increased transmission during lambing. Observations from several other scrapie outbreaks also showing seasonal incidence patterns support these conclusions.
Full-text · Article · May 2006 · Archives of Virology
[Show abstract][Hide abstract] ABSTRACT: Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTR of the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and miR-206 that are highly expressed in skeletal muscle. This causes the down-regulation of this muscle-specific chalone and hence contributes to the muscular hypertrophy of Texel sheep. We demonstrate that polymorphisms which alter the content of putative miRNA target sites are common in human and mice, and provide evidence that both conserved and nonconserved target sites are selectively constrained. We speculate that these polymorphisms might be important mediators of phenotypic variation including disease. To facilitate studies along those lines, we have constructed a database (www.patrocles.org) listing putative polymorphic microRNA-target interactions.
Full-text · Article · Feb 2006 · Cold Spring Harbor Symposia on Quantitative Biology
[Show abstract][Hide abstract] ABSTRACT: Five different sheep flocks with natural outbreaks of scrapie were examined to determine associations between individual performance (lifetime breeding success, litter size and survival) and scrapie infection or PrP genotype. Despite different breed composition and forces of infection, consistent patterns were found among the flocks. Regardless of the flock, scrapie-infected sheep produced on average 34 % fewer offspring than non-scrapie-infected sheep. The effect of scrapie on lifetime breeding success appears to be a function of lifespan as opposed to fecundity. Analysis of litter size revealed no overall or genotype differences among the five sheep flocks. Survival, however, depends on the individual's scrapie status (infected or not) and its PrP genotype. Susceptible genotypes appear to perform less well in lifetime breeding success and life expectancy even if they are never affected with clinical scrapie. One possible explanation for these results is the effect of pre-clinical scrapie. Additional evidence supporting this hypothesis is discussed.
Full-text · Article · May 2005 · Journal of General Virology
[Show abstract][Hide abstract] ABSTRACT: A QTL for muscle hypertrophy has been identified in the Belgian Texel breed. A population of F2 and backcross lambs created from crosses of Belgian Texel rams with Romanov ewes was studied. Effects on carcass traits and muscle development of the Belgian Texel breed polygenes and Belgian Texel single QTL were compared. In both cases, carcass conformation and muscularity were improved. The Texel polygenic environment improved conformation mainly through changes in skeletal frame shape. Segments were shorter and bone weight lower. Muscles were more compact, shorter, and thicker. The single QTL affected muscle development. Thickness and weight of muscles were increased. Composition in myosin changed toward an increase of fast contractile type. The relative contribution of hind limb joint to carcass weight was increased. Differences in skeletal frame morphology among the three genotypes of the single QTL were small. Conformation scoring was mainly influenced by leg muscularity. Back and shoulder muscle development, which largely contributed to variability of muscularity, were less involved in the conformation scoring. Lastly, the QTL explains a small part of differences between these Belgian Texel and Romanov breeds for conformation or muscle development. A large part of genetic variability remains to be explored.
No preview · Article · Dec 2004 · Journal of Animal Science
[Show abstract][Hide abstract] ABSTRACT: To demonstrate the possible role of nematode parasites in the modification of host susceptibility to scrapie, experiments were conducted using sheep naturally exposed to scrapie, chosen by their genotype at the PrP gene, and infected with Teladorsagia circumcincta. Two 4-year duration experiments demonstrated that the nematode infection shortened the development of scrapie with a significant regression between the level of infection and age at first scrapie symptoms (P < 0.006). Investigations by ELISA tests in different species of nematode parasites of the digestive tract collected from scrapie infected ewes did not reveal the presence of PrPSc. In scrapie-infected C57BL mice, infected or not with Heligmosoides polygyrus at various times, parasitized animals showed a slight but significantly longer survival period. Assays on transmission by the larvae hatching from eggs collected from scrapie-infected mice were unsuccessful. We concluded that nematodes modify host susceptibility to scrapie, but their role in the horizontal transmission of the disease was not demonstrated.
No preview · Article · Aug 2004 · Parasitology Research
[Show abstract][Hide abstract] ABSTRACT: Because variant Creutzfeldt-Jakob disease (vCJD) in humans probably results from consumption of products contaminated with tissue from animals with bovine spongiform encephalopathy, whether infectious prion protein is present in ruminant muscles is a crucial question. Here we show that experimentally and naturally scrapie-affected sheep accumulate the prion protein PrP(Sc) in a myocyte subset. In naturally infected sheep, PrP(Sc) is detectable in muscle several months before clinical disease onset. The relative amounts of PrP(Sc) suggest a 5,000-fold lower infectivity for muscle as compared to brain.
[Show abstract][Hide abstract] ABSTRACT: This experiment was conducted to assess the efficiency of selection on the basis of response to artificial challenges in order to breed sheep resistant to natural infection. A short-term divergent selection process was designed to estimate the genetic parameters of these two traits. Two flocks, including 100 Romanov ram lambs each, were challenged in 1990 when they were 6 months old. One flock received three artificial infections with 20 000 third-stage Teladorsagia circumcincta larvae, at intervals of 7 weeks. Faecal egg counts (FEC) were performed on Days 22, 25 and 28 post infection (p.i.) and the animals were drenched on Day 28 p.i. The other flock was grazed for 5 months on a pasture contaminated with the same species. Faecal samples were taken from the lambs at similar ages. About 5 rams with the lowest FEC and 5 with the highest FEC were selected in each flock and mated with unselected ewes. Their offspring (200 animals) were challenged in 1992, half in the same way as their sires, and the other half by the other method. Because of a drought in the summer of 1990, it was necessary to repeat part of the experiment, and in 1992 the 5 and 8 rams with the lowest and highest FEC, respectively, were selected from the offspring challenged on the pasture in 1992 and were mated with unselected ewes. Their progeny (about 80 animals) were challenged in 1994, half by natural infection, half by artificial infection. The mean FEC of the flock increased from the first to the third artificial infection. The natural infection was highly variable in different years, reflecting the difficulty of assessing resistance using this mode of challenge. Genetic parameters were estimated using animal models and REML solutions. The repeatabilities of the FEC following artificial and natural infection were 0.49 and 0.70 respectively within a period of one week, and 0.22 and 0.41 respectively for periods separated by intervals of 7 weeks; the heritabilities of the single egg count were 0.22 and 0.38 respectively. The genetic correlation was 0.87: the FEC recorded under natural or artificial infection appear to depend on the same genetic potential.
Preview · Article · Mar 2004 · Genetics Selection Evolution
[Show abstract][Hide abstract] ABSTRACT: The investments at INRA for the study of transmissible spongiform encephalopathy (TSE) in animal populations, on farms or in experimental conditions are described: a large scale PrP gene genotyping laboratory, the experimental farm of Langlade where sheep submitted to natural scrapie are followed, an important protected animal building (Installations Nationales Protégées pour l'étude des Encéphalopathies Spongiformes Transmissibles "INPREST") for large farm animals, the sheep house of the Toulouse National Veterinary School (ENVT), the protected rodent buildings on the INRA sites of Nouzilly and Jouy-en-Josas and Toulouse (ENVT). All these investments give scientists the means necessary to carry out their investigations on the physiopathology of animal TSE, the genetic determinants of the sensitivity/ resistance of these pathologies, the nature of the pathogenic agent and notably its variability as well as the evaluation of risks and the diagnostic.
[Show abstract][Hide abstract] ABSTRACT: The diagnosis of transmissible spongiform encephalopathies (TSE) in ruminants relies on the detection of PrPres, the proteinase K (PK)-resistant pathological isoform of the prion protein. The latter can be detected in situ by immuno-histochemical methods, or by immunological methods following extraction from tissues and PK treatment (Western-blot, Enzyme Linked ImmunoSorbent Assay). Although considerable progress has been made in recent years in routine TSE diagnosis, it remains a post-mortem detection that is only possible in brain tissues from adult animals in which sufficient amounts of PrPres have accumulated. Tonsil biopsies allow an ante-mortem diagnosis only in animals whose lymphoid tissues contain PrPres, i.e. sheep of susceptible genotypes and goats. Other methods are currently being explored : these are aimed at detecting in the blood either PrPres or a marker specifically expressed during the incubation period. In addition, a search is currently under way for tests that could distinguish strains of TSE, or specifically recognise the bovine spongiform encephalopathy strain. Such improvements should represent a considerable progress towards a better understanding of TSE transmission and epidemiology, which in turn may help in defining new prevention strategies.
[Show abstract][Hide abstract] ABSTRACT: Among Transmissible Spongiform Encephalopathies (TSE), scrapie in sheep represents a model of natural infection, which is characterised by a panel of diverse strains of the prion, by the major role played by genetic determinants controlling sensibility and susceptibility, and by a frequent inter-individual transmission. Contamination occur mainly by the oral route. In genetically predisposed animals (PrP VRQ/VRQ) (the first clinical signs are detected between 20 and 24 months), the PrPsc protein has been detected in the ileal Peyer patches as early as the 21st day of age. Most of the secondary lymphoid structures become contaminated after 3 to 6 months. In the lymphoid tissues, PrPsc accumulates first in CD68+ cells (dendritic cells or macrophages), then in follicular dendritic cells. From the myenteric nervous plexus, PrPsc may reach the central nervous system via sympathetic and parasympathetic nerves. Schwann cells may be at play during this transfer. Spinal cord invasion begins at about the age of 9 to 10 months, in the dorsal node of the vagus nerve, and the T4-T9 medullary segments. From the lymphoid and nervous organs, PrPsc contaminates other tissues, in particular the placenta and the muscles. The mode of dissemination, through the blood stream or nervous tissue, remains evasive. In the placenta of infected ewes, PrPsc accumulation in the trophoblast cells is controlled by the genotype of the fetus. In the muscles, during the incubation and clinical phases, PrPsc can be detected in particular structures, the neuromuscular tubes, at concentrations which are 5000-fold lower than those measured in the obex of clinically affected animals. For scrapie, these data (sites of replication, kinetics) are strongly related to the PrP genotype of the host and probably to the prion strain. Generalisation to other animal or human situations should be cautious.
[Show abstract][Hide abstract] ABSTRACT: Placentas from scrapie-affected ewes are known to be infectious. Nevertheless, placenta infectivity in such ewes is not systematic. Maternal transmission to lambs is highly suspected but contamination of the foetus in utero has not been demonstrated. Using ewes from a naturally scrapie-infected flock, it was demonstrated that abnormal prion protein (PrP(Sc)) accumulation in the placenta (i) is controlled by polymorphisms at codons 136, 154 and 171 of the foetal PrP gene and (ii) is restricted mainly to placentome foetal trophoblastic cells. In order to go deeper into the role of the placenta in scrapie transmission, the pattern of PrP(Sc) dissemination was established in susceptible lambs (genotype VRQ/VRQ) sampled from 140 days post-insemination to the age of 4 months from either VRQ/VRQ ewes with PrP(Sc)-positive placentas or ARR/VRQ ewes with PrP(Sc)-negative placentas. In both VRQ/VRQ lamb groups, PrP(Sc) spatial and temporal accumulation patterns were similar, suggesting post-natal rather than in utero contamination.
Preview · Article · Nov 2002 · Journal of General Virology
[Show abstract][Hide abstract] ABSTRACT: Inheritance of the ovulation rate (OR) in the Lacaune meat breed was studied through records from a small nucleus of 36 hyper-prolific ewes screened on farms on the basis of their natural litter size, and from progeny data of three selected Lacaune sires. These sires were chosen at the AI centre according to their breeding values estimated for the mean and the variability of their daughters' litter size. Non-carrier Lacaune dairy ewes were inseminated to produce 121 F1 daughters and 27 F1 sons. Twelve sons (four from each sire) were used in turn to inseminate non-carrier Lacaune dairy ewes providing 260 BC progeny ewes. F1 and BC progeny were brought from private farms and gathered after weaning on an experimental farm where ovulation rates were recorded in the first and second breeding seasons. With an average of 6.5 records each, the mean OR of hyper-prolific ewes was very high (5.34), and 38.4% of records showed a rate of 6 or more. F1 data showed high repeatability of OR (r = 0.54) within ewe, with significant variability among ewes. High OR (> or = 4) were observed in each family. A segregation analysis provided a significant likelihood ratio and classified the three founders as heterozygous. BC ewes also displayed high repeatability of OR (r = 0.47) and the mean OR varied considerably between families (from 1.24 to 1.78). Seven of the 12 BC families presented high-ovulating ewes (at least one record > or = 4) and segregation analysis yielded a highly significant likelihood ratio as compared to an empirical test distribution. The high variability of the mean ovulation rate shown by a small group of daughters of BC ewes inseminated by putative carrier F1 rams, and the very high ovulation rate observed for some of these ewe lambs, confirmed the segregation of a major gene with two co-dominant alleles borne by an autosome. The difference between homozygous non-carriers and heterozygous ewes was about one ovulation on the observed scale and 2.2 standard deviations on the underlying scale.
[Show abstract][Hide abstract] ABSTRACT: Carcass conformation or morphology in sheep is an important trait for breeders, farmers and meat traders. The commercial value of carcasses is partially based on visual assessment of conformation. This trait is often subject to controversy because of its subjectivity and its weak relationship to muscle yield. The aims of this report are to present results on the biological significance of conformation and to evaluate the reliability of conformation assessment for the genetic improvement of butcher's qualities. This report is a synthesis of three independent studies, each based on the comparison of two genetic types, one with a good conformation and the other with a worse conformation. Conformation reflects muscle morphology, especially muscle deepness which is an important trait when retail products are whole carcasses or joints. Modification of individual muscle thickness is differential according to anatomical location. Conformation improvement increases carcass yield and muscle yield. Muscle to bone ratio is also increased, corresponding to a reduction of bone percentage and sometimes to an increase of muscle percentage. Often, individual muscle weights showed differential repartition on carcass segments. Fatness is not increased. Muscle thickness increase is related to a switch of contractile traits to fast myosin isoforms. These studies have shown that some modifications of biological features are rather related to breed characteristics than to a better conformation.
No preview · Article · Feb 2002 · Productions Animales -Paris- Institut National de la Recherche Agronomique-
[Show abstract][Hide abstract] ABSTRACT: Information from a scrapie epidemic in a closed INRA Romanov flock is presented. Performances, pedigree, histopathological diagnoses and PrP genotypes were recorded from the beginning of the outbreak (in 1993). Between 1st of April, 1993 and 1st of May, 1997, 1015 animals were exposed to scrapie, and 304 died from this disease. A major influence of the polymorphisms at codons 136, 154 and 171 is shown, A136H154Q171 allele carriers proving to be nearly as resistant as A136R154R171 carriers. A possible relationship between gastrointestinal parasitism and scrapie is discussed. There is evidence of maternal transmission, with a risk ratio for artificially fed lambs of 67 percent of the risk of lambs fed by their mother. Our results strongly suggest that resistant animals were not healthy carriers or at least were less infectious when comparing risk for lambs born to healthy dams either of resistant (risk = 0.431) or of susceptible (risk = 1.000) genotype.
No preview · Article · Feb 1999 · Archives of Virology
[Show abstract][Hide abstract] ABSTRACT: In several species (man, mouse, sheep), the susceptibility to transmissible subacute spongiform encephalopathies is highly regulated by the host genotype. A major part of the observed genetic variability depends on one gene. This gene is likely the Prn-p gene, which codes for the host prion protein PrP. According to an hypothesis supported by several authors, this protein could be the causal agent of these diseases or it could be associated with the causal agent. Molecular analysis of the structure of the Prn-p gene in sheep demonstrates segregating alleles that differ from each other by a single mutation. It could be interesting, therefore, to examine the possibility of controlling scrapie in sheep by selective breeding on the basis of laboratory analyses of the Prn-p gene polymorphism. Before selecting against this susceptibility, however, different questions need to be answered: Could resistant animals act as a source of infection? Could animals resistant to one scrapie strain be susceptible to another? How expensive would such a selection scheme be? How should the selection be organised in practice?