首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 31 毫秒
1.
The susceptibility of sheep to scrapie is under the control of the host’s prion protein (PrP) gene and is also influenced by the strain of the agent. PrP polymorphisms at codons 136 (A/V), 154 (R/H) and 171 (Q/R/H) are the main determinants of susceptibility/resistance of sheep to classical scrapie. They are combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programmes have been undertaken on this basis in the European Union and the USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report the results of a multi-flock study showing the protective effect of polymorphisms other than those at codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 378 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the PrP gene. The distribution of variations other than those at the standard three codons, between scrapie cases and negative controls, was statistically different in all flocks. In particular, the AT137RQ and ARQK176 alleles showed a clear protective effect. This is the first study demonstrating a protective influence of alleles other than ARR under field conditions. If further investigations in other sheep breeds and with other scrapie sources confirm these findings, the availability of various protective alleles in breeding programmes of sheep for scrapie resistance could be useful in breeds with a low frequency of the ARR allele and would allow maintaining a wider variability of the PrP gene.  相似文献   

2.
There have been no reports of natural scrapie in Irish Blackface Mountain (BM) sheep which account for approximately 16% of the Irish national sheep flock. The aim of this study was to determine if Irish BM sheep had unusual clinical and/or pathological features of scrapie which would account for failure to diagnose the disease in this breed. BM (n=7), Texel (n=3) and Suffolk sheep (n=1) of scrapie-susceptible PrP genotypes (ARQ/ARQ and VRQ/ARQ) were orally challenged with scrapie-infected brain inoculum. The incubation period, clinical signs, pathology and distribution of disease specific prion protein (PrP(d)) in scrapie-affected BM sheep were similar to scrapie in the Texel and Suffolk sheep. It was concluded that there was no evidence to suggest that scrapie in BM sheep differs clinicopathologically from scrapie in other breeds of sheep.  相似文献   

3.
Nor98 is an atypical scrapie strain characterized by a molecular pattern and brain distribution of the pathological prion protein (PrPSc) different from classical scrapie. In Italy, 69 atypical cases have been identified so far and all were characterized as Nor98 strain. In this paper we report an unusual case in a sheep which showed immunohistochemical and molecular features of PrPSc different from the other atypical cases. The sheep was from an outbreak where the index and the other four cases were affected by classical scrapie. Histopathological, immunohistochemical and Western blot analyses on the brain of the unusual case revealed the simultaneous presence of pathological features characteristic of Nor98 and classical scrapie. Interestingly, the prevalent disease phenotype in the brainstem was classical scrapie-like, while in the cerebral cortex and cerebellum the Nor98 phenotype was dominant. The sub-mandibular lymph node was positive and showed a PrPSc molecular pattern referable to classical scrapie. The PrP genotype was AL141RQ/AF141RQ. Taken together, the occurrence of classical scrapie in the outbreak, the PrP genotype, the involvement of different cellular targets in the brain and the pathological and molecular PrPSc features observed suggest that this unusual case may result from the co-existence of Nor98 and classical scrapie.  相似文献   

4.
Within the framework of the active surveillance for transmissible spongiform encephalopathies in sheep in Sweden, 4 cases of the atypical form of scrapie, Nor98, were identified during 2003. Nor98 is a recently recognized and poorly understood variant of scrapie, first described in Norway. The cases were positive by the rapid test (enzyme-linked immunosorbent assay). Immunohistochemical staining showed diffuse thin-granular staining of the cerebellar cortex. Western immunoblotting analysis of specimens of brain stem and cerebellum showed a light band of approximately 12 kDa. Typical scrapie was ruled out based on the confirmatory testing. The affected ewes were from 4 different flocks. They were between 7 and 9 years old. Two were of the ARQ/ARQ genotype, 1 ARR/ARQ, and 1 ARR/AHQ. Two ewes had shown ataxia, and the other 2 had no clinical signs. Whole-flock slaughter was applied, and testing of the flock mates did not reveal additional cases. Nor98 differs from typical scrapie in its epidemiology, frequency of genotypes of sheep affected, clinical signs, microscopic lesions, distribution of scrapie prion protein in the brain, and characteristics of the immunostaining and immunoblotting profiles.  相似文献   

5.
The frequencies of prion protein (PrP) genotypes were investigated in 15 scrapie-affected flocks in Great Britain. The flocks were heterogeneous in the frequencies of different genotypes and alleles, and in their age distributions. The median flock frequency of animals with VRQ-containing genotypes was 21 per cent (range 2 to 82 per cent, mean 25 per cent). The VRQ-containing and other non-ARR genotypes made up 11 to 82 per cent of a flock (median 46 per cent, mean 48 per cent). In comparison with data from the general population the scrapie-affected population had a lower frequency of the ARR/ARR genotype, and so of the ARR allele, and had a higher frequency of VRQ/non-ARR heterozygote genotypes, and thus of the VRQ allele.  相似文献   

6.
Between October 2001 and January 2003 the prion protein (PrP) genotypes of over 250,000 sheep were determined through the operation of the National Scrapie Plan (NSP); the results for 38 breeds were analysed to provide an estimate of the underlying PrP genotype distribution of the British sheep population. Although there was marked variability among the genotype profiles of the different breeds, several trends emerged. A comparison of the allele frequencies demonstrated that the breeds could be grouped into three categories: breeds dominated by ARR and ARQ in which the frequency of ARR exceeded the frequency of ARQ; breeds dominated by ARR and ARQ in which the frequency of ARQ exceeded the frequency of ARR; and breeds with significant levels of either AHQ, ARH or VRQ. Hill breeds were more likely to have a lower proportion of animals at low risk of scrapie (NSP type 1) and a higher proportion of animals at an intermediate risk of scrapie (NSP type 3) than other breeds. Most breeds had a small proportion of animals at high risk of scrapie (NSP type 5). The frequency of ARR/VRQ (NSP type 4) was variable.  相似文献   

7.
In sheep, susceptibility to scrapie is mainly determined by codons 136, 154, and 171 of the PRNP gene. Five haplotypes are usually present (ARR, ARQ, ARH, AHQ, and VRQ). The ARR haplotype confers the greatest resistance to classical scrapie while VRQ renders animals most susceptible. In 2004, the European Union implemented a breeding program that promotes selection of the ARR haplotype while reducing the incidence of VRQ. From 2006 to 2011 in Belgium, frequency for the ARR/ARR genotypes increased from 38.3% to 63.8% (n = 6,437), the ARQ haplotype diminished from 21.1% to 12.9%, and the VRQ haplotype decreased from 2.0% to 1.7%. The status of codon 141, a determinant for atypical scrapie, was also evaluated. Out of 27 different breeds (n = 5,163), nine were abundant. The ARR/ARR frequency increased in eight of these nine major breeds. The selection program has had a major impact on the ARR haplotype frequency in Belgium. However, the occurrence of atypical scrapie represents a critical point for this program that warrants the continuous monitoring of scrapie. Additionally, genotype frequencies among the breeds varied greatly. Texel, a breed that is common in Belgium, can still be selected for due to its average ARR frequency.  相似文献   

8.
Two new PCR-based methods were developed to decode prion protein (PrP) gene polymorphisms at codons 136, 154 and 171: a PCR-restriction fragment length polymorphism (RFLP) analysis consisting of two PCR reactions followed by three enzymatic digestions, and a real-time PCR consisting of four reactions with seven fluorogenic probes. Both methods were used to study the distribution of PrP gene polymorphisms in a representative sample (1297 animals) of the populations of the two native breeds of sheep of the Spanish Basque Country, Latxa and Carranzana. Fourteen genotypes were found in the Latxa breed, in which ARQ/ARQ was the genotype most frequently observed (49.3 per cent), followed by ARR/ARQ (32.6 per cent) and ARQ/ARH (5.8 per cent). The genotype associated with the highest resistance to scrapie (ARR/ARR) was present in 5 per cent of the animals analysed. Similar results were observed in the Carranzana sheep.  相似文献   

9.
Prion protein (PrP) genotype data from statutory confirmed cases and from three non-case datasets have been used to calculate the odds ratio (or) for the development of clinical scrapie for an individual sheep of a given PrP genotype, compared with one possessing the "wild-type" ARQ/ARQ genotype. Logistic regression has been used to estimate the ors, and a multiple-test procedure has been used to evaluate the statistical significance of each comparison. The results are similar to those observed in other studies: the VRQ/VRQ genotype has or point estimates greater than 20; the ARQ/VRQ and ARH/VRQ genotypes have or point estimates between 5 and 20; AHQ/VRQ between 0.03 and 0.1; ARR/VRQ 0.4 and 0.5; all the other PrP genotypes, excluding ARR/ARR, ARR/ARH and AHQ/ARH for which no clinical cases have been recorded have or point estimates of less than 0.3. The estimates derived from each dataset are comparable, but not identical. This can be explained by plausible biases inherent in the sampling of the non-case populations.  相似文献   

10.
OBJECTIVE: To characterize an outbreak of valine-associated scrapie, assess the relative risk of scrapie infection in relation to allele frequency at codon 136, and investigate lateral transmission of infection in a sheep flock within the United States. ANIMALS: 1,006 sheep. PROCEDURE: To determine genotypes, blood or semen samples were assessed via commercial testing; in 190 slaughtered sheep, scrapie status was determined via immunohistochemical evaluation of tissues. Scrapie-positive sheep born to scrapie-negative dams and sheep infected after 1 year of age were identified to assess lateral transmission. RESULTS: Genotypes were determined for codon 171 (164 sheep) or codons 136 and 171 (842 sheep). Forty-four of 160 slaughtered sheep of known genotype were scrapie positive. In these sheep, the presence of at least 1 valine allele at codon 136 (V136) was highly correlated with scrapie-positive status. Lateral transmission was the probable source of infection for 4 scrapie-positive sheep born to scrapie-negative dams and for 11 sheep in which scrapie was diagnosed at > 50 months of age. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the outbreak of scrapie was associated with a relatively high frequency of V136 in the flock, introduction of a valine-dependent scrapie strain, and the occurrence of lateral transmission. Genotyping of sheep may assist management decisions following diagnosis of scrapie in a sheep with at least 1 V136. It may be prudent to remove sheep of the diploid genotype AVQR (at codons 136 and 171) from infected flocks.  相似文献   

11.
The Cheviot flock at the Institute for Animal Health's Neuropathogenesis Unit (npu) has endemic scrapie, which affects primarily vrq/vrq sheep and at high frequency. A new flock with a full range of PrP genotypes, including the highly susceptible vrq/vrq, has been produced on a separate site, from animals in the npu breeding flock, and it remains scrapie-free after eight years. In contrast, in a parallel flock at the npu farm, scrapie has reappeared after five years, although the animals were kept in separate accommodation from the scrapie-affected sheep. During this time the npu breeding flock continued to have scrapie cases. Although it is known that highly susceptible sheep can remain free of infection in a clean environment, this is the first report of the infection being removed successfully from the bloodlines of scrapie-affected sheep. The results confirm that scrapie is not a genetic disease dependent only on the PrP gene sequence, but requires both genetic susceptibility and an infectious agent.  相似文献   

12.
Our aim was to compare the efficiency of different surveillance strategies for detecting scrapie-infected sheep flocks in the Norwegian population using simulation modelling.The dynamic Monte Carlo simulation model has the flock as the unit. The input parameters include properties of the sheep population (number of flocks, flock size, age distribution, reasons for culling, breeds, prion protein-allele distribution); properties of scrapie (genotype-dependent infection rate and incubation periods, and age- and genotype-dependent prevalence of scrapie); properties of the surveillance strategy (selection of sheep for examination, period in which infected sheep are detectable, and properties of the diagnostic tests). For simplification, the prion protein-alleles were grouped into three allele groups: VRQ, ARR, and ARQ' (ARQ' represents ARQ, ARH and AHQ).Through either abattoir surveillance or surveillance of fallen stock, 70% of the detected sheep (compared to 33% in the underlying population). The model output was sensitive to the susceptibility of infection for the genotype ARQ'/ARQ'. The effect was large for abattoir surveillance (increased susceptibility increased the efficiency of abattoir surveillance).  相似文献   

13.
ABSTRACT: Total number and genotypes of animals in holdings selected for the genotype & cull option in the Compulsory Scrapie Flock Scheme (CSFS) in Great Britain were extracted from the National Scrapie Plan data warehouse. The association between various genotype-related measures and scrapie prevalence infection was tested using zero-inflated negative binomial models with the counts of positive cases as dependent variable, and country, number of flocks in the scheme, flock size, surveillance source and the following genotype-related measurements: the centered-log ratios (clr) oof the 15 genotypes, of the proportions of the 5 alleles at codons 136, 154 and 171, of the proportions of the 5 NSP types, and two flock-susceptibility risk indicators, as explanatory variables. A total of 319341 genotyped animals from 168 holdings were included in the analysis. An increased proportion of the ARR/ARR genotype corresponded to a decrease in the number of scrapie cases. ARR/AHQ, AHQ/VRQ, ARH/VRQ and ARQ/VRQ genotypes, NSP type V, ARH, ARQ, AHQ and VRQ alleles and the low and high-susceptibility risk indicators are all associated with an increase risk in the number of scrapie cases.Regardless the management practices; the increased susceptibility that the non-ARR alleles confer on an individual could be extrapolated at the population level. Increasing prevalence of ARR allele reduces the overall risk of scrapie at population level. At genotype level, the VRQ/VRQ genotype, present a very low frequency in the study population, seems to play a residual effect in the overall risk of scrapie in a flock.  相似文献   

14.
Since scrapie and bovine spongiform encephalopathy (BSE) in sheep are clinicopathologically indistinguishable, BSE in sheep may have been misdiagnosed as scrapie. Disease-specific prion protein (PrP(d)) patterns in archival tissues of 38 Irish ARQ/ARQ sheep diagnosed as scrapie-affected were compared to those in four Dutch BSE-challenged sheep. When medulla oblongata was immunolabelled with an antibody directed against amino acids 93-99 of ovine prion protein (ovPrP), intraneuronal PrP(d) was apparent in all 38 Irish sheep but was absent in BSE-challenged sheep. When lymphoid follicles were immunolabelled with antibodies directed against amino acids 93-106 of ovPrP, granule clusters of PrP(d) were seen in 34 of the 38 Irish sheep. Follicles of the remaining four archive sheep contained either no PrP(d) or single PrP(d) granules, similar to follicles from BSE-challenged sheep. Based on the medulla results, none of the archival cases had BSE-derived disease. The identification of some scrapie sheep with little or no intrafollicular PrP(d) suggests that this technique may be limited in discriminating between the two diseases.  相似文献   

15.
The allele and genotype frequencies of the prion protein gene (PrP), known to have an impact on scrapie susceptibility, were determined by real-time PCR for 500 Quebec purebred rams. Molecular beacons were very efficient in discriminating the 5 alleles investigated. Polymorphisms at coding positions 136, 154, and 171 of the PrP gene were analyzed using 3 separate real-time PCR reactions and a total of 7 molecular beacons. A total of 4 different alleles (ARQ, ARR, AHR, and VRQ) were observed at different frequencies among the 7 breeds of sheep investigated. Results show that more than 50% of the rams in every breed carried at least one ARR allele, which is considered the most resistant to scrapie. The susceptibility ARQ allele was also present in every breed and together with the ARR allele, they were the most frequent alleles found in Quebec rams. The VRQ allele associated with the highest susceptibility to scrapie occurred in 5 of the 7 breeds, although at low frequencies. Overall, the results indicate that the frequencies of PrP alleles and genotypes in common breeds of sheep in Quebec make it feasible to reduce scrapie risk by selective breeding.  相似文献   

16.
AIMS: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) from non-infected and infected sheep of different PrP genotypes.

METHODS: Using published data on the distribution of PrP genotypes within the New Zealand sheep flock and the prevalence of cases of scrapie in these genotypes in the United Kingdom, the annual expected number of cases of scrapie per genotype was estimated, should scrapie become established in New Zealand, assuming a total population of 28 million sheep. A non-infected panel of RLN was collected from 737 sheep from New Zealand that had been culled, found in extremis or died. Brain stem samples were also collected from 131 of these sheep. A second panel of infected samples comprised 218 and 117 RLN from confirmed scrapie cases that had originated in Europe and the United States of America, respectively. All samples were screened using two commercial, rapid, transmissible spongiform encephalopathy ELISA kits: Bio-Rad TeSeE ELISA (ELISA-BR), and IDEXX HerdChek BSE-Scrapie AG Test (ELISA-ID).

RESULTS: If scrapie became established in New Zealand, an estimated 596 cases would occur per year; of these 234 (39%) and 271 (46%) would be in sheep carrying ARQ/ARQ and ARQ/VRQ PrP genotypes, respectively. For the non-infected samples from New Zealand the diagnostic specificity of both ELISA kits was 100%. When considering all infected samples, the diagnostic sensitivity was 70.4 (95% CI=65.3–75.3)% for ELISA-BR and 91.6 (95% CI=88.2–94.4)% for ELISA-ID. For the ARQ/ARQ genotype (n=195), sensitivity was 66.2% for ELISA-BR and 90.8% for ELISA-ID, and for the ARQ/VRQ genotype (n=107), sensitivity was 81.3% for ELISA-BR and 98.1% for ELISA-ID.

CONCLUSIONS: In this study, the ELISA-ID kit demonstrated a higher diagnostic sensitivity for detecting scrapie in samples of RLN from sheep carrying scrapie-susceptible PrP genotypes than the ELISA-BR kit at comparable diagnostic specificity.

CLINICAL RELEVANCE: The diagnostic performance of the ELISA-ID kit using ovine RLN merits the consideration of including this assay in the national scrapie surveillance programme in New Zealand.  相似文献   

17.
The National Scrapie Plan (NSP) for Great Britain is a voluntary scheme that, through PrP genotype testing and restricted breeding, aims to reduce the risk of scrapie in the national sheep flock. To gauge the progress in member flocks and within breeds, the genotype profile of successive crops of ram lambs was monitored between 2002 and 2004. In each of the 11 most frequently sampled breeds, the proportion of ram lambs testing in the most resistant genotype category (NSP type 1: ARR/ARR) increased, and there was a reduction in the proportion of genotypes associated with the highest disease risk, that is X/VRQ, where X is an allele other than ARR. Changes in the proportion of ram lambs testing for ARR-heterozygous genotypes (NSP type 2: ARR/X, where X is not VRQ) appeared to be influenced by whether the sheep were hill breeds or non-hill breeds. In each of six frequently sampled hill breeds these genotypes expanded, in relative terms, whereas they declined in four of five prominent lowland/crossing breeds. The proportion of ram lambs that carried neither ARR nor VRQ (NSP type 3) declined consistently in the top 11 breeds, but there was little change in the ARR/VRQ genotype (NSP type 4). Among individual flocks that had ram lambs tested in all three years 2002 to 2004, the majority experienced an increase in the proportion testing ARR/ARR, and of those that had VRQ ram lambs in 2002, most recorded a decrease in their frequency by 2004.  相似文献   

18.
During active surveillance for transmissible spongiform encephalopathies (TSEs) in sheep, an initial reactor was detected using a rapid test on a brain sample. Immunohistochemistry confirmed an atypical TSE presentation that closely resembled the previously described Nor98 cases. Sequencing of the prnp gene confirmed the ARQ/AHQ genotype with the L141F mutation at codon 141 associated with this phenotype. The head, including the brain and cranial lymphoid tissues, was sampled and examined thoroughly. Non-purulent encephalitis, with ectopic lymphoid follicle formation within the brain, was diagnosed concomitant to the TSE. When scrapie-associated prion protein (PrP(sc)) deposition was studied by immunohistochemistry there was a noticeable lack of lymphotropism. The distribution of PrP(sc) in the brain differed considerably from that of classical scrapie cases. Astrogliosis and microgliosis were demonstrated by histochemical procedures.  相似文献   

19.
ABSTRACT: Susceptibility to scrapie, a transmissible spongiform encephalopathy in sheep, is modulated by the genetic make-up of the sheep. Scrapie control policies, based on selecting animals of resistant genotype for breeding, have recently been adopted by the Netherlands and other European countries. Here we assess the effectiveness of a breeding programme based on selecting rams of resistant genotype to obtain outbreak control in classical scrapie-affected sheep flocks under field conditions. In six commercially-run flocks following this breeding strategy, we used genotyping to monitor the genotype distribution, and tonsil biopsies and post-mortem analyses to monitor the occurrence of scrapie infection. The farmers were not informed about the monitoring results until the end of the study period of six years. We used a mathematical model of scrapie transmission to analyze the monitoring data and found that where the breeding scheme was consistently applied, outbreak control was obtained after at most four years. Our results also show that classical scrapie control can be obtained before the frequency of non-resistant animals is reduced to zero in the flock. This suggests that control at the national scale can be obtained without a loss of genetic polymorphisms from any of the sheep breeds.  相似文献   

20.
This report describes the genetics of the prion protein gene (PRNP) at codons 136, 154, and 171 for sheep diagnosed with naturally acquired classical scrapie in Canada between 1998 and 2008. Genotyping analysis was performed on 249 sheep with confirmed classical scrapie infection representing 98 flocks from 6 provinces. A further case-control analysis of 3 of these flocks compared the genotypes between infected sheep (n = 72) and those of their healthy flockmates (n = 1990). The incidence of classical scrapie in the Canadian sheep population was highly associated with the ARQ haplotype (91.8%) and the ARQ/ARQ genotype (91.6%). In addition, the ARQ haplotype was found at significantly higher frequency in scrapie-infected sheep when compared with their healthy flockmates. Comparison with other published data suggests that the scrapie risk of PRNP genotypes differs between Canada and countries where the VRQ allele is associated with the highest susceptibility to infection.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号