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1.
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   

2.
Polymorphisms at the prion protein locus were studied in 965 animals, representative of 13 native and 3 exotic sheep breeds in Portugal. In general, ARQ was the predominant allele in most breeds, but the desirable ARR allele was present in all breeds studied. A different pattern was found in Ile de France, where ARR was predominant and VRQ had the highest frequency among the breeds analysed. In most of the breeds, especially in those of the coarse-wool type, the major hurdle in selecting for genetic resistance to clinical scrapie was the elimination of ARQ rather than VRQ alleles. Breeding schemes aiming at the creation of ARR-homozygous selection nuclei were simulated for representative breeds, and results indicate that, with intense selection, it would take between 4 years in Ile de France and 11 years in Mondegueira to obtain homozygosity in the nucleus, and the length of time needed for fixation was not affected by the type of mating (random or assortative) used. Nevertheless, intense selection for the PrP genotype alone would have undesirable consequences in terms of inbreeding, and correlated responses in production and adaptation traits should be evaluated before such a scheme is adopted.  相似文献   

3.
Polymorphisms of PRNP gene have been strongly correlated to the susceptibility/resistance to scrapie in sheep. Variants at the coding positions 136, 154 and 171 have been the most frequently associated to susceptibility to classical scrapie. The aim of this study was to estimate PRNP haplotype and genotype frequencies in a sample of 1400 sheep from 13 different breeds that are representative of the main production regions in Brazil. A total of four different alleles (ARR, ARQ, AHQ and VRQ) and nine genotypes were observed at different frequencies among the investigated breeds. There were distinct patterns of allelic distribution between naturalized and commercial/specialized breeds and different geographic regions. These results will influence the development and management of breeding and conservation programs and will help to develop Brazilian efforts to avoid scrapie epidemics.  相似文献   

4.
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   

5.
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   

6.
Genetic susceptibility to scrapie is closely linked to variations at codons 136, 154, and 171 of the prion protein (PRNP) gene. This association between the PRNP genotype and susceptibility to scrapie is the basis of breeding programs for scrapie resistance in different countries. In this paper, we describe the method used with 2 Spanish dairy sheep breeds (Churra and Castellana) to ascertain the initial status of protection against scrapie as a first step toward adapting their breeding schemes to include resistance as a complementary selection criterion. The procedure for genotype identification is based on multiplex minisequencing methodology and has been shown to be accurate, easy to interpret, and to have a medium throughput. The frequency of the ARQ allele was similar in the 2 populations at nearly 70%. The ARR allele, associated with resistance in the homozygous state, reaches around 23% in Churras and nearly 20% in Castellanas. The high-risk VRQ allele appeared at a relatively low frequency in both breeds. No other haplotypes were found in these 2 breeds. Furthermore, in this screening we found a new allele carrying leucine at codon 154. This new genetic variant might play a role in susceptibility to scrapie because codon 154 belongs to a region considered to have an important role in conformational conversion of the cellular to the pathogenic protein.  相似文献   

7.
The association between scrapie and polymorphisms of the prion protein (PrP) gene was studied in 1108 German sheep of 33 different breeds. The aim of the investigation was the determination of the codons 136, 154 and 171 of the PrP gene, which are important for scrapie susceptibility. In addition to the published allelic variants ARR, ARQ, AHQ, ARH and VRQ, two novel, rare haplotypes (AHR and VRR) were found in the breeds of Texel, Nolana and Suffolk. A comparison of PrP genotype frequencies among the analysed different breeds revealed distinct variations. Breeds such as Texel showed a complex genotype distribution over 17 variants, while breeds such as Friesian Milk Sheep indicated only seven different genotypes.  相似文献   

8.
The aim of this study was to analyze the epidemiology and prion protein (PrP) genetics in scrapie-affected sheep flocks in Germany. For this purpose, 224 German scrapie cases in sheep diagnosed between January 2002 and February 2006 were classified as classical or atypical scrapie and the amino acids at codons 136, 141, 154 and 171 were determined. Likewise, representative numbers of flock mates were genotyped. Significant epidemiological differences were observed between classical and atypical scrapie cases in regard to the numbers of scrapie-affected sheep within a flock, the sizes of flocks with only a single scrapie-positive sheep or more than one scrapie-positive sheep and the age distribution of the scrapie-positive sheep. Sheep with the ARQ/ARQ genotype had by far the highest risk for acquiring classical scrapie, but the risk for atypical scrapie was the highest for sheep carrying phenylalanine (F) at position 141 (AF(141)RQ) and/or the AHQ haplotype. However, atypical scrapie also occurred with a notable frequency in sheep with the PrP haplotypes ARR and/or ARQ in combination with Leucine at position 141 (AL(141)RQ). Furthermore, six atypical scrapie-positive sheep carried the PrP genotype ARR/ARR. The high proportion of sheep flocks affected by atypical scrapie underscores the importance of this scrapie type.  相似文献   

9.
A total of 162 individuals, belonging to three Burkinabé and one Niger sheep populations, were analysed for prion protein (PrP) gene polymorphism at codons 136, 154 and 171. The ARQ allele was the most frequent in both the Burkinabé (86.7%) and the Niger (67.5%) sheep populations. The highly sensitive allele VRQ was not found in the sampled individuals. The highly resistant ARR allele was in very low frequency in the Burkina-Sahel (4.4%) and Mossi (3.2%) populations and was not present in the Djallonké and Touareg populations. Only 4 out of 15 possible PrP genotypes were identified in the sampled individuals. No favourable ARR/ARR genotypes were found in either of the breeds. Sequencing a subgroup of the samples allowed the identification of other five polymorphisms on the PrP gene sequence at codons 116, 138, 151, 237 and 240. The very low frequency of the ARR allele in the West African sheep should dissuade the implementation of a preventive selection programme aimed to increase resistance to scrapie, to avoid an extreme erosion of the genetic stock.  相似文献   

10.
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   

11.
There is concern about potential antagonistic correlated responses due to intensive selection for scrapie-resistant haplotypes of the prion (PRNP) gene in sheep. The objective of the present research was to test for associations of PRNP haplotypes for codons 136, 154, and 171 with growth, carcass, and meat quality traits in an F2 Dorset x Romanov population (n = 415) segregating the 2 callipyge alleles. Haplotypes of the 3 PRNP codons were determined for each sheep, and breed of origin of each gamete was predicted by genotyping 6 microsatellite markers flanking the PRNP locus. Twenty-five growth, carcass, and meat quality traits were evaluated. Data were analyzed using a basic model consisting of fixed effects of year, sex, and callipyge genotype, the random effect of sire, and 7 covariates corresponding to the probability that a lamb inherited a specific PRNP haplotype of either Dorset or Romanov origin. A fixed effect of litter size was added to the model for growth traits. The model for carcass traits contained the linear and quadratic effects of chilled carcass weight and the interactions among callipyge genotype and linear and quadratic terms. For meat quality traits, the model contained chilled carcass weight as a covariate and the interaction between callipyge genotype and chilled carcass weight. A contrast between the resistant ARR haplotype and the average effect of other PRNP haplotypes was tested to investigate the effects of potential selection for ARR within each breed of origin (Dorset, ARR vs. ARQ, VRQ, and AHQ; Romanov, ARR vs. ARQ and VRQ). There was limited evidence that selecting for scrapie resistance would cause correlated responses due to linkage disequilibrium. Associations of only 3 traits with PRNP haplotypes were detected in either breed of origin. In Romanov, the ARR haplotype was associated with longer carcasses (P < 0.013), narrower rumps (P = 0.038), and less marbling (P = 0.022) than the average of ARQ and VRQ haplotypes. No significant contrasts were detected for Dorset. This study is the first to account for breed of origin while investigating haplotype associations in an F2 population. This study provided limited evidence of associations between PRNP haplotypes and growth, carcass, and meat quality traits.  相似文献   

12.
In total 31,669 blood samples were collected from 1187 flocks of 27 rare breeds of sheep in the UK, and their genotype profiles at the prion protein locus were determined. The frequencies of the five alleles varied widely among the breeds and some had only two of the alleles and others had all five; the average was three. The average allele frequencies across all 27 breeds were 49.7 per cent for ARR, 4.4 per cent for AHQ, 2.7 per cent for ARH, 37.4 per cent for ARQ and 5.8 per cent for VRQ. The highest frequencies for each allele were 90.7 per cent for ARR in the Leicester Longwool, 24.7 per cent for AHQ in the Hebridean, 68.7 per cent for ARH in the Manx Loghtan, 98.7 per cent for ARQ in the North Ronaldsay and 28.4 per cent for VRQ in the Boreray. All 27 breeds had the ARR allele, 21 had AHQ, 11 had ARH, 26 had ARQ and 20 had VRQ.  相似文献   

13.
Breeding plans are being adopted in many countries to eradicate scrapie from the sheep populations. The European plans are based on selection for increased frequency of the resistant ARR haplotype and removal of the most scrapie susceptible haplotype (VRQ). This approach of a genotype eradication breeding programme incurs a number of risks including those associated with novel spongiform encephalopathy causing agents that are as yet unknown, but may emerge in the future and the possible loss of favourable attributes of a breed either through linkage or pleiotropic effects when selecting on a specific haplotype. Semen gene banks have been proposed to provide the potential for future reintroduction of removed haplotypes. Computer simulations were run for hill, crossing and terminal breed types to investigate the restorative potential of a gene bank required for the reintroduction of an alternative haplotype in the future. Differences existed in the restorative potential between the different breed types considered. This was largely dictated by variable levels of fertility, litter size, survival and mating ratio. It was shown that terminal breeds would require two and a half times as many semen straws as hill breeds to produce the same frequency of ewes homozygous for the desired haplotype in the population after a ten year reintroduction period.  相似文献   

14.
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   

15.
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   

16.
AIM: To use an established high through-put genotyping procedure to gain an estimate of the frequency of alleles of the prion protein (PrP) gene in some common sheep breeds in New Zealand. METHODS: Using a genotyping procedure based on matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF), DNA samples from 3,024 sheep from New Zealand, including breeds such as Romney, Texel, Coopworth, Merino and mixed breed, were isolated, genotyped and the results analysed. RESULTS: The 15 scrapie genotypes commonly reported, and derived from the five commonly reported allelic variants (ARR, ARQ, AHQ, ARH and VRQ), were all observed in the samples analysed. The estimates were indicative of the frequencies in the population of alleles present in breeds of sheep in New Zealand. There was a significant difference between the frequencies of alleles between breeds, but the ARQ, followed by the ARR allele, were, except in Carwell sheep, the most common alleles present. CONCLUSION: This study gave an indication of the percentages of PrP gene alleles in sheep in New Zealand, including data previously unreported from breeds in this country. It is of interest because of the relatively large size of the sheep population in New Zealand compared with many countries, and it provides some useful information on the genetic susceptibility or resistance of the sheep population in New Zealand to scrapie. The frequencies of the alleles can be different for an individual breed compared between countries.  相似文献   

17.
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   

18.
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   

19.
Three thousand one hundred and ninety-three Merino-breeding males were genotyped for Scrapie-resistance gene. They showed a high frequency of ARQ allele while VRQ allele frequency, linked to the highest susceptibility, was close to 0. Alleles linked to Scrapie-susceptibility frequencies have been studied in different Merino flocks. Most of the variability is intraflock, not interflock. In addition, there is an excess of heterozygotes due to crossbreeding or Wahlund effect.

Five control and prevention strategies were studied: first genotyping males and females and eliminating VRQ carriers and ARQ/ARQ rams; second genotyping males and females and eliminating VRQ carriers; third genotyping males and eliminating VRQ carriers and ARQ/ARQ rams; fourth genotyping males and using only as breeders ARR/ARR, ARR/AHQ, AHQ/AHQ and ARQ/ARQ rams; fifth genotyping males and using only as breeders ARR/ARR, ARR/AHQ and AHQ/AHQ rams. They were simulated from allelic and genotypic frequencies to decide which animals had to be genotyped and which animals had to be eliminated due to their genotypes and risk levels. The third option, to genotype rams and to eliminate ARQ/ARQ and VRQ carriers, would be the best strategy to improve the resistance and would cause minimal cost and loss of animals.  相似文献   


20.
AIM: To use an established high through-put genotyping procedure to gain an estimate of the frequency of alleles of the prion protein (PrP) gene in some common sheep breeds in New Zealand.

METHODS: Using a genotyping procedure based on matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF), DNA samples from 3,024 sheep from New Zealand, including breeds such as Romney, Texel, Coopworth, Merino and mixedbreed, were isolated, genotyped and the results analysed.

RESULTS: The 15 scrapie genotypes commonly reported, and derived from the five commonly reported allelic variants (ARR, ARQ, AHQ, ARH and VRQ), were all observed in the samples analysed. The estimates were indicative of the frequencies in the population of alleles present in breeds of sheep in New Zealand. There was a significant difference between the frequencies of alleles between breeds, but the ARQ, followed by the ARR allele, were, except in Carwell sheep, the most common alleles present.

CONCLUSION: This study gave an indication of the percentages of PrP gene alleles in sheep in New Zealand, including data previously unreported from breeds in this country. It is of interest because of the relatively large size of the sheep population in New Zealand compared with many countries, and it provides some useful information on the genetic susceptibility or resistance of the sheep population in New Zealand to scrapie. The frequencies of the alleles can be different for an individual breed compared between countries.  相似文献   

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