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1.
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   

2.
OBJECTIVE: To determine whether selection for the homozygous A136 R171 genotype that confers resistance to classic scrapie infection negatively affects production traits in sheep. ANIMALS: 996 commercial lambs obtained from 2 flocks at separate locations across 3 consecutive years. Procedures-Genotyping at codon 136 and 171 was performed by use of commercially available testing or a single-nucleotide polymorphism assay. Carcass data were collected without knowledge of genotype approximately 24 hours after slaughter by an experienced grader. The model to analyze associations between prion protein (PRNP) genotype and production traits was based on genotype, breed, or both as fixed effects and days on feed as a covariate. RESULTS: Average daily gain was significantly associated with only combined codons 136 and 171. In flock 1, weaning average daily gain was significantly greater in AA136 sheep than heterozygotes; the difference between QR171 and RR171 sheep, compared with QQ171 sheep, were not significant although QR171 and RR171 sheep had higher values. However, in flock 2, average daily gain was significantly greater in AV136 sheep than AA136 sheep and in QR171 sheep than QQ171 sheep. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest there is an advantage for average daily gain in lambs with an arginine allele at codon 171, but there were no other genotype effects on production traits. Thus, selection for the resistant arginine allele at codon 171 to comply with USDA scrapie eradication guidelines should not be detrimental to lamb production in commercial flocks. Effects of codon 136 on average daily gain were ambiguous.  相似文献   

3.
The PrP genotypes associated with natural scrapie in Ireland were determined and a comparison was made between genotypes found in scrapie-infected sheep and those found in healthy animals from scrapie-infected flocks. Seven PrP genotypes were identified in scrapie-infected animals: VV(136)RR(154)QQ(171),VA(136)RR(154)QQ(171),VA(136)RR(154)QR(171),VA(136)RR(154)QH(171),AA(136)RR(154)QQ(171),AA(136)RR(154)QH(171) and AA(136)RR(154)HH(171). Of 11 scrapie-infected flocks, 15 genotypes were identified in the healthy flock-mates. The genotypes identified in scrapie-affected animals were also all identified in healthy flock-mates. In 9 of the 11 flocks studied, the genotype frequencies among scrapie-infected animals were significantly different from those among healthy flock-mates. The results show that there is a significant risk of developing the clinical signs of scrapie associated with particular PrP genotypes in the Irish sheep population. The association between the V(136)R(154)Q(171) allele and scrapie was evident, as was the association between A(136)R(154)R(171) and resistance to developing the clinical signs of scrapie. The presence of the A(136)H(154)Q(171) allele in the flocks examined resulted in a decreased risk of developing scrapie compared to the presence of the A(136)R(154)Q(171).  相似文献   

4.
Amino acid polymorphisms of PrP gene in Mongolian sheep   总被引：7，自引：0，他引：7  
To characterize amino acid polymorphisms in sheep prion protein (PrP), we analyzed the PrP genes from 271 sheep of 4 breeds (Khalkh, Yeroo, Orkhon and Khangai) raised in central Mongolia (Tuv, Uvurkhangai and Selenge prefectures). A total of 16 genotypes and 8 allelic variants of the PrP gene at codons 112, 136, 154 and 171 were found. At codon 171, 1.8% of the sheep had arginine/arginine (R/R) (resistant to scrapie) and 66.8% had glutamine/glutamine (Q/Q) (susceptible to scrapie). Several Yeroo and Orkhon sheep raised in Selenge prefecture had valine at codon 136 (136V) (highly susceptible to scrapie). Several Yeroo, Orkhon and Khangai sheep raised in Selenge prefecture had histidine at codon 154 (154H). Novel polymorphisms of valine (V) and serine (S) at codon 127, lysine (K) at codon 171, and leucine (L) and arginine (R) at codon 189 were also found in Khalkh, Yeroo and Orkhon sheep. It is not known whether these novel polymorphisms affect scrapie susceptibility.  相似文献   

5.
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   

6.
OBJECTIVE: To compare incubation time and clinical signs of scrapie in codon 136/171 alanine-valine/glutamine-glutamine (AVQQ) experimentally inoculated sheep with that in sheep with the more common 136/171 AAQQ genotype. ANIMALS: 60 Suffolk sheep. PROCEDURE: Twenty-seven 171 QQ ewes purchased from 2 private flocks were bred with a 171 QQ Suffolk ram before being inoculated with a 20% solution of scrapie-positive brain homogenate (5 mL, PO) from sheep containing genotypes 136/154/171 AA/arginine-arginine (RR)/QQ, AVRRQQ, and VVRRQQ that had died of scrapie. Ewes had 33 lambs, which were inoculated in the same manner on the day of birth. RESULTS: All 16 genotype 136/154/171 AVRRQQ sheep that died of scrapie were 9 to 11 months of age; clinical signs lasted 1 day to 3 weeks with no wasting and only mild pruritus. The first AARRQQ sheep died with typical clinical signs of scrapie 27 months after inoculation, and 14 were still alive 37 to 42 months after inoculation. The 136/171 AVQQ sheep had minimal accumulation of modified cellular protein (PrP(SC)) as determined by immunohistochemical (IHC) staining within affected cells; thus the severity of clinical signs and time of death were not associated with brain lesions or the amount of PrP(SC) in brain TISSUE OF 136/154/171 AVRRQQ sheep as determined by IHC staining. CONCLUSIONS AND CLINICAL RELEVANCE: The rapid incubation time may have been influenced by the codon 136 genotype, a new unreported valine (V)-dependent strain of scrapie similar to strain SSBP/1, or the inoculum may have contained a traditional strain and a V-dependent or SSBP/1-like strain of scrapie.  相似文献   

7.
The objective of this study was to develop a reliable Taqman 5' Nuclease Assay for genotyping sheep for scrapie susceptibility. The sheep prion gene contains 2 single nucleotide polymorphisms (SNPs) that may mediate resistance to classical scrapie, one at codon 136, alanine (A) or valine (V), and another at codon 171, arginine (R) or glutamine (Q). The R allele appears to confer resistance to classical scrapie, with the AA(136) RR(171) genotype the most resistant to scrapie and QR(171) only rarely infected in the US sheep population. The Assays by Design protocol was used for development of probes and primers for codon 136 and Primer Express for codon 171. Commercially available kits were used to isolate genomic DNA from blood or muscle. For validation, 70 SNP determinations for each codon were compared to commercial testing with an error rate of less than 1%. Then, 935 samples from blood (n = 818) and muscle (n = 117) were tested for both codons with 928 successful determinations and only 7 samples (<1% of total samples) that needed repeating. Genotypes were AA QQ (n = 102; 11.0%), AV QQ (n = 28; 3.0%), AA QR (n = 396; 42.7%), AV QR (n = 54; 5.8%), and AA RR (n = 348; 37.5%). Thus, 86% of the sheep tested (n = 798) contained R at codon 171 and were expected to be scrapie-resistant. This new Taqman 5' Nuclease SNP genotyping assay is accurate, easy to perform, and useful in the study of classical scrapie in sheep and its prevention through selective breeding programs to eliminate highly susceptible animals.  相似文献   

8.
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   

9.
This study presents preliminary data on the polymorphism in the prion protein gene of Swiniarka sheep using temperature gradient gel electrophoresis (TGGE). Available data indicate that sensitivity to scrapie is associated with polymorphisms in three codons of prion protein gene: 136,154, and 171. The TGGE method was used to detect point mutations in these codons responsible for sensitivity or resistance to scrapie. This study revealed presence of an allele encoding valine (V) in codon 136, which is associated with high sensitivity to scrapie and occurred in the form of heterozygous allele together with alanine (AV). The highest variability was observed in codon 171, with presence of arginine (R) and glutamine (Q) in the homozygous (RR or QQ) as well as the heterozygous form (RQ). The results of examination of fifty sheep DNA samples with mutations in codons 136, 154, and 171 demonstrated that TGGE can be used as a simple and rapid method to detect mutations in the PrP gene of sheep. Several samples can be run at the same time, making TGGE ideal for the screening of large numbers of samples.  相似文献   

10.
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   

11.
Genetic susceptibility to scrapie is associated with polymorphisms in three different codons of the ovine prion protein (PrP) gene (136, 154, 171). Studies of PrP genotypes linked to scrapie have revealed the resistance of homozygous PrPARR/PrPARR animals and the high risk of PrPVRQ/PrPVRQ and PrPvRQ/PrPARQ animals in scrapie-affected flocks. The selection of PrPARR/PrPARR genotypes may therefore provide a strategy for controlling clinical scrapie. The genotypes of 1361 German breeding sheep from 15 different breeds in northern Germany were determined. Apart from the wildtype allele PrPARQ, at least four mutually exclusive allelic variants were found. The greatest variability within the PrP gene was encountered in texel sheep, in which 14 PrP genotypes were found. In the important meat breeds, Suffolk, German whiteheaded mutton and German blackheaded mutton, the PrPARR allele was predominant, and in these breeds the breeding of scrapie-resistant pedigree flocks within four generations seems to be a feasible option. In the texel sheep, the German merino, the German milk and the German land sheep breeds, the frequency of the PrPARR allele was much lower, and in several breeds no homozygous rams were available for breeding purposes. In these breeds the breeding strategy would depend on the number of heterozygous rams available, but resistant pedigree flocks could be achieved within nine generations.  相似文献   

12.
Scrapie, an ovine and caprine transmissible spongiforme encephalopathy, is widely spread among sheep populations in many European countries. As it is known that susceptibility to scrapie is determined genetically, breeding programmes aiming at providing scrapie-resistant flocks have been established. Selection is based on the prion protein (PrP) genotype, which is used to classify animals into risk groups of susceptibility (R1-R5) according to the amino acids encoded by codons at positions 136, 154 and 171, respectively. At position 136 (136V-->136A) alanine and at position 154 (154H-->154R) as well as 171 (171Q-->171R) arginine are the favoured amino acids. Whereas PrP genotyping data are available for many of the European sheep breeds, comparable data for local Austrian sheep breeds are missing. The most known among these are Tyrolean mountain sheep, forest sheep. Tyrolean stone sheep and Carynthian sheep. The genotypes of 112 sheep from these four local breeds were determined. In terms of PrP genetics, Austrian breeds belong to the group of non-valine-breeds, with the exception of the Carynthian sheep, that exhibited a frequency of 136V of 4.2%. The most frequent allele was ARQ with 64.6-71.2% (depending on the breed), followed by ARR (14.8-25.8%). In contrast to the above-mentioned findings, scrapie has never been diagnosed in any of the Austrian sheep breeds. Native Austrian sheep breeds exhibit a very robust constitution, a pronounced adaptation to harsh climates and good reproduction parameters as well as a marked mother instinct. Therefore, these breeds are often used in crossbreeding programmes. Beside the above-mentioned characteristics, our results indicate that the investigated breeds may be effectively used in crossing-out breeding programmes for eliminating valine at position 136 of PrP.  相似文献   

13.
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   

14.
Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrPsc, in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrPsc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrPsc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrPsc deposition in various tissues using single- and dual-label immunohistochemistry. Scrapie, as defined by PrPsc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrPsc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrPsc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrPsc deposition in the brain but widespread PrPsc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrPsc accumulation preceding deposition in the brain. PrPsc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrPsc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrPsc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrPsc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171: PrPsc deposition was restricted to PrP genotype AA136RR154QQ171 in 12/13 cases or AV136RR154QQ171 in 1/13 cases. The earliest accumulation was observed in the single VRQ/ARQ heterozygous animal, consistent with the reported high scrapie susceptibility and brief incubation period observed in breeds with predominance of the V136R154Q171 allele. Disease occurred within, as well as independent of, mother-daughter lines, suggesting both maternal and nonmaternal transmission in the flocks.  相似文献   

15.
Sheep possessing alleles for the prion protein with glutamine (Q) or histidine, both reported as Q, at codon 171 are highly susceptible to scrapie. Incidence of scrapie infection is rare when animals possess at least one allele for arginine (R) at codon 171. The current USDA APHIS scrapie eradication program utilizes genotyping for alleles that confer resistance to scrapie. Although it has not been a criterion of registration, genotyping has been utilized in the University of Wyoming Ram Performance test since 2002. Performance test records from 2002 to 2006 (n=518) were analyzed to determine if any production loss or benefit was associated with scrapie resistance in rams. Performance of rams with scrapie resistant genotypes was equal to or better than scrapie susceptible rams. Based on test performance as an acceptable indicator of sire superiority, selection for rams with scrapie resistant genotypes should not negatively impact flock performance.  相似文献   

16.
Susceptibility to scrapie in sheep is linked to variation at codons 136, 154, and 171 in the host prion protein gene (PRNP). A number of techniques are available for detecting these polymorphisms, but none allow for a rapid and accurate determination of genotype. Here we describe PCR coupled with single-strand conformational polymorphism (SSCP) analysis, which allows for the accurate identification of ovine PRNP alleles. A gene region including codons 136 to 171 was amplified by PCR, and the amplimers were then denatured and subjected to electrophoresis in a nondenaturing polyacrylamide gel. Nine unique SSCP patterns, representing nine different alleles of the ovine PRNP gene, could be resolved. A new polymorphism (I/T) at codon 142 also was detected. The profiles produced by SSCP allowed for the accurate differentiation of PRNP alleles and could be employed to genotype PRNP in sheep.  相似文献   

17.
To determine the levels of background scrapie-like pathology in the brains of clinically normal adult sheep, the brains of 1106 sheep from 28 known scrapie-infected flocks and nine apparently uninfected flocks were examined during 1998 and 1999. One per cent of the brains had vacuolar pathology and disease-specific accumulations of prion protein consistent with a diagnosis of scrapie. All the positive animals had at least one allele of the prion protein gene encoding valine at codon 136, and originated from flocks in which cases of clinical scrapie had been confirmed within the last four years. The parasympathetic nucleus of the vagal nerve was the most consistently and severely affected nucleus in the medulla oblongata, suggesting that the infection enters the brain via ascending fibres of the vagus nerve.  相似文献   

18.
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   

19.
To characterize amino acid polymorphisms of sheep prion protein (PrP) gene, DNA from 740 sheep of nine breeds raised in Mongolia was isolated and analyzed. A total of 16 genotypes and seven allelic variants of the PrP gene at codons 112, 136, 154, and 171 were found. The MARQ/MARQ genotype associated with susceptibility to scrapie was found in 82.6% of the sheep while the MARR/MARR genotype associated with resistance to scrapie was found in 1.8% of the sheep. The polymorphisms of valine and serine at codon 127, and leucine and arginine at codon 189 were detected in eight Mongolian sheep breeds, suggesting that these polymorphisms are a common feature among Mongolian sheep breeds.  相似文献   

20.
Natural scrapie is associated with polymorphisms in the prion protein (PrP) gene. In Suffolks, codon 171 is the codon at which most variation is found; RR171 is thought to be associated with resistance to developing the clinical signs of the disease and QQ171 is associated with susceptibility to the disease. The objectives of this study were first to determine the PrP genotypes of Suffolk stock rams in Ireland, and secondly to compare the genotype profiles of ram lambs from flocks where a breeding programme based on the genotype AA136RR154RR171 had been initiated and from flocks where there was no breeding programme based on PrP genotype. Approximately 13 per cent of the stock rams genotyped in the Irish population were genetically susceptible to showing the clinical signs of the disease. However, lambs from farms that had initiated a selective breeding strategy for RR171 over the past year had a larger proportion of RR171 and a smaller proportion of QQ171 than the stock rams or ram lambs from farms not applying a breeding strategy.  相似文献   

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