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.
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   

2.
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   

3.
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   

4.
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   

5.
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   

6.
Scrapie free adult sheep were introduced to a sheep flock specifically maintained to maximise scrapie infection. Native born sheep of the highly susceptible VRQ/VRQ genotype in this flock show highly efficient transmission, evidenced by 100% infection, with an age at death of less than 2 years. Infection in introduced sheep was identified by biopsy of tonsilar and nictitating membrane lymphoid tissue. Progeny of these sheep were monitored and clinical disease confirmed by examination of the brain using routine diagnostic methods. Na?ve sheep of New Zealand origin introduced to the flock in adulthood became infected, demonstrating that lateral transmission had occurred. Lambs born to introduced ewes became infected and died at the same age as lambs born to native ewes, consistent with lateral transmission of scrapie to lambs. Although maternal transmission cannot be totally excluded for the lambs in this study, the data are consistent with lateral transmission being the most important means of spread leading to the high incidence of scrapie observed in this flock.  相似文献   

7.
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   

8.
OBJECTIVE: To develop new and improved tests to detect alleles at codons 136 and 171 of the ovine prion protein locus and to evaluate the frequency of these alleles. ANIMALS: 159 Suffolk sheep belonging to 3 flocks. PROCEDURE: Polymerase chain reaction (PCR) analysis that contained diagnostic restriction site variation for each allele were developed for the relevant gene regions. Alleles were determined by analyzing DNA isolated from buccal swab specimens or blood samples. RESULTS: At codon 136, frequencies of the alanine and valine alleles were found to be 97 and 3%, respectively. At codon 171, frequencies of the glutamine, arginine, and histidine alleles were found to be 57, 41, and 2%, respectively. CONCLUSIONS: Little variation was detected in codon 136, whereas noteworthy variation was found in codon 171; > 40% of the alleles at this locus coded for glutamine. Because the glutamine allele at codon 171 confers susceptibility to scrapie, reduction of its frequency is of importance to management of sheep flocks. CLINICAL RELEVANCE: Genotyping of sheep, using the tests reported here, should facilitate selective breeding programs designed to decrease the risk of scrapie.  相似文献   

9.
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   

10.
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   

11.
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   

12.
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   

13.
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   

14.
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   

15.
Scrapie is one of several transmissible spongiform encephalopathies of livestock. Disease susceptibility is linked to polymorphisms in the normal prion protein gene that encodes the mammalian prion precursor. Codon 171 of this gene is a major determinant of scrapie susceptibility. Selection for arginine (R) at codon 171 is encouraged by the USDA to decrease the incidence of scrapie. Objectives of this study were to determine the frequency of R allele variants at codon 171 in a sample of sheep from five breeds (Columbia, Hampshire, Rambouillet, Suffolk, and Targhee) and western white-faced commercial ewes and to determine whether the R allele is associated with ewe and lamb production traits. Genotyping was performed on 532 ewes and 901 lambs from the University of Wyoming flock, in addition to 820 rams from 52 sheep producers from Wyoming and surrounding areas, using a DNA mismatch assay that discriminated the R allele from others at codon 171. Genotyping was performed by DNA sequencing on 127 rams representing all breeds, except Hampshire from the USDA Sheep Experiment Station at Dubois, ID. The 171R allele was found in all five breeds and in the commercial western white-faced ewes. Genotype frequencies varied (P < 0.001) by breed in ewe and ram populations. Influence of R-allele frequency on ewe lambing records and individual lamb records was analyzed for Columbia (62, 161, 121), Hampshire (89, 193, 162), Rambouillet (87, 179, 133), Suffolk (67, 178, 161), and commercial sheep (227, 463, 324) for numbers of ewes, total number of ewe production records, and individual lamb records, respectively. Suffolk ewes without the R allele (non-R/non-R) gave birth to more (P or= 0.08) by ewe genotype. Lamb birth and weaning weights were not influenced (P >or= 0.12) by lamb genotype in any of the breeds or in the commercial flock. In this population, ultimate lamb production was only influenced by genotype at codon 171 in the Suffolk flock.  相似文献   

16.
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   

17.
It has long been established that the sheep Prnp genotype influences the susceptibility to scrapie, and some studies suggest that it can also determine several aspects of the disease phenotype. Other studies, however, indicate that the source of infection may also play a role in such phenotype. To address this question an experiment was set up in which either of two different natural scrapie sources, AAS from AA136 Suffolk and VVC from VV136 Cheviot sheep, were inoculated into AA136, VA136 and VV136 sheep recipients (n = 52). The immunohistochemical (IHC) profile of disease-associated PrP (PrPd) accumulation in the brain of recipient sheep was highly consistent upon codon 136 homologous and semi-homologous transmission, but could be either similar to or different from those of the inoculum donors. In contrast, the IHC profiles were highly variable upon heterologous transmission (VVC to AA136 and AAS to VV136). Furthermore, sheep of the same Prnp genotype could exhibit different survival times and PrPd profiles depending on the source of infection, and a correlation was observed between IHC and Western blot profiles. It was found that additional polymorphisms at codons 112 or 141 of AA136 recipients resulted in a delayed appearance of clinical disease or even in protection from infection. The results of this study strongly suggest that the scrapie phenotype in sheep results from a complex interaction between source, donor and recipient factors, and that the Prnp genotype of the recipient sheep does not explain the variability observed upon codon 136 heterologous transmissions, arguing for other genetic factors to be involved.  相似文献   

18.
An accidental infection from a vaccine was suggested as the explanation for the sudden increase in outbreaks of scrapie in Italy in 1997 and 1998. This paper describes a recent outbreak of scrapie in sheep and goats which were exposed to the same vaccine. No ewes or goats had been imported into the herd since 1992, but a vaccine against Mycoplasma agalactiae had been administered twice, in 1995 and 1997. High rates of crude mortality and scrapie incidence were experienced by both species, all birth cohorts were involved and a large proportion of aged animals was affected. A pattern of brain lesions was observed, with slight differences between the sheep and goats, which was very similar to the pattern observed in animals previously exposed to the same vaccine but clearly different from that observed in the brains of sheep with scrapie in a flock not exposed to the vaccine. Regardless of their exposure status, genotype analysis of the sheep showed the presence of polymorphism only at codon 171. The patterns of both incidence and brain lesions provide evidence that the epidemic of scrapie was due to the use of the vaccine.  相似文献   

19.
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   

20.
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   

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