scholarly journals Novel Variations at Three Different Positions of Prion Protein Coding Gene in Ethiopian Sheep Breeds and the Resistance/Susceptible Status to Classical and Atypical Scrapie

2019 ◽  
Author(s):  
Eden Yitna Teferedegn ◽  
Yalcin Yaman ◽  
Cemal Un
Keyword(s):  
Prion Protein ◽  
Current Knowledge ◽  
Classical Scrapie ◽  
The Novel ◽  
Atypical Scrapie ◽  
Protein Coding ◽  
Essential Information ◽  
Sheep Population ◽  
Sheep Breeds ◽  
Scrapie Susceptibility

Abstract Background: Classical Scrapie susceptibility in sheep has been linked to three polymorphisms at positions 136, 154, and 171 in the PRNP gene whereas atypical scrapie susceptibility is related to a polymorphism at position 141. Many other variants over the length of the prion protein coding gene were reported. Since infectious prion protein itself seems to be polymorphic, the identified novel PRNP gene variations may play a crucial role in fighting against the emergence of a new form of scrapie disease. Many studies conducted around the world to identify disease resistant status and new variants of PRNP gene in different breeds. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breeds PRNP gene provides essential information to the current knowledge. This study aimed to identify potential novel variations in the Ethiopian sheep PRNP gene, thereby determine the uniqueness of the native breeds and predict scrapie status of sheep population based on the genotypes distribution. Results : Five novel variants were identified in the PRNP gene of native Ethiopian sheep. Four non-synonymous heterozygous substitutions at H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) variants were detected. In addition to the novel variations, polymorphisms at 126,127,138,142,146,231, and 237 positions were also identified. The haplotype ARR was observed only in Menz and Afar breeds with frequencies 0.02 and 0.05 respectively. However, neither ARR/ARR nor VRQ/VRQ genotypes were identified in all of the breeds. Conclusion: Two of the novel variations at position 99 and 103 that are placed closer to the cleavage site and variant at 116 spotted in the palindrome region along with variants at position 127 in Glycine repeat domain may influence the conformational flexibility of prion protein. The low frequency of ARR haplotype and the sole variant 141L demonstrated that Ethiopian sheep are susceptible to classical scrapie and resistant to atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies against scrapie during inbreeding, crossbreeding and help to take precautious measures.

scholarly journals Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds

2020 ◽  
Author(s):  
Eden Yitna Teferedegn ◽  
Yalcin Yaman ◽  
Cemal Un
Keyword(s):  
Prion Protein ◽  
Prnp Gene ◽  
Potential Effect ◽  
Classical Scrapie ◽  
Proteinase K ◽  
The Novel ◽  
Atypical Scrapie ◽  
Sheep Breeds ◽  
Novel Variants ◽  
Scrapie Susceptibility

Abstract Background Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene (PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at codon 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.

scholarly journals Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds

2020 ◽  
Author(s):  
Eden Yitna Teferedegn ◽  
Yalcin Yaman ◽  
Cemal Un
Keyword(s):  
Prion Protein ◽  
Prnp Gene ◽  
Potential Effect ◽  
Classical Scrapie ◽  
Proteinase K ◽  
The Novel ◽  
Atypical Scrapie ◽  
Sheep Breeds ◽  
Novel Variants ◽  
Scrapie Susceptibility

Abstract Background Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene ( PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at position 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA) and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231 and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie. Keywords: Ethiopian sheep; Novel Variations; Polymorphism; Prion gene; Scrapie Susceptibility

scholarly journals Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds

2020 ◽  
Author(s):  
Eden Yitna Teferedegn ◽  
Yalcin Yaman ◽  
Cemal Un
Keyword(s):  
Prion Protein ◽  
Prnp Gene ◽  
Potential Effect ◽  
Classical Scrapie ◽  
Proteinase K ◽  
The Novel ◽  
Atypical Scrapie ◽  
Sheep Breeds ◽  
Novel Variants ◽  
Scrapie Susceptibility

Abstract Background: Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene (PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at position 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results : Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion: Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.

scholarly journals Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds

2020 ◽  
Author(s):  
Eden Yitna Teferedegn ◽  
Yalcin Yaman ◽  
Cemal Un
Keyword(s):  
Prion Protein ◽  
Prnp Gene ◽  
Potential Effect ◽  
Classical Scrapie ◽  
Proteinase K ◽  
The Novel ◽  
Atypical Scrapie ◽  
Sheep Breeds ◽  
Novel Variants ◽  
Scrapie Susceptibility

Abstract Background Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene (PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at codon 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.

Prion Evolvability and the Hazard of Atypical Scrapie in Small Ruminants

2020 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
David B. Adams
Keyword(s):  
Disease Transmission ◽  
Western Europe ◽  
Current Knowledge ◽  
Small Ruminants ◽  
Classical Scrapie ◽  
Atypical Scrapie ◽  
Sheep And Goats ◽  
Preparedness Planning ◽  
Strain Behaviour ◽  
Third Stage

AbstractObservations on strain behaviour and direct demonstrations of natural selection establish that the scrapie agent and prions in general are able to evolve. Accordingly, it is conceivable that atypical non-contagious scrapie in sheep and goats can transform to classical contagious scrapie under particular circumstances. In consequence, atypical scrapie can be regarded as a latent hazard that warrants comprehensive risk assessment and biosecurity preparedness planning. Evidence for this proposition comes from differences in the expression of atypical and classical scrapie that may make scrapie contagious, historical records of scrapie in Western Europe, and contemporary accounts of the epidemiology of atypical scrapie. Biosecurity preparedness can be based on current knowledge of pathophysiology and epidemiology and can be built around a three-stage model for the endogenous emergence of a propagating epidemic of scrapie. The first stage concerns the occurrence of atypical scrapie. The second stage concerns the acquisition of communicability in prion populations provided by atypical scrapie and the third stage concerns circumstances allowing disease transmission and the initiation of a propagating epidemic. The range of component causes envisaged for possible outbreaks of endogenous classical scrapie is broad. However, exposure of sheep and goats to cyanobacterial toxins qualifies for special attention.

scholarly journals A decade of using small-to-medium throughput allele discrimination assay to determine prion protein gene (Prnp) genotypes in sheep in Slovenia

2017 ◽  
Vol 30 (1) ◽  
pp. 144-149 ◽  
Author(s):  
Jelka Zabavnik ◽  
Marko Cotman ◽  
Polona Juntes ◽  
Ivan Ambrozic
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Classical Scrapie ◽  
Prion Protein Gene ◽  
Atypical Scrapie ◽  
Susceptible Genotype ◽  
Pcr Assay ◽  
Breeding Programs ◽  
Resistant Genotypes ◽  
Selection Of

Sheep with valine (V) at codon 136 and glutamine (Q) at codon 171 of the prion protein gene ( Prnp) are highly susceptible to classical scrapie, whereas phenylalanine (F) at codon 141 and histidine (H) at codon 154 play a major role in the susceptibility to atypical scrapie. A TaqMan real-time PCR assay was developed to determine Prnp alleles at codons 136, 141, 154, and 171 and used in classical scrapie eradication and breeding programs adopted in Slovenia. The frequency of the most resistant genotypes ARR/ARR and ARR/ARQ increased significantly in tested animals ( n = 35,138) from 6.7 and 27.1% of the tested sheep in 2006 to 12.1 and 32.4%, respectively, in 2015. Frequencies of more susceptible genotypes ARQ/ARQ and ARQ/VRQ decreased significantly from 36.4 and 3.5% in 2006 to 31.1 and 1.8%, respectively, in 2015. The most susceptible genotype VRQ/VRQ was detected in <0.5% of tested sheep. Frequencies of alleles AFRQ and AHQ affecting the susceptibility to atypical scrapie did not change significantly. The developed assay was suitable for genotyping on a small-to-medium throughput scale and was successfully used in classical scrapie eradication, as well as for the selection of classical scrapie–resistant sheep within breeding programs in Slovenia.

Breeding for scrapie resistance in the Hungarian sheep population

2008 ◽  
Vol 56 (2) ◽  
pp. 173-180 ◽  
Author(s):  
László Fésüs ◽  
Attila Zsolnai ◽  
István Anton ◽  
László Sáfár
Keyword(s):  
Capillary Electrophoresis ◽  
Prion Protein ◽  
Genotype Frequency ◽  
Breeding Programme ◽  
Atypical Scrapie ◽  
Frequency Data ◽  
Sheep Population ◽  
New Developments ◽  
First Results ◽  
Efficiency Of Selection

The first results of the Hungarian sheep prion protein (PrP) genotyping programme are discussed in this paper. To obtain initial genotype frequency data 10 commercial (Hungarian Merino, German Mutton Merino, Merino Landschaf, German Blackheaded, Suffolk, Texel, Ile de France, Charollais, Lacaune, British Milksheep) and 4 indigenous (Gyimes Racka, Hortobágy Racka, Tsigaja, Cikta) breeds were sampled in 2003 and 2004, and the PrP genotypes were determined by microsequencing analysis with capillary electrophoresis. In all commercial breeds, a higher number of sheep were genotyped in 2005 (3648) and in 2006 (3834) within the breeding programme to increase scrapie resistance, and the estimated frequency data were compared to the initial figures to evaluate the efficiency of selection. The new developments arising from the identification of the so-called ‘atypical’ scrapie cases are also discussed.

scholarly journals Prion protein gene polymorphisms in classical scrapie-affected flocks of sheep in Central Macedonia

2018 ◽  
Vol 69 (2) ◽  
pp. 931
Author(s):  
C. KIOUTSIOUKIS ◽  
E. PAPADOGIANNAKIS ◽  
V. PALASKA ◽  
V. KONTOS ◽  
D. PAPAKOSTAKI ◽  
...  
Keyword(s):  
Prion Protein ◽  
Gene Polymorphisms ◽  
Protein Gene ◽  
Risk Groups ◽  
Classical Scrapie ◽  
Reference Laboratory ◽  
Prion Protein Gene ◽  
Sheep Population ◽  
Predominant Genotype ◽  
Frequency Distributions

The allele and genotype frequency distributions of the prion protein gene polymorphisms at codons 136, 154 and 171 were determined by real-time PCR for 1,456 sheep from 7 classical scrapie-affected flocks of Thessaloniki and Imathia, Central Macedonia, Greece. The blood samples were collected by official veterinarians and were examined by the National Reference Laboratory (NRL) for TSEs, Veterinary Laboratory of Larisa, Greece, in the framework of the National Program for Scrapie Surveillance and Control between 2009 and 2013. Among the 1,456 sheep, 340 were of Chios breed, 633 Chios crossbred and 483 crossbred. The examined sheep showed high genotype variability, as a total of 7 haplotypes and 23 different genotypes were found. The predominant allele and the predominant genotype were ARQ and ARQ/ARQ respectively, in all breeds studied, followed by the ARR allele and the ARR/ARQ genotype. The TRQ allele was frequent in Chios and Chios crossbred, while the VRQ allele was rare for all the breeds. Interestingly, 3 genotypes (ARH/TRQ, ARR/ARK and ARK/VRQ) were detected for the first time in Greece and two of them (ARH/TRQ and ARK/VRQ) have, to our knowledge, never been previously reported. Furthermore, it is emphasized that our country outnumbers all European countries in classical scrapie cases of sheep every year. Therefore, there is an urgent need to reduce the incidence of classical scrapie through the implementation of selective breeding programs. This is supported by the fact that the prevalence of classical scrapie in the Greek sheep population is highly associated with the predominant genotype ARQ/ARQ. Therefore, the elimination of the ARQ/ARQ and the other susceptible genotypes (belonging to Risk Groups 3 and 5, according to the National Scrapie Plan of Great Britain) would reduce dramatically the incidence of classical scrapie in Greece.

scholarly journals Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep Bovine Spongiform Encephalopathy and Atypical Scrapie

2009 ◽  
Vol 15 (8) ◽  
pp. 1214-1221 ◽  
Author(s):  
Juan-Carlos Espinosa ◽  
María-Eugenia Herva ◽  
Olivier Andréoletti ◽  
Danielle Padilla ◽  
Caroline Lacroux ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Protein Resistant

scholarly journals Review: Update on Classical and Atypical Scrapie in Sheep and Goats

2018 ◽  
Vol 56 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Justin J. Greenlee
Keyword(s):  
Prion Protein ◽  
Environmental Contamination ◽  
Protein Misfolding ◽  
Transmissible Spongiform Encephalopathy ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Sheep And Goats ◽  
Scrapie Agent ◽  
Scrapie Strains

Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) or prion disease of sheep and goats. Scrapie is a protein misfolding disease where the normal prion protein (PrPC) misfolds into a pathogenic form (PrPSc) that is highly resistant to enzymatic breakdown within the cell and accumulates, eventually leading to neurodegeneration. The amino acid sequence of the prion protein and tissue distribution of PrPSc within affected hosts have a major role in determining susceptibility to and potential environmental contamination with the scrapie agent. Many countries have genotype-based eradication programs that emphasize using rams that express arginine at codon 171 in the prion protein, which is associated with resistance to the classical scrapie agent. In classical scrapie, accumulation of PrPSc within lymphoid and other tissues facilitates environmental contamination and spread of the disease within flocks. A major distinction can be made between classical scrapie strains that are readily spread within populations of susceptible sheep and goats and atypical (Nor-98) scrapie that has unique molecular and phenotype characteristics and is thought to occur spontaneously in older sheep or goats. This review provides an overview of classical and atypical scrapie with consideration of potential transmission of classical scrapie to other mammalian hosts.

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