scholarly journals Genetic Variation in the Prion Protein Gene (PRNP) of Two Tunisian Goat Populations

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1635
Author(s):  
Samia Kdidi ◽  
Mohamed Habib Yahyaoui ◽  
Michela Conte ◽  
Barbara Chiappini ◽  
Mohamed Hammadi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Transmissible Spongiform Encephalopathies ◽  
Prion Protein Gene ◽  
Breeding Programs ◽  
Low Frequencies ◽  
Spongiform Encephalopathies ◽  
Prolonged Incubation ◽  
Global View ◽  
First Time

Scrapie is a fatal prion disease. It belongs to transmissible spongiform encephalopathies (TSEs), and occurs in sheep and goats. Similarly, to ovine species, the prion protein gene (PRNP) plays a major role in conferring resistance or susceptibility to TSE in goats. This study assesses the variability of PRNP in native and crossed-breed goat populations raised in the Southeast of Tunisia and provides information on the distribution of PRNP haplotypes and genotypes in these goat populations. A total of 116 unrelated goats including 82 native and 34 crossed-breed goats were screened for PRNP polymorphisms using Sanger sequencing. Sequence analysis revealed 10 non-synonymous polymorphisms (G37V, M137I, R139S, I142M, H143R, N146D, R154H, R211Q, Q222K, and S240P), giving rise to 12 haplotypes and 23 genotypes. Moreover, four silent mutations were detected at codons 30, 42, 138, and 179; the former was reported for the first time in goat (nucleotide 60 c→t). Interestingly, the PrP variants associated with resistance (D146 and K222) or with a prolonged incubation time of goat to scrapie (M142, R143, H154, Q211) were absent or detected with low frequencies except for H154 variant, which is present with high frequency (1%, 1%, 4%, 0%, 88%, and 6%, respectively, for native goats, and 0%, 1%, 0%, 1%, 78%, and 1%, respectively, for crossed goats). The analysis of PRNP polymorphisms of goats raised in other regions of the country will be useful in getting a global view of PRNP genetic variability and the feasibility of goat breeding programs in Tunisia.

scholarly journals Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong-Chan Kim ◽  
Seon-Kwan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Allele Frequencies ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Prion Protein Gene ◽  
Indel Polymorphism ◽  
Spongiform Encephalopathies ◽  
Direct Dna Sequencing ◽  
Significant Difference

Abstract Prion diseases in sheep and goats are called scrapie and belong to a group of transmissible spongiform encephalopathies (TSEs) caused by the abnormal misfolding of the prion protein encoded by the prion protein gene (PRNP). The shadow of the prion protein gene (SPRN) is the only prion gene family member that shows a protein expression profile similar to that of the PRNP gene in the central nervous system. In addition, genetic susceptibility of the SPRN gene has been reported in variant Creutzfeldt–Jakob disease (CJD), bovine spongiform encephalopathy (BSE) and scrapie. However, genetic studies of the SPRN gene have not been carried out in Korean native black goats. Here, we investigated the genotype and allele frequencies of SPRN polymorphisms in 213 Korean native black goats and compared these polymorphisms with those previously reported for scrapie-affected animals. We found a total of 6 polymorphisms including 1 nonsynonymous single nucleotide polymorphism (SNP) and 1 synonymous SNP in the open reading frame (ORF) region and 3 SNPs and 1 indel polymorphism (c.495_496insCTCCC) in the 3′ untranslated region (UTR) by direct DNA sequencing. A significant difference in the allele frequency of the c.495_496insCTCCC indel polymorphism was found between the Italian scrapie-affected goats and the Korean native black goats (P < 0.001). Furthermore, there was a significant difference in the allele frequencies of the c.495_496insCTCCC indel polymorphism between Italian healthy goats and Korean native black goats (P < 0.001). To evaluate the biological impact of the novel nonsynonymous SNP c.416G > A (Arg139Gln), we carried out PROVEAN analysis. PROVEAN predicted the SNP as ‘Neutral’ with a score of −0.297. To the best of our knowledge, this is the first genetic study of the SPRN gene in Korean native black goats.

scholarly journals Functional disruption of the prion protein gene in cloned goats

2006 ◽  
Vol 87 (4) ◽  
pp. 1019-1027 ◽  
Author(s):  
Guohua Yu ◽  
Jianquan Chen ◽  
Huiqing Yu ◽  
Siguo Liu ◽  
Juan Chen ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Cellular Prion Protein ◽  
Abnormal Development ◽  
Transmissible Spongiform Encephalopathies ◽  
Membrane Glycoprotein ◽  
Prion Protein Gene ◽  
Spongiform Encephalopathies ◽  
Scrapie Infection ◽  
Large Animals

The cellular prion protein (PrPC), a membrane glycoprotein anchored to the outer surface of neurons, lymphocytes and other cells, is associated directly with the pathogenesis of the transmissible spongiform encephalopathies (TSEs) occurring mainly in humans, cattle, sheep and goats. Although mice lacking PrPC develop and reproduce normally and are resistant to scrapie infection, large animals lacking PrPC, especially those species in which TSE occurs naturally, are currently not available. Here, five live PRNP +/− goats cloned by gene targeting are reported. Detailed RNA-transcription and protein-expression analysis of one PRNP +/− goat showed that one allele of the caprine PRNP gene had been disrupted functionally. No gross abnormal development or behaviour could be seen in these PRNP +/− goats up to at least 3 months of age. These heterozygous PRNP +/− goats are ready to be used in producing homozygous PRNP −/− goats in which no PrPC should be expressed.

scholarly journals PRION PROTEIN GENE SEQUENCES ANALYSIS IN TWELVE SHEEP BREEDS OF PAKISTAN

AGROFOR ◽  
2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Mohammad Farooque HASSAN
Keyword(s):  
Sequence Analysis ◽  
Prion Protein ◽  
Protein Gene ◽  
Mammalian Species ◽  
Pcr Amplification ◽  
Transmissible Spongiform Encephalopathies ◽  
Prion Protein Gene ◽  
Spongiform Encephalopathies ◽  
Sheep Breeds ◽  
Abnormal Form

Prions are considered the only agents of transmissible spongiform encephalopathies (TSEs) and are harmful pathogens of mammals. These infectious agents of host are made up through aggregation of conformational isomers (PrPSc) and encode glycoprotein (PrPC) of 33-35 kDa. TSEs are the fatal group of diseases which are neurodegenerative and include chronic wasting disease in deer and elk, Creutzfeldt-Jakob disease (CJD) and transmissible mink encephalopathy (TME) in humans and scrapie in goats and sheep. The accumulation of abnormal form of the normal protein (PrP) is common in all diseases related TSE. This abnormal form of PrP called PrPSc is resistant to proteolysis as well as infectious. Present study was conducted in order to do sequence analysis of prion protein gene in twelve breeds of the sheep. We studied this gene to elucidate 12 of Pakistani sheep breeds and to compare gene order with other mammalian species. PCR amplification of 771 bp fragment was done on selected samples from all twelve breeds followed by sequencing. Sequence analysis was done and some sites were found to be heterozygous. These findings on prion protein gene in sheep will provide assistance for further studies on pathogenesis, cross-species transmission, breeding programs, resistance and susceptibility to scrapie.

scholarly journals Low frequency of the scrapie resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

2004 ◽  
Vol 85 (10) ◽  
pp. 3165-3172 ◽  
Author(s):  
P. L. Acutis ◽  
L. Sbaiz ◽  
F. Verburg ◽  
M. V. Riina ◽  
G. Ru ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Prion Protein ◽  
Negative Selection ◽  
Protein Gene ◽  
Low Frequency ◽  
Allele Frequencies ◽  
Transmissible Spongiform Encephalopathies ◽  
Prion Protein Gene ◽  
Spongiform Encephalopathies ◽  
Total Frequency

Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele was also found, with the highest frequency reported so far in an ovine breed (2·5 %). ARK/--- genotypes had a total frequency of 4·9 %. The resistance-associated ARR allele was seen at a low frequency (8·3 %). Only 1·4 % of animals examined had a resistant ARR/ARR PrP genotype. Semi-resistant (ARR/ARQ, ARR/ARH and ARR/AHQ) PrP genotypes had a total frequency of 12·6 % and PrP genotypes that are associated with high scrapie susceptibility (e.g. VRQ/VRQ and ARQ/ARQ) had a total frequency of 81·1 %. Statistical analysis comparing PrP allele frequencies between pure-bred and cross-bred animals showed that the ARR allele occurred at a significantly lower frequency in pure-bred rams. Furthermore, comparison of PrP allele frequencies between pure-bred rams over 18 months of age and those below 18 months of age showed a significant decrease in the ARR allele in breeding rams over 18 months of age. Based on these results, breeding for scrapie resistance in the Biellese breed will have to take into account the low frequency of the ARR allele, which also seems to be subject to negative selection by farmers. Further investigation is required to understand whether the ARK allele is also associated with resistance to transmissible spongiform encephalopathies.

scholarly journals Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene (PRNP) in Dogs—A Resistant Animal of Prion Disease

2020 ◽  
Vol 21 (11) ◽  
pp. 4160 ◽  
Author(s):  
Dong-Ju Kim ◽  
Yong-Chan Kim ◽  
An-Dang Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Hydrogen Bonds ◽  
Prion Protein ◽  
Protein Gene ◽  
Direct Sequencing ◽  
Transmissible Spongiform Encephalopathies ◽  
Prion Protein Gene ◽  
Genetic Characteristics ◽  
Aggregation Propensity ◽  
Wide Range ◽  
The Impact

Transmissible spongiform encephalopathies (TSEs) have been reported in a wide range of species. However, TSE infection in natural cases has never been reported in dogs. Previous studies have reported that polymorphisms of the prion protein gene (PRNP) have a direct impact on the susceptibility of TSE. However, studies on polymorphisms of the canine PRNP gene are very rare in dogs. We examined the genotype, allele, and haplotype frequencies of canine PRNP in 204 dogs using direct sequencing and analyzed linkage disequilibrium (LD) using Haploview version 4.2. In addition, to evaluate the impact of nonsynonymous polymorphisms on the function of prion protein (PrP), we carried out in silico analysis using PolyPhen-2, PROVEAN, and PANTHER. Furthermore, we analyzed the structure of PrP and hydrogen bonds according to alleles of nonsynonymous single nucleotide polymorphisms (SNPs) using the Swiss-Pdb Viewer program. Finally, we predicted the impact of the polymorphisms on the aggregation propensity of dog PrP using AMYCO. We identified a total of eight polymorphisms, including five novel SNPs and one insertion/deletion polymorphism, and found strong LDs and six major haplotypes among eight polymorphisms. In addition, we identified significantly different distribution of haplotypes among eight dog breeds, however, the kinds of identified polymorphisms were different among each dog breed. We predicted that p.64_71del HGGGWGQP, Asp182Gly, and Asp182Glu polymorphisms can impact the function and/or structure of dog PrP. Furthermore, the number of hydrogen bonds of dog PrP with the Glu182 and Gly182 alleles were predicted to be less than those with the Asp182 allele. Finally, Asp163Glu and Asp182Gly showed more aggregation propensity than wild-type dog PrP. These results suggest that nonsynonymous SNPs, Asp182Glu and Asp182Gly, can influence the stability of dog PrP and confer the possibility of TSE infection in dogs.

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.

scholarly journals Genetic and Pathological Follow-Up Study of Goats Experimentally and Naturally Exposed to a Sheep Scrapie Isolate

2015 ◽  
Vol 89 (19) ◽  
pp. 10044-10052 ◽  
Author(s):  
Caterina Maestrale ◽  
Maria G. Cancedda ◽  
Davide Pintus ◽  
Mariangela Masia ◽  
Romolo Nonno ◽  
...  
Keyword(s):  
Prion Protein ◽  
Gene Sequence ◽  
Protein Gene ◽  
Brain Homogenate ◽  
Prion Protein Gene ◽  
Wild Type ◽  
Related Factors ◽  
Sheep And Goats ◽  
First Time ◽  
Sheep Scrapie

ABSTRACTThirty-seven goats carrying different prion protein genotypes (PRNP) were orally infected with a classical scrapie brain homogenate from wild-type (ARQ/ARQ) sheep and then mated to obtain 2 additional generations of offspring, which were kept in the same environment and allowed to be naturally exposed to scrapie. Occurrence of clinical or subclinical scrapie was observed in the experimentally infected goats (F0) and in only one (F1b) of the naturally exposed offspring groups. In both groups (F0and F1b), goats carrying the R154H, H154H, R211Q, and P168Q-P240P dimorphisms died of scrapie after a longer incubation period than wild-type, G37V, Q168Q-P240P, and S240P goats. In contrast, D145D and Q222K goats were resistant to infection. The immunobiochemical signature of the scrapie isolate and its pathological aspects observed in the sheep donors were substantially maintained over 2 goat generations, i.e., after experimental and natural transmission. This demonstrates that the prion protein gene sequence, which is shared by sheep and goats, is more powerful than any possible but unknown species-related factors in determining scrapie phenotypes. With regard to genetics, our study confirms that the K222 mutation protects goats even against ovine scrapie isolates, and for the first time, a possible association of D145 mutation with scrapie resistance is shown. In addition, it is possible that the sole diverse frequencies of these genetic variants might, at least in part, shape the prevalence of scrapie among naturally exposed progenies in affected herds.IMPORTANCEThis study was aimed at investigating the genetic and pathological features characterizing sheep-to-goat transmission of scrapie. We show that in goats with different prion protein gene mutations, the K222 genetic variant is associated with scrapie resistance after natural and experimental exposure to ovine prion infectivity. In addition, we observed for the first time a protective effect of the D145 goat variant against scrapie. Importantly, our results demonstrate that the phenotypic characteristic of the wild-type sheep scrapie isolate is substantially preserved in goats carrying different susceptiblePRNPgene variants, thus indicating that the prion protein gene sequence, which is shared by sheep and goats, plays a fundamental role in determining scrapie phenotypes.

scholarly journals Multiple Amino Acid Residues within the Rabbit Prion Protein Inhibit Formation of Its Abnormal Isoform

2003 ◽  
Vol 77 (3) ◽  
pp. 2003-2009 ◽  
Author(s):  
Ina Vorberg ◽  
Martin H. Groschup ◽  
Eberhard Pfaff ◽  
Suzette A. Priola
Keyword(s):  
Amino Acid ◽  
Prion Protein ◽  
Neurological Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Amino Acid Residues ◽  
Spongiform Encephalopathies ◽  
Prolonged Incubation ◽  
Culture Cells ◽  
Scrapie Agent

ABSTRACT Transmissible spongiform encephalopathies (TSEs) are neurological diseases that are associated with the conversion of the normal host-encoded prion protein (PrP-sen) to an abnormal protease-resistant form, PrP-res. Transmission of the TSE agent from one species to another is usually inefficient and accompanied by a prolonged incubation time. Species barriers to infection by the TSE agent are of particular importance given the apparent transmission of bovine spongiform encephalopathy to humans. Among the few animal species that appear to be resistant to infection by the TSE agent are rabbits. They survive challenge with the human kuru and Creutzfeldt-Jakob agents as well as with scrapie agent isolated from sheep or mice. Species barriers to the TSE agent are strongly influenced by the PrP amino acid sequence of both the donor and recipient animals. Here we show that rabbit PrP-sen does not form PrP-res in murine tissue culture cells persistently infected with the mouse-adapted scrapie agent. Unlike other TSE species barriers that have been studied, critical amino acid residues that inhibit PrP-res formation are located throughout the rabbit PrP sequence. Our results suggest that the resistance of rabbits to infection by the TSE agent is due to multiple rabbit PrP-specific amino acid residues that result in a PrP structure that is unable to refold to the abnormal isoform associated with disease.

scholarly journals Pathological prion protein in muscles of hamsters and mice infected with rodent-adapted BSE or vCJD

2006 ◽  
Vol 87 (1) ◽  
pp. 251-254 ◽  
Author(s):  
Achim Thomzig ◽  
Franco Cardone ◽  
Dominique Krüger ◽  
Maurizio Pocchiari ◽  
Paul Brown ◽  
...  
Keyword(s):  
Public Health ◽  
Prion Protein ◽  
Health Risks ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Mammalian Muscle ◽  
Public Health Risks ◽  
Jakob Disease ◽  
First Time

Recently, pathological prion protein (PrPTSE) was detected in muscle from sheep infected with scrapie, the archetype of transmissible spongiform encephalopathies (TSEs). This finding has highlighted the question of whether mammalian muscle may potentially also provide a reservoir for TSE agents related to bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob Disease (vCJD). Here, results are reported from studies in hamsters and mice that provide direct experimental evidence, for the first time, of BSE- and vCJD-associated PrPTSE deposition in muscles. Our findings emphasize the need for further assessment of possible public-health risks from TSE involvement of skeletal muscle.

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