Polymorphism of the prion protein gene (PRNP) in Polish Merino and Suffolk sheep flocks

The aim of the study was to investigate the distribution of prion protein PRNP alleles in flocks of Polish Merino and Suffolk sheep. The research was conducted in 2012-2017 on ewes and rams kept in the Golina Wielka sheepfold (Greater Poland Voivodeship, Poland). All animals (264 ♀ and 64 ♂ Polish Merino; 98 ♀ and 73 ♂ Suffolk) were up to one year old. PRNP gene polymorphism was identified in the sheep. The frequency of scrapie alleles and genotypes was found to be highly significantly influenced by the breed and significantly influenced by the year in the case of Polish Merino sheep. Five alleles (ALRR, ALRQ, ALHQ, AFRQ and VLRQ) were detected in Polish Merino sheep, leading to the identification of 10 PRNP genotypes. In the Suffolk breed, three alleles (ALRR, ALRQ and ALHQ) and three genotypes were identified. In the Polish Merino breed, the frequency of the ALRR/ALRQ genotype was high and was the highest among all genotypes, followed by ALRR/ALRR. The level of genotypes containing valine at codon 136 was very low. In the Suffolk breed, the frequency of the ALRR/ALRR genotype was very high, and there were no alleles with valine at codon 136. In addition, in Polish Merino sheep, phenylalanine at codon 141 was detected only in the AFRQ allele, which appeared in two genotypes (in combination with ALRR and ALRQ).

Download Full-text

Polymorphism of the PrP prion protein gene in Polish Merino and old-type Polish Merino from Brylewo flock

Bulletin of the Veterinary Institute in Pulawy ◽

10.1515/bvip-2015-0047 ◽

2015 ◽

Vol 59 (2) ◽

pp. 321-326

Author(s):

Roman Niżnikowski ◽

Artur Oprządek ◽

Grzegorz Czub ◽

Marcin Świątek ◽

Dariusz Kubasik ◽

...

Keyword(s):

Prion Protein ◽

High Frequency ◽

Protein Gene ◽

Frequency Of Occurrence ◽

Prion Protein Gene ◽

Very High Frequency ◽

Significant Frequency ◽

Merino Sheep ◽

One Year ◽

Very High

Abstract The study was conducted on Polish Merino (143♀ and 39♂) and old-type Polish Merino sheep (176♀ and 61♂) in Brylewo flock (Wielkopolskie Province). The examined sheep were at the age of one year. Prion protein (PrP) genotype was determined in all animals. In both breeds four alleles (ARR, ARQ, AHQ, VRQ) were found. Highly significant effect of breed and insignificant impact of gender within breed was observed in regard to the frequency of occurrence of alleles and genotypes susceptible to classical scrapie in the sheep. Eight different PrP genotypes in Polish Merino and nine genotypes in old-type Polish Merino were identified. Very high frequency of ARR/ARR genotype in old-type Polish Merino and high frequency of ARR/ARQ genotype in Polish Merino were found, with relatively significant frequency of occurrence of the genotypes containing VRQ allele. In old-type Polish Merino, three animals (of both genders) had VRQ/VRQ genotype. Breeding work involving elimination of animals encoding valine at codon 136, and introduction of rams with ARR allele to the population increased the frequency of occurrence of ARR/ARR genotype and ARR allele in the population of old-type Polish Merino. To improve the distribution of the genotypes genetically resistant to scrapie in the flock of Polish Merino only rams with ARR/ARR genotype were left. This guarantees an increase in the frequency of occurrence of genotypes genetically resistant to scrapie in the offspring.

Download Full-text

The First Report of the Prion Protein Gene (PRNP) Sequence in Pekin Ducks (Anas platyrhynchos domestica): The Potential Prion Disease Susceptibility in Ducks

Genes ◽

10.3390/genes12020193 ◽

2021 ◽

Vol 12 (2) ◽

pp. 193

Author(s):

Min-Ju Jeong ◽

Yong-Chan Kim ◽

Byung-Hoon Jeong

Keyword(s):

Prion Protein ◽

Dna Sequence ◽

Prion Disease ◽

Protein Gene ◽

Prnp Gene ◽

Pekin Duck ◽

Prion Protein Gene ◽

First Report ◽

Aggregation Propensity ◽

Pekin Ducks

Pathogenic prion protein (PrPSc), converted from normal prion protein (PrPC), causes prion disease. Although prion disease has been reported in several mammalian species, chickens are known to show strong resistance to prion diseases. In addition to chickens, the domestic duck occupies a large proportion in the poultry industry and may be regarded as a potential resistant host against prion disease. However, the DNA sequence of the prion protein gene (PRNP) has not been reported in domestic ducks. Here, we performed amplicon sequencing targeting the duck PRNP gene with the genomic DNA of Pekin ducks. In addition, we aligned the PrP sequence of the Pekin duck with that of various species using ClustalW2 and carried out phylogenetic analysis using Molecular Evolutionary Genetics Analysis X (MEGA X). We also constructed the structural modeling of the tertiary and secondary structures in avian PrP using SWISS-MODEL. Last, we investigated the aggregation propensity on Pekin duck PrP using AMYCO. We first reported the DNA sequence of the PRNP gene in Pekin ducks and found that the PrP sequence of Pekin ducks is more similar to that of geese than to that of chickens and mallards (wild ducks). Interestingly, Pekin duck PrP showed a high proportion of β-sheets compared to that of chicken PrP, and a high aggregation propensity compared to that of avian PrPs. However, Pekin duck PrP with substitutions of chicken-specific amino acids showed reduced aggregation propensities. To the best of our knowledge, this is the first report on the genetic characteristics of the PRNP sequence in Pekin ducks.

Download Full-text

The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (PRNP) with Sporadic Creutzfeldt–Jakob Disease

Cells ◽

10.3390/cells10113132 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3132

Author(s):

Yong-Chan Kim ◽

Byung-Hoon Jeong

Keyword(s):

Prion Protein ◽

Protein Gene ◽

Meta Analysis ◽

Prnp Gene ◽

Case Control ◽

Prion Protein Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Jakob Disease ◽

Sporadic Cjd

Prion diseases are fatal, chronic, and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from endogenous forms of prion protein (PrPC). Several case–control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene (PRNP) is significantly associated with susceptibility to sporadic Creutzfeldt–Jakob disease (CJD). However, since some case–control studies have not shown these associations, the results remain controversial. We collected data that contain the genotype and allele frequencies of the M129V single-nucleotide polymorphism (SNP) of the PRNP gene and information on ethnic backgrounds from sporadic CJD patients. We performed a meta-analysis by collecting data from eligible studies to evaluate the association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD. We found a very strong association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using a meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found that the MM homozygote is a potent risk factor for sporadic CJD compared to the MV heterozygote in the heterozygote comparison model (MM vs. MV, odds ratio = 4.9611, 95% confidence interval: 3.4785; 7.0758, p < 1 × 10−10). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD.

Download Full-text

Identification of Prion Disease-Related Somatic Mutations in the Prion Protein Gene (PRNP) in Cancer Patients

Cells ◽

10.3390/cells9061480 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1480 ◽

Cited By ~ 3

Author(s):

Yong-Chan Kim ◽

Sae-Young Won ◽

Byung-Hoon Jeong

Keyword(s):

Cancer Patient ◽

Cancer Patients ◽

Prion Protein ◽

Patient Population ◽

Somatic Mutations ◽

Protein Gene ◽

Prion Diseases ◽

Prnp Gene ◽

Prion Protein Gene ◽

Total Cancer

Prion diseases are caused by misfolded prion protein (PrPSc) and are accompanied by spongiform vacuolation of brain lesions. Approximately three centuries have passed since prion diseases were first discovered around the world; however, the exact role of certain factors affecting the causative agent of prion diseases is still debatable. In recent studies, somatic mutations were assumed to be cause of several diseases. Thus, we postulated that genetically unstable cancer tissue may cause somatic mutations in the prion protein gene (PRNP), which could trigger the onset of prion diseases. To identify somatic mutations in the PRNP gene in cancer tissues, we analyzed somatic mutations in the PRNP gene in cancer patients using the Cancer Genome Atlas (TCGA) database. In addition, to evaluate whether the somatic mutations in the PRNP gene in cancer patients had a damaging effect, we performed in silico analysis using PolyPhen-2, PANTHER, PROVEAN, and AMYCO. We identified a total of 48 somatic mutations in the PRNP gene, including 8 somatic mutations that are known pathogenic mutations of prion diseases. We identified significantly different distributions among the types of cancer, the mutation counts, and the ages of diagnosis between the total cancer patient population and cancer patients carrying somatic mutations in the PRNP gene. Strikingly, although invasive breast carcinoma and glioblastoma accounted for a high percentage of the total cancer patient population (9.9% and 5.4%, respectively), somatic mutations in the PRNP gene have not been identified in these two cancer types. We suggested the possibility that somatic mutations of the PRNP gene in glioblastoma can be masked by a diagnosis of prion disease. In addition, we found four aggregation-prone somatic mutations, these being L125F, E146Q, R151C, and K204N. To the best of our knowledge, this is the first specific analysis of the somatic mutations in the PRNP gene in cancer patients.

Download Full-text

First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle

International Journal of Molecular Sciences ◽

10.3390/ijms21124246 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4246 ◽

Cited By ~ 2

Author(s):

Sae-Young Won ◽

Yong-Chan Kim ◽

Byung-Hoon Jeong

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Prion Protein ◽

Somatic Mutation ◽

Prion Disease ◽

In Silico ◽

Somatic Mutations ◽

Protein Gene ◽

Prnp Gene ◽

Spongiform Encephalopathy ◽

Prion Protein Gene

Bovine spongiform encephalopathy (BSE) is a prion disease characterized by spongiform degeneration and astrocytosis in the brain. Unlike classical BSE, which is caused by prion-disease-contaminated meat and bone meal, the cause of atypical BSE has not been determined. Since previous studies have reported that the somatic mutation in the human prion protein gene (PRNP) has been linked to human prion disease, the somatic mutation of the PRNP gene was presumed to be one cause of prion disease. However, to the best of our knowledge, the somatic mutation of this gene in cattle has not been investigated to date. We investigated somatic mutations in a total of 58 samples, including peripheral blood; brain tissue including the medulla oblongata, cerebellum, cortex, and thalamus; and skin tissue in 20 individuals from each breed using pyrosequencing. In addition, we estimated the deleterious effect of the K211 somatic mutation on bovine prion protein by in silico evaluation tools, including PolyPhen-2 and PANTHER. We found a high rate of K211 somatic mutations of the bovine PRNP gene in the medulla oblongata of three Holsteins (10% ± 4.4%, 28% ± 2%, and 19.55% ± 3.1%). In addition, in silico programs showed that the K211 somatic mutation was damaging. To the best of our knowledge, this study is the first to investigate K211 somatic mutations of the bovine PRNP gene that are associated with potential BSE progression.

Download Full-text

Prion protein gene polymorphism and genetic risk evaluation for scrapie in all Turkish native sheep breeds

Virus Genes ◽

10.1007/s11262-012-0744-7 ◽

2012 ◽

Vol 45 (1) ◽

pp. 169-175 ◽

Cited By ~ 7

Author(s):

H. Meydan ◽

B. Yüceer ◽

R. Degirmenci ◽

M. M. Özkan ◽

M. A. Yildiz

Keyword(s):

Gene Polymorphism ◽

Prion Protein ◽

Genetic Risk ◽

Risk Evaluation ◽

Protein Gene ◽

Prion Protein Gene ◽

Sheep Breeds ◽

Native Sheep

Download Full-text

Clinicopathologic characteristics of sporadic Japanese Creutzfeldt–Jakob disease classified according to prion protein gene polymorphism and prion protein type

Acta Neuropathologica ◽

10.1007/s00401-006-0111-7 ◽

2006 ◽

Vol 112 (5) ◽

pp. 561-571 ◽

Cited By ~ 43

Author(s):

Yasushi Iwasaki ◽

Mari Yoshida ◽

Yoshio Hashizume ◽

Tetsuyuki Kitamoto ◽

Gen Sobue

Keyword(s):

Gene Polymorphism ◽

Prion Protein ◽

Protein Gene ◽

Prion Protein Gene ◽

Clinicopathologic Characteristics ◽

Jakob Disease

Download Full-text

Effect of PRNP Gene Polymorphism on Reproductive Performance of Mother Sheep and their Offspring Growth

Bulletin of the Veterinary Institute in Pulawy ◽

10.2478/v10213-012-0050-0 ◽

2012 ◽

Vol 56 (3) ◽

pp. 279-282 ◽

Cited By ~ 1

Author(s):

Tomasz M. Gruszecki ◽

Monika Greguła-Kania ◽

Roman Niżnikowski ◽

Mirosław Pięta ◽

Krzysztof Kostro ◽

...

Keyword(s):

Amino Acids ◽

Gene Polymorphism ◽

Prion Protein ◽

Reproductive Performance ◽

Prnp Gene ◽

High Susceptibility ◽

Sheep Population ◽

Offspring Growth ◽

Very High ◽

Reproduction Efficiency

Abstract The polymorphism of prion protein (PrP) amino acids in codons 136 (A/V), 154 (R/H); and 171 (Q/R/H) was established. Reproductive performance of mother sheep was evaluated analysing the fertility coefficient and litter size, i.e. the number of born and reared lambs. The studies included mothers of synthetic lines BCP - 111 sheep and SCP - 104 sheep born in 2001-2007. In the examined ovine PRNP gene, the following four alleles were identified: ARR, AHQ, ARQ, and VRQ, with the absence of the ARH allele. The highest frequency was determined for the ARR (49.8%) and ARQ (45.8%) alleles. In the studied sheep population, the occurrence of seven different genotypes was reported. It was found that 71.6% of the animals had the genotypes ARR/ARR, ARR/ARQ, and ARR/AHQ, which are regarded as the most resistant to scrapie, while 7.9% of the population had ARR/VRQ-bearing genotypes (low resistance) or ARQ/VRQ ones (high susceptibility to scrapie). The analysis of the obtained results indicates that the PRNP genotype does not affect reproduction efficiency of mothers, or their offspring growth. It was concluded that flock elimination of ewes of genotypes with high and very high susceptibility to scrapie will not reduce the reproduction parameters of ewes or growth of their lambs.

Download Full-text