Protective effect of the AT<sub>137</sub>RQ and ARQK<sub>176</sub>PrP allele against classical scrapie in Sarda breed sheep

Vaccari, Gabriele; Scavia, Gaia; Sala, M.; Cosseddu, Gian Mario; Chiappini, Barbara; Conte, Michela; Esposito, Elena; Lorenzetti, Raniero; Perfetti, G; Marconi, Paola; Scholl, Francesco; Barbaro, Kátia Cristina; Bella, Antonino; Nonno, Romolo; Agrimi, Umberto

doi:10.1051/vetres/2009002

Cited by 39 publications

(53 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An M112T variant on the ARQ haplotype has been associated with scrapie resistance in orally-inoculated Suffolk sheep in the U.S. (Laegreid et al 2008). M137T and N176K variants on the ARQ haplotype have been associated with scrapie resistance in intercranially-inoculated, orally-inoculated, and naturally-infected Italian Sarda breed sheep (Vaccari et al 2007;Vaccari et al 2009). Variations at codon 141 can be related to the atypical scrapie form Nor98 (Mazza et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

et al. 2011

View full text Add to dashboard Cite

Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc). This isoform presents an altered conformation that leads to aggregation in the host's central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be influenced by specific genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal's genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171). The most variable codon was 171, where all described alleles were identified. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons, all of them corresponding to the wild-type prion protein. Regarding the risk degree of developing scrapie, most of the animals (96%) had genotypes corresponding to risk groups 1 to 3 (very low to moderate), with only 4% in the higher risks group. Our data is discussed in relation to preventive measures involving genotyping and positive selection to control the disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

et al. 2011

View full text Add to dashboard Cite

show abstract

“…As concerns subtype M112T in association with ARQ haplotype, it has been associated with susceptibility to scrapie in the US Suffolk breed (Laegrid et al 2008;Heaton et al 2010, Harington et al, 2010, and the variants of haplotype ARQ -M137T and N176K have been associated with scrapie resistance in intercranially-inoculated, orally inoculated, and naturally infected Italian Sarda breed sheep (Vaccari et al, 2007(Vaccari et al, , 2009). The existence of some subtypes of the ARQ genotype resistant to scrapie opens up the possibility of MAS, without the presence of homozygote ARR/ ARR.…”

Section: Genetics Of Scrapie Diseasementioning

confidence: 99%

Current understanding of PrnP Genetics: A tool for Molecular Assisted Selection in Sheep Populations (A review)

Coşier¹,

Dărăban²

2016

BUASVMCN-ASB

View full text Add to dashboard Cite

Scrapie is a neurodegenerative prion disease of sheep, goats and mouflons, belonging to the group of transmissible spongiform encephalopathies (TSEs), which affects humans as well. Even though classical scrapie has been known for over 250 years, the 1985 BSE crisis related to the advent of new forms of the Creutzfeldt-Jakob disease (vCJD) in humans imposed the implementation of rapid coercive legal measures of prevention, control and eradication of TSEs. According to the prion hypothesis, the transmissible agent is the pathological isoform (PrP Sc ) of cellular prion protein (PrP C ). Specific polymorphisms of the gene that encodes cell prion protein (PrnP) in sheep have been associated with resistance / natural susceptibility to the development and progression of the disease. Combinations of alleles at three adjacent codons (136 [A/V], 154 [H/R], 171 [H/Q/R]) underpin the classification of 15 possible genotypes in risk classes, applicable in selection schemes where the maximum resistance is conferred by ARR allele, and the minimum by the VRQ allele. Although, after applying these programmes, the genetic structure of sheep populations has changed favourably, genotype association studies showed that no genotype is completely resistant to the infection, including homozygote ARR / ARR. With the discovery of atypical scrapie (Nor98), it became evident that the connection between the genetics of prion protein gene polymorphisms and susceptibility to the disease must be re-evaluated individually for each breed. In scrapie monitoring and control programmes, three diagnostic categories of the disease are observed: classical scrapie, atypical scrapie and BSE scrapie in small ruminant. This review shows the chronology of progress in the fight for the eradication of TSEs in sheep, 30 years after the BSE epidemic outburst, focusing especially on the link between the molecular diagnostic forms and the genetics of the disease.

show abstract

“…Genotyping analysis of codons 136, 154, and 171 was performed following the protocol described by Vaccari et al (2009) PrP genotypes were reconstructed on the assumption that all polymorphisms are mutually exclusive. The allele shall be defined by reference to the amino acids (three-letter code e.g.…”

Section: Dna Extraction and Genotyping Analysismentioning

confidence: 99%

“…The PRNP gene portion (1229 bp) where the entire CDS sequence is located, has been amplified in the homozygous ARQ samples as described by Vaccari et al (2009) in a Mastercycler ® ep gradient S (Eppendorf ® , Hamburg, Germany). PCR fragments were purified with QIAquick ® PCR purification kit (Qiagen ® , Hilden, Germany) according to manufacturer's recommendations.…”

Section: Sequencing Analysismentioning

confidence: 99%

“…Sarda sheep breed shows two alleles associated to classical scrapie resistance, AT137RQ and ARQK176 (Maestrale et al, 2009;Vaccari et al, 2009;Bucalossi et al, 2011). In a clinical study that involved the Barbado breed, heterozygous ARQ-ARK171 showed a prolonged average incubation time of 30 months before the onset of clinical signs (Greenlee et al, 2012) and similarly, in infected Suffolk sheep, heterozygous AM112RQ-AT112RQ showed lower attack and increased survival rates (Chianini et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biodiversity and Genetic Polymorphisms Against Scrapie inSopravissanaSheep Breed

Curcio

Lasagna

Sarti

et al. 2015

Italian Journal of Animal Science

View full text Add to dashboard Cite

Scrapie is a neurodegenerative disease affecting ovine and it is one of several transmissible spongiform encephalopathies (TSEs). Scrapie is recognized as two forms -classical and atypical. Susceptibility or resistance to classical scrapie is strongly regulated by the polymorphisms at codons 136, 154 and 171 of the PRNP gene. Genetic role in atypical scrapie has been described at codons 141 and 154, these ones are involved in the occurrence of the disease at different risk degrees. The aim of this study was to assess the allelic and genotypic frequencies in Sopravissana breed, an endangered autochthon breed of central Italy; in addition, the presence and the frequency of potential protective ARQ allele variants able to increase scrapie resistance by preserving a higher variability of PRNP were evaluated. Three alleles (ARQ, ARR and AHQ) and seven genotypes were observed based on codons 136, 154 and 171 with different frequencies. Moreover, the entire coding sequence of prion protein (PRNP) of the ARQ/ARQ was sequenced; two non-synonymous L141F (23.8%) and H143R (16.7%), also two synonymous polymorphisms (codons 231 and 237) were found. The results showed that the ARQ/ARQ sheep should be considered as a genetic class, which may potentially include animals with different scrapie susceptibility because of the presence of additional polymorphisms. This may allow the application of alternative strategies for breeding programmes in this endangered breed.

show abstract

Protective effect of the AT₁₃₇RQ and ARQK₁₇₆PrP allele against classical scrapie in Sarda breed sheep

Cited by 39 publications

References 41 publications

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

Current understanding of PrnP Genetics: A tool for Molecular Assisted Selection in Sheep Populations (A review)

Biodiversity and Genetic Polymorphisms Against Scrapie inSopravissanaSheep Breed

Contact Info

Product

Resources

About

Protective effect of the AT137RQ and ARQK176PrP allele against classical scrapie in Sarda breed sheep

Cited by 39 publications

References 41 publications

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

Current understanding of PrnP Genetics: A tool for Molecular Assisted Selection in Sheep Populations (A review)

Biodiversity and Genetic Polymorphisms Against Scrapie inSopravissanaSheep Breed

Contact Info

Product

Resources

About

Protective effect of the AT₁₃₇RQ and ARQK₁₇₆PrP allele against classical scrapie in Sarda breed sheep