Scrapie Resistance in ARQ Sheep

Laegreid, William W.; Clawson, Marion; Heaton, Michael P.; Green, B. T.; O’Rourke, Katherine I.; Knowles, Don

doi:10.1128/jvi.00710-08

Cited by 38 publications

(36 citation statements)

References 21 publications

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“…According to Laegreid et al (2008), animals homozygous for threonine at the 112 codon ([T/T]ARQ) did not develop the disease when orally challenged, ,whereas heterozygous animals for the same codon ([M/T]ARQ) developed the disease. These ϐindings reinforced the suggestion that different haplotypes associations are important to determine the resistance to developing scrapie.…”

Section: Resultsmentioning

confidence: 99%

“…Sequences derived (Goldmann et al, 1990, GenBank accession M31313). b Laegreid et al (2008) form the remaining samples had a Phred score bellow 20 for the consensus sequence at this region, making it impossible to determine the genotype with accuracy. Codons 116,127,137,138,141,151,167,168,176 and 180 all had genotypes corresponding to the wild type PrP gene (GenBank accession M31313, Tables 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…Codon variants at positions other than 136, 154, and 171 are also associated with scrapie resistance. 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).…”

Section: Introductionmentioning

confidence: 99%

“…Also important is the fact that sheep with the ARQ haplotype are not uniformly susceptible to scrapie, with implications for scrapie eradication programs, where ARQ sheep have previously been considered as a homogenous group, leading to losses of economically important sheep germplasm (Laegreid et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…15 In addition, specific PRNP alleles have been associated with TSE susceptibility in sheep. 16,17 In classical BSE, variation in the promoter region of the PRNP locus has also been shown to be associated with risk Pathway 28 databases and were included if the gene was known to be expressed in nervous tissue, was involved in proteolysis, protein folding or unfolding or protein transport.…”

Section: Introductionmentioning

confidence: 99%

The identification of candidate genes and SNP markers for classical bovine spongiform encephalopathy susceptibility

Thomson

Bowles

Choi

et al. 2012

Prion

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Report of outbreaks of classical scrapie in Dorper sheep and associated prion protein gene polymorphisms in affected flocks

Andrade

Oliveira

Leal

et al. 2015

Trop Anim Health Prod

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Scrapie is an infectious neurodegenerative disease affecting sheep and goats, related with conformational alteration of an isoform of the prion protein that leads to deposition and aggregation in the host's central nervous system. Occurrence of the natural disease can be influenced by host genetic factors, such as a single nucleotide polymorphism of the prion protein gene. This study reports three scrapie-affected Dorper flocks located on three different farms in Brazil. The objective of this study was to analyze these three flocks using scrapie diagnostics, combining histology, immunohistochemistry, genotyping, and western blot assays. For immunohistochemistry, 192 sheep were selected and 308 sheep blood samples were taken for genotyping. A total of 22 sheep were scrapie positive by immunohistochemistry. Of these, four presented clinical signs and had scrapie immunoreactivity at the obex in western blot assays. The sheep without clinical signs were positive in lymphoid organs, such as the third eyelid and rectal mucosa. The major genotypes found on the flocks were ARQ/ARQ, ARQ/ARR, and ARQ/VRQ for codons 136, 154, and 171. Most of the sheep were considered to be at moderate to high risk, based on risk groups for developing scrapie. Some blood samples were sequenced, and polymorphisms were identified in other codons, such as 127, 142, and 143. Our data demonstrate the importance of preclinical scrapie diagnosis in Brazilian sheep, as most of the affected sheep showed no clinical signs, and emphasize the relevance of genotyping other Dorper sheep to determine the genotypic profile of the breed.

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Scrapie Resistance in ARQ Sheep

Cited by 38 publications

References 21 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

The identification of candidate genes and SNP markers for classical bovine spongiform encephalopathy susceptibility

Report of outbreaks of classical scrapie in Dorper sheep and associated prion protein gene polymorphisms in affected flocks

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