Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, J.P.M.; Ekateriniadou, Loukia; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

doi:10.1099/jgv.0.000843

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…This has been experimentally confirmed by studies where 222Q-Tg501 and 222K-Tg516 mice were challenged by the prion. These experiments showed that 222K-Tg516 mice were resistant to all inoculates, while heterozygous 222QK mice were clearly more resistant to various scrapie isolates compared to 222Q-Tg501 mice, concluding that the 222K allele provides a dominant negative effect over the wild-type PrP sequence [ 51 ]. However, in our study, polymorphisms at codon 222 were not found to affect the likelihood of a goat to be infected by scrapie or originate from a scrapie-positive herd.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of Codons 110, 146, 211 and 222 at the Goat PRNP Locus and Their Association with Scrapie in Greece

Gelasakis

Boukouvala²,

Babetsa³

et al. 2021

Animals

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Scrapie is considered an endemic disease in both sheep and goats in Greece. However, contrary to sheep, in goats more than one prion protein (PrP) polymorphism has been recognized as a candidate for resistance breeding against the disease. For an impression, candidates which are circulating, (i) brain samples (n = 525) from scrapie-affected (n = 282) and non-affected (n = 243) animals within the national surveillance program, and (ii) individual blood samples (n = 1708) from affected (n = 241) and non-affected (n = 1467) herds, in a large part of mainland Greece and its islands, were collected and assayed. A dedicated Taqman method was used to test for amino acid polymorphisms 110T/P, 146N/S/D, 211R/Q, and 222Q/K. Highly prevalent genotypes were 110TT, 146NN, 211RR, and 222QQ. The frequencies of polymorphisms in blood and negative brain samples for codons 110P, 211Q, and 222K were 4.0%, 3.0%, and 1.9%, respectively, while 146D (0.7%) was present only on Karpathos island. Codon 110P was exclusively found in scrapie-negative brains, and homozygous 110P/P in two scrapie-negative goats. It is concluded that breeding programs in Karpathos could focus on codon 146D, while in other regions carriers of the 110P and 222K allele should be sought. Case-control and challenge studies are now necessary to elucidate the most efficient breeding strategies.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms of Codons 110, 146, 211 and 222 at the Goat PRNP Locus and Their Association with Scrapie in Greece

Gelasakis

Boukouvala²,

Babetsa³

et al. 2021

Animals

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“…10,35 Further study of goats heterozygous for the K222 allele that were diagnosed with classical scrapie indicates that the PrP Sc produced is almost entirely composed of the Q222 variant, perhaps due to effect of the additional positive charge of lysine interfering with PrP C to PrP Sc conversion. 108 A small number of goats homozygous for the K222 allele developed classical scrapie with extremely prolonged incubation periods after intracranial inoculation, suggesting that resistance to classical scrapie is not absolute. 99…”

Section: Role Of the Host Prion Protein Gene (Prnp)mentioning

confidence: 99%

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

Greenlee

2018

Vet Pathol

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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 (PrP C) misfolds into a pathogenic form (PrP Sc) 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 PrP Sc 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 PrP Sc 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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“…The S146 and K222 variants have been associated with scrapie resistance after experimental challenge in which none of the NS146 or QK222 goats had tissue accumulation of PrP Sc or developed clinical signs of scrapie for 7.5 years [25]. Further research on the PRNP codon 222 indicated all goats that were diagnosed with classical scrapie were almost entirely composed of the QQ222 variant [27].…”

Section: Introductionmentioning

confidence: 99%

Large-scale survey of prion protein genetic variability in scrapie disease-free goats from the United States

et al. 2021

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Scrapie is a slowly progressive neurodegenerative disease of small ruminants caused by an accumulation of an abnormal isoform of prion protein in the central nervous system. Polymorphisms of the prion protein gene (PRNP) strongly modulate scrapie resistance and incubation period in goats. The aim of this study was to identify PRNP genetic variability in goats across the United States. Blood from a total of 6,029 apparent scrapie disease-free goats from 654 operations and 19 breeds were analyzed. Sequencing of PRNP revealed 26 genotypes with different rates based on eight codons. The GG127, RR154, and QQ222 genotypes were predominant and showed a remarkably high rate across all goats. The QK222 and NS146 genotypes, known to be protective against scrapie, were found in 0.6% [with 95% CI = (0.3, 1.2)] and 22.0% [95% CI = (19.1, 25.2)] of goats, respectively. The QK222 genotype was found in 23.1% of Oberhasli goats tested, with 95%CI = (3.9, 68.7)] and 22.0% of Toggenburg goats tested with 95%CI = (9.7, 42.5)], while NS146 was found in 65.5% of Savannah goats tested, with 95%CI = (30.8, 89.9), 36.7% of Boer goats tested, with 95%CI = (33.1, 40.4), 36.3% of Nubian goats tested, with 95%CI = (27.0, 46.7)], and 35.6% of LaMancha goats tested, with 95%CI = (22.8, 50.8%). The MM142 and IM142 genotypes were found more frequently in goats on dairy operations, while the HR143, NS146, and ND146 genotypes were found more frequently in goats on meat operations. Goats in the east region had a higher percentage of goats with RH154, RQ211, and QK222 genotypes than goats in the west region. The results of this study showed high genetic variability of PRNP among the U.S. goat population, with differences by location and breed, and may serve as a rationale for development of goat breeding programs at the national level to mitigate the risk of scrapie.

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Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

Cited by 5 publications

References 29 publications

Polymorphisms of Codons 110, 146, 211 and 222 at the Goat PRNP Locus and Their Association with Scrapie in Greece

Polymorphisms of Codons 110, 146, 211 and 222 at the Goat PRNP Locus and Their Association with Scrapie in Greece

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

Large-scale survey of prion protein genetic variability in scrapie disease-free goats from the United States

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