Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period

Goldmann, Wilfred; Martin, Trevor; Foster, James D.; Hughes, Steven D.; Smith, G; Hughes, Ken; Dawson, M.; Hunter, Nora

doi:10.1099/0022-1317-77-11-2885

Cited by 162 publications

(206 citation statements)

References 35 publications

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“…Protracted incubation periods, but no protection in terms of attack rate, were observed in methionine carriers at this codon challenged by parenteral routes with a diversity of TSE agents [10], while in this study of natural infection, those polymorphisms appeared to influence the susceptibility to infection. Thus, methionine carriers showed a lower overall prevalence than isoleucine homozygotes, but when doing a combined analysis together with the age, that effect was only seen in goats older than 60 months.…”

Section: Risk Factors For High Prevalence Of Infectioncontrasting

confidence: 67%

“…This is well established for sheep, but less well examined for goats [11]. The most common amino acid polymorphisms in British goat breeds are at codons 127 (glycine or serine), 142 (isoleucine or methionine), 143 (histidine or arginine) and 240 (proline or serine), and an association of polymorphisms at codons 142 and 143 with susceptibility and incubation period has been reported [1,2,10]. A comprehensive review of the goat PNRP gene polymorphisms and their association with disease has recently been published [31].…”

Section: Introductionmentioning

confidence: 99%

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High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect ofPRNPgenotype and age

González¹,

Martin²,

Sisó³

et al. 2009

Vet. Res.

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-Following a severe outbreak of clinical scrapie in 2006-2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and PRNP genotype on the susceptibility to scrapie, the tissue distribution of diseaseassociated PrP (PrP d ), and the comparative efficiency of different diagnostic methods. As determined by immunohistochemical (IHC) examinations with Bar224 PrP antibody, the prevalence of preclinical infection was very high (72/200; 36.0%), with most infected animals being positive for PrP d in lymphoreticular system (LRS) tissues (68/72; 94.4%) compared to those that were positive in brain samples (38/72; 52.8%). The retropharyngeal lymph node and the palatine tonsil showed the highest frequency of PrP d accumulation (87.3% and 84.5%, respectively), while the recto-anal mucosa-associated lymphoid tissue (RAMALT) was positive in only 30 (41.7%) of the infected goats. However, the efficiency of rectal and palatine tonsil biopsies taken shortly before necropsy was similar. The probability of brain and RAMALT being positive directly correlated with the spread of PrP d within the LRS. The prevalence of infection was influenced by PRNP genetics at codon 142 and by the age of the goats: methionine carriers older than 60 months showed a much lower prevalence of infection (12/78; 15.4%) than those younger than 60 months (20/42; 47.6%); these last showed prevalence values similar to isoleucine homozygotes of any age (40/80; 50.0%). Two of seven goats with definite signs of scrapie were negative for PrP d in brain but positive in LRS tissues, and one goat showed biochemical and IHC features of PrP d different from all other infected goats. The results of this study have implications for surveillance and control policies for scrapie in goats.scrapie / goat / prion disease / transmissible spongiform encephalopathy

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Section: Risk Factors For High Prevalence Of Infectioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect ofPRNPgenotype and age

González¹,

Martin²,

Sisó³

et al. 2009

Vet. Res.

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“…IM 142 heterozygotes had a lengthened incubation period after experimental inoculation with BSE and scrapie [32]. A PrP variant with three repeats and an additional W102G polymorphism was also associated with longer incubation periods after experimental challenges [33].…”

Section: Scrapie In Goatsmentioning

confidence: 93%

PrPgenetics in ruminant transmissible spongiform encephalopathies

2008

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-Scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) are prion diseases in ruminants with considerable impact on animal health and welfare. They can also pose a risk to human health and control is therefore an important issue. Prion protein (PrP) genetics may be used to control and eventually eradicate animal prion diseases. The PrP gene in sheep and other representatives of the order Artiodactyles has many polymorphisms of which several are crucial determinants of susceptibility to prion diseases, also known as transmissible spongiform encephalopathies (TSE). This review will present the current understanding of PrP genetics in ruminants highlighting similarity and difference between the species in the context of TSE.

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“…These variants include Met-142, 13,17,21,23 His-154, 14,18,19,21,23 Arg-143, 18 and alleles with stronger protective effects, such as Ser-146, Asp-146, 14,19,20 Gln-211 11,21,23 and Lys-222. 11,[21][22][23] These alleles' relative low occurrence frequency among herds and/or goat breeds examined in field studies, suggests that additional investigations within the context of a well defined experimental scheme, including sufficient test samples and controls, are required prior to gaining further conclusive information on their effects.…”

Section: Discussionmentioning

confidence: 99%

“…6,[9][10][11][12][13][14][15][16] Field studies, conducted in different countries on a variety of goat breeds, assigned some degree of protection against scrapie to the following alleles Met-142, Arg-143, Asp-146, Ser-146, His-154, Gln-211 and Lys-222. 11,13,14,[17][18][19][20][21][22][23] Among these, Met-142 is linked to prolonged incubation period, 13,17,21,23 while Arg-143 18 and His-154 14,18,19,21,23 are associated with moderate protection. Ser-146 or Asp-146, 14,19,20 Gln-211 11,21,23 and Lys-222 11,[21][22][23] are associated with higher degrees of protection, suggesting that they could be used as candidate alleles, targeted by a potential selective breeding strategy.…”

Section: Introductionmentioning

confidence: 99%

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells

Kanata

Arsenakis

Sklaviadis

2016

Prion

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Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period

Cited by 162 publications

References 35 publications

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect ofPRNPgenotype and age

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect ofPRNPgenotype and age

PrPgenetics in ruminant transmissible spongiform encephalopathies

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells

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