Which PrP haplotypes in a French sheep population are the most susceptible to atypical scrapie?

Moréno, Carole; Moazami‐Goudarzi, Katayoun; Laurent, Pascal; Cazeau, Géraldine; Andréoletti, Olivier; Chadi, Sead; Elsen, Jean-Michel; Calavas, Didier

doi:10.1007/s00705-007-0956-7

Cited by 41 publications

(40 citation statements)

References 13 publications

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“…While a clearly increased risk for developing AS is associated with AF 141 RQ and AHQ alleles, the VRQ allele seems to be at lower risk. Strikingly ARR allele carriers (both homozygous and heterozygous) can develop the disease (Moum et al, 2005;Arsac et al, 2007;Moreno et al, 2007). The differences in observed susceptibility of small ruminants to classical and AS illustrate that successful infection with TSE is strongly influenced by the nature of the agent involved, and the genetics of the host.…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Hald

Baggesen

2014

EFSA Journal

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To assess the effectiveness of the strategies implemented in the European Union (EU) to control Classical scrapie (CS), epidemiological data have been compared in the context of the efforts in terms of control measures applied over time. Official EU surveillance data and results from questionnaire surveys of EU Member States (MSs) have been used along with case studies. A spatio-temporal description of the occurrence of small ruminants TSEs in MSs in the period 2002-2012 is provided, with a particular focus on CS in sheep. Based on information collected from MSs, the potential effectiveness of breeding programmes for resistance to CS (BP-CS) in the dissemination of resistance into the general sheep population has been assessed for those countries for which the CS trend analysis has been performed. CS in sheep was reported in 17 MSs (average prevalence: 8.7 cases/10 000 tests), with heterogeneous trends and geographical distribution: among the 13 countries reporting a consistent number of cases, the trend analysis shows a statistically significant decreasing trend only for six of them. Variations in the implementation of genetic and non-genetic measures for the control of CS may explain the failure to improve the disease situation in the remaining seven MSs. At a national level, a reduction in CS seems to be linked to better-achieving BP-CSs. Control options applied to CS in sheep and goats indicate that a CS eradication policy that relies solely on the detection of infected flocks by post-mortem testing and subsequent depopulation would be unlikely to succeed. A minimum frequency of the ARR allele in a sheep population above which CS may be expected to fade-out could be estimated for each specific national sheep population. Recommendations for additional/alternative measures to control CS in sheep and goats are formulated. Scrapie situation in the EU EFSA Journal 2014;12 (7):3781 2 SUMMARYFollowing a request from the European Commission (EC), the EFSA Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the scrapie situation in the European Union (EU) after 10 years of monitoring and control in sheep and goats. In particular, in order to evaluate the measures in place and assess the progress accomplished, the EC consulted EFSA to gain a better understanding of the dynamics of the epidemiological situation of Classical scrapie (CS) and Atypical scrapie (AS), and a retrospective analysis of the effectiveness of the control tools encompassed by EU legislation.The opinion provides background information in relation to CS and AS in sheep and goats, including information on the nature of the agents, genetic susceptibility of the hosts, transmission pathways and epidemiology of the diseases.Based on information from the EU TSE surveillance database, CS and AS in sheep and goats in the period 2002-2012 have been analysed to provide a spatio-temporal description of the occurrence of the diseases, after appropriate statistical adjustment accounting for the main known confounding factor...

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Section: Genetic Susceptibilitymentioning

confidence: 99%

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Hald

Baggesen

2014

EFSA Journal

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“…Evidence so far indicates that atypical scrapie affects animals with PrP genotypes different from classical scrapie [2,3,9,26,27,29,30,33,36]. The appearance of atypical/Nor98 scrapie and classical scrapie in the same flock has not been reported as a common event, although there is no apparent genetic reason for this: indeed the separation of susceptible genotypes would perfectly permit infection with both diseases in an infected flock.…”

Section: Association Of Prp Genetics With Atypical Scrapiementioning

confidence: 99%

Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology

et al. 2008

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-Atypical/Nor98 scrapie cases in sheep were diagnosed for the first time in Norway in 1998. They are now identified in small ruminants in most European countries and represent an increasingly large proportion of the scrapie cases diagnosed in Europe. Atypical/Nor98 scrapie isolates have shown to be experimentally transmissible into transgenic mice and sheep but the properties of the TSE agent involved, like its biological and biochemical features, are so clearly distinct from the agent involved in classical scrapie that they have provided a challenging diagnostic for many years. No strain diversity has yet been identified among the atypical/Nor98 scrapie sample cases. The genetic predisposition of the sheep affected by atypical/Nor98 scrapie is almost inverted compared to classical scrapie, and the exact origin of this sporadic TSE strain is still speculative, but a spontaneous, non-contagious origin, like sporadic CreutzfeldtJakob disease in humans, can not be excluded. Further transmission and epidemiological studies are needed to better address this hypothesis. atypical scrapie / Nor98 / transmissible spongiform encephalopathies TSE / genetics / epidemiology

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“…Genotypes were linearly classifi ed into 5 levels of risk on a log scale (Table 1) according to the odds ratio (OR) estimated for the sheep population in France (19). Many genotypes were missing, mainly for controls because of diffi culties in extracting DNA from hair samples (n = 117) and for a few cases because of unsuitable samples (n = 13).…”

Section: Data Managementmentioning

confidence: 99%

“…Such an effect warrants confi rmation. Genetic factors should be considered when investigating risk factors for atypical scrapie because some mutations of the prnp gene, which codes for prion protein (PrP), modify the risk for this disease (2,18,19). Because all described genotypes of the prnp gene confer susceptibility to sheep, a purely genetic origin is unlikely but a confounding effect could occur.…”

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confidence: 99%

A Case–Control Study on the Origin of Atypical Scrapie in Sheep, France

Fediaevsky¹,

Morignat²,

Ducrot³

et al. 2009

Emerg. Infect. Dis.

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A matched case-control study (95 cases and 220 controls) was designed to study risk factors for atypical scrapie in sheep in France. We analyzed contacts with animals from other fl ocks, lambing and feeding practices, and exposure to toxic substances. Data on the prnp genotype were collected for some case and control animals and included in a complementary analysis. Sheep dairy farms had a higher risk for scrapie (odds ratio [OR] 15.1, 95% confi dence interval [CI] 3.3-69.7). Lower risk was associated with organic farms (OR 0.15, 95% CI 0.02-1.26), feeding corn silage (OR 0.16, 95% CI 0.05-0.53), and feeding vitamin and mineral supplements (OR 0.6, 95% CI 0.32-1.14). Genetic effects were quantitatively important but only marginally changed estimates of other variables. We did not fi nd any risk factor associated with an infectious origin of scrapie. Atypical scrapie could be a spontaneous disease infl uenced by genetic and metabolic factors.

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Which PrP haplotypes in a French sheep population are the most susceptible to atypical scrapie?

Abstract: A French sheep case control study has been organised to estimate the effects of the PrP haplotypes on resistance to atypical scrapie. The ALHQ and AFRQ haplotypes are significantly more susceptible than the others.

Cited by 41 publications

References 13 publications

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology

A Case–Control Study on the Origin of Atypical Scrapie in Sheep, France

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