RESUMO
Susceptibility to prion diseases is largely determined by the sequence of the prion protein gene (PRNP), which encodes the prion protein (PrP). The recent emergence of chronic wasting disease (CWD) in Europe has highlighted the need to investigate PRNP gene diversity in European deer species, to better predict their susceptibility to CWD. Here we report a large genetic survey of six British deer species, including red (Cervus elaphus), sika (Cervus nippon), roe (Capreolus capreolus), fallow (Dama dama), muntjac (Muntiacus reevesii), and Chinese water deer (Hydropotes inermis), which establishes PRNP haplotype and genotype frequencies. Two smaller data sets from red deer in Norway and the Czech Republic are also included for comparison. Overall red deer show the most PRNP variation, with non-synonymous/coding polymorphisms at codons 98, 168, 226 and 247, which vary markedly in frequency between different regions. Polymorphisms P168S and I247L were only found in Scottish and Czech populations, respectively. T98A was found in all populations except Norway and the south of England. Significant regional differences in genotype frequencies were observed within both British and European red deer populations. Other deer species showed less variation, particularly roe and fallow deer, in which identical PRNP gene sequences were found in all individuals analysed. Based on comparison with PRNP sequences of North American cervids affected by CWD and limited experimental challenge data, these results suggest that a high proportion of wild deer in Great Britain may be susceptible to CWD.
Assuntos
Cervos , Polimorfismo Genético , Proteínas Priônicas/genética , Doença de Emaciação Crônica/genética , Animais , República Tcheca , Suscetibilidade a Doenças/veterinária , Predisposição Genética para Doença , Noruega , Análise de Sequência de DNA/veterinária , Reino UnidoRESUMO
Susceptibility of cervids to Chronic Wasting Disease (CWD), a prion disease, can be modulated by variations in the prion protein gene (PRNP), encoding the cellular prion protein (PrPC ). In prion diseases, PrPC is conformationally converted to pathogenic conformers (PrPSc ), aggregates of which comprise infectious prions. CWD has recently been observed in its contagious form in Norwegian reindeer (Rangifer tarandus) and in novel, potentially sporadic forms, here called 'atypical CWD', in moose (Alces alces) and red deer (Cervus elaphus). To estimate relative susceptibility of different Norwegian cervid species to CWD, their non-synonymous PRNP variants were analyzed. In reindeer, seven PRNP alleles were observed and in red deer and moose two alleles were present, whereas roe deer (Capreolus capreolus) PRNP was monomorphic. One 'archetypal' PRNP allele associated with susceptibility was common to all four cervid species. The distribution of PRNP alleles differed between wild and semi-domesticated reindeer, with alleles associated with a high susceptibility occurring, on average, above 55% in wild reindeer and below 20% in semi-domesticated reindeer. This difference may reflect the diverse origins of the populations and/or selection processes during domestication and breeding. Overall, PRNP genetic data indicate considerable susceptibility to CWD among Norwegian cervids and suggest that PRNP homozygosity may be a risk factor for the atypical CWD observed in moose. The CWD isolates found in the Norwegian cervid species differ from those previously found in Canada and USA. Our study provides an overview of the PRNP genetics in populations exposed to these emerging strains that will provide a basis for understanding these strains' dynamics in relation to PRNP variability.
Assuntos
Cervos , Príons , Rena , Doença de Emaciação Crônica , Animais , Cervos/genética , Noruega/epidemiologia , Proteínas Priônicas/genética , Príons/genética , Rena/genética , Doença de Emaciação Crônica/epidemiologia , Doença de Emaciação Crônica/genéticaRESUMO
The emergence of CWD in Europe in 2016 and the first natural infection in wild reindeer warranted disease management. This led to the testing of 2424 hunted or culled reindeer during 2016-2018, from the infected subpopulation in the Nordfjella mountain range in Southern Norway. To identify any association between PRNP variation and CWD susceptibility, we characterized the open reading frame of the PRNP gene in 19 CWD positive reindeer and in 101 age category- and sex-matched CWD negative controls. Seven variant positions were identified: 6 single nucleotide variants (SNVs) and a 24 base pair (bp) deletion located between nucleotide position 238 and 272, encoding four instead of five octapeptide repeats. With a single exception, all variant positions but one were predicted to be non-synonymous. The synonymous SNV and the deletion are novel in reindeer. Various combinations of the non-synonymous variant positions resulted in the identification of five PRNP alleles (A-E) that structured into 14 genotypes. We identified an increased CWD risk in reindeer carrying two copies of the most common allele, A, coding for serine in position 225 (Ser225) and in those carrying allele A together with the 24 bp deletion.