Variation in the PRNP gene of Pere David’s deer (Elaphurus davidianus) may impact genetic vulnerability to chronic wasting disease

2021 ◽  
Author(s):  
Tolulope I. N. Perrin-Stowe ◽  
Yasuko Ishida ◽  
Emily E. Terrill ◽  
Dan Beetem ◽  
Oliver A. Ryder ◽  
...  
Keyword(s):  
Chronic Wasting Disease ◽  
Prnp Gene ◽  
Wasting Disease ◽  
Genetic Vulnerability ◽  
Père David’S Deer ◽  
Elaphurus Davidianus

scholarly journals Variation In The PRNP Gene Of Pere David’s Deer (Elaphurus Davidianus) May Impact Genetic Vulnerability To Chronic Wasting Disease

2021 ◽  
Author(s):  
Tolulope I.N. Perrin-Stowe ◽  
Yasuko Ishida ◽  
Emily E. Terrill ◽  
Dan Beetem ◽  
Oliver A. Ryder ◽  
...  
Keyword(s):  
Captive Breeding ◽  
Chronic Wasting Disease ◽  
Balancing Selection ◽  
Transmissible Spongiform Encephalopathy ◽  
Transmission Risk ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Père David’S Deer ◽  
The Impact ◽  
Elaphurus Davidianus

Abstract Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy caused by prions that has spread across cervid species in North America since the 1960s and recently spread to cervids in Eurasia. The Association of Zoos and Aquariums (AZA) considers CWD to be of major concern for cervids in AZA-accredited facilities because of the indirect transmission risk of the disease and the impact of CWD regulatory protocols on captive breeding programs. Vulnerability to CWD is affected by variation in the PRNP gene that encodes the prion protein. We therefore sequenced PRNP in Pere David’s deer (Elaphurus davidianus), a species that was extinct in the wild for more than a century, and descends from ca. 11 founders. In 27 individuals, we detected two PRNP haplotypes, designated Elad1 (51 of 54 chromosomes) and Elad2 (3 of 54 chromosomes). The two haplotypes are separated by four single nucleotide polymorphisms (SNPs), three of which are non-synonymous. Both Elad1 and Elad2 have polymorphisms that in other cervid taxa are associated with reduced vulnerability to CWD. The two haplotypes are more similar in sequence to PRNP in other cervids than to each other. This suggests that PRNP in cervids may have been under long-term balancing selection, as has been shown for PRNP in non-cervid taxa, and which could account for the presence of multiple haplotypes among founders. There may be a fitness benefit in maintaining both PRNP haplotypes in the species because variation in the prion amino acid sequence can limit transmission of CWD.

scholarly journals Prion Protein Gene (PRNP) Sequences Suggest Differing Vulnerability to Chronic Wasting Disease for Florida Key Deer (Odocoileus virginianus clavium) and Columbian White-Tailed Deer (O. v. leucurus)

2020 ◽  
Vol 111 (6) ◽  
pp. 564-572
Author(s):  
Tolulope I N Perrin-Stowe ◽  
Yasuko Ishida ◽  
Emily E Terrill ◽  
Brian C Hamlin ◽  
Linda Penfold ◽  
...  
Keyword(s):  
Odocoileus Virginianus ◽  
Prion Protein ◽  
Protein Gene ◽  
Chronic Wasting Disease ◽  
Synonymous Substitution ◽  
Spongiform Encephalopathy ◽  
Prion Protein Gene ◽  
Wasting Disease ◽  
Genetic Vulnerability ◽  
Key Deer

Abstract Chronic wasting disease (CWD) is a fatal, highly transmissible spongiform encephalopathy caused by an infectious prion protein. CWD is spreading across North American cervids. Studies of the prion protein gene (PRNP) in white-tailed deer (WTD; Odocoileus virginianus) have identified non-synonymous substitutions associated with reduced CWD frequency. Because CWD is spreading rapidly geographically, it may impact cervids of conservation concern. Here, we examined the genetic vulnerability to CWD of 2 subspecies of WTD: the endangered Florida Key deer (O. v. clavium) and the threatened Columbian WTD (O. v. leucurus). In Key deer (n = 48), we identified 3 haplotypes formed by 5 polymorphisms, of which 2 were non-synonymous. The polymorphism c.574G>A, unique to Key deer (29 of 96 chromosomes), encodes a non-synonymous substitution from valine to isoleucine at codon 192. In 91 of 96 chromosomes, Key deer carried c.286G>A (G96S), previously associated with substantially reduced susceptibility to CWD. Key deer may be less genetically susceptible to CWD than many mainland WTD populations. In Columbian WTD (n = 13), 2 haplotypes separated by one synonymous substitution (c.438C>T) were identified. All of the Columbian WTD carried alleles that in other mainland populations are associated with relatively high susceptibility to CWD. While larger sampling is needed, future management plans should consider that Columbian WTD are likely to be genetically more vulnerable to CWD than many other WTD populations. Finally, we suggest that genetic vulnerability to CWD be assessed by sequencing PRNP across other endangered cervids, both wild and in captive breeding facilities.

scholarly journals New and distinct chronic wasting disease strains associated with cervid polymorphism at codon 116 of the Prnp gene

2021 ◽  
Vol 17 (7) ◽  
pp. e1009795
Author(s):  
Samia Hannaoui ◽  
Elizabeth Triscott ◽  
Camilo Duque Velásquez ◽  
Sheng Chun Chang ◽  
Maria Immaculata Arifin ◽  
...  
Keyword(s):  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Prnp Gene ◽  
Biochemical Properties ◽  
Cellular Prion Protein ◽  
Proteinase K ◽  
Wild Type ◽  
Wasting Disease ◽  
Prion Strains ◽  
The Impact

Chronic wasting disease (CWD) is a prion disease affecting cervids. Polymorphisms in the prion protein gene can result in extended survival of CWD-infected animals. However, the impact of polymorphisms on cellular prion protein (PrPC) and prion properties is less understood. Previously, we characterized the effects of a polymorphism at codon 116 (A>G) of the white-tailed deer (WTD) prion protein and determined that it destabilizes PrPC structure. Comparing CWD isolates from WTD expressing homozygous wild-type (116AA) or heterozygous (116AG) PrP, we found that 116AG-prions were conformationally less stable, more sensitive to proteases, with lower seeding activity in cell-free conversion and reduced infectivity. Here, we aimed to understand CWD strain emergence and adaptation. We show that the WTD-116AG isolate contains two different prion strains, distinguished by their host range, biochemical properties, and pathogenesis from WTD-116AA prions (Wisc-1). Serial passages of WTD-116AG prions in tg(CerPrP)1536+/+ mice overexpressing wild-type deer-PrPC revealed two populations of mice with short and long incubation periods, respectively, and remarkably prolonged clinical phase upon inoculation with WTD-116AG prions. Inoculation of serially diluted brain homogenates confirmed the presence of two strains in the 116AG isolate with distinct pathology in the brain. Interestingly, deglycosylation revealed proteinase K-resistant fragments with different electrophoretic mobility in both tg(CerPrP)1536+/+ mice and Syrian golden hamsters infected with WTD-116AG. Infection of tg60 mice expressing deer S96-PrP with 116AG, but not Wisc-1 prions induced clinical disease. On the contrary, bank voles resisted 116AG prions, but not Wisc-1 infection. Our data indicate that two strains co-existed in the WTD-116AG isolate, expanding the variety of CWD prion strains. We argue that the 116AG isolate does not contain Wisc-1 prions, indicating that the presence of 116G-PrPC diverted 116A-PrPC from adopting a Wisc-1 structure. This can have important implications for their possible distinct capacities to cross species barriers into both cervids and non-cervids.

scholarly journals Association analysis of PRNP gene region with chronic wasting disease in Rocky Mountain elk

2010 ◽  
Vol 3 (1) ◽  
Author(s):  
Stephen N White ◽  
Terry R Spraker ◽  
James O Reynolds ◽  
Katherine I O'Rourke
Keyword(s):  
Association Analysis ◽  
Chronic Wasting Disease ◽  
Rocky Mountain ◽  
Prnp Gene ◽  
Gene Region ◽  
Wasting Disease ◽  
Rocky Mountain Elk

scholarly journals Geographic variation in the PRNP gene and its promoter, and their relationship to chronic wasting disease in North American deer

Prion ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 185-192 ◽  
Author(s):  
Robert M. Zink ◽  
Nadje Najar ◽  
Hernán Vázquez-Miranda ◽  
Brittaney L. Buchanan ◽  
Duan Loy ◽  
...  
Keyword(s):  
Geographic Variation ◽  
North American ◽  
Chronic Wasting Disease ◽  
Prnp Gene ◽  
Wasting Disease

scholarly journals Characterizing the demographic history and prion protein variation to infer susceptibility to chronic wasting disease in a naïve population of white-tailed deer (Odocoileus virginianus)

2020 ◽  
Author(s):  
Sarah E Haworth ◽  
Larissa Nituch ◽  
Joseph M Northrup ◽  
Aaron BA Shafer
Keyword(s):  
High Throughput Sequencing ◽  
Chronic Wasting Disease ◽  
Demographic History ◽  
Population Expansion ◽  
Prnp Gene ◽  
Economic Benefits ◽  
Genomic Variation ◽  
Allele Frequencies ◽  
Wasting Disease ◽  
Tissue Samples

AbstractAssessments of the adaptive potential in natural populations are essential for understanding and predicting responses to environmental stressors like climate change and infectious disease. Species face a range of stressors in human-dominated landscapes, often with contrasting effects. White-tailed deer (deer) are expanding in the northern part of their range following decreasing winter severity and increasing forage availability. Chronic wasting disease (CWD), a prion disease affecting cervids, is likewise expanding and represents a major threat to deer and other cervids. We obtained tissue samples from free-ranging deer across their native range in Ontario, Canada which has yet to detect CWD in wild populations of cervids. We used high-throughput sequencing to assess neutral genomic variation, and variation in the PRNP gene that is partly responsible for the protein misfolding when deer contract CWD. Neutral variation revealed a high number of rare alleles and no population structure, and demographic models suggested a rapid historical population expansion. Allele frequencies of PRNP variants associated with CWD susceptibility and disease progression were evenly distributed across the landscape and consistent with deer populations not infected with CWD. We then estimated the selection coefficient of CWD, with simulations showing an observable and rapid shift in PRNP allele frequencies that coincides with the start of a novel CWD epidemic. Sustained surveillance of genomic and PRNP variation can be a useful tool for CWD-free regions where deer are managed for ecological and economic benefits.

Chronic Wasting Disease Options of Surveillance in Carpathian Cervids: from the Identification of Characteristic Microscopic Pathologic Changes to Prionic Seeded Conversion and Amplification Assays

2001 ◽  
Vol 71 (3) ◽  
pp. 480-486
Author(s):  
Florica Barbuceanu ◽  
Stelian Baraitareanu ◽  
Stefania-Felicia Barbuceanu ◽  
Gabriel Predoi
Keyword(s):  
Enzyme Immunoassay ◽  
Diagnostic Tests ◽  
Chronic Wasting Disease ◽  
Rapid Diagnostic Tests ◽  
Diagnostic Methods ◽  
Wasting Disease ◽  
Western Immunoblotting ◽  
Negative Results ◽  
Antigen Capture ◽  
Confirmatory Tests

This paper describes the current diagnostic methods of Chronic Wasting Disease (CWD) in cervides used between 2013 and 2017 in Romania. The active surveillance of CWD involves the targeted groups screening by using rapid diagnostic tests (e.g., antigen capture enzyme immunoassay). If the first test does not provide certain negative results, then the confirmatory methods have been used, i.e. histopathology, immunohistochemistry and Western immunoblotting. These tests did not lead to the detection of CWD prions (PrPCWD) in Romania. This may be due to the absence or insufficient quantity of PrPCWD in samples, below the threshold of confirmatory tests.

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