Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (<i>Odocoileus virginianus</i>)

Kelly, Amy C.; Mateus‐Pinilla, Nohra E.; Diffendorfer, James E.; Jewell, Emily; Ruiz, Marilyn O.; Killefer, J.; Shelton, Paul; Beissel, Tom; Novakofski, J. E.

doi:10.4161/pri.2.1.6321

Cited by 57 publications

(84 citation statements)

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“…The current study included sequence from 1730 new individuals from a broader sampling area that have not previously been reported. All 14 variable sites that have been previously identified within a 625 bp region of PRNP [34,35,41] were detected. Twenty-six haplotypes were predicted from unphased sequences, of which two (Haplotype Y, with a single nonsynonymous polymorphic site at nt285C (aa95H) and Haplotype Z with two polymorphisms one nonsynonymous at nt286A/aa96S and one synonymous at nt438T/aa185I) are novel, while 24 have been previously reported[34].…”

Section: Resultsmentioning

confidence: 99%

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Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

Brandt

Green

Ishida

et al. 2018

Prion

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Managing and controlling the spread of diseases in wild animal populations is challenging, especially for social and mobile species. Effective management benefits from information about disease susceptibility, allowing limited resources to be focused on areas or populations with a higher risk of infection. Chronic wasting disease (CWD), a transmissible spongiform encephalopathy that affects cervids, was detected in Colorado in the late 1960s. CWD was detected in Illinois and Wisconsin in 2002 and has since spread through many counties. Specific nucleotide variations in the prion protein gene (PRNP) sequence have been associated with reduced susceptibility to CWD in white-tailed deer. Though genetic resistance is incomplete, the frequency of deer possessing these mutations in a population is an important factor in disease spread (i.e. herd immunity). In this study we sequenced 625 bp of the PRNP gene from a sampling of 2433 deer from Illinois and Wisconsin. In north-central Illinois where CWD was first detected, counties had a low frequency of protective haplotypes (frequency <0.20); whereas in northwestern Illinois counties, where CWD cases have only more recently been detected, the frequency of protective haplotypes (frequency >0.30) was much higher (p < 0.05). Protective haplotype frequencies varied significantly among infected and uninfected geographic areas. The frequency of protective PRNP haplotypes may contribute to population level susceptibility and may shape the way CWD has spread through Illinois. Analysis of PRNP haplotype distribution could be a useful tool to assess CWD risk and allocate resources to contain and reduce the spread of infection.

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Section: Resultsmentioning

confidence: 99%

“…A 625 bp region of PRNP that codes amino acids 21 to 227 was amplified by polymerase chain reaction (PCR) using previously published primers CWD-13 and CWD-LA [62] or primers 223 and 224 [37]. Amplification was performed in 25 ul reaction volumes following previously published protocols [34,35,62]. …”

Section: Methodsmentioning

confidence: 99%

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

Brandt

Green

Ishida

et al. 2018

Prion

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“…33 Other factors such as age, genotype, type of tissue, geographic location and home range could influence metal concentrations, and may explain differences between infected and non-infected animals, and between species. 23,28,30,34,35 For instance, Rocky mountain elk (Cervus elaphus nelsoni) with 2 copies of methionine at PrP codon 132 (132MM) accumulated higher levels of Mg in the brain than elk with leucine at codon 132. In contrast, PRNP genotype did not influence blood levels of Cu, Fe, Mn or Mg in sheep, 23 indicating that the effects of genotype are species-specific.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, PRNP genotype did not influence blood levels of Cu, Fe, Mn or Mg in sheep, 23 indicating that the effects of genotype are species-specific. Certain PRNP polymorphisms are correlated with CWD resistance in white-tailed deer, 34 and it would be interesting to determine if this association is related to differences in metal accumulation among genotypes. Regardless, differences in the accumulation of each metal need to be considered for each genotype, species and type of tissue.…”

Section: Discussionmentioning

confidence: 99%

Metals in obex and retropharyngeal lymph nodes of Illinois white-tailed deer and their variations associated with CWD status

Rivera

Novakofski

Weng

et al. 2015

Prion

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ABSTRACT. Prion proteins (PrP C ) are cell membrane glycoproteins that can be found in many cell types, but specially in neurons. Many studies have suggested PrP C 's participation in metal transport and cellular protection against stress in the central nervous system (CNS). On the other hand PrP Sc , the misfolded isoform of PrP C and the pathogenic agent in transmissible spongiform encephalopathies (TSE), has been associated with brain metal dyshomeostasis in prion diseases. Thus, changes in metal concentration associated with protein misfolding and aggregation have been reported for human and animal prion diseases, as well as for other neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. The use of metal concentrations in tissues as surrogate markers for early detection of TSEs has been suggested. Studies on the accumulation of metals in free-ranging white-tailed deer have not been conducted. This study established concentrations of copper, iron, manganese, and magnesium in 2 diagnostic tissues used for CWD testing (obex and retropharyngeal lymph nodes (RLN)). We compared these concentrations between tissues and in relation to CWD status. We established reference intervals (RIs) for these metals and explored their ability to discriminate between CWD-positive and CWD-negative animals. Our results indicate that independent of CWD status, white-tailed deer accumulate higher concentrations of Fe, Mn and Mg in Ó Nelda A Rivera, Jan Novakofski, Hsin-Yi Weng, Amy Kelly, Damian Satterthwaite-Phillips, Marilyn O Ruiz, and Nohra Mateus-Pinilla *Correspondence to: Nohra Mateus-Pinilla; Email:nohram@illinois.edu Received November 21, 2014; Revised January 25, 2015; Accepted February 9, 2015. Color versions of one or more figures in this article can be found online at www.tandfonline.com/kprn. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. ISSN: 1933-6896 print / 1933-690X online DOI: 10.1080/19336896.2015 RLN than in obex. White-tailed deer infected with CWD accumulated significantly lower concentrations of Mn and Fe than CWD-negative deer. These patterns differed from other species infected with prion diseases. Overlapping values between CWD positive and negative groups indicate that evaluation of these metals in obex and RLN may not be appropriate as a diagnostic tool for CWD infection in white-tailed deer. Because the CWD-negative deer were included in constructing the RIs, high specificities were expected and should be interpreted with caution. Due to the low sensitivity derived from the RIs, we do not recommend using metal concentrations for disease discrimination.Prion, 9:48-58, 2015 Published with license by Taylor & Francis Group, LLC

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“…Heterozygosity for the residue 129 M/V polymorphism in PrP in mammals is associated with resistance to prion disease (O'Rourke et al 1997;Kelly et al 2008;Mead et al 2009) for RNQ1, were significantly higher for [PIN+] compared to [pin2] strains, though no difference in mosaic scores was observed at SUP35 (Mann-Whitney U-test P = 0.121).…”

Section: Risk Factors For [Pin+] Infectionmentioning

confidence: 99%

Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

2014

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Prions (infectious proteins) cause fatal neurodegenerative diseases in mammals. In the yeast Saccharomyces cerevisiae, many toxic and lethal variants of the [PSI+] and [URE3] prions have been identified in laboratory strains, although some commonly studied variants do not seem to impair cell growth. Phylogenetic analysis has revealed four major clades of S. cerevisiae that share histories of two prion proteins and largely correspond to different ecological niches of yeast. The [PIN+] prion was most prevalent in commercialized niches, infrequent among wine/vineyard strains, and not observed in ancestral isolates. As previously reported, the [PSI+] and [URE3] prions are not found in any of these strains. Patterns of heterozygosity revealed genetic mosaicism and indicated extensive outcrossing among divergent strains in commercialized environments. In contrast, ancestral isolates were all homozygous and wine/vineyard strains were closely related to each other and largely homozygous. Cellular growth patterns were highly variable within and among clades, although ancestral isolates were the most efficient sporulators and domesticated strains showed greater tendencies for flocculation.[PIN+]-infected strains had a significantly higher likelihood of polyploidy, showed a higher propensity for flocculation compared to uninfected strains, and had higher sporulation efficiencies compared to domesticated, uninfected strains. Extensive phenotypic variability among strains from different environments suggests that S. cerevisiae is a niche generalist and that most wild strains are able to switch from asexual to sexual and from unicellular to multicellular growth in response to environmental conditions. Our data suggest that outbreeding and multicellular growth patterns adapted for domesticated environments are ecological risk factors for the [PIN+] prion in wild yeast. P RIONS cause a variety of transmissible spongiform encephalopathies (TSEs) in mammals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and CreutzfeldtJakob disease (CJD) in humans. With all TSEs, endogenous prion protein (PrP) misfolds into an altered, usually proteaseresistant, isoform, termed "PrP res " (" res" for protease resistant). Several prions have been described in fungi (Wickner 1994), with many prion variants of the [PSI+] and [URE3] prions showing toxic or even lethal effects in Saccharomyces cerevisiae (McGlinchey et al. 2011). The [PSI+] prion of S. cerevisiae is formed from the cytosolic protein Sup35p. There are three distinct regions of Sup35p: a glutamine/ asparagine-rich N-terminal domain (amino acids 1-123) that is necessary and sufficient for prion formation (TerAvanesyan et al. 1994) and that facilitates deadenylation and decay of messenger RNA (Hosoda et al. 2003); a middle M domain (amino acids 124-253) of unknown function; and an essential C-terminal domain that functions during translation termination (reviewed by Wickner et al. 2004 (Derkatch et ...

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Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (Odocoileus virginianus)

Cited by 57 publications

References 58 publications

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

Metals in obex and retropharyngeal lymph nodes of Illinois white-tailed deer and their variations associated with CWD status

Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

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