The effect of PrP Sc accumulation on inflammatory gene expression within sheep peripheral lymphoid tissue

Gossner, Anton

doi:10.1016/j.vetmic.2015.10.013

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Three of the genes within the highest homozygous H score on chromosome 7 (H = 0.85) were the MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2) gene, the APBA3 gene (Amyloid Beta (A4) Precursor Protein-Binding, Family A, Member 3), and the ATCAY gene (Ataxia, cerebellar, Cayman type). These genes could be directly or indirectly involved in modulating scrapie or Yersinia Pseudotuberculosis, two widespread diseases of sheep and goat (Tanahashi and Tabira 1999;King and Turner 2004;Nordström et al 2005;Gossner and Hopkins 2015). It has been observed that Valdostana goats have a difference in several alleles of PRNP (Prion Protein gene: the major gene involved in scrapie) compared to the other breeds of northern Italy even if this difference was not significant (Colussi et al 2008).…”

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confidence: 99%

The Valdostana goat: a genome-wide investigation of the distinctiveness of its selective sweep regions

et al. 2017

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The Valdostana goat is an alpine breed, raised only in the northern Italian region of the Aosta Valley. This breed's main purpose is to produce milk and meat, but is peculiar for its involvement in the "Batailles de Chèvres," a recent tradition of non-cruel fight tournaments. At both the genetic and genomic levels, only a very limited number of studies have been performed with this breed and there are no studies about the genomic signatures left by selection. In this work, 24 unrelated Valdostana animals were screened for runs of homozygosity to identify highly homozygous regions. Then, six different approaches (ROH comparison, Fst single SNPs and windows based, Bayesian, Rsb, and XP-EHH) were applied comparing the Valdostana dataset with 14 other Italian goat breeds to confirm regions that were different among the comparisons. A total of three regions of selection that were also unique among the Valdostana were identified and located on chromosomes 1, 7, and 12 and contained 144 genes. Enrichment analyses detected genes such as cytokines and lymphocyte/leukocyte proliferation genes involved in the regulation of the immune system. A genetic link between an aggressive challenge, cytokines, and immunity has been hypothesized in many studies both in humans and in other species. Possible hypotheses associated with the signals of selection detected could be therefore related to immune-related factors as well as with the peculiar battle competition, or other breed-specific traits, and provided insights for further investigation of these unique regions, for the understanding and safeguard of the Valdostana breed.

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confidence: 99%

The Valdostana goat: a genome-wide investigation of the distinctiveness of its selective sweep regions

et al. 2017

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“…2 , Supplementary Table 2 ). One significant SNP that was detected in our METAL-based analysis via Cochran’s Q -test for heterogeneity was intergenic between PLS3 and DACH2 ; with DACH2 previously implicated in the pathophysiology of scrapie ( Gossner and Hopkins 2015 ). However, it should also be noted that the same SNP implicating DACH2 was also among the top 39 ranked SNPs in a EMMAX GWAA ( Fig.…”

Section: Resultsmentioning

confidence: 94%

Genotype by environment interactions for chronic wasting disease in farmed US white-tailed deer

Seabury

Lockwood

Nichols³

2022

G3 Genes|Genomes|Genetics

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Despite implementation of enhanced management practices, chronic wasting disease (CWD) in U.S. white-tailed deer (Odocoileus virginianus; hereafter WTD) continues to expand geographically. Herein, we perform the largest genome-wide association analysis (GWAA) to date for CWD (n = 412 CWD-positive; n = 758 CWD-non-detect) using a custom Affymetrix Axiom® single nucleotide polymorphism (SNP) array (n = 121,010 SNPs), and confirm that differential susceptibility to CWD is a highly heritable (h2 = 0.611 ± 0.056) polygenic trait in farmed U.S. WTD, but with greater trait complexity than previously appreciated. We also confirm PRNP codon 96 (G96S) as having the largest-effects on risk (P ≤ 3.19E-08; Phenotypic Variance Explained ≥ 0.025) across three U.S. regions (Northeast, Midwest, South). However, 20 CWD-positive WTD possessing codon 96SS genotypes were also observed, including one that was lymph node and obex positive. Beyond PRNP, we also detected 23 significant SNPs (P-value ≤ 5E-05) implicating ≥ 24 positional candidate genes; many of which have been directly implicated in Parkinson’s, Alzheimer’s and prion diseases. Genotype-by-environment (GxE) interaction GWAA revealed a SNP in the lysosomal enzyme gene ARSB as having the most significant regional heterogeneity of effects on CWD (P ≤ 3.20E-06); with increasing copy number of the minor allele increasing susceptibility to CWD in the Northeast and Midwest; but with opposite effects in the South. In addition to ARSB, 38 significant GxE SNPs (P-value ≤ 5E-05) were also detected, thereby implicating ≥ 36 positional candidate genes; the majority of which have also been associated with aspects of Parkinson’s, Alzheimer’s and prion diseases.

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“…In human prion disease, inflammation-regulated expression of the micro RNA miR-146 was enhanced [65, 66]. In a puzzling contrast to the increased induction of inflammatory genes by PrPsc in the mouse brain, lymphoid tissues of sheep infected with PrPsc exhibit reduced expression of inflammatory genes [67]. Increased intracellular accumulation of Ca 2+ is present in the brain of CJD, and activation of the calpain-cathepsin axis occurs at the pre-clinical stage of the disease [68].…”

Section: Prpsc-induced Inflammation In Prion Diseasementioning

confidence: 99%

Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?

Prasad¹,

Bondy

2019

CAS

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Prion diseases are a group of incurable infectious terminal neurodegenerative diseases caused by the aggregated misfolded PrPsc in selected mammals including humans. The complex physical interaction between normal prion protein PrPc and infectious PrPsc causes conformational change from the α- helix structure of PrPc to the β-sheet structure of PrPsc, and this process is repeated. Increased oxidative stress is one of the factors that facilitate the conversion of PrPc to PrPsc. This overview presents evidence to show that increased oxidative stress and inflammation are involved in the progression of this disease. Evidence is given for the participation of redoxsensitive metals Cu and Fe with PrPsc inducing oxidative stress by disturbing the homeostasis of these metals. The fact that some antioxidants block the toxicity of misfolded PrPc peptide supports the role of oxidative stress in prion disease. After exogenous infection in mice, PrPsc enters the follicular dendritic cells where PrPsc replicates before neuroinvasion where they continue to replicate and cause inflammation leading to neurodegeneration. Therefore, reducing levels of oxidative stress and inflammation may decrease the rate of the progression of this disease. It may be an important order to reduce oxidative stress and inflammation at the same time. This may be achieved by increasing the levels of antioxidant enzymes by activating the Nrf2 pathway together with simultaneous administration of dietary and endogenous antioxidants. It is proposed that a mixture of micronutrients could enable these concurrent events thereby reducing the progression of human prion disease.

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The effect of PrP Sc accumulation on inflammatory gene expression within sheep peripheral lymphoid tissue

Cited by 7 publications

References 34 publications

The Valdostana goat: a genome-wide investigation of the distinctiveness of its selective sweep regions

The Valdostana goat: a genome-wide investigation of the distinctiveness of its selective sweep regions

Genotype by environment interactions for chronic wasting disease in farmed US white-tailed deer

Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?

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