First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle

Abstract

Bovine spongiform encephalopathy (BSE) is a prion disease characterized by spongiform degeneration and astrocytosis in the brain. Unlike classical BSE, which is caused by prion-disease-contaminated meat and bone meal, the cause of atypical BSE has not been determined. Since previous studies have reported that the somatic mutation in the human prion protein gene (PRNP) has been linked to human prion disease, the somatic mutation of the PRNP gene was presumed to be one cause of prion disease. However, to the best of our knowledge, the somatic mutation of this gene in cattle has not been investigated to date. We investigated somatic mutations in a total of 58 samples, including peripheral blood; brain tissue including the medulla oblongata, cerebellum, cortex, and thalamus; and skin tissue in 20 individuals from each breed using pyrosequencing. In addition, we estimated the deleterious effect of the K211 somatic mutation on bovine prion protein by in silico evaluation tools, including PolyPhen-2 and PANTHER. We found a high rate of K211 somatic mutations of the bovine PRNP gene in the medulla oblongata of three Holsteins (10% ± 4.4%, 28% ± 2%, and 19.55% ± 3.1%). In addition, in silico programs showed that the K211 somatic mutation was damaging. To the best of our knowledge, this study is the first to investigate K211 somatic mutations of the bovine PRNP gene that are associated with potential BSE progression.

Absence of proteinase K‐resistant PrP in Korean Holstein cattle carrying potential bovine spongiform encephalopathy‐related E211K somatic mutation

“…To date, although extensive investigations on 211K germline mutation have been performed in the United States and Korea, the cattle carrying 211K germline mutation have not been reported thus far (Heaton et al., 2008; Kim & Jeong, 2017). However, recently, we identified potential BSE‐related somatic mutation E211K in 3 Korean Holstein cattle (Won et al, 2020). Furthermore, previous studies have reported that the 23‐bp insertion/deletion polymorphism in the promoter and the 12‐bp insertion/deletion polymorphism in intron 1 of the bovine PRNP gene have been strongly associated with the expression level of bovine prion protein and modulate susceptibility to BSE in cattle (Haase et al., 2007; Jeong et al., 2006; Sanches et al., 2016; Vernerova et al., 2014; Zhao et al., 2015).…”

The First Report of Genetic Polymorphisms of the Equine SPRN Gene in Outbred Horses, Jeju and Halla Horses

“…To date, the exact cause of conversion of PrP C to PrP Sc has not been reported. However, recently, it has been presumed that PRNP genetic mutations, posttranslational modifications, and several genetic factors play a pivotal role in the conversion process of PrP C to PrP Sc [ 5 , 6 , 7 , 8 , 9 ].…”

Strong Association of the rs4986790 Single Nucleotide Polymorphism (SNP) of the Toll-Like Receptor 4 (TLR4) Gene with Human Immunodeficiency Virus (HIV) Infection: A Meta-Analysis

“…In addition, differences in the local crystal structure of the TLR4-MD2-LPS complex were noted between TLR4 with the wild type allele and the G299 allele [ 20 , 21 ]. Since genetic variations confer functional alteration, these studies indicate that the rs4986790 SNP of the TLR4 gene is related to anti-bacterial functions of TLR4 [ 22 , 23 , 24 ]. Interestingly, TLR4/MD2 complex directly interacts with the Tat protein of HIV-1, and HIV-1 modulates the expression level of TLR4 and downstream immune responses, including the NF-κB pathway [ 25 , 26 ].…”