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.
Highlights
Bovine spongiform encephalopathy (BSE) is a well-known prion disease characterized by the accumulation of abnormal prion protein (PrPSc), which shows resistance to proteinase K [1,2,3,4,5,6,7,8,9,10,11,12,13]
Since atypical BSEs, which may refer to sporadically occurring BSE, have been occurring steadily in many countries, it is important to investigate the somatic mutation on E211K of the prion protein gene (PRNP) gene in cattle
We estimated the biological impact of the somatic mutation c.631G>A (E211K) of the bovine PRNP gene using in silico programs, including PolyPhen-2 and PANTHER
Summary
Bovine spongiform encephalopathy (BSE) is a well-known prion disease characterized by the accumulation of abnormal prion protein (PrPSc), which shows resistance to proteinase K [1,2,3,4,5,6,7,8,9,10,11,12,13]. 15% of all human prion diseases, including familial CJD, Gerstmann–Straussler–Scheinker syndrome (GSS), and fatal familial insomnia (FFI), are known to be caused by a germline mutation of the prion protein gene (PRNP) [19,20]. Somatic mutations of the PRNP gene have been reported in the blood and brain tissue of sporadic cases of prion diseases. The E211K mutation of the bovine PRNP gene, which is homologous to the E200K mutation of the human PRNP gene found in familial CJD, was first reported in atypical BSE in the United States in 2006 [25,26,27]. Since atypical BSEs, which may refer to sporadically occurring BSE, have been occurring steadily in many countries, it is important to investigate the somatic mutation on E211K of the PRNP gene in cattle. We estimated a deleterious effect of the E211K somatic mutation on bovine prion protein by in silico evaluation tools such as PolyPhen-2 and PANTHER [28,29]
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