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Title: Association of a bovine prion gene haplotype with atypical BSE

item Clawson, Michael - Mike
item Richt, Juergen
item Heaton, Michael - Mike
item Smith, Timothy - Tim

Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2008
Publication Date: 3/19/2008
Citation: Clawson, M.L., Richt, J., Baron, T., Biacabe, A., Czub, S., Heaton, M.P., Smith, T.P., Laegreid, W.W. 2008. Association of a bovine prion gene haplotype with atypical BSE. PLoS One [serial online]. 3(3):e1830. Available:

Interpretive Summary: Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a class of fatal neurodegenerative disorders that occur in humans, ruminants, cats, and mink. Three distinct TSEs afflict cattle: classical bovine spongiform encephalopathy (BSE) and H- and L-type atypical BSE. Classical BSE was identified in the 1980s and is acquired by cattle through the consumption of feed contaminated with the infectious prion agent. Atypical BSEs have only recently been recognized as distinct cattle prion diseases and are extremely rare. Approximately 30 atypical BSE cases have been found collectively (H- and L-types combined) in North American, European, and Asian cattle. In this study, we identified the association of a particular bovine prion DNA sequence (haplotype) with atypical BSE. The haplotype was identified in H- and L-type atypical BSE cases from Canada, France, and the United States, and appears to have widespread association with atypical BSE. The implicated haplotype is relatively uncommon among general cattle populations, thus, the odds of this association happening by chance were calculated to be one in ten thousand. The implicated haplotype does not predict which cattle will develop atypical BSE since atypical cases are exceedingly rare and many healthy cattle have the haplotype. However, the results of this study indicate that there is a genetic component to atypical BSE susceptibility.

Technical Abstract: Background: Atypical bovine spongiform encephalopathies (BSEs) are recently recognized prion diseases of cattle. Atypical BSEs are rare; approximately 30 cases have been identified worldwide. We tested prion gene (PRNP) haplotypes for an association with atypical BSE. Methodology/Principal Findings: Haplotype tagging polymorphisms that characterize PRNP haplotypes from the promoter region through the three prime untranslated region of exon 3 (25.2 kb) were used to determine PRNP haplotypes of six available atypical BSE cases from Canada, France, and the United States. One or two copies of a distinct PRNP haplotype were identified in five of the six cases (p = 1.3 x 10**-4, two-tailed Fisher’s exact test; CI95% 0.263 - 0.901, difference between proportions). The haplotype spans a portion of PRNP that includes part of intron 2, the entire coding region of exon 3, and part of the three prime untranslated region of exon 3 (13 kb). Conclusions/Significance: This result suggests that a genetic determinant in or near PRNP may influence susceptibility of cattle to atypical BSE.