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 Virus and Prion Research: Ames, IA
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ARS Home Midwest Area Ames, Iowa National Animal Disease Center Virus and Prion Research Research Publications at this Location





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Title:   Author  item
                                            Nicholson, Ericitem
                                            Brunelle, Brianitem
                                            Richt, Juergenitem
                                            Kehrli Jr, Marcusitem
                                            Greenlee, Justin
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 6/12/2008
                                    Publication  Date: 10/8/2008
                                    Citation: Nicholson, E.M., Brunelle, B.W., Richt, J.A., Kehrli, Jr., M.E., Greenlee, J.J. 2008. Identification of a Heritable Polymorphism in the Bovine Prion Gene Associated with Genetic Transmissible Spongiform Encephalopathy: Evidence of Heritable BSE [abstract]. Prion 2008. p. 114.Interpretive Summary:
                                Technical Abstract: Background:  Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle.  Classical BSE is associated with ingestion of BSE-contaminated feedstuffs.  H- and L-type BSE, collectively known as atypical BSE, differ from classical BSE by displaying a different disease phenotype and they have not been linked to the consumption of contaminated feed.  Interestingly, the 2006 U.S. H-type atypical BSE animal had a polymorphism at codon 211 of the bovine prion gene resulting in a glutamic acid to lysine substitution (E211K).  This substitution is analogous to the most prevalent form of heritable TSE in humans, and it is considered to have caused BSE in the 2006 U.S. atypical BSE animal.  

Objectives and Methods:  In order to determine if this amino acid change is a heritable trait in cattle, we sequenced using stand DNA sequencing the prion alleles of the only known offspring of this animal, a 2-year-old heifer.

Results:  Sequence analysis revealed that both the 2006 U.S. atypical BSE animal and its 2-year-old heifer were heterozygous at bovine prion gene nucleotides 631 through 633 for GAA (glutamic acid) and AAA (lysine).  Both animals carry the E211K polymorphism, indicating that the allele is heritable and may persist within the cattle population.

Discussion:  This is the first evidence that the E211K polymorphism is a germline polymorphism, not a somatic mutation, indicating BSE may be transmitted genetically in cattle.  This also provides the first evidence that all 3 etiologic forms of TSEs (spontaneous, hereditary, and infectious) are present in a non-human species.  Atypical BSE arising as both genetic and spontaneous disease, in the context of reports that at least some forms of atypical BSE can convert to classical BSE in mice, suggests a cattle origin for classical BSE.


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