Bovine Prion Protein Gene (PRNP) Promoter Polymorphisms Modulate PRNP Expression and May Be Responsible for Differences in Bovine Spongiform Encephalopathy Susceptibility

Abstract

The susceptibility of humans to the variant Creutzfeldt-Jakob disease is greatly influenced by polymorphisms within the human prion protein gene (PRNP). Similar genetic differences exist in sheep, in which PRNP polymorphisms modify the susceptibility to scrapie. However, the known coding polymorphisms within the bovine PRNP gene have little or no effect on bovine spongiform encephalopathy (BSE) susceptibility in cattle. We have recently found a tentative association between PRNP promoter polymorphisms and BSE susceptibility in German cattle (Sander, P.,

PrPgenetics in ruminant transmissible spongiform encephalopathies

“…Two prominent insertion/deletion (indel) polymorphisms were detected in the PrP promoter and intron I: a 23 bp indel (position 47836) and a 12 bp indel (position 49729, reference sequence AJ298878). Both sequences are transcription factor binding motifs [77].…”

Identification of a Novel Endoplasmic Reticulum Stress Response Element Regulated by XBP1

“…The levels of PrP influence prion disease transmission. The absence of PrP eliminates infection by transmissible prion diseases, and low levels of PRNP gene expression associated with promoter nucleotide polymorphisms decrease the risk of infection by bovine spongiform encephalopathy (1)(2)(3). In contrast, transgenic overexpression of PRNP accelerates transmissible prion disease progression (1,4,5).…”

Effects of PRNP polymorphisms on sperm quality traits in Chinese Holstein bulls

“…And then, a total of 388 polymorphic sites had been localized, including 351 of the SNP types and 37 of the in-del types (Clawson et al 2006). Among these PRNP polymorphic sites, a 23-bp in-del polymorphism in promoter and a 12-bp in-del polymorphism in intron 1 region had a relationship with resistance to BSE (Sander et al 2005), a 24-bp in-del polymorphism in encoding region had a relationship not only with resistance to BSE, incubation period, but also with the prion diseases transmission rate (Derdowski et al 2010). The analysis of sequence diversity in the PRNP of German cattle showed an association between 12-bp and 23-bp polymorphisms and resistance to BSE (Sander et al 2004), especially for 12-bp in-del polymorphism which had main effects on resistance (Juling et al 2006).…”

“…Previous reports have shown that several PRNP polymorphisms were associated with resistance to BSE in cattle (Sander et al 2005;Haase et al 2007;Kashkevich et al 2007). In particular, a 23-bp in-del polymorphism within the PRNP promoter region and a 12-bp in-del polymorphism within intron 1 seemed to affect the binding sites for the transcriptional factors RP58 and SP1, respectively, and might influence PRNP expression (Sander et al 2004;Sander et al 2005;Xue et al 2008). Furthermore, an octapeptide repeat or 24-bp in-del in the open-reading frame might be associated with resistance to BSE (Castilla et al 2005;Brun et al 2007).…”