HAPLOTYPE STRUCTURE OF THE BOVINE PRION GENE COMPLEX AND ASSOCIATION WITH BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)
Title: PRNP haplotype associated with classical BSE incidence in European Holstein cattle
| Murdoch, Brenda - |
| Yue, Samuel - |
| Basu, Urmila - |
| Mckay, Stephanie - |
| Settles, Matthew - |
| Capoferri, Rossana - |
| Laegreid, William - |
| Williams, John - |
| Moore, Stephen - |
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 23, 2010
Publication Date: September 16, 2010
Citation: Murdoch, B.M., Clawson, M.L., Yue, S., Basu, U., McKay, S., Settles, M., Capoferri, R., Laegreid, W.W., Williams, J.L., Moore, S.S. 2010. PRNP haplotype associated with classical BSE incidence in European Holstein cattle. PLoS One [serial online]. 5(9): e12786.
Interpretive Summary: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a class of invariably fatal neurodegenerative disorders that occur in humans, ruminants, cats, and mink. The most common TSE of cattle is classical bovine spongiform encephalopathy (BSE), with over 190,000 cases reported in 26 countries. TSEs do not occur in the absence of the prion protein, and variation in the prion gene correlates with TSE susceptibility in some mammals including cattle. Two bovine prion gene variants are known to associate with classical BSE resistance. However, genetic variation in the bovine prion gene is complex, and the extent to which prion gene variants associate with classical BSE was not clear from previous studies. Accordingly, prion gene variants were systematically tested for an association with classical BSE in European Holstein cases and controls. This resulted in the identification of a new variant association with classical BSE resistance. When compared to the two other prion variants with known associations with classical BSE, the newly implicated variant had the highest overall significance with resistance. This suggests that the newly implicated variant may be the most effective marker for classical BSE resistance identified within the prion gene to date.
Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease of cattle. The bovine prion gene (PRNP) contains regions of both high and low linkage disequilibrium (LD) that appear to be conserved across Bos taurus populations. The region of high LD, which spans the promoter and part of intron 2, contains polymorphic loci that have been associated with classical BSE status. However, the complex genetic architecture of PRNP has not been systematically tested for an association with classical BSE.
Methodology/Principal Findings: In this study, haplotype tagging single nucleotide polymorphisms (htSNPS) within PRNP were used to test for association with BSE disease incidence. A combination of goldengate assay, sequencing and PCR amplification was used to genotype 19 htSNPs and 2 InDels for 330 BSE case and control animals. A haplotype within the region of high LD was found to associate with BSE unaffected animals (p-value is less than 0.0005).
Conclusion/Significance: A PRNP haplotype association with classical BSE incidence has been identified. The result suggests that a genetic determinant in or near PRNP may influence classical BSE incidence in cattle.