Abstract
BackgroundBovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD) and haplotype networks within the bovine prion gene (PRNP) is important for 1) testing rare or common PRNP variation for an association with BSE and 2) interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes.ResultsA 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb). PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb). Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS) which characterize variation within and across PRNP.ConclusionThe number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle.
Highlights
Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein
The aim of this study was to characterize the extent of linkage disequilibrium (LD) and haplotype networks within PRNP ranging from the promoter past the 3'UTR (25.2 kb) in 192 U.S cattle (16 beef and five dairy breeds)
The amplification primers do not hybridize with PRNP regions containing any of the polymorphisms observed in this study, nor do any of the 150 sequencing primers used for redundant coverage of PRNP nucleotides
Summary
Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S cattle genomes. A 23-bp insertion/deletion (indel) polymorphism in the putative promoter region and a 12-bp indel within intron I have been associated with German BSE-affected animals [9]. These polymorphisms are present in U.S cattle [10]. Most of PRNP has not been characterized in a population as diverse as U.S cattle outside of the coding region and 3'UTR of exon III, and portions of the promoter and intron I [10,11,12]. The extent of PRNP polymorphisms, linkage between PRNP alleles, recombination events, and haplotype diversity within PRNP is not known
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