title: Prion gene haplotypes of U.S. cattle.
abstract: BACKGROUND
  Bovine 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, U,S, Meat Animal Research Center, Clay Center, NE 68933, USA. clawson@email.marc.usda.gov
authors.forename: Michael L
authors.initials: ML
authors.lastname: Clawson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Heaton
authors.forename: John W
authors.initials: JW
authors.lastname: Keele
authors.forename: Timothy P L
authors.initials: TP
authors.lastname: Smith
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Harhay
authors.forename: William W
authors.initials: WW
authors.lastname: Laegreid
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D000818:Animals; D002417:Cattle / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D053263:Gene Regulatory Networks; D006239:Haplotypes / Q000235:genetics*; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011328:Prions / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D014481:United States
chemical_list: D020413:3' Untranslated Regions; D011328:Prions