Submitted to: Plant and Animal Genome Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: November 1, 2005
Publication Date: January 14, 2006
Citation: Clawson, M.L., Heaton, M.P., Keele, J.W., Smith, T.P., Laegreid, W.W. 2006. Linkage disequilibrium and haplotype structure in the prion gene of U.S. beef and dairy cattle (abstract). Plant and Animal Genome Conference Proceedings. p. 145. Technical Abstract: Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. In U.S. cattle, the extent of nucleotide diversity in most of the non-coding regions of the prion gene (PRNP) was previously unknown. Defining this variation is necessary to interpret the potential influence of PRNP alleles on genetic predisposition to BSE. The objective of this study was to identify and characterize the genetic variation of PRNP from the promoter region through the 3’UTR in U.S. cattle. A 25.1-kb genomic region containing PRNP was sequenced from 192 cattle representing 16 beef and 6 dairy breeds prevalent in U.S. herds. For 95% of the animals sequenced, two or more high quality reads were obtained for each nucleotide (24.7 kb total). Sequence analyses identified 388 total polymorphisms: 350 single nucleotide polymorphisms (SNPs) and 38 insertions/deletions. The majority of these polymorphisms (287) have not previously been reported, including 42 with a minor allele frequency greater than 0.05 in U.S. cattle. There is strong linkage disequilibrium between polymorphism alleles in the promoter region of bovine PRNP. Excluding breeds influenced by Brahman germplasm, there were 23 PRNP haplotypes identified with a frequency greater than or equal to 0.01. These haplotypes accounted for 178 of the 198 PRNP alleles analyzed and were defined by 20 haplotype tagging SNPS (htSNPs). The htSNPs represent an efficient set of polymorphisms for genotyping PRNP haplotype diversity and may facilitate genetic epidemiologic studies of BSE.