Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Polymorphisms that alter the prion protein of sheep or humans have been associated with transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that non-synonymous mutations in the bovine prion gene (PRNP) are associated with classical BSE disease susceptibility. However, two bovine PRNP insertion/deletion polymorphisms, one within the promoter region and the other in intron 1, have been associated with susceptibility to classical BSE. These associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. To test for associations with BSE susceptibility, we conducted a genome wide scan using a panel of 3,072 single nucleotide polymorphism markers on 814 animals representing cases and control Holstein cattle from the United Kingdom BSE epidemic. A higher resolution, 50K SNP, genome-wide scan was used with a sub-set (N=330) of animals to test for association with BSE incidence. Further, the bovine prion gene was tested, 19 haplotype tagging SNPs and 2 insertion/deletion alleles for association with BSE disease incidence.
The Holstein case and control cattle analyzed here consisted of two sets, one set with known family relationships and the second set with BSE cases with paired controls. The family set comprised of half-sibling progeny from six sires, revealed 27 SNPs representing 18 chromosomes associated with incidence of BSE disease, confirming previously reported chromosomal regions. Further analysis of the BSE case and paired control samples using the 50K SNP chip a polymorphic locus was identified on chromosome 1 at 29,147,078 bp with a moderate significant association (p=3.09E-5) and over-represented in BSE affected animals. Further, analysis of the prion gene and the paired BSE case and control animals revealed a haplotype within the region of high LD to associate with BSE un-affected animals (p-value =0.000114). It is clear from our analyses that several regions of the genome are statistically associated with the incidence of classical BSE in European Holstein cattle. / Animal Science
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1453 |
| Date | 11 1900 |
| Creators | Murdoch, Brenda Mae |
| Contributors | Moore, Stephen (Agricultural, Food and Nutritional Science), Dixon, Walter (Agricultural, Food and Nutritional Science), Okine, Erasmus (Agricultural, Food and Nutritional Science), Allison, William (Biological Sciences), Aiken, Judd (Agricultural, Food and Nutritional Science), Mead, Simon (MRC Prion Unit, UCL) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 2527940 bytes, application/pdf |
| Relation | Murdoch BM, Clawson ML, Laegreid WW, Stothard P, Settles M (2010) A 2 cM genome-wide scan of European Holstein cattle affected by classical BSE. BMC Genet 11: 20, Murdoch BM et al. Prion haplotype associated with classical BSE incidence European Holstein Cattle. PLoS ONE 2010 |
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