GENETIC AND BIOLOGICAL DETERMINANTS OF RESPIRATORY DISEASE SUSCEPTIBILITY
Title: A 2cM Genome-Wide Scan of European Holstein Cattle Affected by Classical BSE
| Murdoch, Brenda - |
| Laegreid, William - |
| Stothard, Paul - |
| Settles, Matthew - |
| Mckay, Stephanie - |
| Prasad, Aparna - |
| Wang, Zhiquan - |
| Moore, Stephen - |
| Williams, John - |
Submitted to: BioMed Central (BMC) Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 29, 2010
Publication Date: March 29, 2010
Citation: Murdoch, B.M., Clawson, M.L., Laegreid, W.W., Stothard, P., Settles, M., McKay, S., Prasad, A., Wang, Z., Moore, S.S., Williams, J.L. 2010. A 2cM Genome-Wide Scan of European Holstein Cattle Affected by Classical BSE. BioMed Central (BMC) Genetics [serial online]. 11:20. Available: http://www.biomedcentral.com/1471-2156/11/20.
Interpretive Summary: Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a class of invariably fatal neurodegenerative disorders that occur in humans, ruminants, felines, and mink. Classical bovine spongiform encephalopathy (BSE) is a TSE of cattle that is typically acquired through the consumption of meat and bone meal contaminated with the infectious prion agent. There is a genetic component to classical BSE susceptibility, and the extent to which variation throughout the bovine genome contributes to that susceptibility is unknown. To address this issue, whole-genome scans were conducted collectively on 814 BSE case and control cattle originating from the United Kingdom. These scans implicated genetic variation distributed within multiple regions and chromosomes of the bovine genome for an association with classical BSE incidence. The biological significance of these associations is presently unknown, and would require additional research.
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 variations in 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 3072 single nucleotide polymorphism (SNP) markers on 814 animals representing case and control Holstein cattle from the United Kingdom BSE epidemic.
Two sets of BSE affected Holstein cattle were analyzed in this study, one set with known family relationships and the second set with no known relationship. The genome scan of the family based set enhanced the resolution of a previous microsatellite genome analysis of the same families by approximately ten fold. The results revealed several SNPs associated with incidence of BSE disease, confirming a region previously reported on chromosome 20, and identifying additional regions on chromosomes 2, 14, 16, 21 and 28 that were statistically associated with BSE incidence. The genome scan of the unrelated animals did not identify SNP association that passed a stringent genome-wide significance threshold.
Several regions of the genome are statistically associated with the incidence of classical BSE in European Holstein cattle. Further investigation of loci on chromosomes 2, 14, 16, 20, 21 and 28 will be required to uncover any biological significance underlying these marker associations.