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Molecular evolution of the sheep prion protein gene

Slate, J. (2005) Molecular evolution of the sheep prion protein gene. Proceedings of the Royal Society B: Biological Sciences, 272 (1579). pp. 2371-2377. ISSN 1471-2954


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Transmissible spongiform encephalopathies (TSEs) are infectious, fatal neurodegenerative diseases characterized by aggregates of modified forms of the prion protein (PrP) in the central nervous system. Well known examples include variant Creutzfeldt-Jakob Disease (vCJD) in humans, BSE in cattle, chronic wasting disease in deer and scrapie in sheep and goats. In humans, sheep and deer, disease susceptibility is determined by host genotype at the prion protein gene (PRNP). Here I examine the molecular evolution of PRNP in ruminants and show that variation in sheep appears to have been maintained by balancing selection, a profoundly different process from that seen in other ruminants. Scrapie eradication programs such as those recently implemented in the UK, USA and elsewhere are based on the assumption that PRNP is under positive selection in response to scrapie. If, as these data suggest, that assumption is wrong, eradication programs will disrupt this balancing selection, and may have a negative impact on the fitness or scrapie resistance of national flocks.

Item Type: Article
Copyright, Publisher and Additional Information: © 2005 The Royal Society
Keywords: heterozygote advantage, Tajima's D, allele frequency, negative frequency-dependent selection
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Animal and Plant Sciences (Sheffield)
Depositing User: Repository Officer
Date Deposited: 19 Jun 2006
Last Modified: 13 Jul 2016 18:47
Published Version: http://www.journals.royalsoc.ac.uk/openurl.asp?gen...
Status: Published
Publisher: The Royal Society
Refereed: Yes
Identification Number: 10.1098/rspb.2005.3259
URI: http://eprints.whiterose.ac.uk/id/eprint/1318

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