Genetic evaluation of the ovine and bovine prion protein genes (PRNP)

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of inevitably fatal neurodegenerative diseases that occur in mammalian species. Ovine susceptibility to scrapie, the prototypical TSE, is predominantly modulated by nonsynonymous polymorphisms within exon 3 of the ovine...

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Main Author: Seabury, Christopher Mark
Other Authors: Derr, James N.
Format: Others
Language:en_US
Published: Texas A&M University 2006
Subjects:
BSE
Online Access:http://hdl.handle.net/1969.1/3333
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spelling ndltd-tamu.edu-oai-repository.tamu.edu-1969.1-33332013-01-08T10:38:10ZGenetic evaluation of the ovine and bovine prion protein genes (PRNP)Seabury, Christopher MarkPRNPBSEprionevolutionTransmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of inevitably fatal neurodegenerative diseases that occur in mammalian species. Ovine susceptibility to scrapie, the prototypical TSE, is predominantly modulated by nonsynonymous polymorphisms within exon 3 of the ovine prion protein gene (PRNP). Investigation of PRNP exon 3 for two hair-sheep breeds revealed a novel predicted amino acid substitution (P116) associated with the ovine ARQ allele (P116A136R154Q171). Additionally, two novel ovine PRNP genotypes (PARQ/ARR; PARQ/ARQ) also were detected, and most of the hair sheep sampled possessed PRNP exon 3 genotypes associated with some degree of resistance to scrapie and/or experimental BSE (bovine spongiform encephalopathy). Unlike sheep, expression of bovine spongiform encephalopathy (BSE) in cattle and other bovids has not been associated with nucleotide variation within bovine PRNP exon 3. However, BSE susceptibility has been tentatively associated with specific insertion-deletion (indel) polymorphisms within the putative bovine PRNP promoter, and to a lesser extent intron 1, for a few German cattle breeds. Evaluation of the patterns of nucleotide variation associated with bovine PRNP exon 3 provided evidence that strong purifying selection has intensely constrained bovine exon 3 over the long-term evolutionary history of the subfamily Bovinae, as well as evidence for significant purifying selection in regions of bovine PRNP exon 3 that are considered to be of functional, structural, and pathogenic importance in other mammalian species. Evaluation of the frequencies of known indel polymorphisms within the putative bovine PRNP promoter for a panel of U. S. cattle sires revealed no significant differences in the distribution of promoter alleles and/or genotypes between U. S. cattle sires and BSEaffected German cattle. Notably, a nonsynonymous PRNP exon 3 polymorphism (T50C) identified in American bison (Bison bison) was tentatively associated with Brucella spp. seropositivity. Specifically, a significant overabundance (P = 0.021) of Yellowstone National Park bison possessing the CC genotype were Brucella spp. seropositive. Furthermore, the T-allele and TT genotype were observed at significantly higher frequencies in three bison populations that were either founded from Brucella spp. seronegative stock or previously subjected to test-and-slaughter management to eradicate brucellosis.Texas A&M UniversityDerr, James N.2006-04-12T16:06:48Z2006-04-12T16:06:48Z2004-122006-04-12T16:06:48ZBookThesisElectronic Dissertationtext661574 byteselectronicapplication/pdfborn digitalhttp://hdl.handle.net/1969.1/3333en_US
collection NDLTD
language en_US
format Others
sources NDLTD
topic PRNP
BSE
prion
evolution
spellingShingle PRNP
BSE
prion
evolution
Seabury, Christopher Mark
Genetic evaluation of the ovine and bovine prion protein genes (PRNP)
description Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of inevitably fatal neurodegenerative diseases that occur in mammalian species. Ovine susceptibility to scrapie, the prototypical TSE, is predominantly modulated by nonsynonymous polymorphisms within exon 3 of the ovine prion protein gene (PRNP). Investigation of PRNP exon 3 for two hair-sheep breeds revealed a novel predicted amino acid substitution (P116) associated with the ovine ARQ allele (P116A136R154Q171). Additionally, two novel ovine PRNP genotypes (PARQ/ARR; PARQ/ARQ) also were detected, and most of the hair sheep sampled possessed PRNP exon 3 genotypes associated with some degree of resistance to scrapie and/or experimental BSE (bovine spongiform encephalopathy). Unlike sheep, expression of bovine spongiform encephalopathy (BSE) in cattle and other bovids has not been associated with nucleotide variation within bovine PRNP exon 3. However, BSE susceptibility has been tentatively associated with specific insertion-deletion (indel) polymorphisms within the putative bovine PRNP promoter, and to a lesser extent intron 1, for a few German cattle breeds. Evaluation of the patterns of nucleotide variation associated with bovine PRNP exon 3 provided evidence that strong purifying selection has intensely constrained bovine exon 3 over the long-term evolutionary history of the subfamily Bovinae, as well as evidence for significant purifying selection in regions of bovine PRNP exon 3 that are considered to be of functional, structural, and pathogenic importance in other mammalian species. Evaluation of the frequencies of known indel polymorphisms within the putative bovine PRNP promoter for a panel of U. S. cattle sires revealed no significant differences in the distribution of promoter alleles and/or genotypes between U. S. cattle sires and BSEaffected German cattle. Notably, a nonsynonymous PRNP exon 3 polymorphism (T50C) identified in American bison (Bison bison) was tentatively associated with Brucella spp. seropositivity. Specifically, a significant overabundance (P = 0.021) of Yellowstone National Park bison possessing the CC genotype were Brucella spp. seropositive. Furthermore, the T-allele and TT genotype were observed at significantly higher frequencies in three bison populations that were either founded from Brucella spp. seronegative stock or previously subjected to test-and-slaughter management to eradicate brucellosis.
author2 Derr, James N.
author_facet Derr, James N.
Seabury, Christopher Mark
author Seabury, Christopher Mark
author_sort Seabury, Christopher Mark
title Genetic evaluation of the ovine and bovine prion protein genes (PRNP)
title_short Genetic evaluation of the ovine and bovine prion protein genes (PRNP)
title_full Genetic evaluation of the ovine and bovine prion protein genes (PRNP)
title_fullStr Genetic evaluation of the ovine and bovine prion protein genes (PRNP)
title_full_unstemmed Genetic evaluation of the ovine and bovine prion protein genes (PRNP)
title_sort genetic evaluation of the ovine and bovine prion protein genes (prnp)
publisher Texas A&M University
publishDate 2006
url http://hdl.handle.net/1969.1/3333
work_keys_str_mv AT seaburychristophermark geneticevaluationoftheovineandbovineprionproteingenesprnp
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