Texas A&M University
1.
Seabury, Christopher Mark.
Genetic evaluation of the ovine and bovine prion protein genes (PRNP).
Degree: PhD, Genetics, 2006, Texas A&M University
URL: http://hdl.handle.net/1969.1/3333 
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.
Advisors/Committee Members: Derr, James N. (advisor), Womack, James E. (committee member), Templeton, Joe W. (committee member), Honeycutt, Rodney L. (committee member).Subjects/Keywords: PRNP; BSE; prion; evolution
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APA (6th Edition):
Seabury, C. M. (2006). Genetic evaluation of the ovine and bovine prion protein genes (PRNP). (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/3333
Chicago Manual of Style (16th Edition):
Seabury, Christopher Mark. “Genetic evaluation of the ovine and bovine prion protein genes (PRNP).” 2006. Doctoral Dissertation, Texas A&M University. Accessed February 27, 2021.
http://hdl.handle.net/1969.1/3333.
MLA Handbook (7th Edition):
Seabury, Christopher Mark. “Genetic evaluation of the ovine and bovine prion protein genes (PRNP).” 2006. Web. 27 Feb 2021.
Vancouver:
Seabury CM. Genetic evaluation of the ovine and bovine prion protein genes (PRNP). [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1969.1/3333.
Council of Science Editors:
Seabury CM. Genetic evaluation of the ovine and bovine prion protein genes (PRNP). [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/3333
Texas A&M University
2.
Schutta, Christopher John.
Bovine SLC11A1: genomic sequence variation and functional analysis in cattle naturally resistant and susceptible to bovine brucellosis.
Degree: PhD, Veterinary Microbiology, 2009, Texas A&M University
URL: http://hdl.handle.net/1969.1/ETD-TAMU-1874
Previous analysis of the bovine SLC11A1 complementary DNA (cDNA)
failed to identify any nucleotide variations other than a microsatellite length
variation within the 3' untranslated region functionally associated with bovine
brucellosis. In this study I set out to identify mutations in the genomic complement
of the gene that may be associated with resistance or susceptibility to bovine
brucellosis, and to determine if the microsatellite length polymorphism in the
3'UTR of bovine SLC11A1 modulates gene expression and subsequent disease
resistance in a phase dependent manner. The results of this study demonstrate that
there are seventy-five total single nucleotide polymorphic (SNP) sites (excluding
indels) located within the bovine genomic SLC11A1 sequence of a Brucella abortus
resistant bull and a susceptible cow. Twenty of these SNPs segregated between
resistant and susceptible populations, with 3 non-synonymous SNPs significantly
associating with resistance or susceptibility to B. abortus infection. An A695G
within exon 2 resulted in a histidine (resistant allele) to arginine (susceptible allele) amino acid substitution and was in significant linkage disequilibrium with the
previously described 3' untranslated region (UTR) microsatellite length variation
associated with brucellosis resistance. A transcriptional element search in the 3'
UTR revealed a ETS-domain PU.1 site, an IFN-γ activation site (GAS), an
Interferon Consensus Sequence Binding Protein site (ICSBP) and several Initiation
Response sites (Inr), suggesting a possible function for this region in regulation of
the expression of SLC11A1. A mobility shift assay confirmed sequence-specific
DNA-protein interaction within this region. A luciferase reporter assay indicated
that the 3'UTR of SLC11A1 could act as a downstream enhancer for expression.
Macrophage killing assays with RAW264.7 cells expressing bovine SLC11A1
demonstrated that the microsatellite repeat is functionally associated with the
macrophage killing efficiency, but not in a phase-dependent manner, suggesting
that these length polymorphisms do not affect the angular orientation between
cooperatively binding transcription factors, and leaves the possibility that the
3'UTR microsatellites regulate SLC11A1 transcription through some alternate
mechanism, possibly mRNA stability.
Advisors/Committee Members: Templeton, Joe W. (advisor), Adams, L. Garry (committee member), Davis, Donald S. (committee member), Derr, James N. (committee member).Subjects/Keywords: SLC11A1; brucellosis; natural disease resistance
Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Schutta, C. J. (2009). Bovine SLC11A1: genomic sequence variation and functional analysis in cattle naturally resistant and susceptible to bovine brucellosis. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-1874
Chicago Manual of Style (16th Edition):
Schutta, Christopher John. “Bovine SLC11A1: genomic sequence variation and functional analysis in cattle naturally resistant and susceptible to bovine brucellosis.” 2009. Doctoral Dissertation, Texas A&M University. Accessed February 27, 2021.
http://hdl.handle.net/1969.1/ETD-TAMU-1874.
MLA Handbook (7th Edition):
Schutta, Christopher John. “Bovine SLC11A1: genomic sequence variation and functional analysis in cattle naturally resistant and susceptible to bovine brucellosis.” 2009. Web. 27 Feb 2021.
Vancouver:
Schutta CJ. Bovine SLC11A1: genomic sequence variation and functional analysis in cattle naturally resistant and susceptible to bovine brucellosis. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1874.
Council of Science Editors:
Schutta CJ. Bovine SLC11A1: genomic sequence variation and functional analysis in cattle naturally resistant and susceptible to bovine brucellosis. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1874
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