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dc.contributor.advisorWomack, James E.en_US
dc.creatorTaylor, Kristen Hawkinsen_US
dc.date.accessioned2004-09-30T01:46:40Z
dc.date.available2004-09-30T01:46:40Z
dc.date.created2004-05en_US
dc.date.issued2004-09-30
dc.identifier.urihttp://hdl.handle.net/1969.1/219
dc.description.abstractThrough a binding partner the CARD15 gene activates NF-kB, a molecule with a role in the initiation of the inflammatory immune response. The gene is highly conserved in both structure and function in human and mouse and has recently been implicated as a disease resistance gene in Crohn's disease and Blau Syndrome in human. The gene's relationship to disease and its conservation between species suggests that it may also have a conserved role in bovine disease resistance. To elucidate the potential role of bovine CARD15 in disease resistance, the gene was characterized in cattle. Bovine CARD15 is located 4.2 cR5000 telomeric to ADCY7 on chromosome 18. It spans ~30 kb and is comprised of 12 exons, 11 of which are coding. Bovine CARD15 is expressed in many tissues, but is most abundant in peripheral blood leukocytes. An extensive comparative analysis between the bovine, mouse and human CARD15 genes revealed high levels of inter-species conservation in sequence, genomic structure and protein domains. Conserved putative regulatory motifs were identified in the three species comparison of the 5'UTR, 3'UTR and the intronic sequences flanking exons. Additionally, diverse regulatory motifs were identified in each of the species indicating an evolutionary divergence in the mechanisms of regulation of gene expression. To assess the extent of genetic diversity within bovine CARD15, 41 individuals from nine breeds representing two subspecies were sequenced and screened for polymorphisms. Thirty-six single nucleotide polymorphisms (SNPs) were identified including 26 within the gene transcript. Haplotypes were estimated for each individual and parsimonious SNP sets were identified with which the multi-locus Bos taurus and Bos indicus haplotypes may be reconstructed. There was a significantly higher rate of substitutions within Bos indicus than in Bos taurus. A significantly higher rate of nonsynonymous to synonymous substitutions was found in Bos taurus indicating that positive Darwinian selection is acting on the gene within this subspecies. Association analyses were performed between these SNP loci and haplotypes with Johne's disease. No overwhelming evidence for a simple causal relationship was detected. Assays are provided to screen populations of cattle for variation in the CARD15 gene.en_US
dc.format.extent735945 bytes
dc.format.extent223639 bytes
dc.format.mediumelectronicen_US
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_USen_US
dc.publisherTexas A&M Universityen_US
dc.subjectCARD15en_US
dc.subjectNOD2en_US
dc.subjectbovineen_US
dc.subjectdisease resistanceen_US
dc.subjectCrohn'sen_US
dc.subjectJohne'sen_US
dc.titleGenetic analyses of bovine CARD15, a putative disease resistance geneen_US
dc.typeBooken
dc.typeThesisen
thesis.degree.departmentVeterinary Pathobiologyen_US
thesis.degree.disciplineGeneticsen_US
thesis.degree.grantorTexas A&M Universityen_US
thesis.degree.nameDoctor of Philosophyen_US
thesis.degree.levelDoctoralen_US
dc.contributor.committeeMemberDerr, James N.en_US
dc.contributor.committeeMemberAdams, L. Garryen_US
dc.contributor.committeeMemberRoussel, Allen J.en_US
dc.type.genreElectronic Dissertationen_US
dc.type.materialtexten_US
dc.format.digitalOriginborn digitalen_US


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