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Abstract:
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Through 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 . |