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Published on: January 30, 2017
Identification of genetic variation and putative regulatory regions in bovine CARD15
Kristen H Taylor1, Jeremy F Taylor, Stephen N White
1Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas 77843-4467, USA.
Insights
Comparative analysis of CARD15 (caspase recruitment domain 15) in cattle, mice, and humans reveals conserved function but species-specific regulation. Genetic diversity in bovine CARD15 was assessed, finding no direct link to Johne
Area of Science:
- Genomics
- Comparative genomics
- Molecular biology
Background:
- Mutations in caspase recruitment domain 15 (CARD15) are linked to Crohn's disease and Blau Syndrome in humans.
- Understanding CARD15 function in cattle is crucial for investigating bovine disease resistance.
Purpose of the Study:
- To compare bovine, murine, and human CARD15 transcripts for functional insights.
- To identify regulatory elements and assess genetic diversity within bovine CARD15.
- To explore the potential role of CARD15 in bovine disease resistance, specifically Johne's disease.
Main Methods:
- Comparative analysis of CARD15 transcripts and intronic sequences across species.
- Identification of conserved and species-specific regulatory motifs.
- Sequencing and polymorphism screening of CARD15 in 41 bovine individuals from two subspecies.
- Haplotype prediction and association analysis with Johne's disease.
Main Results:
- High conservation of CARD15 sequence, genomic structure, and protein domains across cattle, humans, and mice.
- Identification of species-specific regulatory elements in untranslated regions.
- Discovery of 31 conserved intronic regulatory element binding motifs.
- Identification of 36 single nucleotide polymorphisms (SNPs) and 20 subspecies-specific haplotypes in bovine CARD15.
Conclusions:
- CARD15 exhibits conserved functionality across mammals, but regulatory mechanisms have diverged.
- Significant genetic diversity exists within bovine CARD15, characterized by numerous SNPs and haplotypes.
- No direct causal relationship was found between identified CARD15 SNP loci/haplotypes and Johne's disease susceptibility.
Abstract:
Mutations in caspase recruitment domain 15 (CARD15) are associated with susceptibility to Crohn's disease and Blau Syndrome. We performed comparative analyses of the bovine, murine, and human CARD15 transcripts to elucidate functionality of bovine CARD15 and examine its potential role in bovine disease resistance. Comparative analyses of intronic sequence across seven divergent species were performed to identify putative regulatory element binding motifs. High levels of interspecies conservation in sequence, genomic structure, and protein domains were detected indicating common functionality for CARD15 in cattle, human, and mouse. We identified species-specific regulatory elements in the 5' and 3' untranslated regions, suggesting that modes of regulation may have diverged across species. Thirty-one conserved putative regulatory element binding motifs were identified in the CARD15 intronic sequence of seven species. To assess the extent of genetic diversity within bovine CARD15, 41 individuals from two subspecies were sequenced and screened for polymorphisms. Thirty-six single nucleotide polymorphisms (SNPs) were identified. Finally, 20 subspecies-specific haplotypes were predicted with 7 and 13 unique haplotypes explaining the diversity within B. taurus taurus and B. taurus indicus animals, respectively. Strong evidence for a simple causal relationship between these SNP loci and their haplotypes with Johne's disease was not detected.
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