| Autor: |
Killick, K. E., McLoughlin, K. E., Nalpas, N. C., Burkitt-Gray, L., Richardson, I. W., Wiencko, H. L., Magee, D. A., Browne, J. A., Villarreal-Ramos, B., Vordermeier, H. M., Berry, D. P., Bradley, D. G., Gormley, E., Gordon, S. V., MacHugh, D. E. |
| Zdroj: |
Journal of Animal Science; September 2016, Vol. 94 Issue: 1, Number 1 Supplement 4 p160-161, 2p |
| Abstrakt: |
Mycobacterium bovis, the causative pathogen of bovine tuberculosis (BTB), is responsible for an estimated $3 billion losses to global agriculture annually. The impacts of M. bovisinfection are manifold, including risks to animal and public health, disruptions to trade, and reduced agricultural productivity, particularly in developing countries. Previous microarray and RNA-seq transcriptomics experiments have facilitated reconstruction of gene regulatory networks and cellular pathways underlying the bovine host response to infection with M. bovis. In addition, it is well established that intra- and inter-population genetic variation exists for BTB susceptibility/resistance, with documented heritability estimates ranging from 0.08 to 0.19. For the present study, we therefore used a network-based approach to integrate gene expression data with high-density single-nucleotide polymorphism (SNP) genome-wide association (GWA) data to enhance detection of genomic variants for susceptibility/resistance to M. bovisinfection. A range of bovine host RNA-seq data have been generated by our research group; these include data from an ex vivo experimental M. bovisanimal infection time course and in vitro macrophage challenge experiments using M. bovis. These gene expression data were superimposed on a base network of the mammalian host response to mycobacterial infections. Following this, systems approaches identified key subnetworks and contextual hub genes. These gene subsets were then used to rank and prioritize SNP variants from a GWA study of individual animal estimated breeding values (EBVs) for BTB susceptibility with SNP genotype data (Illumina® Bovine HD Genotyping BeadChip-597,144 filtered SNPs) generated for 842 Holstein-Friesian dairy bulls. These prioritized statistically robust SNP variants will provide an important reference for genome-enabled breeding programs for BTB resistance traits. Importantly, the approach and methods described here may also be applied to comparable transcriptomics and GWA data generated for studies of the human response to infection with Mycobacterium tuberculosis. |
| Databáze: |
Supplemental Index |
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