Project description:The obligate intracellular bacterium, Ehrlichia ruminantium (ER) is the causal agent of Heartwater, a fatal disease in ruminants. It is transmitted by ticks of the genus Amblyomma. Here, we report the genomic comparative and the global transcriptional profile of 4 strains of ER, Gardel and Senegal, two distant virulent strains with their corresponding attenuated strains. Our results showed a higher metabolic activity in attenuated strains compared to virulent strains, suggesting a better adaptation in vitro of attenuated strains to the host cells. There was a strong modification of membrane protein encoding genes expression for the 4 strains. A major over-expression of map1-related genes was observed for virulent strains, whereas attenuated strains over-expressed genes encoding for hypothetical membrane proteins. This result suggests that in vivo, MAP-1 related proteins could induce non-protective immune responses for virulent strains. For the attenuated strains, the lack of expression of map1-related genes and over-expression of other membrane proteins encoding genes could be important in induction of efficient immune responses.The diminution of expression of many genes in attenuated Senegal was caused by severe mutation. One of them, the gene recO is involved in DNA repair and its mutation could explain the higher proportion of mutated genes in attenuated Senegal, inducing the faster attenuation of Senegal compared to Gardel.
2016-05-01 | GSE55726 | GEO
Project description:NYUAD Genomes submission of different Algal species 2017-2024
Project description:Transcriptome-wide association studies (TWAS) to pinpoint enhanced expression of genes involved in DNA repair attributed to viral resistance of atxr5 atxr6.
Project description:To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five new histotype-specific EOC risk regions (P-value < 5 x 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (P-value < 10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue data sets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (FDR < 0.05). Finally, by integrating genome-wide HiChIP interactome analysis with TWAS, variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8 and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by GWAS.