Project description:DNA methylation appears to play an essential mechanistic role in the pathogenesis of ALL, thereby potentiate its use as a biomarker for diagnosis and prognosis (Milani, Lundmark et al. 2010; Geng, Brennan et al. 2012; Sandoval, Heyn et al. 2013), and even a potential target of novel therapeutic approaches in ALL. In present study, we collected blood specimens for 4 pairs of monozygotic twins (MZ) and 1 pair of dizygotic twin (DZ) that are discordant for ALL. We sought to comprehensively assess the magnitude of genetic and epigenetic differences between ALL-affected and unaffected twins. we conducted whole genome and whole methylome sequencing on these five pairs of ALL-discordant twins. We also examined both the MZ and DZ twins using whole-genome bisulfite sequencing (WGBS). At first, the methylation differences across the genome were addressed globally by Circos software. And then tried to characterize the co-twin methylation divergence in specific genomic regions between ALL-discordant twin pairs. These patterns of dynamic co-twin methylation changes in these discordant ALL samples were generally consistent among MZ and DZ twins, indicating similarities of methylation abnormalities. As a result, 780, 566, 309, 293 and 2110 DMRs were identified, with a similar distribution pattern across different genomic elements among the five twin pairs.Then we annotate whether these DMRs were located in regulatory elements and identification of genes with recurring methylation alterations in a cohort of ALL patients. We collected blood specimens from 4 pairs of MZ twins and 1 pair of DZ twin that are discordant for ALL. At first, the methylation differences across the genome were addressed globally by Circos software. And then tried to characterize the co-twin methylation divergence in specific genomic regions and differentially methylated gene regions (DMRs) were identified between ALL-discordant twin pairs. Then we annotate whether these DMRs were located in regulatory elements and identification of genes with recurring methylation alterations in a cohort of ALL patients.

Project description:Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays. Results. UC patients showed a dysbiotic microbiota with lower diversity and more species belonging to Actinobacteria and Proteobacteria phyla. On the contrary, their healthy siblings’ microbiota contained more bacteria from the Lachnospiracea and Ruminococcaceae family than did healthy individuals . Sixty-three host transcripts significantly correlated with bacterial genera in healthy individuals whereas only 43 and 32 correlated with bacteria in healthy and UC siblings from discordant pairs, respectively. Several transcripts related to oxidative and immune responses were differentially expressed between unaffected and UC siblings. Conclusion. A loss of crosstalk between gut microbiota and host was highlighted in UC patients. This defect was also striking in healthy siblings from discordant pairs, as was the lower biodiversity within the microbiota. Our results suggest disease-relevant interactions between host transcriptome and microbiota. Moreover, unusual aerobic bacteria were noticed in UC mucosal microbiota, whereas healthy siblings from discordant pairs had higher percentages of potentially beneficialusual commensal bacterial species.

Project description:Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays. Results. UC patients showed a dysbiotic microbiota with lower diversity and more species belonging to Actinobacteria and Proteobacteria phyla. On the contrary, their healthy siblingsM-bM-^@M-^Y microbiota contained more bacteria from the Lachnospiracea and Ruminococcaceae family than did healthy individuals . Sixty-three host transcripts significantly correlated with bacterial genera in healthy individuals whereas only 43 and 32 correlated with bacteria in healthy and UC siblings from discordant pairs, respectively. Several transcripts related to oxidative and immune responses were differentially expressed between unaffected and UC siblings. Conclusion. A loss of crosstalk between gut microbiota and host was highlighted in UC patients. This defect was also striking in healthy siblings from discordant pairs, as was the lower biodiversity within the microbiota. Our results suggest disease-relevant interactions between host transcriptome and microbiota. Moreover, unusual aerobic bacteria were noticed in UC mucosal microbiota, whereas healthy siblings from discordant pairs had higher percentages of potentially beneficialusual commensal bacterial species. Paired samples (twins) were analyzed to obtain data independent of genetic variation

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