Using Blood-Informative Transcripts in Geographical Genomics: Impact of Lifestyle on Gene Expression in Fijians
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ABSTRACT: This study explores the impact of lifestyle and environment on gene expression through whole transcriptome profiling of peripheral blood samples in Fijian population (native Melanesians and Indians) living in the rural and urban areas. 41 individuals (14 urban Melanesians, 10 rural Melanesians and 17 urban Indians) of both gender were sampled under informed consents. Only healthy individuals aged between 18 and 65 were sampled. RNA from each sample was hybridized to an Illumina array. No replicates were done in this study
Project description:This study explores the impact of lifestyle and environment on gene expression through whole transcriptome profiling of peripheral blood samples in Fijian population (native Melanesians and Indians) living in the rural and urban areas.
Project description:The Study Of Urban and Rural Crohn disease Evolution (SOURCE, n=380) characterized exposures, diet, and host and microbial factors in rural and urban Chinese controls and newly diagnosed Crohn Disease (CD), and in treatment-naïve Israeli CD and controls. We considered diet-omics domains simultaneously to detect complex interactions in the gut to prioritize potential beneficial and pathogenic factors.
Project description:Epigenetic variation has the potential to control environmentally dependent development and contribute to phenotypic responses to local environments. Environmental epigenetic studies of sexual organisms confirm the responsiveness of epigenetic variation, which should be even more important when genetic variation is lacking. A previous study of an asexual snail, Potamopyrgus antipodarum, demonstrated that different populations derived from a single clonal lineage differed in both shell phenotype and methylation signature when comparing lake versus river populations. Here, we examine methylation variation among lakes that differ in environmental disturbance and pollution histories. The differential DNA methylation regions (DMRs) identified among the different lake comparisons suggested a higher number of DMRs and variation between rural Lake 1 and one urban Lake 2 and between the two urban Lakes 2 and 3, but limited variation between the rural Lake 1 and urban Lake 3. DMR genomic characteristics and gene associations were investigated. Observations suggest there is no effect of geographic distance or any consistent pattern of DMRs between urban and rural lakes. Environmental factors may influence epigenetic response.
Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/µl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.
Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.
Project description:Forty-six percent of the world's population resides in rural areas, the majority of whom belong to vulnerable and low-income groups. They mainly use cheap solid fuels for cooking and heating, which release a large amount of PM2.5 and cause adverse effects to human health. PM2.5 exhibits urban-rural differences in its health risk to the respiratory system. However, the majority of research on this issue has focused on respiratory diseases induced by atmospheric PM2.5 in urban areas, while rural areas have been ignored for a long time, especially the pathogenesis of respiratory diseases. This is not helpful for promoting environmental equity to aid low-income and vulnerable groups under PM2.5 pollution. Thus, this study focuses on rural atmospheric PM2.5 in terms of its chemical components, toxicological effects, respiratory disease types, and pathogenesis, represented by PM2.5 from rural areas in the Sichuan Basin, China (Rural SC-PM2.5). In this study, organic carbon is the most significant component of Rural SC-PM2.5. Rural SC-PM2.5 significantly induces cytotoxicity, oxidative stress, and inflammatory response. Based on multiomics, bioinformatics, and molecular biology, Rural SC-PM2.5 inhibits ribonucleotide reductase regulatory subunit M2 (RRM2) to disrupt the cell cycle, impede DNA replication, and ultimately inhibit lung cell proliferation. Furthermore, this study supplements and supports the epidemic investigation. Through an analysis of the transcriptome and human disease database, it is found that Rural SC-PM2.5 may mainly involve pulmonary hypertension, sarcoidosis, and interstitial lung diseases; in particular, congenital diseases may be ignored by epidemiological surveys in rural areas, including tracheoesophageal fistula, submucous cleft of the hard palate, and congenital hypoplasia of the lung. This study contributes to a greater scientific understanding of the health risks posed by rural PM2.5, elucidates the pathogenesis of respiratory diseases, clarifies the types of respiratory diseases, and promotes environmental equity.
Project description:The molecular basis of evolutionary change is assumed to be genetic variation. However, growing evidence suggests that epigenetic mechanisms, such as DNA methylation, may also be involved in evolutionary change. An important first step in evaluating this hypothesis is to test for the presence of epigenetic variation between natural populations living under different environmental conditions. In the current study we explored variation between populations of Darwin’s finches living in adjacent “urban” and “rural” environments on Santa Cruz Island in the Galápagos. We tested for morphological, genetic, and epigenetic differences between the urban and rural populations of each of two species of ground finches, Geospiza fortis and G. fuliginosa. Using data collected from more than 1000 birds, we found significant morphological differences between populations of G. fortis, but not G. fuliginosa. We did not find genetic differences between populations of either species, based on comparisons of copy number variation (CNV). In contrast, we did find epigenetic differences between the urban and rural populations of both species, based on DNA methylation analysis. We explored genomic features and gene associations of the differentially methylated regions (DMR), as well as their possible functional significance. In summary, our study documents local population epigenetic variation within species of Darwin’s finches.
Project description:Sub-Saharan Africa currently experiences an unprecedented wave of urbanization, which has important consequences for health and disease patterns. This study aimed to investigate and integrate the immune and metabolic consequences of rural or urban lifestyles and the role of nutritional changes associated with urban living. In a cohort of 323 healthy Tanzanians, urban as compared to rural living was associated with a pro-inflammatory immune phenotype, both at the transcript and protein levels. We identified different food-derived and endogenous circulating metabolites accounting for these differences. Serum from urban dwellers induced reprogramming of innate immune cells with higher tumor necrosis factor production upon microbial re-stimulation in an in vitro model of trained immunity. These data demonstrate important shifts toward an inflammatory phenotype associated with an urban lifestyle and provide new insights into the underlying dietary and metabolic factors, which may affect disease epidemiology in sub-Sahara African countries.
Project description:This study aimed to shed light on the gene regulatory networks underlying plant leaf responses to air particulate matter. Our investigation focused on shrubs of Photinia x fraseri grown in pots located in two contrasting areas: a highly polluted traffic road and rural countryside within the same town (Altopascio, Lucca, Italy). RNA-seq data were related to leaf morphological traitsand air particulate matter, allowing to identify key players in modulating the capabilities of plants to phyllo-remediate high air particulate matter levels in urban environment.