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Geographical Genomics of Human Leukocytes Gene Expression Variation

ABSTRACT: Genome-wide association studies of transcript abundance in peripheral blood samples or derivative cell lines have demonstrated a preponderance of eSNP effects that, for the most part, involve regulatory polymorphisms in the differentially expressed gene. Several of these highlight associations that contribute to a variety of disease conditions, but the question arises as to how the associations are affected by the environment. Here we address the robustness of eSNP associations to environmental geography and population structure in a comparison of 194 Arab and Amazigh individuals from a city and two villages in southern Morocco.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17065 | GEO | 2009/12/01

SECONDARY ACCESSION(S): PRJNA119845

REPOSITORIES: GEO

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Project description:BACKGROUND: Metagenomic studies carried out in the past decade have led to an enhanced understanding of the gut microbiome in human health, however, the Indian gut microbiome is not well explored yet. We analysed the gut microbiome of 110 healthy individuals from two distinct locations (North-Central and Southern) in India using multi-omics approaches, including 16S rRNA gene amplicon sequencing, whole genome shotgun metagenomic sequencing, and metabolomic profiling of faecal and serum samples. </br> RESULTS: The gene catalogue established in this study emphasizes the uniqueness of the Indian gut microbiome in comparison to other populations. The gut microbiome of the cohort from North-Central India, which was primarily consuming a plant-based diet, was found to be associated with Prevotella, and also showed an enrichment of Branched Chain Amino Acid (BCAA) and lipopolysaccharide (LPS) biosynthesis pathways. In contrast, the gut microbiome of the cohort from Southern India, which was consuming an omnivorous diet, showed associations with Bacteroides, Ruminococcus and Faecalibacterium, and had an enrichment of Short Chain Fatty Acid (SCFA) biosynthesis pathway and BCAA transporters. This corroborated well with the metabolomics results, which showed higher concentration of BCAAs in the serum metabolome of the North-Central cohort and an association with Prevotella. In contrast, the concentration of BCAAs were found higher in the faecal metabolome of the Southern-India cohort, and showed a positive correlation with the higher abundance of BCAA transporters. </br> CONCLUSIONS: The study reveals the unique composition of Indian gut microbiome, establishes the Indian gut microbial gene catalogue, and compares it with the gut microbiome of other populations. The functional associations revealed using metagenomic and metabolomic approaches provide novel insights on the gut-microbe-metabolic axis, which will be useful for future epidemiological and translational researches.

Project description:Fibroblast growth factor (FGF) 2 (FGF2 or basic FGF) mediates a wide range of biological functions, such as regulating proliferation, angiogenesis, migration, differentiation and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza virus (IAV) -induced lung injury remain largely unexplored. In this study, we firstly report miR-194 expression is significantly decreased in A549 cells following influenza virus A/Beijing/501/2009 (BJ501) infection. MiR-194 directly targeting FGF2, a novel antiviral regulator, could suppress FGF2 expression both in mRNA and protein levels. Overexpression miR-194 facilitate IAV replication via negatively regulating type I IFN production, and reintroduction of FGF2 abrogates miR-194-induced effects on promoting IAV replication. On the contrary, inhibition of miR-194 alleviate IAV induced lung injury via promoting type I IFNs antiviral activities in vivo. Importantly, contrary to FGF2 activated RIG-I signaling pathway, miR-194 suppressed TBK1 and IRF3 phosphorylation. Taken together, our findings demonstrated that miR-194-FGF2 axis play a vital role in IAV-induced lung injury, and miR-194 antagonism might be as a potential therapeutic target during IAV infection. Fibroblast growth factor (FGF) 2 (FGF2 or basic FGF) mediates a wide range of biological functions, such as regulating proliferation, angiogenesis, migration, differentiation and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza virus (IAV) -induced lung injury remain largely unexplored. In this study, we firstly report miR-194 expression is significantly decreased in A549 cells following influenza virus A/Beijing/501/2009 (BJ501) infection. MiR-194 directly targeting FGF2, a novel antiviral regulator, could suppress FGF2 expression both in mRNA and protein levels. Overexpression miR-194 facilitate IAV replication via negatively regulating type I IFN production, and reintroduction of FGF2 abrogates miR-194-induced effects on promoting IAV replication. On the contrary, inhibition of miR-194 alleviate IAV induced lung injury via promoting type I IFNs antiviral activities in vivo. Importantly, contrary to FGF2 activated RIG-I signaling pathway, miR-194 suppressed TBK1 and IRF3 phosphorylation. Taken together, our findings demonstrated that miR-194-FGF2 axis play a vital role in IAV-induced lung injury, and miR-194 antagonism might be as a potential therapeutic target during IAV infection.

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Geographical Genomics of Human Leukocytes Gene Expression Variation

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