Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

<p>Abstract</p> <p>Background</p> <p>Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.</p> <p>Methods</p> <p>rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.</p> <p>Results</p> <p>Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV₁and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.</p> <p>Conclusion</p> <p>Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.</p

The evolution of living beings started with prokaryotes and in interaction with prokaryotes

In natural world, no organism exists in absolute isolation, and thus every organism must interact with the environment and other organisms. Next-generation sequencing technologies are increasingly revealing that most of the cells in the environment resist cultivation in the laboratory and several prokaryotic divisions have no known cultivated representatives. Based on this, we hypothesize that species that live together in the same ecosystem are more or less dependent upon each other and are very large in diversity and number, outnumbering those that can be isolated in single-strain laboratory culture. In natural environments, bacteria and archaea interact with other organisms (viruses, protists, fungi, animals, plants, and human) in complex ecological networks, resulting in positive, negative, or no effect on one or another of the interacting partners. These interactions are sources of ecological forces such as competitive exclusion, niche partitioning, ecological adaptation, or horizontal gene transfers, which shape the biological evolution. In this chapter, we review the biological interactions involving prokaryotes in natural ecosystems, including plant, animal, and human microbiota, and give an overview of the insights into the evolution of living beings. We conclude that studies of biological interactions, including multipartite interactions, are sources of novel knowledge related to the biodiversity of living things, the functioning of ecosystems, the evolution of the cellular world, and the ecosystem services to the living beings