 Hello, my name is Aristea Binyam and I will talk to you about a recent article in Human Mutation with the title functional polymorphism affecting meat binding within the promoter of the program Death Cell Domain IV is associated with severe asthma in children. Our study combined genetic analysis and functional assays and it identified a mechanism exclusive for severe asthma in children. Initially we followed the result of a genome-wide association study conducted in childhood asthma and this was the first study that reported the highly significant association between 70q21 locus and severe asthma in children. We selected from these results the 10 top hits to genotype them in independent groups of severe asthmatic children and adults and controls. These first results showed that there was a significant association between only severe asthma in children and a polymorphism within the program Death Cell Domain IV. The next step included fine mapping analysis in which we selected a number of polymorphisms within the region of PDCD IV to genotype them in severe cases and controls and also a panel of family trios with an asthmatic probant. We additionally used data from the 1958 birth cohort study from Great Britain as controls to our study. So we selected five additional SNPs, two of them in the promoter of PDCD IV, two of them in entrance and one of them in action V. From all these SNPs, three of them were significantly associated with severe asthma in children, in the case control analysis and in the family trios analysis. The results remained significant after correcting for multiple testing. Now these results were replicated also in an independent population of asthmatic children and controls from Germany. In particular, polymorphism RS 65-85-018 was significantly associated with total IgE levels. The final step of our study included the functional validation of these findings. First, we performed bioinformatics prediction analysis and electromobility shift assays. These results showed that RS 65-85-018 has the ability to disrupt the binding of MEAP transcriptional user. Reporter RS's results confirmed these findings and showed that that polymorphism has a regulatory role affecting the transcription of the gene. Overall, our mechanism proposed a functional SNP within the promoter of PDCD IV gene to have the ability to influence the binding of MEAP, in particular when AALIL is present in the promoter. MEAP can bind, resulting in increased transcription of PDCD IV. When GAALIL is present, the mechanism is absent, resulting in a reduced transcription of PDCD IV. So we propose that the mechanism is important in asthmatic inflammatory responses and PDCD IV molecule a target for future therapeutic interventions. Thank you very much for your attention. We're looking forward to your comments.