This project describes the role of the lab of Stephanie London in the Laboratory of Respiratory Biology in support of her epidemiologic studies. The laboratory is engaged in selection of polymorphisms for analysis, using bioinformatic methods and genotyping analysis of samples from Dr. London's epidemiologic studies of respiratory disease. In the past year, we have focused on the study of childhood asthma in Mexico City (described under project entitled Genetic And Environmental Factors In Childhood Respiratory Health). We have taken two approaches in this study. As with most other investigators, we previously focused on candidate gene association. We have examined promising asthma candidate genes that we can then examine for interaction with secondhand smoke and ozone. We also examine genes that are highly likely to be involved in respiratory or immune response to these agents. In the field of asthma genetics, genes identified through positional cloning have not always replicated well in association studies. We took advantage of the whole genome association genotyping that we did in our Mexico City study to do the most comprehensive analysis of asthma candidate genes to date. This work is in under review. The other approach that we are taking is whole genome association. We recently published the results from our genome wide association study. This involved replication genotyping in another Mexican population (Hancock et al., 2009). We are also interested in the potential role of epigenetic changes in respiratory disease in children and adults. To this end, we have been evaluating commercially available kits for detecting the percent of methylated DNA. We are evaluating whether these methods are sensitive and reproducible enough for us to use on our human peripheral blood DNA samples. This is am important issue to evaluate because these kits have been developed to detect differences between tumor and normal tissue which are much larger. We are also interested in epigenetic influences on respiratory disease. This is a burgeoning area with new assays to detect epigenetic changes being developed. The challenge is to evaluate the available assays and choose those most suitable for examination of peripheral blood DNA in humans given that many were developed to detect the much greater differences between cancer tissue and normal tissue. We have been evaluating commercially available kits for assessment of percent methylation. We plan to use these data that we generate to select a platform for e
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