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The Druley lab is focused on rare individual genetic variation--substitutions, insertions, deletions, epigenetic changes--and how such variation influences the onset and treatment of complex disease. The "Rare Variant" hypothesis posits that much of complex disease presentation and treatment is influenced by the unique combination of rare inherited DNA mutations within each person. While a specific polymorphism in a specific gene may be individually rare, an affected population may carry many different mutations to that gene or other genes in the same pathway - thus resulting in the same disease phenotype.
To study this question, we have developed a method for pooling the genomic DNA from hundreds to thousands of individuals, targeting genes or regions of interest by PCR on the pooled genomic DNA followed by deep resequencing of the PCR products using next-generation DNA sequencing. To analyze these pooled DNA experiments, we have designed and validated novel computational algorithms for unraveling the mass of sequence data in a highly accurate manner.
The lab has two goals: 1) to better understand the general impact of rare variation on population diversity and complex disease as well as 2) applying genomic technology to identifying genes and pathways associated with specific disease states. As a pediatric oncologist interested in understanding how cancer develops in children, we are currently working to identify germline variants responsible for predisposing children to acute lymphoblastic leukemia (ALL). The long-term goals are to better understand the pathophysiology of pediatric cancer as well as providing the ability to identify all of the pertinent germline variants within a pediatric cancer patient prior to starting therapy in order to provide a genetically customized treatment plan designed to maximize anti-cancer activity while minimizing toxicity and morbidity.
Other lab projects currently ongoing include studying the distribution of genetic variation globally - using DNA from 25,000 individuals from four geographically distinct locations, and we're working to develop single molecule mutation analysis. In addition to a variety of established collaborations across a variety of complex diseases, there are a variety of opportunities available to conduct exciting research in the Druley lab.
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