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Development of a Genotyping Microarray for Studying the Role of Gene-Environment Interactions in Risk for Lung Cancer
Authors:Don A. Baldwin  Christopher P. Sarnowski  Sabrina A. Reddy  Ian A. Blair  Margie Clapper  Philip Lazarus  Mingyao Li  Joshua E. Muscat  Trevor M. Penning  Anil Vachani  Alexander S. Whitehead
Abstract:A microarray (LungCaGxE), based on Illumina BeadChip technology, was developed for high-resolution genotyping of genes that are candidates for involvement in environmentally driven aspects of lung cancer oncogenesis and/or tumor growth. The iterative array design process illustrates techniques for managing large panels of candidate genes and optimizing marker selection, aided by a new bioinformatics pipeline component, Tagger Batch Assistant. The LungCaGxE platform targets 298 genes and the proximal genetic regions in which they are located, using ∼13,000 DNA single nucleotide polymorphisms (SNPs), which include haplotype linkage markers with a minimum allele frequency of 1% and additional specifically targeted SNPs, for which published reports have indicated functional consequences or associations with lung cancer or other smoking-related diseases. The overall assay conversion rate was 98.9%; 99.0% of markers with a minimum Illumina design score of 0.6 successfully generated allele calls using genomic DNA from a study population of 1873 lung-cancer patients and controls.
Keywords:genetic association   environmental exposures   Tagger Batch Assistant   LungCaGxE
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