title: Development of a genotyping microarray for studying the role of gene-environment interactions in risk for lung cancer.
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.
authors.affiliation: Pathonomics LLC, Philadelphia, Pennsylvania 19104, USA; ; Center of Excellence in Environmental Toxicology.
authors.forename: Don A
authors.initials: DA
authors.lastname: Baldwin
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Sarnowski
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Reddy
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
authors.forename: Margie
authors.initials: M
authors.lastname: Clapper
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarus
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Muscat
authors.forename: Trevor M
authors.initials: TM
authors.lastname: Penning
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Whitehead
mesh_terms: D016022:Case-Control Studies; D059647:Gene-Environment Interaction; D060005:Genotyping Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide
keywords: LungCaGxE; Tagger Batch Assistant; environmental exposures; genetic association