Genome-Wide Association Studies and Genotyping Technologies

Publisher Summary This chapter discusses genome-wide association studies with an overview of two commonly used genotyping platforms, Illumina Infinium Assay and Affymetrix GeneChip. The Illumina genotyping technology is based on 3μ silicon beads that have hundreds of thousands of DNA oligomers attached to the surface. For Illumina's genotyping BeadChip, the attached oligomers consist of a stretch of 75 nucleotides. The first 25 nucleotides serve as a barcode to identify the location of specific beads on the array and the next 50 bases are complementary to a genomic region containing specific single nucleotide polymorphisms. On an average, there is an 18-fold redundancy of each bead type on the BeadChip. The placement of the beads is a random process, requiring a decoding step, which involves multiple hybridizations to the 25-oligomer address. This identifies the location of each bead and performs a functional quality control for each bead on the BeadChip. The Infinium I assay uses an allele-specific primer extension reaction in which fluorescently labeled nucleotides are inserted at the 3' end of the primer. It takes two bead types to determine the genotype at a single SNP. The Infinium II assay involves a single-base extension reaction that occurs on a single bead type for each SNP. Most of Illumina's off-the-shelf BeadChips use the Infinium II assay.