Whole-genome genotyping on bead arrays.

In this review, we describe the laboratory implementation of Infinium whole genome genotyping (WGG) technology for whole genome association studies and copy number studies. Briefly, the Infinium WGG assay employs a single tube whole genome amplification reaction to amplify the entire genome; genomic loci of interest are captured on an array by specific hybridization of picomolar concentrations amplified gDNA. After target capture, single nucleotide polymorphisms (SNPs) are genotyped on the array by a primer extension reaction using hapten-labeled nucleotides. The resultant hapten signal is amplified by immunhistochemical sandwich staining and the array is read out on a high resolution confocal scanner. We have combined this Infinium assay with high-density BeadChips to create the first array platform capable of genotyping over 1 million SNPs per slide. Additionally, the complete Infinium assay is automated using Tecan GenePaint slide processing system. Hybridization, washing, array-based primer extension and staining are performed directly in the Tecan capillary gap Te-Flow Through chambers. This automation process greatly increases assay robustness and throughput while enabling Laboratory Information Management System (LIMS) control of sample tracking. Finally, we give several examples of how this advance in genotyping technology is being applied in whole genome association and copy number studies.