SeattleSNPs Genotyping Resources
Background Methodology Genes Genotyped

TagSNP site selection

We have developed an efficient selection algorithm (LDSelect) that is based on the linkage disequilibrium statistic r² and doesn’t require direct haplotype inference(Carlson et al. 2004). This algorithm selects a subset of variants that efficiently describe all common patterns of variation in a gene, based on two primary criteria – 1) the minor allele frequency (MAF) of a SNP  and 2)  the minimum level of association between assayed and unassayed SNPs, measured by the linkage disequilibrium statistic r². Given these parameters, LDSelect identifies bins of SNPs such that one tagSNP per bin can be genotyped. All SNPs above the MAF threshold will either be directly genotyped or will exceed the specified level of allelic association with a SNP that is genotyped.  For the large-scale genotyping we have selected tagSNPs from our representative European (CEPH) and African-American samples (i.e. panel 1) used for the initial four years of the SeattleSNPs project.  Binning criteria for tagSNP selection were MAF cutoff of 5% and an r² threshold of 0.65.

Genotyping platform

The Illumina BeadArray technology provides a robust and accurate genotyping platform using highly multiplexed ligation assays with multiple levels of specificity to obtain optimal results (Fan et al. 2003). Currently, Illumina produces a scaleable, high specificity multiplexed, system based (384 to 1536 SNPs/assay) on self-assembling bead arrays(Oliphant et al. 2002). The processing of 96 samples within a standard plate format also makes this system amenable to high throughput genotyping.