TagSNP site selection

We have developed an efficient selection algorithm (LDSelect) that is based on the linkage disequilibrium statistic r² and that 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 the multi-ethnic PDR90 panel used during the first three years of this project. Cosmopolitan tagSNPs from this set were genotyped on the HapMap samples.

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.