The mechanics of genotype imputation in unrelated individuals are illustrated in Figure 2. Here, study samples genotyped for a relatively large number of genetic markers (perhaps, 100,000 – 1,000,000) are compared to a reference panel of haplotypes that includes detailed information on a much larger number of markers (Panel A). To date, the HapMap Consortium database has typically served as the reference panel (104), but we expect that in the future larger sets of individuals characterized at larger numbers of markers will be available. Stretches of shared haplotype are then identified (Panel B) and missing genotypes for each study sample can be filled in by copying alleles observed in matching reference haplotypes (Panel C). In analyses of samples of European ancestry, comparisons with genotypes for the HapMap CEU panel typically yield shared haplotypes that range from about 100 – 200kb in length. Thus, in a GWAS that examines 300,000 SNP markers, these shared stretches will typically include 10 – 20 genotyped markers. When there is ambiguity about which haplotype stretch should be “copied” to fill in missing genotypes for a
