A much more attractive approach for cross study analyses is to combine genotypes generated by the International HapMap Consortium, [The International HapMap Consortium, 2005] with genotypes from individual studies, and then use a haplotyping algorithm that can handle genome scale data to impute genotypes at untyped markers in each study [Scheet and Stephens, 2006]. This strategy results in a situation where all studies are “genotyped” at all the markers examined by the HapMap consortium (albeit some markers are genotyped using conventional means and others are genotyped in silico [Burdick et al., 2006]). The approach relies on the intuition that even two apparently “unrelated” individuals can share short stretches of haplotype inherited from distant common ancestors. Once one of these stretches is identified using genotypes for a few SNPs, alleles for intervening SNPs that are measured in one of the individuals, but not the other, can be imputed. Provided shared haplotype stretches are identified correctly, imputed genotypes will be accurate unless they have been disrupted by gene conversion or mutation events.
