In principle, any of the methods typically used to estimate missing haplotypes – whether based on a simple heuristic (18) or on a E-M algorithm (30) or on more sophisticated coalescent models (99) could be used to impute missing genotypes. In fact, most haplotyping programs will automatically “impute” missing genotypes during the haplotype estimation process. In practice, most researchers now use one of tools that have been specifically enhanced to facilitate genotype imputation based analyses. These tools typically provide convenient summaries of the uncertainty surrounding each genotype estimate or, perhaps, convenient built-in association testing. Genotype imputation tools typically fall into two categories: (i) computationally intensive tools such as IMPUTE (64), MACH (59) and fastPHASE/BIMBAM (92, 95) that take into account all observed genotypes when imputing each missing genotype and (ii) computationally more efficient tools such as PLINK (80), TUNA (71), WHAP (114) and BEAGLE (11) that typically focus on genotypes for a small number of nearby markers when imputing each missing genotype. Tools in the first category can be further sub-divided into those that compare the potential haplotypes for each
