The technologies used in human genetic studies are rapidly improving. We expect several enhancements to genetic imputation technologies. First, we expect that as better characterized reference panels are developed, it will become possible to use genotype imputation methods to study not only single nucleotide polymorphisms but also other types of genetic variants, such as copy number variants (33, 66) or classical HLA types (55). Second, we expect that improved algorithms for genotype imputation will continue to be developed, motivated by the desire of geneticists to tackle ever more complex problems. Similar pressures previously motivated constant development of methods for pedigree analysis, both for large pedigrees (29, 51, 54, 73) and for smaller ones (2, 37, 46-48, 65). Still, the most useful advance that we expect, in the context of genotype imputation based analyses, is the development of larger reference panels. As illustrated in Figure 5, the accuracy of genotype imputation based analyses should increase substantially as the size of reference panels increases. This increase in accuracy occurs because haplotype stretches shared between study samples and samples in the reference panel increase in length and are easier to identify unambiguously with a larger reference panel.
