The ability to combine relatively modest amounts of sequence data across many individuals to generate high-quality sequence data for all may become one of the most common uses of imputation technologies in the next several years. For a given sequencing effort, genotype imputation based analyses may allow an increase in the number of individuals to be sequenced by 5 to 10-fold with minimal loss of accuracy in individual genotypes. This sort of increase in sample size is critical when attempting gene-mapping for complex diseases. Of course, even before massively parallel sequencing technologies are deployed more widely, one immediate change will occur with the completion of the 1,000 Genome Project (see www.1000genomes.org). Specifically, we expect these data will include accurate genotype information on >10 million common variants and quickly replace the HapMap Consortium genotypes as the reference panel of choice for imputation studies. Two immediate consequences will be that imputation based analyses will be able to examine even more genetic markers and that each of these markers will, on average, be imputed much more accurately.
