The identification of rare, potentially causal variants that are poorly tagged by existing geno-typing platforms will require sequencing DNA from large numbers of people for the genomic regions showing strong associations with complex traits (22). The 1000 Genomes Project plans to produce modest sequence coverage (an average of four sequencing reads at any place in the genome) of ~1500 individuals that will extend the catalog of human genetic variation to variants present in 1%–5% of the population (10). It will thus limit the follow-up sequencing needed for investigating specific association findings to the search for very rare variants. Fine-mapping of candidate regions with common and rare SNPs optimally chosen, based on HapMap data, to maximize the regional genomic variation captured while minimizing costs, will refine association signals and narrow the list of possible functional variants.
