Over the last five years, the widespread availability of high-throughput DNA sequencing technologies has permitted the sequencing of the whole genomes or exomes (the protein-coding regions of genomes) of hundreds of thousands of humans. In theory, these data represent a powerful source of information about the global patterns of human genetic variation, but in practice, are difficult to access for practical, logistical, and ethical reasons; in addition, their utility is complicated by the heterogeneity in the experimental methodologies and variant calling pipelines used to generate them. Current publicly available datasets of human DNA sequence variation contain only a small fraction of all sequenced samples: the Exome Variant Server, created as part of the NHLBI Exome Sequencing Project (ESP)1, contains frequency information spanning 6,503 exomes; and the 1000 Genomes (1000G) Project, which includes individual-level genotype data from whole-genome and exome sequence data for 2,504 individuals2.
