The ability of sequencing to detect a site that is segregating in the population is dominated by two factors: whether the nonreference allele is present among the individuals chosen for sequencing, and the number of high quality and well mapped reads that overlap the variant site in individuals who carry it. Simple models show that for a given total amount of sequencing, the number of variants discovered is maximised by sequencing many samples at low coverage23, 24. This is because high coverage of a few genomes, while providing the highest sensitivity and accuracy in genotyping a single individual, involves considerable redundancy and misses variation not represented by those samples. The low coverage project provides us with an empirical view of the power of low coverage sequencing to detect variants of different types and frequencies.
