Over the last few years the use of next generation sequencing technologies has lead to new insights in both population and disease genetics, by providing a more complete characterization of DNA sequences than is possible using genome-wide micro arrays. However, high coverage sequencing in large cohorts is still prohibitively expensive, and an experimental design involving low-coverage sequencing has become popular. For example, the 1000 Genomes project (1000GP) is using 4× coverage sequencing of ~2,500 samples from a diverse set of worldwide populations [1]. A consequence of the low-coverage sequencing is that some genotypes are only partially observed, and directly calling genotypes one site at a time can lead to low-quality call rates [2].
