Direct determination of diploid genome sequences

Determining the genome sequence of an organism is challenging, yet fundamental to understanding its biology. Over the past decade, thousands of human genomes have been sequenced, contributing deeply to biomedical research. In the vast majority of cases, these have been analyzed by aligning sequence reads to a single reference genome, biasing the resulting analyses and, in general, failing to capture sequences novel to a given genome.\n\nSome de novo assemblies have been constructed, free of reference bias, but nearly all were constructed by merging homologous loci into single consensus sequences, generally absent from nature. These assemblies do not correctly represent the diploid biology of