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Toward $1000 Genomes The ability to generate human genome sequence data that is complete, accurate, and inexpensive is a necessary prerequisite to perform genome-wide disease association studies. Drmanac et al. (p. 78, published online 5 November) present a technique advancing toward this goal. The method uses Type IIS endonucleases to incorporate short oligonucleotides within a set of randomly sheared circularized DNA. DNA polymerase then generates concatenated copies of the circular oligonucleotides leading to formation of compact but very long oligonucleotides which are then sequenced by ligation. The relatively low cost of this technology, which shows a low error rate, advances sequencing closer to the goal of the $1000 genome. A low-cost sequencing technique advances us closer to the goal of the $1000 human genome. Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.

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