Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays

doi:10.1126/science.1181498

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Originally published in Science Express on 5 November 2009
Science 1 January 2010:
Vol. 327. no. 5961, pp. 78 - 81
DOI: 10.1126/science.1181498

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Reports

Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays

Radoje Drmanac,¹^,* Andrew B. Sparks,¹^, Matthew J. Callow,¹^, Aaron L. Halpern,¹^, Norman L. Burns,¹^, Bahram G. Kermani,¹^, Paolo Carnevali,¹^, Igor Nazarenko,¹^, Geoffrey B. Nilsen,¹^, George Yeung,¹^, Fredrik Dahl,¹^,^, Andres Fernandez,¹^, Bryan Staker,¹^, Krishna P. Pant,¹^, Jonathan Baccash,¹ Adam P. Borcherding,¹ Anushka Brownley,¹ Ryan Cedeno,¹ Linsu Chen,¹ Dan Chernikoff,¹ Alex Cheung,¹ Razvan Chirita,¹ Benjamin Curson,¹ Jessica C. Ebert,¹ Coleen R. Hacker,¹ Robert Hartlage,¹ Brian Hauser,¹ Steve Huang,¹ Yuan Jiang,¹ Vitali Karpinchyk,¹ Mark Koenig,¹ Calvin Kong,¹ Tom Landers,¹ Catherine Le,¹ Jia Liu,¹ Celeste E. McBride,¹ Matt Morenzoni,¹ Robert E. Morey,¹^, Karl Mutch,¹ Helena Perazich,¹ Kimberly Perry,¹ Brock A. Peters,¹ Joe Peterson,¹ Charit L. Pethiyagoda,¹ Kaliprasad Pothuraju,¹ Claudia Richter,¹ Abraham M. Rosenbaum,² Shaunak Roy,¹ Jay Shafto,¹ Uladzislau Sharanhovich,¹ Karen W. Shannon,¹^,|| Conrad G. Sheppy,¹ Michel Sun,¹ Joseph V. Thakuria,² Anne Tran,¹ Dylan Vu,¹ Alexander Wait Zaranek,² Xiaodi Wu,³ Snezana Drmanac,¹ Arnold R. Oliphant,¹ William C. Banyai,¹ Bruce Martin,¹ Dennis G. Ballinger,¹^,* George M. Church,² Clifford A. Reid¹

Genome sequencing of large numbers of individuals promises toadvance the understanding, treatment, and prevention of humandiseases, among other applications. We describe a genome sequencingplatform that achieves efficient imaging and low reagent consumptionwith combinatorial probe anchor ligation chemistry to independentlyassay each base from patterned nanoarrays of self-assemblingDNA nanoballs. We sequenced three human genomes with this platform,generating an average of 45- to 87-fold coverage per genomeand identifying 3.2 to 4.5 million sequence variants per genome.Validation of one genome data set demonstrates a sequence accuracyof about 1 false variant per 100 kilobases. The high accuracy,affordable cost of $4400 for sequencing consumables, and scalabilityof this platform enable complete human genome sequencing forthe detection of rare variants in large-scale genetic studies.

¹ Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, CA 94043, USA.
² Department of Genetics, Harvard Medical School, Cambridge, MA 02115, USA.
³ School of Medicine, Washington University, St. Louis, St. Louis, MO 63110, USA.

These authors contributed equally to this work.