Accurate whole genome sequencing as the ultimate genetic test.

Abstract

Featured Article: Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 2010;327:78–81.4 Even 30 years ago, it was obvious that Sanger sequencing had limited throughput, and a more efficient process could replace many tedious gene and genome mapping projects. It would take until the mid-2000s for massively parallel sequencing (MPS)5 technologies to demonstrate they could overtake the Sanger sequencing hegemony. Our paper was not the first description of a viable MPS technology, but it firmly established that human whole genome sequencing (WGS) could be done affordably (<US$5000 in reagent cost), with high accuracy (<1 error in 100 kb), and with high throughput, thus heralding the arrival of personal genome sequencing. This work was the result of a long effort that started in Serbia in 1987 with a proposal for sequencing by hybridization (SBH) on dot-blot DNA arrays. SBH on random bead microarrays prepared by emulsion PCR, in which a micron-sized bead replaced a millimeter-sized DNA dot, offered a first MPS solution (www.rdrmanac.com). The US Department of Energy and NIST grants funded most of these initial efforts. After the events of September 11, 2001, the NIH received an increase in biodefense funding, and our US$2.3 million grant for ligation-based MPS technology on genomic DNA microarrays was awarded in 2003 by …