Researchers Use 454 Sequencing to Publish the Complete Genome of an Individual Human, Achieving a Key Milestone on the Path to Personalized Genome Sequencing

454 Life Sciences, a centre of excellence of Roche Applied Science, today announced that researchers at Baylor College of Medicine and 454 have published the complete DNA sequence and analysis of an individual human diploid genome. The genome was analyzed using the 454 Sequencing technology to 7.4 redundancy, facilitating a detailed comparison against the publicly available reference human sequence. The study, entitled “The complete genome of an individual by massively parallel DNA sequencing” appears today in the journal Nature.

“This project sets a high standard for the key metrics from next-generation sequencing projects,” said Dr. Richard A. Gibbs, Co-senior author on the Nature study and The Wofford Cain Professor, Department of Molecular and Human Genetics and Director, Human Genome Sequencing Center, Baylor College of Medicine. “The number of genetic variants that were detected and the completeness of how much of the genome was characterized both show the high quality of the data. It replaces the Sanger sequencing methods. The 454 technology has improved even more since the project, and we are looking forward to carrying out more whole human genome sequencing projects with even better performance.”

The groundbreaking sequencing effort has been hailed for the reduction in time and cost by orders of magnitude over conventional Sanger sequencing technology. However, the key metrics of this project’s success are the quality of the mapped sequence data as well as establishing a more complete representation of the human genome from those first published in 2001 and in 2003. Similar to the recent publication of a diploid human genome led by J. Craig Venter, Ph.D., and his team at the J. Craig Venter Institute, the data analysis revealed the presence of many single nucleotide polymorphisms (SNPs), 3.3 million including more than 600,000 previously uncharacterized SNPs compared to the reference sequence. Furthermore, the 454 Sequencing data was of such high quality that researchers were also able to detect over 200,000 insertion and deletion polymorphisms as well as copy number variations including the large scale gain and loss of chromosomal segments. Importantly, 454 Sequencing technology eliminates the major sources of bias seen in conventional Sanger sequencing due to bacterial cloning and consequently, the study reveals the identification of novel human sequence including several additional genes not previously identified.

“Our previous publication of the HuRef genome coupled now with this publication in Nature sets a very high bar for future human genome sequencing projects,” said Dr. Venter, Founder and President of the J. Craig Venter Institute. Dr. Venter was a leading figure in the race to sequence the first analysis of the human genome and in 2007 published his entire diploid genome which was done with conventional Sanger sequencing technology. “The era of personalized genomics is just beginning and will only have the greatest impact on clinical medicine and all lives when there are a significant number of full diploid genomes in the public domain. I applaud 454 and Baylor for advancing this cause with this publication and their promising new sequencing technology.”

The initial sequencing phase of the project was completed a year ago on the Genome Sequencer FLX System, a production sequencing instrument available to researchers worldwide since February 2007. His personal genome sequence was presented to Dr. James D. Watson on a portable hard drive at a ceremony at the Baylor College of Medicine on May 31, 2007. Dr. Watson, after consultation with a genetic counselor, chose to make the sequence data publicly available, omitting only the Apo E gene and neighboring sequence associated with Alzheimer’s Disease. The sequence data has since been available to researchers worldwide. The data and viewing software can be found online at www.jimwatsonsequence.cshl.edu.

“Our study proves that generating high-quality sequence from humans, quickly and affordably, is now feasible. This study is just one of several early milestones on our path to routine human sequencing” said Dr. Michael Egholm, Ph.D. co-author on the Nature study and Vice President of R&D at 454 Life Sciences. “Later in 2008, we will again decrease the cost and increase the quality of sequencing by launching new reagent kits for the Genome Sequencer FLX. These new kits will increase the instrument’s throughput by at least five-fold and extend the read length beyond 400 bases.”

“I am proud of the entire team at 454 for this achievement which reflects Roche’s commitment to innovation in healthcare, from basic research through patient care,” said Chris McLeod, President of 454 Life Sciences. “Understanding the genetic basis of disease is a critical component of our vision for personalized health care. 454 Sequencing technology has repeatedly demonstrated its ability to characterize DNA to a level that is truly changing our understanding of how genetics works, and this will consequently play a leading role at the intersection of basic research, diagnostics, and therapeutics.”