New technologies speed development of personal genomes

HOUSTON -- (April 16, 2008) -- Sequencing the personal genetic blueprint of Nobel laureate and DNA pioneer James D. Watson – first announced nearly a year ago – signals a new technological era that points the way to development of techniques that will make personal genomic medicine possible, said researchers from Baylor College of Medicine in Houston and the company 454 Life Sciences – Roche Diagnostics in a report published today in the journal Nature.

Realizing the potential of personal genomic medicine will require overcoming the barrier presented by the enormous size of the human genome – 6 gigabases. Sequencing the Watson genome took two months using new sequencing machinery and techniques. The cost was one-hundredth of more traditional methods, said Dr. David Wheeler, first author of the Nature paper and a leader in the effort. Wheeler is also an associate professor of molecular and human genetics at BCM.

Identify sequences associated with disease

"A key aim of personal genome sequencing is to identify genome sequences that may be associated with disease, or are predictive of response to medication. The need to make genotype (gene-based)–phenotype (symptom or outward signs) correlations before having predictive value is at the heart of both the excitement and the dilemma of the new era of genomic medicine. Thus the ability to sequence individuals readily using highthroughput, scaleable, low-cost, completely in vitro technology, as demonstrated here, is an important milestone in our ability to connect 'personalized genomes' to 'personalized medicine' and enable these critical correlations to be made," the authors wrote.

The new technique also enabled researchers to sequence new areas of the genome that were not previously identified by traditional means. Novel genes in these areas were also missed previously.

Next-generation technology

"This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome' sequencing," the authors wrote.

The use of 454 Sequencing machines enabled the rapid elucidation of Watson's DNA with extremely low error rates, said Dr. Richard Gibbs, director of the Baylor Human Genome Sequencing Center. The Watson project is a first step in that direction.

Others who took part in the work include Yufeng Shen, Lei Chen, Amy McGuire, James R. Lupski, Craig Chinault, Xing-zhi Song, Yue Liu, Ye Yuan, Lynne Nazareth, Xiang Qin, Donna M. Muzny and George M. Weinstock, all of BCM, and Maithreyan Srinivasan, Michael Egholm, Wen He, Yi-Ju Chen, Vinod Makhijani, G. Thomas Roth, Xavier Gomes, Karrie Tartaro, Faheem Niazi, Cynthia L. Turcotte, Gerard P. Irzyk, and Marcel Margulies of 454 Life Sciences – Roche Diagnostics. Jonathan Rothberg of Rothberg Institute for Childhood Diseases in Guilford, Connecticut, is a senior author.

Funding for this work came from 454 Life Sciences and Baylor College of Medicine.