eBriefing

Toward the $1,000 Genome: Next-Generation Strategies for DNA Sequencing

Toward the $1,000 Genome
Reported by
Sarah Webb

Posted January 24, 2008

Overview

Researchers have been working toward next-generation sequencing techniques that move the cost of sequencing an individual human genome from an estimated $10 million for J. Craig Venter's genome to a more reasonable $1000 to $10,000 range. The Archon Genomics X-Prize will award $10 million to the first team that sequences 100 genomes in 10 days at a cost of $10,000 per genome or less, spurring the research forward into a full-scale race. During a November 8, 2007, meeting researchers discussed advances that may one day lead to routine individual genome sequencing.

Some topics of discussion were the expendability of the proofreading function of DNA polymerase for high quality sequencing data, DNA polymerases that can be engineered to accept chain terminators and fluorescently-labeled nucleotides, and high-throughput single molecule sequencing.

Web Sites

Helicos Biosciences Web Site
Helicos is commercializing single molecule sequencing-by-synthesis technology.


Books

Kieleczawa J. 2004. DNA Sequencing: Optimizing the Process and Analysis. Jones and Bartlett Publishers, Inc.; Sudbury, MA.

Mitchelson K, ed. 2007. New High Throughput Technologies for DNA Sequencing and Genomics. Elsevier Science, Amsterdam.


Journal Articles

Aksyonov SA, Bittner M, Bloom LB, et al. 2006. Mulitplexed DNA sequencing-by-synthesis. Anal. Biochem. 348: 127-138.

Braslavsky I, Hebert B, Kartalov E, Quake SR. 2003. Sequence information can be obtained from single DNA molecules. Proc. Natl. Acad. Sci. USA 100: 3960-3964. Full Text

Fidalgo da Silva E, Reha-Krantz, L. 2007. DNA polymerase proofreading: active site switching catalyzed by the bacteriophage T4 DNA polymerase. Nucleic Acids Res. 35: 5452-5463. Full Text

Hariharan C, Bloom LB, Helquist SA, et al. 2006. Dynamics of nucleotide incorporation: snapshots revealed by 2-aminopurine fluorescence studies. Biochemistry 45: 2836-2844.

Hariharan C, Reha-Krantz LJ. 2005. Using 2-aminopurine fluorescence to detect bacteriophage T4 DNA polymerase-DNA complexes that are important for primer extension and proofreading reactions. Biochemistry 44: 15674-15684.

Ju J, Kim DH, Bi L, et al. 2006. Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators. Proc. Natl. Acad. Sci. USA 103: 19635-19640. Full Text

Ruparel H, Bi L, Li Z, et al. 2005. Design and synthesis of a 3?-O-allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis. Proc. Natl. Acad. Sci. USA 102: 5932-5937. Full Text

Seo TS, Bai X, Kim DH, et al. 2005. Four-color DNA sequencing by synthesis on chip using photocleavable fluorescent nucleotide analogues. Proc. Natl. Acad. Sci. USA 102: 5926-5931. Full Text

Wu J, Zhang S, Meng Q, et al. 2007. 3?-O-modified nucleotides as reversible terminators for pyrosequencing. Proc. Natl. Acad. Sci. USA 104: 16462-16467. Full Text

Speakers

Linda Reha-Krantz, PhD

University of Alberta
e-mail | web site | publications

Linda Reha-Krantz received her undergraduate degrees in chemistry and biology from the University of Washington and completed her PhD in biochemistry at Johns Hopkins University, studying DNA polymerases. She completed postdoctoral research at Albert Einstein College of Medicine in New York and at the Institut de Recherches Cliniques in Montreal. Reha-Krantz started her independent career in 1980 at the University of Alberta in Edmonton, Alberta, Canada, where she is currently a professor of biological sciences and a scientist of the Alberta Heritage Foundation for Medical Research.

Jingyue Ju, PhD

Columbia University
e-mail | web site | publications

Jingyue Ju received his BS in chemistry from Inner Mongolia University in China and an MS in organic chemistry from the Chinese Academy of Sciences before completing his PhD in bioorganic chemistry at the University of Southern California in 1994. He was a DOE Human Genome Distinguished Postdoctoral Fellow at the University of California, Berkeley before taking a senior scientist position at Incyte Genomics in 1995. He moved to Columbia University in 1999 where he is professor and director of the Center for Genome Technology & Biomolecular Engineering.

Ido Braslavsky, PhD

Ohio University
e-mail | web site | publications

Ido Braslavsky completed his BA (1992) and PhD (1998) in physics at the Technion in Haifa, Israel. After postdoctoral research at the Weizmann Institute of Science, he worked with Stephen Quake at Caltech from 2000 to 2003, studying single molecule methods for DNA sequencing. He is currently an assistant professor of physics and astronomy at Ohio University and a consultant to Helicos BioSciences in Cambridge, Massachusetts.

Patrice Milos, PhD

Helicos Biosciences
e-mail | web site | publications

Patrice Milos received her MS and PhD from Rensselaer Polytechnic Institute in Troy, New York. She then completed postdoctoral fellowships at Brown University and Harvard University. From 1993 to 2007, she worked at Pfizer, serving most recently as executive director at Pfizer Global Research and Development. She serves on the National Advisory Council for the National Human Genome Research Institute and is currently the vice president and chief scientific officer of Helicos BioSciences in Cambridge, Massachusetts.


Sarah Webb

Before hanging up her labcoat, Sarah Webb earned a PhD in bioorganic chemistry from Indiana University. Based in Brooklyn, NY, she writes about science, health, and technology for publications including Science, Science News, Discover, and Nature Reports Stem Cells.