By Thomas Guengerich
Right: John T Speck, Vice President of the National Center for Genome Resources, with the Illumina Genome Sequencer.
SANTA FE, N.M., Jan. 23, 2009 – The National Center for Genome Resources announced Friday, Jan. 23, that it has broken the 20 billion DNA sequence barrier for the first time using an Illumina Genome Analyzer.
The Center in Santa Fe operates under the auspices of New Mexico Tech, a state-supported science, engineering and research university in Socorro.
Center director and CEO Dr. Stephen Kingsmore said the new benchmark is akin to breaking the land-speed record. He said an astonishing facet of the recent results is the low error rate of 0.91 percent, a significant improvement over previous trials.
Using a single Illumina flowcell, scientists at the Center generated more than 20 billion bases (or letters) of high-quality human DNA sequence – seven-times the length of a human genome – in 10 days. Computer analysis of the genome took another 10 days.
“The long sequences, high throughput and low error rates that we are achieving with Illumina’s sequencing platform are enabling entirely new types of experiments to be performed,” said, Gregory May, Vice President and Genome Center Director, “These include metagenomics – sequencing communities of organisms – and de novo or initial sequencing of the largest genomes. These advances are having huge impact on research to improve the quality and yield of food crops.”
The new milestone also improves the outlook for understanding human disease and health issues. The individual whose genome was sequenced suffers from multiple sclerosis. The project seeks to identify changes in the DNA code that increase risk of multiple sclerosis. The project was funded by Small Ventures USA, the Brass Family Foundation and the Nancy Davis Foundation. Center scientists collaborated with researchers at the University of California-San Francisco Department of Neurology and Illumina Inc.
“We’re excited that scientists at NCGR have validated the scalability of the Genome Analyzer and are generating this level of data. As long time collaborators, we believe this achievement is a direct result of their continued work to cost-effectively study human disease,” said Joel McComb, Senior Vice President and General Manager of Illumina’s Life Science Business Unit.
New Mexico Tech biology professor Dr. Rebecca Reiss specializes in DNA and genomic research. She has collaborated on several projects at the Center since its opening in 2006.
“Basically, this process personalizes medicine to treat not just the disease, but also how the disease interacts with the person’s genome,” Reiss said. “Ultimately, we hope to be able to predict how medications will work and which medications will be appropriate for an individual.”
Reiss said antidepressants are a good example because each person reacts differently to distinct medications.
Ryan Kim, Deputy Director of the Center’s Genome Center said this milestone is a direct result of close collaboration between scientists at NCGR and Illumina.
“DNA sequence throughput has been steadily increasing over the last several months,” he said. “We are delighted with the combination of accuracy and throughput that we have achieved.”
Kingsmore said that the Center has set ambitious goals over the past year. Just 12 months ago, the Center’s staff aimed to get to 4 billion bases in one run. With that goal achieved six months ago, the Center set a new goal of 10 gigabases, which they achieved in late November 2008. Now just two months later, the Center has successfully shown that it can efficiently and accurately decode 20 gigabases – or 20 billion markers – at a time.
This milestone brings significantly closer the ability to decode individual genomes cost-effectively, which is widely heralded to transform understanding of human disease, its diagnosis and prevention, Kingsmore said.
The DNA sequencing industry has two important benchmark goals – the $10,000 genome and the $1,000 genome. At $1,000 per individual, the human genome could be considered an affordable part of a person’s standard medical file.
The X Prize Foundation and Archon Genomics have offered a $10 million award to the first organization that can consistently produce a $10,000 genome. Specifically, the winner of the X Prize for genomics will have to sequence 100 human genomes in 10 days for less than $10,000 each.
“We think that it’ll be another five or 10 years before anyone actually does it,” Reiss said. “This is leading edge science and this milestone is a significant step toward reaching that goal.”
One key component of decoding and sequencing a person’s DNA is the accuracy. Kingsmore said that an erroneous reading could lead to a faulty diagnosis or in appropriate medical treatment. To ensure accuracy, an individual’s DNA is typically processed at least 15 times. Therefore, the $1,000 is still a distant goal.
New Mexico Tech Vice President of Research Dr. Van Romero said the new results prove the Center is at the forefront of DNA sequencing and will provide more opportunities for university students and professors to conduct ground-breaking research.
“The high through-put they’ve achieved means we can take samples and have results in a fraction of the time it previously took,” Romero said. “This opens the door for genomic research for faculty and students at New Mexico Tech.”
Technical details: 20.5 billion bases of DNA sequence passed quality metrics with a paired-end library on an Illumina Genome Analyzer II instrument and single flowcell using improved sequencing chemistry and sequence cluster generation. Human DNA sequence was generated in seven of eight flowcell channels, creating about 13 million sequences per channel, each of which was 212 bases in length (pairs of 106 base sequences).
The average quality score of the sequence was greater than 25 and average error rate was 0.91 percent. In addition, 18.8 billion bases of DNA sequence passed quality metrics with a long-insert (4000 bases) paired-end library from a single flowcell on a second individual, also comprising pairs of 106 base sequences. The latter is part of the first Korean genome sequence and was funded and performed in collaboration with Macrogen Inc. and the ILCHUN Genomic Medicine Institute at Seoul National University.
The NCGR Genome Center is a collaboration with the New Mexico Institute of Mining and Technology (New Mexico Tech). It was made possible through the concerted efforts of New Mexico Gov. Bill Richardson, Sens. Jeff Bingaman and Tom Udall and the New Mexico Legislature, specifically Sen. Carlos Cisneros.
The state legislature has provided the Center with more than $600,000 in operating costs from 2006 to 2008.
The NCGR Genome Center currently operates six Illumina Genome Analyzers II and provides large scale sequencing and analysis services to collaborators worldwide. Other sequencing projects at NCGR include the schizophrenia genome project, and sequencing the genomes of cotton, the major pathogen of chile and numerous legume crop sequencing projects.
The Center’s mission is to improve health, nutrition and the environment by genome sequencing and analysis. NCGR is the only organization in North America to receive certification for Illumina-based sequencing under the CSProTM Program. For more information please go to www.ncgr.org.
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