Oct 17, 2005 | The evolution of DNA sequencing is driven by a cheaper-faster-better mantra and an increasingly rich array of applications in biomedical research. The latest production-scale capillary electrophoresis (CE) sequencer can analyze up to 2 million base pairs of DNA within 24 hours. By comparison, the first automated DNA sequencer in 1986 analyzed a mere 4,800 base pairs per day.
To date, nearly 300 species have a complete genome available for scientific inquiry. Genome sequencing continues to have an important role in comparative analysis and functional genomics, in areas such as resequencing, mutation detection, gene expression, and genotyping. Such studies are identifying new functional mutations and genetic variants involved in disease.
DNA sequencing is no longer an isolated practice among a few specialized scientists, but an enabling technology for the development of emerging applications. As these areas advance, they will continue to push the capacity of existing technologies and further the commercialization of faster, cheaper, and better DNA analysis technologies. Sequencing’s future relies heavily on the development of innovative technologies that will make genome-scale sequencing data accessible not only to genome centers but also to academic researchers and, ultimately, to the practicing physician.
In June, the National Human Genome Research Institute announced the Large-Scale Sequencing Research Network to target 13 additional organisms — part of an ongoing program to expand biological knowledge by means of genomic data. The thriving field of comparative genomics is revealing critical structural and functional elements of the human genome.
The use of DNA analysis technologies in directed sequencing (resequencing or medical sequencing) as well as forensics and biosecurity has grown tremendously. The National Institute of Genomic Medicine of Mexico recently established the Applied Biosystems Sequencing and Genotyping Unit to conduct collaborative research studies focused on health issues important to the Mexican population.
Security and Opportunity
In biosecurity, researchers at the Translational Genomics Research Institute in Arizona are analyzing genomes of deadly agents that could potentially be used in a biological attack. These scientists are also developing molecular identification tools for public-health-related pathogens responsible for illnesses such as sepsis, which affects billions of individuals worldwide. Large-scale sequencing and genotyping of pathogens provides insight into how virulent pathogens evolve. Such an understanding is key to fighting threats such as the emerging avian influenza A (H5N1).
While the marathon to develop technology enabling the $100,000 or even $1,000 genome endures, CE remains — for now — the gold standard for most applications. CE sequencing is credited with the sequencing of the human genome and the identification of genetic variants associated with numerous diseases.
Next-generation sequencing methodologies based on single-molecule detection are generating enormous excitement with their promise to deliver the $1,000 genome. These technologies show great promise in simplifying sample preparation, decreasing out-of-phase chemistry problems, and dramatically increasing read lengths. While technical challenges still remain for successful commercialization of the $1,000 genome, the rewards of delivering such a promise are immense.
Sequencing capability at such high throughput and low cost promises fundamental new opportunities in life science research, clinical practice, and personalized medicine. Physicians could generate a whole genome sequence as part of a patient’s in-depth physical examination. This information would serve the patient as a lifelong guide to preventative and personalized medicine. Public health professionals would have immediate access to the genetic blueprint of a new pathogen, facilitating rapid development of anti-infective agents and vaccines. Agricultural and environmental scientists could unlock the promises hidden within the vast potential of the earth’s immense microbial diversity.
To create faster, cheaper, and better solutions for DNA analysis, we must remain committed to improving both current and new sequencing technologies. By delivering longer reads and higher data quality — and dramatically reducing project costs — these sequencing systems will make it possible for labs to undertake a broad array of projects. Research that just a short while ago might have been considered too complex, too expensive, or just inconceivable is now well within our grasp.
Dennis A. Gilbert, Ph.D., is chief scientific officer of Applied Biosystems. E-mail: email@example.com.