How DNA Sequencing Is Changing Medicine by Jacqueline Vanacek In April 2013, we celebrated the 10th anniversary of the completion of the Human Genome Project. Led by the National Institutes of Health, the Human Genome Project (HGP) was completed 2.5 years ahead of schedule and well under budget. “For the first time, anyone could freely read the fundamental instruction set needed to make a human body.” But it took years and billions of dollars to reach this point. How did we get here? And where are we headed? While those in the field point to “next gen sequencing” as a primary accelerator for the HGP, I wanted to explore what that meant. So I visited the nexus of the HGP — the National Human Genome Research Institute – to hear the history and tour the laboratory with NIH Intramural Sequencing Center (NISC) Director Jim Mullikin, PhD and Head of IT Systems Don Preuss from the National Center for Biotechnology Information (NCBI). The NIH Intramural Sequencing Center delivers high throughput DNA sequencing to support NHGRI’s basic research into both cause and treatments for genetic diseases. NISC experts “manufacture” high outputs of usable genomics data from samples of purified DNA or RNA for clinical investigators. And NCBI provides the advanced software tools and databases to study these “biologically important molecules.” The NISC tour included a look at past and present DNA sequencers with Jim Mullikin. “First Generation” DNA Sequencing NHGRI defines DNA sequencing as a “laboratory technique used to determine the exact sequence of bases (A, C, G and T) in a DNA molecule. The DNA base sequence carries the information a cell needs to assemble protein and RNA molecules” which govern how our bodies are built and function. While recently deceased genomics pioneer and Nobel Laureate Frederick Sanger developed rapid DNA sequencing chemical methods in the 1970s, it was not until ten years later, in 1986, that the first fully automated DNA sequencing instrument appeared on the market. These early automated sequencers were used in the Human Genome Project and could decipher about 700-1000 base-pair long DNA fragments at a time. There was no ability or expectation to decipher and map a full human genome back then. And with 3 billion DNA building blocks making up a single human genome, the HGP required thousands of scientists mapping thousands of fragments to eventually be reconstructed into one complete sequence. Back then, each DNA sequencer cost about $1 million. And when one considers how labor-intensive this early work was, it’s easy to understand why it took 13 years and cost about $3.5 billion in total to map the 99% of the Human Genome DNA blueprint that is identical for all of us. “Next Generation” DNA Sequencing When Dr. Francis Collins, then Director of NHGRI, challenged the genomics community to reduce the cost of mapping a personal genome from $100 million to $1000, advances in DNA sequencers skyrocketed. The subsequent miniaturization of sequencers has allowed for smaller DNA sample sizes, less chemical reagents and the ability to run multiple DNA samples in parallel. All of these factors have dramatically reduced the time and cost of analysis. Today, a variety of sequencers exists, ranging from those that can survey a full human genome in eleven days to jumpstart a research investigation — to solid state sequencers that can do a partial analysis in just a day for quality control or to zero in on a specific chromosome. Where DNA Sequencing Is Headed Even with so many advances in DNA sequencing, there is another wave yet to come! For example, Jim Mullikin talked about the Genome in a Bottle Consortium’s collaboration with the National Institute of Standards. NIST will develop whole genome reference materials to ensure accuracy of high throughput DNA sequencing done in a clinical setting. Recent studies show that false positives or negatives in genetic variants or mutations could arise from different sequencing and bioinformatics analysis methods. The reference materials would ensure that any risk is minimized. Finally, Don Preuss described the emerging genome-in-a-box concept, with a myriad of vendor approaches. For example, from Harvard Medical School, George Church’s Knome company is offering a “plug-and-play” human genome interpretation system. It combines hardware and genomic interpretation software to simplify getting “useful medical information from a patient’s DNA.” This approach supports data privacy and regulatory compliance. Genomics leader Illumina’s “lab in a box” model permits customers to “upload their DNA sequences to a cloud-based data storage and analysis system for interpretation.” And Bina Technologies offers a pay-per-use Genomic Analysis Platform or on premise appliance that can process a whole human genome in only 4 hours...... onforb.es/IJzvuR
Posted on: Tue, 03 Dec 2013 16:19:24 +0000
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