Something New: An Interview with Radoje Drmanac
نویسنده
چکیده
Each year when I attend the American Society of Human Genetics meeting, I stroll up and down the vendor exhibits to see what’s new, and, at the most recent meeting, I noticed one booth that stopped me in my tracks. The company was Complete Genomics, and I asked the rep about the cost of sequencing small stretches of the genome for a project in the lab. She told me they only do ‘‘complete’’ sequencing—full human genome sequencing. ‘‘That’s why it’s called ‘Complete’,’’ she added. OK, I get it—so how much does it cost? ‘‘$20,000 per sample if you order sequence for eight samples.’’ Figuring that anybody who can produce accurate full sequence for that kind of money has to have a clever idea, I looked at the exhibit materials more closely. Part of their success comes from employing ‘‘rolling circle’’ replication to amplify a small circular piece of genomic DNA that is interrupted by four adapters. The long, single-stranded DNA that spools off collapses in on itself by base-pairing of separated, inverted repeats lying in the adapters, as I later learned, forming a tight and highly charged ‘‘DNA nanoball.’’ These nanoballs can be uniformly distributed onto a prepared grid, and the high concentration of target sequence allows for very quick and cost-effective imaging. The four adapter sequences then serve as the anchors for sequencing—not by enzymatic extension, but rather by sequential hybridization and ligation of pairs of oligonucleotides for each base position. The exhibit drew out my inner geek, and I wanted to learn more. The rep pointed me in the direction of the inventor and company co-founder, Radoje Drmanac (Image 1), informally called ‘‘Rade,’’ who was deep in conversation with someone else, so I moved on. A few months later, I was prompted by his first-author publication in Science reporting a US$4,000 genome to delve a little deeper. I discovered that Rade’s scientific career has been driven by his ambition to sequence human genomic DNA using oligonucleotides. In 1988, while still a graduate student in his native Serbia (Yugoslavia at the time), he published his first idea, dubbed ‘‘sequencing by hybridization’’ (SBH), in Genomics and followed that up with a publication in 1990 about doing PCR in emulsion to produce abundant template. After working at Argonne Laboratories and forming two prior companies, he co-founded Complete Genomics, finally bringing to fruition his goal for efficient sequencing of the human genome.
منابع مشابه
Supporting Online Material for Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays
Radoje Drmanac,* Andrew B. Sparks, Matthew J. Callow, Aaron L. Halpern, Norman L. Burns, Bahram G. Kermani, Paolo Carnevali, Igor Nazarenko, Geoffrey B. Nilsen, George Yeung, Fredrik Dahl, Andres Fernandez, Bryan Staker, Krishna P. Pant, Jonathan Baccash, Adam P. Borcherding, Anushka Brownley, Ryan Cedeno, Linsu Chen, Dan Chernikoff, Alex Cheung, Razvan Chirita, Benjamin Curson, Jessica C. Eber...
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