My Own Private Genome

So you want your own genome sequenced. What's that going to cost?

By | February 1, 2006

Suppose I walked into a lab, set a vial of blood on a bench, and requested my genome sequence. What would it cost? How long would it take? Is anyone anywhere near winning J. Craig Venter?s $10 million prize for the first $1,000 genome?

Today?s gold standard, Applied Biosystems? 96-capillary 3730xl DNA sequencer ($365,000) can generate some 2.8 million bases of raw sequence per day using the company?s new TargetSeq run module. At that rate, I?d need 2,100 days (nearly six years) to collect six billion bases (three billion bases from two sets of chromosomes). That?s a long time, but, says Harvard geneticist George Church, ?There?re very few emergency situations where you need your genome sequence right now.? Yet even if the lab were as efficient as a genome center ? which, according to product manager Suresh Pisharody, operate at better than $0.75 per sample total cost ? I?d be looking at a cost of nearly $11 million.

What if I got one of those newfangled sequencers from 454 Life Sciences, instead? Like many next-generation sequencing companies, 454 has abandoned traditional Sanger chemistry for new single-molecule approaches. 454?s Genome Sequencer 20 ($500,000) uses an on-bead sequencing-by-synthesis approach to generate some 40 million bases of raw data per four-hour run, meaning I could squeeze out a human genome in just under a month. With per-run reagent costs of $6,000, my genome would cost a mere $900,000.

But that?s just one sequence pass, and according to vice president for molecular biology Michael Egholm, ?It?s simply ludicrous to say you can sequence a human genome with 1x coverage.? He suggests 8x or 15x coverage, which would boost my costs to between $7.2 million and $13.5 million, and increase my sequencing time to about a year.

Another firm, Solexa, announced in December its plans to sequence a human genome in 2006. According to chief scientist David Bentley, ?We?re aiming for one billion bases per [two-day] run? on the company?s new single-molecule sequencer, the 1G Genetic Analyzer. At that rate 15-fold genome coverage is just six months of work. Solexa has announced its sequencing of a 162,000-bp human BAC, but has yet to publish its findings in a peer-reviewed journal.

Bentley says Solexa will begin shipping instruments in the second quarter of 2006. Pricing has not been fixed, but, ?We anticipate a similar unit price to a single high-end capillary electrophoresis machine, plus around $3,000 per run for reagents [initial costs].? He adds, ?We?re aiming to go to 30-fold coverage for $100,000.?

Helicos Biosciences, the only company in this market to adopt a true single-molecule sequencing approach ? that is, one that doesn?t involve DNA amplification ? announced in December its sequencing of bacteriophage M13 (6,400 bp). That?s a good deal shorter than Helicos? intended targets: CEO Stan Lapidus says Helicos? first-generation instrument will produce about 125 million bases per hour, but planned improvements in chemistry could boost that to 7.5 billion bases per hour. ?That translates into six human genomes per day with 10x coverage.?

Last year Church showed that a relatively low-cost next-generation sequencer ($140,000) could be built from an optical microscope, from which he can collect about 240 million bases in 60 hours per instrument, at one-seventieth the cost of traditional methods. That?s 10x genome coverage in 625 days (Harvard has licensed the technology to Agencourt Bioscience). If I retrofit two microscopes I could trim that time to under a year, and still spend less than 454 Life Sciences? pricing.

But I prefer no cost to low cost, which brings me to Church?s ?Personal Genome Project.? The idea, as GenomeWeb reported, is for ?highly informed? individuals to consent to having their genome sequences released along with identifying data and medical records, to ?provide ?a richer data set? for researchers to mine for links between genotype and phenotype.? Church says he currently has ?three tentative volun­teers? and is hoping to recruit another 100.

Though I?m high on the technology, I won?t be among those recruits. Six billion bases for zero dollars sounds great, but I don?t really want to know what story those As, Cs, Ts, and Gs tell if I can?t do anything about it yet. n

jperkel@the-scientist.com

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