Stanford University professor sequences own genome with 'low-cost'
26 August 2009
A Stanford University professor has sequenced his entire genome for
less than $50,000 and with a team of just two other people. He found out
that he has a gene for grumpiness, which he admits his wife could have
told him — for nothing!
The first few times that scientists mapped out all the DNA in a human
being in 2001, each effort cost hundreds of millions of dollars and
involved more than 250 people. Even last year, when the lowest reported
cost was $250,000, genome sequencing still required almost 200 people.
In other words, a task that used to cost as much as a Boeing 747
airplane and required a team of people that would fill half the plane,
now costs as much as a mid-priced luxury sedan and the personnel would
fill only half of that car.
The dramatic lowering of the cost is due to new technology and a
commercially available laboratory instrument that the professor was
involved in developing.
The research was published this month online in Nature
“This is the first demonstration that you don’t need a genome enter
to sequence a human genome,” said Stephen Quake, PhD, professor of
bioengineering. “It’s really democratizing the fruits of the genome
revolution and saying that anybody can play in this game.”
There are at least two reasons why lowering the cost and effort
required to sequence all the genetic information of individuals is
important. The more examples scientists have of the whole human genetic
code, the more they can discern about how specific genes and mutations
result in the traits that make us all different, the diseases that
plague us and our response to medicines.
As that understanding increases
and costs drop, doctors could then sequence their patients’ genomes and
provide personalized medicine in which prevention and treatment of
disease would be informed by the patient’s exact genetic profile.
“This can now be done in one lab, with one machine, at a modest
cost,” said Quake, the Lee Otterson Professor in the School of
Engineering and a member of Stanford’s Cancer Center. “It’s going to
unleash an enormous amount of creativity and really broaden the field.”
Quake’s genome, one of less than a dozen sequenced so far because of
the cost and resources needed, is now available to researchers
worldwide. Quake’s colleagues at Stanford’s School of Medicine have been
looking through it and sometimes examining Quake himself, mining the
data for interesting connections between what they can observe about
him, his DNA and his family history.
““Some of the doctors are starting to poke and prod me to see how they
can couple my genome with medicine,” he said.
To sequence his genome, Quake’s team used a commercially available,
refrigerator-sized instrument called the Helicos Biosciences SMS
Heliscope. Quake, who pioneered the underlying technology in 2003, is a
co-founder of the Cambridge, Mass.- based company and chairs its
scientific advisory board.
The technology — the SMS in the instrument’s name — is called single
molecule sequencing. While many techniques require generating thousands
of copies of a subject’s DNA, the single molecule technique does not,
reducing the cost and effort involved. Instead, the technique requires
chopping the 3 billion or so fundamental units of DNA (called bases)
into strands about 30 bases long. The four bases in DNA are adenine
(abbreviated A), cytosine (C), guanine (G), and thymine (T).
Each base of DNA matches with a specific other base: For example, T
only matches with A. The machine captures each of the millions of
strands on a specially treated glass plate, holds them there and washes
successive waves of fluorescently labeled bases over the plate. As each
complementary letter sticks next to a strand, the machine can read out
the sequence of each strand.
Assembling the strands back into a cohesive genome is then done by
powerful computers, which compare it to the reference genomes that have
been compiled before. The process is akin to assembling an enormous
jigsaw puzzle by referring frequently to the picture on the box. The
team said the sequencing process took about one month to complete.
Still, several tricky problems had to be solved before the machine
could reliably sequence a whole human genome. Quake worked with Norma
Neff, a research manager in Quake’s lab, and physics doctoral student
Dmitry Pushkarev to write a sophisticated algorithm that would enable
them to determine how accurate the process is.
Overall, the genome is 95 percent complete, a rate comparable with
other sequenced genomes, the team found. In the paper, the authors are
careful to note that all genome-sequencing technologies, including the
one they’ve demonstrated, have produced incomplete approximations of the
actual genome. Still, it is enough to help produce genuine insights
about a person’s traits and health.
Quake’s genome has already yielded a few interesting connections
between his genetics and his health. One is that he carries a rare
mutation associated with a heart disorder; the revelation, he said,
sheds light on what members of his family have always wondered with
regard to the health of prior generations. The good news, he said, is
that he’s also apparently genetically predisposed to respond well to
common cholesterol-lowering tatin medicines.
Quake said the information has also forced him to take heed of that
history. “If you know your uncle had something, you kind of discount
that you can get it, but to see you’ve inherited the mutation for that
is another matter altogether,” he said.
OOne amusing “revelation” is that Quake’s code contains a form of a
gene that has sometimes been associated with increased disagreeability,
“Of course, you don’t need my genome to tell you that,” Quake
acknowledged. “My wife could have told you that and certainly the dean
could have as well.”
A video of the sequencing process can be seen at:
The details of the genetic code can be found at:
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