Researchers found that sequencing a person's whole
genome — all three billion or so DNA nucleotides in the chromosomes — required a significant amount of manpower for a small payoff.
They also found that identifications of potentially significant
variations were not always reliable and doctors disagreed on how to
One of the study's authors said the cost of sequencing a person's
entire genome has dropped in recent years, but the technology has
been mostly used for research.
"We thought the time had come to do a small pilot study of patients
in the clinical setting," Dr. Euan Ashley told Reuters Health.
Ashley is a specialist in genomics and medicine at the Stanford
School of Medicine in California.
For the new study published in JAMA, he and his colleagues recruited
12 unrelated people between November 2011 and March 2012 to have
their full genomes sequenced.
The goal was to see how whole-genome sequencing may work in a
real-world setting, such as a hospital or doctor's office.
After drawing blood from the participants, the researchers sent all
twelve samples to be sequenced by one large company and nine of the
samples were also sent to a second sequencing company to see how
comparable the sequence results would be.
The two sets of sequences mostly agreed when it came to common
genetic variants (versions) of genes, but there were greater
differences in the results among less common variants. For about 10
percent to 19 percent of genes that may be related to inherited
diseases, the sequences were not reliable enough to ensure accuracy.
The researchers also used a computer program to sift the
participants' genetic data to identify the mutations that should be
examined more closely — about 100 per participant.
It took researchers about one hour to research each mutation, which
ended up costing about $15,000 per patient in manpower.
Experts who examined the data also disagreed on the significance of
some of the specific variants examined.
Overall, a handful of genetic variants for each patient were
reported to a group of primary care doctors, who then made
recommendations about whether the patient should receive additional
tests or be referred to specialists.
recommended between one and three referrals or medical tests per
patient based on the results. The cost for that testing ranged from
about $350 to $800.
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"The use of whole genome sequencing was associated with
incomplete coverage of inherited disease genes, low reproducibility
of genetic variation with the highest potential clinical effects,
and uncertainty about clinically reportable whole genome sequencing
findings," the researchers write.
However, they note that one participant did find out about a gene
variant that put her at an increased risk for breast and ovarian
cancer. That led her to have surgery and increased cancer
"This paper should essentially give people pause and make them
think about some of the hard work that is yet to be done," Dr. W.
Gregory Feero told Reuters Health.
Feero, who wrote an editorial accompanying the new study, is a
contributing editor to JAMA and on the faculty of the Maine
Dartmouth Family Medicine Residency in Fairfield, Maine.
"I think right now there are very few places that would be
contemplating using this tool on patients clinically," he said.
"While there is great opportunity from the standpoint of medicine
for this technology, we have to remain cautious," Ashley said.
But Feero said that whole-genome sequencing is not too far off.
"I think at the pace things are moving right now, this will be
employed clinically faster than many people would have thought even
five years ago," he said.
JAMA, online March 11, 2014.
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