Challenges remain before docs use whole-genome sequencing to diagnose disease

Before doctors use technology to evaluate every "letter" in a person's DNA to detect or diagnose medical conditions, several hurdles must be overcome, according to a new study.

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 proceed.

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.

The doctors 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.

"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 screenings.

"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.