Cheap, reliable whole-genome sequencing? Not so fast, say Stanford researchers

Everyday access to the contents of our genes draws nearer and nearer. But the industry is currently complicated by a mix of rapidly advancing technology and just-emerging science: Despite the fact that we can read our genes, we don’t necessarily know what they mean.

A Stanford University study that will be published tomorrow in the Journal of the American Medical Association took a look at whole-genome sequencing for clinical use and found that it has more substantial obstacles to overcome than many people might realize.

“We need to be very honest about what we can and cannot do at this point in time,” paper co-author Euan Ashley said in a release. “Our hope is that the identification of specific hurdles will allow researchers in this field to focus their efforts on overcoming them to make this technique clinically useful.”

The Stanford team evaluated obstacles by sequencing the genomes of 12 healthy people. They then manually analyzed about 100 genetic variations in each person. It took an hour for each variation to determine if it might increase the risk for disease.

After looking at each of the variations, the researchers settled on two to six per person that merited a follow up test. One test participant found out she was at risk for breast and ovarian cancer.

“Although there are clearly challenges in bringing whole-genome sequencing into the clinic, this finding was clearly medically significant,” co-lead paper author Frederick Dewey said in the release. “It’s not possible to predict from a study of 12 people how often this type of clinically actionable discovery will occur, but it definitely supports the use of this technology.”

But catching that one instance of disease risk came at a great cost: 100 hours of labor, which boosted the cost of sequencing to $17,000. Three genetic counselors, three clinicians and one medical pathologist pored over each of the results because there is no straightforward way to determine if a single gene mutation poses a risk. Instead, the team consulted medical literature and made the call if all of a patient’s gene mutations together called for a follow up test. Follow ups cost from $351 to $776.

The team also found that it is impossible for currently available off-the-shelf tests to achieve the same level of accuracy in genome sequencing.

“These off-the-shelf genome sequencing techniques were developed to provide generally good coverage of most of the genome,” Dewey said in the release. “But there are some regions that remain to be covered well that we care very deeply about. We still need to supplement this information with additional sequencing in some regions to make clinically usable decisions.”