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Assessing the challenges and opportunities when bringing whole-genome sequencing to the bedside

B0001669 DNA sequencing autoradiograph - colouredAs advances in technology drive down the cost of whole-genome sequencing, the potential for the practice to be used in mainstream health care inches closer to reality. New research from Stanford investigated some of the challenges - and highlighted some lifesaving results - of the technique.

In the study, which will be published tomorrow in the Journal of the American Medical Association, researchers examined the whole genomes of a dozen healthy people and calculated how long it took to manually analyze each participant’s results, the projected costs of recommended follow-up medical tests, and the degree of sequencing accuracy necessary to make clinical decisions for each person. My colleague Krista Conger describes the findings in a release:

The researchers estimated a cost of about $17,000 per person to sequence the genome and interpret and analyze the average of nearly 100 genetic variations deemed important enough for follow-up in each person. Each variation required approximately one hour of investigation to assess the relevant scientific literature and determine whether the change was indeed likely to modify disease risk in the individual. After this process, the researchers were left with approximately two to six results they felt could be clinically important; doctors who reviewed the results as part of the study suggested follow-up tests that carried costs of less than $1,000 per person.

In one of the 12 cases, however, the payoff of this intensive process was big: A woman with no family history of breast or ovarian cancer learned she carried a potentially deadly deletion in her BRCA1 gene. After confirmation of the finding in a clinical cancer genetics setting, she was able to take action to reduce her future risk for breast and ovarian cancer.


One significant challenge is the need to decisively determine the sequence of genes already known to be associated with disease. [Postdoctoral scholar and cardiology fellow Frederick Dewey, MD,] and his colleagues found that commercially available whole-genome sequencing does not achieve the accuracy necessary to identify every nucleotide in about 7 to 16 percent of genes known to be associated with increased disease risk. While a degree of uncertainty is allowable during studies of populations, which look for trends by comparing hundreds of genomes, it makes it impossible to make accurate predictions about one individual’s health status.

Conger goes on to note that, while some of the study results are sobering, researchers still believe the field of whole-genome sequencing will eventually transform clinical medicine. Euan Ashley, MD, associate professor of medicine and of genetics, and one of three senior authors of the paper, said in the release:

We need to be very honest about what we can and cannot do at this point in time... It’s clear that if we sequence enough cases, we can change someone’s life. But with this opportunity comes the responsibility to do this right. 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.

Previously: Coming soon: A genome test that costs less than a new pair of shoesStanford researchers work to translate genetic discoveries into widespread personalized medicineNew recommendations for genetic disclosure released and Ask Stanford Med: Genetics chair answers your questions on genomics and personalized medicine 
Photo by Wellcome Images

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