Scientists Report New Method of Whole-Genome Sequencing

Jul 12 2012

NEW YORK, NY—Researchers said they had developed a low-cost, accurate method of whole-genome sequencing that gives doctors a more complete picture of a person’s genetic makeup and requires only a small amount of DNA, potentially making the sequencing technique more accessible to patients.

The researchers, who were led by genomics company Complete Genomics Inc. and reported their findings in the journal Nature, said the technique enables scientists not only to identify gene mutations that may cause medical problems but also to immediately determine if the faulty gene is inherited from the mother, the father or both parents.

This information is often critical to interpreting the results of whole-genome sequencing, which maps out an individual’s entire genetic profile.

Each person has an estimated 3 million to 4 million genetic variations that make everyone unique. Most cause no problems, but others can lead to disease or increase the likelihood of getting a condition. If it turns out that a gene mutation is inherited from only one parent, then having one working copy of the gene from the other parent may stave off medical problems.

Currently, when researchers want to find out this information, they have to take additional complex steps, including sequencing the parents, a process that is more costly and time-consuming, and not practical outside a research setting.

“To make whole-genome sequencing more usable in a clinic, we need to have as complete a story as possible from the first genetic effort,” said David B. Goldstein, director of the Center for Human Genome Variation at Duke University School of Medicine, referring to the paper. He wasn’t involved with the study.

The technique reported in the paper uses a new method to prepare the DNA for sequencing combined with computational and statistical analysis to determine where each gene comes from. This allows for a more complete and accurate “read” of the genome, the researchers said.

The cost of whole-genome sequencing continues to drop rapidly, with some experts anticipating that it will soon be possible to offer a “$1,000 genome.” But most of the work to date has been done as part of research at academic centers, where price is less relevant, since the work is funded by grants.

There are growing efforts to figure out ways to bring the technology into the clinic. Lowering the price to one that insurers might reimburse and figuring out how to return medically relevant results when so much of the genome is still not understood have both been barriers.

Clifford A. Reid, chairman, president and CEO of Complete Genomics, of Mountain View, Calif., said the company would offer the genome-sequencing method to clinics this year at a cost of $5,000 to $10,000, with prices falling as volume increases. The research was funded largely by Complete Genomics, with some work funded by grants from federal agencies.

Radoje Drmanac, an author of the paper and co-founder and chief scientific officer of the company, said the researchers had already sequenced more than 50 genomes using the new approach.

Dr. Reid said they expect that the technique will first be used to help identify genetic diseases in undiagnosed children who have rare conditions and in cancer, where current sequencing methods have trouble identifying complex mutations.

The method requires a very small number of human cells; the scientists were able to get accurate results with only 10 to 20, whereas traditional methods can require thousands. The researchers wrote that the method could eventually be used to do whole-genome sequencing in situations where only a small amount of DNA is available, such as on an embryo created during in-vitro fertilization before it is implanted in a woman or on circulating tumor cells in a cancer patient’s blood.

By Amy Dockser Marcus | New York