New DNA reader to move promise

By Sharon Begley

NEW YORK |
Tue Jan 10, 2012 7:53am EST

NEW YORK (Reuters) – A new DNA reader could move genetics to medical clinics.

After years of predictions that a “$1,000 genome” – a read-out of a person’s finish genetic information for about a cost of a dental crown – was usually around a corner, a U.S. association is announcing Tuesday that it has achieved that spectacle and taken a record several stairs ahead.

The new genome-sequencing appurtenance from Ion Torrent, a multiplication of Life Technologies Corp. (LIFE.O), in Guilford, Connecticut, is 1,000 times some-more absolute than existent technology, says CEO and authority Jonathan Rothberg.

Taking adult about as many space as an bureau printer, it can method an whole genome in a singular day rather than 6 to 8 weeks compulsory usually a few years ago. The new sequencer, says cardiologist Eric Topol, arch educational officer of private California sanatorium and alloy network Scripps Health, “represents an well-developed allege and can change medicine.”

Ion Torrent will sell a tabletop machine, called a Ion Proton Sequencer, for $99,000 to $149,000, creation it affordable for vast medical practices or clinics; existent sequencers cost adult to $750,000. The mechanism chip and biochemicals to method a genome will cost $1,000, compared to, for example, $3,000 to exam for mutations usually in a BRCA genes that lift a risk of breast and ovarian cancer and $5,000 for a finish genome sequencing by Ion Torrent aspirant Illumina Inc (ILMN.O).

For a striking on a timorous cost of genome sequencing, see: link.reuters.com/xys85s

For now, Rothberg expects investigate labs to be his categorical customers, regulating Proton to obtain a finish genome method of people with cancer or autism, for instance, and thereby clarify a disease’s underlying genetic causes as good as probable ways to yield it. The association has sealed on Baylor College of Medicine, Yale School of Medicine and a Broad Institute as a initial customers.

Other scientists and physicians, however, contend a long-awaited attainment of a $1,000 genome opens a doorway to widespread whole-genome sequencing even of people who are not ill. And that raises ethical, legal, and medical issues that experts are usually commencement to fastener with.

“I’m a vast proponent of bringing genetics into a clinic,” says Thomas Quertermous, arch of a multiplication of cardiovascular medicine during Stanford University and an consultant in a genetics of heart disease. “But it has to be finished in a timely way, and not before a time.”

Babies competence be initial in line for whole-genome sequencing. Every state requires newborns to be screened for during slightest 29 genetic diseases.

“If a cost of whole-genome sequencing gets amply low, we could method all a genes in a newborn” for reduction than a sole tests and follow-ups compulsory when one comes behind positive, says Richard Lifton, authority of a genetics dialect during Yale University. “I’m increasingly assured that’s going to happen. But we need to be clever how we implement this information. Do we tell a newborn’s relatives his apoE status” — that is, either he has a form of a gene that raises a risk of Alzheimer’s disease?

The cost of whole-genome sequencing will continue to plummet. Lifton foresees a “zero-dollar genome,” creation it expected that “we will usually do it as prejudiced of slight clinical care” for children and adults. A Yale group led by Murat Gunel has already used prejudiced genome sequencing of a 1.5 percent of a genome, called a exome, that codes for proteins to establish a means of a puzzling and still unnamed genetic illness that formula in critical mind malformations.

Because no genes had been identified as causing a malformation, it was not probable to do a customary genetic test, that reveals either a sole gene is normal or mutated. But exome sequencing showed that a formerly opposite gene on chromosome 19 is responsible, he and colleagues reported in 2010. “The new Proton instrument is a vast step up,” says Lifton. “It promises to considerably boost a speed and revoke a cost of genome-level sequencing.”

TSUNAMI OF DATA

The find of a spin behind a puzzling genetic commotion demonstrated a advantage of whole-genome sequencing compared to single-gene tests, as scientists can’t exam for a gene they don’t know exists. Beyond such uses, contend experts, whole-genome sequencing competence not be a medical spectacle that proponents forecast.

One problem is that a costs usually start with a tangible sequencing. “The cost of bargain a method will be much, many higher,” says bioethicist Hank Greely of Stanford University. He participated in a 2010 plan that sequenced a full genome of Stanford bioengineer Stephen Quake. The sequencing cost $48,000.

But since it found 2.6 million DNA misspellings and 752 other genetic glitches, says Greely, “it took a few hundred thousand dollars value of labor from Ph.D. students and expertise operative 4,000 to 5,000 hours to know what a method meant” — that Quake had a higher-than-average risk of remarkable cardiac death, a reduce risk of Alzheimer’s, and a aloft risk of prostate cancer.

Another plea is that whole-genome sequencing generates a tsunami of data. It would take a genetic advisor some 5 hours to explain what a standard genome means, serve adding to a loyal cost. The United States has about 2,500 genetic counselors, not scarcely adequate to accommodate a need if whole-genome sequencing becomes widespread. Might doctors take adult a slack? “Surveys expose that 90 percent of patients trust their medicine to explain genomics information to them,” says Scripps’ Topol. “And 90 percent of physicians contend they don’t feel gentle with genomics data.”

Although many bioethicists concentration on a psychological mistreat patients competence humour when DNA tests expose an towering risk of cancer, diabetes, Parkinson’s, and other diseases, genomics information could also bluster patients’ earthy health if it is misconstrued. A lady whose DNA sequencing shows she does not lift BRCA mutations that lift her risk of breast cancer “might say, great, we don’t need mammograms,” says Stanford’s Greely. “But a disastrous BRCA exam reduces her risk of breast cancer from 12 percent to 11.96 percent. My dismay is reduction that patients will be shop-worn psychologically and some-more that they will mistake (genome method data) and do foolish things.”

Unlike tests that detect glitches in genes that a studious or medicine asks to have checked (those that lift a risk of, say, colon cancer if that illness runs in a family), and distinct a dozens of genes that “personal genetics” companies exam for, whole-genome sequencing reveals each bit of information a genome contains about diseases or traits.

Given a ubiquity of mutations, everybody carries genes that prejudice them to some-more than one critical or fatal disease. Bioethicists are usually commencement to investigate how that trust competence impact someone’s decisions, from marrying or carrying children to saving for retirement.

Another plea is that nonetheless a person’s genome doesn’t change, a definition will. As scientists expose some-more DNA variants that strengthen opposite illness and variants that make it some-more likely, a genome method that meant one thing in 2012 will have a opposite definition in 2013, not to discuss 2020.

A DNA various that was once suspicion to be dangerous “might spin out to be soft if countered by another,” says Greely. “Whose shortcoming will it be to tell we that, years later?” Today’s DNA contrast companies offer subscriptions that give business unchanging updates like that.

Geneticists are also still struggling with a fact that many of a risk genes lift a odds that a authority will rise a illness usually slightly. “The bottom line is, a outcome distance is so tiny it’s substantially considerate clinically,” says Quertermous. “So how should doctors incorporate that trust into their armamentarium? They won’t be means to demeanour during 6 billion information bits” – a volume in a whole-genome indicate – “and weigh what it means for patients.”

Knowing a patient’s whole-genome sequence, even if it raises a risk of diseases by usually a few percent, competence lead malpractice-wary doctors to sequence follow-up tests. If someone’s genome suggests an towering risk of heart disease, for instance, a medicine competence feel compelled to sequence unchanging cardiac CT angiograms, that cost $1,500 or more.

That would not usually lift health-care costs, though competence put patients by a physically and psychologically toilsome distress unnecessarily. “There is no justification that ‘positive’ (DNA) tests, formed usually on a screening for common genetic variations, will clear a specific medical follow-up and gain a medical advantage to individuals,” argues geneticist Thierry Frebourg of University Hospital in Rouen, France in a explanation in an arriving emanate of a European Journal of Human Genetics. Instead, whole-genome sequencing competence join a ranks of diagnostics, such as PSA tests for prostate cancer, that cost tens of millions of dollars a year though do not advantage patients, let alone save lives.

INEFFECTIVE DRUGS

Full-genome sequencing could yield genuine advantages in last that patients will advantage from a drug. For instance, usually half a hepatitis C patients who take Pegasys, a $50,000-a-year drug from Roche Holding AG’s (ROG.VX) Genentech, and half a rheumatoid arthritis patients who take $26,000-a-year Enbrel from Amgen Inc (AMGN.O) and Pfizer Inc (PFE.N), advantage from them, records Scripps’ Topol, who analyzes a intensity advantages of genomic medicine in his arriving book, The Creative Destruction of Medicine.

Using genomic information to brand that patients will and will not advantage could save patients and insurers tens of billions of dollars a year now spent on ineffectual drugs.

If genetic information causes patients to take improved caring of themselves – eating some-more healthfully if they lift genes that lift a risk of diabetes or heart disease, for instance – they can urge health. One 2010 investigate found that of people who bought direct-to-consumer genetic contrast by companies such as 23andme, 34 percent pronounced a formula done them some-more clever about their diet and 14 percent exercised more.

Others wrongly see DNA as destiny, and appreciate an increasing genetic risk of, say, plumpness as a permit to overeat, meditative they are doomed to be fat. “Good” genes competence lead to equally dangerous behavior. “A studious with hypertension competence be told by his doctor, ‘I’ve looked during your DNA and you’re clean!’,” says Stanford’s Quertermous. “He competence think, great, we don’t need to check my blood vigour anymore or even take my medication.”

As a scholarship advances, however, a value of whole-genome sequencing to patients will grow. The common DNA variants that have been identified “account for usually a tiny prejudiced of a heritability of disease,” says Kari Stefansson, founder, chairman, and CEO of deCode Genetics of Reykjavik, Iceland.

“The expectancy is that a poignant prejudiced of a blank heritability lies in singular variants, and to find those we have to do whole-genome sequencing.” deCode is sequencing a finish genomes of 3,750 Icelanders, and has so distant identified singular variants with vast effects on a risk of ovarian cancer, glioma, gout, and heart conditions that need a pacemaker. Those discoveries would have been formidable or unfit but whole-genome sequencing.

Whole-genome sequencing also promises to residence one of a many discouraging problems with stream DNA tests, that examine some of a 1,500 or so genes that have been compared with illness out of a sum of 22,000 tellurian genes. But scientists do not know how illness risk is lifted or lowered by “moderator genes,” that impact other genes. “Do we know how combinations of genes impact risk?” Stanford’s Quertermous asks. “The answer is totally no.” As a result, a illness risk that is distributed from stream genetic tests competence be inaccurate. With millions of whole-genome sequences, biologists believe, they can start to work out those essential total effects.

One arriving investigate shows how critical gene combinations can be. In investigate scheduled for announcement in a biography Human Molecular Genetics, scientists led by Charis Eng of a Cleveland Clinic examined a occurrence of breast, thyroid, and other cancers in patients carrying a spin in a gene called PTEN. Such mutations are typically interpreted as lifting a risk of cancer. But Eng found that a participation or deficiency of mutations in another gene, called SDHx, can change that risk.

“Current genetic testing, that looks during usually a few genes, is like perplexing to foresee a batch marketplace by looking during usually 26 stocks,” says Eng of a Cleveland Clinic. Such singular genetic information can be misleading.

In a apart investigate of 44 patients, scheduled for announcement in a European Journal of Human Genetics, Eng and colleagues find that family medical story assessed a risk of breast, colon and prostate cancer some-more accurately than DNA sequencing. For instance, family story rightly personal 8 women as being during high risk for breast cancer. But usually one of a 8 was so personal by DNA. “For now, family health story is a improved predictor of cancer risk than genomic testing, that looks during too few genes,” Eng says.

Because whole-genome sequencing is not nonetheless being marketed to consumers, a U.S. Food and Drug Administration has not taken a position on it. But it is endangered by existent tests that are sole directly to a open by Navigenics, Pathway Genomics and 23andme, and has invited companies that sell them to accommodate with group officials to work out ways “to yield consumers with accurate, arguable kits,” says FDA mouthpiece Erica Jefferson.

Until then, a companies are taboo from selling a tests to a public. “Manufacturers have not supposing systematic justification about a correctness and trustworthiness of their tests, that can lead to improper diagnosis decisions with critical health consequences,” says Jefferson. “The risk of removing a illness depends on a set of formidable interactions,” so “even people with a same genetic make-up might have opposite risks of disease.”

Gene-sequencing companies know a challenges.

“Each genome has substantially 24,000 mutations that we can understand,” says Ion Torrent’s Rothberg. “But there are substantially 400 that have never been seen before” and whose stress for health is an enigma. Ion Torrent is operative on algorithms to establish a medical stress of a millions of DNA glitches that will be found in each genome. Companies such as Personalis, of Palo Alto, California, have sprung adult to establish a medical stress of whole-genome sequences. That will take years.

“We commend this is usually a beginning,” Rothberg says.

(Editing by Michele Gershberg and Cynthia Osterman)