By Krista Conger
Illustration by Christopher Silas Neal
On Feb. 15, 2008, Richard Quake’s 17-year-old daughter met him in the driveway of their Pennsylvania home as he returned from work.
“Dad, you have to get upstairs. It’s Richie. I think he’s dead.”
Quake had wondered why his son’s car was still in the driveway. Nineteen-year-old Richie — a sophomore at Drexel University studying architectural engineering — should have been at work at nearby Sesame Place, where he played Big Bird at the popular theme park.
Instead, he was dead in his upstairs bedroom. The next few hours were a blur as police and paramedics sought to determine why the healthy teen, with a black belt in karate and D.A.R.E. posters on the walls of his room, had died so unexpectedly. Days passed with no clear answer.
“We were desperate to find out what happened to my son,” says Quake, “but by this point my wife and I had begun to fear for the rest of the family, for our two daughters.
“We wondered if he had a disease, maybe a virus or an infection. We had no idea.”
Although the coroner eventually ruled the death was most likely due to a previously undiagnosed heart problem, Quake was not satisfied. He insisted the coroner collect both blood and tissue samples from his son’s body. “I told him, ‘I need you to save everything you possibly can for future testing,’” says Quake. “At the time, I really had no idea why I said that.”
Richard Quake’s request, and his determination to find an answer to the mystery of Richie’s death in the DNA gathered from his tissue, launched him onto the shaky leading edge of personalized medicine, and into some of its most thorny ethical thickets.
Who owns a person’s genetic information? What can be done with it? What should be done with it? Quake’s journey during the subsequent two years traces the evolution of scientific fields of genotyping, whole-genome sequencing and the interpretation of more genomic data than most clinicians and scientists have ever dreamed of, or can even realistically handle. He would eventually gain an ally in the form of a cousin on the other side of the country — Stanford bioengineering professor Stephen Quake, DPhil, who was himself preparing to break scientific and ethical barriers by sequencing his own complete genome with a new sequencing machine he helped invent.
It’s a conundrum in so many ways. The sequence of your genome — all 6 billion nucleotide letters — is the most personal of personal information, encoding the very building blocks of what makes you you. The sheer power and wonder of what arises when that string of letters is steeped in a cell’s biological stew is staggering. And yet your genome is also inextricably bound with that of your mother and your father, your siblings and your children and even that of more distant relatives. How much right, if any, do we have to expose what others may not want known? And are any of us prepared for what we might learn?
On the other hand, genetic information — in whole or in part, of you or, perhaps, of the cells of your cancer — is the key to much of the promise of personalized medicine. With it we can identify which drugs will work best and how much of them to use. We can slice and dice, poke and prod, and parse those letters into messages about longevity or ancestry, a child’s future height or ability to taste the bitter flavors in some vegetables, breast cancer risk and cholesterol levels. In fact, we can learn so much about a person and his or her medical predilections that it would be foolhardy not to pursue what recent technological advances in sequencing and software have laid out for the taking.
Or can we? Experts disagree. To some, the nascent field — whether focused on whole-genome sequencing or commercially available genotyping of select sites in the genome — is so undeveloped as to be practically useless.
“Our technology is outpacing our knowledge,” says Eric Green, MD, PhD, director of the National Human Genome Research Institute. “There is going to be a lengthy period between getting information about someone’s whole-genome sequence and understanding what it means for an individual in a clinical setting. This gap won’t be closed in a year. It probably won’t be closed in a decade.”
Even currently available commercial genotyping tests analyzing a relatively small number of nucleotides (about 2 million of the 6 billion nucleotides that you inherited from your mother and father) come with a list of caveats, what-ifs and maybes that have recently spurred both the U. S. Food and Drug Administration and the Government Accountability Office to take a closer look at whether and how to regulate the industry of personal genomics.
Government involvement doesn’t end there. In May, U.S. Reps. Patrick Kennedy, D-RI, and Anna Eshoo, D-Calif., introduced the Genomics and Personalized Medicine Act of 2010, which aims to create an Office of Personalized Healthcare within the Department of Health and Human Services to coordinate the activities of federal and private agencies involved in personalized medicine. And in 2008, Congress passed the Genetic Information Nondiscrimination Act, the first effort to protect those who’ve taken the plunge into their own genetic pool.
In response, universities, including Stanford, are gearing up with new centers or even departments to optimize what many see as an approaching medical revolution.
“Things are changing so fast,” says Michael Snyder, PhD, director of Stanford’s new Center for Genomics and Personalized Medicine. “Soon you’ll have your entire genome in one hand and your medical history in the other. And you’ll give both to your doctor.”
In early 2008, Richard Quake, a sales manager for an Internet auto auction site, didn’t know anything about genetics or genomics. What he did know was that he couldn’t walk away without learning what had really happened to Richie. Unwilling to simply accept the coroner’s conclusion that his son had died of heart arrhythmia, he spent the months of March and April contacting experts from several institutions to ask what they thought could have happened. Fortunately, he had the tissue samples necessary to test their theories. Just two and a half years ago, the process was more complicated than it would be today. But things were changing quickly.
“I was jumping online every night, getting up on all this heart stuff.”
At the end of 2007 and in early 2008, three companies began offering what’s now known as direct-to-consumer genotyping. Interested people could send in a sample of saliva to Bay Area-based companies 23andMe or Navigenics, or to deCODE Genetics in Iceland. For prices ranging from $985 to $2,500 the companies would scan a customer’s DNA, determine the exact sequence of nucleotide letters in hundreds of thousands of locations throughout the genome, and assess the risks or likelihood of about 12 to 20 diseases or physical traits. (Prices have dropped since that time.)
The ability of the companies to draw conclusions between nucleotide differences known as SNPs (single nucleotide polymorphisms) and disease risk is due to a field of research called genome-wide association studies. These studies sprang from technologies devised during the 10-year push to sequence the entire human genome. Their focus has been on identifying genetic differences among individuals that were associated with either increased risk of or protection from a particular disease. Finding a disease-associated SNP (pronounced “snip”), however, doesn’t necessarily mean that a particular nucleotide change causes the disease, although this can be the case. It’s more like a molecular bar code that indicates that other, surrounding sequences might be involved.
But although some SNPs are quite telling, others are only suggestive. Nonetheless, thousands of people have undergone the tests in the past years despite the fact that most physicians have no clear idea of how to counsel their patients about the results.
“There’s so much we still don’t know,” says bioethicist and associate professor of pediatrics Mildred Cho, PhD. “What does it mean to say you have a 10 percent higher risk of something? Are you going to do anything about it, or just worry?”
Cho is the associate director of Stanford’s Center for Integration of Research on Genetics and Ethics, one of six centers around the country created by the National Human Genome Research Institute to explore the ethical, legal and social implications of genetic research. The centers are one aspect of the Ethical, Legal and Social Implications Research Program established by the institute in 1990.
“When the program first started, we were thinking mostly about things in terms of single-gene disorders,” says Jean McEwen, JD, PhD, director of the ELSI program. “We were looking at one gene at a time. But now with the enormous decrease in the cost of sequencing we can begin to look across the entire genome and try to identify risk factors for complex disorders like cancer and heart disease. But we have to decide how to interpret this data and put it all together. This is where things become very difficult.”
In comparison, the question for Richard Quake was fairly simple: What killed his son? “I was jumping online every night, getting up on all this heart stuff,” he says. “I talked to a specialist at Mayo, and a guy at Penn.” Eventually, after talking to several experts, he asked the coroner to send samples of Richie’s tissue to a specialist in New England to test for a cardiac condition called long QT syndrome that can cause sudden death. Mutations in any of several genes can cause long QT. Two other possible options were Marfan syndrome (like many with Marfan, Richie was very tall and thin, with long arms, legs and fingers) or Brugada syndrome — a heart condition that can cause death unexpectedly during sleep. Mutations in one gene, SCN5A, account for about 20 to 25 percent of Brugada cases.
“It was expensive,” says Quake, “but I said, ‘We do what we have to do.’” Months went by before he received the results of the genetic tests: Richie was negative for any of the mutations known to be involved with the diseases. “Of course they gave me the qualifier, ‘This is new science, we don’t know all the genes that play into this,’” says Quake.
“Then we realized, ‘Hey, we already have someone’s genome.’”
The uncertainty factor has increased exponentially since then with the identification of hundreds of additional disease-associated SNPs and the growing knowledge that most diseases represent the cumulative effect of tens or hundreds of genes and their interaction with a person’s environment. This is one reason some experts are calling for a halt on direct-to-consumer genetic testing. The field of companies offering such tests has swelled to about 30 and, in July of this year, the U.S. House of Representatives Committee on Energy and Commerce presented the results of an undercover investigation by the Government Accountability Office that it said showed a shocking lack of regulation and consumer protection in the field.
“GAO’s fictitious consumers received test results that are misleading and of little or no practical use,” the report concluded, after pointing out that the same DNA sample sent to four companies returned vastly different predictions for the risk of prostate cancer and hypertension and that in at least one case an individual with a heart condition was told he was at decreased risk for the disorder. When the undercover investigators spoke over the phone with representatives from 15 test providers, they were given information and advice that ranged from simply inaccurate to fraudulent and perhaps illegal.
Supporters of the industry contended, however, that the GAO study was flawed in execution and presentation (the companies investigated were not identified so could not offer any defense or clarification, and they did not receive a copy of the findings until after the hearing). Risk predictions are not in themselves diagnostic, they argue, and a few unscrupulous companies shouldn’t be allowed to tarnish the entire field. What’s more, many of the companies have said directly that they would welcome more regulatory oversight and some have actively sought such guidance since their inception.
The Food and Drug Administration has also taken issue with some of the claims touted by direct-to-consumer genetic companies. Between May and July, the FDA sent letters to 20 of the companies warning them that tests meant to diagnose or prevent diseases qualify as medical devices, subject to regulation by the administration.
Setting aside legal and ethical concerns about the behavior of some of the companies, some experts argue that direct-to-consumer testing is inherently flawed. The general public is not qualified to interpret and respond appropriately to test results that may indicate an increased risk of, say, breast cancer, or perhaps a decreased risk of colon cancer. What if an individual decides to forgo routine screening on the basis of a test result that indicates decreased risk?
Arthur Beaudet, MD, chair of molecular and human genetics at Baylor College in Texas, is concerned enough about the repercussions of unfiltered genomic information to say that the sale of the tests to the general public should be prohibited. People who want the information should go through their physician, he argues in an opinion piece in Nature in August, who could help them interpret and act upon the results.
Norbert von der Groeben
Not so, says Gail Javitt, JD, MPH, a research scholar at the Berman Institute of Bioethics at Johns Hopkins University, who points out in the same issue of the journal that many of the tests have been well-validated, including those for sickle cell anemia and cystic fibrosis. Regulate the tests according to the level of information and risk they provide, she argues. Similar to pregnancy tests, some could likely be purchased over the counter and used without any professional interpretation. Others would require gatekeepers in the form of genetic counselors or physicians.
Quake’s relentless research eventually led him to have his own cardiac health assessed, but the results offered no clues to the cause of Richie’s death. It was about that time he heard that a professor at the Stanford School of Medicine had sequenced his entire genome for less than $50,000 and with a team of just three people. The name of the faculty member? Stephen Quake.
In August 2009, Stephen Quake, a Howard Hughes Medical Institute investigator, published the sequence of about 90 percent of his DNA using technology called single molecule sequencing he helped develop. He was pondering the results in his office when colleague Euan Ashley, MD, a cardiologist specializing in cardiomyopathy, walked in. “Hey Euan,” said Quake. “What do you know about this gene here?”
Ashley, who directs Stanford’s Center for Inherited Cardiovascular Disease, knew it well. It was myosin-binding protein C — a gene known to be associated with sudden cardiac death.
Unlike genotyping, whole-genome sequencing returns the entire sequence of a person’s DNA. But it presents unique technical challenges. Although the first human genome sequence took 10 years, several billion dollars and hundreds of researchers, Quake’s sequencing of his own genome took one month, three people and about $50,000. Since then researchers have sequenced a family group of four, and even DNA from a Neanderthal. In September, researchers from Duke University published whole-genome sequence data from 20 people — half with hemophilia and half without. Their findings indicated that it’s possible to identify disease-associated genes by comparing groups of unaffected and affected people.
Clearly, whole-genome sequencing is becoming both relatively easy, and popular. In fact, many experts predict that we’re about to reach what’s known as the “$1,000 genome” — a tipping point at which nearly anyone could afford to have his or her entire genome sequenced. But the real challenge may still be ahead: How are we going to manage and interpret all that data? Each sequence, which includes copies of genes from both parents, has about 6 billion base pairs. That in itself is not that difficult to store on a hard drive. But the assembly of the strings of nucleotides into contiguous sequences, coupled with the resulting analysis and comparison with a reference genome, can easily consume up to two terabytes of memory for each person. “It’s very difficult to parse all this down into a format that can be discussed between a physician and a patient,” says Ashley.
Even if the storage issues can be overcome, as they probably will be, there’s a very real concern as to whether researchers and physicians possess enough technical know-how to deal with the information. “The No. 1 concern I hear when I talk to people about whole-genome sequencing,” says the national genome institute’s Green, “is the ability to handle the computational aspects of this type of research. Few people in medical fields have computational backgrounds, and we need new types of software to analyze the data that pour off of and gush out of these sequencing machines.” Hank Greely, JD, professor and director of Stanford’s Center for Law and the Biosciences, agrees. “Patients, doctors and geneticists are about to be hit by a tsunami of genome sequence data. The experience with Steve Quake’s genome shows we need to start thinking — hard and soon — about how we can deal with that information,” says Greely.
Ashley and Quake and a team of other researchers proved it could be done, though not without considerable effort and resources. Together with several dozen Stanford colleagues they devised a way to take Stephen Quake’s genome and make some predictions about his clinical risk for many diseases. On May 1, they published the first-ever medical interpretation of a complete human genome in the journal Lancet.
“Many of us had already been thinking about how you would take someone’s genomic profile and translate what’s in the billions of base pairs in that DNA to something that’s clinically useful,” says Ashley, who headed the group of geneticists, physicians, bioinformaticians and ethicists involved in the study. “Then we realized, ‘Hey, we already have someone’s genome.’”
What’s more, Atul Butte, MD, PhD, assistant professor of bioinformatics, and his lab members had already done a lot of the necessary legwork: They’d spent the previous 18 months meticulously cataloguing publications that associated SNPs with specific diseases. It was the first time anyone had compiled all the information in one database, which now contains more than 20,000 SNPs linked to over 1,000 diseases.
“We have read nearly 4,000 publications so far,” says Butte, “and we made a list of every single spot in the genome where we know that, for example, the letter A raises the risk of a particular disease, or the letter T confers protection. And then came Steve with his genome, and we were ready.” Together the researchers designed an algorithm to overlay the genetic data upon what was already known about Quake’s inherent risk — based on his age and gender — for 55 conditions, ranging from obesity and diabetes to schizophrenia and gum disease. For example, as a 40-year-old white male, Quake entered the study with a 16 percent chance of developing prostate cancer in his lifetime. But as the computer, based on Quake’s genomic sequence, began to incorporate the data of study after study, his risk scooched first lower, then higher. (The researchers weighted the contribution of each variant according to the number, and sample size, of published studies confirming the association.)
The publication of the resulting clinical recommendations for Stephen Quake added to what had become a vigorous debate as to whether physicians were prepared to incorporate this type of data into the clinic. Although Butte and the others had made their software as user-friendly as possible, it was still not clear whether such an analysis is cost-effective or even useful.
“A lot of people now are talking about the $1,000 genome,” says bioethicist Cho. “But one of the things we’re looking at is the other things that have to happen to make such information clinically relevant. If you assume it took 40 highly trained faculty members to figure out what Steve’s genome meant and to communicate it back to him, you begin to realize that the cost of sequencing may not be what we should be focusing on. We need to think about the infrastructure you would need to do this on a large scale — training physicians in informatics, figuring out how to communicate ideas of risk to patients and even whether this would be cost-effective for the average person.”
Training physicians is no small task. This summer, Stanford offered an elective course to medical and graduate students in which they decided whether to analyze genotyping results of tests performed on their own DNA or on a reference sequence. Although popular, the course sparked a firestorm of debate among faculty members that delayed its start date by more than a year as they grappled with the ethical issues of appearing to encourage students to analyze their own DNA. [See the story, Test questions: Consumer genomics enters the classroom]
“There is no question in my mind that medical educators need to be far more aggressive about incorporating genomic information into their curricula for medical students,” says Green. “But we also need to get much more involved in educating current physicians, who are already under a substantial amount of pressure by patients.”
How many patients might be approaching their physicians with genotyping information? The companies themselves are coy, but Caroline Wright, PhD, the head of science for the international Foundation for Genomics and Population Health, estimates the number of people who purchased and used genotyping kits in 2009 was about 20,000 to 30,000. Not inconsequential, but certainly a minority in a country with a population of more than 300 million. A recent study by the Scripps Research Institute found that more than 80 percent of people undergoing direct-to-consumer genetics testing wanted to know about their risk even for incurable or non-preventable diseases, but that 50 percent also had concerns about the tests.
“We’re funding several grants looking specifically at the direct-to-consumer testing going on,” says the national genome institute’s McEwen. “We’d like to know people’s motivations for wanting to do it, what they are doing with the information and how they are reacting in terms of changing their health behaviors.”
As Stephen Quake looked at his predicted cardiac risk factors, he thought of Richie. He had spoken to his cousin Richard about his experience with sequencing his genome and even sent him a report detailing some of his own predicted risk factors. Now he introduced him to Euan Ashley.
“I shared my research with Dr. Ashley and told him how I couldn’t sleep at night because I was worried about my daughters,” says Richard Quake. “He said, ‘Let’s take a look at your data and maybe run some tests — this is what the center does — maybe we can put your mind at ease.’”
Most of the tests Ashley had in mind were standard cardiac workups of Richard Quake and his wife and daughters. But he set his sights considerably higher for one: whole-genome sequencing of the DNA in Richie’s tissue sample. It’s believed to be the first time the technology has been used in an attempt to determine the cause of death of an individual. A tantalizing scholarly goal, to be sure. But that’s not why Ashley and his team took on the task.
“I’m desperate to find an answer for him,” says Ashley, who himself has two young children. “You can really feel his pain. If we can find a convincing cause of death for his son, maybe we can test his daughters and either rule them out or make them safe.”
Just feet away from Ashley’s office, computers have been churning away to find possible candidate mutations in Richie’s DNA. Because none of the obvious suspect genes seem abnormal, the team resorted to screening all the genes involved in ion transport in the heart muscle. (Ion transport is an important step in stimulating the synchronized contraction of heart muscle cells.)
“There’s no list anywhere of the cardiac ion transport genes,” says Ashley, who has had to turn to finding genes whose sequence resembles that of known ion transport genes. “That’s part of why this is exciting. This kind of ‘molecular autopsy’ we’re doing will generate a lot of new information for future use. We are literally searching for what could be just a one-base-pair difference in millions of nucleotides. But even though for us it’s an exciting research project, we haven’t forgotten that it’s also an absolute tragedy for Richie’s family.”
Currently the researchers are focusing their attention on 230 genetic variants in Richie’s genome — many that have never before been associated with disease. “The power of what we’re doing takes my breath away compared with what’s previously been offered as the state of the art,” says Ashley. But with power comes questions. What does it mean to vary from the norm? Who is the norm, anyway? Butte, the bioinformatics expert, has begun to apply the findings of his SNP database to a reference human genome used by most researchers.
“A lot of people and clinicians think of their genomes in terms of how they compare with the reference genome, which is a composite of 30-some unidentified individuals,” says Butte. “But we’re beginning to learn that the reference genome itself actually contains significant amounts of disease risk.”
In other words, normal doesn’t equal perfect. And because the people used to compile the reference genome were mostly of European ancestry, it’s not clear how well any findings may apply to people of other ethnicities.
“The issues of race and genetics and even behavior are a big area of study,” says McEwen, director of the national genome institute’s Ethical Legal and Societal Implictions Research Program. “There are some very complicated questions where those areas intersect. Allele frequencies do vary, but we have to understand what genetics can and cannot tell us about differences among populations.” As whole-genome sequencing, and even genotyping, becomes more common, researchers and clinicians will face another problem — that of communicating new findings to patients who’ve had their DNA analyzed at some point in the past. Keeping people up to date on new findings involving genetic variants that they carry will be a tricky business. Clinicians of the future will walk a tightrope of informing people who’ve had their genome sequenced of ongoing discoveries while also presenting the information as uncertain and likely to change. In fact, Greely and several colleagues published a companion piece to the Lancet article discussing the special challenges of such knowledge.
“The world of medicine is going to change beyond belief,” says Ashley. “We are all going to have to learn how to deal with questions like these.”
Only one question really matters to Richard Quake’s family. “What killed Richie?” Unbelievably, they may be nearing an answer. The round-the-clock research by Ashley and his colleagues has led them to a likely candidate — a mutation in a gene for an ion channel known to be associated with very rare cases of sudden cardiac death. But more testing remains to be done.
“It’s all going to come down to how confident we are that this is the mutation that caused Richie’s death,” says Ashley. “There’s still more work to be done, but this is our top suspect. If we’re convinced, we can test Richard and his wife and daughters for the mutation and discuss options with them like implantable cardiac defibrillators to keep them safe.”
Is this the end of Richard Quake’s quest? Or the beginning of another saga in which his remaining family members struggle with the same set of uncertainties as they come face to face with their own genomes? Without question, it’s bittersweet.
“My wife and I are just shells of the people we were before Richie died,” Quake says. “If we can save one other life or help one other family, it’s certainly worth it. But, in truth, it feels like a consolation prize.”
Regardless, it may not be a prize that will be available to anyone else any time soon. “I think there’s going to be a lot of push back from the clinical community about incorporating genomics into the clinical system,” says bioethicist Cho. “Physicians are so overwhelmed already that there will have to be very high standards to show that it’s worth it. Think of it: A new drug has to be better, cheaper and easier to use than the standard of care. Otherwise the pressure in the clinical setting will be not to use it.”
“We’re not going to really know what it means for a while,” adds McEwen. “Our basic biological tendency is to rush to find a variant associated with disease, to rush to develop a test and to rush to put it into the clinic. But there needs to be a recognition that this is basic research and it will take some time. We need to have optimism, but still be patient.”
Like Icarus flying too close to the sun, are we expecting more of this technology than it can deliver at this point? Just because we can get the information doesn’t mean that we should. Are we doing more harm than good by pursuing this information now? Maybe yes, maybe no. It’s likely a question that can only fully be answered in retrospect. But Richard Quake, at least, is grateful for the information gleaned from such studies. And maybe one day personalized medicine can help others like Richie.“We take for granted that we are living, breathing beings when really, in fact, life is so incredibly fragile,” says Quake. “All because one little letter in a sequence of billions is off. My son…I kissed him goodnight the night before when he gave me a shirt for my birthday. My wife talked to him that morning; she went in to wake him and he said he was a little chilly. He said he was going to stay in bed for a little bit to warm up. She said, ‘OK, I love you,’ and she kissed him goodbye.”
Listen to the interview.
Photo by Steve Fisch
A batch of personalized-genomics companies have sprung up in the past few years, offering large-scale determinations of the genetic differences that set you apart from every other human being (identical twins excepted). While their analytical techniques vary a bit, the routine for the consumer is fairly uniform: Place your order online, wait until you get the kit in the mail, follow instructions — in a nutshell, spit into the enclosed vial and close the cap — ship it back and receive a report on your results along with a variable amount of interpretation depending on the company. (In some states, it is necessary to get a doctor’s sign off at some point in this process.) Some companies offer follow-up genetic counseling.
Between the time you mail in your spit kit and the time you get the report, a whirl of activity, made possible by advances in molecular biology and engineering, takes place. Here’s the science behind that activity.
A human cell contains a genome consisting of 46 chromosomes, 23 from each parent. Every chromosome contains a molecule of DNA, a long, linear chain composed of a sequence of four different chemical “links.” Along these sequences lie the genes, which are essentially instructions for protein manufacture. Over eons of evolutionary time, mutations — most often, the substitution of one type of link for another type in a particular spot on the chain — creep into genes, causing people’s genomes to diverge as each generation becomes more removed from our common ancestors. Tiny, single-link differences in the genomic chain are called SNPs (pronounced “snips”).
Checking out every single one of the several billion chemical building blocks in your genome remains too expensive for a mass-market test, though prices are dropping. So the personalized-genomics outfits look at fewer, directing attention to the “mere” hundreds of thousands of hot spots on your DNA where SNPs have been observed to pop up with some frequency and where, furthermore, one SNP variant or another has been at least tentatively associated with increased odds of contracting, say, type-2 diabetes, lung cancer or some other disease. These same kinds of tests can assess your probable sensitivity to various drugs. — Bruce Goldman
|Company||Location||Website||Cost of test|
|Navigenics||Foster City, Calif.||navigenics.com||$500-$2,000*|
|23andMe||Mountain View, Calif.||23andme.com||$229|
|Pathway Genomics||San Diego, Calif.||pathway.com||$500|
* Estimated range; the company sells its test to physicians who charge as they see fit
** Cancer or cardio scan, $500; both, $800; both plus neurological and several other conditions, $2,000