Gene Tests Are Quite Telling - Should You Get One?

What gene tests can tell us now and in the future

DNA

Rachel Langosch

It takes me two subway rides, a fifteen-minute walk, one very large cup of coffee, and knocking on two incorrect office doors to arrive at the offices of the Program for Jewish Genetic Health in the Bronx. I am there for a genetic screening designed to indicate which genes I could pass on to a potential child. And though I scheduled the appointment weeks ago, my circuitous arrival builds up the suspense—and my anxiety. Why am I doing this gene test, I think to myself. I'm just opening a can of worms. Will knowing more about the genes I carry actually do me any good?

The genetic counselor, Elisa, walks me through my family's medical history. Do my parents have any genetic conditions that I know about? How about my siblings? What was the cause of death for any deceased grandparents? Then she pulls out what she calls the "menu"—a piece of paper that lists the 38 diseases for which I can get tested. These gene tests make the most sense because, based on my genetic background, I might be a carrier. The conditions range from those that would threaten a child's life, such as cystic fibrosis, to ones that may detract from the child's quality of life but not end it early, such as Gaucher's disease. I read through the options and decide to get tested for all of them, the whole panel. I sign a document, then go get three small vials of blood drawn. In a few weeks, I will find out which diseases I could possibly pass on to my future offspring.

Who Needs Genetic Tests?

For one reason or another, millions of people worldwide are getting their genomes completely or partially sequenced. "The number of genetic tests has been exponentially rising in the last decade," says Susan Klugman, the director of reproductive genetics at Montefiore, where I got my genetic test. Tests are cheaper now than they ever have been, and researchers are starting to understand more about what kinds of conclusions we can draw from the results. Though companies like 23andMe have made genetic information available to those who are simply curious, testing's main use is in medicine; a patient's DNA can help a doctor diagnose medical conditions and select the best possible treatment. Though it's useful even now, this genetic information is becoming more important than ever; the future of medical care, from pharmaceuticals to family planning, is increasingly tailored to our genes.

Though many of us are familiar with the small, specific genetic tests that claim to predict if you'll go bald or how hard it would be to quit smoking, we tend to know less about the kinds of genetic tests our doctors may ask for.

The future of medical care is increasingly tailored to our genes.

What Can They Test For?

Genetic carrier screenings and similar prenatal screenings were the first type of genetic test to become widespread. Expectant parents can test their genes to see which diseases they risk passing on to their child and plan pregnancies accordingly; prenatal screenings are conducted when a mother is already pregnant, often in the early stages of pregnancy, to test the fetus for those mutations. For the handful of diseases that medical professionals check for in these tests, the gene variants tend to be highly "penetrant," says David Mittelman, the chief scientific officer for biotech company Tute Genomics —if a baby receives one mutated gene from each parent, he's very likely to have the disease associated with it. These diseases, which include Tay-Sachs disease and sickle cell anemia, are often very severe.

Genetic tests can also help doctors diagnose a patient. Sometimes patients themselves request these tests before they show any symptoms of a disease, but it’s one for which they predict they have a high risk. For example, a patient may request a test for the BRCA 1 and 2 mutations if she has seen multiple family members struggle with breast cancer. Finding out if she has the mutation would help that patient understand her level of risk for breast cancer so that she can take preventative measures before the onset of the disease, such as medication that could stave off its onset, or, if her risk is particularly high, a preventative mastectomy.

In other cases, a patient is already presenting symptoms, and the doctors want to diagnose the disease to find the best possible treatment. Genes are particularly helpful in diagnosing cancer. Though what we think of as “cancer” is actually hundreds of diseases with different causes and compounding factors, in all of them the genome is altered in some way to make otherwise normal cells grow out of control.

"Genetic tests can help doctors identify and classify the trigger for the cancer and may reveal information about how to best treat it," Mittelman says. Genes can point oncologists towards the drugs that will work best to combat the tumor, which can make the difference between a patient that has succumbed to the disease and one who survives it. In fact, there's a whole field of medicine springing up around finding the best treatment based on genetic information, called personalized or precision medicine.

Finally, a doctor might request a genetic test for a child who may not be developing at the typical rate. Unlike older patients, babies show all the same symptoms whether they have a severe genetic condition or are just colicky, so it’s almost impossible for physicians to tell if something is wrong based on feeding and sleeping habits. But developmental milestones are a better indicator; if a baby doesn’t roll over by the time he is six months old or walk by 18 months, there might be a genetic reason why. “If parents have a child in front of them with an issue that doesn’t fit a particular syndrome, they might want to know the specific disease and its mutations,” Klugman, the reproductive genetics expert, says. “That way the doctors could tailor the disease management and the parents could plan for future siblings. And whole exome sequencing may help elucidate the issue,” When it comes to treatment, the earlier the intervention, the more effective it can be, Mittelman adds.

How Well Do They Work?

Whether patients are looking for family planning or to find the best course of treatment, most of these tests are highly effective. But they aren’t foolproof. “Most of the time people get a genetic test because they want a certain answer,” Klugman says. “Sometimes that answer is yes, sometimes it’s no, sometimes it’s in the realm of the unknown.”

A clean bill of health for a genetic carrier screening.

Alexandra Ossola

Here’s what Klugman means. Genetic carrier screenings look for specific mutations that are known to be highly penetrant and are found at a particular place in the genome. Though these results aren’t foolproof (the mutation could still exist elsewhere in the genome), other types of genetic tests can have even less certain results, like those for mutations that could make a woman at higher risk for developing breast cancer. Certain types of BRCA mutations are linked to increased risk of breast cancer, others are not, and still others are called “variants of unknown significance.” So far, the links between these variants and the disease in question are not well understood and still being investigated, so doctors and patients may not know how to use that information to improve prevention.

While some genetic tests don't reveal as many answers as a patient may like, others reveal more information about the genome than were intended—called incidental findings. For example, after a woman in California had a standard prenatal genetic test earlier this year, her doctors noticed a lot of chromosomal abnormalities, which likely reflected more genetic variants than just in the fetus. Further testing revealed that she had colon cancer and didn't even know it. Genetic counselors have a framework for when they should tell patients about incidental findings. But Klugman also stresses that a genetic counselor usually advises a patient before the test that incidental findings may appear, which will make the conversation a bit easier should any appear.

Will This Change Everything?

Until now, researchers have been focused on a few mutations known to cause disease. But the future of genetic testing is getting much more complicated, in part because now researchers can quickly decode a person’s entire genome, instead of being restricted to just a handful of conspicuous alleles. With so much more data, medical professionals can start to assess a patient’s risk for specific diseases based on her genes. “Risk assessment is often more complex because it’s often tied to complex traits,” Mittelman says. Each individual has a small combination of mutations, and each of them affects which others are expressed. That could have big effects on where the environmental factors fit in and, eventually, whether or not a person develops a disease. “You need a lot of data to figure out how those mutations fit together. Right now, that’s still too complex to interpret,” Mittelman says.

Researchers are already starting to connect that deluge of genetic data to disease and treatments, but they often need a way to process that data. More companies are jockeying to be the premiere data processing tool that assists researchers in this process. On the cancer side, IBM just put its Jeopardy-winning Watson to the task of matching cancer mutations to the right combination of drugs to treat the disease. This means that doctors will be able to tell which treatments will work most effectively on each individual patient, but it will also mean that they'll get a better sense of a person's risk for developing a particular condition later in life.

Prenatal testing is also getting more sophisticated. Current tests, which can be conducted after 9 weeks of pregnancy, extract the baby's DNA from the mother's blood to see if the child has the genetic markers for conditions such as Down syndrome. But soon, those tests will be able to test for many more mutations on the baby's entire genome, says Sara Katsanis, an instructor in science and society at Duke University who focuses on the policy of genetic testing. More people are decoding their baby's genome before the child is even born—in cases of in vitro fertilization, before an embryo is implanted—and are able to ensure that a baby with a fatal genetic disease is never born or, if that baby is born, that they can start treatment as soon as possible to minimize the condition's effect.

Katsanis predicts that, in the next 20 years, more extensive prenatal genetic tests will go beyond severe diseases and allow parents to select children with specific and desirable traits. The debates about prenatal testing that have been going on in this country for decades will continue and intensify, she says. “If there’s a genetic test in 20 years that can predict with 70 percent certainty who will develop bipolar disease, is that something you would want to select in your child?” Katsanis says. “It’s uncharted territory, no one knows the answer to that question. It’s up to society and regulators to decide which traits will be on the menu, which things we say are socially acceptable.”

It's up to society and regulators to decide which traits will be on the menu,

Today, when a person gets a genetic test, the results are usually only shared with the patient and her doctor. But soon, Katsanis predicts, our medical records will hold our entire sequenced genome, along with archives of our childhood vaccines and surgical procedures. This information will be useful to have on hand because it would allow doctors to pinpoint cancerous or disease-causing mutations by comparing a patient’s genome from different times in his life. “It’s a changing landscape—genetic privacy is going to go away eventually. It will all be in the electronic medical record,” Katsanis says.

But genetic tests are already moving outside the realm of physicians. Companies like 23andMe have already been at the forefront of direct-to-consumer genetic tests, though the FDA has stymied some of their efforts out of concerns for misinterpreted results. Mittelman anticipates that these sorts of tests will become more common, but genetic counselors will become even more important in helping people understand what their results really mean.

So? Are You OK, Alex?

Two weeks after my test, I got a call from my genetic counselor: My test came back all negative, like about two-thirds of people who are tested at that center. The counselor congratulated me on my clean bill of health, though she warned me that my results don’t mean that I’m free of all disease-causing mutations. Even for the conditions I was tested for, mutations could be lurking elsewhere in my genome. These caveats echoed a sentiment that experts had mentioned many times before: before genetic tests can reach their full potential in the medical realm and beyond, people need to have a better understanding of how genetics work. This knowledge may help them be less wary of them, which is a good thing, because it’s only a matter of time until genetic tests become so commonplace that we no longer worry about them. “The genetic tests now and those of the future are predictive—that means they don’t imply any sort of certainty [about risk or disease],” Katsanis says. “Until people understand that genetics aren’t a crystal ball, people will continue to fear the information.”

Personally, I’m glad I got the carrier screening. For now, the information isn’t particularly useful, but if I decide to have a child, it will surely come up again with my partner. Given the way medicine is going, it seems increasingly likely that I will have my whole genome sequenced at some future date, which will reveal more about my disease risk and possible treatments. It’s only in this context that the information makes sense for any patient. “Our future has ACG and T in it, not just ‘normal’ written next to it,” Katsanis says. In a very plausible (maybe even inevitable) future where scientists have been able to decode the human genome and connect those genes to health, "normal" won't cut it—for us to understand how our genes relate to health, we have to know how they relate to one another, and be unafraid of what we find.