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The ABCs of DNA testing

Emory medical students are learning to navigate the delicate and rapidly changing field of genetics counseling.

By Quinn Eastman

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A 37-year-old woman, pregnant for the first time, is meeting with her doctor and is concerned about her baby's risk of having Down syndrome (DS). What kinds of tests should the doctor offer her?

A group of first-year medical students at Emory is pondering the question in a class led by Cecelia Bellcross. The genetics counselor has seen a scenario play out repeatedly, in which women with a positive screening result are told that their baby has DS. In fact, Bellcross tells the students, most women who receive positive results under current screening tests will not have babies with chromosomal abnormalities. Plus, according to the NIH, most babies with chromosomal abnormalities such as DS are born to women younger than 35. 

Why the disconnect between reality and what women are told? Originally, screening tests were designed to guide women on decisions about whether to undergo amniocentesis, based on the low—but real—risk of miscarriage from that procedure. The screening tests are indirect, measuring levels of proteins in the mother's blood rather than changes in the fetal DNA. Bellcross says that doctors should make their patients aware of the odds—a difficult task given that statistics is a confusing topic for many people—while being careful not to overemphasize the risk.

The students pepper her with questions. Whose responsibility is it to deliver bad news? When should a genetics counselor get involved? How should statistical risk be presented to patients? 

Near the end of the session, Bellcross throws the students yet another curve to consider. "This whole field may be turned upside down in a couple of years, based on news that came out last week," she says. A biotechnology company has developed a noninvasive method for prenatal diagnosis, she says. The test can detect chromosomal abnormalities by analyzing the fetal DNA present in the mother's blood. It potentially could reduce the number of amniocentesis procedures, but it's unclear about how it will fit into current practice.

The end-of-class twist highlights a challenge facing medical educators: how and what to teach medical students about genetic testing when technology is changing so fast?

Ethical dilemmas

More than 1,600 genetic tests are now available commercially. Consumer-oriented genomics companies offer a person scans of more than a million points in the genome with just one "spit in a cup." In a few years, next-generation sequencing technology is expected to push the price of reading all 3 billion base pairs of someone's entire genome to below $1,000. By the time today's first-year students enter medical practice, what's now considered routine is bound to change even more.

For years, medical students typically have learned about genetics in a semester-long course that runs through a catalog of genetic disorders. But recently, Emory and other medical schools have changed how young doctors approach genetics lessons by emphasizing the ethics behind genetics. That approach in turn is influencing treatment and diagnosis in many fields, from oncology to neurology to cardiology.

"We want to underline how genetics is becoming integrated into many parts of medicine," says Kathryn Garber, director of education for Emory's Department of Human Genetics. "After all, everyone has DNA that somehow affects their health, not only people with rare disorders."

Basic principles

Emory's medical school offers a two-week genetics module for first-year students, which emphasizes a number of principles: among them, how to approach testing and diagnosis and how to talk with patients about difficult topics.

"It all comes back to basics," Bellcross says. "We have to give people the framework and the tools so that they'll be able to evaluate the latest test."

She describes the concepts of clinical validity (a test's consistency and accuracy in predicting whether a patient will develop a particular disease) and clinical utility (whether that prediction can improve someone's life). Doctors need to learn not only how to gauge a test's validity and utility but also be able to distinguish between them, she says.

The results of a test for a gene that causes an incurable neurodegenerative disorder may leave the patient with little to do besides dread the future. On the other end of the spectrum, other tests have limited, practical consequences. They might predict, for example, how well someone will respond to a specific blood pressure medication.

"I think it's good to focus on these genetic questions now because the principles will still be the same later," says medical student Ken Buchanan. "During the module, I kept thinking, if you do all the tests, when does it really change what you would do for the patient."

One message that Bellcross especially wants students to learn is knowing their own limits. Navigating the complexity of genetic tests can be easier by using a team approach, she says, with genetic counselors and specialists collaborating. 

The hard part: interpretation

Geneticists at Emory recently sequenced a patient's entire genome in an effort to determine whether her children could inherit the kidney disease that she had. Mike Rossi, director of Emory's cancer genomics shared resource facility, and his team found that anomalies in the patient's standard DNA—which they thought were causing disease—were present also in the patient's healthy relatives.

"Obtaining vast amounts of information is the relatively easy part," Rossi says. "The hard part is interpreting it."

In a recent Emory class, genetics counselors Dan Wiesman and Dawn Laney engaged in a mock interview to get that very point across to 140 first-year students. Laney played the role of a woman who was planning a family and might be a carrier for a developmental disorder such as fragile X syndrome. In her role, she described her brother and her uncle as "slow." Her grandfather had "the shakes," but she didn't know much about her fiancé's family history. 

The exercise illustrates a scenario that the students will may face one day. Their future patients won't necessarily know their complete medical histories or their relevant genetic information. Therefore, these students will need to be able to explain technical issues in ways that patients will understand. They also will need to recognize that knowledge gained from a genetic test will affect the entire family, not just the person being tested.

Sharing results

Plan with patients in advance for delivery of the findings from genetic tests, Wiesman advises. Give them a chance for an exit. If you're conveying information to them on the phone, make sure they're not driving or in a supermarket.

"Even before you order the test, have a game plan," says one genetics counselor. "Don't just leave patients hanging."

Talking with patients about their families' history of disease, albeit awkward at times, is also important, the counselors advise. In many cases, knowing someone's family history may provide more relevant information about the risk of disease than a limited scan of the genome, they say. 

During a class discussion led by Emory pediatric neurologist Nick Krawiecki, the medical students encountered just such a case: a woman who decided to have a bilateral mastectomy to prevent breast cancer, even though her genetic test results failed to point definitively to an increased risk of disease.

One student shared her own personal experience. A friend with a family history of breast and ovarian cancer received test results that indicated she was not at risk.  However, the tests only covered two genes, and her friend eventually developed ovarian cancer. "My first question would be, how many genes is the test looking at?" she said.

Krawiecki points out that patients may feel compelled to act even if the test results turn out to be ambiguous. Patients need to have a degree of choice, he says. 

WEB CONNECTION: To read more about genetic testing and the new genetic counseling program at Emory, visit genetics.emory.edu/gc_training/.

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