The Why Files The Why Files --

Genetic tests go mainstream

Did Gregor Mendel tweet you from the Consumer Genetics Conference?

No, he didn't tweet us either, but we do wonder what the founder of genetics -- the monk who patiently recorded the color and shape of peas in the garden -- would think about the new, direct - to - consumer approach in genetic testing that was promoted at the June confab in Boston.

The Consumer Genetics Conference -- unthinkable just 10 years ago -- is a sign that genetic testing has muscled into the mainstream medical market, but searching for flaws in DNA is nothing new. Counting chromosomes can reveal whether a newborn will have Down syndrome. Genetic testing of potential parents can prevent Tay Sachs disease, a fatal illness usually found in Jews of Eastern European origin.

Genetic counseling can prevent disease

A family-tree like diagram depicts gene carriers as gray and blue and disease carriers as blue
Pregnant Brynn and her husband, Michael, got genetic counseling. Brynn's nephew has Tay - Sachs disease, and Brynn and Michael want to know if they carry the Tay - Sachs mutation. Brynn has a 1 in 2 chance of having the mutation (and being a disease carrier) since her brother, Donald, is a carrier. Michael, who was adopted, knows nothing of his family history except that he is of Eastern European background and that his birth parents could be Eastern European Jewish. The counselor explains that the carrier rate for Tay - Sachs among Eastern European Jews is approximately 1 in 30. Testing reveals that Brynn is a carrier but Michael is not; therefore, the infant could be a carrier, but will not have Tay - Sachs disease.
A counselor points out analysis results to another woman across a table
A genetic counselor helps families understand their risk, interpret information about the potential disorder, and review testing options and results.
Photo: NIH

Fueled by vastly cheaper - faster - better methods for reading and analyzing genes, genetic testing is exploding. Ten years ago, when reading your entire sequence of DNA (your genome) required a warehouse full of machinery, a busload of technicians, a bucket of bucks, and years of delay, it was no disgrace to be ignorant of the DNA in your genome.

Now, your genome can be deciphered for $48,000, retail. That's cheaper than some weddings, and you can store the whole genome, along with the wedding photos on your iPhone. We can't help wonder if a monologue consisting of 3 billion letters ("CTGTCTDAAACGTGATGTTATACGGGA...") would be any less fascinating than the cell - blather we hear on any street or airport.

Seeking identity

Decoding a genome may provide a clue to identity, says Stephen E. Levick, a psychiatrist at the University of Pennsylvania. "For some individuals willing to pay large sums of money to learn every letter of their genome, an important factor may be the hope to discover who they really are -- a search for a unique self -- identity. On this, I'm afraid that they'll not find a satisfactory answer in the 3 billion base pairs."

The results may be more revealing about the psyche, says Levick, who has written about the psychology of another technology that concerns identity: human cloning (see #1 in the bibliography). "The only answer a person paying to know their entire genome is sure to get is not an answer at all. But there is a consolation prize -- being able to assert: 'I am a person rich enough to afford this, and scientifically hip enough to do it.'"

Three normal chromosomes appear alongside three others with the mutations described
Both genes and chromosomes can become mutated. The three major single - chromosome mutations are deletion, duplication and inversion.

Just a nagging thought

Before we explore whether direct - to - consumer genetic tests could do more harm than good, we must sort out the many forms of genetic tests:

numbers Prenatal genetic tests can detect, for example, Down's syndrome, and the sex of the baby.

numbers Infant and pediatric tests can look for uncommon conditions. These tests are usually done under a doctor's supervision, and whether they lead to treatment, or just help parents understand what is plaguing their children, they may be mandatory, but seldom are controversial. For example, blood from the "heel prick" administered to newborns is used to check for many conditions, including phenylketonuria (PKU), a genetic disorder that can cause retardation and seizures, but can largely be controlled through diet.

numbers Adult tests can be used to diagnose illness -- or determine susceptibility to various diseases. One test, for example, reveals the presence of genes that predispose to early-onset Alzheimer's disease. Cancer patients can get their tumors analyzed to learn whether are likely to grow aggressively. Healthy women can get tested for two breast cancer genes and respond to positive tests by adopting measures designed to prevent cancer. Some tests may have no medical purpose, because they will not affect treatment decisions or prolong life, even if they do provide psychological balm to the patient. And some tests are useful primarily to benefit relatives, who may not know that they face an increased risk of disease.

numbersCrapshoot - wildcard tests can be performed with no real understanding of how and why the results will be used. Placing your entire genome on your phone may qualify for this category, which some mock as "recreational genetics."

Watson is smiling, wearing a white lab coat, and holding a pipette in a graduated flask
Photo: NIH
One of the first full genomes sequenced belonged to genetic pioneer James Watson, who, along with Frances Crick, discovered the 3D structure of DNA in 1953.

As more mutations are identified, the indications for, and benefits of, some genetic tests remain unclear at best. A test can cost money, without returning any proven benefit -- and yet proving the benefits takes time and money. In cancer, for example, it takes years to learn whether any drug or procedure will improve survival. Desperation measures taken in response to genetic tests -- ranging from prophylactic mastectomy to radical changes is diet or behavior -- may turn out to do more harm than good.

Some genetic tests have proven benefits. For example, research published in 2008 showed that patients with the rare brain cancer gliomatosis cerebri, who also have defects in two chromosomes, have a stronger response to the drug temozolomide. "Eighty-eight percent of those people with this genetic signature responded well to temozolomide compared to only 25 percent of those people without the genetic abnormality," said Marc Sanson, a researcher at INSERM, the French government health agency. Because people with the two-chromosome defect survived an average five and half years, compared to only 15 months for others, Sanson says temozolomide thus becomes "our first choice of treatment for patients with gliomatosis cerebri," especially those with those specific mutations.

Dealing with diabetes

Genetic tests are also helpful in a few cases of type 1 diabetes. The disease usually results from an immune system attack on the cells that make insulin, a hormone necessary for proper use of sugar. Type 1 patients must monitor their blood sugar several times a day, and control it with insulin.

The black fissures on the left side of this monochrome MRI brain image are white on the right
Image: Public Domain
Gliomatosis cerebri, a rare brain tumor that commonly infiltrates the cerebral lobes, appears as bright spots on the right side of this brain image.

A few cases of type 1 are due to a defect in channels that allow charged atoms to enter and exit the cells. Although the symptoms resemble those of regular autoimmune diabetes, the insulin-making cells remain intact.

Genetic tests can now identify the lucky diabetics -- an estimated 1,000 in the United States -- who have a mutation that can be treated with pills rather than insulin injections, says Louis Philipson, a professor of endocrinology at the University of Chicago Medical Center. "When we put this together, we can do a miracle. It's a huge win" because patients can reduce their glucose testing and essentially eliminate insulin injections.

News that a few diabetics can quit insulin injections has led to genetic tests that have uncovered new mutations that cause type 1 diabetes, Philipson says. Although patients with these mutations must still take insulin, identifying them could speed the search for drug treatments.

Genetic tests for these diabetes variants also offer another benefit. Although each child of a parent with a mutation has a 50/50 chance of getting diabetes, tests during in vitro fertilization could allow doctors to implant only embryos lacking the diabetes mutations, preventing illness in the next generation.

For many genetic tests, however, the meaning of the mutation is mainly murky.


Terry Devitt, editor; Nathan Hebert, project assistant; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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