What’s in your genes?

An employee’s rare opportunity for genomic sequencing turns up some surprising results – and highlights what genetic testing can and can’t do
Sept. 27, 2016

Last summer, Natalie did something not many others do – at least not yet. She had her genome sequenced. It started simply, with a blood draw, about one-and-a-half teaspoons. It yielded, after extensive processing and analysis, the entire order of the compounds of acids, sugars and bases, known as nucleotides, that make up her DNA. Billions of these nucleotides, arranged in a sequence unique to Natalie, provided her hereditary blueprint.

For all the information processed, Natalie (not her real name) received a report of only a few pages from Illumina, the company that did the sequencing. But within the report were many nuggets of information that she is using to make important decisions about her health care and personal life.

For example, Natalie, who works on the Anschutz Medical Campus, now knows she has a genetic mutation that increases her risk of hemochromatosis, a metabolic disorder that causes the body to retain too much iron from the diet. Without treatment to remove the excess iron from the blood, the condition can lead to cirrhosis and liver failure.

Cellular truths

That’s unlikely to happen now that she’s aware of the risk. She’ll get baseline blood work to check her iron levels and will monitor them over time, in consultation with her primary care provider. She’ll avoid eating too much iron-rich food, like red meat, and will abstain from alcohol. If her iron levels get too high, Natalie can handle the problem relatively simply by periodically having a unit of blood removed.

Along with discovering she has a gene known to cause disease, Natalie also found that she is a genetic carrier for cystic fibrosis (CF), which causes the cells to secrete thick, organ- and airway-plugging mucus. It’s a devastating, life-shortening disease with few treatments available. While Natalie doesn’t have CF, the knowledge that she is a carrier raises important questions. For example, if her significant other is also a carrier, the risk of bearing a child with CF increases dramatically.

The discovery triggered thoughts and conversations about her reproductive decisions, Natalie said, particularly if her partner is a carrier for CF. This piece of knowledge she gained from the sequencing wasn’t positive, obviously, but she said she’s glad she has it.

“It was the truth before the testing, and it’s still the truth,” Natalie said. “It made me think about what it means to have the disease, what to expect and the treatments that are available.”

The sequencing also led to what Natalie called some difficult conversations with her family members. Her older sister, for example, didn’t want to know about “anything that is not actionable,” such as a genetic variation linked to a disease like Alzheimer’s. Her sister did get an iron test after learning about Natalie’s increased risk of hemochromatosis and the link to it in their family’s history.

Reading the genes

Natalie didn’t think through these and other questions alone. As part of her sequencing, she consulted with Matthew Taylor, MD, PhD, director of the Adult Genetics Clinic at University of Colorado Hospital and associate director of UCHealth’s Center for Personalized Medicine. Taylor received a copy of the genome-sequencing report from Illumina, reviewed it and helped explain the findings to Natalie and answer her questions. She also met with Jean Jirikowic, MS, a genetics counselor who is coordinator for the Adult Genetics Clinic, to talk through the report and consider her options.

Jirikowic emphasized that Natalie’s experience is not the standard for those seeking genetic testing – at least for now. For one thing, she’s healthy. The vast majority of people who get tested do so because of specific situations that raise questions: family history of a disease like Huntington’s or various forms of cancer, for example; or “constellations of obscure signs and symptoms” that have defied the efforts of specialists to explain, Jirikowic said.

In addition, Natalie had her genome sequenced as part of an “Understand Your Genome” symposium hosted by the University of Colorado Anschutz Medical Campus and Illumina last June. She was one of a few individuals chosen for the sequencing, a process that is for now too expensive (although the cost has decreased significantly in the past decade) for most people.

Instead, many people interested in a better understanding of their genetic makeup turn to services like 23andMe, which use genotyping rather than sequencing. Instead of providing a look at an individual’s entire genome, genotyping examines pieces of DNA, giving clinicians a view of variations in nucleotides along specific points in the genetic sequence. These “single nucleotide polymorphisms,” or SNPs, can reveal genetic variants that might indicate increased risk of disease, for example, without going through the considerable time and expense of examining every nucleotide in the genome.

The Center for Personalized Medicine, which is building a DNA biorepository on the Anschutz Medical Campus, will use genotyping when the program starts, Taylor said, but he added that the center has plans for sequencing in the future.

Partial pictures

Jirikowic and other genetic counselors meet with patients to work through the information they receive from such tests. Sometimes the considerations are clear. The discovery of mutations in the BRCA1 and BRCA2 genes, for example, significantly increase the risk of breast and ovarian cancer. But family history, lifestyle, ethnicity, environment and many other factors come into play as well, Jirikowic said.

Even when the results of genetic testing are straightforward, Jirikowic added, they rarely if ever exist in a vacuum. They very often affect family members, as Natalie’s example shows.

“Any testing can reveal risk to family members, and it’s our responsibility and role as counselors to communicate that to patients,” Jirikowic said. It’s then up to the individual to decide what to do with the information, she said.

“We’re dealing with adults,” Jirikowic said. “It’s our job to be the messengers.”

Individuals who get the testing sometimes neglect to consider family history, an element Jirikowic and her fellow counselors also take pains to explore. “Patients will sometimes say they didn’t think family history was important,” Jirikowic added. “They don’t always share the information. But it’s very important. It affects other family members.”

Natalie noted that she was aware that her grandfather had hemochromatosis and her mother had “some variant of it,” but “no one ever asked me about my family history.” Jirikowic covered it, however, during their consultations.

No single solutions

The number of genetic tests available continues to grow and with it the caseload for Jirikowic, who along with two other colleagues see patients in the Adult Genetics Clinic (the Prenatal Diagnosis and Genetics Center and the University of Colorado Cancer Center have their own genetic counseling clinics). The number of visits to the Adult Genetics Clinic is up 28 percent thus far in fiscal year 2017 from the previous year, Jirikowic said.

Multicolored rectangles are solid surfaces holding collections of DNA.

With increased volume and interest, however, comes occasional misunderstanding of what genetics can reveal about an individual’s health, she said. Even the most sophisticated testing can offer only a better understanding of levels of risk. Individuals still can do much to improve or worsen their health through lifestyle choices or changes in their environment.

“There can be fear based on misunderstanding of the results of genetic testing,” she said. “Genetics isn’t everything. There is much more that comes into play.” Moreover, patients with the same disease-linked genetic changes can experience different outcomes, Jirikowic said. In one the disease might appear at age 15, in another at age 45. In still another, the disease might not appear at all.

“It’s important in 2016 that we have realistic expectations of what the testing is telling us,” Jirikowic said.

At the same time, Natalie’s experience offers a glimpse of the promise of genetic testing, Jirikowic stressed. With awareness of her increased risk of hemochromatosis, for example, she can choose to change her dietary habits and regularly monitor her blood-iron levels.

“She can be proactive rather than reactive,” Jirikowic said. Knowledge of that type, spread broadly across the health care system, has the potential for revolutionary change.

“The testing helped me to know what to expect and defend against more effectively,” Natalie said. “I can also sleep better instead of wondering what’s coming around the corner.”

About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.