Decoding Your Genetic History

If man with a diabetic grandfather and a woman with a family history of cancer decide that they want to have a child, but they are unsure of whether their families’ health problems may reappear in their children, where can they turn to get answers?  A genetic counselor. What is genetic counseling, you ask?

Genetic counselors provide expertise and counsel in both the research laboratory and the clinic.  In a clinical setting, a genetic counselor provides advice to people with genetic diseases, determines if people are likely to pass genetic mutations to their children, and explains genetic test results.  In a research setting, a genetic counselor collects genomic data from many patients and investigates genetic mutations to determine if the mutations have a connection to specific genetic diseases.  This week we talked to a genetic counselor, Katie Krempely about her work as a genetic counselor.

Katie began her career in a patient-oriented setting, where she provided guidance to patients.  Over time, she became fascinated by the genetic mutations that are associated with the diseases some of her patients carried.  To explore these mutations in greater detail, Katie joined Ambry Genetics, where she now works as a researcher and investigates changes in gene sequences.  Recently, #ISCblog interviewed Katie about what it takes to become a genetic counselor, what kind of work she does, how patient privacy is protected when conducting genomic research studies, and how genetic counselors make a critical difference in the lives of their patients.

What is a genetic counselor?

Katie Krempely

A genetic counselor is a health professional with advanced training in medical genetics and psychology. Becoming a genetic counselor requires attaining a Master’s degree from an accredited program and becoming certified by the American Board of Genetic Counseling after graduation.

Some genetic counselors work in clinical settings, where we discuss the risks for genetic disease with patients and families and help them make informed decisions regarding this information. We interpret family and medical histories in order to provide an accurate risk assessment and educate patients about inheritance, genetic conditions, testing, and managing a diagnosis. Very importantly, we promote patient autonomy and informed decision making. We discuss the benefits, risks, and limitations of genetic testing and help patients and families make the best decision for them.

If a patient chooses testing, we counsel him or her regarding the results and provide information, support, and resources. There are many specialties of clinical genetic counseling, including prenatal/preconception, pediatrics, adult-onset conditions, cancer, cardiology, and neurology.
Additionally, there are non-clinical settings where genetic counselors do not have patient contact. Many work for genetic testing laboratories, where a variety of careers are available.

Some genetic counselors interpret results, compose result reports, and serve as a resource for providers who order testing (this is what I do currently). Others are liaisons between the lab and physicians and other healthcare providers, educating them about genetic conditions, the strengths and limitations of various tests, and how to interpret results for their patients. There are also roles in project management, marketing, and sales. Some non-clinical genetic counselors take jobs at startups, some develop public health initiatives, such as newborn screening programs, and some serve as faculty at genetic counseling graduate programs.

There are a variety of roles for genetic counselors, which is something I like best about the profession. Some genetic counselors prefer jobs that have both clinical and non-clinical aspects. For example, they might interpret test results for a lab and also counsel patients who tested positive for a mutation at that lab. Or they might hold a faculty position and see patients on the days they’re not teaching.

Deoxyribonucleic Acid (DNA)

Where do you work and what do you do there?

I work at a clinical genetic testing laboratory called Ambry Genetics. I review the results for cancer tests and write the reports for the healthcare providers (usually oncologists or clinical cancer genetic counselors) who ordered the tests for their patients. The largest component of putting together a report is researching and assessing the actual test results. Sometimes a genetic test will reveal a change in the gene sequence. We know what many of these changes mean; some are mutations that cause disease and some are just common changes affecting many, many people that don’t cause any problems. But sometimes a test reveals a change in the sequence whose association with disease risk is unknown.

We call these variants of unknown or uncertain significance, or VUSs. My job is to research these variants – utilizing databases, scientific journals, structural biology prediction tools, clinical data, and other tools – and try to figure out if they increase the risk for cancer or are merely benign changes in the gene. I also make sure our records about known mutations are accurate and up-to-date by reviewing recent scientific literature and information from our clinical cohort. Since the field of genetics is fast-paced, with new information and studies being published frequently, we participate in educational training at Ambry at least twice a year. I also attend at least one professional conference a year.

Describe your typical workday.

Photo Courtesy of Ambry Genetics

Not every workday is exactly the same, which is one of the things I love about my job. Generally, though, I spend 80% of the week assessing VUSs and mutations, writing reports, calling clients, and housekeeping tasks like emailing and learning new software and computer systems. I spend the other 20% attending meetings and educational lectures and working on independent research projects.

What path (education, life experience, etc.) led you to where you are now? What types of courses did you take to prepare you for where you are now?

I first became interested in genetics when I was thirteen, due to a combination of Jurassic Park (still one of my favorite movies!) and my dad teaching me about genetically modified corn and other crops. I started college at Illinois Wesleyan University as a pre-med Biology major, thinking that I would become a medical geneticist one day. As time went on, from classes and my professors, I learned about other career paths that involved genetics and molecular biology. Getting my Ph.D. was somewhat appealing, but I wasn’t sure if I was ready for 6+ years of graduate school. Sometime during my junior year, my professor talked about genetic counselors during a lecture, which sparked my initial interest in the career. I left the pre-med track and started looking into the profession and what prerequisites genetic counseling programs required for entry. In terms of coursework, I took primarily biology, chemistry, and psychology classes.

Genetic counseling programs usually have an online list of what courses and experiences are required or recommended, so as I was researching the different programs, I kept track of what prerequisites I had fulfilled and still needed. In addition to class, I volunteered at a sexual assault crisis hotline to gain counseling experience while helping the community. After months of applications and interviews, I decided on Sarah Lawrence College in New York for graduate school.

What influenced you to pursue genetic counseling? What inspired you to move from a clinical setting into a research setting?

When I first learned about genetic counseling, it was appealing for a number of reasons. Notably, the career was a combination of complicated science and interacting with and helping people. One of my biggest hesitations about getting a Ph.D. was the lack of human contact. I liked the idea of making a difference in patients’ lives. I also liked that the career required a two-year Master’s degree (though that may become longer the near future, since there is so much material to cover). I loved being a student, but I was looking forward to finding a job and experiencing the real world.

For about three years, I worked as a clinical genetic counselor in a prenatal setting. The decision to switch to a non-clinical role wasn’t an easy one, because caring for my patients was very fulfilling and enjoyable. Ultimately, though, I became more interested in molecular mechanisms for disease, testing technologies, and solving the puzzles that VUSs posed to the clinical genetics community. It was a good time, logistically, to make a career change, because many labs were hiring genetic counselors. I interviewed with a couple different labs before deciding to take a job with Ambry. Not only was the position exactly what I was interested in, but the company’s goals and culture perfectly aligned with my personality and professional values.

Why would a person/couple see a genetic counselor?

There are many reasons why a patient, a couple, or a family might see a genetic counselor. In a very general sense, people come to see us when they are concerned about their chance to develop a genetic disease or pass one onto their children, to discuss a test result, or to manage a diagnosis of a genetic condition. For the following examples, I’ve broken things down by some of the areas in which genetic counselors specialize.

A genetic counselor works for a fertility center and manages the genetic screening and counseling for potential egg and sperm donors. S/he also sees couples with fertility problems to explore if there is a genetic cause.

A couple’s child has a history of seizures and isn’t meeting developmental milestones. They meet with a genetic counselor and a medical geneticist who evaluate the child for signs of a genetic syndrome. This evaluation involves a physical exam, family, medical, and pregnancy history, and discussion of genetic testing once a differential diagnosis is established.

A woman has a striking family history of breast and ovarian cancer. She meets with a genetic counselor, who takes a detailed family history. S/he goes over the differences between cancers that happen sporadically and those that arise as a result of genetic mutations and explains to the woman which of her family members would be the best, most informative candidates for cancer genetic testing.
In the cardiology center of a hospital, a genetic counselor works closely with cardiologists to assess which patients’ heart diseases and arrhythmias are hereditary and adjusts their follow-up and treatment appropriately.

A 38-year-old pregnant woman sees a genetic counselor, because her age increases the likelihood that the fetus could have a condition caused by an extra chromosome, Down syndrome being one example. The genetic counselor explains the numeric risks and discusses different screening and diagnostic testing options available during the pregnancy.

Sample karyotype from a male human.

Before having predictive genetic testing, patients who have a risk for Huntington Disease (a severe neurological disorder; if a parent has it, your risk to inherit the mutation is 50%) meet with a genetic counselor for information, psychological support, and informed consent.

A couple wants to become pregnant soon, but the husband had a sister who passed away from cystic fibrosis. He knows that he has a chance of being a carrier for cystic fibrosis and is interested in testing for himself. The couple meets with the genetic counselor to discuss the risk for each of them to be a carrier for cystic fibrosis, available testing, and risks and options for a pregnancy if they are both found to be carriers.

What are the benefits of visiting a genetic counselor before pregnancy vs. during pregnancy?

Meeting with a genetic counselor before becoming pregnant ensures that the most options are available. If there is a risk of passing a condition onto a child, a couple is able to explore all the methods of becoming pregnant that can reduce that risk. For example, they could do in vitro fertilization with embryo selection or consider using an egg and/or a sperm donor.

Additionally, patients can learn about all the screening and diagnostic testing options available during a pregnancy and can start planning what tests/procedures they want to do at what time – if they want to do testing at all. Sometimes unforeseen complications arise, such as a positive screening result or an ultrasound finding, and patients meet with genetic counselors at various points in a pregnancy. Time constraints can be inherent in these situations (for example, some testing is only available until a certain week in a pregnancy, or a patient may be considering pregnancy termination, and the state in which she resides has a legal restrictions against having the procedure past a certain gestational age). Genetic counselors, as well as other health providers in prenatal care, do the best they can in caring for patients in tough situations, whether it be changing the schedule so a patient can be seen as early as possible or requesting that a lab rush test results.

What do you find is the most effective way to clearly communicate complicated genetics concepts to patients?

In my experience, one of the most effective ways to start a discussion is asking patients what they already know about a genetic concept, disorder, test result, etc. Sometimes they’ve previously done research on their own or talked things over with their doctor. I also begin a conversation by asking patients what questions they have for me or what is important for them to learn. Genetic counselors have different strategies for communicating complex concepts and probabilities, including analogies, diagrams, and conceptualizing risk numbers in different ways. It’s also crucial to check in with patients to make sure they understand the information. If not, we should offer to explain something again or in a different way. Sometimes patients have trouble staying engaged because of emotional fatigue or information overload. In such a situation, I’ll give them resources to take home and check in with them in a couple days.

With new advances in genetics technology, such as CRISPR, which could eventually be used for gene therapy, some people are thinking about about the prospects of designer babies. What are your views on using gene therapy to eliminate a disease or change characteristics before birth?

I read and think about CRISPR a lot, and I think it’s very exciting and has a lot of potential. For the sake of brevity, I won’t go into too much detail about the history and technology of CRISPR, but these two articles are great, well-written resources for those who want to learn more (article 1 and article 2). CRISPR – standing for “clustered regularly-interspaced short palindromic repeats” – is a gene editing technology that lets scientists target a section of a gene, cut the DNA, and edit it. It’s similar to clicking a sentence in a word processing program, deleting some words, and typing new ones in. This technology has the potential to correct genetic mutation by editing the letters (or base pairs or nucleotides) of DNA, removing duplicated sections of a gene, or inserting sections that were deleted.

Right now we are just cracking the surface of this new technology and its implications; there is a lot of CRISPR-related research being conducted all over the world, but I think it’s going to be quite some time before we’re using it clinically. With that said, the optimism and excitement in the field can be infectious, and if we are able to one day use gene editing technology to treat everything from single gene disorders, like cystic fibrosis and hemophilia, to more complex conditions, like cancer, diabetes, and dementia, it will be a major milestone in human medical history. I think that as time goes on and we learn more, we’ll find other uses for the technology. For example, CRISPR has potential in agriculture and could allow us to grow crops with more nutrients or abilities to resist disease. There is also talk of using it to propagate mutated mosquitos into the population that would be resistant to the Zika virus and other infections. In a hundred years or maybe sooner, we’ll probably be working with ideas that we’re not even thinking about now.

Dolly the Sheep

I think it’s natural for people to feel apprehensive about a new technology, and if you look back through recent history in genetics, every new technological breakthrough was met with a degree of trepidation. The first pregnancy conceived via in vitro fertilization, cloning of Dolly the sheep, gene therapy trials with virus vectors, and preimplantation genetic diagnosis for embryo selection made many people question how far is too far to go with technology. The concept of “designer babies” has been around for a while, but we are very, very far away from that idea becoming a reality.

Genetics is complicated, and the more we learn, the more we realize all that we don’t know. Controlled experiments that use CRISPR to fix mutations in mice or single cells may be promising, but making the transition to clinical treatments for patients is an entirely different ball game. With CRISPR, we have the potential to alter human embryos and correct disease-causing mutations, which would eliminate risks for current, as well as future generations. This kind of therapy is a long way off. How would we test it before offering it to patients? What if a child was healthy until a certain age and then developed other problems? What if some cell lines weren’t corrected by CRISPR and still had mutations? What legal and ethical regulations would we need to establish? Would there be lawsuits? (This is America, after all).

The prospect of designer babies is just as remote, especially when it comes to complex traits like intelligence, which are the result of convoluted networks of multiple genes and regulatory mechanisms interacting in different ways at different times that we don’t really understand (never mind programming them into embryos).

There is a lot to say on these topics, but I’ll wrap up my response to this question. I would be very surprised if we’re able to safely and effectively modify human embryos in my lifetime. This might be the reality several generations from now. Presently, I don’t have a particular stance on designer babies. It’s a very theoretical possibility at this point, and I don’t give the idea much thought. I am in support of using gene editing technology to eliminate disease, and when/if scientists make that breakthrough, it’s possible that a market for selecting other characteristics will arise. At that point, we as a society will have to decide what’s ethically permissible and if the vast, disease-reducing benefits of the technology outweigh other uses that some people may not agree with.

You mentioned looking for mutations that are highly correlated with the incidence of a particular disease. Are most diseases are caused by genetic mutations? Can you comment on the balance of nature vs. nurture in getting genetic diseases?

Some diseases are only caused by genetic mutations; these are generally pretty rare and comprise a small percentage of total diseases. Some examples are Tay-Sachs disease, cystic fibrosis, Fragile X syndrome, sickle cell anemia, and spinal muscular atrophy. Additionally, there are genes that, if mutated, significantly increase your risk to develop a condition but do not guarantee it. For example, there are many genes that, when mutated, increase the risk for various cancers (this was in the news a couple years ago when Angelina Jolie was found to have a mutation in a gene that increased her risk for breast and ovarian cancer).

The majority of human illnesses, though, are due to complex interactions between multiple genes and the environment. These are more common illnesses like diabetes, autoimmune diseases, cancer (by this I mean sporadic cancer, not the cases caused by a mutation in one of the cancer predisposing genes), dementia, heart disease, and many others. For example, two sisters might have a variant of a gene that moderately increases the risk to develop lupus, but only one has the condition. These gene and environmental (which we can also think of as “nurture”) interactions are not well understood at this time, but this is an area of genetics where a lot of work and research is going on. The study of how and when genes are regulated and how this affects development, disease, and inheritance is called epigenetics. This is another area of genetics where we are barely scratching the surface, and I’m excited to see what we learn.

What are the benefits of sharing genome data for disease research? With reference to this New York Times article, how does Ambry Genetics handle patient privacy in reference to its new database?

It’s becoming increasingly popular for genetic testing laboratories to share their data. Ambry Genetics recently contributed significantly to this paradigm with the launch of its new public database, AmbryShare. AmbryShare contains anonymous aggregated genome data from 10,000 patients with breast or ovarian cancer. By making this information available to researchers and medical providers, we hope to advance our understanding of the relationships between genetics and human disease in order to find treatments and cures.

Right now, the database is focused on breast and ovarian cancer, but Ambry plans to include patients with a variety of disease types as the project progresses. Data sharing is beneficial, because it fosters collaboration between members of the scientific and medical communities and expedites knowledge of and treatments for disease. In constructing the database, patient privacy was a priority. Not only was patient information anonymized, the database is aggregated, meaning that each patient’s genome can’t be looked at individually. Instead, users can search by genes and variants without anything linking back to the individuals who provided the samples.

If you’re interested in learning more about the AmbryShare database, here is the link to the website: https://share.ambrygen.com/.

Photo Courtesy of Ambry Genetics

Does Ambry Genetics have positions or internships for aspiring scientists?
Anyone interested in working or interning for Ambry can go to www.ambrygen.com/careers to see available positions. Most of our positions are onsite in Orange County, but we offer several that are remote. Internships are onsite only.

Photo Courtesy of Ambry Genetics

Additional Information

1. To read more about the profession of genetic counseling, visit the website for the National Society of Genetic Counselors.
2. Are you looking to join a genetic counseling program? Here’s a list of accredited programs.
3. The American College of Medical Genetics, is an organization for all genetic professionals. ACMG’s statement: “The ACMG is the only nationally recognized interdisciplinary professional membership organization that represents the interests of the entire medical genetics team including clinical geneticists, clinical laboratory geneticists, and genetic counselors. Together, the ACMG and its members engage in coordinated efforts to improve patient care, ensure optimal reimbursement for genetic service providers, establish standards of care and laboratory policy, and educate members about advances important to their practices” (ACMG).
4. Are you looking for information about genetic disorders?  Check out the NIH-run Genetics Home Reference.