IRP Investigators Answer Burning Genetics Questions
Monday, May 6, 2019
Dr. Laura Koehly and Dr. Alexander Katz
Each year on April 25, we celebrate National DNA Day, which commemorates the completion of the Human Genome Project in 2003 and the discovery of DNA's double helix in 1953. On this day students, teachers, and the public learn more about genetics and genomics. In honor of DNA Day this year, on April 24, the NIH IRP partnered with the NIH's National Human Genome Research Institute (NHGRI) to host a Reddit "Ask Me Anything" (AMA) with three experts on the many ways that advances in the genomic sciences are changing our lives.
IRP investigators Alexander Katz, M.D., and Laura Koehly, Ph.D., along with Saskia Sanderson, Ph.D., of University College London (UCL), answered questions on the latest discoveries and research endeavors in the field of genetics, as well as the ethical and public policy challenges that accompany them. The lively discussion wandered from the inheritance of personality traits to the effects of genes on eating behaviors to the importance of interpersonal relationships for maintaining good health. Read on for some of the most interesting exchanges that took place or check out the full AMA on Reddit.
Question (Q): “Is it true that genetics can 'skip' a generation, or multiple?”
Alex Katz, M.D.: “Genetic conditions show many different inheritance patterns, and these often can result in ‘skipping’ a generation or multiple generations. We have two copies of every gene (except for those found only on the Y chromosome), and some conditions are recessive, meaning that a person can have one defective copy of the related gene and one normal copy of the gene and won’t show any effects at all from the defective copy. Such an individual would be considered a carrier, and if two carriers for a given condition have a child, that child has a 25% chance of being affected. In this way, family pedigrees can look like a condition is present but skips generations (with carriers appearing to be ‘skipped’).
“Another possibility is a dominant inheritance pattern with incomplete penetrance. With these conditions, an affected person can pass on the causative genetic variant to his or her child, but the child does not develop the condition because the variant is not fully penetrant. That ‘unaffected’ child can then pass the variant on to the next generation, and in that generation, the individual who harbors the causative variant does go on to develop the condition.
“These are two examples, but there are many more!”
Q: “In your opinion, what is the most important genetic research that needs to take place? What areas of expertise are we lacking when it comes to genetics?”
Laura Koehly, Ph.D.: “There are amazing discoveries being made at the bench in understanding how genetics impact biological systems and contribute to health and disease. In addition, there are important strides being made in clinical genetics and genomics. All of this work is incredibly important in understanding the role of genetics in human health. However, in my (biased) opinion, the most important arena for genetic research is in understanding how to optimally translate these discoveries to patients, families, and communities in order to benefit all.”
Q: “While conducting research in your respective fields did you ever have a ‘Wow, look at that!’ Moment? If so could you share it?”
Saskia Sanderson, Ph.D.: “I have spent most of my research career working in the field of psychology applied to genomics, and a big focus of this field is conducting research on the impact of personal genetic information on people’s behavior. But before this, I started off in the field of behavioral genetics, looking at the impact of genetics on behavior — specifically, eating behavior in small children. My first job in this field involved going around the country giving four-year-olds plates of cookies, sitting them down in front of a video, and then leaving them for 10 minutes to eat as much as they wanted. Afterward, we weighed the cookies that were left, to see how much they had eaten. When we looked at their genes, we found that the kids with a certain ‘higher risk’ DNA variant in the FTO gene ate significantly more cookies than those with the ‘lower risk’ DNA variant! The data and graph were really clear, and it’s remained one of my favorite graphs from our research. It was one of the first studies to show that variants in people’s genes such as the FTO gene are influencing their body weight at least partly by influencing their eating behavior itself.”
Q: “What are your thoughts about the new wave of genetically modified babies? Leaving the ethical issue to others, do you think the benefits outweighs the problems? Are there any possible long term problems that are yet to be found? Last but not least, why should we even do it?”
The CRISPR/Cas9 gene editing system allows scientists to modify DNA at specific locations.
Dr. Katz: “In terms of using CRISPR to modify an embryo resulting in a live birth, the only documented case is the recent revelation of the extremely controversial and near unanimously condemned (by the medical and scientific community) research by He Jiankui in China. We certainly don’t know enough about the technology (including CRISPR’s possible off-target effects) to consider this right now.
“Leaving aside the ethics (per your question) there are other ways to address genetic diseases in the prenatal setting, such as IVF [in-vitro fertilization] with preimplantation genetic diagnosis, that are more established and safer than CRISPR from a technological standpoint, given the uncertainty associated with CRISPR. However, I would say that there is a foreseeable future in which the technology is studied more robustly, and there should be a discussion about possible responsible uses for CRISPR in the prenatal setting. For example, in the case of rare, devastating disorders in which there is no alternative treatment, CRISPR could one day theoretically be used to increase the number of unaffected, viable embryos available for implantation if an affected couple opts for IVF. As gene editing technology continues to be studied and improved upon, a cost-benefit analysis for such extreme cases will be crucial.
“Goes without saying hopefully, but these are ethically challenging issues and before germline gene editing can be considered for clinical use, there needs to be much more discussion among scientific experts, among various stakeholders and affected patients, and with complete transparency.”
Q: “What is one important thing you think people should know about your field?”
Dr. Koehly: “A meta-analysis by Julianne Holt-Lunstad showed that social relationships yielded a stronger association with mortality than lifestyle behaviors such as smoking and physical inactivity. Unpacking how these interpersonal ties impact health is an important next step and will guide the development of future medical interventions. In my lab, we look at family systems and how interpersonal mechanisms within the family relate to health outcomes, with a particular focus on inherited disease. We consider interpersonal ties from a health promotion perspective — so, can we leverage family relationships in meaningful ways to improve family members’ health through genomics. We also look at these mechanisms from a disease management and caregiving perspective — so, can we identify patterns in how social resources are exchanged within the family that are associated with optimal coping when providing support and care to someone diagnosed with an inherited disease.
"What we find is that family relationships are critical to members’ health. It is through the intergenerational transfer of information that family members learn about their family health history — information that is important to personalized health care. Encouragement from family members to engage in healthful lifestyle behaviors can make the difference in whether members take up those behaviors. In addition to providing support resources, family relationships can also be sources of interpersonal stress — particularly in the context of negotiating caregiving roles — and stress is associated with numerous health outcomes."
Q: “Can (some) personality traits be passed down? If so, what kind?”
Dr. Katz: “Absolutely, almost any personality trait can be passed down to some extent, although the specifics depend on what we mean by ‘passed down.’ Personality traits are probably best thought of as a mixture of genetics and environment (or nature and nurture), and the genetic component is often a result of the interaction of many different genes as opposed to a result of the action of one specific gene or one specific gene variant. Similar personality traits among family members are likely a combination of shared genetics and shared environment.
“It is important to note that when we consider single genetic variants in relation to complex traits like personality, even if a genetic association has been studied, a gene usually has only a small influence on the trait. That is to say, it is unlikely that any single mutation can explain a whole personality trait.”
Dr. Saskia Sanderson
Q: “What are your thoughts on behavioural genetics? Do you believe the concerns are justified?”
Dr. Sanderson: “We have to take seriously the concerns about knowing more about people’s genetics in terms of their cognitions and factors relating to education, as well as about other behaviours such as eating behaviours. The potential harms include stigma, labelling and discrimination. There are also potential positive outcomes of this type of research — for example, it is possible that it will, directly or indirectly, lead to better ways to support children and adults in their learning, and better ways to help people eat in ways that are right for them. The important thing is that we have open discussions and debates in society among all stakeholders, including citizens, scientists, ethicists, and policy makers. It is also important that translational research is conducted to understand what the actual benefits and harms might be — if the harms turned out to outweigh any benefits in controlled research settings, then this would be important for everyone, all stakeholders, to know and to take into account in their views and decision-making.”
Q: “I’m a biology undergraduate considering going into genetics in grad school. What is the field and job market like outside of academia and do you have any advice for my studies?”
Dr. Katz: “Genetics is a great field (I’m biased of course). Most importantly, it is fascinating and changing rapidly, so new opportunities are arising all the time. The job market outside of academia is growing (in genetic counseling, for example, there are tons of jobs available both in and outside of academics and a huge need for good counseling in healthcare systems, academic institutions, and private companies). My advice would be focus on what you enjoy in school and the opportunities to apply the skills you’re learning will be there.”
Question (Q): “So Bill Gates has stated (and I agree with him) that genetics related advances pose a problem of being a cliff that may exacerbate inequality in this country and globally. Do you think this is a major problem? What do you think we can or should do to ensure the benefits of genetics research can help everyone?”
Dr. Sanderson: “I think you’ve hit on a really important point here. If we don’t make concerted efforts to ensure that genomics advances are delivered equitably, then yes for sure we run the risk that genomic discoveries are going to contribute to increasing existing health disparities. So the first thing we need to do is not only develop the technologies and genetic tests arising from those technologies, but we also need to do the research to make sure that the tools and systems are built in ways that are accessible to people from different backgrounds and socioeconomic groups, and that the infrastructure is built to deliver genomic advances to everyone, not only those with the best access to healthcare and the most resources.
“And I think we can also go even further than this. In addition to ensuring access and infrastructure, I believe the second thing we need to do is ask ourselves the question, can we actually design the translational research in ways that are designed to reduce social inequalities in health?
“To do this, we need to have this in our minds right from the start. We need to ask ourselves, ‘Can we develop interventions that take both genomic and environmental challenges that people experience into account?’ For example, efforts are already underway to identify people at high risk of cancer or heart disease in the general population so that risk-reducing strategies and support can be offered to them. Given we know that socioeconomic factors hugely impact any given individual’s risk of, for example, heart disease, then perhaps these interventions should be developed to take both genetic high risk and socioeconomic high risk into account.
“And then, finally, there has been the huge problem that most genomics research has been conducted to date with white populations, with all other populations being underrepresented. It is vital that this is dealt with so that everyone benefits from genomics discoveries, not only some populations and those with the most resources.”
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