Andrew T. DeWan studies the human genome and how genetic abnormalities contribute to specific diseases. He is currently seeking to identify genes that are a factor in pregnancy-related complications such as preeclampsia and early childhood diseases such as asthma. This work entails scanning the entire human genome (more than 20,000 genes) in hundreds of different people in order to pinpoint a genetic difference or differences that may or may not play a role in the onset of disease. Additionally, he has studied the genome for clues about the origins of age-related macular degeneration, non-syndromic hearing loss, renal function and myopia. DeWan, M.P.H., Ph.D., is an assistant professor in the Department of Chronic Disease Epidemiology. He joined the School of Public Health faculty in 2009. Three years later he received the Distinguished Student Mentor Award, an honor that is presented by the student body.
What is the role of genetics in public health today?
AD: We are attempting to not only identify genes contributing to diseases with large public health impact, such as cardiovascular disease and asthma, but to then understand how we can use this information to identify people at risk for developing these diseases, target early interventions and screenings, and design more specific pharmaceuticals. We’ve done a great job at finding genes for rare diseases that are primarily caused by mutations in one gene, but we still have a long way to go finding genes for more common diseases that have multiple genes influencing them along with environmental factors.
How has this changed in the past 10 to 20 years?
AD: The major change over the past two decades is that we can now more quickly and more accurately identify the genes playing a role in disease and then find specific mutations within these genes that may be responsible for the disease. The mapping of the human genome just over a decade ago provided us with a much more detailed roadmap of the genome that has allowed us to more rapidly identify small regions that may contain a mutation that is responsible for a disease.
Would you describe this change as a scientific revolution?
AD: This change was absolutely a revolution. Without the complete sequencing of the human genome we would still be hunting through very large pieces of the genome to find disease-related genes.
Can you provide an example of how genetics has provided new insights into a disease or disease transmission?
AD: In age-related macular degeneration (AMD), the discovery, made here at the at the Yale School of Public Health by Josephine Hoh and her collaborators, of a mutation in the complement factor H (CFH) gene being a major player in the disease opened up a whole new avenue of research into other genes that interact with CFH that may contain mutations related to AMD. This was the first time a gene in this biological pathway had been shown to be involved in AMD and since that discovery several other related genes have been shown to contain mutations related to AMD.
What are some other areas of public health where genetics are being widely used?
AD: Genetic carrier screening of parents for genes for rare recessive disease, ones in which a mutated copy must be inherited from both parents, prior to conception have been effective in reducing the rates of these diseases within certain populations. The incidence of Tay-Sachs diseases, a fatal neurodegenerative disease, has been reduced by 90 percent in the United States and Canada in the Jewish population since screening began in 1970. This is an excellent example of how genetics can be used as a public health prevention tool.
How are you using genetics in your research?
AD: I have an interest in identifying genes that are influencing pregnancy-related complications and early childhood diseases. I have been working for several years on projects to identify genes for childhood asthma and preeclampsia using various techniques that scan through the entire human genome of hundreds of subjects to find genetic differences in individuals that have the disease compared to those that don’t.
What are the limitations or shortcoming of genetics or genetic epidemiology as a public health tool?
AD: As mentioned previously, there have been some successes in reducing the incidence of rare, single-gene diseases through screening programs. But this approach is not going to be possible for common diseases because there are likely tens or hundreds of genes influencing the trait and “perfect” matings to avoid all common diseases is not going to be possible. Where genetics will hopefully be used effectively as a public health tool is to identify individuals at risk for common diseases and prescribing early prevention or lifestyle changes to mitigate the effects of the disease.
In terms of utilizing the potential of genetics as a public health tool, where are we?
AD: Despite having mapped hundreds of genetic markers for diseases with a large public health impact, such as heart disease and stroke, we cannot yet predict with any certainty who is at increased risk of developing these diseases based on known genetic markers. We need to know so much more about how these genes act in concert to cause disease along with environmental risk factors in order to build better risk prediction models for individuals.
How are students responding to the growing role of genetics in public health?
AD: Wonderfully! For the past three years I have had students from across all departments in YSPH in my introductory elective course, “Genetic Concepts in Public Health.” I have many students take my course who have very little background in biology, but they want to be able to understand the literature in their specific field of public health, from epidemiology to public policy, that incorporate some aspects of genetics, which is becoming more widespread throughout public health.
Once the gene or genes that are responsible for a specific disease have been pinpointed, what is the next step?
AD: The next step is to find the specific mutation(s) within the gene that may be causing a change in how the gene functions. This is generally done by sequencing the gene in multiple individuals, sometimes several hundreds or thousands of individuals, and looking for mutations that are likely to result in a change in the protein that the gene codes. You then need to demonstrate that the specific mutation in the gene actually results in a biological change that is related to the disease you’re studying. This can involve studying this mutation in animal models, cell lines and human tissues. It is a long process from finding an association between a gene and a disease and actually demonstrating what is going wrong with the gene that results in the disease.
Is it now possible, or will it be in the future, to repair the gene in question and thus prevent a certain disease or illness in the future?
AD: It’s not possible now and I think we are still a decade or more away from routinely using gene therapy to repair defective genes. There are very real safety issues in how these good genes are delivered to an individual, but I think new advances in nanotechnology may be able to mitigate some of these risks.
Can you put into context the difficulty involved in isolating a gene that is responsible for, say, asthma? Is it the equivalent of finding a needle in a haystack, or a needle in several haystacks?
AD: More like many needles in several haystacks, but once you find them you don’t understand how they can work together to sew a shirt. In a survey of the asthma genetics literature we identified about 250 genes that have been reported to be associated with asthma, but the real challenge is to determine which of these associations are real and then the role each plays in asthma.
The science of genetics is evolving rapidly. What is one of the most interesting applications of genetics you see on the horizon from a public health perspective?
AD: It was described over a decade ago that during pregnancy there is DNA from the fetus circulating in the mother’s blood supply. Recently, several groups have developed sequencing techniques that can determine the sequence of the fetus using DNA isolated from the mother’s blood stream. There are now prenatal tests that use this DNA to determine if the fetus is carrying duplications of whole chromosomes that will tell the parents if the child will have a condition such as Down syndrome. This has routinely been done using a more invasive and risky procedure called amniocentesis, but I think this new prenatal test has the potential to reduce the number of amniocentesis tests performed and consequently reduce the number of adverse outcomes that directly result from the test itself.