Beyond paternity: Applying DNA study in healthcare and disease management

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OPINION

By Dr Diana Kisakye Kabbale

Early this year, Uganda hosted the inaugural African Society of Human Genetics and Bioinformatics conference. As a researcher in genetics, this was an exciting opportunity to learn about advances in the field on the African continent.

When Professor Segun Fatumo, the conference chair, was interviewed on local TV stations, reporters focused primarily on whether DNA testing for paternity ascertainment would be discussed. This focus on paternity testing, while understandable given its familiarity, highlighted an opportunity to broaden public awareness about the many other applications of DNA research and underscored the important role media plays in informing the public and shaping their understanding of science.

Since we are in an era where DNA research is rapidly advancing, I believe it would be useful to shed more light on why scientists are particularly interested in studying this complex molecule in the context of health and disease and explore some of the applications of this kind of research.

Simply put, DNA is the blueprint of life. It is present in all living organisms and contains instructions that determine an organism's attributes/features, both at coarse and fine levels. To ease us into the subsequent sections, I will use an analogy of DNA being a large book of instructions found in each cell of an organism. This book contains letters (DNA bases), words, sentences (genes) and chapters (chromosomes). For related individuals, their books are highly similar and can be used to identify them, which is the basis for paternity testing.

Beyond paternity testing, how else is studying DNA important in the context of health and disease?

1. To diagnose and treat genetic disorders

Studying DNA can help scientists identify diseases that are caused by mutations in DNA, the equivalent of typographical errors (typos) in words, using our book analogy. Typos that change the meaning of an instruction usually have severe consequences. Sickle cell disease is an example of one such condition, which occurs when people inherit from both their parents a typo in the gene (sentence) that contains instructions for making haemoglobin, the molecule that carries oxygen around the body.

Exciting prospects for a potential cure for sickle cell disease using gene therapy have arisen in the developed world. Uganda is not being left behind, with plans underway to establish a gene therapy unit at the Joint Clinical Research Centre (JCRC) in Lubowa. While it is still prohibitively expensive, gene therapy holds promise as a game-changer for people living with sickle cell disease. From our analogy, this fancy technology works by correcting the typo in the haemoglobin gene.

Down Syndrome is another relatively common genetic disorder in the community, which occurs when individuals are born with an extra chromosome / extra chapter from our book analogy. This kind of genetic disease is not commonly inherited but occurs during the early stages when a baby is formed in the mother's uterus. While affected individuals have characteristic physical features, the diagnosis can be confirmed by carrying out a special DNA test called a karyotype.

2. To identify genetic risk factors for non-communicable diseases

Minor typos in the DNA sequence may not be problematic on their own; for example, one might erroneously spell 'receive' as 'recieve' in a sentence, but the sentence would still be sensible. However, typos in several key sentences, which in our book analogy represent genes, can increase one's risk of acquiring non-communicable diseases (NCDs) such as diabetes, cardiac disease, and kidney disease. These minor typos are usually inherited and, when compounded with environmental factors such as a sedentary lifestyle and unhealthy diet, can cause non-communicable diseases.

Studying DNA can, therefore, reveal an individual's genetic risk of suffering from NCDs, allowing healthcare providers to advise high-risk individuals on appropriate preventative measures.

3. To identify inherited cancer risk, diagnose and treat cancer

Cancer occurs when body cells divide and grow uncontrollably. These cells become unresponsive to signals instructing them to die if old/damaged. In other cases, cell division and growth signals are switched on without inhibition. Cancer cells acquire this behaviour as a result of typos in genes that are involved in cell growth, division and DNA repair. These typos can be inherited by an individual from their parents or can occur due to certain environmental exposures. These environmental exposures, called carcinogens, are compounds which, if an individual is exposed to, increase their risk of acquiring cancer. Examples of carcinogens include tobacco smoke, ultraviolet rays, and aflatoxins, among others.

By studying the DNA of cancer cells, a diagnosis can be made more precisely. Once a diagnosis of cancer is made, for some cancers, treatment can be chosen based on the kind of typos/genetic features in the cancer cells. For those for whom DNA testing reveals an inherited risk of cancer, routine screening and preventative measures can be recommended.

4. To identify disease-causing and drug-resistant micro-organisms

Since we earlier mentioned that DNA is a blueprint all organisms have, we can test people with symptoms of deadly infections such as Ebola to identify the virus with precision. Identification of these organisms with precision allows scientists to name and characterise them. For example, by examining its DNA, the recent Ebola outbreak strain early this year was found to be the Sudan virus and not the Zaire virus (the Zaire virus is responsible for the outbreaks in the neighbouring DRC).

The more accurately scientists can identify and characterise an organism, the more likely they are to advise policymakers on infection, prevention and treatment (IPT) measures that are tailored to the offending infectious agent, resulting in an appropriate and effective response. These measures can include designing appropriate vaccines, rapid diagnostic tests to detect outbreak strains and identifying high-risk populations for whom IPT measures can be prioritised.  Thus, because of the availability of DNA testing platforms in-country, response to outbreaks has been strengthened, and it is no wonder that the recent Ebola outbreak was quickly contained.

Studying DNA also enables scientists to discover drug resistance mediating typos in micro-organisms, which cause drugs to be ineffective. For instance, identifying these typos guides clinicians on the most appropriate drug combinations for patients who fail to respond to the first line or preferred medications for diseases such as Tuberculosis and HIV. This same strategy can be applied in the management of other infectious diseases for which patients are unresponsive to first-line drugs and has demonstrated utility in resolving diagnostic odysseys, where a patient has persistent fever which cannot be attributed to routinely screened infectious organisms.

5. To investigate why some drugs work differently for different people and tailor treatment to their genetic makeup

Our bodies contain proteins that are responsible for the absorption, distribution, breakdown and excretion of drugs. Sometimes variations in the blueprint of these proteins occur in some individuals, causing certain types of drugs to be ineffective for them even at the recommended doses. For other individuals, some drugs may be toxic at the recommended doses. In recognition of this, the United States Food and Drug Administration published a list of drugs for which doses can be adjusted, or alternative drugs provided,  for people who have certain typos in their DNA that could cause drugs to be toxic or ineffective for them. This kind of approach to treatment is also called personalised treatment.

In conclusion, the study of DNA extends far beyond its popular association with paternity testing in Uganda. As we have seen, DNA research is revolutionising healthcare in multiple ways - from diagnosing and treating genetic disorders, identifying the risk of suffering from non-communicable diseases and cancer, diagnosing and treating cancer, identifying infectious organisms with precision, and personalising treatment.

With initiatives like the planned gene therapy unit at the JCRC and advanced in-country platforms for DNA testing currently available for infectious organisms, Uganda is positioning itself at the forefront of the genetics and genomics revolution. However, the deployment of such DNA testing platforms for clinical utility in-country remains a critical need.

The writer is a PhD Scholar, Makerere University