Unraveling the Hidden Truth: Text and Context

Aug 25, 2017

Anand Andiappan

Senior Research Scientist

Singapore Immunology Network

The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

In the last post, we were discussing that there is more to traditional genetics that affect our risk for disease. We all know that the genetic code of DNA is made up of the bases A (adenine), T(thymine), G(guanine) and C(cytosine). Just like any language, meaning comes from reading letters in context. To understand DNA, the language of genetics, we need the context of epigenetics. The basis of health and disease could be understood if we understand how to read the text in context.

The secret in genetics – epigenetics!

The term epigenetics refers to heritable traits 'outside of' genetics. So what causes these changes in addition to the effects of the genetic sequence? It can be anything from air pollutants, allergens, microbes, diet and toxins, among others. Genetics refer to the part of your DNA which doesn't change over the years. However the epigenetics of your DNA can and do change! While genetics are the physical code consisting of nucleotides, there are chemical switches, or 'epigenetic tags', which can turn genes on or off without altering the genetic code. This is a fascinating new area of research which helps us understand how our genes and the environment we are exposed to lead to diseases.

Do our genes have memory?

For a long time, we did know that we inherited our genes from our parents. With epigenetics however, we are now seeing evidence that we might also inherit the environment or experience of our parents. In one study of this surprising phenomenon, male mice were trained to fear a specific odor by receiving an electric shock upon exposure. When these mice had babies, they too were afraid of the odor, as were their offspring, the 'grandchildren' of the trained mice. These two generations of rats had not been trained by shock on odor exposure. However the scientists observed that both the father and the babies had epigenetic tags that associated with additional neurons in the nose and altered activity in the brain. Mice! What about humans?

Context matters!

At the population level, there seems to be some evidence for transgenerational inheritance.Data from the Netherlands, where the population suffered a famine in the winter of 1944-45, showed that children born during the famine were smaller and had higher risks of obesity, cardiovascular diseases and mental disorders as adults. Strikingly, they in turn had children who were smaller, even though they had improved living conditions. Although this is still observational, it makes us wonder if our exposure and experience could affect both our offspring and their children. In particular, what about asthma and allergies?

It's all in the family!

Smoking and air pollution are strong environmental risk factors for asthma. Recent evidence shows that exposure to air pollution during pregnancy is associated with changes in the epigenetic pattern of the newborn in stress-related genes. Interestingly, the smoking status of a grandmother during her pregnancy is associated with her grandchild's risk for asthma, even if the grandchild's mother didn't smoke. In a study of the parents of 24,168 offspring, fathers who smoked during adolescence increased the risk of their children having asthma by 3-fold. So there is some evidence that risk for disease involves more than just the genetic code in DNA. The main issue, however, is that most studies have been looking at either genetics or epigenetics, few studies look at both.

We can't simplify what's complex!

At this point in time, we have only started scratching the surface of this vast field of epigenetics. It's exciting to see that there have already been some exciting findings which hold great promise! However, we need to be careful not to ignore the complexity of complex diseases such as asthma, diabetes, obesity, cardiovascular diseases, and so on. We need to carefully document the genetics and epigenetics in the context of environmental exposure, family history and possibly even population history. Our group along with our collaborators have started doing this to study allergies and asthma.

Dr Anand Andiappan is a Senior Research Scientist at the Singapore Immunology Network. For over a decade he has been studying allergies, particularly focusing on allergy prevalence in Singapore. He graduated with a doctorate in biology from NUS and has been since working with A*STAR. He also collaborates with allergy researchers worldwide to understand the unique situation in Singapore better. His current research focus is to understand the risk factors related to manifestation of allergies by studying the underlying genetics, epigenetics and corresponding immune responses in individuals.