Epigenome: the missing link

A model of a nucleosome. Strands of DNA are coiled around proteins to form a nucleosome core particle. These combine into still larger and more complex structures to build a chromosome.
A model of a nucleosome. Strands of DNA are coiled around proteins to form a nucleosome core particle. These combine into still larger and more complex structures to build a chromosome.

Research in the field of epigenetics is revealing valuable and powerful information about how, when and why our genes behave the way they do. Chris Sheedy discovers how the science could change dentistry

A paper recently published in the Australian Dental Journal carried the title, ‘Epigenetics: a new frontier in dentistry’. It is a bold claim for a field that many practitioners know very little about, but it is one that is well supported by those at the cutting edge of academic research.

The paper, authored by Scott Williams from the School of Dentistry at the University of Adelaide (co-authored by T.E. Hughes, C.J. Adler, A.H. Brook and G.C. Townsend), states that in 2007 the journal Science referred to epigenetics as the breakthrough of the year. Time magazine also lauded the importance of the science, putting epigenetics in second place in their list of the top ten discoveries of 2009.

So, what exactly is epigenetics? Associate Professor Toby Hughes, one of the paper’s co-authors and also from the School of Dentistry at the University of Adelaide, says we usually discuss the way dental characteristics present themselves as an interaction between an individual’s environment and their genes. The epigenome, however, takes things a step further by being the interface between the environment and an individual’s genes.

“The epigenome relates to how the external environment can play a role in how an individual’s genes are expressed in different parts of their bodies and at different stages throughout their lives,” A/Prof Hughes explains. “This goes some way towards explaining how we can have billions of cells in our body, all of which contain the same genetic material but which do not do the same thing at the same time. Different micro-environments and macro-environments play a role in mediating how cells act or interact, switch on and switch off, within their environment. That is all at the level of the epigenome.”

Our genetic code is encoded within our DNA. But the program that determines when each gene is expressed—when certain elements of our DNA are required to function—is within our epigenetic code. If the DNA is the orchestra, the epigenetic code is the conductor telling when each instrument should begin and end playing.

The question is, how then do we define the ‘external environment’ that influences how and when an individual’s genes may be expressed?

“The answer to this is relatively contextual,” A/Prof Hughes says. “It might depend on what particular characteristic we’re talking about as to what environment it exists within. If we’re talking about an individual gene and its environment is within a cell, then it will be the molecular events that are going on around it. If you’re talking about an individual cell sitting within a group of cells, then we are talking about the external environment provided by those other cells, and the molecular and physical interactions between those cells. Then you work all the way up through the tissue to the organ and to the organism and up to a population of individuals existing within an environment.”

While dentists always think of the macro-environment that we exist within as individuals—considering influences such as weather, diet, general health, socioeconomic status, types of nutrients we have access to during our physical development, etc—smaller variations all the way down to genetic level also have unique influence over our bodies and behaviour.

For the dental clinician in a suburban practice, the science of epigenetics may not mean a great deal right now. But increasingly, over the next 10 to 15 years, technology and processes will come to the stage where such information can begin to be utilised, in conjunction with other physical evidence, to produce a truly individualised treatment plan for each patient.

“We’re constantly getting more of a handle on genetic variation and its role in normal dental development, abnormal dental development and susceptibility or liability for diseases such as dental caries or periodontitis,” A/Prof Hughes says. “We’re coming to terms with the genes involved and those that have a primary influence in terms of our disease susceptibility.

“The next step will be to ascertain whether there are epigenetic mechanisms that further explain the complexity of such diseases. There is a complex interplay between an individual’s environment, their diet, the microbes in their mouth, their DNA and the individual’s epigenetic expression of particular genes. This interplay will make them more less susceptible.”

In the past 15 years, A/Prof Hughes says, academics have gone from having only a very basic understanding of genetic architecture to having completed subsequent detailed research following on from the Human Genome Project.

“Certainly in terms of the technology available to us and our capacity to do large-scale sequencing of genetic variation relatively cheaply and quickly, we have taken several major steps forward,” he says.

“When I am teaching my dental students about what they might expect as clinicians, I tell them we’re certainly at the point where, particularly for those in the US, we will have the capacity for purchasing technology that enables us to scan an entire genome within a relatively short space of time. So, a patient might come in and the clinician might take a tissue, saliva or blood sample and screen the individual across their entire genome. They can get information on all of the genetic variants that exist within that person’s genome.

“The next step is to interpret the information contextually relative to the individual’s disease status. That is where we’re not quite ready yet. We
have the technology but in terms of applying the technology, we’re still several steps away. But certainly in the lifetimes of the current crop of dentists, we will see genomic screening becoming a lot more common.”

Epigenomic screening, A/Prof Hughes says, will likely be around 10 to 15 years down the track and will require the integration of several disciplines.

“This is not just a job for the clinical dentist but also for professionals such as geneticists, bio statisticians and other individuals capable of interpreting what is relatively complex data in the context of the way an individual presents,” says A/Prof Hughes. “It is an example of how different disciplines are going to need to pull together to make use of this information at a clinical level.”

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