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Tuesday 17 September 2013

What Can Our DNA Really Tell Us About Ourselves?

Artist's impression of DNA with the word SECRET written in light beneath it
Image credit: Jurvetson
Looking in the mirror – what can you see? Blue eyes or brown? Red hair or fair? You don't need to delve into your DNA to find out what physical attributes you have, but how much can the code hidden deep inside your cells tell you about what diseases you're susceptible to, what you'll pass onto your children or how long you'll live?

Science Fiction or Fact?

At the end of the last century the whole history of genetic research, from Gregor Mendel investigating the principles of inheritance1 to the discovery of the nucleotide structure of DNA2, led inevitably to the Human Genome Project (HGP).

The project's aims were to look at the sequence of human DNA along with the location of genes and sections associated with inherited disease. As a project it felt monumental, not only within the scientific community, but to society as a whole. It was a project that captured the public imagination, inspiring both hopes and fears for the information it would give us. Would we be designing our own babies? Could we eradicate human disease or alter our genetic codes to enhance intelligence or perhaps sporting prowess?

Essentially, how comfortable are we 'playing God' with our own genetic material?

So in the ten years since the full sequence was published3, what has the Human Genome Project and subsequent research into the twists and turns of our DNA actually revealed about us, or rather, about you?

A Study In Susceptibility

Deoxyribonucleic acid (DNA)
Deoxyribonucleic acid (DNA) is a molecule which serves as the genetic blueprint for all known living organisms. Image credit: ynse
The ability to sequence entire genomes of data – 6 billion base pairs – has led to the rise of genome-wide association studies, scanning through millions of markers in a large number of people to find the genetic variations that are associated with a particular disease. So, what have we found so far?

In recent years the susceptibility to a wide-range of complex traits has been studied, from type 2 diabetes to age-related macular degeneration to prostate cancer, but only very small proportions of their genetic risks have been explained.

For example, type 2 diabetes has been deemed a particular success with 36 loci identified that are associated with the disease4. However, although studies have shown that heritability of the disease is greater than 50%4 the variants found so far only account for somewhere between 10[5]. and 30%6. of this. And more than that, most results are only a correlation between areas on a chromosome, rather than the identification of the specific genetic elements that are causing the disease.

So, what does it all really mean to the rest of us?

These common diseases are called complex for a reason. It's not as easy as gene = disease or even 30 genes = disease. Whether you get a disease is a complicated interaction of a large number of genetic factors, each with a small effect7, along with an individual's environment.

Let's take the FTO gene, associated with both obesity and body mass index8, as a particularly pertinent example as obesity-rates continue to rise. The FTO gene has 2 versions, one of which if you carry it in either one copy or two copies will increase your susceptibility to an increased BMI, and in turn obesity. That doesn't mean that having the risk variant means you will be fatter, but more that your physical chemistry means you're more susceptible to putting on weight – a fact that you probably already knew without having to carry out expensive tests.

So can this, and other disease-related genetic information, be used to provide a basis for treating everyone on an individual basis, taking their genetic and environmental information into consideration. The answer is not quite yet.

Would you really want to know?

With new scientific developments, at some point comes the question of 'should we?' Surely most people would opt to know about their propensity for certain diseases if interventions were possible, like changing their behaviour or receiving early medical screenings or treatment. Rather than just presuming we all would, the Sanger Institute is asking the general public questions about what information we should receive from investigations into our genomes. You can join the debate here.

Currently genetic testing for disease is limited to those rarer diseases that are caused by a single gene, such as cystic fibrosis, which can be used in families with a history of the disease to inform their future decisions about starting a family.

map of molecular genetic epidemiology of cystic fibrosis by World Health Organization
The detection rate of Cystic Fibrosis for the different countries of the world. A colour code is used for different detection rates, as shown in the inset. For the regions coloured in white, no data are available. Image credit: World Health Organization

But what about those diseases with a strong genetic component that can't be prevented yet?

Would you want to know that Alzheimer's or Parkinson's was waiting for you, without the ability to treat it? Whatever your thoughts, being able to identify those at risk is an important first step towards developing, or at least testing, a cure. In fact research is already underway to find an early diagnostic test for Alzheimer's and a survey on public attitudes to such a test9 showed demand could be high.

These are the ethical issues we, and our children, will have to consider as research continues to pick apart our genomes, and tease out the information.

The Fountain of Youth

Painting "The Fountain of Youth" by Lucas Cranach the Elder.
People have been searching for the fountain of youth for at least two and a half thousand years. Image credit: Lucas Cranach the Elder (public domain)
Perhaps the real question on everyone's lips is whether our DNA holds the key to an extended life. Researchers have been chasing the internal fountain of youth10 for some time – looking to see whether our genetics can answer questions, such as why we age, when it starts and whether it can be delayed.

While research into ageing in mice has revealed some interesting results11, leading to theories that have implications for possible anti-ageing interventions in humans-at the moment this is all just theory and won't be producing a miracle cream any time soon.

Your Ancestry

Most people are interested in what their DNA can tell them about their future, or what they'll be passing down the family line to their children, but our DNA also holds the key to our past. It has become so easy to look into our personal, biological codes and find out who our parents, children or siblings are that relationship testing is now incredibly common, and even used as a tool on TV programmes.

Tests that look into your genetic ancestry are now available to trace your maternal or paternal line back even further or look deeper into your ethnicity. This allows us to get a clearer idea of our place in the world, though how accurate the information that can be gleaned from such tests is still in debate.

But, rather than looking at the past, where is the future for the use of our personal genetic information?

Personalised Medicine

Our DNA holds more than just information about the genes that cause rare disease or our risk of complex disease, but can also, perhaps more significantly, reveal how we will respond to treatment for such diseases.

Rather than a 'one size fits all' approach to healthcare our genetic information can reveal how we would respond to certain drugs, an area of research known as pharmacogenetics, helping decisions about dosage or warning of adverse effects.

For example, information on genetic differences that affect the metabolism of warfarin12, which is prescribed for conditions caused by blood clots, is being used as part of a more accurate personalised dosage regime. In the future it's thought that this will expand, seeing drug companies developing tests to that will identify those who'll respond positively to medication. This will mean that your individual reaction to treatment can be tested before it's even prescribed13, improving the efficiency and success of treatment, personalised just for you.

Ten years after the full sequence of the human genome was published the amount that we've learnt as a species about our DNA has been massive. How well that data will translate into tangible information about our past and our future is still being debated, but the positive message is that we're in an age of discovery, laying foundations for massive strides forward into disease prediction, personalised medicine and perhaps even science fiction level predictions of our individual futures.

But whatever our DNA can tell us, it's best to look both ways at the traffic lights as no-one can ever really know what life has in store for them.

James Duval is a technology expert, whose interests lie in a wide-range of subjects.

why don't all references have links?

[1] Miko, I. (2008) Gregor Mendel and the principles of inheritance. Nature Education 1(1)
[2] Rettner, R. DNA: Definition, Structure & Discovery (2013) LiveScience
[3] Collins, FS et al. Finishing the euchromatic sequence of the human genome. Nature 431.7011 (2004): 931-945. doi: 10.1038/nature03001
[4] Herder, C. and Roden, M. (2011), Genetics of type 2 diabetes: pathophysiologic and clinical relevance. European Journal of Clinical Investigation, 41: 679–692. doi: 10.1111/j.1365-2362.2010.02454.x
[5] Feero, W Gregory, Alan E Guttmacher, and Mark I McCarthy. Genomics, type 2 diabetes, and obesity. New England Journal of Medicine 363.24 (2010): 2339-2350. doi: 10.1056/NEJMra0906948
[6] Morris, Andrew P et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature genetics 44.9 (2012): 981-990. doi:  10.1038/ng.2383
[7] Mark I. McCarthy and Joel N. Hirschhorn. Genome-wide association studies: potential next steps on a genetic journey Hum. Mol. Genet. (2008) 17 (R2): R156-R165 doi:10.1093/hmg/ddn289
[8] Frayling, Timothy M et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316.5826 (2007): 889-894.
[9] Wikler, Elizabeth, Robert Blendon, and John Benson. Would you want to know? Public attitudes on early diagnostic testing for Alzheimer's disease. Alzheimer's research & therapy 5.5 (2013): 43. doi:10.1186/alzrt206
[10] Jin, Kunlin. Modern biological theories of aging. Aging and disease 1.2 (2010): 72. PMID: 21132086 [PubMed] PMCID: PMC2995895
[11] Callaway, E. Telomerase reverses ageing process Nature News. (2010). doi:10.1038/news.2010.635
[12] Rettie AE, Tai G. The pharmocogenomics of warfarin: closing in on personalized medicine. Mol Interv. 2006 Aug;6(4):223-7. PMID: 16960144
[13] Ferrara, Joseph. Personalized medicine: Challenging pharmaceutical and diagnostic company business models. McGill Journal of Medicine: MJM 10.1 (2007): 59.

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