The clues in the code

Associate Professor VICKY CAMERON is a geneticist at the University of Otago, Christchurch. She specialises in the impact of genetics on heart disease. She has inherited a gene variation linked to a higher risk of developing heart disease, which is the subject of much current research in Christchurch and overseas.

In the past decade, scientists' understanding of genetics has accelerated.

The rate of progress is so significant, it is comparable with Columbus discovering the Americas and James Cook exploring the Pacific within five years of each other.

Some highlights have hit the headlines, including the recent sequencing (decoding) of the Neanderthal genome and, lately, the generation of a bacteria-like cell regulated by a completely man-made set of genes.

New developments have allowed scientists to "read" an individual's unique DNA sequence at an affordable cost and within a realistic timeframe. DNA variations associated with inherited risk for many diseases can be identified. New technologies are also revealing genetic reasons for different responses to drugs, bringing us closer to the goal of personalised medicine.

Major genetic initiatives

In 1990, The Human Genome Project began to determine the sequence, or code, that makes up human DNA.

During the project, technology has advanced dramatically.

It took 10 to 15 years for the first draft of the human genome. A similar amount of sequencing can now be performed in three days. However, this includes only raw data (akin to providing sentences from a book in a jumbled order), not the complex analysis required to link these into something meaningful.

A second project, The International Hap Map Project, was launched in 2002. It created a catalogue of 1.4 million common single-base differences, specifying their exact locations across the entire human genome.

This information is freely available to researchers worldwide. It has been critical to advances in understanding a host of complex diseases, such as heart disease, that result from an interaction of multiple genes and environmental factors, such as diet or sun exposure.

A third initiative, Genome Wide Association, has altered the face of medical genetics. Only 15 years ago, understanding the causes of diseases arising from complicated interactions of multiple genes and environmental factors seemed an impossible goal.

But now, Genome Wide Association technology makes miniature "DNA chips" that record all genetic variants carried by an individual.

Scientists can now compare the gene chips of thousands of people and see common DNA variants among patients who suffer from the same disease.

In the past few years, scientists have identified genetic variants associated with hundreds of human diseases or clinical characteristics, such as obesity and cholesterol.

Mysteriously, some of the DNA regions associated with disease are not located within any known genes but in areas between genes, previously considered "junk DNA".

For example, a region on chromosome 9 not located within or near any known genes is strongly associated with the risk of heart disease.

Within the same chromosome 9 region, other DNA variants have been shown to be independently associated with different diseases, including type-2 diabetes and melanoma.

Several companies are now offering personal genetic testing for a fee. The reports are meant to give customers information about either a limited number of medical conditions for which they may be at risk, or their ancestral background. However, there are concerns about the validity of some of the testing and whether the reports are meaningful for customers without a doctor helping them understand the test results.

Most of the gene tests will not predict whether individuals with certain gene combinations will definitely get a specific disease, because there are many factors in the environment that interact with our genetic makeup to cause these diseases.

What do these developments mean for us?

People's responses to drugs - or pharmacogenetics - are influenced by numerous genetic and environmental factors, which determine why some patients, for example, experience no benefit or side effects from some medications.

Already genetic technology has improved the understanding of complex diseases and, in some cases, changed what dose of drugs or which treatments are most appropriate for an individual. This is the holy grail of personalised medicine that has been promised since the origin of the Human Genome Project but has not happened until now.

Should we be concerned about powerful genetic technologies?

Science in developed countries operates under a number of regulatory bodies to protect individual privacy and the ethics of medical and genetic research. These regulations are becoming more stringent to address the unease of a public concerned about the potential abuse of genetic information, the spectre of eugenics (selective breeding to improve the human race) or even exploitation of an individual's genetic information for commercial gain. Codes of practice are set not by the conscience of individual scientists, but by a mandate of public opinion and expert advisers. The quiet revolution in new genetic technology is changing the face of medical genetics, but, with the appropriate constraints, has the power to do a world of good.

What are genes and how do they affect our risk of disease?

All humans have the same set of genes, approximately 24,000 of them. Each gene carries part of the inherited information essential to build and maintain an organism, cell-by- cell, and to pass genetic traits to offspring. Each gene consists of a span of DNA that spells out information in a sequence of "bases" (a subunit of DNA) that makes up our genetic code. However, the code is not precise and it is these variations that make us individuals and can affect our susceptibility to certain diseases and our body's response to drugs and environmental factors. Every species has its own genome, which is all the genetic material in an organism, including its chromosomes, genes and DNA.

The coronary heart disease puzzle

Coronary heart disease is New Zealand's biggest killer. Genetic factors make some families more susceptible to developing it. In 2007, several large, international studies looked at all gene variations relating to heart disease across thousands of coronary patients and healthy people. These "genome-wide association studies" all identified a region on chromosome 9 as associated with coronary disease risk. However, it was not clear how inheriting this "hot spot" influences heart disease. Recently, researchers at the University of Otago, Christchurch, led by Associate Professor Vicky Cameron, investigated the impact of the chromosome 9 region on a person's survival after a diagnosis of heart disease. Cameron has a personal interest in this subject, as she inherited the "hot spot" gene from both her parents. This led her to investigate whether carrying the risk variant was associated with better or worse survival in about 2000 heart disease patients and healthy people. Dr Katrina Ellis worked with Cameron on the project. They found the progression of heart disease in people who carried the chromosome 9 variation was no different from those without it. Patients with it were no more likely to die or be readmitted to hospital up to nine years after a heart attack. However, people with it were likely to develop heart disease three to five years, on average, earlier than others. The research, soon to be published in Circulation: Cardiovascular Genetics, was funded by the Health Research Council and National Heart Foundation of New Zealand.

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