Variations on a gene

Around 10 years ago scientists celebrated the milestone that revealed an entire sequence of a human genome, the information on our chromosomes. 

At the same time scientists had already started to discover clues to many diseases as a result of our genes by looking at sequence variations, or mutations, in our DNA.   

Combine these two activities and you get the Human Variome Project (HVP), an international collaboration whose mission is to identify, interpret and curate data about sequence variations in the Human genome responsible for disease. 

The knowledge derived will be applied to health care on a global scale. It’s been under way since 2006 and it’s the best thing since… well…. the discovery of DNA. 

Professor Richard Cotton at the University of Melbourne is the founder and driving force of the Human Variome Project. 

HVP has now grown to be an international consortium of over 1000 members from 80 countries, with the International Co-ordinating Office situated in the University of Melbourne and supported by the Howard Florey Institute. 

Paul Waring, the Chair and Professor of Pathology and Graham Taylor, the Chair of Medical Genomics at the Department of Pathology at the University are heading the Australian HVP national facility, which is part of an international network compiling the data and knowledge of human genetic variation. It involves collaborations with UNESCO, the World Health Organization, governments, scientists, diagnosticians, bio-informaticians and clinicians across the world, all channeling the wealth of genetic and clinical research knowledge into improving tomorrow’s global health care practices. 

Professor Cotton’s initial work was on developing early diagnostic techniques for diseases, to prevent disease progression and human suffering.  He worked on genetically-based metabolic diseases like Phenylketonuria (PKU), which can result in mental retardation if not treated early with strict diets. He and his colleague Dr David Danks recognised that DNA was the ultimate point of diagnosis and together they created a genetic research facility at the Murdoch Children’s Research Institute.  

Professor Cotton also started a journal called Human Mutation so scientists could share the data globally, but the amount of information coming in was astronomical and the information flow to health care was also needed. 

The University of Melbourne’s HVP operations manager Heather Howard says the facts are scientists no longer work in isolation.

“There has to be international effort to understand the mutations and variations of the human genome,” she says.  “We are a human community when it comes to the genome. Translating that knowledge will alleviate suffering and cut escalating costs in health care systems.”  

To put genetic diseases into perspective, if we all walked though a hypothetical metal detector at the airport that also detected our genetic mutations, every single one of us would trigger flashing lights and alarm bells. All of us have genetic variations that have the potential to give us health problems. 

We inherit them and we are carriers to the next generation where a mixing and matching could result in conditions like cystic fibrosis, thalassemi and haemophilia. Not only that, we can develop genetic variations within our lifetime as our cells grow, replicate and replace themselves, because there are copying errors in the DNA. At some point this can impact health. 

“It’s the variations in our DNA that make us who we are, it makes you unique, but it also provides clues to predispositions to illness, like Alzheimer’s, epilepsy, hypertension, coronary heart disease, cancer and diabetes,” Professor Cotton says..

“An American population study showed that 60 per cent of us will be affected by such genetic variations during our lifetime and this figure doesn’t include the cancer genes. Ten per cent of Australians are living with a rare disease, and 80 per cent of these have a genetic basis. In one way, as a group, being rare is becoming quite common.  So the project’s future health care outcomes will very likely involve someone in your future family.”

HVP’s charter on the face of it looks bigger than the proverbial Ben Hur, as it spans international and political borders. The HVP has an impressive charter of ethical knowledge-sharing, transparency and processes for interpreting data, ensuring standards are met globally. 

So far the Human Variome Project consortium has collected data on 5000 of our 20,000 genes. For clinicians challenges still lie ahead including implementing this health care and then ensuring the health care is available in developing nations.

www.humanvariomeproject.org