The European Science Foundation has revealed how impressive advances in our understanding of the genetic basis of disease were outlined at its third Functional Genomics Conference.
The mysteries of the human genome are slowly being revealed - but the more we uncover, the more complicated the picture becomes.
This was one key message to emerge from the ESF's third Functional Genomics Conference held in Innsbruck, Austria, on 1-4 October 2008.
Functional genomics describes the way in which genes and their products - proteins - interact together in complex networks in living cells.
If these interactions are abnormal, diseases can result.
Mike Taussig of Babraham Bioscience Technologies in Cambridge, UK, who organised the conference, said: 'The human genome is just a string of letters that has to be interpreted so that we can understand the function of the genes.' More than 450 scientists from across Europe were told of new developments in research ranging from pinpointing genes involved in diabetes and cancer to using the genetic sequences of different breeds of dog to throw light on human diseases.
Taussig added: 'What we have tried to do is bring together genome knowledge as it is now, the work which has been done, what it means in functional terms and where it affects our susceptibility to disease.
'Conferences like these are important because we try to cover a broad field - there are so many aspects of genomics that it would be impossible to encompass everything in a single lecture.
'It is useful for researchers who want to improve their general view of the field, because when you are immersed in one specialty you often do not appreciate how well-connected everything is.' Dr Patrik Kolar, head of the unit for genomics and systems biology in the European Commission's research directorate, said: 'Functional genomics and systems biology is an important and integral part of our health research programme because an understanding of these basic biological processes has huge potential and real applications for understanding disease, and when you understand disease you can design new drugs.' Kolar added: 'This kind of conference is one of the things that brings together the European community in functional genomics and I am happy to see that most of the participants are from collaborative projects funded though our Framework programme.' The unexpected complexity of the role of genes in disease was illustrated by Prof Mark McCarthy of the University of Oxford in the UK, who is searching for genes involved in type 2 diabetes.
Here, so-called genome-wide scans, which compare the genetic profiles of healthy people with those who have the disease, have so far revealed around 20 individual gene mutations that can be present in people with type 2 diabetes.
However, these variants explain only a small proportion of people's overall susceptibility to the condition.
McCarthy said: 'If you look at the variants we are finding from really large sample sizes, the effects are pretty small.
'For diabetes, weight and age are still better predictors of risk than the gene profile.
'So, on the one hand we are happy that we have found more signals than we might have imagined, but on the other hand we are disappointed because we are explaining so little of the variance.
'There is much work to be done to turn these association signals into function and mechanism.' Mutations in cancer genes have also turned out to be far more complicated than people might have first suspected.
Prof Mike Stratton, head of the Cancer Genome Project at the Wellcome Trust Sanger Institute in Cambridge, UK, led the team that mapped and identified the high-risk breast cancer susceptibility gene BRCA2.
His group is searching for particular types of gene mutations in cancer cells, and is revealing new insights into a class of mutation called rearrangement, where one gene breaks and is fused to another.
This rearrangement process could result in the creation of a rogue protein that promotes cancer.
Until recently it has been difficult to study rearrangement mutations because technologies have been lacking.
Stratton said: 'For many years we have wanted a screen that would allow us to extract rearranged parts of the cancer genome and make a catalogue.' Techniques have now been developed that are allowing researchers to pinpoint rearrangements and look at them in detail.
He added: 'New sequencing technologies are enabling us to look at a much larger number of rearrangements, allowing us to do genome-wide screens to identify fusion genes that could be cancer genes.
'It turns out there is a lot of complexity in these rearrangements that we would not anticipated before we started.' For example, it is becoming clear that while there are many more rearrangement mutations than people first thought, the majority of these seem to be effectively harmless, or 'passenger' mutations.
The significant mutations are the 'drivers', and these are much more elusive to track down.
Meanwhile Dr Kerstin Lindblad-Toh of Uppsala University in Sweden and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, is analysing gene mutations in different breeds of dog to throw light on human diseases.
Because dogs have been reared as distinct breeds with clear isolated populations, it is often easier to detect a genetic flaw than it is in humans, and dogs are susceptible to many similar diseases that occur in man.
Prof Olli Kallioniemi's team at the Institute for Molecular Medicine in Finland is working on ways to discover the effects of small strands of RNA, called small interfering RNAs (siRNAs), which can 'silence' genes and are showing promise in the fight against diseases such as cancer.
The Finnish researchers have developed new high-throughput techniques for testing thousands of different siRNAs on living cells in one go.
Kallioniemi said: 'This is a new cell array screening platform that we think has great potential for showing real utility in biological experiments.' Prof Patrik Brundin of Lund University in Sweden leads a team that is learning how best to repair the brain of people with neurodegenerative disorders such as Parkinson's disease, where a part of the brain called the substantia nigra degenerates, leading to slow movement and tremors.
Brundin told the meeting that his university has over the past 20 years transplanted brain tissue into 18 patients with Parkinson's, whose condition improved markedly and remained stable for many years.
However, certain unexplained side effects have arisen, including uncontrollable movements.
Brundin said: 'Nigral transplants have clearly worked well in select cases, but the technique needs refinement and is difficult to perform in large series of patients.' One key issue is a safe and sustainable supply of tissue, and embryonic stem cells could hold promise.
However, Brundin warned that many hurdles remain to be overcome.
He said: 'Today some people are saying that you can do this with stems cells, but stem cell transplantation to the brain is currently science fiction and should remain so for the moment - there are many challenges before we can do clinical trials.' In all, 12 key lectures were given at the meeting by leading scientists from Europe and the US.
In addition there were more than 40 symposia, with topics ranging from the role of proteins in ageing to new ways to disable viruses that cause influenza.
