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The MHC on the short arm of chromosome 6 is the most gene-dense region of our DNA with around 230 genes all crammed into this stretch of our genome.

The MHC, or major histocompatibility complex, is known to play a pivotal role in our immune system, and around a third of the genes encoded there are known to have immune functions (the functions of all the genes are not known as yet, so it could be more).

So it’s not surprising that DNA variations in this region have been linked to many autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and coeliac disease. But the MHC has also been linked to diseases not related to the immune system, including breast cancer, asthma, infectious diseases and the adverse effects of certain drugs. It’s the genetic region with the largest number of diseases associations, period.

But finding a genetic link to a condition is one thing. Determining the specific DNA changes that cause the increased risk of disease is another.

‘It’s a long-standing problem,’ according to Dr Julian Knight of the Wellcome Trust Centre for Human Genetics [WTCHG] at Oxford University, and it’s a problem that is particularly testing in the MHC.

The reason is that large lengths of DNA in the MHC, including whole lines of genes, tend to get inherited together. So people end up grouped with whole sets of DNA variations in common.

Because this co-inheritance of variations, or ‘linkage disequilibrium’, is particularly strong in the MHC, it is very difficult to unpick what lies behind any one DNA change linked with a disease. It could be something to do with that particular gene that is having an effect, or it could be another of the many genes closely coupled to it.

Then there is the problem of defining at what level the change in DNA might be acting. The body has many layers of control to make sure genes are only active in the right places and in the right amounts.

The central process is the same of course – a DNA sequence is read out into RNA code, from which proteins are produced – but at each stage there are checks and balances to make sure each gene and its products are working at the right level to keep the biological processes they encode ticking over.

Perhaps a DNA change might alter the structure of a protein encoded by a gene, but it may also alter the activity of that gene or another it controls. It could turn a gene on or off like a switch, turn its activity up or down like a volume dial, or change the final form of the protein that is produced.

Claire Vandiedonck, Julian Knight and colleagues set out to probe some of these possibilities by investigating how sets of co-inherited DNA variants in the MHC might lead to changes in ‘gene expression’.

Controlling gene expression – the amount of RNA produced from a gene – is a way of turning up and down the gene’s activity.

The researchers mapped gene expression across the MHC for three common sets of coinherited DNA variants people can have that are known to be associated with disease. Their results were recently published in the journal Genome Research.

To do this they had to design and construct their own custom DNA chip to be able to deal with the sequence variety in the MHC region. ‘We just couldn’t take an off-the-shelf microarray to get these results,’ Julian explains.

They found that the set of variants you have in the MHC does lead to differences in gene expression, and this was a common effect. 96 out of 230 genes in the MHC showed differences in expression.

‘There were a lot more differences in gene expression that we might have guessed,’ says Julian. ‘There was also a great deal of expression from areas of DNA in between genes; a third of the RNAs produced come from outside of known genes.'

It’s likely that these are non-protein-coding RNAs. That is, these bits of DNA sequence are read off to produce RNA. But no protein is then made from the RNA sequence.

It’s been gradually recognised over the past decade and more that noncoding RNAs play an important role in regulating gene activity – it’s another layer of control to the action of our genes. This study may offer an indication of just how important these RNAs are in regulating genes in the MHC.

The researchers also found a lot more ‘alternative splicing’ in the MHC than happens in other regions of our genome.

Alternative splicing describes a process where the same initial piece of RNA produced from a single gene is cut up and stuck back together in different ways to give different proteins. The result is shorter and longer proteins, potentially carrying out different roles in the cell.

‘The greater alternative splicing in the MHC will mean a greater diversity in the proteins produced from the DNA sequence,’ explains Julian. ‘It increases the diversity of a region that already has the greatest number of possible gene variants.’

But most importantly, pinpointing where gene expression differs could identify a set of candidates for which genes are causing increased risk of some autoimmune diseases. That’s what this study takes a step towards. These candidate genes can then be looked at in more detail.

‘We now have a route map of gene expression in the MHC that can help us understand what lies behind gene associations with various common diseases,’ Julian adds. ‘These findings have underlined the fact that we need to understand gene regulation as well as DNA sequence.’

He predicts that there will be many more of these studies in the future, as geneticists move on to unpick what lies behind genes known to be connected to many common diseases.

It seems that finding connections between DNA sequence and common conditions is one thing, but understanding how they are connected will involve investigating the many different levels of gene control and regulation there are in the body.

We’ll need to expand our knowledge of how our sequence of DNA letters is read out in organised phrases, sentences and whole paragraphs to really get the language of genetics and what it means for us. Expect stories about our genetics to get more complex before they get clearer.

It was on 1 January 1995 that a wave over 25 metres high was recorded at the Draupner platform in the North Sea off the coast of Norway.

Ever since researchers have been attempting to understand the mechanisms which produced the ‘Draupner wave’ and are responsible for other abnormally large or ‘freak’ waves.

In Proceedings of the Royal Society A this week Thomas Adcock and Paul Taylor of Oxford University’s Department of Engineering Science report that their new analysis may have the answers.

I asked Thomas about giant waves, predictions and The Poseidon Adventure…

OxSciBlog: How have people explained freak waves in the past?
Thomas Adcock: Freak waves will occur when the crests of many small waves come together to form a large wave. The random nature of waves means that this will occasionally happen – we are interested in any mechanism which will enhance this focusing.

Waves may be steered, either by currents (for instance, off South Africa) or by the sea-bed (such as near Hawaii), to produce abnormal waves. If all the waves are all moving in the same direction, then complex non-linear interactions can produce wave focusing. However, real ocean waves never all move in quite the same direction and it is a point of contention as to whether this really causes freak waves at sea.

OSB: Why is the Draupner wave interesting to study?
TA: The Draupner wave is one of few (possibly the only) instance of a high quality measurement of a freak wave in deep water. None of the mechanisms we discussed seem responsible for producing this wave.

One interesting feature is that under a large wave we expect to see a small but long and low depression (up to 1m deep) under a large wave group. Dan Walker, when a DPhil student in Oxford, found that the opposite was true for the Draupner wave. This confirms that there was something unusual about this wave.

OSB: What clues does it give to how freak waves form?
TA: The occurrence of the long low rise rather than a depression for the Draupner wave leads us to suggest the giant wave is the sum of two wave groups that were travelling at roughly right angles through each other. Mariners know that crossing sea-states are very unpleasant for the crew and potentially dangerous for ships – the wave which hit the Queen Mary in World War II, and which inspired the film The Poseidon Adventure, occurred in a crossing sea.

The idea for this paper was inspired by watching this video showing an unusual wave hitting a ship from the side. We began to think what would the consequences be if this was how the Draupner wave formed – and we realised this would explain the features which had been puzzling people about the wave.

OSB: How might your findings help to predict/mitigate their impact?
TA: Engineers and scientists are quite good at forecasting the general sea-state; Radio 4 long wave listeners will be familiar with the shipping forecast. If we can identify in which sea-states freak waves are likely then we can use this in design. For instance, if we forecast a storm in which freak waves are likely then we could route a ship around the storm.

OSB: What further research is needed in this area?
TA: Whilst scientists understand the basic features of most sea-states fairly well, we do not really understand at a local level the physics when a sea-state changes rapidly – for example if the wind suddenly starts blowing in a different direction. What we really need is far more high quality measurements of individual large waves – without this we cannot know whether our theories are right.

Dr Thomas Adcock and Professor Paul Taylor are based at Oxford University's Department of Engineering Science.

The full results of a trial show that people with chronic kidney disease can reduce their heart risk by taking a combination drug that lowers levels of ‘bad’ cholesterol.

Taking cholesterol-lowering drugs such as statins to combat heart disease is pretty standard in people without kidney problems.

But there was a great deal of uncertainty about using such treatments in people with impaired kidney function because of concerns about drug toxicity (the kidneys are key in getting rid of harmful substances). This is despite kidney patients being at high risk of heart problems.

The study findings were first reported at an American Society of Nephrology conference in Denver in November, and in our news story at the time, but the full results have now been published in The Lancet.

The SHARP trial found that patients receiving the daily pill – a combination of simvastatin and ezetimibe produced by Merck – had one-sixth fewer heart attacks, strokes or operations to unblock arteries than those receiving a placebo ‘dummy’ pill. And importantly, there were no safety concerns with the drug, which is already being taken by many people with normal kidney function to lower their cholesterol.

Professor Colin Baigent of the Clinical Trial Service Unit (CTSU) at Oxford University, the trial’s principal investigator, says: ‘This is good news for kidney patients. People with this disease are in desperate need of new treatments not only to combat the disease itself, but also to reduce pain and suffering, such as heart attacks and strokes, due to side effects of the illness.

‘Over half of people with kidney disease will eventually be killed, not by their kidney disease, but by cardiovascular diseases. We now know there is something we can do about this – and I believe this study will have a positive impact on the lives of many millions of people currently being treated for chronic kidney disease in the UK and around the world.’

Chronic kidney disease is very common, affecting up to one in twenty of the middle-aged population, and substantially more of those who are older. Although people with chronic kidney disease are known to have an increased risk of a stroke or heart attack, it has been very unclear what treatments could prevent these conditions in this group of patients.

Dr Martin Landray, co-principal investigator of the trial at CTSU, says: ‘Some doctors had thought that damaged kidneys might cause a type of cardiovascular disease that would not be preventable by lowering cholesterol, but the SHARP trial showed clearly that lowering cholesterol does reduce the risk of cardiovascular disease in people with kidney disease.’

The culmination of this long-running, large-scale trial involving 9,500 patients in 18 countries – planning for which began in the 1990s – marks the end of work in which Colin Baigent has had a great personal interest.

He developed kidney disease himself 30 years ago and needed dialysis before receiving a kidney transplant. He is clear that, ‘Many of the young people who were receiving dialysis at the same time as me are now dead from cardiovascular disease.

‘Progress in the prevention of cardiovascular disease with drug treatments in kidney patients has lagged behind other patient groups,’ he says. ‘The research community has tended to neglect testing promising treatments in kidney patients, partly because of fears that some drugs may turn out to be dangerous in people with damaged kidneys.

‘The SHARP study now shows clearly, however, that it is possible to find safe and effective drugs for the prevention of cardiovascular disease in kidney patients.’

With over 3% of the NHS budget currently devoted to treating kidney patients, and that figure likely to rise, there is a need for better care of such patients, and the prevention of cardiovascular disease should be a high priority, says Colin Baigent.

Scientists have identified a new type of supernova or exploding star which is ten times brighter than any other type of stellar explosion.

Astrophysicist Dr Mark Sullivan of Oxford University’s Department of Physics is among researchers reporting the discovery in this week's Nature.

Until now scientists have been aware of two basic types of supernova – ‘Type Ia supernovae’, which are thermonuclear explosions of small and very dense stars called white dwarfs – and slightly fainter ‘core collapse supernovae’, brought about by the deaths of very massive stars (possibly with masses up to 50-100 times that of the sun). This second type of supernova was featured in the BBC’s Wonders of the Universe.

The new research is published by 27 academics from Oxford, Caltech, the universities of California and Toronto, the Weizmann Institute and other leading institutions. 

It demonstrates the existence of a new, exceptionally bright, kind of supernova, 10 times more luminous than most Type Ia supernovae and with unique characteristics.

These new supernovae show no trace of hydrogen or helium, and emit significant ultraviolet flux for long periods, which means the exploding star was probably low in metals and from a very faint galaxy with few stars. Its light output decays in a way that suggests something other than radioactivity - which powers the light from all other supernova explosions - is the cause of its deterioration.

‘The mechanism of the explosion is unknown, which is the most exciting part,’ Dr Sullivan says. ‘The high luminosity means that these supernovae can be used to probe the very distant universe.’

Because the new supernovae are rare, it took a new type of search to find them - the Palomar Transient Factory [PTF]. The PTF is a systematic search for cosmic explosions and uses the Palomar Observatory in San Diego.

Oxford University is helping fund the project via the John Fell OUP Research Fund and the research is providing material for Galaxy Zoo Supernova which featured on the BBC’s Bang Goes the Theory.

‘Practically every chemical element in the universe (other than hydrogen and helium) gets made in stars,’ Dr Sullivan says. ‘This research has implications for both the study of stellar evolution and the way in which elements in the Universe were formed.’

Erasing data, rather like cleaning a house, should be hard, hot work.

But now a team including Oxford University’s Vlatko Vedral have shown that, in the quantum world at least, it doesn’t always have to be.

They report in this week’s Nature that, under certain conditions, deleting data held in a quantum computer could actually cool the environment down rather than heating it up.

‘Everyone who has ever worked with a computer knows that they get hotter the more we use them,’ Vlatko writes in Scientific American.

‘Physicist Rolf Landauer argued that this needs to be so, elevating the observation to the level of a principle,’ Vlatko comments. ‘The principle states that in order to erase one bit of information, we need to increase the entropy of the environment by at least as much. In other words we need to dissipate at least one bit of heat into the environment (which is just equal to the bit of entropy times the temperature of the environment).’

This heat threshold is something that could potentially hold supercomputers back: that there comes a point when deleting data to perform fresh computations will create so much heat that any system will no longer be able to cool itself down.

Saying that you can erase information from a system and cool the environment at the same time is, he says, a bit like telling a physicist that perpetual motion is possible.

However, the team’s new theoretical study has turned up an exception based on the idea that entropy, the measure of disorder of a system which should always increase, can be ‘negative’ in quantum mechanics.

Vlatko writes: ‘Adding negative entropy is the same as taking entropy away. The key phenomenon behind it is the spookiest of all quantum phenomena, entanglement.’

In a Nature commentary Patrick Hayden describes the team’s findings like this, that: ‘instead of having to invest work to erase the qubit [quantum bit], the process of erasing the qubit can actually generate work, like a tiny quantum-logical wind turbine.’

Vlatko adds: ‘The implications of our result could be important for superfast and superefficient computers. Current computers waste about 10,000 units of heat per computational step. If we can somehow control and manipulate entanglement between the microprocessor and the computer memory, then we could erase computations to make room for new ones, but keep the environment cool.’

More about this work in Vlatko Vedral's article for Scientific American.

Professor Vlatko Vedral is based at Oxford University's Department of Physics.