One small change to the DNA sequence can cause more weighty changes to the human body, according to a new study released today. The discovery comes thanks to a worldwide consortium of researchers that includes Professor and Chair of Quantitative Genetics at The University of Queensland (UQ), Peter Visscher, from the Queensland Brain Institute (QBI) and Diamantina Institute (DI) at UQ.

He and his team have found a single change in genetic sequence at the gene FTO had a significant effect on the variability of body mass index (BMI). BMI is a commonly used measure of obesity. It measures someone’s weight adjusted for his or her height.

Professor Visscher said that the genetic change, called a single nucleotide polymorphism (SNP), was the replacement of one nucleotide – the units that make up our DNA – with another. “They are the most abundant type of variation in the human genome,” he said. “SNPs occur normally throughout our DNA and most have no effect on our health, however, we’ve found one that does have a small but significant effect on variation in BMI.”

After analysing data from almost 170,000 people, he and his team established that those with a sequence variant in the FTO gene not only weighed more on average, but the measured weights varied more than in the group without the variant. The variability of BMI within the group with two copies of the variant was, in fact, 7 per cent larger than the group without the variant.

Professor Visscher said this equated to around half a kilogram difference in the standard deviation of weight. “So as a group, people with two copies of the weight increasing variant are a few kilograms heavier and vary more,” he said. Genetic differences in variability of specific traits have been seen in many plant and animal species but specific genes or mechanisms to explain the phenomenon had not been identified.

Professor Visscher’s study is the first to look systematically at genetic effects on variation of a complex trait in humans using a very large sample size. “The study is important because it demonstrates that genes can be found that affect trait variability. “This is a first step towards understanding how genes control variation,” Professor Visscher said.

This study is also the first to offer researchers an indirect method to measure genotype by environment interactions without having a measure of specific environmental factors. “If a gene interacts with specific environmental factors then this can be observed with our method,” Professor Visscher said.

“For example, if the effect of a gene on weight is smaller in people who physically exercise than in people who do not, then this will lead to less variation among people with two copies of the weight decreasing variant.

“In our study we did not measure specific environmental effects such as physical exercise so we can’t say for sure whether our results are due to a genotype-environment interaction.”

This is the second study Professor Visscher has published in the prestigious journal Nature this year. Earlier this year he identified that genetic differences also affect how intelligence changes across a lifetime. The work also suggested these changes in intelligence were largely influenced by environmental factors.

(Source: uq.edu.au)

The rare disorder Wolfram syndrome is caused by mutations in a single gene, but its effects on the body are far reaching. The disease leads to diabetes, hearing and vision loss, nerve cell damage that causes motor difficulties, and early death.

Now, researchers at Washington University School of Medicine in St. Louis, the Joslin Diabetes Center in Boston and the Novartis Institutes for BioMedical Research report that they have identified a mechanism related to mutations in the WFS1 gene that affects insulin-secreting beta cells. The finding will aid in the understanding of Wolfram syndrome and also may be important in the treatment of milder forms of diabetes and other disorders.

The study is published online in the journal Nature Cell Biology

“We found something we didn’t expect,” says researcher Fumihiko Urano, MD, PhD, associate professor of medicine in Washington University’s Division of Endocrinology, Metabolism and Lipid Research. “The study showed that the WFS1 gene is crucial to producing a key molecule involved in controlling the metabolic activities of individual cells.” That molecule is called cyclic AMP (cyclic adenosine monophosphate).

Insulin-secreting beta cells in the pancreas (above) cannot make enough cyclic AMP in patients with Wolfram syndrome. As a result, the pancreas produces and secretes less insulin, and the cells eventually die.

In insulin-secreting beta cells in the pancreas, for example, cyclic AMP rises in response to high blood sugar, causing those cells to produce and secrete insulin.

“I would compare cyclic AMP to money,” Urano says. “You can’t just take something you make to the store and use it to buy food. First, you have to convert it into money. Then, you use the money to buy food. In the body, external signals stimulate a cell to make cyclic AMP, and then the cyclic AMP, like money, can ‘buy’ insulin or whatever else may be needed.”

The reason patients with Wolfram syndrome experience so many problems, he says, is because mutations in the WFS1 gene interfere with cyclic AMP production in beta cells in the pancreas.

“In patients with Wolfram syndrome, there is no available WFS1 protein, and that protein is key in cyclic AMP production,” he explains. “Then, because levels of cyclic AMP are low in insulin-secreting beta cells, those cells produce and secrete less insulin. And in nerve cells, less cyclic AMP can lead to nerve cell dysfunction and death.”

By finding that cyclic AMP production is affected by mutations in the WFS1 gene, researchers now have a potential target for understanding and treating Wolfram syndrome.

“I don’t know whether we can find a way to control cyclic AMP production in specific tissues,” he says. “But if that’s possible, it could help a great deal.”

Meanwhile, although Wolfram syndrome is rare, affecting about 1 in 500,000 people, Urano says the findings also may be important to more common disorders.

“It’s likely this mechanism is related to diseases such as type 2 diabetes,” he says. “If a complete absence of the WFS1 protein causes Wolfram syndrome, perhaps a partial impairment leads to something milder, like diabetes.”

(Source: news.wustl.edu)

Hear the word “party” and memories of your 8th birthday sleepover or the big bash you attended last New Year’s may come rushing to mind. But it’s exactly these kinds of memories, embedded in a specific place and time, that people with depression have difficulty recalling.

Research has shown that people who suffer from, or are at risk of, depression have difficulty tapping into specific memories from their own past, an impairment that affects their ability to solve problems and leads them to focus on feelings of distress.

In a study forthcoming in Clinical Psychological Science, a new journal of the Association for Psychological Science, psychological scientists Hamid Neshat-Doost of the University of Isfahan, Iran, Laura Jobson of the University of East Anglia, Tim Dalgleish of the Cognition and Brain Sciences Unit, Medical Research Council, Cambridge and colleagues investigated whether a particular training program, Memory Specificity Training, might improve people’s memory for past events and ameliorate their symptoms of depression.

In Iran, the researchers recruited 23 adolescent Afghani refugees who had lost their fathers in the war in Afghanistan and who showed symptoms of depression. Twelve of the adolescents were randomly assigned to participate in the memory training program and 11 were randomly assigned to a control group that received no training.

All of the adolescents completed a memory test in which they saw 18 positive, neutral, and negative words in Persian and were asked to recall a specific memory related to each word. Their responses were categorized as either a specific or a non-specific type of memory. They also completed questionnaires design to measure symptoms of depression and anxiety symptoms.

For five weeks, the adolescents assigned to the training attended a weekly 80-minute group session, in which they learned about different types of memory and memory recall, and practiced recalling specific memories after being given positive, neutral, and negative keywords.

At the end of the five weeks, both the training group and the control group were given the same memory test that they were given at the beginning of the study. And they took the memory test again as part of a follow-up visit two months later.

The adolescents who participated in the training were able to provide more specific memories after the training than those who did not receive intervention. They also showed fewer symptoms of depression than the control group at the two month follow-up. The researchers found that the relationship between participant group (training or control) and their symptoms of depression at follow-up could be accounted for by changes in specific memory recall over time.

These findings are promising because they suggest that a standalone training program that focuses on specific memory recall can actually improve depression symptoms.

Based on the results of this study, Jobson, Dalgleish, and colleagues conclude that, for individuals suffering from depression, “including a brief training component that targets memory recall as an adjunct to cognitive behavioral therapy or prior therapy may have beneficial effects on memory recall and mood.”

What makes a person altruistic? Philosophers throughout the ages often pondered the question but failed to get concrete answers. New research from the University of Zurich in Switzerland shows that the answer may lie in our brains, or more accurately, that the volume of a small brain region can influences one’s predisposition for altruistic behaviour. The results, presented in the journal Neuron, indicate that individuals who behave more altruistically than others have more grey matter at the junction between the parietal and temporal lobe. This shows for the very first time that there is a connection between brain anatomy, brain activity and altruistic behaviour.

Contary to past studies that showed that social categories like gender, income or education cannot fully explain differences in altruistic behaviour, recent research in the area of neuroscience have demonstrated that differences in brain structure might be linked to differences in personality traits and abilities. Now, for the first time, a team of researchers from the University of Zurich, headed by Ernst Fehr, the director of the Department of Economics, demonstrates that there is a connection between brain anatomy and altruistic behaviour.

For their study, the researchers asked volunteers to divide money between themselves and someone else who was anonymous. The participants always had the option of sacrificing a certain portion of the money for the benefit of the other person. The monetary sacrifice was considered to be altruistic because it helped someone else at one’s own expense. The researchers found major differences in this respect: some participants were almost never willing to sacrifice money to benefit others while others behaved very altruistically.

Previous studies showed that the place where the parietal and temporal lobes meet is linked to the ability to put oneself in someone else’s shoes in order to understand their thoughts and feelings, an ability the researchers considered closely related to altruism.

So the team hypothesised that individual differences in this part of the brain might be linked to differences in altruistic behaviour. And, according to Yosuke Morishima, a postdoctoral researcher at the Department of Economics at the University of Zurich, they were right: ‘People who behaved more altruistically also had a higher proportion of grey matter at the junction between the parietal and temporal lobes.’

The researchers also discovered that the subjects displayed marked differences in brain activity while they were deciding how to split up the money. In the case of selfish people, the small brain region behind the ear is already active when the cost of altruistic behaviour is very low. In altruistic people, however, this brain region only becomes more active when the cost is very high. The brain region is activated especially strongly when people reach the limits of their willingness to behave altruistically. The reason, the researchers suspect, is that this is when there is the greatest need to overcome man’s natural self-centeredness by activating this brain region.

Said Dr Fehr: ‘These are exciting results for us. However, one should not jump to the conclusion that altruistic behaviour is determined by biological factors alone.’

It appears that the volume of grey matter can also be influenced by social processes. According to Dr Fehr, the findings therefore raise the question as to whether it is possible to promote the development of brain regions that are important for altruistic behaviour through training or social norms.

(Source: cordis.europa.eu)