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Inactive genes surprisingly common in humans

(Medical Xpress) -- Every person carries on average 100 variants that disable genes - yet very few suffer ill effects, an international team of researchers led by Yale University and Wellcome Trust Sanger Institute report in the Feb. 17 issue of the journal Science.

Scientists were surprised to find so many of these variants in healthy individuals because loss of gene functions leads to diseases such as cystic fibrosis and muscular dystrophy. The findings will allow researchers to better pinpoint new disease-causing mutations by helping them differentiate between frequently occurring but harmless genetic variants and rare dangerous ones, the authors say.

The study is the latest coming from the 1000 Genomes Project, a massive international personal genomics effort aiming to provide a comprehensive resource of human genetic variation that will help speed the development of personalized therapies based on the genetic makeup of patients.

The team analyzed the genomes of 185 individuals from Europe, Asia, and Africa looking for so-called loss-of-function variants, mutations that disable a gene’s ability to make protein.

“Even though previous studies have shown that loss-of-function variants exist in the general population, their extent has been underappreciated. This is the first time we have a definite sense of variation in the numbers of functional genes between individuals,” said Suganthi Balasubramanian, the lead Yale author in the paper.

The study shows no individual has a full complement of functional genes.  On average, each individual has 20 genes where both copies of the gene are disabled.

“In total, this study identified 253 such genes. This means at least one percent of human genes can be shut down without causing serious disease,” explains Mark Gerstein, Albert L. Williams Professor of Biomedical Informatics, co-senior author from Yale University.

The catalog of loss-of-function variants in healthy genomes will be invaluable to clinicians as they begin to use personalized genomic analysis to help diagnose and treat disease, the authors say.

 “Our research will be beneficial for current DNA sequencing studies underway in disease patients,” says Dr Chris Tyler-Smith, co-senior author from the Wellcome Trust Sanger Institute. “The common loss-of-function variants were typically in genes that can be shut down without causing serious effects.”

Scientists also found a large number of extremely rare variants and “we believe these will be the most interesting cases in terms of a potential role in human disease,” says  Dr Daniel MacArthur from the Wellcome Trust Sanger Institute, lead author on the study.

The study also showed that as many as a quarter of the loss-of-function variants involve large stretches of DNA (so-called structural variants), rather than mutations of single base pairs, which were believed to be the primary source of genetic variation. Structural variants are not yet well characterized in the human population and represent a major Yale contribution to 1000 Genomes Project. The Yale team is also looking at variants outside of regions of DNA that code for genes, an area that constitutes the vast majority of the genome.

More information: "A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes," by D.G. MacArthur, Science, 2012.

Provided by Yale University

"Inactive genes surprisingly common in humans." February 16th, 2012. http://medicalxpress.com/news/2012-02-inactive-genes-surprisingly-common-humans.html

Posted by
Robert Karl Stonjek

Aging studies suggest older people are happier

Lab manager Julia Harris (right) places glasses with a mobile tracking device on Derek Isaacowitz, associate professor of psychology, in the Lifespan Emotional Development Lab (LEDlab). Credit: Mary Knox Merrill.

(Medical Xpress) -- We get wrinkles. Our hair turns gray, or we lose it altogether. Our job prospects diminish and our chances of incurring disease increase. Researchers across the globe focus their efforts on increasing our life span because so many of us believe getting old stinks.

But that may not be so, according to Derek Isaacowitz a newly appointed associate professor of psychology in the College of Science. Contrary to popular opinion, he says, older people are happier than their younger counterparts.

“Self-report studies of happiness typically find that older people are happier,” Isaacowitz explains. But for the psychologist, who joined the Northeastern faculty after spending a decade at Brandeis, self-reporting is not enough. He wants to know why older people are happier.

To tackle this question, he employs a state-of-the-art testing method not typically used in aging research: eye tracking.

Eye tracking, he says, follows a participant’s eye movements by taking 60 snapshots of his or her pupils each second. Isaacowitz couples self-reports of mood with eye tracking data to pinpoint exactly what a person is looking at while rating his or her mood.

“We can analyze data in a moment to say, ‘how does what you’re looking at relate to what you feel?’” Isaacowitz says.

Results revealed that older and younger participants might regulate their emotions in vastly different ways. As Isaacowitz puts it, “One way of regulating emotion is to change your thinking about something, to see something upsetting and say ‘no’.” This seems to be the strategy of most younger test subjects.

On the other hand, older people tend to look at negative images less often, possibly indicating that they regulate emotion by distracting themselves from negative stimuli.

Isaacowitz says this makes sense, since the elderly tend to have fewer resources than the young: “If I made you really tired or gave you something else to do, it would be easier to distract instead of reappraise.”

While Isaacowitz’ research has already confirmed a cognitive difference between older and younger people, many questions remain about how this difference may relate to the role of age in regulating day-to-day emotion.

Isaacowitz was eager to join the Affective Science Institute at Northeastern and help advance the university’s strength in aging research. He says his lab on campus will conduct a number of new studies, including an analysis of subjects in a more natural environment. “We’ll be nicely set up to do that in the lab here,” he says.

Provided by Northeastern University

"Aging studies suggest older people are happier." February 16th, 2012. http://medicalxpress.com/news/2012-02-aging-older-people-happier.html

Posted by
Robert Karl Stonjek

Computer programs may be able to identify individuals most at risk of anxiety, mood disorders

 

An MRI scan of the sagittal section of the brain. Credit: Wellcome Images.

(Medical Xpress) -- Computer programs can be taught to differentiate between the brain scans of healthy adolescents and those most at risk of developing psychiatric disorders, such as anxiety and depression, according to research published yesterday in the open access journal PLoS ONE. The research suggests that it may be possible to design programs that can accurately predict which at-risk adolescents will subsequently develop these disorders.

There are no known biomarkers - biological measures - that can accurately predict future psychiatric disorders in individual adolescents. Even genetic risk cannot accurately predict individual risk for future psychiatric illness: for example, a family history of bipolar disorder confers a 10 per cent risk of future bipolar disorder, as well as a 10 to 25 per cent risk of disorders such as attention deficit hyperactivity disorder, major depression and anxiety disorders, but it is impossible to accurately determine whether an individual will develop these disorders.

The early identification of individuals at high risk of future psychiatric illness is critical. Most psychiatric disorders typically have an onset in adolescence or early adulthood, and early detection and treatment could potentially delay, or even prevent, the onset of these illnesses in high-risk adolescents.

Now, a team of researchers led by Dr Janaina Mourao-Miranda, a Wellcome Trust Research Career Development Fellow at UCL (University College London), has shown that computer programs can distinguish between brain scans of healthy but genetically at-risk adolescents and healthy low-risk controls.

Sixteen healthy adolescents who each had a parent with bipolar disorder took part in the study, along with 16 healthy adolescents whose parents had no history of psychiatric illness. The adolescents performed an emotional face gender-labelling task in a functional magnetic resonance imaging (fMRI) scanner, which measures activity in the brain.

In the first experiment, the faces presented had happy or neutral expressions; in the second experiment, the faces had fearful or neutral expressions. The researchers then used a computer program capable of machine learning to predict the probability that an individual belonged to the low-risk or the at-risk group.

They found that the program was accurate in three out of four cases. The predictive probabilities were significantly higher for at-risk adolescents who subsequently developed a psychiatric disorder, such as anxiety and depression, than for those who remained healthy at follow-up. This suggests that it may be possible, in time, to develop a computer program able to identify those individuals at greatest risk of developing psychiatric disorders.

Interestingly, the researchers found that the best discrimination between at-risk and low-risk adolescents occurred when neutral faces were presented in the happy face experiment. This supports previous studies that suggest that individuals diagnosed with anxiety or mood disorders are more likely to perceive neutral faces as ambiguous or potentially threatening.

"Combining machine learning and neuroimaging, we have a technique which shows enormous potential to help us identify which adolescents are at true risk of developing anxiety and mood disorders, especially where there is limited clinical or genetic information," says Dr Mourao-Miranda.

Coauthor Professor Mary Phillips, from the Clinical and Translational Affective Neuroscience Program at University of Pittsburgh, adds: "Anxiety and mood disorders can have a devastating effect on the individuals concerned and on their families and friends. If we are able to identify those individuals at greatest risk early on, we can offer early and appropriate interventions to delay, or even prevent, onset of these terrible conditions."

The study was funded by the National Institute of Mental Health, the Wellcome Trust and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazil).

More information: Mourao-Miranda J et al. Pattern recognition and functional neuroimaging help to discriminate healthy adolescents at risk for mood disorders from low risk adolescents. PLoS One 2012 (epub ahead of print).

Provided by Wellcome Trust

"Computer programs may be able to identify individuals most at risk of anxiety, mood disorders." February 16th, 2012.http://medicalxpress.com/news/2012-02-individuals-anxiety-mood-disorders.html

Posted by
Robert Karl Stonjek

A mile in their shoes: understanding empathy

Credit: iStockphoto.com

The human brain evolved to ensure our survival. One example of that survival instinct is our sense of competition – historically, it’s part of what drives us to wage wars over power and resources. But an equally powerful survival tactic is our ability to love and cooperate with others.

“A lot of times, that story never gets told,” says Karen Gerdes, a social worker at ASU. She is interested in empathy, which is the ability to perceive the world from other people’s points of view and to feel what they are feeling. Empathy is a complex emotion because it involves both unconscious, involuntary responses and conscious, cognitive processes. For example, suppose you’ve had a traumatic experience, like losing a loved one.

“You see someone else who is going through that experience, and your brain automatically starts firing as if it’s happening to you. That helps you to understand a little bit better about what that person is going through,” Gerdes says.

People who are very empathic tend to be more understanding and have stronger relationships. For a social worker, empathy is also an essential part of the job.

“Social work is all about improving quality of life for people,” Gerdes says. “We do that by helping them to be their better self, and by creating a society that is more supportive. Empathy is at the core of both of those things.”

Gerdes is an associate professor in the School of Social Work in the College of Public Programs. She began studying empathy in 2006 after learning about new research from the field of social cognitive neuroscience.

“They’ve confirmed that our brain is set up to process information in a way that helps us to be more empathic and cooperative,” Gerdes said.

Using functional magnetic resonance imaging (FMRI), neuroscientists can watch empathy in action in a person’s brain through the interaction of four neural networks – groups of neurons that perform specific functions. When all four of these neural networks are engaged, that person is expressing empathy.

Have you ever felt yourself smiling after seeing a stranger laugh, or feeling sad after watching someone else cry?

This emotional “mirroring” phenomenon is called affective sharing, and it’s one of the observable neural networks that define empathy.

“People that are especially sensitive could find themselves feeling angry or irritable or annoyed and not even know why, and it’s because they’re picking up on the emotion of another person who is actually feeling those things,” Gerdes says.

Affective sharing is an automatic, unconscious phenomenon, but there’s more to empathy than just mirroring another person’s emotions. You also must be able to put yourself in their shoes. This is the function of another neural network, called perspective taking. It’s that cognitive ability to understand a situation from the perspective of someone else that separates empathy from sympathy, which is just an expression of concern or sorrow.

The third neural network that defines empathy is self-awareness, or the ability to differentiate between your own experience and that of the person with whom you are empathizing. In the example of losing a loved one, it may be helpful for the brain to remind you of those feelings so you can empathize with a friend, but you also must recognize that your experience is separate from theirs.

“You’re there with them, but you’re open to listening, because their experience is not going to be exactly the same as yours. You need to be able to differentiate that so you’re not imposing things on them that worked for you,” Gerdes says.

Additionally, empathy requires emotion regulation – the fourth neural network. Emotion regulation allows a person to tone down the mirroring emotions that result from affective sharing. Social workers often work with people who lack emotion regulation.

“If you put it in the context of a man that abuses his wife, he understands when his wife gets frustrated, the affect sharing is working, but the emotion regulation piece isn’t,” Gerdes says. “He may be feeding off his own anxiety as well as the people around him, and because he can’t control that, he takes it out on the people closest to him.”

Once you understand how these neural networks function, you can actually cultivate empathy. For example, to improve emotion regulation, Gerdes suggests using mindfulness techniques, such as meditation or focused breathing.

“It helps people to cope better with the emotions they’re picking up on from others, to function better at a higher level,” Gerdes says.

It can also be helpful to simply bring the emotional contagion aspect of empathy to consciousness, Gerdes says. Next time you start feeling anxious or irritated for no reason, take note of your surroundings. Are other people in the room angry or sad? Being aware of the contagious quality of emotion can help you determine whether someone’s bad mood is rubbing off on you.

To build your capacity for perspective taking, Gerdes suggests watching movies or reading books about the specific group of people you want to understand. The more you know about the context of a person’s life, the more empathic you can be.

Since empathy is at the core of social work, it’s important to be able to measure it. Gerdes says one of the most accurate measures is the multi-faceted empathy test (MET), which is based on social cognitive neuroscience research. It asks participants to look at 23 sets of photographs of people in emotionally charged situations and then try to determine each person’s emotional state, perspective and intentions.

While MET is an effective test, it is also relatively expensive and requires some training to administer. Most researches tend to rely on self-report measures because they are inexpensive. The most widely used self-report measure is the interpersonal reactivity index (IRI), which was developed in the ‘80s. The problem with IRI is that it ends up assessing a person’s level of sympathy rather than empathy.

“Sympathy and empathy are completely different constructs. They’re probably correlated with each other, but they’re not the same thing,” Gerdes says.

Gerdes is developing a new self-report measure called the empathy assessment index (EAI), which is based on the latest neuroscience research. In a recent study, she tested the measure by comparing data from a group of offenders with a group of social workers. The offenders included men who had been charged with domestic violence or sexual molestation, and at-risk parents struggling with anger management issues.

“We wanted to compare the offenders’ scores on our instrument, the assessment index, to the social workers’ scores. If it’s a valid measure, there should be a significantly significant difference in their scores, and thank goodness there was,” Gerdes says. She hopes to see a shift from the outdated IRI self-report measure to the new, research-based EAI measure, which will be more accurate but just as inexpensive to use.

Empathy is a relatively new word, only having come about in the 20th century. While most social work classes discuss empathy to some extent, few schools have incorporated the latest research into the curriculum. But Gerdes believes they soon will, because empathy is an important concept for both social workers and the general public.

“When you have an empathy deficit, like Hitler did, you have genocide,” Gerdes says. “When you have appropriate empathy, those things don’t happen because you’ll interfere with them happening. You’ll do everything you can, because it’s at the core of our human interaction that I try to understand you and you try to understand me.”

Provided by Arizona State University

"A mile in their shoes: understanding empathy." February 16th, 2012. http://medicalxpress.com/news/2012-02-mile-empathy.html

Posted by
Robert Karl Stonjek