Posts tagged genes
Articles and news from the latest research reports.
Geneticists Find Causes for Severe Childhood Epilepsies
Researchers at the University of Arizona have successfully determined the genetic mutations causing severe epilepsies in seven out of 10 children for whom the cause of the disorder could not be determined clinically or by conventional genetic testing.
Instead of sequencing each gene one at a time, the team used a technique called whole-exome sequencing: Rather than combing through all of the roughly 3 billion base pairs of an individual’s entire genome, whole-exome-sequencing deciphers only actual genes, and nearly all of them simultaneously.
"My initial hope was that we would find something in one out of the 10 children in our study. But a 70 percent success rate is beyond anyone’s imagination," said study leader Michael Hammer, who is a research scientist in the UA’s Arizona Research Labs Division of Biotechnology and a member of the UA BIO5 Institute.
For Hammer, the research hit very close to home. Just last year, his lab tracked down the mutation that had caused the severe – and ultimately fatal – epilepsy in his teenage daughter.
"I figured, if we could do this for one child, we could do it for others." Hammer explained. "These are children who have had every test imaginable and tried every possible drug combination, and nobody has figured out where their seizures come from and how to stop them."
The children who participated in the study, published online in the journal Epilepsia, all suffered from severe seizure disorders, and most of them started having seizures within the first year or two after birth.
Unlike individuals afflicted with epilepsy later in life, many of whom can live normal lives with the right medical oversight and medications, early-onset epilepsy can be devastating. Children often develop other severe complications such as intellectual disability, autism and loss of muscle tone or coordination. Early death is not uncommon.
"Because their seizures are not well controlled, and that firestorm of electrical activity in the brain is bad for brain development, the damage can be extensive," added Linda Restifo, a professor in the UA department of neurology and a BIO5 member who co-authored the study. "The earlier the seizures start and the more severe and frequent they are, the more likely they are to leave the child with permanent developmental disability."
"The sooner we can catch problems in children and understand what is causing them, the better the chance we have to try and correct them," Hammer added.
To identify changes in the DNA that are the most likely cause of the disorders, the team focused on a class of mutations called de novo mutations: “typos” in the DNA sequence that are present only in the child. In order to find such mutations, the study included both parents and their child.
Overall, the team found 15 mutations in nine children, seven of which are known or likely to cause epilepsy. No mutations could be found in one of the children.
"In four of the patients. we found mutations that were already known to be associated with epilepsy," said Krishna Veeramah, a postdoctoral fellow in Hammer’s group and the study’s first author. "However, three patients had mutations in genes that were not previously associated with epilepsy in humans but presented plausible explanations for the disorder."
"The fact that we found three genes – in a study involving only 10 subjects – that had never been implicated in epilepsy before suggests that many more genetic defects related to developmental brain disorders remain to be discovered," Veeramah said.
One of the participants in the study was Ashley Wilhelm, a 14-year-old girl from Phoenix, Ariz., whose seizures started when she was only 5 months old. Her first seizures appeared to be triggered by fever, leading doctors to believe they were just that – a side effect of the fever.
"But she soon began to have more and more seizures, and they would last half an hour or longer," said her mother, Ann. "We had all sorts of tests done, but the doctors kept saying her brain was normal, and that they didn’t see any reason she’d have those seizures."
Ashley, whose development has severely suffered as a consequence of the repeated seizures, was enrolled in the study through her neurologist, Dinesh Talwar, who co-authored the paper.
Even though her treatment is unlikely to change with the new information, the family said the results brought “more relief than we can explain.”
"Since insurance wouldn’t pay for the testing, and we couldn’t afford it on our own, we were very grateful we were able to participate in the study," said Jeff Wilhelm, Ashley’s father. "If such a test could be done much earlier, it would ease the pain for everyone involved. What if our son had decided not to consider having children of his own out of concern they might have the disorder?"
"The results from this study have at last given us a breakthrough," said the mother of another participating teenager. "We had pursued every possible avenue to understand what might be responsible for his epilepsy – magnetic resonance imaging, CT scans, searches for gross chromosome abnormalities or markers associated with epilepsy – with no success."
"Although the discovery doesn’t yet give us a treatment, it gives us hope for finding one," she said. "As more research is done on this mutation, drugs to control our son’s seizures will be identified. If more children with epilepsy can be studied and families with children with similar mutations can organize and share resources, there will be more progress."
Hammer said the approach is applicable to other conditions in which conventional genetic testing has failed to reveal the cause.
"Our work bridges research and clinical practice," he added. "We can sequence all the genes in your genome in a matter of days and report it to the patient’s family and the physician. That may make a difference in the treatment and management of the disorder in question."
Centers with the capabilities to do this kind of analysis are few and far between.
"Other centers that do this kind of work will sequence your genome and tell you where and what the mutation is in the DNA sequence, but it’s not that simple," Hammer said. "In most cases, we find a mutation in a gene not previously known to cause disease, so we need to perform a follow-up study to find out what that mutation actually does."
To perform these follow-up studies, the UA team has established collaborations with leading scientists at the UA and at other institutions.
"Right now, the benefit to families is primarily to get answers," said Restifo. "The long-term goal is to collect this kind of information from more children, which will hopefully lead to new research into medications that improve brain development and function."
Hammer added: “In the meantime, a molecular diagnosis provides immediate relief to the unnecessary guilt parents might feel for their role in causing their child’s suffering. They want answers, not endless doctors visits and tests with negative results, or to have their hopes raised and dashed over and over.”
Encouraged by the success of their approach so far, Hammer and his colleagues already have bigger plans.
"We hope to involve other clinical areas such as cardiology, immunology, gastroenterology – anything that we can apply molecular diagnostics or clinical genomics to at the UA, we want to explore. We want to make the University the core for clinical diagnostics using new sequencing technologies for at least the entire Southwest."
UA pediatric geneticist Robert Erickson, another co-author and member of the UA Steele Children’s Research Center added, “these efforts will be very important in the diagnosis of newborns with unusual birth defects.”
Unusual comparison nets new sleep loss marker
For years, Paul Shaw, PhD, a researcher at Washington University School of Medicine in St. Louis, has used what he learns in fruit flies to look for markers of sleep loss in humans.
Shaw reverses the process in a new paper, taking what he finds in humans back to the flies and gaining new insight into humans as a result: identification of a human gene that is more active after sleep deprivation.
“I’m calling the approach cross-translational research,” says Shaw, associate professor of neurobiology. “Normally we go from model to human, but there’s no reason why we can’t take our studies from human to model and back again.”
Shaw and his colleagues plan to use the information they are gaining to create a panel of tests for sleep loss. The tests may one day help assess a person’s risk of falling asleep at the wheel of a car or in other dangerous contexts.
PLOS One published the results on April 24.
Scientists have known for years that sleep disorders and disruption raise blood serum levels of interleukin 6, an inflammatory immune compound. Shaw showed that this change is also detectable in saliva samples from sleep-deprived rats and humans.
Based on this link, Shaw tested the activity of other immune proteins in humans to see if any changed after sleep loss. The scientists took saliva samples from research participants after they had a normal night’s sleep and after they stayed awake for 30 hours. They found two immune genes whose activity levels rose during sleep deprivation.
“Normally we would do additional human experiments to verify these links,” Shaw says. “But those studies can be quite expensive, so we thought we’d test the connections in flies first.”
The researchers identified genes in the fruit fly that were equivalent to the human genes, but their activity didn’t increase when flies lost sleep. When they screened other, similar fruit fly genes, though, the scientists found one that did.
“We’ve seen this kind of switch happen before as we compared families of fly genes and families of human genes,” Shaw says. “Sometimes the gene performing a particular role will change, but the task will still be handled by a gene in the same family.”
When the scientists looked for the human version of the newly identified fly marker for sleep deprivation, they found ITGA5 and realized it hadn’t been among the human immune genes they screened at the start of the study. Testing ITGA5 activity in the saliva samples revealed that its activity levels increased during sleep deprivation.
“We will need more time to figure out how useful this particular marker will be for detecting sleep deprivation in humans,” Shaw says. “In the meantime, we’re going to continue jumping between our flies and humans to maximize our insights.”
Persistent pain after stressful events may have a neurobiological basis
A new study led by University of North Carolina School of Medicine researchers is the first to identify a genetic risk factor for persistent pain after traumatic events such as motor vehicle collision and sexual assault.
In addition, the study contributes further evidence that persistent pain after stressful events has a specific biological basis. A manuscript of the study was published online ahead of print by the journal Pain on April 29.
“Our study findings indicate that mechanisms influencing chronic pain development may be related to the stress response, rather than any specific injury caused by the traumatic event,” said Samuel McLean, MD, MPH, senior author of the study and assistant professor of anesthesiology. “In other words, our results suggest that in some individuals something goes wrong with the body’s ‘fight or flight’ response or the body’s recovery from this response, and persistent pain results.”
The study assessed the role of the hypothalamic-pituitary adrenal (HPA) axis, a physiologic system of central importance to the body’s response to stressful events. The study evaluated whether the HPA axis influences musculoskeletal pain severity six weeks after motor vehicle collision (MVC) and sexual assault. Its findings revealed that variation in the gene encoding for the protein FKBP5, which plays an important role in regulating the HPA axis response to stress, was associated with a 20 percent higher risk of moderate to severe neck pain six weeks after a motor vehicle collision, as well as a greater extent of body pain. The same variant also predicted increased pain six weeks after sexual assault.
"Right now, if an someone comes to the emergency department after a car accident, we don’t have any interventions to prevent chronic pain from developing," McLean said. Similarly, if a woman comes to the emergency department after sexual assault, we have medications to prevent pregnancy or sexually transmitted disease, but no treatments to prevent chronic pain. This is because we understand what causes pregnancy or infection, but we have no idea what the biologic mechanisms are that cause chronic pain. Chronic pain after these events is common and can cause great suffering, and there is an urgent need to understand what causes chronic pain so that we can start to develop interventions. This study is an important first step in developing this understanding."
"In addition, because we don’t understand what causes these outcomes, individuals with chronic pain after traumatic events are often viewed with suspicion, as if they are making up their symptoms for financial gain or having a psychological reaction," McLean said. "An improved understanding of the biology helps with this stigma," McLean said.
(Source: news.unchealthcare.org)
Zebrafish Genome Found Strikingly Similar to Humans
According to a paper published in Nature, 70 per cent of protein-coding human genes are related to genes found in the zebrafish (Danio rerio), and 84 per cent of genes known to be associated with human disease have a zebrafish counterpart.
The team developed a high-quality annotated zebrafish genome sequence to compare with the human reference genome. Only two other large genomes have been sequenced to this high standard: the human genome and the mouse genome. The completed zebrafish genome will be an essential resource that drives the study of gene function and disease in people.
Zebrafish are remarkably biologically similar to people and share the majority of the same genes as humans, making them an important model for understanding how genes work in health and disease.
“Our aim with this project, like with all biomedical research, is to improve human health. This genome will allow researchers to understand how our genes work and how genetic variants can cause disease in ways that cannot be easily studied in humans or other organisms,” said study senior author Dr Derek Stemple of the Wellcome Trust Sanger Institute.
Zebrafish research has already led to biological advances in cancer and heart disease research, and is advancing our understanding of muscle and organ development. Zebrafish have been used to verify the causal gene in muscular dystrophy disorders and also to understand the evolution and formation of melanomas or skin cancers.
“The vast majority of human genes have counterparts in the zebrafish, especially genes related to human disease. This high quality genome is testament to the many scientists who worked on this project and will spur biological research for years to come. By modeling these human disease genes in zebrafish, we hope that resources worldwide will produce important biological information regarding the function of these genes and possibly find new targets for drug development,” explained senior author Prof Jane Rogers, also of the Wellcome Trust Sanger Institute.
The zebrafish genome has some unique features, not seen in other vertebrates. They have the highest repeat content in their genome sequences so far reported in any vertebrate species: almost twice as much as seen in their closest relative, the common carp. Also unique to the zebrafish, the team identified chromosomal regions that influence sex determination.
The zebrafish genome contains few pseudogenes – genes thought to have lost their function through evolution – compared to the human genome.
The team identified 154 pseudogenes in the zebrafish genome, a fraction of the 13,000 or so pseudogenes found in the human genome.
“To realize the benefits the zebrafish can make to human health, we need to understand the genome in its entirety – both the similarities to the human genome and the differences. Armed with the zebrafish genome, we can now better understand how changes to our genomes result in disease,” said Prof Christiane Nüsslein-Volhard, co-author and Nobel laureate from the Max Planck Institute for Developmental Biology.
“This genome will help to uncover the biological processes responsible for common and rare disease and opens up exciting new avenues for disease screening and drug development,” Dr Stemple said.
Suppressing Protein May Stem Alzheimer’s Disease Process
Scientists funded by the National Institutes of Health have discovered a potential strategy for developing treatments to stem the disease process in Alzheimer’s disease. It’s based on unclogging removal of toxic debris that accumulates in patients’ brains, by blocking activity of a little-known regulator protein called CD33.
“Too much CD33 activity appears to promote late-onset Alzheimer’s by preventing support cells from clearing out toxic plaques, key risk factors for the disease,” explained Rudolph Tanzi, Ph.D., of Massachusetts General Hospital and Harvard University, a grantee of the NIH’s National Institute of Mental Health (NIMH) and National Institute on Aging (NIA). “Future medications that impede CD33 activity in the brain might help prevent or treat the disorder.”
Tanzi and colleagues report on their findings April 25, 2013 in the journal Neuron.
“These results reveal a previously unknown, potentially powerful mechanism for protecting neurons from damaging toxicity and inflammation,” said NIMH Director Thomas R. Insel, M.D. “Given increasing evidence of overlap between brain disorders at the molecular level, understanding such workings in Alzheimer’s disease may also provide insights into other mental disorders.”
Variation in the CD33 gene turned up as one of four prime suspects in the largest genome-wide dragnet of Alzheimer’s-affected families, reported by Tanzi and colleagues in 2008. The gene was known to make a protein that regulates the immune system, but its function in the brain remained elusive. To discover how it might contribute to Alzheimer’s, the researchers brought to bear human genetics, biochemistry and human brain tissue, mouse and cell-based experiments.
They found over-expression of CD33 in support cells, called microglia, in postmortem brains from patients who had late-onset Alzheimer’s disease, the most common form of the illness. The more CD33 protein on the cell surface of microglia, the more beta-amyloid protein and plaques – damaging debris – had accumulated in their brains. Moreover, the researchers discovered that brains of people who inherited a version of the CD33 gene that protected them from Alzheimer’s conspicuously showed reduced amounts of CD33 on the surface of microglia and less beta-amyloid.
Brain levels of beta-amyloid and plaques were also markedly reduced in mice engineered to under-express or lack CD33. Microglia cells in these animals were more efficient at clearing out the debris, which the researchers traced to levels of CD33 on the cell surface.
Evidence also suggested that CD33 works in league with another Alzheimer’s risk gene in microglia to regulate inflammation in the brain.
The study results – and those of a recent rat study that replicated many features of the human illness – add support to the prevailing theory that accumulation of beta-amyloid plaques are hallmarks of Alzheimer’s pathology. They come at a time of ferment in the field, spurred by other recent contradictory evidence suggesting that these presumed culprits might instead play a protective role.
Since increased CD33 activity in microglia impaired beta-amyloid clearance in late onset Alzheimer’s, Tanzi and colleagues are now searching for agents that can cross the blood-brain barrier and block it.
(Source: nimh.nih.gov)
Epigenetic changes shed light on biological mechanism of autism
Scientists from King’s College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits.
The study, published in Molecular Psychiatry, is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits.
ASD affects approximately 1 in 100 people in the UK and involves a spectrum of disorders which manifest themselves differently in different people. People with ASD have varying levels of impairment across three common areas: deficits in social interactions and understanding, repetitive behaviour and interests, and impairments in language and communication development.
Evidence from twin studies shows there is a strong genetic component to ASD and previous studies suggest that genes that direct brain development may be involved in the disorder. In approximately 70% of cases, when one identical twin has ASD, so does the other. However, in 30% of cases, identical twins differ for ASD. Because identical twins share the same genetic code, this suggests non-genetic, or epigenetic, factors may be involved.
Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence – they are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies.
The researchers studied an epigenetic mechanism called DNA methylation. DNA methylation acts to block the genetic sequences that drive gene expression, silencing gene activity. They examined DNA methylation at over 27,000 sites across the genome using samples taken from 50 identical twin pairs (100 individuals) from the UK Medical Research Council (MRC) funded Twins Early Development Study (TEDS): 34 pairs who differed for ASD or autism related behaviour traits, 5 pairs where both twins have ASD, and 11 healthy twin pairs.
Dr Chloe Wong, first author of the study from King’s College London’s Institute of Psychiatry, says: “We’ve identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder.”
DNA methylation at some genetic sites was consistently altered for all individuals with ASD, and differences at other sites were specific to certain symptom groups. The number of DNA methylation sites across the genome was also linked to the severity of autism symptoms suggesting a quantitative relationship between the two. Additionally, some of the differences in DNA methylation markers were located in genetic regions that previous research has associated with early brain development and ASD.
Professor Jonathan Mill, lead author of the paper from King’s College London’s Institute of Psychiatry and the University of Exeter, says: “Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed. Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions.”
Dr Alycia Halladay, Senior Director of Environmental and Clinical Sciences from Autism Speaks who funded the research, says: “This is the first large-scale study to take a whole genome approach to studying epigenetic influences in twins who are genetically identical but have different symptoms. These findings open the door to future discoveries in the role of epigenetics – in addition to genetics – in the development of autism symptoms.”
(Source: kcl.ac.uk)
Those resistant to ‘love hormone’ may also be easier to hypnotize
People with genes that make it tough for them to engage socially with others seem to be better than average at hypnotizing themselves. A study published today in Psychoneuroendocrinology concludes that such individuals are particularly good at becoming absorbed in their own internal world, and might also be more susceptible to other distortions of reality.
Psychologist Richard Bryant of the University of New South Wales in Sydney and his colleagues tested the hypnotizability of volunteers with different forms of the receptor for oxytocin, a hormone that increases trust and social bonding. (Oxytocin’s association with emotional attachment also earned it the nickname of ‘love hormone’.) Those with gene variants linked to social detachment and autism were found to be most susceptible to hypnosis.
Hypnosis has intrigued scientists since the nineteenth-century physician James Braid used it to alleviate pain in a variety of medical conditions, but it has never been fully understood. Hypnotized people can undergo a range of unusual experiences, including amnesia, anaesthesia and the loss of the ability to move their limbs. But some individuals are more affected by hypnosis than others — and no one knows why.
Hormones and hypnotism
How susceptible someone is to persuasion is an important factor in how easily they can be hypnotized by someone else. Bryant and his colleagues have previously shown that spraying a shot of oxytocin up people’s noses makes them more hypnotizable, and more likely to engage in potentially embarrassing activities such as swearing or dancing at a hypnotist’s suggestion.
When it comes to self-hypnosis, however, the team wondered whether people who can easily disengage from the external world and become lost in their own imagination might do better. In their latest study, they asked 185 volunteers to hypnotize themselves with the aid of an audio recording, then assessed the depth of their hypnosis using checks such as whether they were unable to open their eyes, or could hallucinate a sound.
The researchers used a questionnaire to test the participants’ ability to become absorbed in internal and imagined experiences, and tested them for variants of the oxytocin-receptor gene at two places in the gene sequence — rs53576 and rs2254298 — that that increase the risk of social detachment and autism. Participants with these variants scored highest for hypnotizability and absorption.
Bryant suggests that as well as being more hypnotizable, such individuals might “be influenced to have a range of experiences that more reality-based people cannot”. For example, this capacity might help to explain why some people respond better to placebos, or are more likely to accept paranormal or religious experiences.
“At this point we do not know anything about genetic bases of suggestibility per se,” says Bryant. “The current finding does provide some direction for exploring this.”
Aleksandr Kogan of the University of Cambridge, UK, who works on the genetics of social psychology, says that the results fit well with what is known about the oxytocin-receptor gene, particularly for variants at site rs53576. Among white people, these influence an individual’s sensitivity to social cues, he says. “That this would reflect a difference in internal experiences makes sense.”
(Source: nature.com)
Discovery of genetic defect which triggers epilepsy
Researchers at the University Department of Neurology at the MedUni Vienna have identified a gene behind an epilepsy syndrome, which could also play an important role in other idiopathic (genetically caused) epilepsies. With the so-called “next generation sequencing”, with which genetic changes can be identified within a few days, it was ascertained that the CNTN2 gene is defective in this type of epilepsy.
This was investigated by a team led by Elisabeth Stögmann in collaboration with Cairo’s Ain Shams University and the Helmholtz Centre Munich with reference to a particular Egyptian family, in which five sick children have resulted from the marriage of one healthy cousin to his, likewise healthy, second cousin. The children affected suffer from a specific epilepsy syndrome, in which different types of epileptic attacks occur. This constellation has the “advantage”, according to Stögmann, that both alleles of the gene, which is how one designates different forms of the gene, demonstrate this defect: “As a result the defect becomes symptomatic and identifiable.
"20,000 to 25,000 genes, including all the "protein coding" ones, were sequenced for this. When this was done a mutation was found in the CNTN2 gene. CNTN2 undertakes an important function in the anchoring of potassium channels to the synapses. The mutation makes it no longer possible to generate this protein and, as a consequence, the potassium channels no longer remain affixed to the synapses. The researchers suspect that the epilepsy in this family is triggered by the altered function of the potassium channels.
This discovery, which has now been published in the top journal “Brain”, is providing the stimulus for further research to investigate this particular gene in other epilepsy patients as well. Approximately one percent of the population suffers from active epilepsy in which regular epileptic fits occur. The danger of suffering from an epileptic fit once in your life lies at approximately four to five percent. Genetic factors play a major part in the occurrence of epilepsies.
(Source: meduniwien.ac.at)
Researchers Confirm Multiple Genes Robustly Contribute to Schizophrenia Risk in Replication
Multiple genes contribute to risk for schizophrenia and appear to function in pathways related to transmission of signals in the brain and immunity, according to an international study led by Virginia Commonwealth University School of Pharmacy researchers.
By better understanding the molecular and biological mechanisms involved with schizophrenia, scientists hope to use this new genetic information to one day develop and design drugs that are more efficacious and have fewer side effects.
In a study published online in the April issue of JAMA Psychiatry, the JAMA Network journal, researchers used a comprehensive and unique approach to robustly identify genes and biological processes conferring risk for schizophrenia.
The researchers first used 21,953 subjects to examine over a million genetic markers. They then systematically collected results from other kinds of biological schizophrenia studies and combined all these results using a novel data integration approach.
The most promising genetic markers were tested again in a large collection of families with schizophrenia patients, a design that avoids pitfalls that have plagued genetic studies of schizophrenia in the past. The genes they identified after this comprehensive approach were found to have involvement in brain function, nerve cell development and immune response.
“Now that we have genes that are robustly associated with schizophrenia, we can begin to design much more specific experiments to understand how disruption of these genes may affect brain development and function,” said principal investigator Edwin van den Oord, Ph.D., professor and director of the Center for Biomarker Research and Personalized Medicine in the Department of Pharmacotherapy and Outcomes Science at the VCU School of Pharmacy.
“Also, some of these genes provide excellent targets for the development of new drugs,” he said.
One specific laboratory experiment currently underway at VCU to better understand the function of one of these genes, TCF4, is being led by Joseph McClay, Ph.D., a co-author on the study and assistant professor and laboratory director in the VCU Center for Biomarker Research and Personalized Medicine. TCF4 works by switching on other genes in the brain. McClay and colleagues are conducting a National Institutes of Health-funded study to determine all genes that are under the control of TCF4. By mapping the entire network, they aim to better understand how disruptions to TCF4 increase risk for schizophrenia.
“Our results also suggest that the novel data integration approach used in this study is a promising tool that potentially can be of great value in studies of a large variety of complex genetic disorders,” said lead author Karolina A. Aberg, Ph.D., research assistant professor and laboratory co-director of the Center for Biomarker Research and Personalized Medicine in the VCU School of Pharmacy.
(Image: iStockphoto)
Couch Potatoes May Be Genetically Predisposed to Being Lazy
Studies show 97 percent of American adults get less than 30 minutes of exercise a day, which is the minimum recommended amount based on federal guidelines. New research from the University of Missouri suggests certain genetic traits may predispose people to being more or less motivated to exercise and remain active. Frank Booth, a professor in the MU College of Veterinary Medicine, along with his post-doctoral fellow Michael Roberts, were able to selectively breed rats that exhibited traits of either extreme activity or extreme laziness. They say these rats indicate that genetics could play a role in exercise motivation, even in humans.
“We have shown that it is possible to be genetically predisposed to being lazy,” Booth said. “This could be an important step in identifying additional causes for obesity in humans, especially considering dramatic increases in childhood obesity in the United States. It would be very useful to know if a person is genetically predisposed to having a lack of motivation to exercise, because that could potentially make them more likely to grow obese.”
In their study published in the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology on April 3, 2013, Roberts and Booth put rats in cages with running wheels and measured how much each rat willingly ran on their wheels during a six-day period. They then bred the top 26 runners with each other and bred the 26 rats that ran the least with each other. They repeated this process through 10 generations and found that the line of running rats chose to run 10 times more than the line of “lazy” rats.
Once the researchers created their “super runner” and “couch potato” rats, they studied the levels of mitochondria in muscle cells, compared body composition and conducted thorough genetic evaluations through RNA deep sequencing of each rat.
“While we found minor differences in the body composition and levels of mitochondria in muscle cells of the rats, the most important thing we identified were the genetic differences between the two lines of rats,” Roberts said. “Out of more than 17,000 different genes in one part of the brain, we identified 36 genes that may play a role in predisposition to physical activity motivation.”
Now that the researchers have identified these specific genes, they plan on continuing their research to explore the effects each gene has on motivation to exercise.