Posts tagged genes
Articles and news from the latest research reports.
New brain gene born, study shows
Scientists have taken a step forward in helping to solve one of life’s greatest mysteries - what makes us human?
Image: Irish Wildcat
An international team of researchers have discovered a new gene that helps explain how humans evolved from apes. Scientists say the gene - calledmiR-941 - appears to have played a crucial role in human brain development and may shed light on how we learned to use tools and language. Researchers say it is the first time that a new gene - carried only by humans and not by apes - has been shown to have a specific function within the human body.
Unique finding
A team at the University of Edinburgh compared the human genome to 11 other species of mammals, including chimpanzees, gorillas, mouse and rat, to find the differences between them. The results, published in Nature Communications, showed that the gene - miR-941 - is unique to humans. The researchers say that it emerged between six and one million years ago, after humans had evolved from apes. The gene is highly active in two areas of the brain that control our decision making and language abilities. The study suggests it could have a role in the advanced brain functions that make us human.
Startling results
It is known that most differences between species occur as a result of changes to existing genes, or the duplication and deletion of genes. But scientists say this gene emerged fully functional out of non-coding genetic material, previously termed “junk DNA”, in a startlingly brief interval of evolutionary time. Until now, it has been remarkably difficult to see this process in action. Researcher Dr Martin Taylor, who led the study at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, said the results were fascinating.
This new molecule sprang from nowhere at a time when our species was undergoing dramatic changes: living longer, walking upright, learning how to use tools and how to communicate. We’re now hopeful that we will find more new genes that help show what makes us human. -Dr Martin Taylor (Programme leader, Biomedical Systems Analysis)
(Source: ed.ac.uk)
Alzheimer gene may boost young brains but contributes to ‘burnout’ in later years
A gene that confers a higher risk for dementia in old age could also promote better-than-average memory and verbal skills in youth, according to a new University of Sussex-led study.
Neuroscientists tested the cognitive abilities of those with a particular gene variant, known as ‘APOE e4’, found in approximately 25 per cent of the population, against those without it. They also looked at the brain structure and brain activities of both groups during the tasks.
They found that young people with the e4 variant performed better in attention tests (one involving episodic memory of words, the other requiring participants to spot number sequences), which correlated with increased task-related brain activation as detected by MRI scans. The researchers also noticed subtle differences in the white matter of the brains of those with the variant.
Lead researcher Professor Jennifer Rusted said: “Earlier studies suggested that those with the e4 variant outperform those without it in tasks such as memory, speed of processing, mental arithmetic and verbal fluency.
But it is also well-established that this gene is a risk factor for Alzheimer’s disease. The suggestion is that while this confers cognitive advantages in early life, leading to higher achievement, it may also increase susceptibility to memory failure as we enter old age.
“Our study is the first to show that subtle differences in the structure and activation of the brain during cognitive tasks in APOE e4 carriers are linked to their cognitive performance. It is possible that the brain over-activations that we see in youth have negative effects over the longer term and contribute to a kind of ‘burnout’ in older adulthood.”
‘APOE e4 polymorphism in young adults is associated with improved attention andindexed by distinct neural signatures’, by Professor Jennifer Rusted, Dr Simon Evans and Dr Sarah King in the School of Psychology, Dr Nick Dowell and Professor Paul Tofts in the Clinical Imaging Sciences Centre at the Brighton and Sussex Medical School (BSMS), and Dr Najo Tabet in the BSMS Institute of Postgraduate Medicine, is published in NeuroImage.
(Source: sussex.ac.uk)
Why do we get older? When do we die and why? Is there a life without ageing? For centuries, science has been fascinated by these questions. Now researchers from Kiel (Germany) have examined why the polyp Hydra is immortal – and unexpectedly discovered a link to ageing in humans. The study carried out by Kiel University together with the University Medical Center Schleswig-Holstein (UKSH) will be published this week in the Proceedings of the National Academy of Sciences of the United States of America (PNAS). It was funded by the German Research Foundation DFG.
Schizophrenia Genetic Networks Identified; Connection to Autism Found
Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify. In the past few years, researchers have implicated several genes, but it is unclear how they act to produce the disorder. A new study by researchers at Columbia University Medical Center identifies affected gene networks and provides insight into the molecular causes of the disease.
The paper was published in the online edition of the journal Nature Neuroscience.
Using an unbiased collection of hundreds of mutations associated with schizophrenia, the Columbia researchers applied a sophisticated computational approach to uncover hidden relationships among seemingly unrelated genes. The analysis revealed that many of the genes mutated in schizophrenia are organized into two main networks, which take part in a few key processes, including axon guidance, synapse function, neuron mobility, and chromosomal modification.
The study also uncovered an intriguing connection between schizophrenia and autism. “If we hadn’t known that these were two different diseases, and had put all the mutations into a single analysis, it would have come up with very similar networks,” said the study’s senior author, Dennis Vitkup, PhD, associate professor in the Department of Biomedical Informatics, the Center for Computational Biology and Bioinformatics, and the Columbia Initiative in Systems Biology at Columbia University Medical Center. “It shows how closely the autism and schizophrenia genetic networks are intertwined,” he added.
Fat cells store excess energy and signal these levels to the brain. In a new study this week in Nature Medicine, Georgios Paschos PhD, a research associate in the lab of Garret FitzGerald, MD, FRS director of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, shows that deletion of the clock gene Arntl, also known as Bmal1, in fat cells, causes mice to become obese, with a shift in the timing of when this nocturnal species normally eats. These findings shed light on the complex causes of obesity in humans.
The Penn studies are surprising in two respects. “The first is that a relatively modest shift in food consumption into what is normally the rest period for mice can favor energy storage,” says Paschos. “Our mice became obese without consuming more calories.” Indeed, the Penn researchers could also cause obesity in normal mice by replicating the altered pattern of food consumption observed in mice with a broken clock in their fat cells.
This behavioral change in the mice is somewhat akin to night-eating syndrome in humans, also associated with obesity and originally described by Penn’s Albert Stunkard in 1955.
The second surprising observation relates to the molecular clock itself. Traditionally, clocks in peripheral tissues are thought to follow the lead of the “master clock” in the SCN of the brain, a bit like members of an orchestra following a conductor. “While we have long known that peripheral clocks have some capacity for autonomy – the percussionist can bang the drum without instructions from the conductor – here we see that the orchestrated behavior of the percussionist can, itself, influence the conductor,” explains FitzGerald.
Dramatic expansion of the human cerebral cortex, over the course of evolution, accommodated new areas for specialized cognitive function, including language. Understanding the genetic mechanisms underlying these changes, however, remains a challenge to neuroscientists.
A team of researchers in Japan, led by Hideyuki Okano of Keio University School of Medicine and Tomomi Shimogori of the RIKEN Brain Science Institute, has now elucidated the mechanisms of cortical evolution. They used molecular techniques to compare the gene expression patterns in mouse and monkey brains.
Using the technique called in situ hybridization to visualize the distribution of mRNA transcripts, Okano, Shimogori and their colleagues examined the expression patterns of genes that are known to regulate development of the mouse brain. They compared these patterns to those of the same genes in the brain of the common marmoset. They found that most of the genes had similar expression patterns in mice and marmosets, but that some had strikingly different patterns between the two species. Notably, some areas of the visual and prefrontal cortices showed expression patterns that were unique to marmosets.
The researchers also found differences in gene expression within regions that connect the prefrontal cortex and hippocampus, a structure that is critical for learning and memory.
Humans, Chimpanzees and Monkeys Share DNA but Not Gene Regulatory Mechanisms
Humans share over 90% of their DNA with their primate cousins. The expression or activity patterns of genes differ across species in ways that help explain each species’ distinct biology and behavior.
DNA factors that contribute to the differences were described on Nov. 6 at the American Society of Human Genetics 2012 meeting in a presentation by Yoav Gilad, Ph.D., associate professor of human genetics at the University of Chicago.
Dr. Gilad reported that up to 40% of the differences in the expression or activity patterns of genes between humans, chimpanzees and rhesus monkeys can be explained by regulatory mechanisms that determine whether and how a gene’s recipe for a protein is transcribed to the RNA molecule that carries the recipe instructions to the sites in cells where proteins are manufactured.
In addition to improving scientific understanding of the uniqueness of humans, studies such as the investigation conducted by Dr. Gilad and colleagues could have relevance to human health and disease.
"Through inter-species’ comparisons at the DNA sequence and expression levels, we hope to identify the genetic basis of human specific traits and in particular the genetic variations underlying the higher susceptibility to certain diseases such as malaria and cancer in humans than in non-human primates," said Dr. Gilad.
Dr. Gilad and his colleagues studied gene expression in lymphoblastoid cell lines, laboratory cultures of immortalized white blood cells, from eight humans, eight chimpanzees and eight rhesus monkeys.
They found that the distinct gene expression patterns of the three species can be explained by corresponding changes in genetic and epigenetic regulatory mechanisms that determine when and how a gene’s DNA code is transcribed to a messenger RNA (mRNA) molecule.
Dr. Gilad also determined that the epigenetics process known as histone modification also differs in the three species. The presence of histone marks during gene transcription indicates that the process is being prevented or modified.
"These data allowed us to identify both conserved and species-specific enhancer and repressor regulatory elements, as well as characterize similarities and differences across species in transcription factor binding to these regulatory elements," Dr. Gilad said.
Among the similarities among the three species were the promoter regions of DNA that initiated transcription of a particular gene.
In all three species, Dr. Gilad’s lab found that transcription factor binding and histone modifications were identical in over 67% of regulatory elements in DNA segments that are regarded as promoter regions.
The researchers presentation is titled, “Genome-wide comparison of genetic and epigenetic regulatory mechanisms in primates.”
(Source: sciencedaily.com)
Genes, depression and life satisfaction
Vulnerability to major depression is linked with how satisfied we are with our lives. This association is largely due to genes.
This is the main finding of a new twin study from the Norwegian Institute of Public Health in collaboration with the University of Oslo. The researchers compared longitudinal information from identical and fraternal twins to determine how vulnerability to major depression is associated with dispositional (overall) lifetime satisfaction.
Previous studies have systematically shown that life satisfaction is considerably stable over time. People who are satisfied at any one point in life are often also satisfied at other times in their lives. This stability—the dispositional life satisfaction—is often said to reflect an underlying positive mood or a positive disposition. Previous studies have also shown that people with such a positive disposition are less depressed, but very few studies have examined the mechanisms behind this relationship.
Results
• Both men and women who met the criteria for lifetime major depression (15.8% and 11.1% respectively) reported lower life satisfaction.
• 74% of the relationship between major depression and life satisfaction could be explained by genes.
• The remaining association (26%) could be explained by unique environmental factors.
• The researchers also calculated the heritability of dispositional life satisfaction and major depression separately. The heritability of dispositional life satisfaction, which has not previously been reported, was estimated to be 72%. In other words, it is largely genes that explain why we differ in our tendency to be satisfied and content with our lives.
• Major depression had a heritability of 34%, which is highly consistent with previous studies.
“The stable tendency to see the bright side of life is associated with lower risk of major depression because some genetic factors influence both conditions”, says researcher Ragnhild Bang Nes from the Division of Mental Health. Genes involved in satisfaction and positivity thus give protection against major depression. Nes is the main author of the study that was recently published in the Journal of Affective Disorders.
Susceptibility to both depression and overall life satisfaction is partly influenced by the same set of genes, but is also influenced by genes that are unique to each.
“The heritability figures mean that 72% of the individual differences in overall satisfaction, and 34% of the differences in depression, are caused by genes. These figures do not provide information on the importance of specific genes for an individual’s life satisfaction or risk of major depression. Traits and propensities like dispositional life satisfaction and vulnerability to major depression are not heritable in themselves. Heritability refers to the importance of genes for explaining the differences between people and the estimates may vary across time and place”, explains Nes.
Although the heritability of major depression was lower than that of life satisfaction, this does not necessarily mean that life satisfaction is far more heritable than depression. The researchers used questionnaire data from two time points to measure dispositional life satisfaction, and a single clinical interview to measure the prevalence of lifetime major depression. The use of only a single assessment to measure depression may partly explain why the heritability of depression is so much lower than life satisfaction.
Can we prevent depression by promoting life satisfaction?
“We found that depression and life satisfaction did not share as many environmental factors as genetic factors. This means that environmental factors of importance to life satisfaction (for example, activities and interventions that make you happy and content) only to a small extent protect against depression”, says Nes.
“Although our underlying disposition to life satisfaction and positivity appears to be relatively stable, small actions in our daily lives may provide temporary pleasures, and these are also important. How we spend our time is tremendously important for our happiness and well-being. It is therefore important to encourage and follow up on activities that make us happy”.
Nes adds:
“To some extent, positive experiences may also accumulate over time and create favorable conditions for our quality of life”.
(Source: fhi.no)
Stimulating brain cells with light
Introducing a light-sensitive protein in transgenic nerve cells… transplanting nerve cells into the brains of laboratory animals… inserting an optic fibre in the brain and using it to light up the nerve cells and stimulate them into releasing more dopamine to combat Parkinson’s disease… These events may sound like science fiction but they are soon to become a reality in a research laboratory at Lund University in Sweden.
For the time being, this is basic research but the long term objective is to find new ways of treating Parkinson’s disease. This increasingly common disease is caused by degeneration of the brain cells producing signal substance dopamine.
Many experiments have been conducted on both animals and humans, transplanting healthy nerve cells to make up for the lack of dopamine, but it is difficult to study what happens to the transplant.
“We don’t know how the new nerve cells behave once they have been transplanted into the brain. Do they connect to the surrounding cells as they should, and can they function normally and produce dopamine as they should? Can we use light to reinforce dopamine production? These are the issues we want to investigate with optogenetics”, says Professor Merab Kokaia.
Optogenetics allows scientists to control certain cells in the brain using light, leaving other cells unaffected. In order to do this, the relevant cells are equipped with genes for a special light-sensitive protein. The protein makes the cells react when they are illuminated with light from a thin optic fibre which is also implanted in the brain. The cells can then be “switched on” when they are illuminated.
“If we get signals as a response to light from the host brain, we know that they come from the transplanted cells since they are the only ones to carry the light-sensitive protein. This gives us a much more specific way of studying the brain’s reactions than inserting an electrode, which is the current method. With an electrode, we do not know whether the electric signals that are detected come from “new” or “old” brain cells”, explains Merab Kokaia.
The work will be conducted on laboratory rats modelling Parkinson’s disease. The transplanted cells will be derived from skin from an adult human and will have been “reprogrammed” as nerve cells. Merab Kokaia will be collaborating with neuro-researchers Malin Parmar and Olle Lindvall on the project.
The three Lund researchers have received a grant of USD 75 000 from the Michael J. Fox Foundation, started by actor Michael J. Fox and dedicated to Parkinson’s research.
The light-sensitive protein is obtained from a bacterium, which uses light to gain energy. Since it is not a human protein, the safety checks will be extra strict if the method is to be used on humans.
”We know that this is long term research. But the methodology is interesting and it will be exciting to see what we can come up with,” says Merab Kokaia.
(Source: lunduniversity.lu.se)
New epilepsy gene discovered
In a national research partnership, Dr Sarah Heron from the University of South Australia’s Sansom Research Institute, epilepsy research group, has been working to map the genes responsible for a rare form of epilepsy - autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Dr Heron and her team’s latest research to identify a new gene for this form of epilepsy has been published in Nature Genetics this month.
She says while ADNFLE affects a relatively rare group of people, the symptoms and impact of the condition can be devastating.
“ADNFLE usually develops in childhood and characterised by clusters of seizures during sleep,” Dr Heron says.
“It can have an association with cognitive deficits and or psychiatric comorbidity.
“Our research has identified that mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy and associated intellectual and or psychiatric disability.”
Dr Heron says the identification of the gene has important implications for genetic counselling and also for understanding more about the full spectrum of epilepsy disorders.