Neuroscience

ScienceDaily (Aug. 21, 2012) — How abnormal protein deposits in the brains of Alzheimer’s patients disrupt the signalling between nerve cells has now been reported by researchers in Bochum and Munich, led by Dr. Thorsten Müller from the Medizinisches Proteom-Center of the Ruhr-Universität, in the journal Molecular and Cellular Proteomics. They varied the amount of APP protein and related proteins associated with Alzheimer’s disease in cell cultures, and then analysed how this manipulation affected other proteins in the cell. The result: the amount of APP present was related to the amount of an enzyme that is essential for the production of neurotransmitters and therefore for communication amongst nerve cells.

Mass spectrometer: The proteins are injected into the apparatus via a very thin needle. (Credit: © RUB-Pressestelle, Marion Nelle)

Proteomics: analysing all the proteins of the cells at once

Amyloid plaques are a characteristic feature of Alzheimer’s disease. They consist largely of cleavage products of the so-called amyloid precursor protein APP, which occur in excess in the brains of Alzheimer’s patients. What role APP plays in healthy people and why the abnormal accumulation of amyloid disrupts the regular functioning of the brain is still largely unclear. To understand the function of APP, the RUB researchers established a new cell model. The new cells produced only a very small amount of APP. What impact this had on all the other proteins of these cells was examined by the researchers through the use of mass spectrometry, among other things. With this method they identified over 2000 proteins and determined their concentrations. They were looking specifically for molecules whose concentrations in the newly established low-APP cells were different than in the reference cells that contained normal amounts of APP.

Abnormal protein able to curb neurotransmitter production

"One candidate has particularly caught our attention, this being the enzyme methionine adenosyltransferase II, alpha, MAT2A for short," Thorsten Müller said. Among other things, the enzyme is crucially involved in the production of neurotransmitters. Low-APP cells contained less MAT2A than the reference cells. To confirm the connection between the "Alzheimer’s protein" APP and the neurotransmitter-producing MAT2A, the team studied tissue samples from the brains of deceased Alzheimer’s patients and from healthy individuals. In the tissue of the Alzheimer’s patients there was less MAT2A than in the healthy samples. These results suggest that APP and MAT2A concentrations are related and are linked to the synthesis of neurotransmitters. "Our results point to a new mechanism by which the defective cleavage of the APP protein in Alzheimer’s disease could be directly related to altered neurotransmitter production," Müller said. "As a result, the signal transduction of nerve cells could be disrupted, which, over an extended period, could possibly also cause the death of cells."

Source: Science Daily

Aug. 20, 2012 by Quinn Eastman

People with Parkinson’s disease performed markedly better on a test of working memory after a night’s sleep, and sleep disorders can interfere with that benefit, researchers have shown.

The ability of sleep to improve scores on a test of working memory specifically depends on how much slow wave sleep Parkinson’s patients obtain, researchers have found.

While the classic symptoms of Parkinson’s disease include tremors and slow movements, Parkinson’s can also affect someone’s memory, including “working memory.” Working memory is defined as the ability to temporarily store and manipulate information, rather than simply repeat it. The use of working memory is important in planning, problem solving and independent living.

The findings underline the importance of addressing sleep disorders in the care of patients with Parkinson’s, and indicate that working memory capacity in patients with Parkinson’s potentially can be improved with training. The results also have implications for the biology of sleep and memory.

The results were published this week in the journal Brain.

"It was known already that sleep is beneficial for memory, but here, we’ve been able to analyze what aspects of sleep are required for the improvements in working memory performance," says postdoctoral fellow Michael Scullin, who is the first author of the paper. The senior author is Donald Bliwise, professor of neurology at Emory University School of Medicine.

The performance boost from sleep was linked with the amount of slow wave sleep, or the deepest stage of sleep. Several research groups have reported that slow wave sleep is important for synaptic plasticity, the ability of brain cells to reorganize and make new connections.

Sleep apnea, the disruption of sleep caused by obstruction of the airway, interfered with sleep’s effects on memory. Study participants who showed signs of sleep apnea, if it was severe enough to lower their blood oxygen levels for more than five minutes, did not see a working memory test boost.

In this study, participants took a “digit span test,” in which they had to repeat a list of numbers forward and backward. The test was conducted in an escalating fashion: the list grows incrementally until someone makes a mistake. Participants took the digit span test eight times during a 48-hour period, four during the first day and four during the second. In between, they slept.

Repeating numbers in the original order is a test of short-term memory, while repeating the numbers in reverse order is a test of working memory.

"Repeating the list in reverse order requires some effort to manipulate the numbers, not just spit them back out again," Scullin says. "It’s also a purely verbal test, which is important when working with a population that may have motor impairments."

54 study participants had Parkinson’s disease, and 10 had dementia with Lewy bodies: a more advanced condition, where patients may have hallucinations or fluctuating cognition as well as motor symptoms. Those who had dementia with Lewy bodies saw no working memory boost from the night’s rest. As expected, their  baseline level of performance was lower than the Parkinson’s group.

Participants with Parkinson’s who were taking dopamine-enhancing medications saw their performance on the digit span test jump up between the fourth and fifth test. On average, they could remember one more number backwards. The ability to repeat numbers backward improved, even though the ability to repeat numbers forward did not.

Patients needed to be taking dopamine-enhancing medications to see the most performance benefit from sleep. Patients not taking dopamine medications, even though they had generally had Parkinson’s for less time, did not experience as much of a performance benefit. This may reflect a role for dopamine, an important neurotransmitter, in memory.

Scullin and Bliwise are planning an expanded study of sleep and working memory, in healthy elderly people as well as patients with neurodegenerative diseases.

"Many elderly people go through a decline in how much slow wave sleep they experience, and this may be a significant contributor to working memory difficulties," Scullin says.

Source: Emory

ScienceDaily (Aug. 20, 2012) — The more that we understand the brain, the more complex it becomes. The same can be said about the genetics and neurobiology of psychiatric disorders. For “Mendelian” disorders, like Huntington disease, mutation of a single gene predictably produces a single clinical disorder, following relatively simple genetic principals. Compared to Mendelian disorders, understanding bipolar disorder has been extremely challenging. Its biology is not well understood and its genetics are complex.

In a new paper, Dr. Inti Pedroso and colleagues utilize an integrative approach to probe the biology of bipolar disorder. They combined the results of three genome-wide association studies, which examined the association of common gene variants with bipolar disorder throughout the genome, and a study of gene expression patterns in post-mortem brain tissue from people who had been diagnosed with bipolar disorder. The findings were analyzed within the context of how brain proteins relate to each other based on the Human Protein Reference Database protein-protein interaction network.

"None of our research approaches provides us with sufficient information, by itself, to understand the neurobiology of psychiatric disorders. This innovative paper wrestles with this challenge in a creative way that helps us to move forward in thinking about the neurobiology of bipolar disorder," commented Dr. John Krystal, Editor of Biological Psychiatry.

Dr. Pedroso explained, “We combined information about genetic variation from thousands of cases and controls with brain gene expression data and information from protein databases to identify networks of genes and proteins in the brain that are key in the development of bipolar disorder.”

The analysis resulted in the ability to define risk gene variants that were deemed functional, by virtue of the association with changes in gene expression levels, and to group these functional gene variants in biologically meaningful pathways.

The results implicated genes involved in several neural signaling pathways, including the Notch and Wnt signaling pathways. These pathways are key processes in neurotransmission and brain development and these findings indicate they are also likely to be involved in causing this severe disorder. The authors noted that three features stand out among these genes: i) they localized to the human postsynaptic density, which is crucial for neuronal function; ii) their mouse knockouts present altered behavioral phenotypes; and iii) some are known targets of the pharmacological treatments for bipolar disorder.

Dr. Gerome Breen, senior author on the study and Senior Lecturer at King’s College London Institute of Psychiatry, said, “Our study provides some of the first evidence to show the biochemical and developmental processes involved in causing risk for developing this life-long and costly illness. We have highlighted potential new avenues for new drug treatments and intervention.”

Source: Science Daily

ScienceDaily (Aug. 20, 2012) — Scientific advances in understanding the “addiction circuitry” of the brain may lead to effective treatment for obesity using deep brain stimulation (DBS), according to a review article in the August issue of Neurosurgery, official journal of the Congress of Neurological Surgeons.

Electrical brain stimulation targeting the “dysregulated reward circuitry” could make DBS — already an accepted treatment for Parkinson’s disease — a new option for the difficult-to-treat problem of obesity. Dr. Alexander Taghva of Ohio State University and University of Southern California was lead author of the new review.

New Insights into ‘Reward Circuitry’

Obesity is a major public health problem that is notoriously difficult to treat. Although various approaches can promote weight loss, patients typically gain weight soon after the end of treatment. Drug options have shown limited success, with several products removed from the market because of serious adverse effects. Bariatric surgery is effective in many cases of obesity but has a significant failure rate and is associated with side effects.

Drug treatments for obesity have targeted the homeostatic (self-regulating) mechanism regulating appetite and body weight. The homeostatic mechanism is thought to involve the “feeding center” in the hypothalamus, which produces hormones (such as leptin and insulin) that affect feeding behavior.

Initial experiments exploring DBS as a treatment for obesity have targeted the hypothalamus. However — as with drug options focusing on the homeostatic mechanisms — success has been limited.

Possible Role of DBS for Obesity

More recent studies have explored a different mechanism: specifically, the “reward circuitry,” of the brain. Research has suggested that obesity is associated with a “relative imbalance” of the reward circuitry. Studies show that obese subjects — like those with addictive behaviors — are more impulsive and less able to delay gratification. The reward circuitry is intimately interconnected with the homeostatic mechanisms.

Together, these studies raise the possibility of new DBS approaches to the treatment of obesity. In DBS, a small electrode is surgically placed in a precise location in the brain. A mild electrical current is delivered to stimulate that area of the brain, with the goal of interrupting abnormal activity. Deep brain stimulation has become a standard and effective treatment for movement disorders such as Parkinson’s disease.

Just as stimulation of the brain areas responsible for abnormal movement helps “turn off” tremors in patients with Parkinson’s disease, stimulation of the areas involved in dysregulated reward circuitry might be able to “turn off” abnormal feeding behaviors in obese patients. The authors outline evidence implicating several different brain areas involved in the brain’s reward circuitry — particularly the “frontostriatal circuitry” — which could be useful targets for DBS.

Previous reports in individual patients have suggested that DBS performed for other reasons — particularly severe obsessive-compulsive disorder — have unexpectedly had unpredicted beneficial effects on addictive behaviors like smoking and overeating. Dr. Taghva and colleagues hope their review will open the way to further exploration of DBS as part of new and effective strategies for the treatment of obesity, perhaps in combination with therapies targeting the homeostatic mechanism.

Source: Science Daily

The simple act of picking up a pencil requires the coordination of dozens of muscles: The eyes and head must turn toward the object as the hand reaches forward and the fingers grasp it. To make this job more manageable, the brain’s motor cortex has implemented a system of shortcuts. Instead of controlling each muscle independently, the cortex is believed to activate muscles in groups, known as “muscle synergies.” These synergies can be combined in different ways to achieve a wide range of movements.

This graphic shows the brain, with the motor cortex highlighted in yellow.
Graphic: Christine Daniloff

A new study from MIT, Harvard Medical School and the San Camillo Hospital in Venice finds that after a stroke, these muscle synergies are activated in altered ways. Furthermore, those disruptions follow specific patterns depending on the severity of the stroke and the amount of time that has passed since the stroke.

The findings, published this week in the Proceedings of the National Academy of Sciences, could lead to improved rehabilitation for stroke patients, as well as a better understanding of how the motor cortex coordinates movements, says Emilio Bizzi, an Institute Professor at MIT and senior author of the paper.

“The cortex is responsible for motor learning and for controlling movement, so we want to understand what’s going on there,” says Bizzi, who is a member of the McGovern Institute for Brain Research at MIT. “How does the cortex translate an idea to move into a series of commands to accomplish a task?”

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17 August 2012

A WA study of an isolated population of Eastern European Gypsies known as “Bowlmakers” has unlocked clues about a serious developmental disease - congenital cerebellar ataxia.

Professor Luba Kalaydjieva and Dr Dimitar Azmanov, from The University of Western Australia, say the discovery of an important genetic mutation is likely to inspire other scientific work around the world.

The result of their research for the UWA-affiliated Western Australian Institute for Medical Research (WAIMR) was published online today in the prestigious American Journal of Human Genetics.

It involved working collaboratively with other Australian and European researchers to discover mutations within a gene which has never before been linked to this form of heredity ataxia in humans.

Ataxias are a large group of neurodegenerative disorders that affect the ability to maintain balance, and learn and maintain motor skills.  While many genes have already been implicated in hereditary ataxias, understanding their molecular basis is far from complete.  New knowledge will help the understanding of normal brain development and function, and the mechanisms of degeneration. 

"Gypsies are a founder population," Professor Kalaydjieva said.  "They are derived from a small number of ancestors and have remained relatively isolated from surrounding populations.  The Bowlmakers - known for their wooden handicrafts such as bowls and spoons - were an ideal group to study because they are a younger sub-isolate, showing limited genetic diversity.

"We studied a novel form of ataxia in 3 families in this ethnic group.  Clinical and brain-imaging investigations were done in Bulgaria, in collaboration with radiologists from Sir Charles Gairdner Hospital and Princess Margaret Hospital, and were followed-up by genetic studies at WAIMR and the Walter and Eliza Hall Institute (WEHI), Melbourne.

"Signs of ataxia were detected in early infancy when motor skills like crawling and rolling over did not develop.  The affected individuals presented with global developmental delay, ataxia and intellectual deficit.  MRI scans showed signs of degeneration of the cerebellum, which is part of the brain controlling motor and learning skills.  Overall, the life expectancy is not decreased but the quality of life is severely affected.

"The parents of the affected individuals did not present with any clinical symptoms of the ataxia, suggesting recessive inheritance," Dr Azmanov said.  "Our genetic studies showed unique changes in the gene encoding metabotropic glutamate receptor 1 (GRM1), which is important for the normal development of the cerbellar cortex.  The mutations inherited by all affected individuals from their unaffected carrier parents dramatically altered the structure of the GRM1 receptor.”

Professor Kalaydjieva said the exact pathogenetic mechanisms leading to the clinical manifestations and cerebellar degeneration are yet to be explained and that this opens novel research avenues for the wider scientific community.  ”It also remains to be seen if other ataxia patients around the world carry mutations in GRM1,” she said.

Source: The University of Western Australia

The human genome that researchers sequenced at the turn of the century doesn’t really exist as we know it.

The Human Genome project sequenced “the human genome” and is widely credited with setting in motion the most exciting era of fundamental new scientific discovery since Galileo. That’s remarkable, because in important ways “the human genome” that we have labeled as such doesn’t actually exist.

cosmin4000, istockphoto

Plato essentially asserted that things like chairs and dogs, which we observe in this physical world, and even concepts like virtues, are but imperfect representations or instances of some ideal that exists, but not in the material world. Such a Platonic ideal is “the human genome,” a sequence of about 3 billion nucleotides arrayed across a linear scale of position from the start of chromosome 1 to the end of the sex chromosomes. Whether it was obtained from one person or several has so far been shrouded in secrecy for bioethical reasons, but it makes no real difference. What we call the human genome sequence is really just a reference: it cannot account for all the variability that exists in the species, just like no single dog on earth, real or imagined, can fully incorporate all the variability in the characteristics of dogs.

Nor is the human genome we have a “’normal” genome. What would it mean to be “normal” for the nucleotide at position 1,234,547 on chromosome 11?  All we know is that the donor(s) had no identified disease when bled for the cause, but sooner or later some disease will arise. Essentially all available whole genome sequences show potentially disease-producing variants, even including nonfunctional genes, in donors who were unaffected at the time.

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August 16th, 2012

A parasite thought to be harmless and found in many people may actually be causing subtle changes in the brain, leading to suicide attempts.

New research appearing in the August issue of The Journal of Clinical Psychiatry adds to the growing work linking an infection caused by the Toxoplasma gondii parasite to suicide attempts. Michigan State University’s Lena Brundin was one of the lead researchers on the team.

About 10-20 percent of people in the United States have Toxoplasma gondii, or T. gondii, in their bodies, but in most it was thought to lie dormant, said Brundin, an associate professor of experimental psychiatry in MSU’s College of Human Medicine. In fact, it appears the parasite can cause inflammation over time, which produces harmful metabolites that can damage brain cells.

“Previous research has found signs of inflammation in the brains of suicide victims and people battling depression, and there also are previous reports linking Toxoplasma gondii to suicide attempts,” she said. “In our study we found that if you are positive for the parasite, you are seven times more likely to attempt suicide.”

The work by Brundin and colleagues is the first to measure scores on a suicide assessment scale from people infected with the parasite, some of whom had attempted suicide.

The Toxoplasma gondii parasite has been linked to inflammation in the brain, damaging cells. Image adapted from MSU press release image.

The results found those infected with T. gondii scored significantly higher on the scale, indicative of a more severe disease and greater risk for future suicide attempts. However, Brundin stresses the majority of those infected with the parasite will not attempt suicide: “Some individuals may for some reason be more susceptible to develop symptoms,” she said.

“Suicide is major health problem,” said Brundin, noting the 36,909 deaths in 2009 in America, or one every 14 minutes. “It is estimated 90 percent of people who attempt suicide have a diagnosed psychiatric disorder. If we could identify those people infected with this parasite, it could help us predict who is at a higher risk.”

T. gondii is a parasite found in cells that reproduces in its primary host, any member of the cat family. It is transmitted to humans primarily through ingesting water and food contaminated with the eggs of the parasite, or, since the parasite can be present in other mammals as well, through consuming undercooked raw meat or food.

Brundin has been looking at the link between depression and inflammation in the brain for a decade, beginning with work she did on Parkinson’s disease. Typically, a class of antidepressants called selective serotonin re-uptake inhibitors, or SSRIs, have been the preferred treatment for depression. SSRIs are believed to increase the level of a neurotransmitter called serotonin but are effective in only about half of depressed patients.

Brundin’s research indicates a reduction in the brain’s serotonin might be a symptom rather than the root cause of depression. Inflammation, possibly from an infection or a parasite, likely causes changes in the brain’s chemistry, leading to depression and, in some cases, thoughts of suicide, she said.

“I think it’s very positive that we are finding biological changes in suicidal patients,” she said. “It means we can develop new treatments to prevent suicides, and patients can feel hope that maybe we can help them.

“It’s a great opportunity to develop new treatments tailored at specific biological mechanisms.”

Source: Neuroscience News

ScienceDaily (Aug. 16, 2012) — Researchers have found what they believe is the key to understanding why the human brain is larger and more complex than that of other animals.

The human brain, with its unequaled cognitive capacity, evolved rapidly and dramatically.

"We wanted to know why," says James Sikela, PhD, who headed the international research team that included researchers from the University of Colorado School of Medicine, Baylor College of Medicine and the National Institutes of Mental Health. "The size and cognitive capacity of the human brain sets us apart. But how did that happen?"

"This research indicates that what drove the evolutionary expansion of the human brain may well be a specific unit within a protein — called a protein domain — that is far more numerous in humans than other species."

The protein domain at issue is DUF1220. Humans have more than 270 copies of DUF1220 encoded in the genome, far more than other species. The closer a species is to humans, the more copies of DUF1220 show up. Chimpanzees have the next highest number, 125. Gorillas have 99, marmosets 30 and mice just one. “The one over-riding theme that we saw repeatedly was that the more copies of DUF1220 in the genome, the bigger the brain. And this held true whether we looked at different species or within the human population.”

Sikela, a professor at the CU medical school, and his team also linked DUF1220 to brain disorders. They associated lower numbers of DUF1220 with microcephaly, when the brain is too small; larger numbers of the protein domain were associated with macrocephaly, when the brain is too large.

The findings were reported today in the online edition of The American Journal of Human Genetics. The researchers drew their conclusions by comparing genome sequences from humans and other animals as well as by looking at the DNA of individuals with microcephaly and macrocephaly and of people from a non-disease population.

"The take home message was that brain size may be to a large degree a matter of protein domain dosage," Sikela says. "This discovery opens many new doors. It provides new tools to diagnose diseases related to brain size. And more broadly, it points to a new way to study the human brain and its dramatic increase in size and ability over what, in evolutionary terms, is a short amount of time."

Source: Science Daily

ScienceDaily (Aug. 16, 2012) — In multiple sclerosis, the immune system attacks nerves in the brain and spinal cord, causing movement problems, muscle weakness and loss of vision. Immune cells called dendritic cells, which were previously thought to contribute to the onset and development of multiple sclerosis, actually protect against the disease in a mouse model, according to a study published by Cell Press in the August issue of the journal Immunity. These new insights change our fundamental understanding of the origins of multiple sclerosis and could lead to the development of more effective treatments for the disease.

"By transfusing dendritic cells into the blood, it may be possible to reduce autoimmunity," says senior study author Ari Waisman of University Medical Center of Johannes Gutenberg University Mainz. "Beyond multiple sclerosis, I can easily imagine that this approach could be applied to other autoimmune diseases, such as inflammatory bowel disease and psoriasis."

In an animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE), immune cells called T cells trigger the disease after being activated by other immune cells called antigen-presenting cells (APCs). Dendritic cells are APCs capable of activating T cells, but it was not known whether dendritic cells are the APCs that induce EAE.

In the new study, Waisman and his team used genetic methods to deplete dendritic cells in mice. Unexpectedly, these mice were still susceptible to EAE and developed worse autoimmune responses and disease clinical scores, suggesting that dendritic cells are not required to induce EAE and other APCs stimulate T cells to trigger the disease. The researchers also found that dendritic cells reduce the responsiveness of T cells and lower susceptibility to EAE by increasing the expression of PD-1 receptors on T cells.

"Removing dendritic cells tips the balance toward T cell-mediated autoimmunity," says study author Nir Yogev of University Medical Center of Johannes Gutenberg University Mainz. "Our findings suggest that dendritic cells keep immunity under check, so transferring dendritic cells to patients with multiple sclerosis could cure defects in T cells and serve as an effective intervention for the disease."

Source: Science Daily

By: Richard C. Lewis | 2012.08.16

Everyone knows the adage: “If something sounds too good to be true, then it probably is.” So, why, then, do some people fall for scams and why are older folks especially prone to being duped?

An answer, it seems, is because a specific area of the brain has deteriorated or is damaged, according to researchers at the University of Iowa. By examining patients with various forms of brain damage, the researchers report they’ve pinpointed the precise location in the human brain, called the ventromedial prefrontal cortex, that controls belief and doubt, and which explains why some of us are more gullible than others.

Patients with damage to the ventromedial prefrontal cortex were roughly twice as likely to believe a given ad, even when given disclaimer information pointing out it was misleading. And, they were more likely to buy the item, regardless of whether misleading information had been corrected. Photo by Bill Adams.

“The current study provides the first direct evidence beyond anecdotal reports that damage to the vmPFC (ventromedial prefrontal cortex) increases credulity. Indeed, this specific deficit may explain why highly intelligent vmPFC patients can fall victim to seemingly obvious fraud schemes,” the researchers wrote in the paper published in a special issue of the journal Frontiers in Neuroscience.

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16 August 2012

Ten out of 11 patients with severe Tourette’s Syndrome have reported improvement after receiving deep brain stimulation surgery, according to University of New South Wales research published in the American Journal of Psychiatry. 

Tourette’s Syndrome is a neurological disorder characterised by repetitive involuntary movements and vocalisations called tics and can also include behavioural difficulties. 

Deep brain stimulation is a therapeutic technique that involves placing electrodes at specific sites in the brain to deliver continuous stimulation from an implanted generator.

Study leader, UNSW Scientia Professor Perminder Sachdev, says deep brain stimulation may have an important role in treating Tourette’s Syndrome in its most severe form. He says tics are generally treated with medications that work well in about 50 to 70 per cent of cases. Drugs, however, can have side effects in some patients. 

Eleven patients, eight of them in their late thirties with severe Tourette’s Syndrome, underwent deep brain stimulation at St Andrew’s Hospital in Brisbane - under the care of neurologist Professor Peter Silburn and neurosurgeon Associate Professor Terry Coyne - as part of the study. They were followed up initially one month after surgery and then around a year after the procedure.

Ten out of the 11 patients involved in the joint UNSW Medicine and Asia-Pacific Centre for Neuromodulation study reported immediate improvement in tic severity soon after the treatment, with an overall 48 per cent reduction in monitor tics and a 57 per cent reduction in phonic tics at final follow-up. Associated psychiatric symptoms also improved.

“Because deep brain stimulation involves brain surgery, it has some risks, even though these are low. It is therefore only likely to be used in individuals who are significantly affected by their tics,” Scientia Professor Sachdev says.

“Our study demonstrates that when suitably selected, patients can benefit greatly from deep brain stimulation.”

Source: University of New South Wales

TAU research says genetics can reveal your geographic ancestral origin

While your DNA is unique, it also tells the tale of your family line. It carries the genetic history of your ancestors down through the generations. Now, says a Tel Aviv University researcher, it’s also possible to use it as a map to your family’s past.

Prof. Eran Halperin of TAU’s Blavatnik School of Computer Science and Department of Molecular Microbiology and Biotechnology, along with a group of researchers from University of California, Los Angeles, are giving new meaning to the term “genetic mapping.” Using a probabilistic model of genetic traits for every coordinate on the globe, the researchers have developed a method for determining more precisely the geographical location of a person’s ancestral origins.

The new method is able to pinpoint more specific locations for an individual’s ancestors, for example placing an individual’s father in Paris and mother in Barcelona. Previous methods would “split the difference” and place this origin inaccurately at a site between those two cities, such as Lyon.

Published in the journal Nature Genetics, this method has the potential to reveal the ancestry, origins, and migration patterns of many different human and animal populations. It could also be a new model for learning about the genome.

Points of origin

There are points in the human genome called SNPs that are manifested differently in each individual, explains Prof. Halperin. These points mutated sometime in the past and the mutation was then passed to a large part of the population in a particular geographic region. The probability of a person possessing these mutations today varies depending on the geographical location of those early ancestors.

"We wanted to ask, for example, about the probability of having the genetic mutation ‘A’ in a particular position on the genome based on geographical coordinates," he says. When you look at many of these positions together in a bigger picture, it’s possible to group populations with the same mutation by point of origin.

To test their method, Prof. Halperin and his fellow researchers studied DNA samples from 1,157 people from across Europe. Using a probabilistic mathematical algorithm based on mutations in the genome, they were able to accurately determine their ancestral point or points of origin using only DNA data and the new mathematical model, unravelling genetic information to ascertain two separate points on the map for the mother and father. The researchers hope to extend this model to identify the origins of grandparents, great-grandparents, and so on.

The new method could provide information that has applications in population genetic studies — to study a disease that impacts a particular group, for example. Researchers can track changes in different genomic traits across a map, such as the tendency for southern Europeans to have a mutation in a gene that causes lactose intolerance, a mutation missing from that gene in northern Europeans.

A closer look at migration

The researchers believe that their model could have also relevance for the animal kingdom, tracking the movement of animal populations. “In principle, you could figure out where the animals have migrated from, and as a result learn about habitat changes due to historical climate change or other factors,” says Prof. Halperin.

Source: Tel Aviv University