Before spending a lot of money on piano and singing lessons some day parents will be able to get their kids genetically tested to check for musically inclined genetic profiles. Why waste all that money on a kid who might turn out to be innately tone deaf? A fairly preliminary study in Finland finds evidence for a genetic component to musical ability.
Molecular and statistical genetic studies in 15 Finnish families have shown that there is a substantial genetic component in musical aptitude. Musical aptitude was determined using three tests: a test for auditory structuring ability (Karma Music test), and the Seashore pitch and time discrimination subtests. The study represents the first systematic molecular genetic study that aims in the identification of candidate genes associated with musical aptitude.
The identified regions contain genes affecting cell extension and migration during neural development. Interestingly, an overlapping region previously associated with genetic locus for dyslexia was found raising a question about common evolutionary background of music and language faculties. The results show that musical aptitude is likely to be regulated by several predisposing genes/variants.
“The identification of genes/genetic variants involved in mediating music perception and performance would offer new tools to understand the role of music in human brain function, human evolution and its relationship to language faculty”, says the leader of the study, Dr. Irma Järvelä from the University of Helsinki.
While this study did not identify specific genetic variants as causes of differences in musical ability that level of detail will not be a long time in coming. The continued rapid decline in genetic sequencing costs will make complete personal genetic sequencing affordable in the 2010s. The resulting flood of genetic sequencing data will make identification of genetic causes of cognitive abilities far easier to do than is the case today.
By the year 2035 I expect enhanced musical ability to become a very popular option for parents making genetic engineering decisions in the design of their children.
Some kids have genes that make them better able to handle abuse with fewer long term repercussions.
Some forms of a gene that controls the body's response to stress hormones appear to protect adults who were abused in childhood from depression, psychiatrists have found.
People who had been abused as children and who carried the most protective forms of the gene, called corticotropin-releasing hormone receptor one (CRHR1), had markedly lower measures of depression, compared with people with less protective forms, the researchers found in a recent study.
The findings could guide doctors in finding new ways to treat depression in people who were abused as children, says senior author Kerry Ressler, MD, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine.
This is not the first report of genetic variations of brain genes that affect how well developing children handle abuse and adversity. Previous research found that children who carry the low MAOA activity allele (MAOA-L) and who are abused demonstrate more aggressive and violent behavior as adults.
Some kids have genes that let them shrug off all sorts of abuse and basically keep trucking. Other kids aren't so lucky. Those latter kids become problems for the rest of us too. Violence prone adults pose a danger to whoever they come into contact with.
Early identification of kids with genetic vulnerabilities might some day get used to guide more aggressive state intervention into bad families. You can imagine social workers arguing to take a kid out of an abusive home more quickly if the has genes that make him or her vulnerable to permanent and problematic behavioral and personality alterations.
Once offspring genetic engineering becomes possible we can't assume parents should avoid giving offspring these genetic variations that make kids more vulnerable to abuse. There might be benefits to these alleles in more benign environments. Though I see a more compelling argument for discouraging the passing along of these alleles if either prospective parent has a genetic profile and brain scans that suggests he or she is likely to abuse kids.
Here is news some new moms can use. Whether breast feeding will boost offspring IQ comes down to which genetic variations the babies carry.
DURHAM, N.C. – The known association between breast feeding and slightly higher IQ in children has been shown to relate to a particular gene in the babies, according to a report this week in the Proceedings of the National Academy of Sciences.
In two studies of breast-fed infants involving more than 3,000 children in Britain and New Zealand, breastfeeding was found to raise intelligence an average of nearly 7 IQ points if the children had a particular version of a gene called FADS2.
The distribution of FADS2 genetic variants probably varies around the world. Anyone know of a source of data for FADS2 genetic variant distributions in human races and local ethnic groups? That information would probably indicate whether results would hold up in all human populations.
"There has been some criticism of earlier studies about breastfeeding and IQ that they didn't control for socioeconomic status, or the mother's IQ or other factors, but our findings take an end-run around those arguments by showing the physiological mechanism that accounts for the difference," said Terrie Moffitt, a professor of psychological and brain sciences in Duke University's Institute for Genome Sciences and Policy.
Moffitt, who performed the research with her husband and co-author Avshalom Caspi at King's College in London, found that the baby's intellectual development is influenced by both genes and environment or, more specifically, by the interaction of its genes with its environment.
"The argument about intelligence has been about nature versus nurture for at least a century," Moffitt said. "We're finding that nature and nurture work together."
These results suggest that most women should breast feed. Only 10% of the women in the study groups had babies with genetic profiles which prevented a benefit from breast feeding.
Ninety percent of the children in the two study groups had at least one copy of the "C" version of FADS2, which yielded higher IQ if they were breast-fed. The other 10 percent, with only the "G" versions of the gene, showed no IQ advantage or disadvantage from breastfeeding.
A cheap test for FADS2 variants could help millions of women weigh the costs and benefits of breast feeding. Find out from a genetic test whether newly born junior will turn out smarter if you structure your life so that breast feeding is practical.
The benefit of the "C" version of FADS2 might come from its ability to convert other fatty acids to DHA.
The gene was singled out for the researchers' attention because it produces an enzyme that helps convert dietary fatty acids into the polyunsaturated fatty acids DHA (docosahexaenoic acid) and AA (arachidonic acid) that have been shown to accumulate in the human brain during the first months after birth.
A baby formula high in DHA might deliver the same benefit as breast feeding and deliver that benefit regardless of genetic variations carried by a baby. Mom eating salmon every day and then breast feeding might similarly deliver that benefit regardless of genetic variation.
A 7 point IQ boost is a really big deal. A country that boosted its average IQ by 7 points would experience a huge boost in economic growth and a rise in per capita GDP as the smarter kids made their way into the labor market.
The variation of apolipoprotein E known as apoE4 gene doesn't just increase the risk of Alzheimer's Disease. Carriers of the apoE4 genetic variant show differences in mental performance as children.
PORTLAND, Ore. - Children who possess a gene known to increase the risk of Alzheimer's disease already show signs of reduced cognitive function, an Oregon Health & Science University study has found.
Scientists in the OHSU School of Medicine discovered that 7- to 10-year-olds with a member of a family of genes implicated in development, nerve cell regeneration and neuroprotection display reduced spatial learning and memory, associated with later-life cognitive impairments.
Results of the study, presented today at Neuroscience 2007, the 37th annual meeting of the Society for Neuroscience in San Diego, suggest that changes predisposing a person to Alzheimer's and other forms of dementia might occur much sooner in the brain than previously thought.
"One of our questions has been is this a risk that only happens with age, or is it already - early on - the cause of differences in performance," said study co-author Jacob Raber, Ph.D., associate professor of behavioral neuroscience and neurology in the OHSU School of Medicine. "This study suggests there already are cognitive differences very early on in life."
The researchers looked at 55 kids aged 7 to 10.
"When we looked at non-demented healthy elderly, we saw the clear effect of apoE4," he said. "So it's not just Alzheimer's disease. ApoE4 carriers generally do worse in our tests. Among the nondemented oldest old, where the mean age is 82, those who have apoE4 do less well" on cognitive tests.
In their study on children, Raber and colleagues - lead author Summer Acevedo, Ph.D., OHSU postdoctoral fellow, and Byung Park, Ph.D., senior biostatistics associate in the OHSU Biostatistics & Bioinformatics Shared Resource - examined 55 healthy boys and girls ages 7 to 10. Among them were eight girls and six boys who carried the apoE4 gene, and 17 girls and 24 boys who didn't.
Quite a few leftists want us to accept as a matter of secular faith that genetic variants don't create substantial differences in intellectual performance. But the accumulating evidence unsurprisingly (after all, the mind is a manifestation of physical phenomena) says otherwise.
Falling costs and falling risks for starting pregnancies in vitro are probably going to lead many prospective parents to select against embryos that carry apoE4. What ambitious parent wants their son or daughter to do poorly on the "Memory Island" test? None I hope.
Raber, Acevedo and Park found that apoE4 carriers scored lower in location recognition tests, and non-apoE4 carriers outperformed apoE4 carriers in the "Memory Island" test by navigating closer to the visible target location. Also, non-apoE4 carriers showed spatial memory retention when a target wasn't present and searched more frequently for the targets in the appropriate quadrants while apoE4 carriers did not.
In all, 75.6 percent non-apoE4 carriers showed target preference compared with only 43 percent of apoE4 carriers.
I'd like to know the frequency of apoE4 as a function of social class, level of education, tested IQ, and income. Does apoE4 show up at lower frequency in smarter people?
I'd also like to know what advantage apoE4 confers that allowed it to become fairly frequent in human populations. One source on apoE4 frequencies in different populations puts it at 11.7% in Tyrolean Europeans, 37% in Khoi San blacks, and 4.9% in Chinese. In recent centuries has apoE4 experienced selective pressure against it?
There's been controversy on whether those who take selective serotonin reuptake inhibitor (SSRI) antidepressants are at greater risk of thinking suicidal thoughts. It is a difficult effect to tease out since people depressed enough to take SSRIs are already at greater risk of depression and some of them probably become less at risk of suicide because SSRIs brighten their mood. But maybe others react to SSRIs by becoming more suicidal. Well, genetic testing might have allowed some scientists to discover who will be at greater risk of suicidal thoughts as a result of taking an SSRI. People taking the SSRI drug citalopram who have certain variants of glutamate receptor genes are at much higher risk of suicide thoughts.
Specific variations in two genes are linked to suicidal thinking that sometimes occurs in people taking the most commonly prescribed class of antidepressants, according to a large study led by scientists at the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH). Depending on the particular mix inherited, these versions increased the likelihood of such thoughts from 2- to15-fold, the study found. About 1 percent of adult patients were deemed to be at high genetic risk, 41 percent at elevated risk and 58 percent at lower risk.
If confirmed, the findings may hold promise for genetic testing, as more such markers are identified.
The "If confirmed" is important. They looked at many genes and so a false positive just by chance is possible.
Risk increased proportionately if a participant had two, as opposed to just one of the suspect versions. Both genes code for components of the brain’s glutamate chemical messenger system, which recent studies suggest is involved in the antidepressant response.
Overall, about 6 percent of 1,915 patients with depression reported that they started to have suicidal thoughts while taking an antidepressant. This rate soared to 36 percent among the few patients with both of the suspect gene versions; 59 percent of the patients who had suicidal thoughts had at least one of the versions.
Francis J. McMahon, M.D., Gonzalo Laje, M.D., NIMH Mood and Anxiety Disorders Program, and colleagues at the National Human Genome Research Institute (NHGRI), Mount Sinai School of Medicine, and the University of Texas Southwestern Medical Center, report on their findings in the October, 2007 issue of The American Journal of Psychiatry.
We are well within 10 years of widespread use of genetic testing when choosing between drugs and making other treatment decisions. Clinical practice will take a big turn when genetic tests can predict which drugs will cause which side effects in each patient.
The researchers found that certain versions of two genes that code for glutamate receptors – the receiving stations for the neurotransmitter’s chemical messages – were more prevalent in patients with suicidal thinking. How the newly identified versions affect the workings of glutamate receptors to confer increased risk remains to be discovered. It’s also not yet known whether the findings generalize to other antidepressants.
One percent of the study participants had a version of the kainate receptor gene, GRIK2, that increased the odds for suicidal thinking more than 8-fold. Forty-one percent of participants had a version of the AMPA receptor gene, GRIA3, that raised the odds nearly 2-fold. About one-half of 1 percent of participants had both high risk gene versions, boosting the odds 15 fold – but this was the case for only 11 participants, of whom four developed suicidal thinking.
The size of the observed effects makes it likely that their finding is real. It is the sort of result that could be confirmed pretty quickly with sufficient funding.
A discovery like this one is not just useful for making drug choices. It also provides clues about what causes people to become suicidal. A better understanding of the mechanisms which cause suicidal thoughts will lead to ways to stop suicidal thoughts.
Philadelphia, PA, September 26, 2007 – Do gene variants that convey risk for schizophrenia affect apparently healthy individuals" Although these genes are present in every human, individuals may have different versions of these genes, called alleles. While many people who possess these “risk alleles” do not end up with schizophrenia, this does not mean they are unaffected by the presence of the risk allele. In the largest study of its kind to date, scheduled for publication in the October 1st issue of Biological Psychiatry, researchers sought to examine the impact of a few particular genes, known to be associated with a diagnosis of schizophrenia, on a healthy population.
Stefanis and colleagues recruited more than 2000 young men and measured dimensions of their cognitive abilities that tend to be impaired in individuals diagnosed with schizophrenia. The authors also measured schizotypal personality traits, which represent behaviors that are associated with schizophrenia, such as atypical behaviors and beliefs, suspiciousness or paranoia, and discomfort in social situations. They then genotyped these volunteers in relation to the four most prominent schizophrenia candidate genes: Neuregulin1 (NRG1), Dysbindin (DTNBP1), D-amino-acid oxidase activator (DAOA), and D-amino-acid oxidase (DAAO). According to Nicholas Stefanis, the lead author on the paper, their study showed “that apparently normal individuals who posses several risk alleles within these susceptibility schizophrenia genes, have indeed minute decrements in cognitive ability such as decreased attentional capacity and worse performance on memory tasks, and alterations in schizotypal beliefs and experiences.” In other words, they found that the healthy individuals who possessed the risk variants within the DNTBP1, NRG1, and DAAO genes exhibited small reductions in their cognitive performance and had atypical experiences that might be associated with schizophrenia.
How many people have atypical beliefs because they are smart enough to think their way outside the box of the conventional consensus? How many have atypical beliefs because they carry genetic variations that alter the way they view evidence?
Do we as a total society benefit from some people carrying alleles that make them think atypical thoughts? Are smart people with schizophrenia risk genes who do not get schizophrenia more creative, on average, than smart people without these schizophrenia risk genes? Is there some optimal small dose schizophrenia risk alleles that, when combined with high IQ, produces great scientists, inventors, and innovators? Whatever genes made the unusual mind of Vincent Van Gogh might get clipped out of future generations of humanity.
One of my concerns with mental illness risk genes going forward comes from the ability we are gaining to screen and choose amongst our genes to decide what to pass on to our offspring. Will prospective parents take such a risk minimizing approach to offspring genetic allele selection that future generations will have brains that make them more likely to accept the conventional wisdom and to go along with the consensus of elites and masses? Will future societies become more sheepish and less free as a result?
A variation in a gene called GRIK4 appears to make people with depression more likely to respond to the medication citalopram (Celexa) than are people without the variation, a study by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, has found. The increased likelihood was small, but when people had both this variation and one in a different gene shown to have a similarly small effect in an earlier study, they were 23 percent more likely to respond to citalopram than were people with neither variation.
The finding addresses a key issue in mental health research: the differences in people’s responses to antidepressant medications, thought to be based partly on differences in their genes. Some patients respond to the first antidepressant they attempt, but many don’t. Each medication takes weeks to exert its full effects, and patients’ depression may worsen while they search for a medication that helps. Genetic studies, such as the one described here, may lead to a better understanding of which treatments are likely to work for each patient.
The ability to avoid the use of drugs that will fail will reduce time until effective treatments are used and therefore, reduce suffering, speed recovery, and reduce costs.
Genetic variations for serotonin and glutamate neuotransmitter receptors influenced how well people responded to citalopram.
In the newest study, researchers examined the genetic material of more of the patients who had participated in STAR*D, for a total of 1,816 samples, and repeated the comparison of DNA from citalopram responders and nonresponders. They discovered that people with the variation in the GRIK4 gene had a higher likelihood of response, and again found that the variation in the HTR2A gene also made people more likely to respond. The results were reproduced, strengthening their validity.
The protein produced by HTR2A acts as a receptor on brain cells for the chemical messenger serotonin, one of several neurotransmitters that enable the cells to communicate with each other. The discovery that a variation in a serotonin-related gene could affect response to citalopram was not entirely surprising, since the serotonin system is known to be involved in depression. Citalopram targets this system.
But GRIK4 makes a protein that acts as a receptor in a different neurotransmitter system, the glutamate system. Recent studies suggest that the glutamate system also is involved in depression, an assertion supported by the new finding.
Genetic testing for drug selection will also help to avoid drugs that will cause patients side effects. For each drug genetic profiles will be found that put one at much higher risk of adverse reactions,. Everyone will have a complete genetic profile that will help guide drug selection for most effect results with least risk of side effects.
A genetic variant of a neuron adrenergic receptor that binds neurotransmitter noradrenaline boosts recall of emotionally intense memories.
People with a particular gene variant are better at remembering emotionally laden memories than people with the more common version of the gene, research shows. The gene, called ADRA2B, is involved in detecting brain chemicals related to emotional arousal.
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The research highlighted the effect of the gene in stark terms: survivors of the 1994 Rwandan genocide were more likely to harbour persistent memories of the conflict if they had the variant version of the gene. The variant is present in 12% of people of African ancestry and in 30% of Causasians.
The researchers showed Swiss and Rwandan experimental subjects pictures with neutral, emotionally negative, and emotionally positive content. Later they had the subjects write down memories of what they saw in the pictures. The Rwandans were refugees living in Uganda who had seen some terrible things in the intertribal kill-fests in Rwanda.
While more Europeans carry the genetic variant that enhances emotionally laden memory recall the Rwandans who had that genetic variant had better recall of negative emotional events.
The researchers found that, in both groups, people carrying the ADRA2B gene variant were "substantially more likely" to remember both positive and negative pictures than people with other forms of the gene. Neutral images were recalled to the same degree by people with and without the variant.
However, Rwandans with the variant had far higher recall of negative emotional events than the Europeans who carried it – and this was unrelated to whether or not they suffered from post traumatic stress disorder.
The Rwandans might have some other genetic variants that work synergistically with ADRB2B to enhance negative memory recall.
Think about the implications. Groups differ in their average tendency to remember bad memories. Does that make some groups and some individuals more likely to hold grudges, seek revenge, and dwell on past events? Do people who better remember bad and good events try harder to set themselves up for repeats of great past events and to avoid repeats of terrible past events? Does this create different cultures in different parts of the world?
As gene testing costs go down by orders of magnitude we are going to see a flood of reports of genetic variations that influence cognitive function in a large variety of ways. The amount of human behavior ascribed to free will is going to shrink. The amount ascribed to current environmental influences will shrink as well.
A new research report in Plos One provides support for the theory that abused children who have low level expression of the gene for monoamine oxidase A (MAOA) are more at risk of becoming violent and anti-social.
Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOA×ETLE (F1,227 = 8.20, P = 0.005) and gender×MAOA×ETLE (F1,227 = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed G×E interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.
The first report I came across a few years ago on a relationship between low levels of monoamine oxidase A (MAOA), abused children, and violent behavior came from a Dunedin New Zealand twins study. See my post A violence promoting gene and the follow-up and additional related info in the post Serotonin Transporter Gene Linked To Depression, Binge Drinking. Plus, see the post Initial Bullying In Late In Adolescence Causes Most Harm.
What I find interesting about the MAOA variations: The variation that makes one more violent in response to abuse basically makes humans more sensitive to environmental influence. The higher MAOA activity variation makes humans less sensitive to the environment. So the ability of humans to be influenced by the environment is under genetic control.
The fact that genetic variations cause differences in environmental sensitivity has future implications. When offspring genetic engineering enters the realm of the safely doable prospective parents are going to choose against genetic variations that cause environmental sensitivity for behavioral attributes where the parents have strongly held preferences. For example, parents who want total "Goodie Two Shoes" kids are going to choose against genetic variations that create the risk that the kids might turn out violent.
My prediction: Parents will choose genetic variations that make their kids more genetically determined, not less. Parents will choose against genetic variations that put them at 10% risk of some undesired attribute if some other genetic variations would make them at only 1% or a tenth of a percent risk of that the undesirable attribute. Similarly, parents will choose genetic variations that greatly increase the odds of various desired attributes. Basically, genetic variations that leave offspring at moderate odds (say 30% to 70%) of some outcome will get rejected in favor of genetic variations that make attributes either highly likely or highly unlikely.
A twins study provides evidence for genetic causes of both altruism and religiousness.
Minneapolis – April 05, 2007 - A new study in Journal of Personality shows that selfless and social behavior is not purely a product of environment, specifically religious environment. After studying the behavior of adult twins, researchers found that, while altruistic behavior and religiousness tended to appear together, the correlation was due to both environmental and genetic factors.
According to study author Laura Koenig, the popular idea that religious individuals are more social and giving because of the behavioral mandates set for them is incorrect. “This study shows that religiousness occurs with these behaviors also because there are genes that predispose them to it.”
“There is, of course, no specific gene for religiousness, but individuals do have biological predispositions to behave in certain ways,” says Koenig. “The use of twins in the current study allowed for an investigation of the genetic and environmental influences on this type of behavior.”
This research is another example of the way that genes have an impact on behavior. “Society as a whole assumes that home environments have large impacts on behavior, but studies in behavior genetics are repeatedly showing that our behavior is also influenced by our genes,” says Koenig.
Famed University of Minnesota twins researcher Thomas Bouchard is one of the names on the research paper. Koenig is working with experienced twins researchers. Here's an excerpt from the paper's abstract:
In order to investigate this question, religiousness, antisocial behavior, and altruistic behavior were assessed by self-report in a sample of adult male twins (165 MZ and 100 DZ full pairs, mean age of 33 years). Religiousness, both retrospective and current, was shown to be modestly negatively correlated with antisocial behavior and modestly positively correlated with altruistic behavior.
So religious people are both more altruistic and less anti-social on average. This part is interesting. Sounds like the same genetic factors that increase religiousness also increase altruism. What does that tell us about religiousness?
Altruistic behavior also shared most all of its genetic influence, but only half of its shared environmental influence, with religiousness.
My question: Is altruism getting selected for in industrialized societies? I suspect so because religiousness is getting selected for. Also, selfish people are probably less willing to have kids due to all the work entailed.
Also see my post about previous research by Koenig: Twins Study Finds Adult Religiosity Heritable
A professor at the University of Maryland Child Development Laboratory claims the short version of a gene involved in metabolism of neurotransmitter serotonin combined with stress creates a shy kid.
In a study published in the February issue of Current Directions in Psychological Science, Nathan Fox, professor and director of the Child Development Laboratory, and his team found that kids who are consistently shy while growing up are particularly likely to be raised by stressed-out parents, and to possess a genetic variant associated with stress sensitivity.
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Like all genes, the particular serotonin-related gene examined in this study has 2 alleles, which can be long or short. The protein produced by the short form of the gene is known to predispose towards some forms of stress sensitivity.
Fox's research found that among children exposed to a mother's stress, it was only those who also inherited the short forms of the gene who showed consistently shy behavior.
"If you have two short alleles of this serotonin gene, but your mom is not stressed, you will be no more shy than your peers as a school age child," says Fox. "But we found that when stress enters the picture, the gene starts to show a strong relationship to the child's behavior," says Fox. "If you are raised in a stressful environment, and you inherit the short form of the gene, there is a higher likelihood that you will be fearful, anxious or depressed."
From this press release we do not know the sample size of his study. But his result is at least plausible.
Suppose this gene's short version works as advertised. When offspring genetic engineering becomes possible will prospective parents choose to make shyness a thing of the past? Will some future generation be anywhere between extroverted and extremely extroverted? If so, what will we lose? My guess is that governments will become more corrupt as people with genetically engineered lack of shyness feel less fear of getting held up to public condemnation.
People are known to differ markedly in their response to sleep deprivation, but the biological underpinnings of these differences have remained difficult to identify. Researchers have now found that a genetic difference in a so-called clock gene, PERIOD3, makes some people particularly sensitive to the effects of sleep deprivation. The findings, reported by Antoine Viola, Derk-Jan Dijk, and colleagues at the University of Surrey's Sleep Research Center, appear online this week in the journal Current Biology, published by Cell Press.
There are two variants of the PERIOD3 gene found in the human population, encoding either long or short versions of the corresponding protein. Each individual will possess two copies of the gene, either of which might be the long or short form. Previous work had indicated that the different forms of the gene appear to influence characteristic morning and evening activity levels—for example, "owl" versus "lark" tendencies.
In the new work, a multidisciplinary research team consisting of biological scientists and psychologists compared how individuals possessing only the longer gene variant and those possessing only the shorter one coped with being kept awake for two days, including the intervening night. The researchers found that although some participants struggled to stay awake, others experienced no problems with the task.
The results were most pronounced during the early hours of the morning (between 4 and 8 a.m.), during which individuals with the longer variant of the gene performed very poorly on tests for attention and working memory.
But how do the carriers of the short and long versions perform during the day when they have plenty of sleep?
Carriers of the longer version spent a larger portion of their sleep time in the deepest sleep state. My guess is that confers some sort of advantage. Any idea what that advantage might be?
An additional finding was that the effects of this gene on performance may be mediated by its effects on sleep. When the volunteers were allowed to sleep normally, those possessing only the longer form of the gene spent about 50% more of their time in slow-wave sleep, the deepest form of sleep. Slow-wave sleep is a marker of sleep need, and it is known that carrying a sleep debt makes it very difficult to stay awake and perform at night.
What I'd like to know: Do the people with the longer form of the gene form more memories when they sleep? I ask this because if there are two versions of the gene widespread then likely each version provides advantages and disadvantages. What advantage does the long version provide that compensates for its disadvantages when one stays up all night?
When offspring genetic engineering becomes possible prospective parents are going to be faced with thousands or even tens of thousands of trade-offs between different genetic variations for their offspring. Make your kid a night owl? Or make him wake up at the crack of dawn? Make your kid able to handle lots of sleep disruptions and get by on less sleep? Or perhaps make her brain age more slowly or form more memories per time asleep?
BUDAPEST, HUNGARY, March 9 – Ever wonder why some women seem to be more ill-tempered than others? University of Pittsburgh researchers have found that behaviors such as anger, hostility and aggression may be genetic, rooted in variations in a serotonin receptor gene. Indrani Halder, Ph.D., of the Cardiovascular Behavioral Medicine Program at the University of Pittsburgh, will present the findings today at the American Psychosomatic Society's Annual Meeting, held in Budapest, Hungary.
Previous studies have associated the hormone serotonin with anger and aggression in both humans and animals and have shown that increased serotonin activity is related to a decrease in angry and aggressive behaviors. In the study being presented today, researchers sought to determine if this relationship was genetically determined. The study is the first to look at the relationship between variations in the serotonin receptor 2C gene and anger and hostility.
Completed at the University of Pittsburgh's Behavioral Physiology Laboratory, the study looked at 550 unrelated women of European descent. In order to find normal variations in genes and behavior, the women were not prescreened for behavioral type. Researchers found that those who had one or both of two alterations in the promoter region of the serotonin receptor 2C gene were more likely to score lower on two common tests for anger, hostility and aggression.
But not so fast. Robert Plomin, who has spent years trying to find gene alleles that produce differences in intelligence, thinks the search for genes that influence cognitive qualities is so hard that these latest results are unlikely to be correct.
"Individual differences in aggression and anger are influenced by genes -- as are all personality traits -- but progress in identifying the genes has been slower than researchers expected," added Prof Robert Plomin, deputy director of the Social, Genetic and Development Psychiatry Centre, London. "Thousands of reports of this gene or that gene being related to complex traits or common disorders in the end fail to replicate, not just for behaviour but also for medical problems such as dementia and heart disease."
I am very keen to find out which genetic variations create differences in personality, intelligence, and other aspects of cognitive function. But since Plomin and other scientists think each mental trait is controlled by many gene alleles and each variation contributes only a small amount to the total result. So identifying a genetic influence above the background noise of other genetic variations and environmental influences is very difficult.
The solution to this problem? Huge decreases in the cost of DNA testing. Gene chips that test hundreds of thousands of single letter DNA differences at once have already hit the market quite recently. We need gene testing cheap enough that thousands or tens of thousands of genetic variations can be checked in each person in a study. We also need costs so low that thousands or even tens of thousands of people can get checked at once. Then scientists will be able to control for enough genetic variations at once to identify those that are really influencing cognitive function.
We are waiting for advances in gene chip and microfluidics biotechnology so that scientific questions about human genomes become easy to answer. Most of what we are going to learn about human genetic differences is going to be figured out in a short period of time after decades of attempts to answer those questions. The instrumentation advances are more important than any one or ten of the scientific discoveries that will come from them.
Some serious engineering trade-offs came with making humans more intelligent.
Most people inherit a version of a gene that optimizes their brain's thinking circuitry, yet also appears to increase risk for schizophrenia, a severe mental illness marked by impaired thinking, scientists at the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) have discovered. The seeming paradox emerged from the first study to explore the effects of variation in the human gene for a brain master switch, DARPP-32.
The researchers identified a common version of the gene and showed how it impacts the way two key brain regions exchange information, affecting a range of functions from general intelligence to attention.
If higher intelligence was a longer running trait in the human species it is unlikely that we'd have IQ-boosting genetic variations that come with such serious downsides. Bad side effects of genes that provide some benefit are usually a sign that the genetic adaptation in question is a recent response to a recent selective pressure.
Three fourths of subjects studied had at least one copy of the version that results in more efficient filtering of information processed by the brain's executive hub, the prefrontal cortex. However, the same version was also more prevalent among people who developed schizophrenia, a severe mental illness marked by delusions, hallucinations and impaired emotion that affects one percent of the population.
"We have found that DARPP-32 shapes and controls a circuit coursing between the human striatum and prefrontal cortex that affects key brain functions implicated in schizophrenia, such as motivation, working memory and reward related learning," explained Andreas Meyer-Lindenberg, M.D.
"Our results raise the question of whether a gene variant favored by evolution, that would normally confer advantage, may translate into a disadvantage if the prefrontal cortex is impaired, as in schizophrenia," added Daniel Weinberger, M.D. "Normally, enhanced cortex connectivity with the striatum would provide increased flexibility, working memory capacity and executive control. But if other genes and environmental events conspire to render the cortex incapable of handling such information, it could backfire -- resulting in the neural equivalent of a superhighway to a dead-end."
I expect when offspring genetic engineering becomes widespread people will have to face many tough questions about how to weigh the benefits and risks of large numbers of genetic variations they could give their offspring. Some humans are not cognitively well designed to model complex trade-offs that involve probabilities I expect a lot of bad decision-making by prospective parents.
A study on twins and their offspring provides another chunk of evidence that the effect of environment has been overrated. The parents fight because it is in their genes to do so and so their kids behave poorly due to the same genes.
Children's conduct problems--skipping school, sneaking out of the house, lying to parents, shoplifting, or bullying other children--are a major source of concern for parents and teachers. As a potential cause of these problems, parents' marital conflict has received a lot of research attention. Now a new study finds that parents' fighting may not be to blame but rather that parents who argue a lot may pass on genes for disruptive behavior to their children.
The findings are published in the January/February 2007 issue of the journal Child Development.
A group of researchers from the University of Virginia and several other universities looked at this question, studying 1,045 twins and their 2,051 children. Some of the parents were identical twins and shared all of their genes and some were fraternal and shared only half of their genes. The study found that parents' fighting is not likely a cause of children's conduct problems. On the other hand, parents' genes influenced how often they argued with their spouses and these same genes, when passed to their children, caused more conduct problems.
"This study suggests that marital conflict is not a major culprit, but genes are," said K. Paige Harden, the lead researcher and professor of psychology at the University of Virginia. "Our findings have potential implications for treating conduct problems: Focusing on a child's parents, as is common in family therapy, may not be as effective as focusing on the child."
So if your kids are bad you and your spouse are still to blame. But you are to blame for your genes, not for your behavior.
What I want to know: When offspring genetic engineering becomes possible will people who tend to have low triggers for violence decide to edit out the genetic sequences that cause this when choosing genes for their offspring? Or will they give their kids even stronger doses of the genes that make them carry on yelling and screaming and fighting?
The completion of the Allen Institute for Brain Science's inaugural project signals a remarkable leap forward in one of the last frontiers of medical science -- the brain.
The Institute today announced the completion of the groundbreaking Allen Brain Atlas, a Web-based, three-dimensional map of gene expression in the mouse brain. Detailing more than 21,000 genes at the cellular level, the Atlas provides scientists with a level of data previously not available.
Since humans share more than 90 percent of their genes with mice, the Atlas offers profound opportunity to further understanding of human disorders and diseases such as Alzheimer's, Parkinson's, epilepsy, schizophrenia, autism and addiction. About 26 percent of American adults -- close to 58 million people -- suffer from a diagnosable mental disorder in a given year.
Many human brain diseases have mouse equivalents developed using genetic engineering on lab mice. As the cost of measuring gene activity drops a logical next step would be to repeat this work using mice which have a variety of brain disorders.
You can access the Brain Atlas for free online.
"This project is an unprecedented union of neuroscience and genomics," said philanthropist and Microsoft co-founder Paul G. Allen, who provided $100 million in seed money to launch the Allen Institute for Brain Science and its first project, the Allen Brain Atlas, in 2003. "The comprehensive information provided by the Atlas will help lead scientists to new insights and propel the field of neuroscience forward dramatically."
Publicly available at no cost, the map shows which genes are active -- or "expressed" -- within the brain and which regions and cells they are expressed in, thereby linking them to particular brain functions.
The brain uses most of the genome.
The project has already led to several significant new findings about the brain. It reveals that 80 percent of genes are turned on in the brain, much higher than the 60 to 70 percent scientists previously believed.
It indicates that very few genes are turned on in only one region of the brain -- paving the way for additional insight about the benefits and potential side effects of drug treatments. And it shows the location of genes associated with specific functions, providing scientists with valuable information about regional brain activity.
Many brain scientists use the Atlas.
Even before its announced completion, the Atlas was receiving more than 4 million hits monthly and being accessed by approximately 250 scientists on any given work day. Users are not required to provide information about their work, but anecdotal evidence indicates that the Atlas is already assisting research projects.
"I use it around the clock, night and day. My whole lab does," said Stanford University neurobiology professor Ben A. Barres, who is using the Atlas to confirm his team's findings about glial cells, a type of non-neuronal cell within the nervous system.
"It's completely essential. It's saved us years and years of work, maybe decades. We could never have done all this, either financially or in terms of the amount of labor and time. It was just so incredibly generous of Mr. Allen to do this, and I think it's hard to even overstate what the payoff is going to be for research."
Researchers at the Allen Institute created the database using a process known as in-situ hybridization. A mouse brain is sliced into thin layers and then labeled with a DNA "probe" that binds only to a single gene, highlighting the expression pattern for that gene.
In-situ maps were made for every gene in the mouse genome, then loaded into a massive database. To complete the entire database, researchers processed 170 genes per day, and produced some 1,000 gigabytes of data each day. The finished atlas cost about $41 million to produce.
The development of gene array chips and other technologies for measuring many parts of a biological system at once look set to continue to accelerate the rate at which scientists can collect information from cells and organisms. The Brain Atlas couldn't have been developed 10 years ago. 10 years from now we'll have still more orders of magnitude improvement in the ability to measure and collect data on the activites inside cells and organisms.
A map of gene activity in the human brain neocortex is next up for the Allen Institute.
The next project, Jones said, will be to develop a digital, three-dimensional, interactive map of the genes at work in a human brain's neocortex, the outer layer that is the seat of higher thought and emotion, using brains from cadavers as well as tissue removed during brain surgeries.
We are coming to the end of the dark ages of how the human brain works.
Some people spend their whole lives in search of happiness and escape from a feeling of hopelessness and ennui. They lack the technology that would grant them immediate satisfaction. Knock out a gene and be happy.
A new breed of permanently 'cheerful' mouse is providing hope of a new treatment for clinical depression. TREK-1 is a gene that can affect transmission of serotonin in the brain. Serotonin is known to play an important role in mood, sleep and sexuality. By breeding mice with an absence of TREK-1, researchers were able create a depression-resistant strain. The details of this research, which involved an international collaboration with scientists from the University of Nice, France, are published in Nature Neuroscience this week.
"Depression is a devastating illness, which affects around 10 percent of people at some point in their life," says Dr. Guy Debonnel an MUHC psychiatrist, professor in the Department of Psychiatry at McGill University, and principal author of the new research. "Current medications for clinical depression are ineffective for a third of patients, which is why the development of alternate treatments is so important."
Mice without the TREK-1 gene ("knock-out" mice) were created and bred in collaboration with Dr. Michel Lazdunski, co-author of the research, in his laboratory at the University of Nice, France. "These 'knock-out' mice were then tested using separate behavioral, electrophysiological and biochemical measures known to gauge 'depression' in animals," says Dr. Debonnel. "The results really surprised us; our 'knock-out' mice acted as if they had been treated with antidepressants for at least three weeks."
One of the reasons I watch for mouse gene knock-out studies is that they are a glimpse into the choices prospective parents (and domineering governments) will face when it becomes possible to tinker with the DNA of eggs, sperm, and embryos. In the future some people will opt for offspring genetic engineering to make their kids congenitally happy uncurable optimists. Other people will genetically engineer their kids to be highly objective analytical realists. Not a few of the latter will want to come up with ways to infect the obnoxiously optimistic with viruses that will reprogram them for more realism and less optimism.
Other future parents will opt for drugs instead of genetic engineering to make their kids happy, calm, content, and confident. Make Johnny and Jill grow up as joyful kids but then tell them at age 18 they just have to stop taking the pills and they'll be able to suffer all the doubts, depression, and sadness that the older generations experienced.
Gene knock-out studies also provide glimpses into just how little free will we have (if we even have any at all).
The discoveries from gene knock-out studies will become a torrent when efforts to create mice with gene knock-outs for each mouse gene achieve their goals.
Genetic causes of behavior matter because they influence us right now. But they will matter even more in the future when offspring genetic engineering becomes a reality. I think it unlikely that people will consciously choose the same frequencies of genetic variations for their offspring as occur naturally. Every human nature that has some genetic causes is going to become either more or less frequent when people can choose which genetic variations to give their offspring. Hence every report about genetic causes of some human behavior is a report about something humans do that they'll become either more or less inclined to do in the future. Will parents choose to use genetic engineering make their kids more entrepreneurial?
Scott Shane, the Mixon Professor of Entrepreneurial Studies at Case Western Reserve University's Weatherhead School of Management; Nicos Nicolaou, a lecturer in entrepreneurship at the Tanaka School of Business of Imperial College London; and Janice Hunkin, Lynn Cherkas, and Tim Spector of the Twin Research & Genetic Epidemiology Unit at St Thomas' Hospital in London, home of the UK Twin registry of over 10,000 twins collaborated in this unique study. They compared rates of entrepreneurship between and among more than 1,200 pairs of identical and fraternal twins in the U.K and conclude that nearly half—48 percent—of an individual's propensity to become self-employed is genetic.
The authors studied self-employment among 609 pairs of identical twins, and compared it to self-employment among 657 pairs of same-sex fraternal twins in the U.K. Identical twins share 100% of their genetic composition, while fraternal twins share about 50%, on average. Thus differences in the rates at which pairs of identical twins both become entrepreneurs and the rates at which both members of fraternal twins both become entrepreneurs are attributable to genetics. "One can look at the patterns of concordance (the numbers of pairs of twins in which both members are or are not entrepreneurs) and reasonably infer that genetic factors account for the differences," says Shane.
The authors propose several methods by which genetic factors might influence people's tendency to become entrepreneurs. For example, genes may predispose an individual to develop traits such as being sociable and extroverted, which in turn facilitate skills such as salesmanship, which are vital to entrepreneurial success.
In addition, genes have been shown to affect the level of education an individual receives, and more highly educated people are likelier to become entrepreneurs because they are better able to recognize new business opportunities when they arise.
It is likely that entrepreneurship comes as a result of other qualities as mentioned above. Will parents choose those qualities based on a desire to make their kids self-employed? Or will they choose those qualities mainly for other reasons and will the effect on entrepreneurial behavior come as a side effect of choices made for other reasons?
People in different cultures, economic classes, occupations, religions, and with different genetically determined qualities for their own minds will make different choices on average. Will this tend to make the human race diverge? Or will there be a wide consensus on all the important genetically controlled qualities of the mind and will humanity tend to converge?
One split I expect: I predict some religious folks will choose genetic qualities that make their kids more inclined to have faith. Whereas more empirically minded folks will choose genetic qualities that make their kids highly skeptical, critical, and empirical. Though some of a more socialistic bent might choose qualities that make kids turn out more altruistic and group-oriented.
Scientists at the National Institutes of Health’s (NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual’s risk for obsessive-compulsive disorder (OCD). The new functional variant, or allele, is a component of the serotonin transporter gene (SERT), site of action for the selective serotonin reuptake inhibitors (SSRIs) that are today’s mainstay medications for OCD, other anxiety disorders, and depression.
“Improved knowledge of SERT‘s role in OCD raises the possibility of improved screening, treatment, and medications development for that disorder,” said Ting-Kai Li, M.D., Director, National Institute on Alcohol Abuse and Alcoholism. “It also provides an important clue to the neurobiologic basis of OCD and the compulsive behaviors often seen in other psychiatric diseases, including alcohol dependence.”
Approximately 2 percent of U.S. adults (3.3 million people) have OCD, the fourth most prevalent mental health disorder in the United States. Individuals with OCD have intrusive, disturbing thoughts or images (obsessions) and perform rituals (compulsions) to prevent or banish those thoughts. Many other individuals demonstrate obsessive-compulsive behaviors that do not meet OCD diagnostic criteria but alter the individuals’ lives.
Drs. David Goldman, Chief, and Xianzhang Hu, Research Scientist, in NIAAA’s Laboratory of Neurogenetics discovered the linkage aided by new functional analyses of the SERT genetic variant. The researchers first compared the genotypes of 169 OCD patients to those of 253 controls in a large U.S. patient population[i] and found that the OCD patients were twice as likely to have the variant. Then they studied transmission and non-transmission of the variant in a Canadian population[ii] of 175 OCD parent-child trios (two healthy parents and a child with OCD) and found that the risk variant was twice as likely to be transmitted from a parent to a child with OCD. Specifically, of 86 informative trios, 48 children carried the new risk variant and 26 did not.
Not surprisingly considering this result Stanford researchers found that a serotonin selective reuptake inhibitor, citalopram, provides some relief from OCD.
The pace of genetic studies like the one above happen at a rate mostly driven by the cost of DNA sequencing. When DNA sequencing costs fall orders of magnitude further then scientists will able able to perform massive comparisons of gene sequences between people with and without a large number of disorders and diseases. This will lead to the discovery of large numbers of other genetic variations that influence cognitive function and the risk of cognitive and other disorders.
People are going to become far more interested in the sequences of other people once we know how many different genetic variations influence behavior. Companies will want to hire managers with genetic profiles that mark them as bound to perform well. Ditto for engineers, sales reps, and other types of workers.
Also see my previous posts "Gene Mutations Cause Rare Form Of Obsessive Compulsive Disorder" and "Compulsive Hoarders Have Unique Brain Scan Patterns".
Variations in the enzyme Monoamine Oxidase-A (which breaks down neurotransmitters such as serotonin) have been previously found to affect whether abuse as a child causes greater tendency toward anti-social behavior and violence. Now some researchers have looked at brains with the two different MAO-A variations and found that people with the short variation of MAO-A have less brain gray matter in an area that regulates mood.
The gene is one of two common versions that code for the enzyme monoamine oxydase-A (MAO-A), which breaks down key mood-regulating chemical messengers, most notably serotonin. The previously identified violence-related, or L, version, contains a different number of repeating sequences in its genetic code than the other version (H), likely resulting in lower enzyme activity and hence higher levels of serotonin. These, in turn, influence how the brain gets wired during development. The variations may have more impact on males because they have only one copy of this X-chromosomal gene, while females have two copies, one of which will be of the H variant in most cases.
Several previous studies had linked increased serotonin during development with violence and the L version of MAO-A. For example, a 2002 study* by NIMH-funded researchers discovered that the gene’s effects depend on interactions with environmental hard knocks: men with L were more prone to impulsive violence, but only if they were abused as children. Meyer-Lindenberg and colleagues set out to discover how this works at the level of brain circuitry.
Using structural MRI in 97 subjects, they found that those with L showed reductions in gray matter (neurons and their connections) of about 8 percent in brain structures of a mood-regulating circuit (cingulate cortex, amygdala) among other areas. Volume of an area important for motivation and impulse regulation (orbital frontal cortex) was increased by 14 percent in men only. Although the reasons are unknown, this could reflect deficient pruning — the withering of unused neuronal connections as the brain matures and becomes more efficient, speculates Meyer-Lindenberg.
The researchers then looked at effects on brain activity using functional MRI (fMRI) scans. While performing a task matching emotionally evocative pictures — angry and fearful faces — subjects with L showed higher activity in the fear hub (amygdala). At the same time, decreased activity was observed in higher brain areas that regulate the fear hub (cingulate, orbital frontal, and insular cortices) — essentially the same circuit that was changed in volume.
While these changes were found in both men and women, two other experiments revealed gene-related changes in men only. In a task which required remembering emotionally negative information, men, but not women, with L had increased reactivity in the fear (amygdala) and memory (hippocampus) hubs. Men with L were also deficient during a task requiring them to inhibit a simple motor response; they failed to activate a part of the brain (cingulate cortex) important for inhibiting such behavioral impulses. This region was, conspicuously, the cortex area that was most reduced in volume.
The findings echo those of a 2005 NIMH study** showing how another serotonin-related gene variant shapes the same mood-regulating circuit. In this study also, the gene version that boosts serotonin levels resulted in impaired emotion-related lower brain structures, increased fear hub activation and a weaker response of its regulatory circuits. Yet, the effects of the L version of MAO-A were more extensive, perhaps reflecting the fact that it also impacts another key mood-regulating neurotransmitter, norepinephrine.
The weakened regulatory circuits in men with L are compounded by intrinsically weaker connections between the orbital frontal cortex and amygdala in all men, say the researchers.
Next time someone tries to punch you out in a bar just calmly explain to him that he's only trying to beat you up because he doesn't have enough gray matter in his cingulate cortex and amygdala.
Do you believe in free will? I'm sure that there's some set of genetic variations that cause you to think such a thought.
LA JOLLA – Brains are marvels of diversity: no two look the same -- not even those of otherwise identical twins. Scientists at the Salk Institute for Biological Studies may have found one explanation for the puzzling variety in brain organization and function: mobile elements, pieces of DNA that can jump from one place in the genome to another, randomly changing the genetic information in single brain cells. If enough of these jumps occur, they could allow individual brains to develop in distinctly different ways.
This result might explain why humans differ in their intellectual abilities and behavioral tendencies in ways that are not accounted for by genetic inheritance or environment. Humans may end up being even more controlled by their genes than twins studies would suggest because some of the genetic patterns that control them are generated during fetal development.
"This mobility adds an element of variety and flexibility to neurons in a real Darwinian sense of randomness and selection," says Fred H. Gage, Professor and co-head of the Laboratory of Genetics at the Salk Institute and the lead author of the study published in this week's Nature. This process of creating diversity with the help of mobile elements and then selecting for the fittest is restricted to the brain and leaves other organs unaffected. "You wouldn't want that added element of individuality in your heart," he adds.
Precursor cells in the embryonic brain, which mature into neurons, look and act more or less the same. Yet, these precursors ultimately give rise to a panoply of nerve cells that are enormously diverse in form and function and together form the brain. Identifying the mechanisms that lead to this diversification has been a longstanding challenge. "People have speculated that there might be a mechanism to create diversity in brain like there is in the immune system, and the immune system's diversity is perhaps the closest analogy we have," says Gage.
The researchers were aware that the immune system rather systematically reshuffles antibody genes to produce a large variety of immune cells that make many different antibodies for different antigens it might encounter.
In the immune system, the genes coding for antibodies are shuffled to create a wide variety of antibodies capable of recognizing an infinite number of distinct antigens.
In their study, the researchers closely tracked a single human mobile genetic element, a so-called LINE-1 or L1 element in cultured neuronal precursor cells from rats. Then they introduced it into mice. Every time the engineered L1 element jumped, the affected cell started glowing green [WHY?]. "We were very excited when we saw green cells all over the brain in our mice," says research fellow and co-author M. Carolina N. Marchetto, "because then we knew it happened in vivo and couldn't be dismissed as a tissue culture artifact."
Transposable L1 elements, or "jumping genes" as they are often called, make up 17 percent of our genomic DNA but very little is known about them. Almost all of them are marooned at a permanent spot by mutations rendering them dysfunctional, but in humans a hundred or so are free to move via a "copy and paste" mechanism. Long dismissed as useless gibberish or "junk" DNA, the transposable L1 elements were thought to be intracellular parasites or leftovers from our distant evolutionary past.
It has been known for a long time that L1 elements are active in testis and ovaries, which explains how they potentially play a role in evolution by passing on new insertions to future generations. "But nobody has ever demonstrated mobility convincingly in cells other than germ line cells," says Gage.
Apart from their activity in testis and ovaries, jumping L1 elements are not only unique to the adult brain but appear to happen also during early stages of the development of nerve cells. The Salk team found insertions only in neuronal precursor cells that had already made their initial commitment to becoming a neuron. Other cell types found in the brain, such as oligodendrocytes and astrocytes, were unaffected.
At least in the germ line, copies of L1s appear to plug themselves more or less randomly into the genome of their host cell. "But in neuronal progenitor cells, these mobile elements seem to look for genes expressed in neurons. We think that's because when the cells start to differentiate the cells start to open up genes and expose their DNA to insertions," explains co- author Alysson R. Muotri. "What we have shown for the first time is that a single insertion can mess up gene expression and influence the function of individual cells," he adds.
However, it is too early to tell how often endogenous L1 elements move in human neurons and how tightly this process is regulated or what happens when this process goes awry, cautions Gage. "We only looked at one L1 element with a marker gene and can only say that motility is likely significantly more for endogenous L1 elements," he adds.
Maybe some mental illnesses are caused by L1 elements inserting in places where they mess up the functioning of some brain neurons.
If I'm right in my suspicion that this result shows how we could be even more genetically determined than twins studies suggest then we are genetically determined in ways that introduce randomness at an early stage of brain development. This leaves even less room for social environment to influence development. Eventually biotechnological means will be found to reduce the degree of randomness in the L1 insertions so that outcomes of the development of offspring will become more predictable. See my post Children Of The Future May Be More Genetically Determined for further elaboration of that argument.
The idea of jumping genes in our brains triggers a memory of Mark Twain's The Notorious Jumping Frog of Calaveras County. Seems faintly related because the genes jumping around in our brains seem whimsical. Oh, and for some reason unknown to me the story is also known as The Celebrated Jumping Frog of Calaveras County. So which title was the original?
ATLANTA - Why are some people shy while others are outgoing? A study in the current issue of Science demonstrates for the first time that social behavior may be shaped by differences in the length of seemingly non-functional DNA, sometimes referred to as junk DNA. The finding by researchers at the Yerkes National Primate Research Center of Emory University and the Atlanta-based Center for Behavioral Neuroscience (CBN) has implications for understanding human social behavior and disorders, such as autism.
In the study, Yerkes and former CBN graduate student Elizabeth A.D. Hammock, PhD, and Yerkes and CBN researcher Larry J. Young, PhD, also of the Department of Psychiatry and Behavioral Sciences at Emory University's School of Medicine, examined whether the junk DNA, more formally known as microsatellite DNA, associated with the vasopressin receptor gene affects social behavior in male prairie voles, a rodent species. Previous studies, including Dr. Young's gene-manipulation study reported in Nature's June 17, 2004, issue, have shown the vasopressin receptor gene regulates social behaviors in many species.
The researchers bred two groups of prairie voles with short and long versions of the junk DNA. By comparing the behavior of male offspring after they matured, they discovered microsatellite length affects gene expression patterns in the brain. In the prairie voles, males with long microsatellites had higher levels of vasopressin receptors in brain areas involved in social behavior and parental care, particularly the olfactory bulb and lateral septum. These males spent more time investigating social odors and approached strangers more quickly. They also were more likely to form bonds with mates, and they spent more time nurturing their offspring.
I picture women who want their men to stay faithful some day surreptitiously injecting gene therapy into neck arteries of sleeping boyfriends or husbands to reprogram their microsatellite DNA to longer lengths around the vasopressin gene. And here's the twist: If the guy discovers he has been reprogrammed by his woman he'll be so attached to her that he won't want to leave her because of it.
"This is the first study to demonstrate a link between microsatellite length, gene expression patterns in the brain and social behavior across several species," said Young. "Because a significant portion of the human genome consists of junk DNA and due to the way microsatellite DNA expands and contracts over time, microsatellites may represent a previously unknown factor in social diversity."
Hammock and Young's finding extends beyond social diversity in rodents to that in apes and humans. Chimpanzees and bonobos, humans' closest relatives, have the vasopressin receptor gene, yet only the bonobo, which has been called the most empathetic ape, has a microsatellite similar to that of humans. According to Yerkes researcher Frans de Waal, PhD, "That this specific microsatellite is missing from the chimpanzee's DNA may mean the last common ancestor of humans and apes was socially more like the bonobo and less like the relatively aggressive and dominance-oriented chimpanzee."
The researchers' finding also has set a clear course for the next step. They want to build upon previous studies that identified a microsatellite sequence in the human vasopressin receptor that varies in length. "The variability in the microsatellite could account for some of the diversity in human social personality traits," explains Hammock. "For example, it may help explain why some people are naturally gregarious while others are shy." In particular, Young wants his research team to expound upon studies that have identified a link with autism.
Research in prairie voles has provided evidence about vasopressin effects on pair bonding in prairie voles that led to the discovery that pair bonding in humans involves some of the same brain areas as are seen in prairie voles. It is not far fetched to take the discovery of vasopressin receptor microsatellite DNA's role behavior in prairie voles as a reason to look for similar DNA in humans playing a regulatory role in human behavior.
The researchers first showed in cell cultures that the vole vasopressin receptor microsatellites could modify gene expression. Next, they bred two strains of a monogamous species, the prairie vole – one with a long version of the microsatellites and the other with a short version. Adult male offspring with the long version had more vasopressin receptors in brain areas involved in social behavior and parenting (olfactory bulb and lateral septum). They also checked out female odors and greeted strangers more readily and were more apt to form pair bonds and nurture their young.
"If you think of brain circuits as locked rooms, the vasopressin receptor as a lock on the door, and vasopressin as the key that fits it, only those circuits that have the receptors can be 'opened' or influenced by the hormone," added Hammock. "An animal's response to vasopressin thus depends upon which rooms have the locks and our research shows that the distribution of the receptors is determined by the length of the microsatellites."
Prairie voles with the long version have more receptors in circuits for social recognition, so release of vasopressin during social encounters facilitates social behavior. If such familial traits are adaptive in a given environment, they are passed along to future generations through natural selection.
Variability in vasopressin receptor microsatellite length could help account for differences in normal human personality traits, such as shyness, and perhaps influence disorders of sociability like autism and social anxiety disorders, suggest the researchers.
Will humans choose to biologically engineer their male offspring to be much more social? If future generations of men want to gossip endlessly about human relations this could be a problem for those of us with natural male brains. If due to rejuvenation therapies I live to see society dominated by highly social males I'm going to found a club of old style men who can hang around and talk about cars or airplanes or anything else for that matter. Or better yet, go through long periods of not talking at all.
Dr. Essi Viding of the London Kings College Institute of Psychiatry and colleagues have found the tendency toward psychopathic behavior has a strong genetic component. (same press release here)
New research on the origins of antisocial behaviour, published in the Journal of Child Psychology and Psychiatry, suggests that early-onset antisocial behaviour in children with psychopathic tendencies is largely inherited.
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Dr Viding's research looked into the factors that contribute to antisocial behaviour in children with and without psychopathic tendencies. By studying sets of 7-year-old twins, Dr. Viding and her colleagues were able to pinpoint to what extent antisocial behaviour in these two groups was caused by genetic and/or environmental risk factors.A sample of 3687 twin pairs formed the starting point for this research. Teacher ratings for antisocial behaviour and psychopathic tendencies (i.e. lack of empathy and remorse) were used to classify the twins. Those who were in the top 10% of the sample for antisocial behaviour were separated into two groups - those with and without psychopathic tendencies.
Following analysis, the results showed that, in children with psychopathic tendencies, antisocial behaviour was strongly inherited. In contrast, the antisocial behaviour of children who did not have psychopathic tendencies was mainly influenced by environmental factors. These findings are in line with previous research showing that children with psychopathic tendencies are at risk to continue their antisocial behaviour and are often resistant to traditional forms of intervention.
For those who recognize the name note that Robert Plomin is one of the co-authors.
Evidence for substantial genetic risk for psychopathy in 7-year-olds (Essi Viding, R. James R. Blair, Terrie E. Moffitt, Robert Plomin) is published in the June 2005 issue of The Journal of Child Psychology and Psychiatry.
The bad kids who feel no remorse are genetically bad.
Preliminary findings from the Twins Early Development Study (TEDS) indicate that within the early-onset group there are at least two etiologically distinct groups of children. Antisocial behavior in 7-year-old children with callous and unemotional traits is under strong genetic influence, whereas antisocial behavior in children without such personality traits is primarily environmentally mediated.
Such findings of etiological differences are prompting the search for risk genes, as well as highlighting the need to study environmental risk within a genetic framework. It must be emphasized that high heritability is not equivalent to immutability. Better understanding of gene-environment interactions can come to inform successful prevention programs that target young children. These prevention programs may well be different for etiologically distinct subgroups of children at risk for violent and antisocial outcomes.
Psychopathy is strongly genetically infuenced.
Twin studies can help distinguish between genetic and environmental determinants of violence, said Essi Viding of the Institute of Psychiatry in London. In antisocial 7-year-olds with callous and unemotional traits, Viding found, the antisocial behavior was strongly genetic in origin (a group heritability of 80%). If these youths can be identified early, perhaps with a genetic test on cells from a cheek swab, one could target programs for them. "Genes are not a blueprint that determines outcome," said Viding. "Rather, they act together with other risk or protective factors to increase or reduce the risk of disorder."
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Antisocial behavior and physical violence, it turns out, are moderately heritable. A recent meta-analysis of behavioral genetic studies estimated that 41% of the variance on antisocial behavior is due to genetic factors, about 16% to shared environmental factors, and about 43% to nonshared environmental factors.
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Viding's group is currently trying to find genes associated with callous-unemotional traits. If such genes can be identified, the researchers can explore how environment affects the outcomes of children who carry the genes. For example, they may be able to see whether the same genes place children at risk for both antisocial behavior and hyperactivity. They may also be able to assess how risk genes interact with risk environments throughout development.
Genes are not a blueprint that determines outcome. Genes alone are neither sufficient, nor necessary, in causing the antisocial behavior.
I am highly skeptical of claims that genes alone are never sufficient to cause antisocial behavior. Certainly some genotypes make people more at risk of being violent or antisocial only in response to specific types of environmental influences. But surely other genotypes must make other children born "bad to the bone". Claims that environmental interventions can always override genetic influences strike me as denial. Sorry, sometimes the genome wins.
To put my argument another way: Some people are more genetically determined than others. (and I predict people will become more genetically determined in the future) Some people have genes that make them highly susceptible to programming by environmental influences. But others have genes that make them highly resistant to various types of environmental influences. For example, some people are going to be happy or unhappy regardless of their environment. Others will have moods and motivations that are greatly influenced by disappointments or good fortune. Some will become violent as a result of child abuse. Others will stay pacifist no matter how much abuse they suffer.
Also, in some cases where genes make someone highly susceptible to environmental influences the effect is to make that person more prone to become criminal or otherwise problematic for the rest of us. Genes can make a person prone to going down an undesirable developmental path or so prone to antisocial behavior that without taking some rather severe steps to isolate such people from "the slings and arrows of outrageous misfortune" some of them are going to go over to the "dark side of the force". The degree to which they can be triggered by environmental stimuli is so great that the ability of environment to influence them is not a reason for optimism.
Even in cases where one twin becomes a psychopath and the other does not become a psychopath that is not automatic proof that therefore social environment made the difference. Some part of deveopmental outcome is due to random noise. Genes do not perfectly control development. Hardwired differences in brains of twins will be present at birth due to chance. Throw in additional noise in very early childhood and before many social influences are felt genetic and non-genetic but developmentally caused and irreversible (at least with current biotechnology) differences will already be well established.
Genes control the extent to which a person is susceptible to various events in the environment and genes exercise great influence over how a person will respond to abuse as a child or a threat uttered in a bar or other events in a person's life. Genes even control the extent to which developmental outcomes are due to random noise from the environment and from Brownian motion. Hopes that socialization can always compensate for genetic inheritance to prevent antisocial thought patterns and behavior strike me as hopelessly naive.
Once psychopathy as a genetically caused condition becomes accepted and genetic testing and genetic engineering becomes possible do you favor or oppose the use of either genetic testing (for selective abortion) or genetic engineering (perhaps delivered in utero) to prevent the development of psychopaths? Consider your other choices. Early and lifetime institutionalization of kids who are bad to the bone would prevent them from preying on others but conflict with the assumption of "innocent until one has committed a crime", let alone "innocent until proven guilty". The other option is what we do now: let those kids grow up and victimize people before being caught committing crimes. That latter option consigns some people to future victimhood and, worse yet, not all psychopaths are ever caught by the criminal justice system. "Successful psychopaths" with an increased corpus callosum but with a symmetrical hippocampus are much less likely to get caught by the police than psychopaths that also have an asymmetrical hippocampus.
Suppose early environmental conditioning techniques which can reverse psychopathy are discovered. Parentheticaly I'm extremely skeptical of the notion than any socialization practices can counteract the effects of gross differences in brain morphology characteristic of psychopaths. But suppose I'm wrong. Would you favor removing a very young budding psychopath from his parents in order to put him through a social conditioning therapy to reverse his psychopathy?
A German team has found that congenital prosopagnosia (CP), a conditon where a person has a hard time recognizing faces, is genetically inherited. Thomas Grüter, himself a CP sufferer, and his team at the Institute for Human Genetics in Münster, Germany traced CP in 7 families and found evidence that CP is inherited through a single genetic defect.
The team recruited members of a prosopagnosia support group and their families into the study, plus Grüter's own relatives. Using a questionnaire to identify prosopagnosia symptoms, the team found 38 prosopagnosics in seven families. By plotting the condition on family trees, the team showed that the inheritance pattern is consistent with the trait being carried by a single gene: just one defective copy of the gene could make the carrier face-blind.
Other people suffer from prosopagnosia due to trauma to the brain that caused brain damage. But for those who have prosopagnosia from birth the open question has been whether the condition is the result of trauma or toxin exposure during early development or inheritance.
The fact that this disorder can be caused by genetic defect demonstrates that at least for one important cognitive ability the brain's structure that supports that ability is coded for genetically. This result then is another piece of evidence against a blank slate view of the brain.
PITTSBURGH--Recognizing faces is effortless for most people, and it's an ability that provides great evolutionary and social advantages. But this ability is impaired in people who have suffered brain damage or in those with a rare congenital condition, and research by Carnegie Mellon University psychologists reveals startling insights into how the brains of those individuals operate. Psychology Professor Marlene Behrmann and postdoctoral associate Galia Avidan have found that people with congenital prosopagnosia--in which their ability to recognize faces is impaired from birth--are not just deficient at recognizing individuals they know, but they are also poor at simply discriminating between two faces when presented side by side. The researchers also have discovered through functional Magnetic Resonance Imaging (fMRI) scans that, contrary to their expectations, the regions of the brain that are activated when normal individuals perceive and recognize faces also are activated in individuals with congenital prosopagnosia (CP). Behrmann and Avidan will summarize the results of their findings in the April issue of the journal Trends in Cognitive Sciences.
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Behrmann and Galia said that much remains to be learned from the individuals in their research. They have begun to examine the anatomical details of the brains of their participants, and preliminary findings show that some brain structures are smaller in the region known to control face recognition.
Did Michelangelo or Leonardo Da Vinci have a larger region of their brains for facial recognition? Did they from birth have more neurons dedicated to understanding facial structures? Or were their mental gifts due to more general enhancements of cognitive abilities?