Epigenetics – Exercise Runs In The Family

It is common fact that people who exercise frequently are more likely to live a longer healthier life, but now new studies show that if a person exercises it can also result in a better life for his or her children and even grandchildren. Before the study of epigenetics people always thought the genome they are born with it the genome they are stuck with. However new science has shown exercise not only changes the outward appearance of our muscles and overall physical health, but also changes our DNA.

Exercise, astonishingly, can effect gene shape, function, and turn them on and off. Scientists now know that genes can actually be quieted or amplified through exercise because biochemical signals are sent out every time a person exercises. This is where epigenetics comes in. Epigenetics doesn’t simply change the gene all together, but instead works its magic on the outside of each gene through a process called methylation. A cluster of atoms surround the genes either denying or amplifying biochemical signals. Scientists believe that even one day of exercise can change methylation patterns.

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One study done by scientists at the Karolinska Institute in Stockholm put the theory of exercise and epigenetic’s to the test. They studied 23 young and healthy men and women. They asked all the participants to work out half of their lower body for three months. This way each member of the study was his or her own control and experimental group. Obviously, after the three months each members leg that was worked out was stronger than the other, but what was much more intriguing was the results at the molecular level. The scientists found significant methylation changes in the cells of the leg that were worked out, averaging 5,000 sights on the genome where there was a new methylation pattern. Many of these methylation patterns were changed on enhancers, which are important for amplifying gene expression. The genes that were most affected were those that play a role in energy metabolism, insulin response, and inflammation within muscles. Exercise, along with many other healthy lifestyle tasks, has shown to cause changes in a persons epigenome. Changes that make a person healthier, but perhaps even more significantly, can make his or her children and grandchildren healthier.

 

http://well.blogs.nytimes.com/2014/12/17/how-exercise-changes-our-dna/?_r=0

 

Epigenetics and Dopamine Activity

Researchers at the University of California in Irvine have correlated erratic dopamine activity as an underlying cause of complex neuropsychiatric disorders, specifically because of the epigenetic alterations caused by low levels of dopamine. This study, overseen by Emiliana Borelli, a UCI professor of microbiology & molecular genetics, provides clues to the possible causes of complicated disorders like schizophrenia.

Dopamine is a neurotransmitter (and hormone) that fuels our daily life, acting as our prime motivator and pleasure inducer, while also being linked to memory, and cognitive function. Many addictive drugs increase the amounts of dopamine released to exhausting levels, eventually wearing out the neurotransmitters notwithstanding the negative effects of the drugs themselves. High dopamine levels can also be achieved via everyday pleasures like exercise or sex, which can also spur addiction.

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Dopamine, therefore, has an irrefutable role in our everyday lives, and according to Borelli, “Genes previously linked to schizophrenia seem to be dependent on the controlled release of dopamine at specific locations in the brain. Interestingly, this study shows that altered dopamine levels can modify gene activity through epigenetic mechanisms despite the absence of genetic mutations of the DNA.”

In short, it is quite likely that Dopamine is an epigenetic hub of sorts, that can cause powerful changes in gene regulation when functioning in a disrupted or excessive manner. Borelli, knowing the consequences of excess dopamine release, tested the opposite effect on mice, hindering dopamine release by turning off mid brain dopamine receptors in rats, leading to mild dopamine synthesis. The results were profound, as Borelli found there to be decreased expression in approximately 2,000 genes in the prefrontal cortex. This epigenetic surge of decrease in genetic expression was reinforced by the increase in change of DNA proteins called histones, which are associated with reduced gene activity. The now mutated mice suffered from ranging psychotic behavior and episodes, and were then treated with dopamine activators for a duration of time before seeing their behavior normalize.

Borelli’s and others’ work will provide useful clues for understanding these complex neurological disorders, while serving to reinforce the newfound importance of comprehending gene regulation and expression. These studies seem to point to a new era in which it is not just your genetic make up that determines your future, but also the regulation of your genes.

 

 

Genetics and Mental Illness

Brain Lobes

Scientists have tirelessly searched through the genetic makeup of people with metal illnesses trying to find a common variation(s) that could account for conditions such as schizophrenia and bipolar disorder. However this has been inconclusive so researchers have turned to epigenetics, the study of how experience and environment effect the expression of certain genes. Epigenetic marks regulate when and how much protein is made with out actually altering the DNA itself. It is believed that these “marks” can affect behavior, and thus may interfere with metal health. This idea was tested in a study with rats.  Researchers proved that affectionate mothering alters the expression of genes, allowing them to dampen their physiological response to stress, which was then passed on to the next generation. This is thought to be similar in humans and these markers develop as an animal adapts to its environment.  Epigenetic research led scientists to prove that offspring of parents who experienced famine are at a higher risk for developing schizophrenia. Additionally, some people who have autism, epigenetic markers had silenced the gene which helps produce the hormone oxytocin which helps the brain’s social circuit. And therefore a brain that lacks this hormone would most likely struggle in social situations. Thomas Lehner of genomics research at the National Institute of Mental Health says that studies and research have shown that epigenetic modifications impact behavior and he also believes that these effects can be reversed. By studying genes at the “epi” level, researchers are hoping to find patterns that were hidden at the gene level.  Finding and targeting these patterns can lead to more effective treatment of and management of certain mental illnesses. There are many projects and studies at some of the most prestigious institutes, such as Tufts and Johns Hopkins, that are focused on the study of things at the epigenetic level.

Original Article

Further Information:

Epigenetic Markers and Heredity

Epigentetics and Autism 

Genetics and the Brain

 

 

 

 

The Gene Switch

Researchers at the Stowers Institute for Medical Research have created a high-resolution mechanism to “precisely and reliably map individual transcription factor binding sites in the genome.” This new technique, published in Nature Biology today, has proven to be more efficient and successful than those previously studied.

All of the cells in an organism carry DNA; however different cells in the body express different portions of it to function properly. For instance, nerve cells express genes that facilitate them carrying messages to other nerve cells. This process is known as gene expression and is responsible for making our bodies function the way we do. Despite our limited knowledge on gene expression, researchers are aware that it is is controlled by proteins called transcription factors that bind to specific sites around a gene and,  in the right order, allow the gene’s sequence to be read.

Transcription factor binding sites in DNA are extremely difficult to locate but, thanks to new technology, it is becoming easier to track their location. “The transcription factor binding sites that are likely functional leave behind clear footprints, indicating that transcription factors consistently land on very specific sequences. In contrast, questionable binding sites that were previously detected as bound showed a more scattered unspecific pattern that was no longer considered bound.”

These techniques are implemented through a method called chromatin immunoprecipitation or ChIP, a tool that determines the relativity of the proteins to their positions on the DNA, cuts the DNA into reasonable sizes, and then isolates the sections that are bound by the proteins. While the research is largely preliminary, scientist Zeitlinger attests to the significance of this creation; ”If we do this kind of analysis for lots of transcription factors, we will gather information needed to better understand gene expression.”

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chIP mechanism

Epigenetics for Asthmatics


In a recent study, a group of scientists obtained findings that could lead to a new approach to treating allergies. Instead of looking at the genes of their test subjects, they looked at something “above” the genome. Here we reach the field of Epigenetics.
Let us first define “Epigenetics” as the study on the activity and regulation of genes. In the world of Epigenetics, one can think of the epigenome as the on-off switch for the expression of genes. In terms of the study lead by Professors William Cookson and Miriam Moffatt, they focus on genes that trigger Asthma in patients. As Asthma cannot be ‘cured’, is there a way to shut down the genes that cause it?

The research team searched for a correlation between Asthma-causing antibodies and low methylation levels. Methylation is the process by which a methyl group attaches to certain genes in order to regulate their activity. Scientists already know that people with asthma have higher levels of an antibody called “Immunoglobin E” (IgE). This antibody is involved in triggering the symptoms of asthma. It is already known that genes responsible for producing IgE are hyperactive in asthma patients. The question became whether methylation had something to do with it. So to answer this question, the researchers obtained volunteers with asthma, but with varying IgE levels. The group found significant results surrounding lower levels of methylation with the patients that had higher levels of IgE than those with lower levels of IgE in their blood. This suggests that the lower methyl levels on certain genes evokes an overactivity of IgE producing genes.

After reading the article myself, I wonder if asthma patients could find ways to have higher methyl levels in their body to shut down the overactive IgE-producing genes. Perhaps they could consume a methyl rich diet? I guess it’s not that simple. Further research should obviously go into epigenetics, since I feel it is a newly discovered field. Anyways, here are the head scientists reactions to the experiments:

Professor Moffatt: “The genes we identified represent new potential drug targets for allergic diseases as well as biomarkers that may predict which patients will respond to existing expensive therapies.”

Professor Cookson: “Our pioneering approach, using epigenetics, allowed us to obtain insights that we weren’t able to get from traditional genetics. It isn’t just the genetic code that can influence disease and DNA sequencing can only take you so far. Our study shows that modifications on top of the DNA that control how genes are read may be even more important.”

This article (and the entire study of Epigenetics) shows how scientific knowledge and thought is always changing. Before recent research showing a link between one’s living environment and their genetic activity came along, scientists widely believed that one only passes down inherited genes to their offspring. This potentially makes scientists now look twice at Lamarck and Darwin’s theories of evolution. Due to the new research conducted on Epigenetics, Lamarck’s (originally rejected) theory of how an animal’s environment will affect that animal’s offspring can now be regarded in a whole new light.

Original Article: http://www.sciencedaily.com/releases/2015/02/150218073057.htm

Further Reading: http://www.extremetech.com/extreme/180963-lamarcks-revenge-the-epigenetics-revolution-may-redeem-one-of-darwins-oldest-rivals

Editing the Brain Using Epigenetic Tools

Epigenetics is a huge part of our life and influences us in ways we may not be aware of. Did you know that it is impossible to create and save new memories without epigenetic tags? The brain is heavily reliant on Epigenetics to do its functions, and this makes it a huge topic of research to figure out the ways in which the epigenetics of the brain could affect certain diseases or memory. Recently special epigenetic molecular tools have been created that can erase specific epigenetic markers throughout the genome. The possible effects these tools could have on the curing of diseases of the brain or psychological ailments are tremendous.

These “epigenetic editing” procedure use either CRISPR (clustered, regularly interspaced, short, palindromic repeats) or TALE (Transcription activator-like effector) systems of modification. These systems can carry an Epigenome modifying enzyme and deliver it a specific site they are programmed to go to. This allows researchers to target very specific epigenetic changes and either shut them down or turn them on and possibly determine their correlation with certain ailments of the brain. “We’re going from simply being able to observe changes to being able to manipulate and recapitulate those changes in a controlled way,” Day said. This quote from Day, one of the researchers of this project, shows that we advance from only being able to observe epigenetic influences on the brain, to being able to manipulate and control them to potential aid us in combating diseases.

Researchers can catalog all of the epigenetic changes involved in forming and preserving a new memory. If we are able to track these epigenetic changes, then could we implant memories in to a person’s mind, by copying similar epigenetic changes? These researchers where also able to trigger not only the place where epigenetic change happens, but also the exact time using optogenetics. This form of using light to control neurons allows researchers to use the TALE system and a light switch apply epigenetic change to very specific brain regions or cell types.

One of the final goals of this research is to eventually be able to use epigenetic as a form of therapy to benefit PTSD, depression, schizophrenia, and cognitive function using the ability to alter epigenetic marks. This can also be used in a similar way to silence mutated genes that are damaging the cells or the body as whole. This form of using TALE and CRISPR to alter epigenetic tags creates a lot of hope for PTSD, depression, schizophrenia, Alzheimer’s, Parkinson’s, Huntington’s and other similar disease treatment options.

Long Term Effects of Bad Diet Linked to Epigenome

Epigenetics has become an increasingly popular topic of scientific study. It is universally understood that DNA carries genes, however the expression of those genes are at the whim of the epigenome. The long-term control of the epigenome over the expression of certain genes is not yet fully understood. Scientist Erik van Kampen of the Leiden Academic Centre for Drug Research at Leiden University in The Netherlands studies epigenetics. He was interested in the mystery of how the epigenome is influenced by diet. He explored the idea of how the effects of a poor diet continue to persist even after a better diet is adopted.

In his study, he used mice that naturally had a high susceptibility to getting high blood cholesterol and atherosclerosis. He fed these mice either a high fat, high-cholesterol diet or a normal diet. After time had passed, bone marrow was isolated from both the unhealthy and healthy diet mice. This bone marrow was transplanted into mice that had their bone marrow destroyed. The new mice with borrowed bone marrow were given a healthy, normal diet for several months. After this time had passed, the mice were measured for development of atherosclerosis in the heart. In addition to this, the mice were measured for the number and status of immune cells throughout the body and epigenetic markings on the DNA in the bone marrow.

The results of this study were staggering. Mr. Kampen found that DNA methylation (which inactivates the expression of genes) in the bone marrow was different in both types of mice. The transplants received from the unhealthy diet mice were seen as having a decreased immune system and increased atherosclerosis in comparison to the ones who had healthy donors. This study proves at least somewhat of a correlation between diet and long-term effects on the body and the expression of genes.

The original article can be found at this address: http://www.sciencedaily.com/releases/2014/11/141103102359.htm

The Harm Stress Causes

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https://www.sciencenews.org/article/chronic-stress-can-wreak-havoc-body

Recently scientists have begun to discover why stress can have a negative effect on the human body. Although stress is needed when dealing with situations which require hormones to trigger a fight or flight, consistent stress can lead to a multitude of health problems. Chronic stress can lead to mental instability, and an increased risk in heart attacks, strokes, infection, etc. The decrease in health is due to inflammation and warped genetic material caused by epigenetics (chemical interactions that activate and deactivate regions of a genome to carry out specific functions). Recently scientists have discovered that  changes in epigenetics can affect activity levels in genes which directly change responsibilities of certain cells including immune cells. The stress causes a genetic response that deactivates certain areas of a genome which stops an immune cell from working properly, which of course leads to an increase in diseases that cannot be properly taken care of. Hopefully, as we continue to understand epigenetics, we will be able to take appropriate steps that will both further our understanding of the human genome, as well as help increase the longevity and immune system of individuals.

Epigenetic breakthrough: A first of its kind tool to study the histone code

 

DNA_methylation

Scientists at the University of North Carolina have recently made a breakthrough in the study of epigenetics, particularly enzyme modification of histones. Histones, the structures to which our DNA binds in the nucleus, play a pivotal role in gene expression. In other words, histone and enzyme interaction control which genes are expressed in which cells during certain times. Epigenetics is the study of how this process works. Tightening or loosening histones can turn a certain gene off or on. The study of this process has been difficult given the size of the genome and number of different histone-enzyme interactions dispersed through the sizable sequence of DNA. The Enzymes place specific chemical markers on the histones that cause the gene regulation to occur, but scientists have been unable to determine which enzymes affect what genes and how. However, the scientists at UNC have recently conducted a study with the fruit fly genome that has given them a large amount of data. The fruit fly genome contains all of its epigenetic markers in the same place. The scientists were able to insert synthesized gene regulating enzymes in place of the originals and determine the function of each individual enzyme by simply observing what was affected by the new enzymes. This research is crucial for the understanding of how the human genome is regulated, possibly leading to the cure for many illnesses.

Article Link: http://www.sciencedaily.com/releases/2015/02/150210142008.htm

A Breath of Fresh Air: Epigenetic Studies Help Asthmatics

Asthma and allergies affect many people worldwide. Up until recently, treatments for both asthma and allergies were administered without an appropriate prediction of responses; However, this is about to change. In a recent study conducted by scientists at Imperial College London, “30 new genes that predispose people to allergies and asthma” were found. The discovery of these genes means that new treatments for allergies are possible and more accurate predictions for current treatment responses will be available.

Photo by Author

Photo by Author

By observing the epigenetic changes, ones that influence gene activity- not genetic code, the scientists were able to identify genes which are linked to triggering allergic responses. Such genes regulate specific antibodies. Genes become inactive through methylation: the attachment of methyl molecules to DNA. The scientists studied white blood cells of families with asthma to see if methylation levels in specific genomic locations were associated with levels of an antibody in the blood. Immunoglobin E (IgE) is the antibody studied in the case. The antibody IgE was known prior to this study, but the genes which activities it regulates were not. After monitoring the IgE levels in the blood, researchers saw a strong correlation between IgE and low methylation at 36 places in 34 genes. These genes are overstimulated in asthmatics, thus the production of IgE is increased, contributing to asthma symptoms. In expanding the investigation, researchers came to believe that IgE-involved genes may activate eosinophils, a type of white blood cell which in asthmatics promotes airway inflammation by gathering and releasing chemicals in airways/lungs. Researchers believed that these genes, and their ability to activate eosinophils, then cause the most damage. In order to test this, researchers isolated eosinophils from the blood of subjects and demonstrated that all 34 genes have high activity levels in asthmatics with high IgE levels. Thanks to the findings of new activation signals, patients can avoid high costs and ineffective “treatment-trials” because we’ll be able to predict responses to treatments with more accuracy. Professors Cookson and Moffatt, the leaders of the investigation, give credit to epigenetics for allowing them to make a breakthrough in discovering new potential drug targets for allergies and asthma and sharpening the accuracy of treatment-response predictions. Professor Cookson explained that, “the genetic code that can influence disease and DNA sequencing can only take you so far. Our study shows that modifications on top of the DNA that control how genes are read may be even more important.”

As someone who suffers from allergic asthma, I find it intriguing how the disease-triggering genes aren’t inactive, thus leading to poor lung function, but rather they are overstimulated. Our genes’ ability to regulate disease-triggering antibody activity is amazing. With new studies like this one, we can see that the solution to proper activity regulation is in epigenetic changes, rather than the broad expectations of “our genes”.  This just goes to show that epigenetics is helping us make strides in the ever-changing world of medicine. It should be interesting to see how epigenetic medical-solutions, the current gold mine of Biological research, evolve in the near future.

 

Does the aging process influence changes on a cellular level or do changes on a cellular level influence the aging process?

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How do humans age? While we are “programmed to die,” there doesn’t seem to be one thing that causes our death by “old age.” For example, one way we carry out our own deaths is found on the cellular level, where we accumulate mutations in the DNA repair process and the cells themselves die, or the enter senescence (non-replicating state) as they age. These processes occur at several different times, overlapping and alternating. Therefore, what appears to be the best time to intervene in order to promote healthy aging? No one knows, but they do know what DNA becomes extremely damaged as time goes on and has an incredible impact on our aging process. The cells have sooner suicide dates where they undergo apoptosis more rapidly than normal, and the loss of too many cells can cause tissue atrophy and dysfunction. In addition to creating a lack of cells, the damaged DNA can even shift epigenetic markers.

Typically, epigenetic marks shift in tumor cells, which can lead to cancerous cells. However, in the early 1990s at Johns Hopkins University, Jean-Pierre Issa was studying changes in DNA methylation in colon cancer cells when he observed shifts in epigenetic markers over time, but not only in tumor cells; he found that (to a lesser degree) these shifts were occurring in healthy cells as well. After mapping DNA methylation in human cells, we know that some areas of the genome become hypermethylated with age while others exhibit reduced methylation. These changes typically occur through DNA replication or DNA damage repair because the histone modifications are not always perfectly reproduced and in order to repair damaged DNA, repair proteins must remove the epigenetic marks to access the damaged genetic material to repair it, and once completed, the epigenetic marks can be omitted or misplaced. These epigenetic alterations have been linked to a reduced regenerative capacity of stem cells with age, and bring up a valuable question:

“Is this an epiphenomenon that happens just because we age, or is it actually causing symptoms or diseases of aging and limiting life span?”

Article source: http://www.the-scientist.com/?articles.view/articleNo/42280/title/How-We-Age/

Biggest Ever Epigenetics Project!!

 

Marian_and_Vivian_Brown

Identical Twins

 

This article is about a project that has recently been planned out with respect to

epigenetics. It is the largest project to date and will cost around $30,000,000 to complete. Epigenetics is the study of cellular and psychological trait variations that are not caused by DNA sequence, but rather what within the DNA is triggered and shown. It is a relatively new field and has exploded in recent years. The heads of this project are TwinsUK and BGI, both very credited organizations in the realm of epigenetics. Epigenetics is the newest and recently the most popular field of all genetics and the goal of this project is to use the twins and the resources given to understand why and how epigenetics occurs.

The plan is to review the patterns of 20,000,000 sites in the DNA of each identical twin (they must be identical because their DNA must be the same and not vary) and compare the DNA with the other twins. The aim is to not look at similarities, but to look at differences and figure out how twins get different diseases if their DNA is identical. They will focus on obesity, diabetes, allergies, heart diseases, etc. at first. Until recently, science did not understand why twins could receive different diseases since their DNA is identical to their other twin, but by studying epigenetics and how genes can be triggered to do different things based on surroundings and circumstance, this idea is plausible.

Being able to locate what genes turn on to trigger certain diseases along with how to control this is something that will benefit not only our general knowledge but will also advance health care to levels that it has never seen. Experiments such as this have been done before but only with a handful of twins. The goal in this experiment is to increase the amount of twins tremendously in order to increase the accuracy of their data.

The Executive Director of BGI, Professor Jun Wang stated that the goal of this experiment is to “unlock many secrets about human genetics that we don’t currently understand, and to accelerate research and applications in human healthcare.”

 

Bullying and its Epigenetic Effect

Unfortunately, bullying is commonplace in most schools in America.  Most people are aware of the mental and psychological harm that bullying can cause, but not until very recently have they been aware of the lasting physical changes it can cause.  With the discovery of epigenetics, or the study of genetic traits or expressions that are not caused by DNA, but rather by the methylation or concealing of genes, a new door into the effects of bullying was opened. A group of researches from the UK and Canada performed a study on identical twins.  At age 5, the twins had not been exposed to bullies and expressed almost all of the same traits, physically and emotionally.  The researchers then waited until the twins were 12, imageand revisited only the twins that had different experiences with bullying (one twin was bullied when the other was not).  The researches found big disparities in the twins epigenome, or the way they express their genes.

 

The bullied twin’s protein that codes for a protein that helps move the neurotransmitter serotonin into neurons called SERT had significantly more DNA methylation in its promoter region.  This change is thought to dial down the amount of proteins that can be made from the SERT gene — meaning the more it’s methylated, the more it’s “turned off.”  Therefore, the bullied twin is unable to produce as much serotonin.  This effect is thought to persist through a person’s life.  The effects of bullying will persist an entire lifetime.

 

The researchers also tested how the twins responded to stressful situations differently.  The bullied twin had a much lower cortisol response than the twin that had not experienced bullying.  Cortisol is a hormone that helps people through stressful situations, like being bullied.  However, having too much cortisol is harmful to the body.  The bullied twin’s body turned off the gene that aids in cortisol production because they were being put in stressful situations so often by bullies that their body couldn’t tolerate the amount of cortisol they were producing.

 

This study is not only interesting from a scientific standpoint, but it is also very important in the movement against bullying.  These scientists proved that bullying not only does immense psychological harm, but it also effects people’s well being in a very real and lasting way.

 

 

 

Link to article: http://www.huffingtonpost.com/sharon-moalem/bullyings-terrible-legacy_b_5142857.html

 

Fear in Your Genes

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Scientists at the University of Virginia recently conducted a study that suggests a connection between social behaviors and epigenetic markers. The study of these markers could predict the social dispositions of individuals and predict future social issues.

The gene for Oxytocin receptor (OXTR) has the ability to carry various amounts of DNA methylation tags. Those low in methyl tags have a greater ability to utilize oxytocin and therefore have a less amplified fear response. Those with many DNA methyl tags are shown to exhibit a more exaggerated fear response. More finitely, the amount of OXTR methylation affected the amount of brain activity in the amygdala, fusiform, and insula. These regions of the brain are directly correlated with face and emotional processing. To prove this, researchers conducted MRI scans on healthy participants while showing them pictures of angry and fearful faces.

The study not only proved the importance of studying the possible effects of epigenetic markers on susceptibility and resistance to disease, but it also shed a light on the possibility of brain disorders such as autism, anorexia, and depression being linked to DNA methyl tags at the oxytocin receptor.

Broadly, this study changes the way we look at how our environment and upbringing shapes our future susceptibility to illness and disorders. As scientific investigation into this topic continues and expands, we may be able to predict an individual’s reaction to social situations with the prick of a finger.

Article Source: http://www.genengnews.com/gen-news-highlights/fear-response-may-be-epigenetically-amplified-or-muted/81250914/

Identical Twins, Identical Lives, Different Disease

Jack and Jeff Gernsheimer are identical twins. Jack has Parkinson’s disease, and his twin Jeff does not. Up until recently, because they have identical genomes, it would have been a mystery as to why Jack could develop Parkinson’s but not Jeff. However, with the discovery of epigenetics, scientists know that genes alone cannot explain why some people get Parkinson’s and other do not. While there are some genetic mutations linked to Parkinson’s, 90 percent of cases are “sporadic”, meaning that the disease did not run in the family. Even twins often do not develop Parkinson’s in tandem. Naturally, if genes don’t explain the development of Parkinson’s, scientists look to environment. There are several environmental factors that are known to link to the disease. People who were POW’s in WWII, for example, have a higher rate of developing Parkinson’s. But, and here’s the interesting part, Jack and Jeff have lived almost identical lives. For almost all of their lives, they have lived less than half a mile apart. Throughout their lives, they have been exposed to the same air, water, pesticides, etc. When they grew up, they built homes five minutes apart (by walk) on their father’s farm in Pennsylvania. Then, when they entered the professional life, they co-founded a design firm, working with their desks pushed up against each other.

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This anomaly, where a pair of humans exist with the same genetics and the same environment yet only one of them got sick is a research “bonanza” for scientists. All expected variables are being held constant, thus whatever is left must be deeply linked to the origins of Parkinson’s. However, there was a small difference in their lives that could provide insight into this anomaly. in 1968, Jack was drafted into the army and Jeff was not. This led to a series of unfortunate events in Jack’s life: first he served two years stateside in the military, got married, had two children, became involved in a long divorce, and suddenly his teenage son died. After this traumatic event, Jack went on to develop Parkinson’s, glaucoma, and prostate cancer, none of which Jeff has.

Jeff and Jack have been more than willing to undergo several studies in hope of finding something that could alleviate Jack’s Parkinson’s. The first study involved collecting embryonic stem cells from the twins. The benefit of stem cell cultures is that they act similarly to how they would in the body even though they are in a petri dish. The mid-brain dopaminergic neurons grown from Jack’s cells created abnormally low amounts of dopamine. Jeff’s produced normal amounts. Surprisingly, even though Jeff showed no signs of Parkinson’s, both twins had a mutation on a gene called GBA. This gene is known to be associated with Parkinson’s. As a result, both of their brain culture cells produced half the normal amount of beta-glucocerebrosidase, an enzyme linked to that gene. Instead of answering questions, this study only raised more to the fascinating case of Jeff and Jack.

I want to add a bit about how Jack’s son died, because it is unimaginably tragic and can show you just how much Jack had to face. Especially if we are considering Jack’s trauma as a contributor to his development of Parkinson’s, it is important to know the story. When Gabe, Jack’s son, was 14 in 1987, he became fascinated with the Vietnam War. Like any good father, Jack rented his son some movies on the war. One of those being The Deer Hunter, in which there is a scene where two prisoners of the Viet Cong are forced to play Russian Roulette. Gabe told his friend that if it were him, he wouldn’t just sit there. He would rather just get it over with. With that conversation, Gabe got his dad’s pistol, that he knew was hidden in the closet drawer, put one bullet in the chamber, put the gun to his head, and shot.

Jack rarely shows emotion. This “pressure cooker” way of dealing with things could explain his illness. Jeff thinks that the parkinson’s is a physical manifestation of how Jack deals with stress, rather how he doesn’t deal with stress. The connection between stress and disease is a very active research topic. And while their lives were very similar, if compared, Jack’s is by far the life with a more stressful environment. Some research might suggest that this stress differential can have a relation to Parkinson’s disease. In 2002, neuroscientists at UPitt subjected rats to stress, and they found that the stressed rats were more likely to experience damage to their dopamine-producing neurons than the non-stressed rats. This led to the term “neuroendangerment”, which means “rather than stress producing damage directly and immediately, it might increase the vulnerability of dopamine-producing cells to a subsequent insult.”

Another hypothesis as to what caused Jack’s Parkinson’s is that it could be linked to chronic inflammation.  Chronic inflammation is the mechanism by which stress can create neurodegeneration. Evidence that suggests this could be the case in Jack and Jeff is presented in their skin. Jack has psoriasis, a condition linked to chronic inflammation, and Jeff does not.

To this day, the search for what caused Jack’s Parkinson’s continues. Last year, NYSCF scientists conducted a study on the twins’ stem cells. They found a few functional differences between their cells. After finding the GBA mutation, they searched harder for other clues as to what might differentiate their brains. They screened 39,000 SNV’s, single nucleotide variants, which are instances where a single nucleotide in the human genome has been altered (either switched, deleted, or duplicated). They found 11 SNV’s, nine of which are linked to Parkinson’s disease. However, all 9 were found in both twins, meaning that this did not explain why Jack was sick and Jeff wasn’t.

Finally, they were able to uncover a relevant difference. Jack had high levels of MAO-B, which is involved in the breakdown of dopamine, whereas Jeff’s levels were close to normal.This hypothesis supposed that there exists a possible molecular mechanism by which stress could lead to neurodegeneration. What’s nice about this finding is that it could present a possible treatment for Parkinson’s. MAO-B inhibitors exist and are actually drugs currently on the market. They were given to Jack, and while it’s too soon to see the effects and to recommend them as treatment for Parkinson’s disease, it’s definitely a start.

Source: http://nautil.us/issue/21/information/did-grief-give-him-parkinsons

Epigenomes may hold the key to curing Alzheimer’s and Cancer

Dna-split

 

Epigenomes are a relatively new discovery in Biology and there is a lot of well deserved excitement about it. Manolis Kellis, an MIT biologist, believes that epigenomes may lead us to the cure of Alzheimer’s and cancer. By understanding epigenomes, we could “reverse the actions of chemical modifications that regulate genes associated with disease”. A study was done on mice to see which genetic mutations were active for certain traits. Surprisingly, the research paired Alzheimer’s to neurons and immune cells. This could potentially mean that the place to look for a cure to Alzheimer’s is in your neurons or immune cells. Since this experiment was done on mice, it isn’t certain that the same will be true for humans, but Kellis believes it is more likely than not.

A second study was done to see which parents passed on which chromosomes. Some chromosomes tend to overpower the other, being dominant. For example, a mother chromosome that is positive for Alzheimer’s might be recessive to a father chromosome that is negative for Alzheimer’s. If scientist can determine the pattern of inheritance, they can predict the likelihood of a child inheriting that gene with greater accuracy.

Research was also done on cancer cells as they tried to figure out the origin of cancers that spread across the body, specifically metastatic cancer. When this cancer spreads it can be tough for doctors to determine the origin cell. If the origin cell can be located using epigenetics, it can increase the accuracy of locating the parent cell to 90%.

Kellis reminds us that it would be years before a cure is found as drug testing and creation are complex. And as we know epigenomes change from environmental factors leading to a vast amount of possibilities making it an even more complex process. However, this is a big step in the right direction.

 

Additional links:

http://scitechdaily.com/engineers-developed-new-method-detect-epigenetic-modifications/

http://scitechdaily.com/researchers-use-bioinformatics-and-epigenetics-to-aid-cancer-research/

Epigenetics and Brain Development

Epigenetics and Brain Development

Pre-natal human brain development helps determine many major qualities a person may have in life. Research at the University of Exeter found that a type of Epigenetics, DNA methylation, helps us understand the differences between male and female brains. They studied that this type of gene regulation in pre-natal brain development may help us grasp more information about “sex differences in behavior, brain function, and disease.”

In the womb, as organs are developing, the brain has extreme plasticity. Professor Jonathan Mill of the University of Exeter explains how it is extremely vulnerable to changes because the brain is creating the structures that “control neurobiological function across life.” The research consisted of measuring genomic patterns of DNA methylation in the womb between 23 and 184 days after conception. DNA methylation is a chemical modification to one of the 4 nitrogen bases that helps create one’s unique genetic code. By studying the DNA methylation, or turning on of selected genes, in the pre-natal period when the brain is being developed, it helps scientists understand the susceptibility of different neurological diseases based on one’s sex. Helen Spiers from King’s College London explains how male and females have unique differences with certain disorders, such as Autism. She says how “autism affects five males to every female.”

The molecular switches that regulate genes were found to be gender specific. They also help differentiate brain cells from other cells in the body. This research gained traction in understanding the unique qualities of the DNA “blueprint” of males and females in their developing stages. The genetic switches that are turned on in pre-natal development for each gender are unique, and a deep topic of study. By doing so, in the future, scientists can research deeper into neurological diseases that are unique to males or females, and how they may be created in the womb.

 

Original Article: http://www.sciencedaily.com/releases/2015/02/150203190223.htm

Link to picture:

http://commons.wikimedia.org/wiki/File:Brain_01.jpg#mediaviewer/File:Brain_01.jpgBrain_01

#EpigeneticInheritance

Professor Marcus Pembrey of the University College of London transcribes the complexity of epigenetics into an understandable definition, simply put as “a change in our genetic activity without changing our genetic code.” The study of “epigenetic/transgenerational inheritance” has been a field of increasing popularity within the last decade, as studies and further research are beginning to show evidence of lifestyle stresses carrying over in the genome of each generation. Now, this is not to say that our grandparents way of living changed our DNA coding but rather potentially altered the way certain genetic information is or is not expressed.

 

To further explore the possibility of epigenetic inheritance, a laboratory in Boston conducted an experiment on three generations of mice.  A pregnant mouse was ill-fed in the late stages of pregnancy and as expected the offspring were born relatively small and later in life developed diabetes. However, the F2 generation experienced a high risk of acquiring diabetes, despite being well nourished. Another study on mice showed similar results; after a father was artificially taught to fear a particular smell, the offspring of that mouse also demonstrated a fear to the same smell.

 

Although the excitement over the groundbreaking research of epigenetics seems promising, researchers are still working to compile a stronger foundation of evidence to prove that this phenomena actually occurs in mammals. Professor Azim Surani of the University of Cambridge fully supports the idea of epigenetic inheritance in plants and worms, but has yet to commit to the same notion in mammals, as their biological processes differ greatly.

 

Regular Exercise Can Change Our DNA

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Most people (hopefully) know that exercise and physical activity are beneficial to almost everyones physical and mental health. Exercising improves one’s mood, boosts energy, controls weight, helps the body fight against diseases, reduces stress, and many more life benefits. A new study  by a group of scientists in Sweden discovered how the influence of physical exercise actually has that beneficial effect on the human body.

The scientists focused their work on 23 young, healthy men and women at the Karolinska Institute in Stockholm. The participants were asked to exercise on stationary bikes for 45 minutes, four times per week, for three months. The scientists understood that it would be difficult to study the full changes on each person because they can’t isolate the other aspects of someone’s life like diet or other behaviors. Because of this issue, each person only exercised one leg so they essentially became their own control group.

After the three months had passed, the scientists clearly saw that the exercised leg was stronger. They also studied the DNA of the muscle cells and compared them between each leg. The genome of muscle cells on the exercised leg had new methylation patterns. DNA Methylation is the process of methyl groups attaching to the outside of a gene and making the gene more or less able to respond to biochemical signals. This entire study is also known as epigenetis. Epigenetics is the study of modifications of DNA influenced by the environment. The scientists found that exercise has a huge effect on human epigenetics based on methylation patterns.

The experiment showed that many of the methylation changes were on the enhancer part of the genome. Enhancers “bind to activator proteins which help connect transcription factors to RNA polymerase and the promotor region to turn on transcription of a gene” (from Mrs. Newitt notes packet). The enhancers amplified the expression of proteins by genes that effect energy, insulin, muscle inflammation and muscle pain.

Exercising is good for you and now we know why. It affects how healthy and fit our muscles become. The results of this study will now help lead other scientists into methylation pattern and gene expression research.

 

Main article:

http://well.blogs.nytimes.com/2014/12/17/how-exercise-changes-our-dna/?_r=0

Other articles of interest:

http://www.ncbi.nlm.nih.gov/pubmed/25484259

http://learningenglish.voanews.com/content/study-regular-exercise-can-change-our-dna/2580467.html

http://www.cell.com/cell-metabolism/abstract/S1550-4131(12)00005-8?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413112000058%3Fshowall%3Dtrue

http://www.mayoclinic.org/healthy-living/fitness/in-depth/exercise/art-20048389?pg=1

Can Stress Affect Pregnancies in Later Generations?

We all know stress isn’t always a good thing, but it could be important to especially avoid it at certain points in one’s life. Recently researchers from the University of Lethbridge in Canada investigated the effects of stress on pregnancies and how it can influence pre-term births. It is already known that pre-term births them selves lead to health issues later in life, but there were some new discoveries involving epigenetics.

 

Epigenetic_mechanisms

 

These researchers studied the length pregnancies of rats, due to the generally small amounts of variation between them, and found something intriguing. They carried out the experiment by first splitting the first generation of rats into “stressed” and “not stressed” groups. What they found was that the daughters of stressed rats had a shorter pregnancy than the daughters of not stressed rats.

This trend continued into the granddaughters of the rats. They also displayed high levels of glucose than the control group, and they weighed less. The stress also compounded, or increased, through generations.

This can all translate into human pregnancies. The researchers believe that the epigenetic changes in the rats is due to microRNA (miRNA) – non-coding RNA molecules that play a role in regulating gene expression. They bind to complementary mRNAs and prevent them from being translated. This is different than what is usual belief with epigenetics which is that epigenomes are affected by DNA methylation of the nucleotide base pairs. Metz, a scientist working on this research states that microRNAs “are important biomarkers of human disease, can be generated by experiences and inherited across generations. We have now shown that maternal stress can generate miRNA modifications with effects across several generations.”

It is very similar to the information found with the generational epigenetic effects of famine in the “Ghost in Our Genes” video that we watched in class.

This research can help determine pre-term births and the causalities that can come along with them. While the research is still not the whole picture, it is another step towards understanding our genetics.