RLS is NOT Hereditary: Welcome to the AMAZING World of Epigenetics! (PART TWO: What is Epigenetics?)

Image“The exploding science of epigenetics will transform our understanding of health and disease.” – Peter A. Jones, PhD, DSc. Professor of Urology and Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California

As you will read below, the science of epigenetics IS exploding onto the scene.  
And with that explosion comes a powerful new awareness that is freeing our minds and spirits as it continues to debunk the old myth that we are “stuck” with the genes that were passed on to us, including the genes that cause RLS.

And we’re only at the beginning. Hope has arrived!

from Randy Jirtle, Geneticist, Dept. of Radiation Oncology at Duke University

“Think of the genome as being like the hardware of a computer. The epigenome would be like the software that tells the computer when to work, how to work, and how much.”

from The Week “Epigenetics: How our experiences affect our offspring.” January 20, 2013    

“New research suggests that people’s experiences, not just their genes, can affect the biological legacy of their offspring

Isn’t our genetic legacy hardwired?

From Mendel and Darwin in the 19th century to Watson and Crick in the 20th, scientists have shown that chromosomes passed from parent to child form a genetic blueprint for development. But in a quiet scientific revolution, researchers have in recent years come to realize that genes aren’t a fixed, predetermined program simply passed from one generation to the next. Instead, genes can be turned on and off by experiences and environment. What we eat, how much stress we undergo, and what toxins we’re exposed to can all alter the genetic legacy we pass on to our children and even grandchildren. In this new science of “epigenetics,” researchers are exploring how nature and nurture combine to cause behavior, traits, and illnesses that genes alone can’t explain, ranging from sexual orientation to autism to cancer. “We were all brought up to think the genome was it,” said Rockefeller University molecular biologist C. David Allis. “It’s really been a watershed in understanding that there is something beyond the genome.”

What is epigenetics?

The word literally means “on top of genetics,” and it’s the study of how individual genes can be activated or deactivated by life experiences. Each one of our cells, from skin cells to neurons, contains an identical DNA blueprint, yet they perform vastly different functions. That’s because epigenetic “tags” block developing fetal cells from following any genetic instructions that don’t pertain to their intended roles. That biochemical process, scientists have discovered, occurs not just during gestation and early development but throughout adulthood, switching genes on or off and altering our mental and physical health.

How does that affect who we are?

We’re only beginning to find out. A woman’s diet during pregnancy seems to have a major impact on her baby’s epigenetic tags. Prenatal diets that are low in folic acid, vitamin B-12, and other nutrients containing “methyl groups” — a set of molecules that can tag genes and cause epigenetic changes — have been linked to an increased risk of asthma and brain and spinal cord defects in children. Stress, too, can alter fetal epigenetic tags. Pregnant women who were traumatized at the World Trade Center on 9/11 were far more likely than other women to give birth to infants who reacted with unusual levels of fear and stress when faced with loud noises, unfamiliar people, or new foods.

Are these insights yielding medical therapies?

Over the past five years, evidence that epigenetics plays a major role in cancer has become “absolutely rock solid,” says Robert A. Weinberg, a biologist at the Whitehead Institute in Cambridge, Mass. Andrew Feinberg, director of Johns Hopkins University’s Epigenetics Center, thinks it’s a factor in autism and diabetes as well. Drugs are in the works aimed at undoing cancerous epigenetic changes. Even eating foods rich in gene-altering methyl groups — such as soybeans, red grapes, and green tea — might protect against disease by silencing detrimental genes. In one famous experiment, researchers fed a methyl-rich diet to pregnant female mice that carried a gene that made them fat, yellow, and prone to cancer and diabetes. Though their offspring carried the same gene, they were born slim, brown, and disease-free. But researchers are still trying to work out how to use this powerful tool to address specific health problems. “Did this change in diet increase cancer risk?” asks McGill University pharmacologist Moshe Szyf. “Did it increase depression? Did it increase dementia or Alzheimer’s? We don’t know yet, and it will take some time to sort it out.”

Imagefrom Newsweek Magazine “Beyond the Book of Life.” Jun 26, 2009

“There’s a revolution sweeping biology today — begrudged by a few, but accepted by more and more biologists — that is changing scientific thinking about the way genes work, the way diseases arise and the way some of the most dreadful among them, including cancer, might be diagnosed and treated. This revolution is called epigenetics, and it is not only beginning to explain some of the biological mysteries that deepened with the Human Genome Project. Because of a series of accidental events, it is already prolonging the lives of human patients with deadly diseases.

Over the past several years, and largely without much public notice, physicians have reported success using epigenetic therapies against cancers of the blood and have even made progress against intractable solid-tumor malignancies like lung cancer. The story is still preliminary and unfolding (dozens of clinical trials using epigenetic drugs are currently underway), but Dr. Margaret Foti, chief executive officer of the American Association for Cancer Research, recently noted that epigenetics is already resulting in “significant improvements” in cancer diagnosis and therapy. “It’s really coming into its own now,” she said. Leaping on the bandwagon, the National Institutes of Health made epigenetics the focus of one of its cutting-edge “Roadmap” initiatives announced last fall.

“I think we were all brought up to think the genome was it,” says C. David Allis, a scientist at Rockefeller University whose research in the 1990s helped catalyze the current interest in epigenetics. “But even when the genome was a done deal, some people thought, ‘Is that the whole story?’ It’s really been a watershed in understanding that there is something beyond the genome.”

The emergence of epigenetics represents a fundamental rethinking of how molecular biology works. Scientists have learned that while DNA remains the basic text of life, the script is often controlled by stage directions embedded in a layer of biochemicals that, roughly speaking, sit on top of the DNA. These modifications, called epimutations, can turn genes on and off, often at inappropriate times. In other words, epigenetics has introduced the startling idea that it’s not just the book of life (in the form of DNA) that’s important, but how the book is packaged.“

from “Epigenetics, Methylation, and Gene Expression.” by Kevin Cann, April 10th, 2013

“Many of us think that we are doomed to a life of obesity or disease because of our genes. The truth is, we may be more genetically predisposed to certain metabolic conditions or disease states, but that does not mean there are not things we can do to alter this gene expression.  The idea that our genes react to environmental and internal stimuli is referred to as epigenetics. Our genetic code is wrapped up into our DNA and paired into 23 sets of chromosomes.

The DNA then wraps itself around alkaline proteins called histones. These histones then give the DNA structure. These newly formed structures are referred to as nucleosomes. On the outside of these histones are chemical messengers that listen for cues from the environment and from our internal systems. This whole structure is known as the epigenome. When the chemical messengers receive a stimuli, they will react by tightening themselves around certain genes to make them inactive so that they cannot be read by other cells. On the other hand they will relax themselves around other genes so that they are easily accessible. Our DNA we are stuck with, but our gene expression can be altered.

Our bodies turn off genes through a process called methylation. To keep it simple this is adding a methyl group to the DNA. As of late researchers have been looking at methylation as a primary role player in the onset of certain diseases. It is believed that methylation plays an important role in the stability of trinucleotides. In a trinucleotide repeat disorder such as Huntington’s Disease, this is important to understand. There are germinal and somatic cells within our system, and methylation is in charge of maintaining their stability.”
from The University of Utah Genetic Science Learning Center “What is Epigenetics”

“The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them.”
Imagefrom Science Watch “Epigenetics: 20 Years and Rising.” by Jeremy Cherfas   

“Over a 20-year period, there has been an eight-fold increase of papers on epigenetics from just over 1,000 papers in 1992 to more than 8,500 in 2011.
Following on this steady rise, epigenetics as a research field will undoubtedly get a further boost from the 2012 Nobel Prize in Physiology or Medicine, awarded to John B. Gurdon and Shinya Yamanaka. Gurdon showed that an adult frog nucleus contains all the genetic information needed to develop into a mature frog. Yamanaka discovered that just four genes could reprogram an adult skin cell into a pluripotent stem cell, capable of differentiating into all the specialized cell lines of an adult mouse. Both were effectively reversing a lifetime of epigenetic modifications to the cell.”

from NOVA scienceNOW “Epigenetics.” July, 2007

“Once nurture seemed clearly distinct from nature. Now it appears that our diets and lifestyles can change the expression of our genes. How? By influencing a network of chemical switches within our cells collectively known as the epigenome. This new understanding may lead us to potent new medical therapies. Epigenetic cancer therapy, for one, already seems to be yielding promising results.

Our lifestyles might affect the health of our children and even grandchildren.”

from The New York Times “Why Fathers Really Matter.” by Judith Shulevitz, September 8, 2012

“Epigenetics means that our physical and mental tendencies were not set in stone during the Pleistocene age, as evolutionary psychology sometimes seems to claim. Rather, they’re shaped by the life we lead and the world we live in right now. Epigenetics proves that we are the products of history, public as well as private, in parts of us that are so intimately ours that few people ever imagined that history could reach them.”

from The University of Utah Genetic Science Learning Center “The Epigenome Learns from its Experiences.”

“Epigenetic tags act as a kind of cellular memory. A cell’s epigenetic profile — a collection of tags that tell genes whether to be on or off — is the sum of the signals it has received during its lifetime.

As a fertilized egg develops into a baby, dozens of signals received over days, weeks, and months cause incremental changes in gene expression patterns. Epigenetic tags record the cell’s experiences on the DNA, helping to stabilize gene expression. Each signal shuts down some genes and activates others as it nudges a cell toward its final fate. Different experiences cause the epigenetic profiles of each cell type to grow increasingly different over time. In the end, hundreds of cell types form, each with a distinct identity and a specialized function.“

Imagefrom The New York Times “Study Finds How Genes That Cause Illness Work.” by Gina Kolata, January 20, 2013

“In a pathbreaking paper, researchers at the Johns Hopkins University School of Medicine and the Karolinska Institute in Sweden report a way to evaluate one gene-regulation system: chemical tags that tell genes to be active or not. Their test case was of patients with rheumatoid arthritis, a crippling autoimmune disease that affects 1.5 million Americans.

Researchers know a gene will remain stable, but the chemical tags that turn the genes on and off are not so reliable. Their presence can be affected by the environment or medications or even the activity of other, distant genes. They can be a consequence of a disease or set off a disease.

The researchers reported measurement techniques that enabled them to sort things out. They found hundreds of chemical tags but only four that seemed truly related to the disease. Those four were in a cluster of genes that controls the immune response and that was known to affect the risk of rheumatoid arthritis, said Dr. Andrew Feinberg of Johns Hopkins, a lead author of the study. In particular, the tags were in a gene called C6orf10 whose function is unknown.

The chemical tags may help determine if a person with a gene that increases risk of developing a disease actually gets the disease. There were people in the control group who had gene variations associated with arthritis risk, but they did not have those four chemical tags and did not have the disease.”

from The Washington Post “Emerging science aims to manipulate human DNA.” by Rachel Saslow, December 15, 2009

“Two mice. One weighs 20 grams and has brown fur. The other is a hefty 60 grams with yellow fur and is prone to diabetes and cancer. They’re identical twins, with identical DNA.

So what accounts for the differences?

It turns out that their varying traits are controlled by a mediator between nature and nurture known as epigenetics. A group of molecules that sit atop our DNA, the epigenome tells genes when to turn on and off.

A growing body of research has some scientists rethinking humans’ genetic destinies. Is our hereditary fate — bipolar disorder or cancer at age 70, for example — sealed upon the formation of our double helices, or are there things we can do to change it? Are we recipients of our DNA, or caretakers of it?

Last year, the National Institutes of Health announced that it would invest $190 million to accelerate epigenetic research. The list of illnesses to be studied in the resulting grants reveals the scope of the emerging field: cancer, Alzheimer’s disease, autism, bipolar disorder, schizophrenia, asthma, kidney disease, glaucoma, muscular dystrophy and more.”

“Prostaglandin E2 promotes intestinal tumor growth via DNA methylation.” by Dianren Xia, Dingzhi Wang, Sun-Hee Kim, Hiroshi Katoh & Raymond N DuBois. Nature Medicine 18, 224–226 (2012). doi:10.1038/nm.2608

“The difference between genetics and epigenetics can be compared to the difference between writing and reading a book. Once a book is written the text (genes or DNA sequence) will be the same in all copies distributed to the audience. However, each individual reader of a book may interpret the story slightly differently, with varying emotions and projections.

In a similar manner, epigenetics would allow different interpretations of a fixed template and result in different read-outs dependent on the variable conditions under which the template is interrogated.”
from Mercola.com “Why Your DNA Isn’t Your Destiny.” January 23, 2010

“For decades, we have stumbled around massive Darwinian roadblocks. DNA, we thought, was an ironclad code that we and our children and their children had to live by. Now we can imagine a world in which we can tinker with DNA, bend it to our will.

It will take geneticists and ethicists many years to work out all the implications, but be assured: the age of epigenetics has arrived.

ImageYour Genetics Are Malleable — Like Clay

Epigenetic “malleability” helps to explain why identical twins become distinct as they age.

Why does one identical twin develop cancer and the other remain healthy when they have identical DNA? Why does one twin become obese and another remain lean?

As you age, your genome does not change but your epigenome changes dramatically, especially during critical periods of life, such as adolescence. It is influenced by physical and emotional stresses — how you respond to everything that happens in your environment, from climate change to childhood abuse.

You do not manifest disease merely by a defective gene, but by your epigenome. In other words, whether or not you develop disease is determined by how your genome is being directed to express itself. There are also “master genes” that can switch on and off clusters of other genes.

Scientists have discovered it is easier to make epigenetic changes than to fix damaged genes. Your epigenome is easier to mess up — but it’s also easier to fix.

That’s good news — you aren’t doomed by bad genes!

Epigenetic therapy, which is essentially the curing of disease by epigenetic manipulation, involves changing the instructions to your cells — reactivating desirable genes and deactivating undesirable ones. This emerging field, now in its infancy, may represent the future of medicine.”

from The New York Times “Genes as Mirrors of Life Experiences.” by Benedict Carey, November 8, 2010

“By studying genes at the “epi” level, scientists are hoping to discover patterns that have been elusive at the level of the genes — and ideally to find targets for calibrated treatments that would not simply shut off errant genes but would gradually turn their activity up or down, like adjusting the balance on a stereo.”

from LiveScience “Why Your DNA May Not Be Your Destiny.” by Denise Chow, June 04, 2013  

“Ten years ago, when researchers completed the first map of all the genes of human beings, the immense undertaking promised to revolutionize the field of molecular medicine. It did, but something was still missing.

“By sequencing the 3 billion chemical base pairs that make up human DNA, scientists were able to glean new information about genes and how they are expressed. Yet there were hints that something else might be controlling which genes are turned on and off” said Jean-Pierre Issa, director of the Fels Institute for Cancer Research and professor of molecular biology at Temple University in Philadelphia.

“When the human genome was sequenced, some scientists were saying, ‘That’s the end. We’re going to understand every disease. We’re going to understand every behavior.'” Issa said. “And it turns out, we didn’t, because the sequence of the DNA isn’t enough to explain behavior. It isn’t enough to explain diseases.”

In the 1950s, an English developmental biologist named Conrad Waddington suggested that something was working on top of the DNA sequence to modulate gene expression.

Scientists who advanced Waddington’s hypothesis began investigating whether experiences or a person’s environment could trigger genetic changes. This work came to be known as epigenetics, and it suggested that human development was not completely hardwired in DNA.

“When you think of nurture and nature, what epigenetics represents is the interface between those two influences,” said Frances Champagne, a behavioral scientist at Columbia University in New York.”
from The Scientist “Decoding DNA: New Twists and Turns.”

“From my perspective,” says Victoria Richon, Vice President, Discovery and Preclinical Research, Sanofi. “I think the reason why we’re really seeing the explosion of information about this field is that we now understand the enzymes and really the machinery that’s catalyzing the … different modifications, which previously we didn’t.”

Imagefrom Jean Pierre Issa M.D. Anderson Cancer Center  

“The idea of epigenetic therapy is to stay away from killing the cell. Rather, what we are trying to do is diplomacy, trying to change the instructions of the cells, reminding the cell, “Hey, you’re a human cell. You shouldn’t be behaving this way.” And we try to do that by reactivating genes.”

from “Phenocopies in families with essential tremor and restless legs syndrome challenge Mendelian laws. Epigenetics might provide answers.” by Zimprich A.  Parkinsonism Relat Disord. 2012 Jul;18(6):711-6. doi: 10.1016/j.parkreldis.2012.03.019.  

“Inheritance of epigenetic mutations along with paramutational events have the potential to explain the non-mendelian features in the genetics of restless legs syndrome.”

from Scientific American “How Acquired Diseases Become Hereditary Illnesses.” by JR Minkel, August 9, 2010

“One of the primary goals of genetics over the past decade has been to understand human health and disease in terms of differences in DNA from person to person. But even a relatively straightforward trait such as height has resisted attempts to reduce it to a particular combination of genes. In light of this shortcoming, some investigators see room for an increased focus on an alternative explanation for heritable traits: epigenetics, the molecular processes that control a gene’s potential to act. Evidence now suggests that epigenetics can lead to inherited forms of obesity and cancer.

The best-studied form of epigenetic regulation is methylation, the addition of clusters of atoms made of carbon and hydrogen (methyl groups) to DNA. Depending on where they are placed, methyl groups direct the cell to ignore any genes present in a stretch of DNA. During embryonic development, undifferentiated stem cells accumulate methyl groups and other epigenetic marks that funnel them into one of the three germ layers, each of which gives rise to a different set of adult tissues. In 2008 the National Institutes of Health launched the $190-million Roadmap Epigenomics Project with the goal of cataloguing the epigenetic marks in the major human cell types and tissues.”

from Potential Magazine “Research Frontiers: The Study of Epigenetics.” by Martie Callaghan, Spring 2009

Are your genes turned on?

“We know that epigenetic phenomena can be transmitted from generation to generation,” says Dr. Walter Kaufmann of the Kennedy Krieger Institute. “We must now identify specific diets or other lifestyle dynamics that can influence and potentially reverse these epigenetic labels that you inherited from your ancestors.”

The implications and applications of epigenetics reach even farther.

“We use a lot of medications in young children and many times there is no alternative but to do that,” Dr. Kaufmann says. “We may be able to think about interventions that are more environment based.”

Imagefrom The Sydney Morning Herald “You are what your mother ate.” by Sarah Berry, March 15, 2012

“Unlike genes, which can take hundreds of years to change, epigenetic changes can occur relatively quickly.”

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