Archives for posts with tag: epigenetics

Greenwire: Prenatal exposures prompt EPA to re-examine chemical regulations.

U.S. EPA regulators convened with scientists last month to discuss how to design regulations for chemicals based on emerging science that connects exposures during pregnancy with disease much later in life.

A mother exchanges with her child in the womb chemicals that have remained constant for much of human evolution. They dictate which genes will be turned on and off in the child, which proteins the child will make in his body and how much of them.

New research, in a field called epigenetics, now suggests that these changes, made during the earliest part of gestation, could spell out the child’s longer-term medical record. It could determine his propensity for mood swings, his tendency to gain weight into the realms of obesity, his risk of developing cardiovascular disease or cancer when he hits 50, and his propensity of passing on his genes to his children.

The idea is that the child adapts to environmental cues in the womb that will reflect the chemical composition of the world, thus conferring a Darwinian fitness advantage.

The mix of chemicals a fetus is exposed to has exploded in the past 200 years, heralded by the Industrial Revolution. Technology has outstripped evolution, said Robert Chapin, senior research fellow in drug safety research and development at Pfizer Inc. People were suddenly surrounded by particulate matter from cars, coal-plant emissions, metals, organic molecules from hand sanitizers, body lotions and other chemicals, some of which could cross into the placenta and merge into the child’s aqueous world.

Some, such as folic acid, were intentionally given to moms as beneficial; others such as bisphenol A became common in the modern environment and had the ability to mimic hormones that are naturally present in humans. Yet others, such as arsenic and tin, are naturally present in some places.

Scientists now suspect that the altered chemical cues during the critical windows of pregnancy — at stages when gender is still developing and the human is little more than a collection of cells — could trigger pathways that manifest as disease well into adulthood.

More . . .


Animation on how mice are used to study changes in DNA that could also occur in humans and eventually lead to cancer. The genetic similarity of mice to humans accounts for mice being a good experimental model to study cancer. Mouse models that mimic human disease play a vital role in understanding the etiology (cause and origin) of cancer. Results of mouse model studies lend evidence toward the next step in biomedical research that leads to early detection of cancer, new cancer drugs, new combinations of treatments, or new methods such as gene therapy.]

From the Montreal Gazzette:

Early childhood living conditions provoke biological changes in genes leading to DNA “memory” that can last a lifetime, an international study has found.

Experts have already noted that income, education and neighbourhood resources can have a dramatic effect on children’s health, and that a poor socio-economic environment in infancy can translate into a higher risk of adult disease and early mortality.

But a study published online Thursday in the International Journal of Epidemiology suggests that early experience works changes that are far more than skin deep.

The environment of early childhood influences brain and biological development and leaves a “memory” in the genetic code that affects the way genes function, say researchers from McGill University, the University of British Columbia and the UCL Institute of Child Health in London, England.

“Biological embedding” may help explain why health disadvantages linked to a lower socio-economic origin — including obesity, mental health problems, heart disease, diabetes and other chronic illnesses — can last a lifetime even if living conditions improve later.

The team focused on a small sample — 40 men — from the ongoing British cohort study, which has followed 10,000 people born in March 1958 from birth onward.

The team looked at the DNA of men aged 45 who came from one of two economic extremes: children whose fathers were unskilled workers; and those whose dads were company CEOs and Oxford/Cambridge graduates.

“We wanted to sample from the extremes so that if there was an epigenetic (gene) signal, it would be as clear as possible — and that’s in effect what emerged,” said Clyde Hertzman, director of the UBC-based Human Early Learning Partnership and an author of the study.

After looking at control areas of 20,000 genes, researchers found twice as many genetic differences (1,252 changes) in those brought up in wealth and comfort compared to those raised in poor living conditions (545 changes), making a link between the economics of early life and the biochemistry of DNA.



[Upstream Contributor] Dr. Frederica Perera touches on how the environment around us can make a big impact very early in life and stick with us for a long time. This short take was shot during a break at Keystone Symposia’s meeting on Environmental Epigenomics and Disease Susceptibility held in March 2011 in Asheville, North Carolina.


From The Globe and Mail:

In the 1980s, back when obesity and diabetes were considered problems, not plagues, a British researcher dished up a wild idea to explain the diet-related ills of the world.

While studying the causes of death for England and Wales, David Barker, an epidemiologist with the University of Southampton, stumbled upon the fact that, in the 1970s, deaths due to heart disease were highest in poor regions that 60 years earlier also had the highest rates of infant mortality.

Prof. Barker considered that curious, since coronary disease was thought to be the result of rich living. He went on to trace the fate of 15,000 people born before 1930 in the English county of Hertfordshire and discovered that those with the lowest birth weights, presumably because their mothers were malnourished, again had the greatest risk of heart disease.

Prof. Barker, who published his initial findings in The Lancet in 1986, eventually came to the conclusion that a mother’s nutrition can shape the metabolic future of her baby – affecting the child’s lifelong risks for heart disease and all the health problems related to it.

At the time, the idea seemed almost absurd. The prevailing view held that susceptibility to disease was something chiselled into your genes from prehistoric times, not dictated by a pregnant woman’s diet. The theory of the thrifty gene ruled the day, with the idea that former hunter-gatherer populations faced steady pressures of feast and famine that gave them fat-storing genes to survive the lean times – thrifty genes that made their descendants, aboriginal people in particular, obese and diabetic in the modern world.

But 25 years on, science, and society, have evolved.

With failed efforts to find a thrifty gene, or any genetic explanation for the rapid global rise in obesity and diabetes, Prof. Barker’s hypothesis, better known today as the developmental origins theory, has emerged as a leading explanation. It’s also a more attractive one: If correct, it suggests that something can be done to turn the tide.

Rewriting nature’s script

Support for the developmental origins idea has grown alongside epigenetics, a budding branch of biology that is forcing a radical rethinking of genetic science as it reveals how the environment can alter DNA.

Dramatic experiments have shown that even small environmental changes can have a powerful, and permanent, impact on the way genes work: Tweaking the diets of pregnant rats, pigs, guinea pigs, rabbits and sheep can induce obesity and a range of other metabolic ills among the offspring. In one case, it changed the colour of a mouse.

The implication is that DNA may be the script that nature provides, but nurturing determines how that script will be performed – and, according to the origins theory, rehearsals begin in the womb.

“It’s almost a sensing system of what’s going on in the environment, so that a fetus can adapt,” says Rosanna Weksberg, an epigenetics researcher at Toronto’s Hospital for Sick Children. Problems can arise when the world outside the womb is dramatically different – “there’s an epigenetic memory of nutrition.”

Growing in a woman who is malnourished – either from eating too little or receiving too few nutrients – primes the fetal DNA to hoard every calorie available, only to be vulnerable to obesity and diabetes in a postnatal world of caloric overload. At the end of the Second World War, for instance, children born to women pregnant during the Dutch “hunger winter” proved susceptible to diabetes, obesity, heart disease and other health problems.


From Living On Earth (portions of an interesting radio discussion of the new field of epigenetics which “demonstrates how environmental factors can also determine diseases in our future, and in our children and grandchildren’s future”):

GELLERMAN: A failed laboratory experiment led to an accidental discovery that is changing the way we understand genetics. It happened in Professor Michael Skinner’s lab at Washington State University. Skinner was studying DNA—the genetic code of life…when he found, by chance, that environmental factors can change the way our genes work for generations far into the future, without damaging the DNA. Professor Skinner is what’s called an epigeneticist and he joins me from Pullman, Washington. Welcome to Living on Earth.

SKINNER: Thank you very much.

GELLERMAN: So, Professor, I looked it up and ‘epi’ is Greek for ‘on or around’ and genetics means ‘source or origins.’ So epigenetics – around the source, yeah?

SKINNER: Correct. So epigenetics would be things around DNA that regulate DNA activity but are independent of DNA sequence, thus, epigenetic.

GELLERMAN: So, something’s gumming up the switch, it’s not destroying the DNA.

SKINNER: Correct, correct. And so basically, sometimes it’s the structure of the DNA, how tightly it’s coiled, or loosened up, that can actually change what genes are turned on and off. And the thing that we study the most is the chemical modification of the DNA, called methylation. A small chemical gets put on the DNA, and that can also regulate what genes are turned on and off. All of this can be influenced by the environment, has nothing to do with changing the DNA sequence.

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GELLERMAN: Is there any population evidence to suggest, historically, that we’ve detected this happening?

SKINNER: So, almost every region of the world has different disease frequencies. So, for example, in Japan they have a very high rate of a stomach disease, and a very low rate of a prostate disease. In North America, we have a very low rate of stomach disease, but a very high rate of prostate disease. If you take someone early in life from Japan and put them in the United States, they will develop generally the North American disease frequency and have prostate disease and low levels of stomach disease. This suggests an environmental impact on disease. And so there’s a lot of epidemiology experiments like that which support that kind of concept.

GELERMAN: So give me an example of something that my mom might have been exposed to that wouldn’t have caused a mutation in me, but would have affected my genetic expression, if you will.

SKINNER: First of all, the most logical one is nutrition. There’s lots of nutritional elements that can regulate programming of the embryo and different tissues. In addition, in our society today, most people are exposed to a wide variety of environmental compounds. Whether it be the bisphenol phthalates (sp?) from the plastics, whether it be agricultural compounds like the fungicide that we used called Encloselin, most people are exposed to these types of compounds on a pretty routine basis. And so these compounds have the ability to alter the epigenetics as well.

GELELRMAN: So we should really be looking at pregnant women.

SKINNER: Pregnant women are definitely the most sensitive population for influencing the fetus’ adult onset of disease. So, yes, these early life events causing later life disease is something we need to think about more, in terms of medicine. What you are is to a large degree determined what your mother did during pregnancy.

GELLERMAN: So are there a lot of epigenticists around? I’ve gotta admit that I’d never heard of it before.

SKINNER: It is a growing field. And I think it does address a lot of our unanswered questions using genetics. For established scientists that have grown up and been trained in genetics, it is a difficult shift in their thinking to consider that there may be something else. And so I think it’s going to be more the younger generation coming in that pushes the epigenetic area.

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The entire transcript, links to the podcast, and related links can all be found here.

Learn more at Dr. Skinner’s website.

From All Things Considered (portions of a radio news story discussing a recent Nature article challenging the conventional wisdom about genetic inheritance):

We can’t change the genes we received from our parents. But our genes are controlled by a kind of instruction manual made up of billions of chemical markers on our DNA, and those instructions can be rewritten by our circumstances — for instance, by obesity. According to the new research, they can even be passed along to children.

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The Grammar Of DNA

[Andy] Feinberg thinks he knows how this may be happening. It’s an example of an “epigenetic” effect, which is his specialty.

This field — epigenetics — is getting a lot of attention these days. It refers to things in and around our DNA, such as billions of chemical markers that attach to it. Those markers are signals that turn genes on and off. They tell the genes of a liver cell to behave differently from genes in a blood cell, for instance.

The sequence of our DNA — the human genome — has been called the book of life. Feinberg has his own metaphor for the billions of added signals that he studies. If the genetic sequence is the words of the book, the epigenome is the grammar, he says. “It helps to tell what the genes are actually supposed to do, and puts them in context.”

Our genes don’t change, or if they do, it’s a rare and random event. But the grammar of the epigenome is changing all the time. It can also be disrupted by chemicals we eat or breathe.

Apparently it can also be disrupted by obesity, because Feinberg thinks those fat dad rats in Australia created sperm cells with a different pattern of epigenetic marks on their DNA; that’s how the effect showed up in their children.

Michael Skinner at Washington State University in Pullman says epigenetic effects are swinging the pendulum of scientific attention from the genetic code back toward the impact of environment.

“I think that we’re eventually going to have sort of a merger of this,” he says. “I think that we’re going to have an appreciation of the fact that there is an environmental influence on biology that probably through more epigenetic mechanisms. There’s also a baseline genetic element of biology. And the two combined will actually give us more information about how things work.”

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The entire story, the podcast, and related links can all be found here.

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