What Determines Junior's DNA?
[Rachel's Introduction: A new field of science is showing us that almost every aspect of our environment -- from stress to our food to toxic exposure -- can affect our genetic makeup in ways that can affect our bodies, and those of the next generation, for life. [See our earlier report on this important new science in Rachel's #876
Isabel Palferro is doing everything she can to make sure her unborn child will be healthy when it enters the world.
The 27-year-old Mississauga[, Ontario] mom-to-be has eliminated alcohol, caffeine and soda from her diet. She eats more fish -- "the healthy kind, low in mercury" -- loads up on fruits and veggies and pops her prenatal vitamins. She avoids household chemicals and paint and gas fumes whenever she can. Her evenings alternate between twilight strolls with her husband, yoga and aquafit classes.
Palferro, who is seven months into her pregnancy, has extra incentive to be vigilant. Four years ago, she was diagnosed with type 2 diabetes. While she has learned to live with the disease, Palferro does not want her child to have to live with it, too.
"There is risk that you might pass it down," says Palferro, who attends a high-risk diabetes clinic at Credit Valley Hospital. "But we decided to try and prevent it and to take all the measures we can ahead of time with diet and routine to try to not pass it down to the child."
For years, pregnant women have been told to be careful what they put in their bodies.
But a new field of science is showing us that almost every aspect of our environment -- from stress to our food to toxin exposure -- can affect our genetic makeup in ways that can affect our bodies, and those of the next generation, for life.
It is called epigenetics and it refers to any process that alters the gene activity in a strand of DNA without changing the genes themselves. And it means DNA can no longer be thought of as a biological inheritance passed from parent to child.
Epigenetic processes are a normal and necessary part of life. Much like a software program that tells a computer how to work, epigenetic processes tell our DNA when, where and how to express each of the body's 25,000 genes. But if they go wrong or work ineffectively, there can be major health consequences. And scientists now believe that epigenetic changes are the root cause of many complex, chronic diseases, including cancer, neurological disorders and type 2 diabetes.
Sidebar: The Science
It was 1983 when scientists first found evidence that epigenetic changes in the human genome could cause cancer. But progress was sluggish until the map of the genome was completed in 2000.
Since then, a host of studies have shown the environment, from diet to lifestyle to toxin exposure, can change the epigenome. Though it's still early days, these seminal studies suggest epigenetic changes may be behind some of the most common -- and most complex -- human diseases.
STUDY: Diet can trigger epigenetic changes
WHO: Randy Jirtle and Robert Waterland at Duke University
WHEN: August 2003 in Molecular and Cellular Biology
WHAT: Pregnant agouti mice -- which carry a gene that makes them fat, yellow and susceptible to obesity, cancer and diabetes -- were fed a diet high in vitamin B12, folic acid, choline and betaine. The methyl- rich diets altered the agouti gene, effectively switching it off so that pups were born skinny, with a brown coat and a reduced risk of disease.
STUDY: Epigenetic changes may persist at least four generations
WHO: Michael Skinner at Washington State University
WHEN: June 2005 in Science
WHAT: Pregnant rats were briefly exposed to high levels of pesticides. Male pups had lower sperm production and higher infertility. Two genes in the affected male pups had been altered. The changes were found in 90 per cent of males four generations later, even with no additional pesticide exposure.
About 850,000 people, or 9 per cent of Ontarians, have type 2 diabetes, far outstripping the World Health Organization's global estimate of 6.4 per cent by 2030. Toronto is the urban epicentre, with 225,000 cases. A groundbreaking study by Toronto's Institute for Clinical Evaluative Sciences showed diabetes rates in poorer neighbourhoods were almost triple that of more populated areas downtown. They pointed to the environment, everything from how far it was to the nearest grocery store or community centre, as a factor.
Scientists have long known that diabetes, much like cancer and other diseases, is caused by a combination of environmental and genetic factors, but no one knew just how much one or the other contributed. Now it looks like the science of epigenetics has come down firmly in the middle.
For decades, scientists have searched for specific genes that cause disease and have had some success. We now know, for example, that cystic fibrosis is caused by a mutation in a single gene.
Raylene Reimer, an associate professor at the University of Calgary, says something other than a single gene mutation is likely behind the dramatic rise in rates of obesity and type 2 diabetes in Canada and across the globe.
She points out there hasn't been a major mutation in the DNA of the human population in the last 100 years. Rather, she says, it is likely environmental cues are triggering epigenetic changes in the genome, which in turn are triggering disease. And the most likely culprit behind the obesity and diabetes epidemics is the food we eat.
Scientists first linked epigenetic changes with nutrition and disease after examining detailed health records from the 1944 Dutch Famine. They found women who became pregnant during the famine had children with an increased chance of becoming obese and getting diabetes. But women in their second or third trimester when the famine hit bore children who had an increased risk of heart disease as adults.
"Something had changed in their gene expression to program whether or not the child is going to be at an increased or decreased risk of obesity, type 2 diabetes or heart disease," Reimer says.
Since the Dutch Famine Birth Cohort Study was published in 1998, researchers have homed in on two critical periods when epigenetic changes can have the most effect: when the fetus is first developing; and during the first 6 to 12 months of life. Both periods are strongly influenced by the maternal environment, especially the amount and type of foods a mother eats.
In 2003, Randy Jirtle, a professor of radiation oncology at Duke University, and graduate student Robert Waterland uncovered startling evidence that epigenetic changes could influence disease in mice. They found feeding pregnant agouti mice -- named for a gene that makes them fat, yellow and susceptible to obesity, cancer and diabetes -- a diet high in specific nutrients could switch off the agouti gene, so pups were born skinny, brown and disease-free.
Jirtle says they found an epigenetic change, called methylation,upstream of the agouti gene in the newborn pups. "It was phenomenal that something you are exposed could alter this process," he says.
Research in epigenetics has soared in the last few years. There is evidence to show mothers who don't have enough to eat or the right nutrients, bear children who are "programmed" to become obese. Scientists believe the programming is caused by a mismatch between a nutritionally bare prenatal environment and a nutritionally abundant postnatal environment.
"If (the fetus) senses there is going to be a low amount of nutrition ... it reprograms gene expressions to be incredibly efficient in storing energy," says Jirtle of the hypothesis. "The real problem is when you sense an environment of low nutrition and are born into an environment like we have now with gobs of calories." Reimer points to rodent studies that show a maternal diet low in protein can trigger obesity in offspring. She's curious about the reverse effect, as most of the Western world eats too much. "What is our high-fat, high- protein diet doing to the programming of fetuses' or infants' genes?" she wonders.
Reimer's initial research suggests diets high in fibre can protect against obesity and disease.
To that end, she and other researchers hope to identify the ideal pregnancy diet, one that will protect unborn babies from a host of diseases, including type 2 diabetes.
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