Environmental conditions, even those experienced prior to birth, impact lifelong disease risks. For example, a pregnant mother who is exposed to carcinogens may pass on an increased risk of cancer for her baby, even through adulthood.
A heriditary basis for this phenomenon has been hypothesized, one that is not based on changes in DNA sequence. However, this has not been conclusively demonstrated in humans. Knowing how inherited traits can be passed on to future generations, even those traits that are not dictated by DNA sequence, may help doctors treat the adverse health consequences they are suspected of causing.
A team of scientists led by Bastiaan Heijmans (Leiden University, The Netherlands) and Lambert Lumey (Columbia University, New York) has addressed this question. They have discovered, on the molecular level, an inherited trait that is directly attributable to a past famine in The Netherlands.
The study group.
The individuals studied for this analysis are those who were exposed to famine during the "Dutch Hunger Winter" prior to birth. This famine was caused by a German food embargo covering parts of The Netherlands near the end of World War 2.
Health care and records continued during this period of famine. This means that survivors can be traced, and its long-term effects studied.
Epigenetics: Inherited traits not dictated by DNA sequence.
The scientists leading this study hypothesized that environmental factors experienced near conception can have life-long genetic consequences. The further suspected that these genetic consequences can be something other than changes in DNA sequence.
An individual's DNA sequence contains all of their genetic information. However, certain protein molecules dictate which parts of this information is utilized.
For example, a liver cell and a kidney cell both possess the same genetic information. However, liver cells have access to certain DNA-encoded information that is not available to kidney cells, and vice versa.
This is how cells become specialized. DNA sequence alone does not exclusively determine inherited traits.
The molecular basis of how protein molecules turn on or off certain regions of DNA's genetic repository, dictated by factors other than the DNA sequence itself, is part of the scientific field known as epigenetics. This is an active field of study, and has potential applications from disease prevention to organ replacement.
Epigenetic trait studied.
The scientists focused their efforts on insulin-like growth factor II (IGF2). This is one of the best-characterized epigenetic gene locations.
Specifically, epigenetic control is over the "differentially methylated region" (DMR) of IGF2. A lower amount of methylation (fewer CH3 chemical units) in IGF2 can be passed on from parent to offspring. This is a trait that is retained for decades.
Why would famine impact DNA methylation? The scientists suspect that a dietetic deficiency in methionine may be the culprit. However, other conditions, such as emotional stress, cannot be ruled out.
Famine and DNA methylation.
The scientists investigated whether differences in IGF2 DMR methylation was associated with exposure to famine conditions near conception, during the Dutch Hunger Winter. Each individual was compared with a same-gender sibling born at another time.
Epigenetic differences were observed. The average methylation percentage in the IGF2 DMR, among individuals exposed to famine near conception, was on average 5.2% less than their unexposed sibling. This result was independent of gender.
In contrast, those individuals exposed to famine later in development did not exhibit these epigenetic differences. This demonstrates that the timing of exposure to famine prior to birth can control DNA expression.
IGF2 DMR methylation was not related to birth weight. Indivduals exposed to famine near conception were of a normal birth weight, while those exposed to famine later in development were 8.6% lighter than normal.
How can doctors use this discovery?
This study suggests that birth weight is an insufficient measure of compromised development. Epigenetic markers, such as those reported here, especially those impacted by nutrition, may be more appropriate.
The scientists note that it will be especially interesting to determine if prebirth conditions more commonly experienced during modern times, such as assisted reproduction technologies, are also correlated with epigenetic changes.
The ultimate goal of such research is to determine if these epigenetic differences are correlated with diseases such as schitzophrenia, and how epigenetics impacts health throughout life. Knowing how DNA expression is regulated, through conditions other than the DNA sequence itself, may help doctors treat and prevent disease.
for more information:
Heijmans, B. T.; Tobi, E. W.; Stein, A. D.; Putter, H.;
Blauw, G. J.; Susser. E. S.; Slagbloom, P. E.; Lumey, L. H.
Persistent epigenetic differences associated with
prenatal exposure to famine in humans.
Proc. Natl. Acad. Sci. USA 2008, 105, 17046-17049.