Friday, July 8, 2011

Genetics, Epigenetics and FASD, Part II

Part II: Epigenetics

Keeping us on our toes, genetics is not the only level at which exposure to alcohol may harm people. Scientist now recognize the significance of epigentics in influencing the the ways genes are and are not expressed.

The difference between genetics and epigetics is often explained using the analogy of a computer. If a human was a computer, it is said that genes would represent our hardware and epigenetics, the software that controls how the hardware is used.

This means that contrary to what some people understood decades ago when scientists first began studying genes, DNA is not destiny.

A person may carry a genetic mutation that is never expressed in his body. Or he may have traits that are determined not by a genetic mutation he acquired (say, as the result of prenatal exposure to alcohol), but by the dis-inhibition in his body of a genetic mutation that occurred generations earlier. Epigenetics has a identified a mind-boggling array of non-genetic factors like nutrition that effect the suppression and expression of genes.

What does that mean for what we understand about FASD? This 2009 article in the journal Biology of Reproduction summarized: "One of the main implications of an epigenetic perspective is that the FASD spectrum is not limited to clinical defects arising from in utero ethanol exposure, suggesting that the concept of a fetal alcohol spectrum should be expanded to include preconceptional effects..." which, the article explains, means the consumption of alcohol by the birth mother --or the birth father --even before the child is conceived may harm a child later born to them.

The article concludes: "Finally, an epigenetic perspective suggests that alcohol exposure outside of the organogenic period (e.g., during preimplantation or prior to conception) might have teratogenic consequences for the CNS [Central Nervous System]. Indeed, the association of paternal alcohol consumption with behavioral and cognitive abnormalities in offspring in some animal and human studies... supports this view. Because such cases are unlikely to receive a diagnosis within the FASD spectrum... this raises the possibility that transgenerational responses to alcohol might account for a significant proportion of idiopathic neurodevelopmental disorders (e.g., idiopathic autism) in humans."

Conclusions like these are not simply outlying findings in a wider body of research. Michelle Ramsay summarized in this April 28, 2010 article in Genome Medicine surveying the field: "A body of knowledge has accumulated to support the role of environmentally induced epigenetic remodeling during gametogenesis and after conception as a key mechanism for the teratogenic effects of FASD that persist into adulthood. Transgenerational effects are likely to contribute to the global burden of alcohol-related disease. FASD results in lifelong disability and preventative programs should include both maternal alcohol abstention and preconception alcohol avoidance."

It is hard to miss the implication: there is no "safe" time for the consumption of alcohol in terms of protecting genes --except well after child-bearing or child-fathering age.

I find that staggering as a parent of a child prenatally exposed to alcohol, and also the product of the first sober generation in a long line of alcoholics in both branches of the family tree.

As a historian I have always wondered about the average women of childbearing age in Colonial America who routinely drank home-brewed "cider" because water was believed to be unsafe (we now know it was contaminated with sewage). Why aren't the annals of history populated with people who obviously had FASD? Maybe because cider-affected children were guided into manual trades that required little formal education so they did not grow up to write the history books...

Or maybe centuries of insults to the human genome from factors like famine, malnutrition, alcohol and genetic mutation have cumulatively compounded to make modern children genetically more susceptible?


friday said...

Carrie, these two posts are fascinating. I too have wondered similarly about pre-natal alcohol consumption by women in history, or in other cultures (my firsthand experience living in Mongolia, for example, where drinking fermented mare's milk and other alcoholic beverages would not be uncommon during pregnancy). This recent research has also given me pause when examining the many branches of my bio-genetic family tree also impacted by alcoholism. I am interested to see what types of therapeutic approaches result from this research.

Nora said...

Aargh! Did it again...posted that last comment from my husband's google id. Oops! Nora