Everyone who's sat through a high school science class knows that DNA makes up the chemical building blocks of human life, determining everything from eye color to predisposition for certain genetic ailments. But what if there's another factor at work, shaping what makes us supremely strong or fundamentally weak? What if physiological traits can't be linked to genetic heritability? In the January/February issue of MIT's Technology Review, Stephen S. Hall explores the X-factor of the human genome:
Large-scale genomic studies over the past five years or so have mainly failed to turn up common genes that play a major role in complex human maladies. More than three dozen specific genetic variants have been associated with type 2 diabetes, for example, but together, they have been found to explain about 10 percent of the disease's heritability -- the proportion of variation in any given trait that can be explained by genetics rather than by environmental influences. Results have been similar for heart disease, schizophrenia, high blood pressure, and other common maladies: the mystery has become known as the "missing heritability" problem. Francis Collins, director of the National Institutes of Health, has sometimes made grudging reference to the "dark matter of the genome" -- an analogy to the vast quantities of invisible mass in the universe that astrophysicists have inferred but have struggled for decades to find.
Joseph H. Nadeau has been on a quest to uncover mechanisms that might account for the missing components of heritability. And he is finding previously unsuspected modes of inheritance almost everywhere he looks.
Nadeau, who until recently was chair of genetics at Case Western Reserve University in Cleveland and is now director of research and academic affairs at the Institute for Systems Biology in Seattle, has done studies showing that certain traits in mice are influenced by specific stretches of variant DNA that appeared on their parents' or grandparents' chromosomes but do not appear on their own. "Transgenerational" genetics, as he calls these unusual patterns of inheritance, fit partly under the umbrella of traditional epigenetics--the idea that chemical changes wrought by environmental exposures and experiences can modify DNA in ways that either muffle a normally vocal gene or restore the voice of a gene that had been silenced. Researchers have begun to find that these changes are heritable even though they alter only the pattern of gene expression, not the actual genetic code. Yet it's both more disconcerting and more profound to suggest, as he does, that genes an ancestor carried but didn't pass down can influence traits and diseases in subsequent generations.
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