How much can we learn about disease from studying genetics? A few months ago, Nature published an interesting article on the possible impossibility of ever finding the faulty genes behind many mental illnesses. Today, Nicholas Wade in the Times had an interesting article on the skeptical geneticist David Goldstein:
Goldstein says the effort to nail down the genetics of most common diseases is not working. "There is absolutely no question," he said, "that for the whole hope of personalized medicine, the news has been just about as bleak as it could be."Of the HapMap and other techniques developed to make sense of the human genome, Dr. Goldstein said, "Technically, it was a tour de force." But in his view, this prodigious labor has produced just a handful of genes that account for very little of the overall genetic risk.
"After doing comprehensive studies for common diseases, we can explain only a few percent of the genetic component of most of these traits," he said. "For schizophrenia and bipolar disorder, we get almost nothing; for Type 2 diabetes, 20 variants, but they explain only 2 to 3 percent of familial clustering, and so on."
The reason for this disappointing outcome, in his view, is that natural selection has been far more efficient than many researchers expected at screening out disease-causing variants.
The end result is that even diseases that look largely genetic in twin studies are caused by an insanely complex confluence of factors, with hundreds of genes contributing to the disorder. (I was talking to a scientist a few weeks ago who said he wouldn't be surprised if a thousand different genes were involved in triggering the range of behaviors typically categorized as "schizophrenia.") But wait: it gets worse. The brain is a plastic machine, constantly altering its patterns of gene expression in response to environmental changes. As a result, the static texts of Nature are constantly being modified by Nurture. Here is how I summarize these epigenetic effects in my book:
Science has discovered that, like any work of literature, our genome is a text in need of commentary, for what George Eliot said of poetry is also true of our DNA: "all meanings depend on the key of interpretation." What makes us human, and what makes each of us our own human, is not simply the genes we have buried in our base pairs, but how our cells, in dialogue with our environment, feedback onto our DNA, changing the way we read ourselves. Life is a dialectic. For example, the code sequence GTAAGT can either be translated as instructions for the amino acids valine and serine; or it can be read as a "spacer", a genetic pause that keeps other protein parts an appropriate distance from each other; or it can be read as a signal to cut the transcript. Our DNA is defined by its multiplicity of possible meanings; it is a code that requires context.
Update: Razib has much more, including a smart discussion on Goldstein's comment on natural selection and intelligence towards the end of the article.
Brain & Behavior
Comments (7)
I'm not sure about "thousands of genes" contributing to single disorders, since the human genome only contains about 20,000. Most of those genes are essential for survival. However, a *single* gene can have a multitude of different polymorphisms that have widely variable effects on the function of the proteins they encode.
Posted by: Joel | September 17, 2008 7:39 PM