Lately, my genetics class has taken a turn, by intent. I start the semester with the basics: Mendel, simple crosses, learning the terminology, all of that simple stuff that most of them see as a review of high school biology. But then, once I’m reasonably confident they know the commonly understood rules, I start adding all the complications that Mendel knew nothing about, and then we start getting into epistasis and the complicated business of translating genotype into phenotype, and I essentially end up telling them that everything they learned before wasn’t exactly true, because real world heredity is a heck of a lot more complicated. You can’t usually reduce complex traits to one gene with alleles that are dominant or recessive.
So what do you know, the New Yorker comes out with an excellent article that highlights complexity and real world genetics: Runs in the Family, about the genetics of schizophrenia.
The notion that a mental illness could be carried across generations by unitary, indivisible factors—corpuscles of information threading through families—would have struck most of Bleuler’s contemporaries as mad in its own right. Still, Bleuler was astonishingly prescient about the complex nature of inheritance. “If one is looking for ‘the heredity,’ one can nearly always find it,” he wrote. “We will not be able to do anything about it even later on, unless the single factor of heredity can be broken down into many hereditary factors along specific lines.”
In the nineteen-sixties, Bleuler’s hunch was confirmed by twin studies. Psychiatrists determined that if an identical twin was schizophrenic the other twin had a forty-to-fifty-per-cent chance of developing the disease—fiftyfold higher than the risk in the general population. By the early two-thousands, large population studies had revealed a strong genetic link between schizophrenia and bipolar disorder. Some of the families described in these studies had a crisscrossing history that was achingly similar to my own: one sibling affected with schizophrenia, another with bipolar disorder, and a nephew or niece also schizophrenic.
“The twin studies clarified two important features of schizophrenia and bipolar disorder,” Jeffrey Lieberman, a Columbia University psychiatrist who has studied schizophrenia for thirty years, told me. “First, it was clear that there wasn’t a single gene, but dozens of genes involved in causing schizophrenia—each perhaps exerting a small effect. And, second, even if you inherited the entire set of risk genes, as identical twins do, you still might not develop the disease. Obviously, there were other triggers or instigators involved in releasing the illness.” But while these studies established that schizophrenia had a genetic basis, they revealed nothing about the nature of the genes involved. “For doctors, patients, and families in the schizophrenia community, genetics became the ultimate mystery,” Lieberman said. “If we knew the identity of the genes, we would find the causes, and if we found the causes we could find medicines.”
Read the whole thing, it’s very good. It also talks about a glimmering of understanding that is gradually emerging — that there is a correlation with certain alleles in proteins of the immune system, which sounds weird until you find the connection, that these same proteins are involved in synaptic remodeling by microglia, and it all begins to make sense. But it’s still not simple.