A Patchwork Mind [Preview]

We each have two parents, but their genetic contributions to what makes us us are uneven. New research shows we are an amalgam of influences from Mom and Dad

Your memories of high school biology class may be a bit hazy nowadays, but there are probably a few things you haven't forgotten. Like the fact that you are a composite of your parents—your mother and father each provided you with half your genes, and each parent's contribution was equal. Gregor Mendel, often called the father of modern genetics, came up with this concept in the late 19th century, and it has been the basis for our understanding of genetics ever since.

In the past couple of decades, however, scientists have learned that Mendel's understanding was incomplete. It is true that children inherit 23 chromosomes from their mother and 23 complementary chromosomes from their father. But it turns out that genes from Mom and Dad do not always exert the same level of influence on the developing fetus. Sometimes it matters which parent you inherit a gene from—the genes in these cases, called imprinted genes because they carry an extra molecule like a stamp, add a whole new level of complexity to Mendelian inheritance. These molecular imprints silence genes; certain imprinted genes are silenced by the mother, whereas others are silenced by the father, and the result is the delicate balance of gene activation that usually produces a healthy baby.

When that balance is upset, big problems can arise. Because most of these stamped genes influence the brain, major imprinting errors can manifest themselves as rare developmental disorders, such as Prader-Willi syndrome, which is characterized by mild mental retardation and hormonal imbalances that lead to obesity. And recently scientists have started to suspect that more subtle imprinting errors could lead to common mental illnesses such as autism, schizophrenia and Alzheimer's disease. A better understanding of how imprinting goes awry could provide doctors with new ways to treat or perhaps even prevent some of these disorders.

Through the study of imprinted genes, researchers are also uncovering clues about how our parents' genes influence our brain—it seems that maternal genes play a more important role in the formation of some brain areas, such as those for language and complex thought, and paternal genes have more influence in regions involved in growing, eating and mating. “You need both Mom and Dad in order to get a normal brain,” says Janine LaSalle, a medical microbiologist at the University of California, Davis, whose lab focuses on imprinting. “We're really at the beginning of understanding what that means.”

To understand the implications of imprinting, it helps to know a few basics. Imprinting is an epigenetic (meaning “beyond genetic”) mechanism, a molecular change that can happen within a cell that affects the degree to which genes are activated, without changing the underlying genetic code. The type of imprinting that happens in egg and sperm cells is known as “genomic imprinting,” a reference to its fundamental heritable nature. Other types of imprinting can happen as a result of environmental influences, such as parental nurturing or abuse.

As recently as a few decades ago, very few people imagined that heritable genetic influences existed beyond the basic genetic code in our DNA. Then, in 1984, biologists at the University of Cambridge and at the Wistar Institute in Philadelphia separately tried to breed mice that had either two copies of a father's chromosomes or two copies of a mother's chromosomes, instead of one copy from each parent. According to Mendelian theory, the baby mice should have been fine—after all, they had the correct number of genes and chromosomes. All the fetuses died, however, suggesting that simply having two of each chromosome is not sufficient—each pair must be made up of one chromosome from Mom and one from Dad. But the researchers did not yet know why.

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