Thursday, July 30, 2009

SciAm Mind - A Patchwork Mind: How Your Parents' Genes Shape Your Brain

Cool article that adds to our knowledge and nature vs nurture debate. The contribution of our parents is more complex than we might imagine when considering how their genetics impact out brain, mind, and consciousness.

A Patchwork Mind: How Your Parents' Genes Shape Your Brain

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

By Melinda Wenner

Key Concepts

  • When passing on DNA to their offspring, mothers silence certain genes, and fathers silence others. These imprinted genes usually result in a balanced, healthy brain, but when the process goes awry, neurological disorders can result.
  • Imprinting errors are responsible for rare disorders such as Angelman and Prader-Willi syndromes, and some scientists are beginning to think imprinting might be implicated in more common illnesses such as autism and schizophrenia.
  • Even typical brains are the result of asymmetric contributions from Mom and Dad. Higher cognitive function seems to be disproportionately controlled by Mom’s genes, whereas the drive to eat and mate is influenced by Dad’s.

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.

But in the past couple of decades, 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, however, 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. [For more on epigenetics, see “The New Genetics of Mental Illness,” by Edmund S. Higgins; Scientific American Mind, June/July 2008.]

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.

Stamps of Silence
The answer is genomic imprinting, as biologists discovered in the early 1990s. In a series of papers published in Nature and Genes and Development, researchers identified the first imprinted genes in mice, all related to a protein called insulinlike growth factor 2 (IGF-2), which plays a role in regulating the size of the pups. Mouse mothers silenced this gene, resulting in smaller, easier-to-carry fetal pups, whereas mouse fathers suppressed a gene that codes for the receptor for IGF-2’s protein—blocking the receptor’s suppressive action so that the pups could grow larger. Since that discovery, scientists have found more than 60 human genes that are typically imprinted by one parent or the other.

Genes are imprinted by the addition of molecules called methyl groups to the gene’s DNA. For reasons that are not totally understood, this methylation prevents the gene’s information from being expressed, or transcribed into RNA and proteins, the basic building blocks of the body. It is as if the imprinting “stamp” blocks the gene’s code from being read by the cell. A woman’s egg carries only the genomic imprints that her mother passed on to her; her father’s imprints are wiped away. Likewise, the genes that a man passes on in his sperm are imprinted in the same way that his father’s genes were.

Normally, a mother’s copy of a particular gene and a father’s copy of the same gene are both expressed. When the genes differ (for instance, if Mom has blue eyes and Dad has brown), both genes are translated into proteins, and the end result is a combination of each gene’s effects (the brown protein obscures the blue—although in reality several genes contribute to eye color). When a mother’s gene is imprinted with a methyl group, however, it effectively becomes silenced—the mother’s gene is then never expressed. Because only the father’s gene product is being made, there is, in effect, half as much of that particular RNA or protein available to the body. Likewise, when a father’s copy of a gene is imprinted, that gene is silenced, and only the mother’s gene is used to make its RNA or protein.

Finding evidence of imprinting is tricky. If the two copies of a person’s gene differ slightly in sequence, geneticists can analyze the RNA made from the gene to see if it, too, has two variants. If they find only one, then the gene may be imprinted, because one of the gene’s copies was not expressed. If the researchers have access to the parents’ DNA, they can verify which parent’s gene was silenced. Because the discovery process is complex and time-consuming, scientists believe they have identified only a small fraction of the genes that are genomically imprinted. Nevertheless, many of the currently known imprinted genes influence the brain—explaining why, when imprinting goes wrong, it can cause profound effects on neurodevelopment.

Balance Skewed
Among the rare disorders that result from imprinting errors is Angelman syndrome, which affects one out of 12,000 to 20,000 children in the world. Children with the syndrome are hyperactive and often smiling and laughing. In addition, studies suggest that more than 40 percent of affected kids suffer from autism spectrum disorders as well—experiencing great difficulty with language and social skills. The syndrome is marked by a reduction of maternally expressed proteins in a small section of chromosome 15, which is also usually paternally imprinted. In other words, genes from Dad are silenced as usual, but Mom’s genes are also imprinted by mistake—they are not as active as they should be to balance Dad’s imprinting effects. The brains of these children develop abnormally: their cerebral cortex is slightly smaller than usual, and a 2008 study in mice showed that cells in the cerebellum are also atypical.

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