While most kids don’t want to pick between their parents, a new study shows that their DNA may have had a preference.
It had been previously understood that each copy of DNA instructions— one inherited from the mother and one from the father— was treated the same.
However, scientists at the University of Utah School of Medicine found that it is not uncommon for cells in the brain to preferentially activate one copy of DNA instructions over the other, breaking the basic tenant of classic genetics and suggesting new ways in which genetic mutations might cause brain disorders.
The scientists showed that in at least one region of a newborn mouse brain inequality was the norm.
Approximately 85 percent of genes in the dorsal raphe nucleus—known for secreting the mood-controlling chemical serotonin—differentially activate their maternal and paternal gene copies. It wasn’t until 10 days later in the juvenile brain that both copies activated equally for all but 10 percent of the genes.
Further tests showed that the disparity also takes place at other sites in the body including the liver and muscles.
“We usually think of traits in terms of a whole person or animal,” Christopher Gregg, Ph.D., assistant professor of neurobiology and anatomy and senior of the study, said in a statement. “We’re finding that when we look at the level of cells, genetics is much more complicated than we thought.”
Among the genes regulated in this way are the risk factors for mental illness.
A gene called DEAF1, which is implicated in autism and intellectual disabilities, shows preferential expression of gene copy in multiple regions of the brain.
A comprehensive study of primates, which acts as a proxy for humans, indicates the same is true for many other genes, including some linked to Huntington’s Disease, schizophrenia, attention deficit disorder and bipolar disorder.
While what the genetic imbalance means for health remains undetermined, the preliminary results suggest that it could shape the vulnerabilities to disease.
Having two copies of a gene normally acts as a protective buffer in case one is defective. Activating a gene copy that is mutated and silencing the healthy copy—even temporarily—could be disruptive enough to cause trouble in specific cells.
Gregg’s team found that some brain cells in transgenic mice preferentially activate mutated gene copies over healthy ones.
“It has generally been assumed that there is correlation between both copies of a gene,” Elliot Ferris, a computer scientist who co-led the study, said in a statement.
To conduct the study, the investigators screened thousands of genes, quantifying the relative levels of activation for each maternal and paternal gene copy. They discovered that expression of the two is different for many genes.
The research team then developed statistical methods to test their validity and determine that they were not due to technical artifacts, nor genetic noise.
They also examined a subset of genes more closely and directly visualized imbalances between gene copies at the cellular level in the mouse and human brain.
Gregg’s research expands on scenarios in which genes play favorites.
Imprinted genes and X-linked genes are specific gene categories that differentially activate their maternal and paternal genes copies. Studies in cultured cells had also determined that some genes vary which copy they express.
However, this study suggests that silencing one gene copy may be a way in which cells fine tune their genetic program at specific times during the lifecycle of the animal or in discrete places.
“Our new findings reveal a new landscape of diverse effects that shape the expression of maternal and paternal gene copies in the brain according to age, brain region, and tissue type,” Gregg said. “The implication is a new view of genetics, one that starts up close.”
