Tiny Variations

UVA professor’s discovery could help explain schizophrenia, bipolar disease and autism

A University of Virginia-led research team has found that an individual’s brain cells can vary genetically, supporting a theory that not every cell in your body has the same genome. The discovery was named one of the top 10 scientific breakthroughs of the year by the director of the National Institute of Mental Health.

The researchers found that 41 percent of the 110 brain cells they mapped genetically either were missing an entire chromosome, parts of a chromosome or had a duplicate piece of one.

Although variations could occur throughout the body, the research involving neurons is intriguing because brain cells don’t grow and die as other cells do and could explain neuropsychiatric diseases, such as schizophrenia, bipolar disease or autism.


Michael McConnell, assistant professor in the department of biochemistry and molecular genetics, led the research using single-cell sequencing, in which scientists map the cell’s genes, to examine individual neurons. The researchers looked at both neurons made from stem cells from the skin of healthy adults and neurons from the donated brains of healthy adults.

 “In the past, we have looked for a single gene, but what we found is that there are hundreds of genes that have some small variations,” McConnell says. “There are cases out there where one identical twin has autism or schizophrenia, but their sibling doesn’t. We couldn’t explain this well before, but now we can appreciate that the genomes in their neurons actually vary.”

 The findings are published in the journal Science.  More on their research can be found at mcconnell-lab.org.

Digging Deeper

New technique could allow brain-injury diagnosis at a microscopic level

Researchers at the University of Virginia may have found a new method for diagnosing traumatic brain injuries (TBI).

Concussions and brain injuries often go undetected by CT and MRI scans. But UVA researchers, including professors James Stone, Stuart Berr, Jiang He and Dongfeng Pan, have found a new use for a compound that attaches itself to neutrophils—white blood cells that flood injured areas—and carries a radioactive label that shows up on brain scans. The compound is similar to those used to identify lung infections.

Previously, doctors have relied on patients’ descriptions of symptoms or signs of trauma such as bruises, tissue tears or blood. However, most traumatic brain injury results from changes on a cellular or molecular level—visible only through a microscope.

The researchers tested the molecule successfully in rats. They will now proceed with research for medical use in humans.

The research, funded by the U.S. military’s Defense Health Program, was presented at the Military Health System Research Symposium in August 2013.

“Hopefully this will help with the diagnosis of the whole range of TBI and concussions, from a bomb blast to football [injuries],” Berr says.

On the Tip of Your Tongue

Occasional difficulty recalling names seems unrelated to Alzheimer’s

Can’t recall names as fast as you once could? Don’t panic.

The loss of a primary aspect of memory and momentary forgetfulness of people and places—called tip-of-the-tongue phenomena—are not linked, according to a new study conducted at UVA.

Psychology professor Timothy Salthouse and undergraduate researcher Arielle Mandell (Col ’13), tested hundreds of peoples’ abilities to name places and identify celebrities in order to create tip-of-the-tongue moments. Those results were then compared with the subjects’ episodic memories, which is the recollection of specific events, situations and experiences.

“We chose to compare tip-of-the-tongue with episodic memory, which is one of main facets of memory tested when trying to determine whether patients have Alzheimer’s,” Mandell says.

Trouble recalling the names of people and places did increase with age, as did difficulty with episodic memory.

But when the tip-of-the-tongue results were controlled for scores on the episodic memory test, “the increase of tip-of-the-tongue moments with age appears to be separate from episodic memory,” Mandell says. “They are independent phenomena.”