‘Dark Matter’ May Be Game Changer
The single genome was taken for granted. But believe or not, scientists say, it may be an idea whose time is done.
What’s more, our brains may have their own genomes, distinct from genomes for other organs.
It gets even weirder still because individuals, it turns out, are able to exchange genomes that migrate.
It’s all pretty mind blowing, and if 2013 was the year of the mosaic brain, as it’s known–and if it’s as important as the nation’s top psychiatrist believes it just might be–then these hidden genomes could herald a new era for brain research.
In a paper that dubs the second genome “the dark matter of psychiatric genetics,” Thomas Insel, the head of the National Institute of Mental Health, suggests the mosaic brain may open unexplored vistas.
“The brain’s genome, or more accurately genomes, may prove to be even stranger than we have imagined,” Insel writes.
Strange enough as it is to consider that one organ, like the heart, may be governed by one set of genes, while another organ, like the brain, may be governed by yet another genome.
Mapping a New Continent
Science has had inklings that there was more than one genome in us, but it was fringe thinking until recently.
In the mid-1900s, when scientists found Type O and Type A blood in a British woman, blood she had received from her twin brother in the womb, including his genome in his blood cells, she came to be known as a chimera.
How widespread chimeras are became noticeable in 2012 when autopsies on the brains of 59 women in Canada found neurons with Y chromosomes in 63 percent of them. Since women don’t have Y chromosomes, the neurons must’ve come from their sons.
So it turns out that mosaicism, as the phenomenon has come to be known, is much more common—even in healthy cells—than previously thought. Fetal cells absorbed into different organs make almost all mothers chimeras!
Papers by Alexander Urban, a geneticist at Stanford University, and others show that the body of any individual may be a patchwork of genetic variation.
“We now know it’s there,” Urban declared. “Now we’re mapping this new continent.”
Brain Has Own Genome
What does the mosaic mean for the complex richness of the 3-pound organ we call the human brain, which powers the mind, one of the greatest mysteries of the entire universe?
For one thing, Insel suggests, it might explain why, when one identical twin develops schizophrenia, it expresses in the other twin only half the time.
If identical twins are genetic copies , and if schizophrenia were purely genetic, it would always develop in both. Might hidden genomes flying under the radar account for the difference?
Insel expects mosaicism in monozygotic twins to be a rich vein of research as both “a proximate cause of mental disorders in individuals with inherited risk” and as “a potential guide to novel treatment targets.”
Other questions, such as why schizophrenia typically erupts just as the brain hits its final growth stages, may one day be revealed in the mysteries of this nomadic dark matter.
On his NIMH blog, Insel says 2013 will be remembered as “the year when we began to realize how much the brain differs from other organs. We already knew that cells in the brain express (translate into protein) more of the genome and use more energy than any other organ.”
He cites research from the University of Virginia that shows a brain may have its own genome, with pervasive variation not found in other organ tissues.
In the frontal cortex, the last thing to stop growing in the human body and brain, research has spotted at least one large mutation (not seen in blood cells, which have been the basis for all psychiatric genetic studies) in 41 percent of the cells.
Equally surprising, the brain epigenome also appears unique, meaning the relationship between nurture (experience) and nature (biology) are completely different in brain cells compared to blood cells or liver cells.
“The lesson is that we cannot use peripheral cells to know what is happening in the brain,” Insel writes.
Mapping brain mosaics won’t be a quick and easy lift though. The single brain cell probes for mutations have to be conducted one cell at a time, one autopsy at a time. Cheek swabs of the sort that 23andMe had been offering for a personalized analysis of DNA (the service was recently suspended by the FDA pending regulatory review) won’t do the trick.
All the excitement is a reminder that the brain is both far more exceptional and far less well understood than assumed. But the broader lesson for 2013 is that science itself need not “evolve one funeral at a time.”
Big breakthroughs can and do fly out of nowhere once in great while, like skiers in speedos.
Let’s face it, the holidays are always a very difficult time of contrasting memories for families with schizophrenia. For some 24 million families worldwide bereft of answers again, news of a game changer is the best way to ring in the new year.
Tracey, P. (2013). ‘Dark Matter’ May Be Game Changer. Psych Central. Retrieved on July 5, 2015, from http://blogs.psychcentral.com/no-family-madder/2013/12/dark-matter-of-brain-a-genetic-game-changer/