Schizophrenia causes paranoia, hallucinations, delusions, and a host of other cognitive problems. The mental disorder affects roughly 1% of all people. Scientists have struggled to define which genes are most important to developing the disease; however, each individual gene associated with the disorder discusses only modest risk.
A new study published in Neuron suggests that certain jumping genes that copy-and-paste themselves throughout the genome may be linked to schizophrenia. Jumping genes, or retrotransposons, are roaming short sequences of DNA that proliferate and relocate across the genome.
A gene is a sequence of DNA that holds information to build and maintain an organism’s cell and pass down those instructions to offspring. Our genes correspond to many biological qualities, sometimes visible, like eye color, height, and blood type. With the copy-and-paste ability, retrotransposons can disrupt the expression of those genes by inserting itself within or near those genes.
One group of retrotransposons named Long Interspersed Nuclear Elements (LINE) make up a large portion of the human genome and is believed to contribute to a number of disorders and disease like cancer.
The nuclear element LINE-1 has shown to be more abundant in brain cells than any other type of cells in the body. Dr. Kazuya Iwamoto from the University of Tokyo, Dr. Tadafumi Kato from the RIKEN Brain Science Institute and colleagues showed that the number LINE-1 copies are elevated in postmortem brains of patients with schizophrenia.
Using mouse and macaque models for schizophrenia and induced pluripotent stem cells they showed that exposure to environmental risk factors during development, as well as the presence of genetic risk factors for schizophrenia led to increased levels of LINE-1 in neurons. This means they found a high number of LINE-1 copies in the brains of schizophrenics compared to other groups.
The copy-and-paste function of LINE-1 into the genes involved in synaptic function or schizophrenia may result in disruptions in normal functions.
The authors concluded, “Our findings strongly suggest that abnormal, enhanced retrotransposition of LINE-1 in neurons, triggered by environmental factors and/or combined with a genetic risk factor, plays a defining role in schizophrenia.”
Alysson Muotri, a neurobiologist at the University of California at San Diego, who was not involved in the study, told LiveScience that the study cannot say whether these genes actually cause schizophrenia, but can say there is a link between the two. LINE-1 genes may have beneficial purposes for people.
"LINE-1 retrotransposition may be a mechanism to generate cognitive diversity in the human population," Muotri said. "This mechanism may have evolved to create outliers in the population, people with extraordinary abilities. On the other hand, the other end of the spectrum may be patients with schizophrenia or autism."