Scientists dig deeper into the genetics of schizophrenia by evaluating microRNAs

May 11, 2008
Human Chromosome
Shown here is human chromosome 22 and the piece of the chromosome missing in some patients with schizophrenia. Loss of this chromosomal piece (22q11) is the only known recurrent copy number mutation associated with schizophrenia. The corresponding region on mouse chromosome 16 is indicated along with the position of the engineered deletion in the mouse model. The engineered deletion results in alterations in microRNA production and as a result neuronal and behavioral deficits. © 2008 Columbia University

Researchers at Columbia University Medical Center have illuminated a window into how abnormalities in microRNAs, a family of molecules that regulate expression of numerous genes, may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders.

In the May 11 issue of Nature Genetics, Maria Karayiorgou, M.D., professor of psychiatry, and Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center explain how they uncovered a previously unknown alteration in the production of microRNAs of a mouse modeled to have the same chromosome 22q11.2 deletions previously identified in humans with schizophrenia.

“We’ve known for some time that individuals with 22q11.2 microdeletions are at high risk of developing schizophrenia,” said Karayiorgou, who was instrumental in identifying deletions of 22q11.2 as a primary risk factor for schizophrenia in humans several years earlier. “By digging further into this chromosome, we have been able to see at the gene expression level that abnormalities in microRNAs can be linked to the behavioral and cognitive deficits associated with the disease.”

The investigators modeled mice to have the same genetic deletion as the one observed in some individuals with schizophrenia and examined what happens in the expression of over 30,000 genes in specific areas of the brain. When they discovered that the gene family of microRNAs was affected, they suspected that the Dgcr8 gene was responsible. The Dgcr8 gene is one of the 27 included in the 22q11.2 microdeletion and has a critical role in microRNA production, so this was a logical hypothesis. Indeed, when they produced a mouse deficient for the Dgcr8 gene, and tested it on a variety of cognitive, behavioral and neuroanatomical tests, they observed the same deficits often observed in people with schizophrenia.

“Our studies show that alterations in microRNA processing result in synaptic and behavioral deficits,” said Dr. Gogos. Drs. Karayiorgou and Gogos have partnered together to decipher the role of individual genes from 22q11 in the development of schizophrenia by using human genetics and animal model approaches.

The significance of this work is that it implicates a completely novel, previously unsuspected group of susceptibility genes and brings investigators a step closer to understanding the biological mechanisms of this disorder. Implication of such a large family of genes (the most recent estimate puts the number of human microRNAs at at least 400 that influence the expression of as many as a third of all genes) could partly account for the genetic complexity associated with this devastating disorder and explain some of the difficulties that the researchers have encountered in their efforts to pinpoint individual genes.

“Our hope is that the more we know about the genes involved in schizophrenia, the more targeted treatment can be,” said Dr. Gogos.

“Much in the way that cancer patients who have tested for a particular gene, such as BRAC1, can be tested and then treated with protocols designed specifically for them, we want to be able to know enough about the schizophrenic brain to target treatments to individual patients.”

The next step for the researchers is to find the many genes whose expression is controlled by the identified deficient microRNAs, which could in turn be involved in the pathogenesis of schizophrenia. Much more study and identification of other genetic variants must be done to further illuminate the disease’s genetic underpinnings, according to Drs. Karayiorgou and Gogos.

Source: Columbia University

Explore further: Breakthrough identifies new mechanism for the development of schizophrenia

Related Stories

Breakthrough identifies new mechanism for the development of schizophrenia

October 10, 2017
Scientists from Trinity College Dublin and the Royal College of Surgeons in Ireland (RCSI) have discovered that abnormalities of blood vessels in the brain may play a major role in the development of schizophrenia, a debilitating ...

Scientists researching drugs that could improve brain function in people with schizophrenia

October 12, 2017
Virginia Commonwealth University researchers are testing if drugs known as HDAC inhibitors improve cognition in patients with schizophrenia who have been treated with the antipsychotic drug clozapine.

Scientists demonstrate path to linking the genome to healthy tissues and disease

October 13, 2017
Our genomes help to determine who we are - the countless variations between individuals that encode the complexity of tissues and functions throughout the body. Since scientists first decoded a draft of the human genome more ...

Neuroscientists identify genetic changes in microglia in a mouse model of neurodegeneration and Alzheimer's disease

October 13, 2017
Microglia, immune cells that act as the central nervous system's damage sensors, have recently been implicated in Alzheimer's disease.

Scientists discover regional differences among chandelier cells

October 10, 2017
The brain is composed of distinct regions that differ in their functional roles and cellular architecture. For example, the hippocampus is an area well-known for its involvement in memory and its dysfunction in diseases such ...

Scientists reveal how astrocytes help neurons form successful connections

October 12, 2017
To have a good phone conversation, you need a good cellular connection. What's true for mobile phones also turns out to be true for neurons.

Recommended for you

Study identifies genes responsible for diversity of human skin colors

October 12, 2017
Human populations feature a broad palette of skin tones. But until now, few genes have been shown to contribute to normal variation in skin color, and these had primarily been discovered through studies of European populations.

Genes critical for hearing identified

October 12, 2017
Fifty-two previously unidentified genes that are critical for hearing have been found by testing over 3,000 mouse genes. The newly discovered genes will provide insights into the causes of hearing loss in humans, say scientists ...

Team completes atlas of human DNA differences that influence gene expression

October 11, 2017
Researchers funded by the National Institutes of Health (NIH) have completed a detailed atlas documenting the stretches of human DNA that influence gene expression - a key way in which a person's genome gives rise to an observable ...

Genetic advance for male birth control

October 10, 2017
When it comes to birth control, many males turn to two options: condoms or vasectomies. While the two choices are effective, both methods merely focus on blocking the transportation of sperm.

Researchers uncover new congenital heart disease genes

October 9, 2017
Approximately one in every 100 babies is born with congenital heart disease (CHD), and CHD remains the leading cause of mortality from birth defects. Although advancements in surgery and care have improved rates of survival ...

Seeing hope: FDA panel considers gene therapy for blindness (Update)

October 9, 2017
A girl saw her mother's face for the first time. A boy tore through the aisles of Target, marveling at toys he never knew existed. A teen walked onto a stage and watched the stunned expressions of celebrity judges as he wowed ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.