Scientists have identified a rare gene mutation which they believe is linked to schizophrenia. The researchers from the University of California, San Diego and Trinity College Dublin performed a genome-wide association scan of CNVs (copy number variations) - the duplication or deletion of large chunks of DNA sequences in the human genome. They detected a rare duplication on chromosome seven that was 14 times more common in individuals with schizophrenia than in a control group. The duplication of the DNA sequence was present in 29 out of 8,290 individuals with schizophrenia (0.35 percent of individuals), and in two out of 7,431 healthy controls (0.03 percent of individuals).
The area involved affects the gene coding for the protein Vasoactive Intestinal Peptide Receptor 2 (VIPR2). This is present in a number of brain regions such as the hippocampus and amygdala, and is thought to be involved in neuron signalling, learning and memory, and maintaining normal circadian rhythms.
The researchers measured levels of VIPR2 in individuals with schizophrenia and a group of controls, and found that the expression and activity levels of the protein were greater in individuals with the DNA duplication than in those without. 'This suggests that the mutations increase signalling in the Vasoactive Intestinal Peptide pathway', said Professor Aiden Corvin, a researcher involved in the study from the psychosis research group at Trinity College Dublin.
'We know that this activity can be modulated by synthetic peptides (compounds where amino acids are linked together) and the next step is to see if these compounds have a therapeutic effect in mice or in cultured human cells that carry the VIPR2 gene mutation'.
'This discovery might be the best target yet to come out of genetic studies of mental illness', said Dr Jonathan Sebat from the University of California, San Diego, who led the study.
Schizophrenia is a complex condition, which is thought to have a genetic component. The psychiatric disorder occurs in one percent of the general population, and in ten percent of individuals with a parent or sibling with the condition. Earlier studies identified CNVs that increased the risk of schizophrenia, however, together these accounted for only a small proportion of cases (1 to 2 percent). This study confirms that the rare CNVs identified in previous research were associated with schizophrenia, and detected a new CNV on chromosome seven, with potential implications for brain functioning.
The researchers concluded that 'the rapidly growing list of rare CNVs that are implicated in schizophrenia indicates that this psychiatric disorder is, in part, a constellation of multiple rare diseases'.
The study was published in the journal Nature.