De novo mutations — new mutations in the carrier, not inherited from either parent — may be responsible for causing schizophrenia, say researchers from the Université de Montréal.
The research gives scientists a better understanding of the genetic basis of schizophrenia and other mental disorders and could lead to better diagnostic tools and treatments.
“We could even call it a small revolution in the domain of psychiatric genetics,” said Simon Girard, who presented the results at the 16th annual Human Genome Meeting in Sydney last week.
Schizophrenia is a multifaceted disorder that shows itself through a wide array of symptoms. The broad diversity of the disease has always made it difficult to diagnose and treat, as well as study its underlying cause.
Although the heritability of the disease is high, schizophrenia and other mental disorders often result in the sufferers not having any children. Because of this, the mutations that cause the disease would be expected to slowly phase out of the human gene pool, along with schizophrenia itself. However, the occurrence of schizophrenia is still surprisingly constant across the world.
This mystery may be explained in these latest findings, as researchers have now identified an unusually high rate of de novo mutations (DNMs) in the genes of schizophrenics.
For the study, geneticists compared the gene sequences of 14 schizophrenia patients with those of their parents. In the genes of the 14 patients, the researchers found 15 DNMs, which is significantly more than six—the number that would reflect the average mutation rate in humans.
It was not clear, however, if the overall rate of DNMs in the patients is higher than normal.
“We were only looking at the genes. Maybe if we were to look at the whole genome, the rates of de novomutation would be the same,” said Girard.
The researchers’ hypothesis of DNMs being responsible for schizophrenia is backed by the findings of two other research groups. These also found strangely high numbers of DNMs in the genes of patients with mental retardation and autism.
“What’s happening right now is that other people are finding the same thing for other, closely related disorders,” said Girard. “It’s very exciting to be right in the middle of that because we might actually be defining a new paradigm for the genetics of psychiatric disorders.”
Peter Visscher, chair of quantitative genetics at the University of Queensland, believes this study is an excellent example of what modern sequencing technologies can do. But he cautions against drawing conclusions which are too strong.
“If you find a mutation, it doesn’t mean per se that that is the mutation that’s causing the disease,” he said. “Normally, in genetics, when we make a statement about a particular variant [mutation] having an effect, it’s because we see the same variant [having the same effect] in different people.”
The researchers ultimately hope to use gene sequencing to diagnose specific subtypes of schizophrenia and then treat each type with specific medication. “But it will take a whole lot more research to get there,” said Girard. “We expect that hundreds of genes are involved in the disease.”
Source: Université de Montréal