Genetic repeats suggest role for DNA instability in schizophrenia
My friend has a glass eye and unless you knew the story you might not think anything of it. His older brother did it. You read that correctly, in a schizophrenic induced confusion he tried to killed him. He never held what happened against his older brother, he was sick, how could he? The courts say, he cannot visit his brother while he’s in prison. This could’ve been avoided with early detection and now international researchers have used a new technique to identify significantly more DNA sequence repeats in patients with schizophrenia than in control individuals.
The team outlined a possible link between genome instability and disease.
Variations in the number of DNA sequence repeats are known to exist between individuals. Some of these copy number variations (CNVs) are associated with disease, as with schizophrenia, wherein rare CNVs on chromosomes, including 1, 15, 16, and 22, are more common among patients than among controls.
However, previous studies have not fully investigated the effect of particular CNVs, especially those on the X chromosome, on patient characteristics. Nor have they examined the genes responsible for CNVs in schizophrenia, which would aid understanding of disease development.
An international research team has now used a technique based on DNA fragments labeled with different fluorescent markers to reveal high levels of genetic heterogeneity (whereby several different genetic defects can cause the same symptoms) in schizophrenia. They also observed that the CNVs associated with schizophrenia affected gene categories controlling repair of DNA damage, which may underlie disease mechanisms.
The technique the researchers used was more sensitive and of a higher resolution than previous methods. This allowed detection of more CNVs, especially small ones, which accounted for 70% of all CNVs. Significantly more clinically important CNVs were seen in the DNA of 1,699 patients with schizophrenia than in the 824 control individuals, while abnormal numbers of X chromosomes were also associated with disease.
High genetic heterogeneity was revealed by the detection of these CNVs at 67 different regions in 9% of patients. Further variation was observed in the effect of the CNVs on patient characteristics in that some CNVs were carried by controls without causing any symptoms.
“Patients with clinically important CNVs showed a range of characteristics, such as developmental problems and refusal to accept treatment,” first author Itaru Kushima says.
“And, the presence of two CNVs resulted in a more severe phenotype.”
The researchers looked closely at the genetic regions containing CNVs to identify several gene categories associated with schizophrenia that may be affected by genetic disturbance. These include oxidative stress response, which leads to DNA damage when imbalanced, and genomic integrity, involving DNA repair and replication.
“We propose that CNVs affecting oxidative stress response and genomic integrity lead to genomic instability that may cause further CNVs”, corresponding author Norio Ozaki says.
“This model helps explain the new CNVs seen in previous studies on schizophrenia, as well as the differences in affected patients’ phenotypes.”
Of course, here in the US we have found a perfect way to help deal with mental illness, just put people in jail for something they can’t control. Or, since they “aren’t really people” just shoot them, because why would we treat them any better than that?
Kushima, I., et al. “High-resolution copy number variation analysis of schizophrenia in Japan.” Molecular psychiatry (2016). DOI: 10.1038/mp.2016.88