AsianScientist (Jan. 6, 2014) – Retrotransposons, which are stretches of DNA often dubbed as “junk DNA,” may play an important role in schizophrenia.
In a study published in the journal Neuron, a Japanese team revealed that LINE-1 retrotransposons are abnormally abundant in the schizophrenia brain. These transposons modify the expression of genes related to schizophrenia during brain development and may be one of the causes of schizophrenia.
Retrotransposons are short sequences of DNA that autonomously amplify and move around the genome. One class of retrotransposons, named long interspersed nuclear elements (LINE), make up a large part of the eukaryotic genome and are believed to contribute to diseases such as cancer.
LINE-1 have been shown to be more abundant in brain cells than in other cells, providing evidence for enhanced activity of LINE-1 in the human brain. However, the role played by LINE-1 in mental disorders, and in particular schizophrenia, remains unclear.
The team, led by Dr. Kazuya Iwamoto from the University of Tokyo and Dr. Tadafumi Kato from the RIKEN Brain Science Institute, demonstrated that the number of copies of LINE-1 is elevated in the post-mortem brains of patients with schizophrenia.
Using mouse and macaque models for schizophrenia and iPS cells, they showed that the combination of environmental and genetic risk factors during development can lead to increased levels of LINE-1 in neurons. Using whole genome analysis, the authors showed that in schizophrenia patients, LINE-1 reinserts into genes involved in synaptic function or schizophrenia, which may disrupt their normal functions.
“This study proposes a brand new mechanism of pathophysiology of schizophrenia. Previously, schizophrenia was regarded as a disease caused by gene-environment interactions, but our study shows that the environment can alter the genome and may contribute to the disease,” said Dr. Kato.
The article can be found at: Bundo M et al. (2014) Increased L1 Retrotransposition in the Neuronal Genome in Schizophrenia.
Source: University of Tokyo; Photo: Life Mental Health/Flickr/CC.
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