Analysis of LINE‐1 insertion sites of the postmortem brains of patients with schizophrenia

Abstract

Somatic mutations are a kind of genomic variants that occur during the developmental stages after fertilization and exist in a mosaic‐like pattern in individuals. Some of the brain‐specific somatic mutations have been reported to cause neurological diseases. We have especially focused on long interspersed nuclear element‐1 (LINE‐1) insertions, a type of retrotransposon, and have found that the LINE‐1 copy number was increased in neurons of schizophrenia patients and that the newly inserted LINE‐1 were located near the genes involved in neuronal functions. To identify the detailed profiles of the LINE‐1 insertion genomic sites, we established a new single‐cell‐level analysis method, NECO‐seq, and performed a case‐control analysis using the postmortem brains of schizophrenia patients. Analysis of a total of more than 1,000 neuronal nuclei showed that LINE‐1 insertions that occurred at a relatively early stage in neurogenesis accumulated near the neuron‐related genes, including neurotransmitter receptors. These LINE‐1 insertions may have a profound effect on neuronal morphology and function.