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Individual variability of brain neuronal chromatin: implication to schizophrenia

Name
Fedor
Surname
Gusev
Scientific organization
The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences
Academic degree
No
Position
Researcher
Scientific discipline
Life Sciences & Medicine
Topic
Individual variability of brain neuronal chromatin: implication to schizophrenia
Abstract
Schizophrenia is a highly heritable neuropsychiatric disorder; but genetic and non-genetic factors for development of this disease are largely unknown. We have analyzed whole-genome epigenetic profiles of open chromatin loci for a cohort of schizophrenia and control individuals, focusing specifically on cortical neurons. The analysis of these profiles provides a unique insight into gene promoter activities and its dysregulation in schizophrenia pathology. We have highlighted a number of novel and known genomic loci, which potentially contribute to the disease development.
Keywords
schizophrenia, epigenetics, chromatin, H3K4me3, brain, neuron.
Summary

Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population. The predisposition factors for developing schizophrenia are largely unknown, yet it is highly heritable, suggesting that genetics play a significant role. However, to date genetic studies did not completely uncover the genetic roots of schizophrenia. Non-genetic factors are also mostly unknown; and some of them can may be epigenetic modifications. Recent technology advances now allow quantifying these modifications; specifically chromatin modifications can be measured by chromatin immunoprecipitation followed by sequencing (ChIP-seq). We took advantage of this method to evaluate the transcriptional activity in brain neurons of individuals diagnosed with schizophrenia to identify genomic loci and genes, which are responsible for disease development.


In this study, we profiled chromatin modifications (specifically, H3K4me3, a marker of active transcription) in brain neurons of schizophrenic and control individuals by ChIP-seq and identified a number of genomic loci that differ in norm and pathology; they include known schizophrenia genetic risk loci and novel, previously not reported, regions. The findings of this study provide an insight into modifications of transcription activity specifically in brain neurons in schizophrenia; it also highlights a number of genes and pathways potentially involved in schizophrenia pathogenesis.