AUTHOR=Ershova Elizaveta S. , Agafonova Oksana N. , Zakharova Natalia V. , Bravve Lidia V. , Jestkova Elizaveta M. , Golimbet Vera E. , Lezheiko Tatiana V. , Morozova Anna Y. , Martynov Andrey V. , Veiko Roman V. , Umriukhin Pavel E. , Kostyuk Georgiy P. , Kutsev Sergey I. , Veiko Natalia N. , Kostyuk Svetlana V. 

TITLE=Copy Number Variation of Satellite III (1q12) in Patients With Schizophrenia

JOURNAL=Frontiers in Genetics

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01132

DOI=10.3389/fgene.2019.01132

ISSN=1664-8021

ABSTRACT=Introduction. It was shown that CNVs of human satellite III (1q12) fragment (f-SatIII) reflects the human cells response to stress of different nature and intensity. Patients with schizophrenia (SZ) experience chronic stress. The major research question: What is the f-SatIII CNVs in human leukocyte as a function of SZ?

Materials and Methods. Biotinylated pUC1.77 probe was used for f-SatIII quantitation in leukocyte DNA by the non-radioactive quantitative hybridization for SZ patients (N = 840) and healthy control (HC, N=401). SZ-sample included four groups. Two groups: first-episode drug-naïve patients  (SZ(M-)) and  medicated patients (SZ(M+)). The medical history of these patients did not contain reliable confirmed information about fetal hypoxia and obstetric complications (H/OCs). Two other groups:  medicated patients with documented H/OCs (hypoxia group (H-SZ(M+))  and medicated patients with documented absence of H/OCs (non-hypoxia group  (NH-SZ(M+)). The content of f-SatIII was also determined in eight post-mortem brain tissues of one SZ patient. 
Results.  f-SatIII in human leukocyte varies between 5.7 to 44 pg/ng DNA. f-SatIII CNVs in SZ  patients depends on the patient’s history of H/OCs. f-SatIII CN in NH-SZ(M+)-group was significantly reduced compared to H-SZ(M+)-group and HC-group (p < 10-30).  f-SatIII CN in SZ patients negatively correlated with the index reflecting the seriousness of the disease (PANSS). Antipsychotic therapy increases f-SatIII CN  in  the untreated SZ patients with a low content of the repeat and reduces the f-SatIII CN in SZ patients with high content of the repeat. In general, the SZ (M+) and SZ (M-) groups do not differ in the content of f-SatIII, but significantly differ from the HC-group by lower values of the repeat content. f-SatIII CN in the eight regions of the brain of the SZ patient varies significantly.
Conclusion.  The content of f-SatIII repeat in leukocytes of the most patients with schizophrenia is significantly reduced compared to the healthy control. Two hypotheses were put forward: (1) the low content of the repeat is a genetic feature of schizophrenia; and/or (2) the genomes of the schizophrenia patients respond to chronic oxidative stress reducing the repeats copies number.