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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01132

Copy Number Variation of Satellite III (1q12) in patients with schizophrenia

Elizaveta S. Ershova1, 2,  Oksana N. Agafonova1, Lidia V. Bravve3, Elizaveta M. Jestkova3, Vera E. Golimbet4, Tatiana V. Lezheiko4,  Natalia V. Zakharova3,  Anna Y. Morozova5, Andrey V. Martynov1, Roman V. Veiko1,  Pavel E. Umriukhin2, 6, Georgiy P. Kostyuk3, Sergey I. Kutsev1,  Natalia N. Veiko1* and Svetlana V. Kostyuk1, 2
  • 1Federal State Budgetary Scientific Institution Research Centre for Medical Genetics (RCMG), Russia
  • 2I.M. Sechenov First Moscow State Medical University, Russia
  • 3Psychiatric Clinical Hospital № 1 named after N.A. Alekseeva, Russia
  • 4Mental Health Research Center of Russian Academy of Medical Sciences, Russia
  • 5V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, Ministry of Health (Russia), Russia
  • 6P.K. Anokhin Institute of Normal Physiology, Russia

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.

Keywords: CNVs, satellite DNA, Schizophrenia, Copy number variance, 1q12

Received: 27 Aug 2019; Accepted: 18 Oct 2019.

Copyright: © 2019 Ershova, Agafonova, Bravve, Jestkova, Golimbet, Lezheiko, Zakharova, Morozova, Martynov, Veiko, Umriukhin, Kostyuk, Kutsev, Veiko and Kostyuk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Natalia N. Veiko, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics (RCMG), Moscow, Moscow Oblast, Russia,