Frontiers in Genetics (Nov 2019)

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

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

DOI
https://doi.org/10.3389/fgene.2019.01132
Journal volume & issue
Vol. 10

Abstract

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Introduction: It was shown that copy number variations (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 (Positive and Negative Syndrome Scale). 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 SZ is significantly reduced compared to the HC. Two hypotheses were put forward: (1) the low content of the repeat is a genetic feature of SZ; and/or (2) the genomes of the SZ patients respond to chronic oxidative stress reducing the repeats copies number.

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