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

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; Georgiy P Kostyuk; Sergey I Kutsev; Natalia N Veiko; Svetlana V Kostyuk

doi:10.3389/fgene.2019.01132

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

Front Genet. 2019 Nov 22:10:1132. doi: 10.3389/fgene.2019.01132. eCollection 2019.

Authors

Elizaveta S Ershova^{1

2}, Oksana N Agafonova¹, Natalia V Zakharova³, Lidia V Bravve³, Elizaveta M Jestkova⁴, Vera E Golimbet⁵, Tatiana V Lezheiko⁵, Anna Y Morozova⁶, Andrey V Martynov¹, Roman V Veiko¹, Pavel E Umriukhin^{2

7}, Georgiy P Kostyuk³, Sergey I Kutsev¹, Natalia N Veiko¹, Svetlana V Kostyuk^{1

2}

Affiliations

¹ Department of Molecular Biology, Research Centre for Medical Genetics, Moscow, Russia.
² I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
³ Moscow Healthcare Department, N. A. Alexeev Clinical Psychiatric Hospital №1, Moscow, Russia.
⁴ Moscow Healthcare Department, P.B. Ganushkin Clinical Psychiatric Hospital №4, Moscow, Russia.
⁵ Department of Clinical Genetics, Mental Health Research Center, Moscow, Russia.
⁶ Department of Basic and Applied Neurobiology, V. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow, Russia.
⁷ P.K. Anokhin Institute of Normal Physiology, Moscow, Russia.

Abstract

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.

Keywords: 1q12; CNV; ROS; hypoxia; satellite III; schizophrenia.