Copy Number Variation of Satellite III (1q12) in Patients With Schizophrenia
| Autor: | 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 |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty lcsh:QH426-470 Chronic oxidative stress medicine.medical_treatment CNV 03 medical and health sciences 0302 clinical medicine Internal medicine Healthy control Genetics medicine Chronic stress In patient Copy-number variation Antipsychotic Genetics (clinical) Original Research 1q12 Positive and Negative Syndrome Scale hypoxia business.industry ROS medicine.disease schizophrenia lcsh:Genetics 030104 developmental biology Endocrinology Schizophrenia 030220 oncology & carcinogenesis Molecular Medicine satellite III business |
| Zdroj: | Frontiers in Genetics, Vol 10 (2019) Frontiers in Genetics |
| ISSN: | 1664-8021 |
| DOI: | 10.3389/fgene.2019.01132 |
| Popis: | 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-naive 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. |
| Databáze: | OpenAIRE |
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