Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients
Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients
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DOI：
10.1016/j.schres.2018.01.001
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发表时间：
2018-07-01
影响因子：
4.5
通讯作者：
Kostyuk, S. V.
中科院分区：
文献类型：
--
作者：
Chestkov, I. V.;Jestkova, E. M.;Kostyuk, S. V.
目的：核糖体是翻译机器的重要组成部分。核糖体的主要成分是核糖体RNA（rRNA）。rRNA生物合成的失调与一些人类疾病有关。影响rRNA生物合成的因素之一是基因组中核糖体RNA基因（rDNA）的拷贝数。本研究的目的是检测精神分裂症患者（SZ）与健康对照者（HC）白细胞rDNA拷贝数（CN）的差异（108例男性/71例女性）与122例HC相比（60名男性/62名女性）使用两种技术：qPCR和非放射性定量杂交（NQH），其基于使用生物素化的rDNA探针。SZ患者的rDNA CN（NQH）和rDNA CN（qPCR）高于对照组（中位数542 vs 384，p = 10 - 25和中位数498 vs 370，p = 10 - 12）。实验证明NQH对严重DNA损伤的敏感性低于qPCR。DNA损伤越多，R = CN（NQH）/CN（qPCR）的比率就越高。15%的SZ患者的rDNA损伤程度明显高于HC患者。结论：部分SZ患者的基因组中含有比HC患者更多的核糖体基因。核糖体基因拷贝数的增加可能是精神分裂症发病的遗传因素之一。这一假设需要进一步的实验研究来证实或反驳。(C)2018年爱思唯尔B。V.保留所有权利。
Objective: The ribosome is a critical component of the translation machinery. The key component of ribosomes is ribosomal RNA (rRNA). Dysregulation of rRNA biogenesis has been implicated in some human diseases. One of the factors affecting rRNA biogenesis is the ribosomal RNA genes (rDNA) copy number in the genome. The aim of this study was to examine the rDNA copy number (CN) variation in the genomes of patients with schizophrenia (SZ) compared to healthy controls (HC).Methods: Weevaluated rDNA CN in leukocytes of 179 subjects with SZ (108 male/71 female) in comparisonwith 122 HC (60 male/62 female) using two techniques: qPCR and nonradioactive quantitative hybridization (NQH), which is based on the use of biotinylated rDNA probes.Results: rDNA CN (NQH) and rDNA CN (qPCR) was higher in SZ patients than in controls (median 542 vs 384, p= 10- 25 and median 498 vs 370, p = 10- 12). NQH was experimentally proved to be less sensitive to severe DNA damage than qPCR. The more DNA damage, the higher the ratio R= CN (NQH)/CN (qPCR). 15% of the SZ patients had significantly higher rDNA damage degree than the HC.Conclusion: Genomes of some SZ patients containmore ribosomal genes than those of HC. The elevated ribosomal genes copy number in human genome can be one of the genetic factors of schizophrenia development. This hypothesis requires further experimental studies to be corroborated or disproved. (C) 2018 Elsevier B. V. All rights reserved.