Research Centre for Medical Genetics (RCMG), Moscow 115478, Russia.
Psychiatric Hospital No 14 of Moscow City Health Department, Moscow 115447, Russia.
Schizophr Res. 2018 Jul;197:305-314. doi: 10.1016/j.schres.2018.01.001. Epub 2018 Jan 12.
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).
We evaluated rDNA CN in leukocytes of 179 subjects with SZ (108 male/71 female) in comparison with 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.
rDNA CN (NQH) and rDNA CN (qPCR) was higher in SZ patients than in controls (median 542 vs 384, p=10 and median 498 vs 370, p=10). 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.
Genomes of some SZ patients contain more 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.
核糖体是翻译机制的关键组成部分。核糖体的关键组成部分是核糖体 RNA（rRNA）。rRNA 生物发生的失调与一些人类疾病有关。影响 rRNA 生物发生的因素之一是基因组中核糖体 RNA 基因（rDNA）的拷贝数。本研究的目的是检查精神分裂症（SZ）患者与健康对照（HC）相比，其基因组中的 rDNA 拷贝数（CN）变化。
我们使用两种技术：qPCR 和基于使用生物素化 rDNA 探针的非放射性定量杂交（NQH），评估了 179 名 SZ 患者（108 名男性/71 名女性）和 122 名 HC（60 名男性/62 名女性）的白细胞中的 rDNA CN。
与对照组相比，SZ 患者的 rDNA CN（NQH）和 rDNA CN（qPCR）更高（中位数 542 对 384，p=10 和中位数 498 对 370，p=10）。NQH 被实验证明比 qPCR 对严重 DNA 损伤的敏感性更低。DNA 损伤越严重，CN（NQH）/CN（qPCR）的比值 R 越高。15%的 SZ 患者的 rDNA 损伤程度明显高于 HC。
一些 SZ 患者的基因组比 HC 含有更多的核糖体基因。人类基因组中核糖体基因拷贝数的增加可能是精神分裂症发展的遗传因素之一。这一假设需要进一步的实验研究来证实或反驳。
