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人类卫星III(1q12)拷贝数变异与衰老

Copy Number Variation of Human Satellite III (1q12) With Aging.

作者信息

Ershova Elizaveta S, Malinovskaya Elena M, Konkova Marina S, Veiko Roman V, Umriukhin Pavel E, Martynov Andrey V, Kutsev Sergey I, Veiko Natalia N, Kostyuk Svetlana V

机构信息

Research Centre for Medical Genetics (RCMG), Moscow, Russia.

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

出版信息

Front Genet. 2019 Aug 7;10:704. doi: 10.3389/fgene.2019.00704. eCollection 2019.

Abstract

Human satellite DNA is organized in long arrays in peri/centromeric heterochromatin. There is little information about satellite copy number variants (CNVs) in aging and replicative cell senescence (RS). Biotinylated pUC1.77 probe was used for the satellite III (f-SatIII) quantitation in leukocyte DNA by the non-radioactive quantitative hybridization for 557 subjects between 2 and 91 years old. The effect of RS and genotoxic stress (GS, 4 or 6 µM of KCrO) on the f-SatIII CNV was studied on the cultured human skin fibroblast (HSF) lines of five subjects. f-SatIII in leukocyte and HSFs varies between 5.7 and 40 pg/ng of DNA. During RS, the f-SatIII content in HSFs increased. During GS, HSFs may increase or decrease f-SatIII content. Cells with low f-SatIII content have the greatest proliferative potential. F-SatIII CNVs in different individuals belonging to the different generations depend on year of their birth. Children (born in 2005-2015 years) differed significantly from the other age groups by low content and low coefficient of variation of f-SatIII. In the individuals born in 1912-1925 and living in unfavorable social conditions (FWW, the Revolution and the Russian Civil War, SWW), there is a significant disproportion in the content of f-SatIII. The coefficient of variation reaches the maximum values than in individuals born in the period from 1926 to 1975. In the group of people born in 1990-2000 (Chernobyl disaster, the collapse of the Soviet Union, and a sharp decline in the population living standard), again, there is a significant disproportion of individuals in the content of f-SatIII. A similar disproportion was observed in the analysis of a group of individuals born in 1926-1975 who in their youth worked for a long time in high-radioactive environment. In generations that were born and who lived in childhood in a period of severe social perturbations or in conditions of environmental pollution, we found a significant increase in leukocyte DNA f-SatIII variability. It is hypothesized that the change of the f-SatIII content in the blood cells reflects the body response to stress of different nature and intensity.

摘要

人类卫星DNA以长阵列形式存在于着丝粒周围的异染色质中。关于衰老和复制性细胞衰老(RS)中卫星拷贝数变异(CNV)的信息很少。使用生物素化的pUC1.77探针,通过非放射性定量杂交法对557名年龄在2至91岁之间的受试者白细胞DNA中的卫星III(f-SatIII)进行定量。在5名受试者的培养人皮肤成纤维细胞(HSF)系中研究了RS和基因毒性应激(GS,4或6μM的KCrO)对f-SatIII CNV的影响。白细胞和HSF中的f-SatIII在5.7至40 pg/ng DNA之间变化。在RS期间,HSF中的f-SatIII含量增加。在GS期间,HSF中的f-SatIII含量可能增加或减少。f-SatIII含量低的细胞具有最大的增殖潜力。不同代的不同个体中的F-SatIII CNV取决于他们的出生年份。儿童(2005 - 2015年出生)的f-SatIII含量和变异系数低,与其他年龄组有显著差异。在1912 - 1925年出生且生活在不利社会条件下(第一次世界大战、革命和俄罗斯内战、第二次世界大战)的个体中,f-SatIII的含量存在显著不均衡。变异系数达到最大值,高于1926年至1975年期间出生的个体。在1990 - 2000年出生的人群组(切尔诺贝利灾难、苏联解体以及人口生活水平急剧下降)中再次观察到,f-SatIII含量在个体间存在显著不均衡。在对1926 - 1975年出生且年轻时在高辐射环境中长时间工作的一组个体的分析中也观察到类似的不均衡。在出生并在童年时期生活在严重社会动荡或环境污染条件下的几代人中,我们发现白细胞DNA中f-SatIII的变异性显著增加。据推测,血细胞中f-SatIII含量的变化反映了身体对不同性质和强度应激的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fb/6692473/8e0bf4a54289/fgene-10-00704-g001.jpg

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