From cytogenetics to proteogenomics: new horizons in the study of aneuploidies.

IF 0.9 Q3 AGRICULTURE, MULTIDISCIPLINARY
K S Zadesenets, N B Rubtsov
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引用次数: 0

Abstract

Aneuploidy is defined as the loss or gain of a whole chromosome or its region. Even at early stages of development, it usually leads to fatal consequences, including developmental defects/abnormalities and death. For a long time, it was believed that the disruption of gene balance results in pronounced effects at both the cellular and organismal levels, adversely affecting organism formation. It has been shown that the gene imbalance resulting from aneuploidy leads to proteotoxic and metabolic stress within the cell, reduced cell proliferation, genomic instability, oxidative stress, etc. However, some organisms have exhibited tolerance to aneuploidies, which may even confer adaptive advantages, such as antibiotic resistance in pathogenic fungal strains. A significant factor likely lies in the complexity of the tissue and organ organization of specific species. Polyploid organisms are generally more tolerant of aneuploidy, particularly those that have recently undergone whole-genome duplication. This review places special emphasis on the examination of sex chromosome aneuploidies in humans. In addition to primary effects, or cis effects (changes in the quantity of the transcripts of genes located on the aneuploid chromosome), aneuploidy can induce secondary or trans effects (changes in the expression levels of genes located on other chromosomes). The results of recent studies have prompted a reevaluation of the impact of aneuploidy on the structural-functional organization of the genome, transcriptome, and proteome of both the cell and the entire organism. Despite the fact that, in the cases of aneuploidy, the expression levels for most genes correlate with their altered copy numbers in the cell, there have been instances of dosage compensation, where the transcript levels of genes located on the aneuploid chromosome remained unchanged. The review presents findings from recent studies focused on compensatory mechanisms of dosage compensation that modify gene product quantities at post-transcriptional and post-translational levels, alleviating the negative effects of aneuploidy on cellular homeostasis. It also discusses the influence of extrachromosomal elements on the spatial organization of the genome and the changes in gene expression patterns resulting from their presence. Additionally, the review specifically examines cases of segmental aneuploidy and changes in copy number variants (CNVs) in the genome. Not only the implications of their composition are considered, but also their localization within the chromosome and in various compartments of the interphase nucleus. Addressing these questions could significantly contribute to enhancing cytogenomic diagnostics and establishing a necessary database for accurate interpretation of identified cases of segmental aneuploidy and CNVs in the genome.

从细胞遗传学到蛋白质基因组学:非整倍体研究的新视野。
非整倍体被定义为整个染色体或其区域的损失或获得。即使在发育的早期阶段,它通常会导致致命的后果,包括发育缺陷/异常和死亡。长期以来,人们认为基因平衡的破坏会在细胞和有机体水平上产生明显的影响,对生物体的形成产生不利影响。研究表明,非整倍体导致的基因失衡会导致细胞内的蛋白质毒性和代谢应激、细胞增殖减少、基因组不稳定、氧化应激等。然而,一些生物体表现出对非整倍体的耐受性,这甚至可能赋予适应性优势,例如致病性真菌菌株的抗生素抗性。一个重要的因素可能在于特定物种的组织和器官组织的复杂性。多倍体生物通常对非整倍体更有耐性,特别是那些最近经历了全基因组复制的生物。本综述特别强调了人类性染色体非整倍体的检查。除了初级效应或顺式效应(位于非整倍体染色体上的基因转录本数量的变化)外,非整倍性还可诱导次生效应或反式效应(位于其他染色体上的基因表达水平的变化)。最近的研究结果促使人们重新评估非整倍体对细胞和整个生物体的基因组、转录组和蛋白质组的结构-功能组织的影响。尽管事实上,在非整倍体的情况下,大多数基因的表达水平与其在细胞中拷贝数的改变相关,但存在剂量补偿的情况,即位于非整倍体染色体上的基因的转录水平保持不变。本文综述了近年来关于剂量补偿机制的研究成果,这些补偿机制在转录后和翻译后水平上改变了基因产物的数量,减轻了非整倍体对细胞稳态的负面影响。它还讨论了染色体外元素对基因组空间组织的影响以及由于它们的存在而导致的基因表达模式的变化。此外,该综述还专门研究了基因组中片段性非整倍体和拷贝数变异(CNVs)变化的病例。不仅考虑了它们组成的含义,而且考虑了它们在染色体和间期核的各个室中的定位。解决这些问题将大大有助于提高细胞基因组学诊断和建立必要的数据库,以准确解释基因组中已确定的片段性非整倍体和cnv病例。
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来源期刊
Vavilovskii Zhurnal Genetiki i Selektsii
Vavilovskii Zhurnal Genetiki i Selektsii AGRICULTURE, MULTIDISCIPLINARY-
CiteScore
1.90
自引率
0.00%
发文量
119
审稿时长
8 weeks
期刊介绍: The "Vavilov Journal of genetics and breeding" publishes original research and review articles in all key areas of modern plant, animal and human genetics, genomics, bioinformatics and biotechnology. One of the main objectives of the journal is integration of theoretical and applied research in the field of genetics. Special attention is paid to the most topical areas in modern genetics dealing with global concerns such as food security and human health.
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