National Research Center of Mental Health, Russian Academy of Medical Sciences.
Curr Genomics. 2010 Sep;11(6):387-96. doi: 10.2174/138920210793176065.
It is hard to imagine that all the cells of the human organism (about 10(14)) share identical genome. Moreover, the number of mitoses (about 10(16)) required for the organism's development and maturation during ontogeny suggests that at least a proportion of them could be abnormal leading, thereby, to large-scale genomic alterations in somatic cells. Experimental data do demonstrate such genomic variations to exist and to be involved in human development and interindividual genetic variability in health and disease. However, since current genomic technologies are mainly based on methods, which analyze genomes from a large pool of cells, intercellular or somatic genome variations are significantly less appreciated in modern bioscience. Here, a review of somatic genome variations occurring at all levels of genome organization (i.e. DNA sequence, subchromosomal and chromosomal) in health and disease is presented. Looking through the available literature, it was possible to show that the somatic cell genome is extremely variable. Additionally, being mainly associated with chromosome or genome instability (most commonly manifesting as aneuploidy), somatic genome variations are involved in pathogenesis of numerous human diseases. The latter mainly concerns diseases of the brain (i.e. autism, schizophrenia, Alzheimer's disease) and immune system (autoimmune diseases), chromosomal and some monogenic syndromes, cancers, infertility and prenatal mortality. Taking into account data on somatic genome variations and chromosome instability, it becomes possible to show that related processes can underlie non-malignant pathology such as (neuro)degeneration or other local tissue dysfunctions. Together, we suggest that detection and characterization of somatic genome behavior and variations can provide new opportunities for human genome research and genetics.
很难想象人体（约 10(14)）的所有细胞都具有相同的基因组。此外，个体发生过程中组织发育和成熟所需的有丝分裂次数（约 10(16)）表明，其中至少有一部分可能异常，从而导致体细胞的大规模基因组改变。实验数据确实表明存在这种基因组变异，并参与了人类的发育以及健康和疾病中的个体间遗传变异性。然而，由于当前的基因组技术主要基于分析大量细胞基因组的方法，因此体细胞基因组的变异在现代生物科学中并未得到充分重视。在这里，我们回顾了在健康和疾病中发生在基因组组织各个层面（即 DNA 序列、亚染色体和染色体）的体细胞基因组变异。通过查阅现有文献，可以证明体细胞基因组具有极高的变异性。此外，由于体细胞基因组变异主要与染色体或基因组不稳定性（最常见的表现为非整倍体）有关，因此与许多人类疾病的发病机制有关。后者主要涉及脑部疾病（如自闭症、精神分裂症、老年痴呆症）和免疫系统疾病（自身免疫性疾病）、染色体疾病和一些单基因综合征、癌症、不孕不育和产前死亡率。考虑到体细胞基因组变异和染色体不稳定性的数据，可以表明相关过程可能是神经退化或其他局部组织功能障碍等非恶性病理学的基础。总的来说，我们认为检测和描述体细胞基因组的行为和变异可以为人类基因组研究和遗传学提供新的机会。
