Somatic Genome Variations

Abstract

The genome of somatic cells is susceptible to change through ontogeny. These variations can take a variety of forms and occur through different mechanisms. Stochastic intercellular variations of the genome are suggested to be involved in a number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging). However, somatic genome variations have been shown to be involved in pathogenesis of a broad spectrum of human diseases (from chromosomal and monogenic diseases to complex disorders). Nonetheless, the contribution of somatic genome variations to human biodiversity and disease is usually underappreciated. The latter is due to consistent questioning the possibility of techniques used for uncovering somatic genome variation. Therefore, technological aspects of studying intercellular variation of the human genome remain an additional important issue for understanding the role of somatic mosaicism in health and disease. Key Concepts: The cellular genome is highly variable both at molecular and at chromosomal level. Somatic variation of the human genome is a likely mechanism for biodiversity either at intercellular or at interindividual level. A number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging) seem to be mediated by somatic genome variations. According to current concepts, the commonest type of intercellular genome variations are those manifested as changes of chromosome numbers (aneuploidy or polyploidy). Somatic genome variations are known to contribute to pathogenesis of hereditary and chromosomal diseases. Intercellular genome variation is a highly probable mechanism of complex disorders (i.e. diseases of the brain and immune system), pre‐natal mortality and cancer. Understanding of the way to uncover somatic genome variations is an important issue for determining the contribution to intercellular/interindividual diversity in health and disease as well as their functional consequences.

Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies

“…For example, it does not properly reflect somatic mosaicism [36-38], which is commonly associated with postnatal morbidity, including brain diseases [37-41]. The pathogenic value of submicroscopic genomic variations can be a matter of conjecture [2-10].…”

The applicability of interphase chromosome-specific multicolor banding (ICS-MCB) for studying neurodevelopmental and neurodegenerative disorders

“…Neurodevelopmental and neurodegenerative disorders have been systematically associated with genomic variations (i.e. chromosome abnormalities, copy number variations and single-gene mutations) [1][2][3][4]. Besides, genomic variations are commonly mosaic.…”

“…Furthermore, somatic mosaicism is likely to be an important genetic mechanism for brain diseases. The most common types of somatic genomic variations are chromosomal mosaicism and instability [1,3,[5][6][7]. However, despite these observations, somatic chromosomal mosaicism is still under observed.…”

“…More importantly, these types of genomic variability may be confined to the diseased brain. The phenomenon of brain-specific chromosomal mosaicism seems to play a significant role in the etiology of neurodevelopmental and neurodegenerative disorders [3,7,19,21]. For instance, chromosomal instability, a process closely related to cancerization, has been uncovered to mediate neurodegeneration using ICS-MCB.…”

“…ICB are currently undetectable by any type of molecular (cytogenetic) techniques apart from ICS-MCB. Brain-specific aneuploidy and copy number variations have been shown to be implicated in molecular and cellular pathways neurodegeneration [3,19,23]. Aneuploidy of chromosomes 21 and X uncovered by ICS-MCB has been found to be a common mechanism for Alzheimer's disease, one of the commonest neurodegenerative diseases in elderly persons [24][25][26].…”