Chromosomal mosaicism goes global

Abstract

: Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy). It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual) diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases) as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome) as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.

Figure 1

Aneuploidy in the fetal human brain. Interphase chromosome-specific multicolor banding (ICS-MCB) allowing bar-coding painting of the whole chromosome 9 in its integrity; from left to right: monosomy, disomy (normal chromosomal complement) and trisomy (partially reproduced from Yurov et al. [13], an open-access article distributed under the terms of the Creative Commons Attribution License).

Figure 2

Current concepts in biology of chromosomal mosaicism: somatic-germline aneuploidization pathway. Normal prenatal and postnatal development is hypothesized to be a matter of balance between two progressive processes: aneuploidization and "antianeuploidization" (the latter is arbitrarily covered by such term because it is still not completely clear what processes underlie the clearance of aneuploid cells in humans). Germline aneuploidzation results into prenatal death of aneuploid embryos or into chromosomal syndromes in newborns. Aneuploidization is observed in fetal germline tissues and in the fetal brain. This, if not cleared, has the potential to produce tissue-specific chromosomal mosaicism that can underlie the pathogenesis of brain diseases either in childhood or in adulthood. It also can be the reason of germline aneuploidization (mentioned earlier). Aneuploidization in adulthood (in some cases, in childhood) is suggested to be a key process of tumorigenesis and aging. This probably originates from the age-/environment-dependant inhibition of "antianeuploidization" processes.