Dynamic nature of somatic chromosomal mosaicism, genetic-environmental interactions and therapeutic opportunities in disease and aging

Somatic chromosomal mosaicism is the presence of cell populations differing with respect to the chromosome complements (e.g. normal and abnormal) in an individual. Here, we hypothesize that dynamic nature of somatic chromosomal mosaicism may result from genetic-environmental interactions creating therapeutic opportunities in the associated diseases and agin

COVID-19 and aging-related genome (chromosome) instability in the brain: another possible time-bomb of SARS-CoV-2 infection

Since genome (chromosome) instability may result from viral infections (Heng, 2019), SARS-CoV-2 interactions with cells of the central nervous system are able to increase the risk for early manifestations of aging-related brain disorders and/or premature brain deterioration mediated by genome and chromosome instability. Here, we have addressed data on SARS-CoV-2-host protein-protein interactomes for assessing potential COVID-19 effects on aging-related genome (chromosome) instability in the brai

Systems cytogenomics: are we ready yet?

With the introduction of systems theory to genetics, numerous opportunities for genomic research have been identified. Consequences of DNA sequence variations are systematically evaluated using the network- or pathway-based analysis, a technological basis of systems biology or, more precisely, systems genomic

Chromosome instability, aging and brain diseases

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain‐specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotype

Molecular cytogenetic and cytopostgenomic analysis of the human genome

To present a heuristic algorithm for molecular cytogenetic and cytopostgenomic analysis of the human genome to uncover mechanisms of genetic (brain/neurodevelopmental) disease

Bioinformatic analysis of microduplications at 5p15.33: identification of TPPP as a candidate gene for autism and intellectual disability

Theidentification of candidate genes by bioinformatic analysis of recurrent copy number variations (CNV) (5p15.33 duplications) revealed by molecular karyotyping in a clinical cohor

Turner’s syndrome mosaicism in girls with neurodevelopmental disorders: a cohort study and hypothesis

Turner’s syndrome is associated with either monosomy or a wide spectrum of structural rearrangements of chromosome X. Despite the interest in studying (somatic) chromosomal mosaicism, Turner’s syndrome mosaicism (TSM) remains to be fully described. This is especially true for the analysis of TSM in clinical cohorts (e.g. cohorts of individuals with neurodevelopmental disorders). Here, we present the results of studying TSM in a large cohort of girls with neurodevelopmental disorders and a hypothesis highlighting the diagnostic and prognostic valu

Somatic mosaicism in the diseased brain

It is hard to believe that all the cells of a human brain share identical genomes. Indeed, single cell genetic studies have demonstrated intercellular genomic variability in the normal and diseased brai

The cytogenomic "theory of everything": Chromohelkosis may underlie chromosomal instability and mosaicism in disease and aging

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are not completely understood. During molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n = 612), we observed colocalization of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n = 47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as "chromohelkosis

Klinefelter syndrome mosaicism in boys with neurodevelopmental disorders: a cohort study and an extension of the hypothesis

Our study provides data on the occurrence of KSM in neurodevelopmental disorders among males. Accordingly, it is proposed that KSM may be a possible element of pathogenic cascades in psychiatric and neurodegenerative diseases. These observations allowed us to extend the hypothesis proposed in our previous report on the contribution of somatic gonosomal mosaicism (Turner’s syndrome mosaicism) to the etiology of neurodevelopmental disorder