Behavioral Variability and Somatic Mosaicism: A Cytogenomic Hypothesis

Vorsanova, Svetlana G.; Zelenova, Maria A; Yurov, Yuri B.; Iourov, Ivan Y.

doi:10.2174/1389202918666170719165339

Cited by 16 publications

(15 citation statements)

References 66 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such epigenetic changes lead to almost exactly the same phenotypic effect as that observed in cases of somatic genomic variations or somatic mosaicism (i.e. number of cells with a causative genomic pathology is proportional to the severity of neurobehavioral or neurodevelopmental phenotype) [15,16]. Summarizing these observations suggests that an increase in the overlap between genetic changes in imprinting disorder genes and neuropsychiatric (neurobehavioral) phenotypes.…”

Section: Imprinting Disorders and Uniparental Disomies: Is There A Plmentioning

confidence: 75%

“…Globally, in accordance with the concepts of systems biology and systems medicine (or even "systems pharmacology"), full implementation of systems science in healthcare provision and drug development requires extended studies of all the components of a system and all their interactions at different hierarchical levels of organization [16,21]. An almost identical is used for studying the (epi) genetic causes of brain diseases.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Runs of Homozygosity and Epigenetic Deregulation of Genomic Imprinting

Iourov¹,

Vorsanova²,

Yurov³

2018

obm genet

View full text Add to dashboard Cite

Runs of homozygosity (ROH) are uninterrupted contiguous regions within the genome exhibiting allelic homozygosity (alleles are inherited from the same parent). Genome-wide analyses consistently demonstrate that megabase-scale ROH are ubiquitous in humans, reflecting individual demographic history. The number and length of ROH correlate increasingly with the degree of consanguinity and can be associated with genetic diseases in both inbred and outbred individuals. Genomic imprinting and uniparental disomy (UPD) are two additional phenomena dependent on parental-origin-specific inheritance that should be noted. Here, we propose genomic imprinting is dysregulated by ROH (functional analogs of segmental UPD or those partially affecting chromosomes) spanning imprinted loci resulting in a phenotype of an imprinting disorder. Interestingly, it has recently been shown that ROH in genomic/chromosomal regions harboring imprinted disease genes are likely to be associated with brain diseases phenotypically resembling imprinting disorders (Angelman, Beckwith-Wiedemann and Prader-Willi syndromes). Therefore, ROH spanning the imprinted genes seem to be

show abstract

Section: Imprinting Disorders and Uniparental Disomies: Is There A Plmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Runs of Homozygosity and Epigenetic Deregulation of Genomic Imprinting

Iourov¹,

Vorsanova²,

Yurov³

2018

obm genet

View full text Add to dashboard Cite

show abstract

“…For more details, see reviews: [12, 21, 41-43, 45, 66]. Behavioral variability and post-traumatic stress disorders are likely to be mediated by genomic/chromosomal instability and somatic mosaicism, as well [67,68]. Here, it is important to note that changes of cell proportions are hypothesized to determine the dynamics of behavioral variability (i.e.…”

mentioning

confidence: 99%

“…Here, it is important to note that changes of cell proportions are hypothesized to determine the dynamics of behavioral variability (i.e. an increase of abnormal cell numbers may lead to more severe behavioral problems, whereas a decrease of abnormal cell numbers is likely to diminish the severity of behavioral problems) [68].…”

mentioning

confidence: 99%

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

2020

Self Cite

View full text Add to dashboard Cite

Background: Somatic chromosomal mosaicism is the presence of cell populations differing with respect to the chromosome complements (e.g. normal and abnormal) in an individual. Chromosomal mosaicism is associated with a wide spectrum of disease conditions and aging. Studying somatic genome variations has indicated that amounts of chromosomally abnormal cells are likely to be unstable. As a result, dynamic changes of mosaicism rates occur through ontogeny. Additionally, a correlation between disease severity and mosaicism rates appears to exist. High mosaicism rates are usually associated with severe disease phenotypes, whereas low-level mosaicism is generally observed in milder disease phenotypes or in presumably unaffected individuals. Here, we hypothesize that dynamic nature of somatic chromosomal mosaicism may result from genetic-environmental interactions creating therapeutic opportunities in the associated diseases and aging. Conclusion: Genetic-environmental interactions seem to contribute to the dynamic nature of somatic mosaicism. Accordingly, an external influence on cellular populations may shift the ratio of karyotypically normal and abnormal cells in favor of an increase in the amount of cells without chromosome rearrangements. Taking into account the role of somatic chromosomal mosaicism in health and disease, we have hypothesized that artificial changing of somatic mosaicism rates may be beneficial in individuals suffering from the associated diseases and/or behavioral or reproductive problems. In addition, such therapeutic procedures might be useful for anti-aging strategies (i.e. possible rejuvenation through a decrease in levels of chromosomal mosaicism) increasing the lifespan. Finally, the hypothesis appears to be applicable to any type of somatic mosacism.

show abstract

“…Additionally, our original bioinformatic techniques were shown to be truly applicable for basic and applied cytogenomics to uncover molecular, cellular, physiological and even neuropsychological mechanisms of diseases caused by chromosome imbalances [ 144 ]. Furthermore, we proposed an original cytogenomic hypothesis suggesting that human behavior might be regulated through changes in proportions of somatic mosaicism levels resulted from complex interaction between mutational burden and environment [ 145 ]. Unfortunately, the issue was published at that time, when Yuri was unable to see it (posthumously), even though its content was prepared in 2016-2017.…”

mentioning

confidence: 99%