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 (<i>n</i> = 612), we observed colocalizat...
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doaj-63a900dd7eba4c6c86ff0665a212f4062020-11-25T04:08:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218328832810.3390/ijms21218328The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and AgingIvan Y. Iourov0Svetlana G. Vorsanova1Yuri B. Yurov2Maria A. Zelenova3Oxana S. Kurinnaia4Kirill S. Vasin5Sergei I. Kutsev6Mental Health Research Center, 117152 Moscow, RussiaMental Health Research Center, 117152 Moscow, RussiaMental Health Research Center, 117152 Moscow, RussiaMental Health Research Center, 117152 Moscow, RussiaMental Health Research Center, 117152 Moscow, RussiaMental Health Research Center, 117152 Moscow, RussiaResearch Centre for Medical Genetics, 115522 Moscow, RussiaMechanisms 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 (<i>n</i> = 612), we observed colocalization of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (<i>n</i> = 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” (from the Greek words chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either in partial/whole chromosome loss (e.g., aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g., prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything”, similar to the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.https://www.mdpi.com/1422-0067/21/21/8328chromosomecopy number variationschromosome instabilitychromosomal mosaicismchromosomal imbalancesaneuploidy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ivan Y. Iourov Svetlana G. Vorsanova Yuri B. Yurov Maria A. Zelenova Oxana S. Kurinnaia Kirill S. Vasin Sergei I. Kutsev |
spellingShingle |
Ivan Y. Iourov Svetlana G. Vorsanova Yuri B. Yurov Maria A. Zelenova Oxana S. Kurinnaia Kirill S. Vasin Sergei I. Kutsev The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging International Journal of Molecular Sciences chromosome copy number variations chromosome instability chromosomal mosaicism chromosomal imbalances aneuploidy |
author_facet |
Ivan Y. Iourov Svetlana G. Vorsanova Yuri B. Yurov Maria A. Zelenova Oxana S. Kurinnaia Kirill S. Vasin Sergei I. Kutsev |
author_sort |
Ivan Y. Iourov |
title |
The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging |
title_short |
The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging |
title_full |
The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging |
title_fullStr |
The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging |
title_full_unstemmed |
The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging |
title_sort |
cytogenomic “theory of everything”: chromohelkosis may underlie chromosomal instability and mosaicism in disease and aging |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-11-01 |
description |
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 (<i>n</i> = 612), we observed colocalization of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (<i>n</i> = 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” (from the Greek words chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either in partial/whole chromosome loss (e.g., aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g., prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything”, similar to the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome. |
topic |
chromosome copy number variations chromosome instability chromosomal mosaicism chromosomal imbalances aneuploidy |
url |
https://www.mdpi.com/1422-0067/21/21/8328 |
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