title: Genomic Copy Number Variation Affecting Genes Involved in the Cell Cycle Pathway: Implications for Somatic Mosaicism.
abstract: Somatic genome variations (mosaicism) seem to represent a common mechanism for human intercellular/interindividual diversity in health and disease. However, origins and mechanisms of somatic mosaicism remain a matter of conjecture. Recently, it has been hypothesized that zygotic genomic variation naturally occurring in humans is likely to predispose to nonheritable genetic changes (aneuploidy) acquired during the lifetime through affecting cell cycle regulation, genome stability maintenance, and related pathways. Here, we have evaluated genomic copy number variation (CNV) in genes implicated in the cell cycle pathway (according to Kyoto Encyclopedia of Genes and Genomes/KEGG) within a cohort of patients with intellectual disability, autism, and/or epilepsy, in which the phenotype was not associated with genomic rearrangements altering this pathway. Benign CNVs affecting 20 genes of the cell cycle pathway were detected in 161 out of 255 patients (71.6%). Among them, 62 individuals exhibited >2 CNVs affecting the cell cycle pathway. Taking into account the number of individuals demonstrating CNV of these genes, a support for this hypothesis appears to be presented. Accordingly, we speculate that further studies of CNV burden across the genes implicated in related pathways might clarify whether zygotic genomic variation generates somatic mosaicism in health and disease.
authors.affiliation: Mental Health Research Center, Moscow 117152, Russia ; Separated Structural Unit "Clinical Research Institute of Pediatrics", Pirogov Russian National Research Medical University, Ministry of Health of Russian Federation, Moscow 125412, Russia ; Department of Medical Genetics, Russian Medical Academy of Postgraduate Education, Moscow 123995, Russia.
authors.forename: Ivan Y
authors.initials: IY
authors.lastname: Iourov
authors.affiliation: Mental Health Research Center, Moscow 117152, Russia ; Separated Structural Unit "Clinical Research Institute of Pediatrics", Pirogov Russian National Research Medical University, Ministry of Health of Russian Federation, Moscow 125412, Russia.
authors.forename: Svetlana G
authors.initials: SG
authors.lastname: Vorsanova
authors.affiliation: Mental Health Research Center, Moscow 117152, Russia ; Separated Structural Unit "Clinical Research Institute of Pediatrics", Pirogov Russian National Research Medical University, Ministry of Health of Russian Federation, Moscow 125412, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Zelenova
authors.affiliation: I.M. Sechenov First Moscow Medical University, Moscow 119991, Russia.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Korostelev
authors.affiliation: Mental Health Research Center, Moscow 117152, Russia ; Separated Structural Unit "Clinical Research Institute of Pediatrics", Pirogov Russian National Research Medical University, Ministry of Health of Russian Federation, Moscow 125412, Russia.
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Yurov