FISH-Based Analysis of Mosaic Aneuploidy and Chromosome Instability for Investigating Molecular and Cellular Mechanisms of Disease

Abstract

Recently, numerous studies have reported convincing data suggesting that chromosome instability may not be only a trigger of cancers but a possible mechanism for a wide spectrum of brain diseases. According to our original experience, chromosome instability is commonly observed during karyotyping of children with neuropsychiatric diseases and congenital malformations. To understand the mechanisms of non-cancerous diseases potentially mediated by chromosome instability, which may represent an important target for molecular diagnosis and therapeutic interventions, new algorithms for molecular cytogenetic diagnostics appear to be required. Here, we address the potential of cytogenetic, molecular cytogenetic and bioinformatic analysis in children with intellectual disability,

Interphase Molecular Cytogenetic Diagnosis of Chromosomal Abnormalities (Fish) in the First Trimester Spontaneous Abortion: Analysis of 1333 Cases

“…Известно также, что мутации хромосом в виде численных аномалий в зародышевых клетках ведут к образованию аберрантных гамет, в результате которых возможна гибель зигот, эмбрионов на ранних стадиях внутриутробного развития. Кроме того, последние исследования отмечают значительную этиологическую роль хромосомного мозаицизма, который представляет хромосомную нестабильность как в нарушении психического развития, так и в нарушении эмбрионального развития [12][13][14][15].…”

Chromohelkosis — A Unusual Form of Chromosome Instability and Somatic Mosaicism Associated With Central Nervous System Diseases in Children

“…Молекулярное кариотипирование было выполнено для анализа хромосомных микроаномалий и CNV в российской когорте детей с заболеваниями ЦНС (такими как задержка психомоторного развития, умственная отсталость, аутизм, эпилепсия) и врожденными пороками (микроаномалиями) развития (n=705). Данная когорта была систематически описана в предыдущих исследованиях [7,9]. SNP-array (молекулярное кариотипирование) выполнялось с помощью биочипов на платформе CytoScan HD Arrays (Affymetrix), включающих в себя примерно 2,7 млн ДНК-маркеров.…”

Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism

“…It is to note that molecular cytogenetic methodology for visualizing interphase chromosomes cannot be completely substituted by single-cell whole genome scanning techniques [241]. Although post-genomic technologies allow single-cell genomic analysis at the highest resolution possible, uncovering chromosomal intercellular heterogeneity still requires visualization of chromosomal loci by cytogenetic karyotyping and FISH-based methods [234,248,249].…”

“…The term cytopostgenomics have been coined to cover an emerging bioscience field dedicated to postgenomic analysis focused on causes and consequences of chromosomal variations and architecture [248]. According these considerations, high-resolution whole genome scanning technologies and post-genomic bioinformatic approaches (specifically developed for molecular cytogenetics, i.e., [149,165,167,180]) are to be used to reveal molecular causes of chromosomal heterogeneity identified by cytogenetic and molecular cytogenetic techniques [241,248,249]. In total, it seems that a successful study of SCM/CIN is likely to be a result of a comprehensive combination of cytogenetic, molecular cytogenetic and post-genomic technologies.…”