Chromosomes in the DNA era: Perspectives in diagnostics and research

Abstract

Chromosomes were discovered more than 130 years ago. The implementation of chromosomal investigations in clinical diagnostics was fueled by determining the correct number of human chromosomes to be 46 and the development of specific banding techniques. Subsequent technical improvements in the field of genetic diagnostics, such as fluorescence in situ hybridization (FISH), chromosomal microarrays (CMA, array CGH) or next-generation sequencing (NGS) techniques, partially succeeded in overcoming limitations of banding cytogenetics. Consequently, nowadays, higher diagnostic yields can be achieved if new approaches such as NGS, CMA or FISH are applied in

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

“…In the post-genomic era, single-cell cytogenetic (cytogenetic karyotyping) and molecular cytogenetic (FISH) genome analyses are generally considered as outdated techniques with limited applicability [50][51][52]. However, a wide spectrum of changes in the genome behavior at the chromosomal level requires cytogenetic and FISH-based analyses (for further details, see [4,7,28,[45][46][47][48]). Furthermore, FISH-based approaches to interphase chromosomes have already been shown to uncover mechanisms for brain diseases [12,39,53,54].…”

“…chromosome fragility, interphase chromosome breakage, morphological alterations to chromosomes etc.) cannot be appropriately addressed by these technologies developed for studying whole fractions of DNA isolated from large cell populations [4,12,20,[45][46][47]. Taking into account the importance of CIN analysis and the importance of CIN as a biomarker, we suggested that there is a need to reconsider the generally accepted diagnostic approaches to chromosomal abnormalities.…”

FISHing for Unstable Cellular Genomes in the Human Brain

“…The applications of FISH-based methods to molecular neurocytogenetic purposes are not limited to detecting chromosomal abnormalities, inasmuch as these may uncover chromosome instability and behavior that are undetectable by single-cell molecular genetic techniques. Even in the post-genomic era, FISH remains an important methodology for human genome analysis [65]. Despite a number of unresolved disadvantages, the resolution of single-cell whole-genome analysis by next-generation sequencing defines this platform as an efficient tool for studying neuronal genomes.…”