Cellular and genomic approaches for exploring structural chromosomal rearrangements

  • Qing Hu
  • Elizabeth G. Maurais
  • Peter LyEmail author


Human chromosomes are arranged in a linear and conserved sequence order that undergoes further spatial folding within the three-dimensional space of the nucleus. Although structural variations in this organization are an important source of natural genetic diversity, cytogenetic aberrations can also underlie a number of human diseases and disorders. Approaches for studying chromosome structure began half a century ago with karyotyping of Giemsa-banded chromosomes and has now evolved to encompass high-resolution fluorescence microscopy, reporter-based assays, and next-generation DNA sequencing technologies. Here, we provide a general overview of experimental methods at different resolution and sensitivity scales and discuss how they can be complemented to provide synergistic insight into the study of human chromosome structural rearrangements. These approaches range from kilobase-level resolution DNA fluorescence in situ hybridization (FISH)-based imaging approaches of individual cells to genome-wide sequencing strategies that can capture nucleotide-level information from diverse sample types. Technological advances coupled to the combinatorial use of multiple methods have resulted in the discovery of new rearrangement classes along with mechanistic insights into the processes that drive structural alterations in the human genome.


Cytogenetics Karyotype FISH Genome instability Chromosome rearrangements Structural variants 



bacterial artificial chromosome


DNA double-strand break


DNA fluorescence in situ hybridization


extrachromosomal DNA


giemsa banding


gross chromosomal rearrangement


nucleolus organizing region


structured illumination microscopy


single-nucleotide polymorphism


stochastic optical reconstruction microscopy


whole-genome sequencing



We thank Kathleen Wilson and Sangeeta Patel (UT Southwestern Medical Center) for providing figures of G-banded karyotypes. This work was supported by the US National Institutes of Health (R00CA218871 to P.L.) and the Cancer Prevention and Research Institute of Texas (RR180050 to P.L.).


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© Springer Nature B.V. 2020

Authors and Affiliations

  1. 1.Department of Pathology, Department of Cell Biology, Harold C. Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallasUSA

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