Directional genomic hybridization (dGH) for detection of intrachromosomal rearrangements

Erin Robinson, Miles J. McKenna, Joel S. Bedford, Edwin H. Goodwin, Michael Cornforth, Susan M. Bailey, F. Andrew Ray

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Fluorescence in situ Hybridization (FISH) techniques, including whole chromosome painting (WCP), spectral karyotyping (SKY), and multicolor FISH (mFISH), are used extensively to characterize and enumerate inter-chromosomal rearrangements (e.g., translocations). Directional genomic hybridization (dGH) is a relatively new cytogenomics-based methodology that combines the strand-specific strategy of Chromosome Orientation-FISH (CO-FISH) with bioinformatics-driven design of single-stranded DNA probe sets that are unique and of like orientation. Such a strategy produces directional probe sets that hybridize to one—and only one—chromatid of prepared (single-stranded) metaphase chromosomes, thereby facilitating high-resolution visualization of intra-chromosomal rearrangements, specifically inversions, and greatly improving our ability to detect such otherwise cryptic structural variants within the genome. In addition to its usefulness in the study of various disease states, including cancer, relevant applications of dGH include monitoring cytogenetic damage caused by exposure to clastogenic agents (e.g., ionizing radiation). dGH can be applied as a discovery tool to globally assess the integrity of the genome, but it can also be used in a more targeted fashion to interrogate fine structural changes at the kilobase level. Consequently, dGH is capable of providing significant mechanistic insight and information not easily obtainable by other approaches.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages107-116
Number of pages10
DOIs
StatePublished - Jan 1 2019

Publication series

NameMethods in Molecular Biology
Volume1984
ISSN (Print)1064-3745

Keywords

  • Biodosimetry
  • Chromosomal inversions
  • Chromosome orientation-specific fluorescence in situ hybridization (CO-FISH)
  • Directional genomic hybridization (dGH)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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    Robinson, E., McKenna, M. J., Bedford, J. S., Goodwin, E. H., Cornforth, M., Bailey, S. M., & Ray, F. A. (2019). Directional genomic hybridization (dGH) for detection of intrachromosomal rearrangements. In Methods in Molecular Biology (pp. 107-116). (Methods in Molecular Biology; Vol. 1984). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-9432-8_13