The Detection and Analysis of Chromosome Fragile Sites

Methods Mol Biol. 2018:1672:471-482. doi: 10.1007/978-1-4939-7306-4_31.


A fragile site is a chromosomal locus that is prone to form a gap or constriction visible within a condensed metaphase chromosome, particularly following exposure of cells to DNA replication stress. Based on their frequency, fragile sites are classified as either common (CFSs; present in all individuals) or rare (RFSs; present in only a few individuals). Interest in fragile sites has remained high since their discovery in 1965, because of their association with human disease. CFSs are recognized as drivers of oncogene activation and genome instability in cancer cells, while some RFSs are associated with neurodegenerative diseases. This review summaries our current understanding of the nature and causes of fragile site "expression", including the recently characterized phenomenon of telomere fragility. In particular, we focus on a description of the methodologies and technologies for detection and analysis of chromosome fragile sites.

Keywords: 53BP1 body; Common fragile site; DNA replication stress; Fluorescence in situ hybridization (FISH); Karyotype; Micronuclei; Mitosis; Rare fragile site; Telomere fragility; Ultrafine DNA bridge (UFB).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Fragile Sites*
  • DNA Replication
  • Gene Expression
  • Genetic Loci
  • Genomic Instability*
  • Humans
  • In Situ Hybridization, Fluorescence* / methods