Chromosome Architecture Studied by High-Resolution FISH Banding in Three Dimensionally Preserved Human Interphase Nuclei



The impact of chromosome architecture on the formation of chromosome aberrations is a recent finding of interphase-directed molecular cytogenetic studies. Until recent years, biomedical research of interphase chromosomes in their integrity was hindered by technical limitations. The introduction of three-dimensional suspension-based fluorescence in situ hybridization (S-FISH) in combination with microdissection-based engineered DNA probes and fluorescence multicolor banding (MCB) allowed studying interphase chromosome organization, numbers, and rearrangements in different kinds of cells. Such studies have already provided comprehensive information on the interphase architecture of normal human sperm, as well as first insights into the influence of chromosomal rearrangements on the 3D structure of sperm nuclei. Also, the influence of additional chromosomal fragments present in a nucleus was successfully visualized by S-FISH. Finally, S-FISH supported the idea that disease-specific chromosomal translocations could be the result of tissue-specific genomic organization. Overall, S-FISH combined with MCB, but also with other DNA probes, is a tool with high potential to resolve the influence of chromosomal imbalances or rearrangements on the interphase architecture, the latter being possibly a part of epigenetic cell regulation.


Interphase Nucleus Chromosome Territory Interphase Chromosome Sister Chromosome Small Supernumerary Marker Chromosome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



 Work supported in part by the DFG (436 ARM 17/11/06, LI 820/15-1, LI 820/21-1, LI 820/24-1, LI 820/33-1), DAAD (A/07/04616), Stefan-Morsch-Stiftung, Monika Kutzner Stiftung, Else Kröner-Fresenius-Stiftung (2011_A42).


  1. Bhatt S, Moradkhani K, Mrasek K, Puechberty J, Manvelyan M, Hunstig F, Lefort G, Weise A, Lespinasse J, Sarda P, Liehr T, Hamamah S, Pellestor F (2009) Breakpoint mapping and complete analysis of meiotic segregation patterns in three men heterozygous for paracentric inversions. Eur J Hum Genet 17:44–50PubMedCrossRefGoogle Scholar
  2. Bickmore WA, Teague P (2002) Influences of chromosome size, gene density and nuclear position on the frequency of constitutional translocations in the human population. Chromosome Res 10:707–715PubMedCrossRefGoogle Scholar
  3. Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, Muller S, Eils R, Cremer C, Speicher MR, Cremer T (2005) Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol 3:e157PubMedCrossRefGoogle Scholar
  4. Branco MR, Pombo A (2006) Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol 4:e138PubMedCrossRefGoogle Scholar
  5. Brianna Caddle L, Grant JL, Szatkiewicz J, van Hase J, Shirley BJ, Bewersdorf J, Cremer C, Arneodo A, Khalil A, Mills KD (2007) Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells. Chromosome Res 15:1061–1073PubMedCrossRefGoogle Scholar
  6. Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301PubMedCrossRefGoogle Scholar
  7. Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA (1999) Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol 45:1119–1131CrossRefGoogle Scholar
  8. Gandhi MS, Stringer JR, Nikiforova M, Medvedovic M, Nikiforov YE (2009) Gene position within chromosome territories correlates with their involvement in distinct rearrangement types in thyroid cancer cells. Genes Chromosomes Cancer 48:222–228PubMedCrossRefGoogle Scholar
  9. Grasser F, Neusser M, Fiegler H, Thormeyer T, Cremer M, Carter NP, Cremer T, Miller S (2008) Replication-timing correlated spatial chromatin arrangements in cancer and in primate interphase nuclei. J Cell Sci 121:1876–1886PubMedCrossRefGoogle Scholar
  10. Hunstig F, Manvelyan M, Bhatt S, Steinhaeuser U, Liehr T (2009) Three-dimensional interphase analysis enabled by suspension FISH. In: Liehr T (ed) Fluorescence in situ hybridization (FISH)—application guide, 1st edn. Springer, BerlinGoogle Scholar
  11. Klein E, Manvelyan M, Simonyan I, Hamid AB, Santos Guilherme R, Liehr T, Karamysheva T (2012) Centromeric association of small supernumerary marker chromosomes with their sister-chromosomes detected by three dimensional molecular cytogenetics. Mol Cytogenet 5:15PubMedCrossRefGoogle Scholar
  12. Lemke J, Claussen J, Michel S, Chudoba I, Mühlig P, Westermann M, Sperling K, Rubtsov N, Grummt UW, Ullmann P, Kromeyer-Hauschild K, Liehr T, Claussen U (2002) The DNA-based structure of human chromosome 5 in interphase. Am J Hum Genet 71:1051–1059PubMedCrossRefGoogle Scholar
  13. Liehr T, Weise A (2007) Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med 19:719–731PubMedGoogle Scholar
  14. Liehr T, Heller A, Starke H, Claussen U (2002) FISH banding methods: applications in research and diagnostics. Expert Rev Mol Diagn 2:217–225PubMedCrossRefGoogle Scholar
  15. Liehr T, Starke H, Weise A, Lehrer H, Claussen U (2004a) Multicolor FISH probe sets and their applications. Histol Histopathol 19:229–237PubMedGoogle Scholar
  16. Liehr T, Claussen U, Starke H (2004b) Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res 107:55–67PubMedCrossRefGoogle Scholar
  17. Liehr T, Starke H, Heller A, Kosyakova N, Mrasek K, Gross M, Karst C, Steinhaeuser U, Hunstig F, Fickelscher I, Kuechler A, Trifonov V, Romanenko SA, Weise A (2006) Multicolor fluorescence in situ hybridization (FISH) applied to FISH-banding. Cytogenet Genome Res 114:240–244PubMedCrossRefGoogle Scholar
  18. Manvelyan M, Hunstig F, Mrasek K, Bhatt S, Pellestor F, Weise A, Liehr T (2008a) Position of chromosomes 18, 19, 21 and 22 in 3D-preserved interphase nuclei of human and gorilla and white hand gibbon. Mol Cytogenet 1:9PubMedCrossRefGoogle Scholar
  19. Manvelyan M, Hunstig F, Bhatt S, Mrasek K, Pellestor F, Weise A, Simonyan I, Aroutiounian R, Liehr T (2008b) Chromosome distribution in human sperm—a 3D multicolor banding-study. Mol Cytogenet 1:25PubMedCrossRefGoogle Scholar
  20. Manvelyan M, Kempf P, Weise A, Mrasek K, Heller A, Lier A, Höffken K, Fricke HJ, Sayer HG, Liehr T, Mkrtchyan H (2009) Preferred co-localization of chromosome 8 and 21 in myeloid bone marrow cells detected by three dimensional molecular cytogenetics. Int J Mol Med 24:335–341PubMedGoogle Scholar
  21. Meaburn KJ, Misteli T, Soutoglou E (2007) Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol 17:80–90PubMedCrossRefGoogle Scholar
  22. Roix JJ, McQueen PG, Munson PJ, Parada LA, Misteli T (2003) Spatial proximity of translocation-prone gene loci in human lymphomas. Nat Genet 34:287–291PubMedCrossRefGoogle Scholar
  23. Steinhaeuser U, Starke H, Nietzel A, Lindenau J, Ullmann P, Claussen U, Liehr T (2002) Suspension (S)-FISH, a new technique for interphase nuclei. J Histochem Cytochem 50:1697–1698PubMedCrossRefGoogle Scholar
  24. Sun HB, Shen J, Yokota H (2000) Size-dependent positioning of human chromosomes in interphase nuclei. Biophys J 79:184–190PubMedCrossRefGoogle Scholar
  25. Weise A, Starke H, Heller A, Claussen U, Liehr T (2002) Evidence for interphase DNA decondensation transverse to the chromosome axis: a multicolor banding analysis. Int J Mol Med 9:359–361PubMedGoogle Scholar
  26. Weise A, Mrasek K, Fickelscher I, Claussen U, Cheung SW, Cai WW, Liehr T, Kosyakova N (2008) Molecular definition of high-resolution multicolor banding probes: first within the human DNA sequence anchored FISH banding probe set. J Histochem Cytochem 56:487–493PubMedCrossRefGoogle Scholar
  27. Williams RE, Fisher AG (2003) Chromosomes, positions please! Nat Cell Biol 5:388–390PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Jena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJenaGermany
  2. 2.Department of Medical GeneticsCentre of Medical Genetics and Primary Health CareYerevanArmenia
  3. 3.Research Center of Maternal and Child Health ProtectionYerevanArmenia
  4. 4.Laboratory of Morphology and Function of Cell StructureInstitute of Cytology and Genetics, Russian Academy of Sciences, Siberian BranchNovosibirskRussian Federation

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