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Multi-Telomere FISH

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Molecular Cytogenetics

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 204))

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Abstract

The standard investigation for suspected chromosomal rearrangements in patients is cytogenetic analysis at a 400–550 band resolution, yet this cannot routinely detect rearrangements smaller than 5 Megabases (Mb), and much larger abnormalities escape notice if they occur in regions where the banding pattern is not distinctive. In the future, this problem will largely be solved by the use of high resolution micro-arrays that will allow the entire genome to be investigated for submicroscopic chromosomal rearrangements. However, until this technology becomes routine, the only way of achieving increased reliability and resolution is to focus on specific chromosomal regions such as the ends of chromosomes (telomeres).

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References

  1. Saccone S., De Sario A., Della Valle G., and Bernardi G. (1992) The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. Proc. Natl. Acad. Sci. USA 89, 4913–4917.

    Article  CAS  PubMed  Google Scholar 

  2. Altherr M. R., Bengtsson U., Elder F. F. B., et al. (1991) Molecular Confirmation Of Wolf-Hirschhorn Syndrome With a Subtle Translocation Of Chromosome-4. Am. J. Hum. Genet. 49, 1235–1242.

    CAS  PubMed  Google Scholar 

  3. Kuwano A., Ledbetter S. A., Dobyns W. B., Emanuel B. S., and Ledbetter D. H. (1991) Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization. Am. J. Hum. Genet. 49, 707–714.

    CAS  PubMed  Google Scholar 

  4. Lamb J., Harris P. C., Wilkie A. O. M., Wood W. G., Dauwerse J. G., and Higgs D. R. (1993) De novo truncation of chromosome 16p and healing with (TTAGGG)n in the α-thalassemia/mental retardation syndrome (ATR-16). Am. J. Hum. Genet. 52, 668–676.

    CAS  PubMed  Google Scholar 

  5. Overhauser J., Bengtsson U., McMahon J., et al. (1989) Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5. Am. J. Hum. Genet. 45, 296–303.

    CAS  PubMed  Google Scholar 

  6. Wilkie A. O. M., Lamb J., Harris P. C., Finney R. D., and Higgs D. R. (1990) A truncated chromosome 16 associated with α-thalassaemia is stablised by the addition of telomeric repeats (TTAGGG)n. Nature. 346, 868–871.

    Article  CAS  PubMed  Google Scholar 

  7. Wong A. C. C, Ning Y., Flint J., et al. (1997) Molecular characterization of a 130-kb terminal microdeletion in a child with mild mental retardation. Am. J. Hum. Genet. 60, 113–120.

    CAS  PubMed  Google Scholar 

  8. Brown W. R. A., MacKinnon P. J., Villasanté A., Spurr N., Buckle V. J., and Dodson M. J. (1990) Structure and polymorphism of human telomere-associated DNA. Cell 63, 119–132.

    Article  CAS  PubMed  Google Scholar 

  9. Royle N. J., Baird D. M., and Jeffreys A. J. (1994) A subterminal satellite located adjacent to telomeres in chimpanzees is absent from the human genome. Nat. Genet. 6, 52–56.

    Article  CAS  PubMed  Google Scholar 

  10. Weber B., Collins C., Robbins C., et al. (1990) Characterization and organization of DNA sequences adjacent to the human telomere associated repeat (TTAGGG)n. Nucl. Acids Res. 18, 3353–3361.

    Article  CAS  PubMed  Google Scholar 

  11. Wilkie A. O. M., Higgs D. R., Rack K. A., et al. (1991) Stable length polymorphism of up to 260 kb at the tip of the short arm of human chromosome 16. Cell 64, 595–606.

    Article  CAS  PubMed  Google Scholar 

  12. Cross S., Lindsey J., Fantes J., McKay S., McGill N., and Cooke H. (1990) The structure of a subterminal repeated sequence present on many human chromosomes. Nucl. Acids Res. 18, 6649–6657.

    Article  CAS  PubMed  Google Scholar 

  13. Rouyer F., de la Chapelle A., Andersson M., and Weissenbach J. (1990) A interspersed repeated sequence specific for human subtelomeric regions. EMBO J. 9, 505–514.

    CAS  PubMed  Google Scholar 

  14. Knight S. J. L., Horsley S. W., Regan R., et al. (1997) Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur. J. Hum. Genet. 5, 1–8.

    CAS  PubMed  Google Scholar 

  15. National Institutes of Health, Institute of Molecular Medicine Collaboration (1996) A complete set of human telomeric probes and their clinical application. Nat. Genet. 14, 86–89.

    Article  Google Scholar 

  16. Giraudeau F., Aubert D., Young I., et al. (1997) Molecular-cytogenetic detection of a deletion of 1p36.3. J. Med. Genet. 34, 314–317.

    Article  CAS  PubMed  Google Scholar 

  17. Youngman S., Bates G., Williams S., et al. (1992). The telomeric 60 kb of chromosome arm 4p is homologous to telomeric regions on 13p, 15p, 21p and 22p. Genomics 14, 350–356.

    Article  CAS  PubMed  Google Scholar 

  18. Wright T. J., Wijmenga C., Clark L. N., Frants R. R., Williamson R., and Hewitt J. E. Fine mapping of the FSHD gene region orientates the rearranged fragment detected by the probe p13E-11. Hum. Mol. Genet. 2, 1673–1678.

    Google Scholar 

  19. Riethman H. C., Spais C., Buckingham J., Grady D., and Moyzis R. K. (1993) Physical analysis of the terminal 240 kb of DNA from human chromosome 7q. Genomics 17, 25–32.

    Article  CAS  PubMed  Google Scholar 

  20. Ning Y., Rosenberg M., Biesecker L. G., and Ledbetter D. H. (1996) Isolation of the human chromosome 22q telomere and its application to detection of cryptic chromosomal abnormalities. Hum. Genet. 97, 765–769.

    Article  CAS  PubMed  Google Scholar 

  21. Nesslinger N. J., Gorski J. L., Kurczynski T. W., et al. (1994) Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am. J. Hum. Genet. 54, 464–472.

    CAS  PubMed  Google Scholar 

  22. Cooke H. J., Brown W. R., and Rappold G. A. (1985) Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature 317, 687–692.

    Article  CAS  PubMed  Google Scholar 

  23. Kvaloy K., Galvagni F., and Brown W. R. (1994) The sequence organization of the long arm pseudoautosomal region of the human sex chromosomes. Hum. Mol. Genet. 3, 771–778.

    Article  CAS  PubMed  Google Scholar 

  24. Knight S. J., Lese C. M., Precht K. S., et al. (2000) An optimized set of human telomere clones for studying telomere integrity and architecture. Am. J. Hum. Genet. 67, 320–332.

    Article  CAS  PubMed  Google Scholar 

  25. Knight S. J., Regan R., Nicod A., et al. (1999) Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 354, 1676–1681.

    Article  CAS  PubMed  Google Scholar 

  26. Brackley K. J., Kilby M. D., Morton J., Whittle M. J., Knight S. J., and Flint J. (1999) A case of recurrent congenital fetal anomalies associated with a familial subtelomeric translocation. Prenat. Diagn. 19, 570–574.

    Article  CAS  PubMed  Google Scholar 

  27. de Vries B. B., Bitner-Glindzicz M., Knight S. J., et al. (2000) A boy with a submicroscopic 22qter deletion, general overgrowth and features suggestive of FG syndrome. Clin. Genet. 58, 483–487.

    Article  PubMed  Google Scholar 

  28. Warburton P., Mohammed S., and Ogilvie C. M. (2000) Detection of submicroscopic subtelomeric chromosome translocations: a new case study. Am. J. Med. Genet. 6, 51–55.

    Article  Google Scholar 

  29. Bacino C. A., Kashork C. D., Davino N. A., and Shaffer L. G. (2000) Detection of a cryptic translocation in a family with mental retardation using FISH and telomere regionspecific probes. Am. J. Med. Genet. 92, 250–255.

    Article  CAS  PubMed  Google Scholar 

  30. Praphanphoj V., Goodman B. K., Thomas G. H., and Raymond G. V. (2000) Cryptic subtelomeric translocations in the 22q13 deletion syndrome. J. Med. Genet. 37, 58–61.

    Article  CAS  PubMed  Google Scholar 

  31. Knight-Jones E., Knight S., Heussler H., Regan R., Flint J., and Martin K. (2000) Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3. Dev. Med. Child Neurol. 4, 2201–2206.

    Google Scholar 

  32. Kleefstra T., van de Zande G., Merkx G., Mieloo H., Hoovers J. M., and Smeets D. (2000) Identification of an unbalanced cryptic translocation between the chromosomes 8 and 13 in two sisters with mild mental retardation accompanied by mild dysmorphic features. Eur. J. Hum. Genet. 8, 637–640.

    Article  CAS  PubMed  Google Scholar 

  33. Vogels A., Devriendt K., Vermeesch J. R., et al. (2000) Cryptic translocation t(5;18) in familial mental retardation. Ann. Genet. 43, 117–123.

    CAS  PubMed  Google Scholar 

  34. de Vries B. B. A., Knight S. J. L., Homfray T., Smithson S. F., Flint J., and Winter R. M. (2001) Submicroscopic subtelomeric 1qter deletions: a recognisable phenotype? J Med Genet. 38, 175–178.

    Article  PubMed  Google Scholar 

  35. Viot G., Gosset P., Fert S., et al. (1999) Cryptic subtelomeric rearrangements detected by FISH in mentally retarded and dysmorphic patients. Am. J. Hum. Genet. 63, Supplement: A10.

    Google Scholar 

  36. Slavotinek A., Rosenberg M., Knight S., et al. (1999) Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres. J. Med. Genet. 36, 405–411.

    CAS  PubMed  Google Scholar 

  37. Rossi E., Piccini F., Zollino M., et al. (2001) Cryptic telomeric rearrangements in subjects with chromosomal phenotype and mental retardation. J. Med. Genet. 38, 417–420.

    Article  CAS  PubMed  Google Scholar 

  38. Anderlid B., Annerén G., Blennow E., and Nordenskjöld M. (1998) Subtelomeric rearrangements detected by FISH in patients with idiopathic mental retardation. Am. J. Hum. Genet. 65, Suppl: A67.

    Google Scholar 

  39. Riegel M., Baumer A., Jamar M., et al. (2001) Submicropic terminal deletions and duplications in retarded patient with unclassified malformation syndromes. Hum. Genet. 109, 286–294.

    Article  CAS  PubMed  Google Scholar 

  40. Colleaux L., Rio M., Heuertz S., et al. (2001) A Novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation. Eur. J. Hum. Genet. 9, 319–327.

    Article  CAS  PubMed  Google Scholar 

  41. Fan Y. S., Zhang Y., Speevak M., Farrell S., Jung H. J., and Siu V. M. (2001) Detection of submicroscopic aberrations in patients with unexplained mental retardation by fluorescence in situ hybridization using multiple subtelomeric probes. Genet. Med. 3, 416–421.

    Article  CAS  PubMed  Google Scholar 

  42. Clarkson B., Pavenski K., Dupuis L., et al. (2002) Detecting rearrangements in children using subtelomeric FISH and SKY. Am. J. Med. Genet. 107, 267–274.

    Article  PubMed  Google Scholar 

  43. Baker E., Hinton L., Callen D. F., et al. (2002) Study of 250 childrren with idiopathic mental retardation reveals nine cryptic and diverse subtelomeric chromosome anomalies. Am. J. Med. Genet. 107, 285–293.

    Article  PubMed  Google Scholar 

  44. Lamb A. N., Lytle C. H., Aylsworth A. S., et al. (1998) Low proportion of subtelomeric rearrangements in a population of patients with mental retardation and dysmorphic features. Am. J. Hum. Genet. 65, Suppl: A169.

    Google Scholar 

  45. Vorsanova S. G., Koloti D., Sharonin V. O., Soloviev V., and Yurov Y. B. (1998) FISH analysis of microaberrations at telomeric and subtelomeric regions in chromosomes of children with mental retardation. Am. J. Hum. Genet. 65, Suppl: A154.

    Google Scholar 

  46. Joyce C. A., Hart H. H., Fisher A. M., and Browne C. E. (1999) Use of subtelomeric FISH probes to detect abnormalities in patients with idiopathic mental retardation and characterize rearrangements at the limit of cytogenetic resolution. J. Med. Genet. 36, Suppl: S16.

    Google Scholar 

  47. Ballif B. C., Kashork C. D., and Shaffer L. G. (2000) The promise and pitfalls of telomere region-specific probes. Am. J. Hum. Genet. 67, 1356–1359.

    CAS  PubMed  Google Scholar 

  48. Anderlid B-M, Schoumans J., Annerén G., et al. (2002) Subtelomeric rearrangements detected in patients with idiopathic mental retardation. Am. J. Med. Genet. 107, 275–284.

    Article  PubMed  Google Scholar 

  49. de Vries B. B., White S. M., Knight S. J., et al. (2001) Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J. Med. Genet. 38, 145–150.

    Article  PubMed  Google Scholar 

  50. Knight S. J. and Flint J. (2000) Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis. J. Med. Genet. 37, 401–409.

    Article  CAS  PubMed  Google Scholar 

  51. Joyce C. A., Dennis N. R., Cooper S., and Browne C. E. (2001) Subtelomeric rearrangements: results from a study of selected and unselected probands with idiopathic mental retardation and control individuals by using high-resolution G-binding and FISH. Hum. Genet. 109, 440–451.

    Article  CAS  PubMed  Google Scholar 

  52. Horsley S. W., Knight S. J. L., Nixon J., et al. (1998) Del(18p) shown to be a cryptic translocation using a multiprobe FISH assay for subtelomeric chromosome rearrangements. J. Med. Genet. 35, 722–726.

    Google Scholar 

  53. Brkanac Z., Cody J. D., Leach R. J., and DuPont B. R. (1998) Identification of cryptic rearrangements in patients with 18q-deletion syndrome. Am. J. Hum. Genet. 62, 1500–1506.

    Article  CAS  PubMed  Google Scholar 

  54. Benzacken B., Monier-Gavelle F., Pierre Siffroi J., Agbo P., Chalvon A., and Philippe Wolf J. (2001) Acrocentric chromosome polymorphisms: beware of cryptic translocations. Prenat. Diagn. 21, 96–98.

    Article  CAS  PubMed  Google Scholar 

  55. Tosi S., Scherer S. W., Giudici G., Czepulkowski B., Biondi A., and Kearney L. (1999) Delineation of multiple deleted regions in 7q in myeloid disorders. Gene. Chromosom. Canc. 25, 384–392.

    Article  CAS  Google Scholar 

  56. Tosi S., Giudici G., Rambaldi A., et al. (1999) Characterization of the human myeloid leukemia-derived cell line GF-D8 by multiplex fluorescence in situ hybridization, subtelomeric probes, and comparative genomic hybridization. Gene. Chromosom. Canc. 24, 213–221.

    Article  CAS  Google Scholar 

  57. Jaju R. J., Haas O. A., Neat M., et al. (1999) A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. Blood 94, 773–780.

    CAS  PubMed  Google Scholar 

  58. Foot N., Neat M. J., Kearney L et al. (1999) Multiple FISH technology to clarify abnormal leukaemic karyotypes. J. Med. Genet. 36, S38.

    Google Scholar 

  59. Wakui K., Tanemura M., Suzumori K., Hidaka E., Ishikawa M., Kubota T., et al. (1999) Clinical applications of two-color telomeric fluorescence in situ hybridization for prenatal diagnosis: identification of chromosomal translocation in five families with recurrent miscarriages or a child with multiple congenital anomalies. J. Hum. Genet. 44, 85–90.

    Article  CAS  PubMed  Google Scholar 

  60. Scriven P. N., Handyside A. H., and Ogilvie C. M. (1998) Chromosome translocations: segregation modes and strategies for preimplantation genetic diagnosis. Prenat. Diagn. 18, 1437–1449.

    Article  CAS  PubMed  Google Scholar 

  61. Handyside A. H., Scriven P. N., and Ogilvie C. M. (1998) The future of preimplantation genetic diagnosis. Hum. Reprod. 13Suppl 4, 249–255.

    PubMed  Google Scholar 

  62. Mackie-Ogilvie C., Harrison R. H., Handyside A. H., and Scriven P. N. (1999) The use of subtelomeric probes in preimplantation genetic diagnosis. J. Med. Genet. 36, Supplement: S15.

    Google Scholar 

  63. Lese C. M., Zhang X., Pinkel D., et al. (1999) Comparative genomic hybridization arrays: Towards a “telomere chip.” Am. J. Hum. Genet. 65, 41.

    Google Scholar 

  64. Ghaffari S. R., Boyd E., Tolmie J. L., Crow Y. J., Trainer A. H., and Connor J. M. (1998) A new strategy for cryptic telomeric translocation screening in patients with idiopathic mental retardation. J. Med. Genet. 35, 225–233.

    Article  CAS  PubMed  Google Scholar 

  65. Rosenberg M. J., Vaske D., Killoran C. E., et al. (2000) Detection of chromosomal aberrations by a whole-genome microsatellite screen. Am. J. Hum. Genet. 66, 419–427.

    Article  CAS  PubMed  Google Scholar 

  66. Borgione E., Giudice M. L., Galesi O., et al. (2001) How microsatellite analysis can be exploited for subtelomeric chromosomal rearrangement analysis in mental retardation. J. Med. Genet. 38, E1.

    Article  CAS  PubMed  Google Scholar 

  67. Rosenberg M. J., Killoran C., Dziadzio L., et al. (2001) Scanning for telomeric deletions and duplications and uniparental disomy using genetic markers in 120 children with malformations. Hum. Genet. 109, 311–318.

    Article  CAS  PubMed  Google Scholar 

  68. Armour J. A., Sismani C., Patsalis P. C., and Cross G. (2000) Measurement of locus copy number by hybridisation with amplifiable probes. Nucl. Acids Res. 28, 605–609.

    Article  CAS  PubMed  Google Scholar 

  69. Sismani C., Armour J. A., Flint J., Girgallia C., Regan R., and Patsalis P. C. (2001) Screening for subtelomeric chromosome abnormalities in children with idiopathic mental retardation using the multiprobe telomere FISH and the new MAPH telomeric assays. Eur. J. Hum. Genet. 9, 527–532.

    Article  CAS  PubMed  Google Scholar 

  70. Granzow M., Popp S., Keller M., et al. (2000) Multiplex FISH telomere integrity assay identifies an unbalanced cryptic translocation der(5)t(3;5)(q27;p15.3) in a family with three mentally retarded individuals. Hum. Genet. 107, 51–57.

    Article  CAS  PubMed  Google Scholar 

  71. Brown J., Saracoglu K., Uhrig S., Speicher M. R., Eils R., and Kearney L. (2001) Subtelomeric chromosome rearrangements are detected using an innovative 12-color FISH assay (M-TEL). Nat. Med. 7, 497–501.

    Article  CAS  PubMed  Google Scholar 

  72. Brown J., Horsley S. W., Jung C., et al. (2000) Identification of a subtle t(16;19)(p13.3;p13.3) in an infant with multiple congenital abnormalities using a 12-colour multiplex FISH telomere assay, M-TEL. Eur. J. Hum. Genet. 8, 903–910.

    Article  CAS  PubMed  Google Scholar 

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Knight, S.J.L., Flint, J. (2002). Multi-Telomere FISH. In: Fan, YS. (eds) Molecular Cytogenetics. Methods in Molecular Biology™, vol 204. Humana Press. https://doi.org/10.1385/1-59259-300-3:155

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  • DOI: https://doi.org/10.1385/1-59259-300-3:155

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-006-9

  • Online ISBN: 978-1-59259-300-2

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