Characterization of the telomeric region of human chromosome 16p

  • D. R. Higgs
  • A. O. M. Wilkie
  • P. Vyas
  • M. A. Vickers
  • V. J. Buckle
  • P. C. Harris
Chapter

Abstract

The terminal regions of chromosomes have specialised molecular and cytological properties, which are reflected in their DNA sequence organisation. Telomeric DNA, the conserved sequence at the extreme ends of chromosomes, comprises in mammals a variable length (2-20 kb in humans; 15-150 kb in mouse) of the simple sequence (TTAGGG)n orientated 5’->3’ toward the chromosome end. It is likely that this repeat motif, together with associated protein components can explain many of the properties of human telomeres; for example, replication of the terminal DNA, protection against exonucleolytic degradation, and the prevention of chromosome fusion (reviewed in Blackburn, 1991).

Keywords

Autosomal Dominant Polycystic Kidney Disease Globin Gene Telomeric Region Subtelomeric Region Human Telomere 
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.
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References

  1. Bird, A.P. (1986) CpG-rich islands and the function of DNA methylation. Nature 321, 209–213.PubMedCrossRefGoogle Scholar
  2. Blackburn, E.H. (1991) Structure and function of telomeres. Nature 350, 569–573.PubMedCrossRefGoogle Scholar
  3. Brown, W.R.A. et al. (1990) Structure and polymorphism of human telomere-associated DNA. Cell 63, 119–132.PubMedCrossRefGoogle Scholar
  4. D.R. Higgs, A.O.M. Wilkie, P. Vyas et al.Google Scholar
  5. Carpenter, A.T.C. (1987) Gene conversion, recombination nodules, and the initiation of meiotic synapsis. BioEssays 6, 232–236.PubMedCrossRefGoogle Scholar
  6. Chandley, A.C. (1989) Asymmetry in chromosome pairing: a major factor in de novo mutation and the production of genetic disease in man. J Med Genet 26, 546–552.PubMedCrossRefGoogle Scholar
  7. Cheng, J.-F., Smith, C.L. and Cantor, C.R. (1989) Isolation and characterization of a human telomere. Nucl Acids Res 17, 6109–6127.PubMedCrossRefGoogle Scholar
  8. Cross, S. et al. (1990) The structure of a subterminal repeated sequence present on many human chromosomes. Nucl Acids Res 18, 6649–6657.PubMedCrossRefGoogle Scholar
  9. de Lange, T. (1992) Human telomeres are attached to the nuclear matrix. EMBO J 11, 717–724.PubMedGoogle Scholar
  10. de Lange, T. et al. (1990) Structure and variability of human chromosome ends. Mol Cell Biol 10, 518–527.PubMedGoogle Scholar
  11. Donis-Keller, H. et al. (1987) A genetic linkage map of the human genome. Cell 51, 319–337.PubMedCrossRefGoogle Scholar
  12. Fischel-Ghodsian, N., Nicholls, R.D. and Higgs, D.R. (1987) Long range genome structure around the human a-globin complex analysed by PFGE. Nucl Acids Res 15, 6197–6207.PubMedCrossRefGoogle Scholar
  13. Forrester, W.C. et al. (1990) A deletion of the human ß-globin locus activation region causes a major alteration in chromatin structure and replication across the entire ß-globin locus. Genes Dell 4, 1637–1649.CrossRefGoogle Scholar
  14. Gardiner-Garden, M. and Frommer, M. (1987) CpG islands in vertebrate genomes. J Mol Biol 196, 261–282.PubMedCrossRefGoogle Scholar
  15. Germino, G.G. et al. (1990) Identification of a locus which shows no genetic recombination with the autosomal dominant polycystic kidney disease gene on chromosome 16. Am J Hum Genet 46, 925–933.PubMedGoogle Scholar
  16. Germino, G.G. et al. (1992) The gene for autosomal dominant polycystic kidney disease lies in a 750-kb CpG-rich region. Genomics 13, 144–151.PubMedCrossRefGoogle Scholar
  17. Grosveld, F. et al. (1987) Position-independent, high-level expression of the human 13-globin gene in transgenic mice. Cell 51, 975–985.PubMedCrossRefGoogle Scholar
  18. Harris, P. and Thomas, S. (1992) Length polymorphism of the subtelomeric regions of both the short (p) and long arms (q) of chromosome 16. Cytogenet Cell Genet In pressGoogle Scholar
  19. Harris, P.C. et al. (1990) A long range restriction map between the a-globin complex and a marker closely linked to the polycystic kidney disease I (PKDI) locus. Genomics 7, 195–206.PubMedCrossRefGoogle Scholar
  20. Higgs, D.R. et ai. (1989) A review of the molecular genetics of the human a-globin gene cluster. Blood 73, 1081–1104.PubMedGoogle Scholar
  21. Higgs, D.R. et al. (1990) A major positive regulatory region located far upstream of the human a-globin gene locus. Genes Dey 4, 1588–1601.CrossRefGoogle Scholar
  22. Jarman, A.P. et al. (1991) Characterization of the major regulatory element upstream of the human a-globin gene cluster. Mol Cell B i o l 11, 4679–4689.Google Scholar
  23. Lamb, J. et al. (1989) Detection of breakpoints in submicroscopic chromosomal translocation, illustrating an important mechanism for genetic disease. Lancet ii, 819–824.CrossRefGoogle Scholar
  24. Laurie, D.A. and Hutten, M.A. (1985) Further studies on chiasma distribution and interference in the human male. Ann Hum Genet (Lond) 49, 203–214.CrossRefGoogle Scholar
  25. Riethman, H.C. et al. (1989) Cloning human telomeric DNA fragments into Saccharomyces cerevisiae using a yeastartificial-chromosome vector. Proc Natl Acad Sci USA 86, 6240–6244.PubMedCrossRefGoogle Scholar
  26. Royle, N.J. et al. (1988) Clustering of hypervariable minisatellites in the proterminal regions of human autosomes. Genomics 3, 352–360.PubMedCrossRefGoogle Scholar
  27. Saccone, S. et al. (1992) The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. Proc Natl Acad Sci USA 89, 4913–4917.PubMedCrossRefGoogle Scholar
  28. Vyas, P. et al. (1992) Cis-acting sequences regulating expression of the human a globin cluster lie within constitutively open chromatin. Cell 69, 781–793.PubMedCrossRefGoogle Scholar
  29. Weber, B. et al. (1991) A low-copy repeat located in subtelomeric regions of 14 different human chromosomal termini. Cytogenet Cell Genet 57, 179–183.PubMedCrossRefGoogle Scholar
  30. Weber, B. et al. (1990) Characterization and organization of DNA sequences adjacent to the human telomere associated repeat (TTAGGG)n. Nucl Acids Res 18, 3353–3361.PubMedCrossRefGoogle Scholar
  31. Wells, R.A., Green, P. and Reeders, S.T. (1989) Simultaneous genetic mapping of multiple human minisatellite sequences using DNA fingerprinting. Genomics 5, 761–772.PubMedCrossRefGoogle Scholar
  32. Wilkie, A.O.M. and Higgs, D.R. (1992) An unusually large (CA)n repeat in the region of divergence between subtelomeric alleles of human chromosome 16p. Genomics 13, 81–88.PubMedCrossRefGoogle Scholar
  33. Wilkie, A.O.M. 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.PubMedCrossRefGoogle Scholar
  34. Wilkie, A.O.M. et al. (1990) A truncated human chromosome 16 associated with a thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature 346, 868–871.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1993

Authors and Affiliations

  • D. R. Higgs
    • 1
  • A. O. M. Wilkie
    • 1
  • P. Vyas
    • 1
  • M. A. Vickers
    • 1
  • V. J. Buckle
    • 1
  • P. C. Harris
    • 1
  1. 1.Institute of Molecular MedicineOxfordUK

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