Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8302–8306. doi: 10.1073/pnas.88.19.8302

Physical map of human Xq27-qter: localizing the region of the fragile X mutation.

A Poustka 1, A Dietrich 1, G Langenstein 1, D Toniolo 1, S T Warren 1, H Lehrach 1
PMCID: PMC52496  PMID: 1924290

Abstract

We describe a physical map of the end of the long arm of the human X chromosome encompassing the region from Xq27.2 to the q telomere, inclusive of the chromosomal band Xq28. This region is of particular interest, since it contains the highest density of genes associated with genetic diseases. The map covers a total of 12 megabases (Mb) of DNA and extends from the telomere to 3 Mb beyond the most likely position of the fragile X mutation, defined by a cluster of translocation breakpoints in somatic cell hybrids. The map determines order and position of loci throughout the Xq28 region and localizes cell line breakpoints marking the fragile X region to an interval of 300-700 kilobases between 8 and 8.7 Mb proximal of the Xq telomere.

Full text

PDF
8302

Images in this article

8303Image
on p.8303
8303Image
on p.8303
8303Image
on p.8303
8303Image
on p.8303
8304Image
on p.8304
8305Image
on p.8305

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arveiler B., Vincent A., Mandel J. L. Toward a physical map of the Xq28 region in man: linking color vision, G6PD, and coagulation factor VIII genes to an X-Y homology region. Genomics. 1989 May;4(4):460–471. doi: 10.1016/0888-7543(89)90269-3. [DOI] [PubMed] [Google Scholar]
  2. Bell M. V., Bloomfield J., McKinley M., Patterson M. N., Darlison M. G., Barnard E. A., Davies K. E. Physical linkage of a GABAA receptor subunit gene to the DXS374 locus in human Xq28. Am J Hum Genet. 1989 Dec;45(6):883–888. [PMC free article] [PubMed] [Google Scholar]
  3. Brown W. R., MacKinnon P. J., Villasanté A., Spurr N., Buckle V. J., Dobson M. J. Structure and polymorphism of human telomere-associated DNA. Cell. 1990 Oct 5;63(1):119–132. doi: 10.1016/0092-8674(90)90293-n. [DOI] [PubMed] [Google Scholar]
  4. Brown W. T. The fragile X: progress toward solving the puzzle. Am J Hum Genet. 1990 Aug;47(2):175–180. [PMC free article] [PubMed] [Google Scholar]
  5. Buckle V. J., Fujita N., Ryder-Cook A. S., Derry J. M., Barnard P. J., Lebo R. V., Schofield P. R., Seeburg P. H., Bateson A. N., Darlison M. G. Chromosomal localization of GABAA receptor subunit genes: relationship to human genetic disease. Neuron. 1989 Nov;3(5):647–654. doi: 10.1016/0896-6273(89)90275-4. [DOI] [PubMed] [Google Scholar]
  6. Dahl N., Goonewardena P., Malmgren H., Gustavson K. H., Holmgren G., Seemanova E., Annerén G., Flood A., Pettersson U. Linkage analysis of families with fragile-X mental retardation, using a novel RFLP marker (DXS 304). Am J Hum Genet. 1989 Aug;45(2):304–309. [PMC free article] [PubMed] [Google Scholar]
  7. Drayna D., Davies K., Hartley D., Mandel J. L., Camerino G., Williamson R., White R. Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. Proc Natl Acad Sci U S A. 1984 May;81(9):2836–2839. doi: 10.1073/pnas.81.9.2836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gitschier J., Wood W. I., Goralka T. M., Wion K. L., Chen E. Y., Eaton D. H., Vehar G. A., Capon D. J., Lawn R. M. Characterization of the human factor VIII gene. Nature. 1984 Nov 22;312(5992):326–330. doi: 10.1038/312326a0. [DOI] [PubMed] [Google Scholar]
  9. Grimaldi G., Skowronski J., Singer M. F. Defining the beginning and end of KpnI family segments. EMBO J. 1984 Aug;3(8):1753–1759. doi: 10.1002/j.1460-2075.1984.tb02042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Herrmann B. G., Barlow D. P., Lehrach H. A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion. Cell. 1987 Mar 13;48(5):813–825. doi: 10.1016/0092-8674(87)90078-x. [DOI] [PubMed] [Google Scholar]
  11. Hofker M. H., Bergen A. A., Skraastad M. I., Carpenter N. J., Veenema H., Connor J. M., Bakker E., van Ommen G. J., Pearson P. L. Efficient isolation of X chromosome-specific single-copy probes from a cosmid library of a human X/hamster hybrid-cell line: mapping of new probes close to the locus for X-linked mental retardation. Am J Hum Genet. 1987 Apr;40(4):312–328. [PMC free article] [PubMed] [Google Scholar]
  12. Kenwrick S., Gitschier J. A contiguous, 3-Mb physical map of Xq28 extending from the colorblindness locus to DXS15. Am J Hum Genet. 1989 Dec;45(6):873–882. [PMC free article] [PubMed] [Google Scholar]
  13. Laird C. D., Lamb M. M., Thorne J. L. Two progenitor cells for human oogonia inferred from pedigree data and the X-inactivation imprinting model of the fragile-X syndrome. Am J Hum Genet. 1990 Apr;46(4):696–719. [PMC free article] [PubMed] [Google Scholar]
  14. Lubs H. A. A marker X chromosome. Am J Hum Genet. 1969 May;21(3):231–244. [PMC free article] [PubMed] [Google Scholar]
  15. Mandel J. L., Willard H. F., Nussbaum R. L., Romeo G., Puck J. M., Davies K. E. Report of the committee on the genetic constitution of the X chromosome. Cytogenet Cell Genet. 1989;51(1-4):384–437. doi: 10.1159/000132801. [DOI] [PubMed] [Google Scholar]
  16. Nathans J., Thomas D., Hogness D. S. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science. 1986 Apr 11;232(4747):193–202. doi: 10.1126/science.2937147. [DOI] [PubMed] [Google Scholar]
  17. Nussbaum R. L., Ledbetter D. H. Fragile X syndrome: a unique mutation in man. Annu Rev Genet. 1986;20:109–145. doi: 10.1146/annurev.ge.20.120186.000545. [DOI] [PubMed] [Google Scholar]
  18. Oberlé I., Camerino G., Wrogemann K., Arveiler B., Hanauer A., Raimondi E., Mandel J. L. Multipoint genetic mapping of the Xq26-q28 region in families with fragile X mental retardation and in normal families reveals tight linkage of markers in q26-q27. Hum Genet. 1987 Sep;77(1):60–65. doi: 10.1007/BF00284716. [DOI] [PubMed] [Google Scholar]
  19. Patterson M. N., Bell M. V., Bloomfield J., Flint T., Dorkins H., Thibodeau S. N., Schaid D., Bren G., Schwartz C. E., Wieringa B. Genetic and physical mapping of a novel region close to the fragile X site on the human X chromosome. Genomics. 1989 May;4(4):570–578. doi: 10.1016/0888-7543(89)90281-4. [DOI] [PubMed] [Google Scholar]
  20. Patterson M., Kenwrick S., Thibodeau S., Faulk K., Mattei M. G., Mattei J. F., Davies K. E. Mapping of DNA markers close to the fragile site on the human X chromosome at Xq27.3. Nucleic Acids Res. 1987 Mar 25;15(6):2639–2651. doi: 10.1093/nar/15.6.2639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Patterson M., Schwartz C., Bell M., Sauer S., Hofker M., Trask B., van den Engh G., Davies K. E. Physical mapping studies on the human X chromosome in the region Xq27-Xqter. Genomics. 1987 Dec;1(4):297–306. doi: 10.1016/0888-7543(87)90028-0. [DOI] [PubMed] [Google Scholar]
  22. Perlino E., Paonessa G., Ciliberto G. Alu sequences transcription in X. laevis oocytes: nuclear-cytoplasmic partitioning and evidence for 3' end processing reactions. Nucleic Acids Res. 1985 Dec 9;13(23):8359–8377. doi: 10.1093/nar/13.23.8359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Persico M. G., Viglietto G., Martini G., Toniolo D., Paonessa G., Moscatelli C., Dono R., Vulliamy T., Luzzatto L., D'Urso M. Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5' non-coding region. Nucleic Acids Res. 1986 Mar 25;14(6):2511–2522. doi: 10.1093/nar/14.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Poustka A. M., Lehrach H., Williamson R., Bates G. A long-range restriction map encompassing the cystic fibrosis locus and its closely linked genetic markers. Genomics. 1988 May;2(4):337–345. doi: 10.1016/0888-7543(88)90023-7. [DOI] [PubMed] [Google Scholar]
  25. Rousseau F., Vincent A., Rivella S., Heitz D., Triboli C., Maestrini E., Warren S. T., Suthers G. K., Goodfellow P., Mandel J. L. Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA). Am J Hum Genet. 1991 Jan;48(1):108–116. [PMC free article] [PubMed] [Google Scholar]
  26. Sherman S. L., Morton N. E., Jacobs P. A., Turner G. The marker (X) syndrome: a cytogenetic and genetic analysis. Ann Hum Genet. 1984 Jan;48(Pt 1):21–37. doi: 10.1111/j.1469-1809.1984.tb00830.x. [DOI] [PubMed] [Google Scholar]
  27. Sutherland G. R., Baker E. Effects of nucleotides on expression of the folate sensitive fragile sites. Am J Med Genet. 1986 Jan-Feb;23(1-2):409–417. doi: 10.1002/ajmg.1320230133. [DOI] [PubMed] [Google Scholar]
  28. Suthers G. K., Callen D. F., Hyland V. J., Kozman H. M., Baker E., Eyre H., Harper P. S., Roberts S. H., Hors-Cayla M. C., Davies K. E. A new DNA marker tightly linked to the fragile X locus (FRAXA). Science. 1989 Dec 8;246(4935):1298–1300. doi: 10.1126/science.2573953. [DOI] [PubMed] [Google Scholar]
  29. Suthers G. K., Oberlé I., Nancarrow J., Mulley J. C., Hyland V. J., Wilson P. J., McCure J., Morris C. P., Hopwood J. J., Mandel J. L. Genetic mapping of new RFLPs at Xq27-q28. Genomics. 1991 Jan;9(1):37–43. doi: 10.1016/0888-7543(91)90218-4. [DOI] [PubMed] [Google Scholar]
  30. Trask B. J., Massa H., Kenwrick S., Gitschier J. Mapping of human chromosome Xq28 by two-color fluorescence in situ hybridization of DNA sequences to interphase cell nuclei. Am J Hum Genet. 1991 Jan;48(1):1–15. [PMC free article] [PubMed] [Google Scholar]
  31. Vincent A., Dahl N., Oberlé I., Hanauer A., Mandel J. L., Malmgren H., Pettersson U. The polymorphic marker DXS304 is within 5 centimorgans of the fragile X locus. Genomics. 1989 Nov;5(4):797–801. doi: 10.1016/0888-7543(89)90121-3. [DOI] [PubMed] [Google Scholar]
  32. Vincent A., Kretz C., Oberlé I., Mandel J. L. A new polymorphic marker very closely linked to DXS52 in the q28 region of the human X chromosome. Hum Genet. 1989 Apr;82(1):85–86. doi: 10.1007/BF00288280. [DOI] [PubMed] [Google Scholar]
  33. Voelckel M. A., Philip N., Piquet C., Pellissier M. C., Oberlé I., Birg F., Mattei M. G., Mattei J. F. Study of a family with a fragile site of the X chromosome at Xq27-28 without mental retardation. Hum Genet. 1989 Mar;81(4):353–357. doi: 10.1007/BF00283690. [DOI] [PubMed] [Google Scholar]
  34. Warren S. T., Knight S. J., Peters J. F., Stayton C. L., Consalez G. G., Zhang F. P. Isolation of the human chromosomal band Xq28 within somatic cell hybrids by fragile X site breakage. Proc Natl Acad Sci U S A. 1990 May;87(10):3856–3860. doi: 10.1073/pnas.87.10.3856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Warren S. T., Zhang F., Licameli G. R., Peters J. F. The fragile X site in somatic cell hybrids: an approach for molecular cloning of fragile sites. Science. 1987 Jul 24;237(4813):420–423. doi: 10.1126/science.3603029. [DOI] [PubMed] [Google Scholar]
  36. Wieacker P., Davies K. E., Cooke H. J., Pearson P. L., Williamson R., Bhattacharya S., Zimmer J., Ropers H. H. Toward a complete linkage map of the human X chromosome: regional assignment of 16 cloned single-copy DNA sequences employing a panel of somatic cell hybrids. Am J Hum Genet. 1984 Mar;36(2):265–276. [PMC free article] [PubMed] [Google Scholar]
  37. Wood W. I., Capon D. J., Simonsen C. C., Eaton D. L., Gitschier J., Keyt B., Seeburg P. H., Smith D. H., Hollingshead P., Wion K. L. Expression of active human factor VIII from recombinant DNA clones. Nature. 1984 Nov 22;312(5992):330–337. doi: 10.1038/312330a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES