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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1988 Oct;43(4):452–461.

Molecular analysis of male-viable deletions and duplications allows ordering of 52 DNA probes on proximal Xq.

F P Cremers 1, T J van de Pol 1, B Wieringa 1, M H Hofker 1, P L Pearson 1, R A Pfeiffer 1, M Mikkelsen 1, A Tabor 1, H H Ropers 1
PMCID: PMC1715498  PMID: 3177387

Abstract

While performing a systematic search for chromosomal microdeletions in patients with clinically complex X-linked syndromes, we have observed that large male-viable deletions and duplications are clustered in heterochromatic regions of the X chromosome. Apart from the Xp21 band, where numerous deletions have been found that encompass the Duchenne muscular dystrophy gene, an increasing number of deletions and duplications have been observed that span (part of) the Xq21 segment. To refine the molecular and genetic map of this region, we have employed 52 cloned single-copy DNA sequences from the Xcen-q22 segment to characterize two partly overlapping tandem duplications and two interstitial deletions on the proximal long arm of the human X chromosome. Together with a panel of somatic cell hybrids that had been described earlier, these four rearrangements enabled us to order the 52 probes into nine different groups and to narrow the regional assignment of several genes, including those for tapetochoroidal dystrophy and anhidrotic ectodermal dysplasia.

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Selected References

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

  1. Aldridge J., Kunkel L., Bruns G., Tantravahi U., Lalande M., Brewster T., Moreau E., Wilson M., Bromley W., Roderick T. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed] [Google Scholar]
  2. Arveiler B., Hofker M. H., Bergen A. A., Mandel J. L. A PstI RFLP detected by probe cpX73 (DXS159) in Xq11-q12. Nucleic Acids Res. 1987 Jul 24;15(14):5903–5903. doi: 10.1093/nar/15.14.5903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arveiler B., Oberlé I., Mandel J. L. Genetic mapping of nine DNA markers in the q11----q22 region of the human X chromosome. Genomics. 1987 Sep;1(1):60–66. doi: 10.1016/0888-7543(87)90105-4. [DOI] [PubMed] [Google Scholar]
  4. Ayazi S. Choroideremia, obesity, and congenital deafness. Am J Ophthalmol. 1981 Jul;92(1):63–69. doi: 10.1016/s0002-9394(14)75909-4. [DOI] [PubMed] [Google Scholar]
  5. Bartley J. A., Patil S., Davenport S., Goldstein D., Pickens J. Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal insufficiency associated with Xp21 interstitial deletion. J Pediatr. 1986 Feb;108(2):189–192. doi: 10.1016/s0022-3476(86)80980-5. [DOI] [PubMed] [Google Scholar]
  6. Carle G. F., Frank M., Olson M. V. Electrophoretic separations of large DNA molecules by periodic inversion of the electric field. Science. 1986 Apr 4;232(4746):65–68. doi: 10.1126/science.3952500. [DOI] [PubMed] [Google Scholar]
  7. Cremers C. W., Hombergen G. C., Scaf J. J., Huygen P. L., Volkers W. S., Pinckers A. J. X-linked progressive mixed deafness with perilymphatic gusher during stapes surgery. Arch Otolaryngol. 1985 Apr;111(4):249–254. doi: 10.1001/archotol.1985.00800060073010. [DOI] [PubMed] [Google Scholar]
  8. Cremers F. P., Brunsmann F., van de Pol T. J., Pawlowitzki I. H., Paulsen K., Wieringa B., Ropers H. H. Deletion of the DXS165 locus in patients with classical choroideremia. Clin Genet. 1987 Dec;32(6):421–423. doi: 10.1111/j.1399-0004.1987.tb03166.x. [DOI] [PubMed] [Google Scholar]
  9. Cremers F. P., Pfeiffer R. A., van de Pol T. J., Hofker M. H., Kruse T. A., Wieringa B., Ropers H. H. An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region. Hum Genet. 1987 Sep;77(1):23–27. doi: 10.1007/BF00284707. [DOI] [PubMed] [Google Scholar]
  10. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. Francke U., Ochs H. D., de Martinville B., Giacalone J., Lindgren V., Distèche C., Pagon R. A., Hofker M. H., van Ommen G. J., Pearson P. L. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am J Hum Genet. 1985 Mar;37(2):250–267. [PMC free article] [PubMed] [Google Scholar]
  13. Francke U. Random X inactivation resulting in mosaic nullisomy of region Xp21.1----p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease. Cytogenet Cell Genet. 1984;38(4):298–307. doi: 10.1159/000132078. [DOI] [PubMed] [Google Scholar]
  14. Gal A., Wieringa B., Smeets D. F., Bleeker-Wagemakers L., Ropers H. H. Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease. Cytogenet Cell Genet. 1986;42(4):219–224. doi: 10.1159/000132282. [DOI] [PubMed] [Google Scholar]
  15. Gerald P. S., Brown J. A. Proceedings: Report of the Committee on the Genetic Constitution of the X Chromosome. Cytogenet Cell Genet. 1974;13(1):29–34. doi: 10.1159/000130228. [DOI] [PubMed] [Google Scholar]
  16. Goodfellow P. N., Davies K. E., Ropers H. H. Report of the Committee on the Genetic Constitution of the X and Y Chromosomes. Cytogenet Cell Genet. 1985;40(1-4):296–352. doi: 10.1159/000132178. [DOI] [PubMed] [Google Scholar]
  17. Grzeschik K. H., Siniscalco M. Identification of a de novo chromosome rearrangement in a man-mouse hybrid clone and its bearing on the cytological map of the human X chromosome. Cytogenet Cell Genet. 1976;16(1-5):149–156. doi: 10.1159/000130577. [DOI] [PubMed] [Google Scholar]
  18. Hodgson S. V., Robertson M. E., Fear C. N., Goodship J., Malcolm S., Jay B., Bobrow M., Pembrey M. E. Prenatal diagnosis of X-linked choroideremia with mental retardation, associated with a cytologically detectable X-chromosome deletion. Hum Genet. 1987 Mar;75(3):286–290. doi: 10.1007/BF00281076. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Hofker M. H., Skraastad M. I., Bergen A. A., Wapenaar M. C., Bakker E., Millington-Ward A., van Ommen G. J., Pearson P. L. The X chromosome shows less genetic variation at restriction sites than the autosomes. Am J Hum Genet. 1986 Oct;39(4):438–451. [PMC free article] [PubMed] [Google Scholar]
  21. Kurnit D. M., Hoehn H. Prenatal diagnosis of human genome variation. Annu Rev Genet. 1979;13:235–258. doi: 10.1146/annurev.ge.13.120179.001315. [DOI] [PubMed] [Google Scholar]
  22. Lange K., Kunkel L., Aldridge J., Latt S. A. Accurate and superaccurate gene mapping. Am J Hum Genet. 1985 Sep;37(5):853–867. [PMC free article] [PubMed] [Google Scholar]
  23. Litt M., White R. L. A highly polymorphic locus in human DNA revealed by cosmid-derived probes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6206–6210. doi: 10.1073/pnas.82.18.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Michelson A. M., Bruns G. A., Morton C. C., Orkin S. H. The human phosphoglycerate kinase multigene family. HLA-associated sequences and an X-linked locus containing a processed pseudogene and its functional counterpart. J Biol Chem. 1985 Jun 10;260(11):6982–6992. [PubMed] [Google Scholar]
  25. Monaco A. P., Bertelson C. J., Middlesworth W., Colletti C. A., Aldridge J., Fischbeck K. H., Bartlett R., Pericak-Vance M. A., Roses A. D., Kunkel L. M. Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment. 1985 Aug 29-Sep 4Nature. 316(6031):842–845. doi: 10.1038/316842a0. [DOI] [PubMed] [Google Scholar]
  26. Moore G. E., Ivens A., Chambers J., Farrall M., Williamson R., Page D. C., Bjornsson A., Arnason A., Jensson O. Linkage of an X-chromosome cleft palate gene. Nature. 1987 Mar 5;326(6108):91–92. doi: 10.1038/326091a0. [DOI] [PubMed] [Google Scholar]
  27. Nakamura Y., Leppert M., O'Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science. 1987 Mar 27;235(4796):1616–1622. doi: 10.1126/science.3029872. [DOI] [PubMed] [Google Scholar]
  28. Nussbaum R. L., Lesko J. G., Lewis R. A., Ledbetter S. A., Ledbetter D. H. Isolation of anonymous DNA sequences from within a submicroscopic X chromosomal deletion in a patient with choroideremia, deafness, and mental retardation. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6521–6525. doi: 10.1073/pnas.84.18.6521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Old J. M., Briand P. L., Purvis-Smith S., Howard N. J., Wilcken B., Hammond J., Pearson P., Cathelineau L., Williamson R., Davies K. E. Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis. Lancet. 1985 Jan 12;1(8420):73–75. doi: 10.1016/s0140-6736(85)91966-x. [DOI] [PubMed] [Google Scholar]
  30. Page D. C., Harper M. E., Love J., Botstein D. Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution. Nature. 1984 Sep 13;311(5982):119–123. doi: 10.1038/311119a0. [DOI] [PubMed] [Google Scholar]
  31. Riddell D. C., Wang H. S., Beckett J., Chan A., Holden J. J., Mulligan L. M., Phillips M. A., Simpson N. E., Wrogemann K., Hamerton J. L. Regional localization of 18 human X-linked DNA sequences. Cytogenet Cell Genet. 1986;42(3):123–128. doi: 10.1159/000132264. [DOI] [PubMed] [Google Scholar]
  32. Rosenberg T., Schwartz M., Niebuhr E., Yang H. M., Sardemann H., Andersen O., Lundsteen C. Choroideremia in interstitial deletion of the X chromosome. Ophthalmic Paediatr Genet. 1986 Dec;7(3):205–210. doi: 10.3109/13816818609004140. [DOI] [PubMed] [Google Scholar]
  33. Royer-Pokora B., Kunkel L. M., Monaco A. P., Goff S. C., Newburger P. E., Baehner R. L., Cole F. S., Curnutte J. T., Orkin S. H. Cloning the gene for an inherited human disorder--chronic granulomatous disease--on the basis of its chromosomal location. Nature. 1986 Jul 3;322(6074):32–38. doi: 10.1038/322032a0. [DOI] [PubMed] [Google Scholar]
  34. Schwartz M., Rosenberg T., Niebuhr E., Lundsteen C., Sardemann H., Andersen O., Yang H. M., Lamm L. U. Choroideremia: further evidence for assignment of the locus to Xq13-Xq21. Hum Genet. 1986 Dec;74(4):449–452. doi: 10.1007/BF00280505. [DOI] [PubMed] [Google Scholar]
  35. Tabor A., Andersen O., Lundsteen C., Niebuhr E., Sardemann H. Interstitial deletion in the "critical region" of the long arm of the X chromosome in a mentally retarded boy and his normal mother. Hum Genet. 1983;64(2):196–199. doi: 10.1007/BF00327127. [DOI] [PubMed] [Google Scholar]
  36. Vejerslev L. O., Rix M., Jespersen B. Inherited tandem duplication dup(X) (q131-q212) in a male proband. Clin Genet. 1985 Mar;27(3):276–281. doi: 10.1111/j.1399-0004.1985.tb00220.x. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Wieringa B., Hustinx T., Scheres J., Renier W., ter Haar B. Complex glycerol kinase deficiency syndrome explained as X-chromosomal deletion. Clin Genet. 1985 May;27(5):522–523. doi: 10.1111/j.1399-0004.1985.tb00244.x. [DOI] [PubMed] [Google Scholar]
  39. Willard H. F., Goss S. J., Holmes M. T., Munroe D. L. Regional localization of the phosphoglycerate kinase gene and pseudogene on the human X chromosome and assignment of a related DNA sequence to chromosome 19. Hum Genet. 1985;71(2):138–143. doi: 10.1007/BF00283369. [DOI] [PubMed] [Google Scholar]
  40. Willard H. F., Riordan J. R. Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders. Science. 1985 Nov 22;230(4728):940–942. doi: 10.1126/science.3840606. [DOI] [PubMed] [Google Scholar]

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