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. 1991 Dec;49(6):1361–1371.

Adrenoleukodystrophy: a complex chromosomal rearrangement in the Xq28 red/green-color-pigment gene region indicates two possible gene localizations.

R Feil 1, P Aubourg 1, J Mosser 1, A M Douar 1, D Le Paslier 1, C Philippe 1, J L Mandel 1
PMCID: PMC1686466  PMID: 1746561

Abstract

We have characterized a complex chromosomal rearrangement in band Xq28, in an adrenoleukodystrophy patient who also has blue-cone monochromacy. A 130-kb region upstream from the color-vision pigment genes was isolated as yeast artificial chromosome or cosmid clones. Another Xq28 sequence, not included in the above region, was obtained by cloning a deletion breakpoint from the patient. Using probes derived from the cloned sequences, we have shown that the rearrangement affects the color-pigment genes and includes two deletions, most likely separated by a large (greater than 110-kb) inversion. One deletion encompasses part of the pigment gene cluster and 33 kb of upstream sequences and accounts for the patient's blue-cone monochromacy. If this rearrangement also caused ALD, the disease gene would be expected to lie within or close to one of the deletions. However, deletions were not detected in a 50-kb region upstream of the red-color-pigment gene in 81 other ALD patients. Two CpG islands were mapped, at 46 and 115 kb upstream from the pigment genes.

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Selected References

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

  1. Albertsen H. M., Abderrahim H., Cann H. M., Dausset J., Le Paslier D., Cohen D. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4256–4260. doi: 10.1073/pnas.87.11.4256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Aubourg P. R., Sack G. H., Jr, Meyers D. A., Lease J. J., Moser H. W. Linkage of adrenoleukodystrophy to a polymorphic DNA probe. Ann Neurol. 1987 Apr;21(4):349–352. doi: 10.1002/ana.410210406. [DOI] [PubMed] [Google Scholar]
  4. Aubourg P. R., Sack G. H., Jr, Moser H. W. Frequent alterations of visual pigment genes in adrenoleukodystrophy. Am J Hum Genet. 1988 Mar;42(3):408–413. [PMC free article] [PubMed] [Google Scholar]
  5. Aubourg P., Feil R., Guidoux S., Kaplan J. C., Moser H., Kahn A., Mandel J. L. The red-green visual pigment gene region in adrenoleukodystrophy. Am J Hum Genet. 1990 Mar;46(3):459–469. [PMC free article] [PubMed] [Google Scholar]
  6. Bellis M., Pagès M., Roizès G. A simple and rapid method for preparing yeast chromosomes for pulsed field gel electrophoresis. Nucleic Acids Res. 1987 Aug 25;15(16):6749–6749. doi: 10.1093/nar/15.16.6749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown W. T., Gross A. C., Goonewardena P., Ferrando C., Dobkin C., Jenkins E. C. Linkage in fragile X families of three distal flanking markers: ST14, DX13, and F8. Am J Med Genet. 1991 Feb-Mar;38(2-3):343–346. doi: 10.1002/ajmg.1320380235. [DOI] [PubMed] [Google Scholar]
  8. Burke D. T., Carle G. F., Olson M. V. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science. 1987 May 15;236(4803):806–812. doi: 10.1126/science.3033825. [DOI] [PubMed] [Google Scholar]
  9. Davies K. E., Mandel J. L., Monaco A. P., Nussbaum R. L., Willard H. F. Report of the committee on the genetic constitution of the X chromosome. Cytogenet Cell Genet. 1990;55(1-4):254–313. doi: 10.1159/000133019. [DOI] [PubMed] [Google Scholar]
  10. Del Mastro R. G., Bundey S., Kilpatrick M. W. Adrenoleucodystrophy: a molecular genetic study in five families. J Med Genet. 1990 Nov;27(11):670–675. doi: 10.1136/jmg.27.11.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feil R., Aubourg P., Heilig R., Mandel J. L. A 195-kb cosmid walk encompassing the human Xq28 color vision pigment genes. Genomics. 1990 Feb;6(2):367–373. doi: 10.1016/0888-7543(90)90578-i. [DOI] [PubMed] [Google Scholar]
  12. Feil R., Palmieri G., d'Urso M., Heilig R., Oberlé I., Mandel J. L. Physical and genetic mapping of polymorphic loci in Xq28 (DXS15, DXS52, and DXS134): analysis of a cosmid clone and a yeast artificial chromosome. Am J Hum Genet. 1990 Apr;46(4):720–728. [PMC free article] [PubMed] [Google Scholar]
  13. Holm C., Meeks-Wagner D. W., Fangman W. L., Botstein D. A rapid, efficient method for isolating DNA from yeast. Gene. 1986;42(2):169–173. doi: 10.1016/0378-1119(86)90293-3. [DOI] [PubMed] [Google Scholar]
  14. Jennings M. W., Jones R. W., Wood W. G., Weatherall D. J. Analysis of an inversion within the human beta globin gene cluster. Nucleic Acids Res. 1985 Apr 25;13(8):2897–2906. doi: 10.1093/nar/13.8.2897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karathanasis S. K., Ferris E., Haddad I. A. DNA inversion within the apolipoproteins AI/CIII/AIV-encoding gene cluster of certain patients with premature atherosclerosis. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7198–7202. doi: 10.1073/pnas.84.20.7198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Karn J., Matthes H. W., Gait M. J., Brenner S. A new selective phage cloning vector, lambda 2001, with sites for XbaI, BamHI, HindIII, EcoRI, SstI and XhoI. Gene. 1984 Dec;32(1-2):217–224. doi: 10.1016/0378-1119(84)90049-0. [DOI] [PubMed] [Google Scholar]
  17. Koeberl D. D., Bottema C. D., Ketterling R. P., Bridge P. J., Lillicrap D. P., Sommer S. S. Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene. Am J Hum Genet. 1990 Aug;47(2):202–217. [PMC free article] [PubMed] [Google Scholar]
  18. Lewis R. A., Holcomb J. D., Bromley W. C., Wilson M. C., Roderick T. H., Hejtmancik J. F. Mapping X-linked ophthalmic diseases. III. Provisional assignment of the locus for blue cone monochromacy to Xq28. Arch Ophthalmol. 1987 Aug;105(8):1055–1059. doi: 10.1001/archopht.1987.01060080057028. [DOI] [PubMed] [Google Scholar]
  19. MacDonald D., Town M., Mason P., Vulliamy T., Luzzatto L., Goff D. K. Deficiency in red blood cells. Nature. 1991 Mar 14;350(6314):115–115. doi: 10.1038/350115a0. [DOI] [PubMed] [Google Scholar]
  20. Migeon B. R., Moser H. W., Moser A. B., Axelman J., Sillence D., Norum R. A. Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5066–5070. doi: 10.1073/pnas.78.8.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nathans J., Davenport C. M., Maumenee I. H., Lewis R. A., Hejtmancik J. F., Litt M., Lovrien E., Weleber R., Bachynski B., Zwas F. Molecular genetics of human blue cone monochromacy. Science. 1989 Aug 25;245(4920):831–838. doi: 10.1126/science.2788922. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Nizetić D., Zehetner G., Monaco A. P., Gellen L., Young B. D., Lehrach H. Construction, arraying, and high-density screening of large insert libraries of human chromosomes X and 21: their potential use as reference libraries. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3233–3237. doi: 10.1073/pnas.88.8.3233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oberlé I., Camerino G., Kloepfer C., Moisan J. P., Grzeschik K. H., Hellkuhl B., Hors-Cayla M. C., Van Cong N., Weil D., Mandel J. L. Characterization of a set of X-linked sequences and of a panel of somatic cell hybrids useful for the regional mapping of the human X chromosome. Hum Genet. 1986 Jan;72(1):43–49. doi: 10.1007/BF00278816. [DOI] [PubMed] [Google Scholar]
  25. Riley J., Butler R., Ogilvie D., Finniear R., Jenner D., Powell S., Anand R., Smith J. C., Markham A. F. A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucleic Acids Res. 1990 May 25;18(10):2887–2890. doi: 10.1093/nar/18.10.2887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sack G. H., Jr, Raven M. B., Moser H. W. Color vision defects in adrenomyeloneuropathy. Am J Hum Genet. 1989 Jun;44(6):794–798. [PMC free article] [PubMed] [Google Scholar]
  27. Schonk D., Coerwinkel-Driessen M., van Dalen I., Oerlemans F., Smeets B., Schepens J., Hulsebos T., Cockburn D., Boyd Y., Davis M. Definition of subchromosomal intervals around the myotonic dystrophy gene region at 19q. Genomics. 1989 Apr;4(3):384–396. doi: 10.1016/0888-7543(89)90346-7. [DOI] [PubMed] [Google Scholar]
  28. Suzuki H., Kawarabayasi Y., Kondo J., Abe T., Nishikawa K., Kimura S., Hashimoto T., Yamamoto T. Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem. 1990 May 25;265(15):8681–8685. [PubMed] [Google Scholar]
  29. 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]
  30. Wanders R. J., van Roermund C. W., van Wijland M. J., Schutgens R. B., van den Bosch H., Schram A. W., Tager J. M. Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty acids. Biochem Biophys Res Commun. 1988 Jun 16;153(2):618–624. doi: 10.1016/s0006-291x(88)81140-9. [DOI] [PubMed] [Google Scholar]
  31. Weichhold G. M., Klobeck H. G., Ohnheiser R., Combriato G., Zachau H. G. Megabase inversions in the human genome as physiological events. Nature. 1990 Sep 6;347(6288):90–92. doi: 10.1038/347090a0. [DOI] [PubMed] [Google Scholar]
  32. Willems P. J., Vits L., Wanders R. J., Coucke P. J., Van der Auwera B. J., Van Elsen A. F., Raeymaekers P., Van Broeckhoven C., Schutgens R. B., Dacremont G. Linkage of DNA markers at Xq28 to adrenoleukodystrophy and adrenomyeloneuropathy present within the same family. Arch Neurol. 1990 Jun;47(6):665–669. doi: 10.1001/archneur.1990.00530060077022. [DOI] [PubMed] [Google Scholar]
  33. Yen P. H., Allen E., Marsh B., Mohandas T., Wang N., Taggart R. T., Shapiro L. J. Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange. Cell. 1987 May 22;49(4):443–454. doi: 10.1016/0092-8674(87)90447-8. [DOI] [PubMed] [Google Scholar]
  34. Youssoufian H., Antonarakis S. E., Aronis S., Tsiftis G., Phillips D. G., Kazazian H. H., Jr Characterization of five partial deletions of the factor VIII gene. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3772–3776. doi: 10.1073/pnas.84.11.3772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. van Oost B. A., van Zandvoort P. M., Tünte W., Brunner H. G., Hoogeboom A. J., Maaswinkel-Mooy P. D., Bakkeren J., Hamel B., Ropers H. H. Linkage analysis in X-linked adrenoleukodystrophy and application in post- and prenatal diagnosis. Hum Genet. 1991 Feb;86(4):404–407. doi: 10.1007/BF00201845. [DOI] [PubMed] [Google Scholar]

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