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
. 1992 Mar 15;89(6):2135–2139. doi: 10.1073/pnas.89.6.2135

Isolation of a candidate gene for choroideremia.

D E Merry 1, P A Jänne 1, J E Landers 1, R A Lewis 1, R L Nussbaum 1
PMCID: PMC48611  PMID: 1549574

Abstract

Choroideremia is an X chromosome-linked retinal dystrophy of unknown pathogenesis. We have isolated cDNAs from a human retinal library with a genomic probe located at the X chromosomal breakpoint in a female with choroideremia and an X;13 translocation. This cDNA spans the breakpoint in the X;13 translocation female and is deleted in males who have choroideremia as part of a complex phenotype including mental retardation and deafness. However, this cDNA detects no alterations in the DNA of 34 males with isolated choroideremia. Nonetheless, the cDNA does detect reduced or absent levels of mRNA in three-quarters of male patients with an apparently intact gene. These data support the hypothesis that this cDNA represents the gene in which mutations cause choroideremia.

Full text

PDF
2136

Images in this article

2137Image
on p.2137
2138Image
on p.2138

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. Boggs B. A., Nussbaum R. L. Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. Somat Cell Mol Genet. 1984 Nov;10(6):607–613. doi: 10.1007/BF01535226. [DOI] [PubMed] [Google Scholar]
  3. Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O'Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990 Jul 13;62(1):193–201. doi: 10.1016/0092-8674(90)90253-b. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Cremers F. P., van de Pol D. J., Diergaarde P. J., Wieringa B., Nussbaum R. L., Schwartz M., Ropers H. H. Physical fine mapping of the choroideremia locus using Xq21 deletions associated with complex syndromes. Genomics. 1989 Jan;4(1):41–46. doi: 10.1016/0888-7543(89)90312-1. [DOI] [PubMed] [Google Scholar]
  6. Cremers F. P., van de Pol D. J., van Kerkhoff L. P., Wieringa B., Ropers H. H. Cloning of a gene that is rearranged in patients with choroideraemia. Nature. 1990 Oct 18;347(6294):674–677. doi: 10.1038/347674a0. [DOI] [PubMed] [Google Scholar]
  7. Cremers F. P., van de Pol T. J., Wieringa B., Hofker M. H., Pearson P. L., Pfeiffer R. A., Mikkelsen M., Tabor A., Ropers H. H. Molecular analysis of male-viable deletions and duplications allows ordering of 52 DNA probes on proximal Xq. Am J Hum Genet. 1988 Oct;43(4):452–461. [PMC free article] [PubMed] [Google Scholar]
  8. Dryja T. P., McGee T. L., Reichel E., Hahn L. B., Cowley G. S., Yandell D. W., Sandberg M. A., Berson E. L. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990 Jan 25;343(6256):364–366. doi: 10.1038/343364a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Flannery J. G., Bird A. C., Farber D. B., Weleber R. G., Bok D. A histopathologic study of a choroideremia carrier. Invest Ophthalmol Vis Sci. 1990 Feb;31(2):229–236. [PubMed] [Google Scholar]
  11. Fodor E., Lee R. T., O'Donnell J. J. Analysis of choroideraemia gene. Nature. 1991 Jun 20;351(6328):614–614. doi: 10.1038/351614b0. [DOI] [PubMed] [Google Scholar]
  12. Ghosh M., McCulloch C., Parker J. A. Pathological study in a female carrier of choroideremia. Can J Ophthalmol. 1988 Jun;23(4):181–186. [PubMed] [Google Scholar]
  13. 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]
  14. Inglehearn C. F., Bashir R., Lester D. H., Jay M., Bird A. C., Bhattacharya S. S. A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa. Am J Hum Genet. 1991 Jan;48(1):26–30. [PMC free article] [PubMed] [Google Scholar]
  15. Inoue T., Cech T. R. Secondary structure of the circular form of the Tetrahymena rRNA intervening sequence: a technique for RNA structure analysis using chemical probes and reverse transcriptase. Proc Natl Acad Sci U S A. 1985 Feb;82(3):648–652. doi: 10.1073/pnas.82.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
  17. Koenig M., Hoffman E. P., Bertelson C. J., Monaco A. P., Feener C., Kunkel L. M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50(3):509–517. doi: 10.1016/0092-8674(87)90504-6. [DOI] [PubMed] [Google Scholar]
  18. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kozak M. At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. J Mol Biol. 1987 Aug 20;196(4):947–950. doi: 10.1016/0022-2836(87)90418-9. [DOI] [PubMed] [Google Scholar]
  20. Lesko J. G., Lewis R. A., Nussbaum R. L. Multipoint linkage analysis of loci in the proximal long arm of the human X chromosome: application to mapping the choroideremia locus. Am J Hum Genet. 1987 Apr;40(4):303–311. [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. MacDonald I. M., Sandre R. M., Wong P., Hunter A. G., Tenniswood M. P. Linkage relationships of X-linked choroideremia to DXYS1 and DXS3. Hum Genet. 1987 Nov;77(3):233–235. doi: 10.1007/BF00284475. [DOI] [PubMed] [Google Scholar]
  23. Matsui Y., Kikuchi A., Araki S., Hata Y., Kondo J., Teranishi Y., Takai Y. Molecular cloning and characterization of a novel type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding protein. Mol Cell Biol. 1990 Aug;10(8):4116–4122. doi: 10.1128/mcb.10.8.4116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Merry D. E., Lesko J. G., Siu V., Flintoff W. F., Collins F., Lewis R. A., Nussbaum R. L. DXS165 detects a translocation breakpoint in a woman with choroideremia and a de novo X; 13 translocation. Genomics. 1990 Apr;6(4):609–615. doi: 10.1016/0888-7543(90)90494-f. [DOI] [PubMed] [Google Scholar]
  25. Merry D. E., Lesko J. G., Sosnoski D. M., Lewis R. A., Lubinsky M., Trask B., van den Engh G., Collins F. S., Nussbaum R. L. Choroideremia and deafness with stapes fixation: a contiguous gene deletion syndrome in Xq21. Am J Hum Genet. 1989 Oct;45(4):530–540. [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Nussbaum R. L., Lewis R. A., Lesko J. G., Ferrell R. Choroideremia is linked to the restriction fragment length polymorphism DXYS1 at XQ13-21. Am J Hum Genet. 1985 May;37(3):473–481. [PMC free article] [PubMed] [Google Scholar]
  28. Rechsteiner M. Regulation of enzyme levels by proteolysis: the role of pest regions. Adv Enzyme Regul. 1988;27:135–151. doi: 10.1016/0065-2571(88)90014-3. [DOI] [PubMed] [Google Scholar]
  29. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  30. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  31. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  32. Rosen K. M., Lamperti E. D., Villa-Komaroff L. Optimizing the northern blot procedure. Biotechniques. 1990 Apr;8(4):398–403. [PubMed] [Google Scholar]
  33. 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]
  34. SORSBY A., FRANCESCHETTI A., JOSEPH R., DAVEY J. B. Choroideremia; clinical and genetic aspects. Br J Ophthalmol. 1952 Oct;36(10):547–581. doi: 10.1136/bjo.36.10.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sankila E. M., Lehner T., Eriksson A. W., Forsius H., Kärnä J., Page D., Ott J., de la Chapelle A. Haplotype and multipoint linkage analysis in Finnish choroideremia families. Hum Genet. 1989 Dec;84(1):66–70. doi: 10.1007/BF00210674. [DOI] [PubMed] [Google Scholar]
  37. Sankila E. M., de la Chapelle A., Kärnä J., Forsius H., Frants R., Eriksson A. Choroideremia: close linkage to DXYS1 and DXYS12 demonstrated by segregation analysis and historical-genealogical evidence. Clin Genet. 1987 May;31(5):315–322. doi: 10.1111/j.1399-0004.1987.tb02815.x. [DOI] [PubMed] [Google Scholar]
  38. Schnur R. E., Ledbetter S. A., Ledbetter D. H., Merry D. E., Nussbaum R. L. New polymorphisms at the DXS98 locus and confirmation of its location proximal to FRAXA by in situ hybridization. Am J Hum Genet. 1989 Feb;44(2):248–254. [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Siu V. M., Gonder J. R., Jung J. H., Sergovich F. R., Flintoff W. F. Choroideremia associated with an X-autosomal translocation. Hum Genet. 1990 Apr;84(5):459–464. doi: 10.1007/BF00195820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Troen B. R. Colony screening of genomic cosmid libraries. Methods Enzymol. 1987;151:416–426. doi: 10.1016/s0076-6879(87)51033-3. [DOI] [PubMed] [Google Scholar]
  43. Wallace M. R., Marchuk D. A., Andersen L. B., Letcher R., Odeh H. M., Saulino A. M., Fountain J. W., Brereton A., Nicholson J., Mitchell A. L. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990 Jul 13;249(4965):181–186. doi: 10.1126/science.2134734. [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