Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome

Nature Genetics volume 10, pages 13–19 (1995)Cite this article

Abstract

Ocular albinism type 1 (OA1) is an X–linked disorder characterized by severe impairment of visual acuity, retinal hypopigmentation and the presence of macromelanosomes. We isolated a novel transcript from the OA1 critical region in Xp22.3–22.2 which is expressed at high levels in RNA samples from retina, including the retinal pigment epithelium, and from melanoma. This gene encodes a protein of 424 amino acids displaying several putative transmembrane domains and sharing no similarities with previously identified molecules. Five intragenic deletions and a 2 bp insertion resulting in a premature stop codon were identified from DMA analysis of patients with OA1, indicating that we have identified the OA1 gene.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. King, R.A., Hearing, V.J., Creel, D.J. & Getting, W.S., in The Metabolic and Molecular Bases of Inherited Disease. (eds Scriver, C. R., Beaudet, A.L., M.D., Sly, W.S. & Valle, D.) 4353–4392 (McGraw-Hill, Inc., New York, 1995).

    Google Scholar 

  2. McKusick, V.A., Francomano, C.A. & Antonarakis, S.E. Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotypes, 10th edition (The Johns Hopkins University Press, Baltimore, 1992).

    Google Scholar 

  3. Falls, H.F. Sex-linked ocular albinism displaying typical fundus changes in the female heterozygote. Am. J. Ophthal. 34, 41–50 (1951).

    Article  CAS  Google Scholar 

  4. Lang, G.E., Rott, H.-D. & Pfeiffer, R.A. X-linked ocular albinism. Characteristic pattern of affection in female carriers. Ophthalmic Paediatr. Genet. 11, 265–271 (1990).

    Article  CAS  Google Scholar 

  5. O'Donnell, F.E. Jr., Hambrick, G.W. Jr., Green, W.R., Iliff, W.J. & Stone, D.L. X-linked ocular albinism: an oculocutaneous macromelanosomal disorder. Arch. Ophthal. 94, 1883–1892 (1976).

    Article  Google Scholar 

  6. Creel, D.J., Summers, C.G. & King, R.A. Visual anomalies associated with albinism. Ophthal. Paediat. Genet 11, 193–200 (1990).

    Article  CAS  Google Scholar 

  7. Kriss, A., Russell-Eggitt, I., Harris, C.M., Lloyd, I.C. & Taylor, D. Aspects of albinism. Ophthal. Paediat. Genet. 13, 89–100 (1992).

    Article  CAS  Google Scholar 

  8. Bergen, A.A.B. et al. Localization of the X-linked ocular albinism gene (OA1) between DXS278/DXS237 and DXS143/DXS16 by linkage analysis. Ophthal. Paediat. Genet. 3, 165–170 (1990).

    Article  Google Scholar 

  9. Bergen, A.A.B. et al. Multipoint linkage analysis in X-linked ocular albinism of the Nettleship-Falls type. Hum. Genet. 88, 162–166 (1991).

    Article  CAS  Google Scholar 

  10. Schnur, R.E. et al. Linkage analysis in X-linked ocular albinism. Genomics 9, 605–613 (1991).

    Article  CAS  Google Scholar 

  11. Charles, S.J., Moore, A.T. & Yates, J.R.W. Genetic mapping of X-linked ocular albinism: linkage analysis in British families. J. med. Genet. 29, 552–554 (1992).

    Article  CAS  Google Scholar 

  12. Ballabio, A. & Andria, G. Deletions and translocations involving the distal short arm of the human X chromosome: review and hypotheses. Hum. molec. Genet. 1, 221–227 (1992).

    Article  CAS  Google Scholar 

  13. Ballabio, A. et al. Isolation and characterization of a steroid sulphatase cDNA clone: Genomic deletions in patients with X-chromosome-linked ichthyosis. Proc. natn. Acad. Sci. U.S.A. 84, 4519–4523 (1987).

    Article  CAS  Google Scholar 

  14. Franco, B. et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 353, 529–536 (1991).

    Article  CAS  Google Scholar 

  15. Franco, B. et al. A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy. Cell 81, 1–20 (1995).

    Article  Google Scholar 

  16. Schaefer, L. et al. A high resolution deletion map of human chromosome Xp22. Nature Genet. 4, 272–279 (1993).

    Article  CAS  Google Scholar 

  17. Wapenaar, M.C. et al. The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions. Hum. molec. Genet 2, 947–952 (1993).

    Article  CAS  Google Scholar 

  18. Wapenaar, M.C. et al. A YAC-based binning strategy facilitating the rapid assembly of cosmid contigs: 1.6 Mb of overlapping cosmids in Xp22. Hum. molec. Genet 3, 1155–1161 (1994).

    Article  CAS  Google Scholar 

  19. Bassi, M.T. et al. A submicroscopic deletion in a patient with isolated X-linked ocular albinism (OA1). Hum. molec. Genet. 3, 647–648 (1994).

    Article  CAS  Google Scholar 

  20. Schiaffino, M.V. et al. Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region. Hum. molec. Genet. 4, 373–382 (1995).

    Article  CAS  Google Scholar 

  21. Page, D.C., Fisher, E.M.C., McGillivray, B. & Brown, L.G. Additional deletion in sex-determining region of human Y chromosome resolves paradox of X,t(Y;22) female. Nature 346, 279–281 (1990).

    Article  CAS  Google Scholar 

  22. Nishimura, S.I. et al. Two cases of steroid sulfatase deficiency with complex phenotype due to contiguous gene deletions. Am. J. med. Genet 40, 260–263 (1991).

    Article  CAS  Google Scholar 

  23. Gamer, A. & Jay, B.S. Macromelanosomes in X-linked ocular albinism. Histopathology 4, 243–254 (1980).

    Article  Google Scholar 

  24. Wong, L., O'Donnell, F.E., & Green, W.R. Giant pigment granules in the retinal pigment epithelium of a fetus with X-linked ocular albinism. Ophthal. Paediat Genet. 2, 47–65 (1983).

    Article  Google Scholar 

  25. Yoshiike, T., Manabe, M., Hayakawa, M. & Ogawa, H. Macromelanosomes in X-linked ocular albinism (XLOA). Acta Derm. Venereol. 65, 66–69 (1985).

    CAS  PubMed  Google Scholar 

  26. Cooper, D.N. & Krawczak, M. Mechanisms of insertional mutagenesis in human genes causing genetic disease. Hum. Genet. 87, 409–415 (1991).

    CAS  PubMed  Google Scholar 

  27. Johnson, G.J., Gillan, J.G. & Pearce, W.G., Albinism in NewFoundland. Canad. J. Ophthal. 6, 237–248 (1971).

    CAS  PubMed  Google Scholar 

  28. Bergen, A.A. et al. Linkage analysis in X-linked ocular albinism. Genomics 9, 605–613 (1991).

    Article  Google Scholar 

  29. Bergen, A.A.B. et al. Refinement of the localization of the X-linked ocular albinism gene. Genomics 16, 272–273 (1993).

    Article  CAS  Google Scholar 

  30. Charles, S.J., Green, J.S., Moore, A.T., Barton, D.E. & Yates, J.R.W. Genetic mapping of X-linked ocular albinism: Linkage analysis in a large Newfoundland kindred. Genomics 16, 259–261 (1993).

    Article  CAS  Google Scholar 

  31. Sambrook, J., Fritsch, E.F. & Maniatis, T., Cloning: A Laboratory Manual. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989).

    Google Scholar 

  32. Sealy, P.G., Whittaker, P.A. & Southem, E.M. Removal of repeated sequences from hybridization probes. Nucl. Acids Res. 13, 1905–1922 (1985).

    Article  Google Scholar 

  33. Frohman, M.A., Dush, M.K. & Martin, G.R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).

    Article  CAS  Google Scholar 

  34. Marck, C.C. ‘DNA Strider’: a ‘C’ program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers. Nucl. Acids Res. 16, 1829–1836 (1988).

    Article  CAS  Google Scholar 

  35. Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5, 874–879 (1989).

    Article  CAS  Google Scholar 

  36. Renieri, A. et al. Small frameshift deletions within the COL4A5 gene in juvenile-onset Alport syndrome. Hum. Genet 92, 417–420 (1993).

    Article  CAS  Google Scholar 

  37. Peissel, B. et al. A novel frameshift deletion in type IV collagen a5 gene in a juvenil-type Alport syndrome patient. Hum. Mut 3, 386–390 (1994).

    Article  CAS  Google Scholar 

  38. Wapenaar, M.C., Kievits, T., Meera Khan, P., Pearson, P.L. & van Ommen, G.J.B. Isolation and characterization of cell hybrids containing human Xp-chromosome fragments. Cytogenet. Cell Genet 54, 10–14 (1990).

    Article  CAS  Google Scholar 

  39. Kyte, J.P. & Doolittle, R.F. A simple method for displaying the hydropathic character of a protein. J. molec. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Maria T. Bassi and M. Vittoria Schiaffino: The first two authors contributed equally to the work.

Authors and Affiliations

  1. Department of Molecular Biology, University of Siena, 53100, Italy

    Maria T. Bassi, Alessandra Renieri, Lucia Galli, Mirella Bruttini & Andrea Ballabio

  2. Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Milano, 20132, Italy

    M. Vittoria Schiaffino, Filomena De Nigris, Marinella Gebbia & Andrea Ballabio

  3. The Netherlands Ophthalmic Research Institute, Amsterdam, 1100AC, The Netherlands

    Arthur A.B. Bergen

  4. Department of Ophthalmology and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Richard A. Lewis

Authors
  1. Maria T. Bassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Vittoria Schiaffino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Renieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filomena De Nigris
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lucia Galli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mirella Bruttini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marinella Gebbia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arthur A.B. Bergen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Richard A. Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andrea Ballabio
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bassi, M., Schiaffino, M., Renieri, A. et al. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet 10, 13–19 (1995). https://doi.org/10.1038/ng0595-13

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0595-13

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing