Skip to main content
SpringerLink
Log in

Von Hippel-Lindau disease: identification of deletion mutations by pulsed-field gel electrophoresis

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Von Hippel-Lindau disease (VHL) is an inherited multisystem neoplastic disorder. We prepared a 2.5-megabase (Mb) restriction map of the region surrounding the VHL gene and identified and characterized overlapping deletions in three unrelated patients affected with VHL. The smallest nested deletion (100 kb) was located within a 510-kb NruI fragment detected by 19–63′. The rearrangements detected will be useful in isolating and evaluating candidate cDNAs for the VHL gene. The detailed physical map will be useful in studying the organization and structure of genes in the VHL region.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albertsen HM, Abderrahim H, Cann HM, Dausset J, Le Paslier D, Cohen D (1990) Construction and characterization of a yeast artificial chromosome library containing seven haploid genome equivalents. Proc Natl Acad Sci USA 87:4256–4260

    Google Scholar 

  • Bird A (1987) CpG islands as gene markers in the vertebrate nucleus. Trends Genet 3:341–347

    Google Scholar 

  • Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms tumor locus. Cell 60:509–520

    Google Scholar 

  • Church GM, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995

    Google Scholar 

  • Delisio J, Latif F, Glenn GM, Yao M, Brauch H, Hampsch K, Orcutt ML, Zbar B, Lerman MI (1991) A new polymorphic probe on chromosome 3p: LIB 19–63′ (D3S601). Nucleic Acds Res 19:966

    Google Scholar 

  • Feinberg AP, Vogelstein B (1984) A technique for radio labeling DNA restriction endonuclease fragments to high specific activity. Addendum. Anal Biochem 137:266–267

    Google Scholar 

  • Ganly PS, Rabbits PH (1991) Polymerase chain reaction (PCR) for detection of HindIII polymorphisms at the D3F15S2 locus. Nucleic Acids Res 19:3758

    Google Scholar 

  • Gemmill R, Coyle-Morris JF, McPeek FD, Ware-Uribe L, Hecht F (1987) Construction of long range restriction maps in human DNA using pulsed field gel electrophoresis. Gene Anal Tech 4:119–131

    Google Scholar 

  • Glenn GM, Daniel LN, Choyke PL, Linehan WM, Oldfield E, Gorin MB, Hosoe S, Latif F, Weiss G, Walther MM, Lerman MI, Zbar B (1991) Von Hippel-Lindau disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet 87:207–210

    Google Scholar 

  • Glenn GM, Linehan WM, Hosoe S, Latif F, Yao M, Choyke P, Gorin MB, Chew E, Oldfield E, Manolatos C, Orcutt ML, Walther MM, Weiss G, Tory K, Jensson O, Lerman MI, Zbar B (1992) Screening for von Hippel-Lindau disease by DNA-polymorphism analysis. JAMA 267:1226–1231

    Google Scholar 

  • Go RCP, Lamiell JM, Hsia YE, Yuen JW-M, Paik Y (1984) Segregation and linkage analyses of von Hippel-Lindau disease among 220 descendants from one kindred. Am J Hum Genet 36:131–142

    Google Scholar 

  • Hosoe S, Brauch H, Latif F, Glenn G, Daniel L, Bale S, Choyke P, Gorin M, Oldfield E, Berman A, Goodman J, Orcutt ML, Hampsch K, Delisio J, Modi W, McBride W, Anglard P, Weiss G, Walther MM, Linehan WM, Lerman MI, Zbar B (1990) Localization of the von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics 8:634–640

    Google Scholar 

  • Joslyn G, Carlson M, Thiveris A, Albertsen H, Gelbert L, Samowitz W, Groden J, Stevens J, Spiro L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, McPherson J, Wasmuth J, Le Paslier D, Abderrahim H, Cohen D, Leppert M, White R (1991) Identification of deletion mutations and three new genes at the familial polyposis locus. Cell 66:601–613

    Google Scholar 

  • Knudson AG Jr (1986) Genetics of human cancer. Annu Rev Genet 20:231–251

    Google Scholar 

  • Kovacs G, Erlandsson R, Boldog F, Ingvarsson S, Muller-Brechlin R, Klein G, Sumegi J (1988) Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci USA 85:1571–1575

    Google Scholar 

  • Lamiell JM, Salazar FG, Hsia YE (1989) Von Hippel-Lindau disease affecting 43 members of a single kindred. Medicine (Baltimore) 68:1–29

    Google Scholar 

  • Latif F, Duh F-M, Gnarra J, Tory K, Kuzmin I, Yao M, Stackhouse T, Modi W, Geil L, Schmidt L, Li H, Orcutt ML, Maher E, Richards F, Ferguson-Smith M, Le Paslier D, Linehan M, Zbar B, Lerman MI (1993 a) Von Hippel-Lindau syndrome: cloning and identification of the plasma membrane Ca++ transporting ATPase isoform 2 gene that resides in the von HippelLindau gene region. Cancer Res 53:861–867

    Google Scholar 

  • Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kusmin I, Modi W, Geil L, Schmidt L, Zhou F, Li H, Wei M, Chen F, Glenn G, Choyke P, Walther MM, Weng Y, Duan D-SR, Dean M, Glavac D, Richards FM, Crossey PA, Ferguson-Smith MA, Le Paslier D, Chumakov I, Cohen D, Chinault AC, Maher ER, Linehan WM, Zbar B, Lerman MI (1993b) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260:1317–1320

    Google Scholar 

  • Liu W, Vance J, Smith DI (1992) cA479 (D3S719): a cosmid mapped telomeric of the von Hippel-Lindau disease gene contains the D3S18 locus. Hum Mol Genet 1:201

    Google Scholar 

  • Maher E, Bentley E, Yates JRW, Barton D, Jennings A, Fellows I, Ponder MA, Ponder BAJ, Benjamin C, Harris R, Ferguson-Smith MA (1990) Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic linkage analysis. J Neurol Sci 100:27–30

    Google Scholar 

  • Maher ER, Iselius L, Yates JRW, Littler M, Benjamin C, Harris R, Sampson J, Williams A, Ferguson-Smith MA, Morion N (1991a) Von Hippel-Lindau disease: a genetic study. J Med Genet 28:443–447

    Google Scholar 

  • Maher ER, Bentley E, Yates JRW, Latif F, Lerman M, Zbar B, Affara NA, Ferguson-Smith MA (1991b) Mapping of the von Hippel-Lindau disease gene to a small region of chromosome 3p by genetic linkage analysis. Genomics 10:957–960

    Google Scholar 

  • Melmon KL, Rosen SW (1964) Lindau's disease: review of the literature and study of a large kindred. Am J Med 36:595–617

    Google Scholar 

  • Nelson DS (1991) Current methods for YAC clone characterization. Genet Anal Tech Appl 7:100–106

    Google Scholar 

  • Neumann HPH, Wiestler OD (1991) Clustering of features of von ippel-Lindau syndrome: evidence of a complex genetic locus. Lancet 337:1052–1054

    Google Scholar 

  • Neumann HPH, Schempp W, Wienker TF (1988) High-resolution chromosome banding and fragile site studies in von Hippel-Lindau syndrome. Cancer Genet Cytogenet 31:41–46

    Google Scholar 

  • Nicholson DH, Green WR, Kenyon KR (1976) Light and electron microscopic study of early lesions in angiomatosis retinae. Am J Ophthalmol 82:193–204

    Google Scholar 

  • Patterson D, Jones C, Morse H, Rumsby P, Miller Y, Davis R (1983) Structural gene coding for multifunctional protein carrying orotate phosphoribosyl-transferase and OMP decarboxylase activity is located on the long arm of human chromosome 3. Somat Cell Genet 9:359–374

    Google Scholar 

  • Richards EM, Maher ER, Latif F, Phipps M, Tory K, Crossey PA, Lush M, Oostra B, Gustavson KH, Green J, Turner G, Yates JRW, Linehan M, Afara NA, Lerman M, Zbar B, Ferguson-Smith MA (1993) Detailed genetic mapping of the von Hippel-Lindau disease tumor supressor gene. J Med Genet 30:104–107

    Google Scholar 

  • Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JWM, Collins D, Majoor-Krakauer D, Bonner T, Matthew C, Rubenstein A, Halperin J, McConkie-Rosell A, Green JS, Trofatter JA, Ponder BA, Eierman L, Bowner MI, Schimke R, Oostra B, Aronin N, Smith DI, Drabkin H, Waziri MW, Hobbs WJ, Martuza RL, Conneally PM, Hsia YE, Gusella JF (1988) Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 332:268–269

    Google Scholar 

  • Seizinger BR, Smith DI, Filling-Katz MR, Neumann H, Green JS, Choyke P, Anderson KM, Freiman RN, Hsia YE, Collins D, Halperin J, Lamiell JM, Oostra B, Waziri MH, Gorin MB, Scherer G, Drabkin HA, Aronin N, Schinzel A, Martuza RL, Gusella JF, Haines JL (1991) Genetic flanking markers refine diagnostic criteria and provide new insights into the genetics of von Hippel-Lindau disease. Proc Natl Acad Sci USA 88:2864–2868

    Google Scholar 

  • Tory K, Brauch H, Linehan M, Barba D, Oldfield E, Filling-Katz M, Seizinger B, Nakamura Y, White R, Marshall FF, Lerman MI, Zbar B (1989) Specific genetic change in tumors associated with von Hippel-Lindau disease. J Natl Cancer Inst 81:1097–1101

    Google Scholar 

  • Tory K, Latif F, Modi W, Schmidt L, Wei M-W, Li H, Cobler P, Orcutt ML, Delisio J, Geil L, Zbar B, Lerman MI (1992) A genetic linkage map of 96 loci on the short arm of human chromosome 3. Genomics 13:275–286

    Google Scholar 

  • Vance JM, Small KW, Jones MA, Stajich JM, Yamaoka LH, Roses AD, Hung W-Y, Pericak-Vance M (1990) Confirmation of linkage in von Hippel-Lindau disease. Genomics 6:565–567

    Google Scholar 

  • Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, Wolff RK, Culver M, Carey JC, Copeland NG, Jenkins NA, White R, O'Connell P (1990) Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62:187–192

    Google Scholar 

  • Zbar B, Brauch H, Talmadge C, Linehan M (1987) Loss of alleles on the short arm of chromosome 3 in renal cell carcinoma. Nature 327:721–724

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, 21702, Frederick, MD, USA

    Masahiro Yao, Farida Latif, Mary Lou Orcutt, Igor Kuzmin, Fang wei Zhou & Michael Lerman

  2. Program Resources Inc., Dyn Corporation, 21702, Frederick, MD, USA

    Thomas Stackhouse, Kalman Tory & Fuh mei Duh

  3. Development of Pathology, Cambridge University School of Medicine, Cambridge, UK

    Frances Richards & Eamonn Maher

  4. Jefferson Cancer Institute, Thomas Jefferson University, 19107, Philadelphia, PA, USA

    Sal LaForgia & Kay Huebner

  5. Centre d'Etude du Polymorphisme Humaine, Paris, France

    Denis Le Pasilier

  6. Urologic Oncology, Surgery Branch, National Cancer Institute, 20892, Bethesda, MD, USA

    Marston Linehan

Authors
  1. Masahiro Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farida Latif
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mary Lou Orcutt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Igor Kuzmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Stackhouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fang wei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kalman Tory
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fuh mei Duh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Frances Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eamonn Maher
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sal LaForgia
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kay Huebner
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Denis Le Pasilier
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Marston Linehan
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Michael Lerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Berton Zbar
    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

Yao, M., Latif, F., Orcutt, M.L. et al. Von Hippel-Lindau disease: identification of deletion mutations by pulsed-field gel electrophoresis. Hum Genet 92, 605–614 (1993). https://doi.org/10.1007/BF00420947

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00420947

Keywords

Search

Navigation