Skip to main content
SpringerLink
Log in

Isolation and regional localization of a large collection (2,000) of single-copy DNA fragments on human chromosome 3 for mapping and cloning tumor suppressor genes

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

Summary

A collection of 2,000 lambda phage-carrying human single-copy inserts (> 700 bp) were isolated from two chromosome-3 flow-sorted libraries. The single-copy DNA fragments were first sorted into 3p and 3q locations and about 700 3p fragments were regionally mapped using a deletion mapping panel comprised of two humanhamster and two-human-mouse cell hybrids, each containing a chromosome 3 with different deletions in the short arm. The hybrids were extensively mapped with a set of standard 3p markers physically localized or ordered by linkage. The deletion mapping panel divided the short arm into five distinct subregions (A-E). The 3p fragments were distributed on 3p regions as follows: region A, 26%; B, 31%; C, 4%; D, 4% and E, 35%. We screened 300 single-copy DNA fragments from the distal part of 3p (regions A and B) with ten restriction endonucleases for their ability to detect restriction fragment length polymorphisms (RFLPs). Of these fragments 110 (36%) were found to detect useful RFLPs: 35% detected polymorphisms with frequency of heterozygosity of 40% or higher, and 25% with frequency of 30% or higher. All polymorphisms originated from single loci and most of them were of the base pair substitution type. These RFLP markers make it possible to construct a fine linkage map that will span the distal part of chromosome 3p and encompasses the von Hippel-Lindau disease locus. The large number of single-copy fragments (2,000) spaced every 100–150 kb on chromosome 3 will make a significant contribution to mapping and sequencing the entire chromosome 3. The 300 conserved chromosome 3 probes will increase the existing knowledge of man-mouse homologies.

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

  • Albertson DC, Sherington PD, Rabbitts PH (1989) Localization of polymorphic DNA probes frequently deleted in lung carcinoma. Hum Genet 83:127–132

    Google Scholar 

  • Aldridge J, Kunken L, Bruns G, Tantravahi U, Lalande M, Latt SA (1984) A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet 36:546–564

    Google Scholar 

  • Anglard P, Tory K, Brauch H, Weiss G, Lerman MI, Merino M, Zbar B, Linehan M (1990) Molecular analysis of DNA sequences on the short arm of chromosome 3 in sporadic human renal cell carcinoma. Cancer Res 51:1071–1077

    Google Scholar 

  • Antonarakis SE (1989) Diagnosis of genetic disorders at the DNA level. N Engl J Med 320:158–163

    Google Scholar 

  • Atchison LM, Naylor SL, Freed JJ, Comis RL (1988) Regional mapping of unique DNA sequences from human chromosome 3 derived from a flow-sorted chromosome library. Cytogenet Cell Genet 48:156–159

    Google Scholar 

  • Aviv H, Leder P (1972) Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acidcellulose. Proc Natl Acad Sci USA 69:1408–1413

    Google Scholar 

  • Barker D, Schafer M, White R (1984) Restriction sites containing CpG show a higher fequency of polymorphisms in human DNA. Cell 36:131–138

    Google Scholar 

  • Bonner T, O'Brien SJ, Nash WB, Rapp UR, Morton CC, Leder P (1984) Two human homologs of the rat (mil) oncogene are located on human chromosomes 3 and 4. Science 223:71–74

    Google Scholar 

  • Brauch H, Johnson B, Hovis J, Yano T, Gazdar A, Pettengill OS, Graziano S, Sorenson GD, Poiesz BJ, Minna J, Linehan M, Zbar B (1987) Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med 317:1109–1113

    Google Scholar 

  • Brauch H, Lerman MI, Glenn G, Hampsch K, Grzeschik K-H, McBride OW, Zbar B (1989) A somatic cell hybrid panel for physical assignment of 3p probes. Cytogenet Cell Genet 51: 968

    Google Scholar 

  • Brauch H, Hosoe S, Li F, Kovacs G, Seizinger B, Decker J, Sandberg AS, Brown RS, Tory K, Linehan WM, Lerman MI, Zbar B (1990a). Loss of the derivative 8 chromosome in hereditary renal cell carcinoma associated with a 3;8 translocation. Am J Hum Genet 43: A3

    Google Scholar 

  • Brauch H, Tory K, Kotler F, Gazdar AF, Pettengill OS, Johnson B, Graziano S, Winton, Buy CHCM, Sorenson GD, Poiesz BJ, Minna JD, Zbar B (1990b) Molecular mapping of chromosome 3p deletion sites in human lung cancer. Genes Chromosomes Cancer 1:240–246

    Google Scholar 

  • Cavanee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL (1983) Expression of recessive alleles by chromosome mechanisms in retinoblastoma. Nature 305:779–784

    Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Article  CAS  PubMed  Google Scholar 

  • Cohen AJ, Li FP, Berg S, Marchetto D, Tsai S, Jacobs S (1979) Hereditary renal cell carcinoma associated with a chromosome translocation. N Engl J Med 301:592–595

    Google Scholar 

  • Comings DE (1973) A general theory of carcinogenesis. Proc Natl Acad Sci USA 70:3324–3328

    Google Scholar 

  • Copeland NG, Gilbert DJ, Jenkins NA, Zbar B, Brauch H, Lerman MI (1990) Markers that flank the human von Hippel-Lindau disease gene in the interval 3p25-p26 map to mouse chromosome 6 at a distance of 1.5 cM. Am J Hum Genet 43:A4

    Google Scholar 

  • Cremer T, Lichter P, Borden J, Ward DC, Mannelidis L (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosomespecific library probes. Hum Genet 80:235–246

    Google Scholar 

  • Deaven LL, Van Dilla MA, Bartholdi MF, Carrano AV, Fuscoe JC, Gray JW, Hildebrand CE, Moyzics RK, Perlman J (1986) Construction of human chromosome-specific DNA libraries from flow-sorted chromosomes. Cold Spring Harbor Symp Quant Biol 51:159–167

    Google Scholar 

  • Detrisac CJ, Sens MA, Garvin JA, Spicer SS, Sens DA (1984) Tissue culture of human kidney epithelial cells of proximal tubule origin. Kidney 25:383–390

    Google Scholar 

  • Donis-Keller H, Green P, Helms C, Cartinhour S, Weifenbach B, Stephens K, Keith TP, Bowden DS, Smith DR, Lander ES, Botstein D, Acots G, Rediker KS, Gravins T, Brown VA, Rising MB, Parker C, Powers JA, Watt DE (1987) A genetic linkage map of the human genome. Cell 51:319–337

    Google Scholar 

  • Drabkin H, Kao F-T, Hartz J, Hart I, Gazdar A, Weinberger C, Evans R, Gerber M (1988) Localized of human ERBA2 to the 3p22→3p24.1 region of chromosome 3 and variable deletion in small cell lung cancer. Proc Natl Acad Sci USA 85:9258–9262

    Google Scholar 

  • Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to a high specific activity. Anal Biochem 137:266–267

    Google Scholar 

  • Fuscoe JC, McNinch JC, Collins CC, Van Dilla MA (1989) Human chromosome-specific DNA libraries: construction and purity analysis. Cytogenet Cell Genet 50:211–215

    Google Scholar 

  • Gerber MJ, Drabkin HA, Firnhaber C, Miller YE, Soggin CH, Smith DI (1988) Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel. Am J Hum Genet 43:442–451

    Google Scholar 

  • Gillian TC, Healey ST, MacDonald ME, Stewart GD, Wasmuth JJ, Tanzi RE, Roy JC, Gusella JF (1987) Isolation of polymorphic DNA fragments from human chromosome 4. Nucleic Acids Res 15:1445–1457

    Google Scholar 

  • Glenn GM, Choyke PL, Zbar B, Linehan WM (1990) Von Hippel-Lindau disease: clinical review and molecular genetics. Probl Urol 4:312–330

    Google Scholar 

  • Goodman BK, Goodman MD, Lubin MB, Braunstein GD, Rotter JI, Schreck RR (1989) Cytogenetic characterization of renal cell carcinoma in von Hippel-Lindau syndrome. Cytogenet Cell Genet 41:242

    Google Scholar 

  • Harris H, Miller OJ, Klein G, Worst P, Tachibana T (1969) Suppression of malignancy by cell fusion. Nature 223:363–368

    Google Scholar 

  • Harris P, Morton CC, Guglielmi P, Li F, Kelly K, Latt SA (1986) Mapping by chromosome sorting of several gene probes, including c-myc, to the derivative chromosomes of a 3;8 translocation associated with familial renal carcinoma. Cytometry 7: 589–594

    Google Scholar 

  • ISCN (1985) An international system for human cytogenetic nomenclature. In: Harnden DG, Klinger HP (eds) Published in collaboration with Cytogenet Cell Genet. Karger, Basel

    Google Scholar 

  • Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823

    Google Scholar 

  • Knudson AG (1978) Retinoblastoma: a protolytic hereditary neoplasm. Semin Oncol 5:57–60

    Google Scholar 

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

    Google Scholar 

  • Lange K, Kunkel L, Aldridge L, Latt SA (1985) Accurate and super-accurate gene mapping. Am J Hum Genet 37:853–867

    Google Scholar 

  • Latif F, Hosoe S, Brauch H, Glenn GM, Daniel L, Orcutt ML, Delisio J, Hampsch K, Linehan WM, Zbar B, Lerman MI (1990) A single recombination event between the von Hippel-Lindau disease (VHL) gene and D3S18 (3q26) loci on human chromosome 3. Am J Hum Genet 43: A11

    Google Scholar 

  • Leppert M, O'Connell P, Nakamura Y, Cartwright P, Lathrop M, Lalouel J-M, White R (1987) Two linkage groups on chromosome 3. Cytogenet Cell Genet 46:648

    Google Scholar 

  • Lerman MI, Thayer RE, Singer MF (1983) KpnI family of long interspersed repeated DNA sequences in primates: polymorphism of family members and evidence for transcription. Proc Natl Acad Sci USA 80:3966–3970

    Google Scholar 

  • Lichter P, Cremer T, Borden J, Mannelides L, Ward DC (1988) Delineation of individual chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet 80:224–234

    Google Scholar 

  • Lichter P, Chang Tang C-J, Call K, Hermanson G, Evans GA, Housman D, Ward DC (1990) High-resolution mapping of human chromosome 11 by in situ hybridization with Cosmid Clones. Science 247:64–69

    Google Scholar 

  • Maniatis T, Hardeson RC, Lacy E, Lauer C, O'Connell D, Quon D, Sim K, Efstratiadis A (1978) The isolation of structural genes from libraries of eucaryotic DNA. Cell 15:687–695

    Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.

    Google Scholar 

  • McBride OW, Battey J, Hollis GF, Swan DC, Siebenlist U, Leder P (1982) Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14. Nucleic Acids Res 10:8155–8170

    Google Scholar 

  • McKusick VA (1986) No. 19330: von Hippel-Lindau syndrome. In: Medelian inheritance in man, 7th edn. The Johns Hopkins University Press, Baltimore London

    Google Scholar 

  • Naylor SL, Sakaguchi AY, Barker D, White R, Shows TB (1984) DNA polymorphic loci mapped to human chromosomes 3, 5, 9, 11,17, 18 and 22. Proc Natl Acad Sci USA 81:2447–2451

    Google Scholar 

  • Naylor SL, Johnson BE, Minna JD, Sakaguchi AY (1987) Loss of heterozygosity of chromosome 3p markers in small cell lung carcinoma. Nature 329:451–454

    Google Scholar 

  • Naylor SL, Bishop DT (1989) Report of the committee on the genetic constitution of chromosome 3. Cytogenet Cell Genet 51: 106–120

    Google Scholar 

  • Patterson B, Jones C, Morse H, Rumsby P, Miller Y, Davis R (1989) Structural gene coding for multifunctional protein carrying orotate phosphoribosyltransferase and OMP decarboxylase activity is located on long arm of human chromosome 3. Somat Cell Genet 9:359–374

    Google Scholar 

  • Rettig WJ, Brzeschik K-H, Yenamandra AK, Garcia E, Old LJ (1988) Definition of selectable cell surface markers for human chromosomes and chromosome segments in rodent-human hybrids. Somatic Cell Mol Genet 14:223–231

    Google Scholar 

  • Rigby RMY, Dieckman M, Rhodes C, Berg P (1977) Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase. J Mol Biol 113:237–251

    Google Scholar 

  • Schumm JW, Knowlton RG, Braman JC, Barker DF, Botstein D, Akots G, Brown VA, Gravins TC, Helms C, Hsiao K, Rediker K, Thurston JG, Donis-Keller H (1988) Identification of more than 500 RFLPs by screening random genomic libraries. Am J Hum Genet 42:143–159

    Google Scholar 

  • Searle AG, Peters J, Lyon MF, Hall JG, Evans EP, Edwards JH, Buckle VJ (1989) Chromosome maps of man and mouse. IV. Ann Hum Genet 53:89–140

    Google Scholar 

  • Seizinger Br, Rouleau GA, Ozelius LJ, Lane LH, Farmer GE, Lamiell JM, Haines J, Yuen JWM, Collins D, Majoor-Krakauer D, Bonner T, Mathew C, Rubenstein A, Halperin J, McConkie-Rosell A, Green JS, Trofatter JA, Ponder BAJ (1988) Von Hippel-Lindau disease maps to the reagion of chromosome 3 assosicated with renal cell carcinoma. Nature 332:268–269

    Google Scholar 

  • Tory K, Brauch H, Linehan M, Barba D, Oldfield D, Filling-Katz M, Seizinger B, Nakamura Y, White R, Marshall F, Lerman MI, Zbar B (1989) Specific genetic changes in tumors associated with von Hippel-Lindau disease. J Natl Cancer Inst 81: 1097–1106

    Google Scholar 

  • Trent JM, Kaneko Y, Mitelman F (1989) Report of the committee on structural chromosome changes in neoplasia. Cytogenet Cell Genet 51:N1–4

    Google Scholar 

  • Wang-Peng J, Kao-Shan CS, Lee EC, Bunn PA, Carney DN, Gazdar AE, Minna JD (1982) Specific chromosome defect associated with human small cell lung cancer: deletion 3p (14–23) Science 215:181–182

    Google Scholar 

  • Waters JJ, Ibson JM, Twentyman PR, Bleehem NM, Rabbitts PH (1988) Cytogenetic abnormalities in human small cell lung carcinoma: cell lines characterized for myc gene amplification. Cancer Genet Cytogenet 30:212–223

    Google Scholar 

  • Yunis JJ, Sawyer JR, Ball DW (1978) The characterization of high-resolution G-banded chromosomes of man. Chromosoma 67:293–307

    Google Scholar 

  • Zabarovsky ER, Allikmets RL (1986) An improved technique for the efficient construction of gene libraries by partial filling-in of cohesive ends. Gene 42:119–123

    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 

  • Zbar B, Hosoe S, Brauch H, Latif F, Glenn GM, Daniel L, Bale S, Choyke P, Gorin M, Oldfield E, Berman A, Goodman J, Orcutt ML, Hampsch K, Delisio J, Modi W, McBride W, Lineham WM, Lerman MI (1990) Close linkage of the von Hippel-Lindau disease gene to a highly polymorphic marker located at 3p26. Am J Hum Genet 43: A205

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Frederick Cancer Research Facility, Program Resources Inc., 21701, Frederick, MD, USA

    Krista Hampsch & John Delisio

  2. Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA

    O. Wesley McBride

  3. Institut für Humangenetik der Universität, Bahnhofstrasse 7a, W-3550, Marburg, Federal Republic of Germany

    Karl-Heinz Grzeschik

  4. NCI-Navy Medical Oncology Branch, Naval Hospital, 20892, Bethesda, MD, USA

    Takashi Takahashi & John Minna

  5. Urologic Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA

    Patrick Anglard & W. Marston Linehan

  6. Laboratory of Immunobiology, National Cancer Institute, National Institute of Health, Frederick Cancer Research Facility, Fort Detrick, Building 560, Room 12–71, 21701, Frederick, MD, USA

    Michael I. Lerman, Farida Latif, Gladys M. Glenn, Lambert N. Daniel, Hiltrud Brauch, Shigeto Hosoe, Mary Lou Orcutt & Berton Zbar

Authors
  1. Michael I. Lerman
    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. Gladys M. Glenn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lambert N. Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiltrud Brauch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shigeto Hosoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Krista Hampsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. John Delisio
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mary Lou Orcutt
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. O. Wesley McBride
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Karl-Heinz Grzeschik
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takashi Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. John Minna
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Patrick Anglard
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. W. Marston Linehan
    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

Lerman, M.I., Latif, F., Glenn, G.M. et al. Isolation and regional localization of a large collection (2,000) of single-copy DNA fragments on human chromosome 3 for mapping and cloning tumor suppressor genes. Hum Genet 86, 567–577 (1991). https://doi.org/10.1007/BF00201543

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00201543

Keywords

Search

Navigation