Skip to main content
Log in

Mitotic chiasmata, gene density, and oncogenes

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

Summary

Chromosomes with regions rich in mitotic chiasmata in Bloom syndrome (1, 3, 6, 11, 12, 17, 19, and 22) have been compared for various parameters to similar-sized chromosomes 2, 4, 7, 10, 9, 18, 20, and 21 with the following results: (1) The number of genes localized on the test chromosomes is significantly higher (248) than that in the control chromosomes (133). (2) The number of trisomic abortions is significantly lower (45) for the test chromosomes than for the control chromosomes (140). (3) Homogeneously stained regions in neuroblastoma lie at chiasma-containing regions on chromosome arms 1p, 6p, 17q, and 19p or q. (4) The average chiasma density of regions with at least one oncogene is 2.414, whereas that of regions containing no known oncogene is 1.137; however, the difference is not statistically significant. The association of constant cancer chromosome breaks is also in the positive direction, but is not statistically significant.

Our tentative conclusion is that the chiasma-rich regions which are Q-dark and early-replicating, and therefore assumed to contain active “housekeeping” genes are extended in interphase. Thus they are available for mitotic crossing-over. In the trisomic state they act as trisomy lethals, leading to early abortions. Being gene-rich they are more likely to contain oncogenes which is reflected also in their agreement with cancer breakpoints. The very high incidence of cancer in Bloom syndrome is a further indication of the possible association of cancer-related phenomena and mitotic crossingover.

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

Access this article

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

  • Biedler JL, Spengler BA (1976) Metaphase chromosome anomaly: Association with drug resistance and cell-specific products. Science 191:185–187

    PubMed  Google Scholar 

  • Bishop JM (1983) Cellular oncogenes and retroviruses. Annu Rev Biochem 52:301–354

    Article  PubMed  Google Scholar 

  • Boué J, Daketsé M-J, Deluchat C, Ravisé N, Yvert S, Boué A (1976) Identification par les bandes Q et G des anomalies chromosomiques dans les avortements spontanes. Ann Genet (Paris) 19:233–239

    Google Scholar 

  • Brito-Bulapulle V, Atkin NB (1981) Breakpoints in chromosome 1 abnormalities of 218 human neoplasms. Cancer Genet Cytogenet 4:215–225

    Article  PubMed  Google Scholar 

  • Cowan J, Halaban R, Lane AT, Francke U (1984) Involvement of 6p in malignant melanoma. Am J Hum Genet 36:27S

    Google Scholar 

  • Dayton AI, Selden JR, Laws G, Dorney DJ, Finan J, Tripputi P, Emanuel BS, Rovera G, Nowell PC, Croce CM (1984) A human c-erb-A oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia. Proc Natl Acad Sci USA 81:4495–4499

    PubMed  Google Scholar 

  • de la Chapelle A, Berger R (1984) Report of the committee on chromosome rearrangements in neoplasia and on fragile sites. Cytogenet Cell Genet 37:274–311

    PubMed  Google Scholar 

  • German J, Crippa LP, Bloom D (1974) Bloom's syndrome. III. Analysis of the chromosome aberration characteristic of this disorder. Chromosoma 48:361–366

    Article  PubMed  Google Scholar 

  • Goldman MA, Holmquist GP, Gray MC, Caston LA, Nag A (1984) Replication timing of genes and middle repetitive sequences. Science 224:686–692

    PubMed  Google Scholar 

  • Hecht F, Hecht BK (1984) Autosomal fragile sites and cancer. Am J Hum Genet 36:718–720

    PubMed  Google Scholar 

  • Holmquist G, Gray M, Porter T, Jordan J (1982) Characterization of Giemsa dark- and light-band DNA. Cell 31:121–129

    Article  PubMed  Google Scholar 

  • Korenberg JR, Therman E, Denniston C (1978) Hot spots and functional organization of human chromosomes. Hum Genet 43:13–22

    PubMed  Google Scholar 

  • Kuhn EM (1974) Nonrandom localization of mitotic crossing-over in Bloom's syndrome. Genetics 77:Suppl 37–38

    Google Scholar 

  • Kuhn EM (1976) Localization by Q-banding of mitotic chiasmata in cases of Bloom's syndrome. Chromosoma 57:1–11

    Article  PubMed  Google Scholar 

  • Kuhn EM (1978) Mitotic chiasmata and other quadriradials in mitomycin C-treated Bloom's syndrome lymphocytes. Chromosoma 66:287–297

    PubMed  Google Scholar 

  • Le Beau MM, Westbrook CA, Diaz MO, Rowley JD (1984) In situ hybridization studies of c-src: Evidence for two distinct loci on human chromosomes No. 1 and No. 20. Am J Hum Genet 36:32S

  • Lindgren V, Ares M, Bernstein LB, Weiner AM, Francks U (1984) Mapping of human small nuclear RNA genes by in situ hybridization. Am J Hum Genet 36:101S

    Google Scholar 

  • McKusick VA (1984) Human gene map. Johns Hopkins, Baltimore

    Google Scholar 

  • Niebugr E (1978) Cytologic observations in 35 individuals with a 5pkaryotype. Hum Genet 42:143–156

    Article  PubMed  Google Scholar 

  • Patau K (1973) Three main classes of constitutive heterochromatin in man: Intercalary, Y-type and centric. In: Wahrman J, Lewis KR (eds) Chromosomes today 4. Wiley, New York, p 430

    Google Scholar 

  • Patau K, Therman E (1969) Mitotic crossing-over in man. Genetics 61:Suppl 45–46

    Google Scholar 

  • Pihko H, Therman E, Uchida IA (1981) Partial 11q trisomy syndrome. Hum Genet 58:129–134

    PubMed  Google Scholar 

  • Rabin M, Watson M, Barker PE, Ryan J, Breg WR, Ruddle FH (1984) NRAS transforming gene maps to region p11»p13 on chromosome 1 by in situ hybridization. Cytogenet Cell Genet 38:70–72

    PubMed  Google Scholar 

  • Rowley JD (1983) Consistent chromosome abnormalities in human leukemia and lymphoma. Cancer Invest 1:267–280

    PubMed  Google Scholar 

  • Sakaguchi AY, Zabel BU, Grzeschik K-H, Law ML, Ellis RW, Scolnick EM, Naylor SL (1984) Regional localization of two human cellular Kirsten ras genes on chromosomes 6 and 12. Mol Cell Biol 4:989–993

    PubMed  Google Scholar 

  • Schimke RT (1982) Summary. In: Schimke RT (ed) Gene amplification. Cold Spring Harbor Laboratory, New York, pp 317–333

    Google Scholar 

  • Schroeder TM, German J (1974) Bloom's syndrome and Fanconi's anemia: Demonstration of two distinctive patterns of chromosome disruption and rearrangement. Hum Genet 25:299–306

    Google Scholar 

  • Taisne C de, Gegonne A, Stehelin D, Bernheim A, Berger R (1984) Chromosomal localization of the human proto-oncogene c-ets. Nature 310:581–583

    PubMed  Google Scholar 

  • Therman E (1980) Human chromosomes: Structure, behavior, effects. Springer, New York

    Google Scholar 

  • Therman E, Kuhn EM (1976) Cytological demonstration of mitotic crossing-over in man. Cytogenet Cell Genet 17:254–267

    PubMed  Google Scholar 

  • Therman E, Kuhn EM (1981) Mitotic crossing-over and segregation in man. Hum Genet 59:93–100

    PubMed  Google Scholar 

  • Therman E, Otto PG, Shahidi NT (1981) Mitotic recombination and segregation of satellites in Bloom's syndrome. Chromosoma 82:627–636

    Article  PubMed  Google Scholar 

  • Tsujimoto Y, Yunis J, Onorato-Showe L, Erikson J, Nowell PC, Croce CM (1984) Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science 224:1403–1406

    PubMed  Google Scholar 

  • Yunis JJ (1983) The chromosomal basis of human neoplasia. Science 221:227–236

    PubMed  Google Scholar 

  • Yunis JJ (1984a) Clinical significance of high resolution chromosomes in the study of acute leukemias and non-Hodgkin's lymphomas. In: Fairbanks VF (ed) Current hematology 3. Wiley, New York, pp 353–391

    Google Scholar 

  • Yunis JJ (1984b) Fragile sites and predisposition to leukemia and lymphoma. Cancer Genet Cytogenet 12:85–88

    Article  PubMed  Google Scholar 

  • Zhou X, Reidy JR, Chen ATL (1982) Chromosome fragility in folic acid-deficient medium. Am J Hum Genet 34:153A

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuhn, E.M., Therman, E. & Denniston, C. Mitotic chiasmata, gene density, and oncogenes. Hum Genet 70, 1–5 (1985). https://doi.org/10.1007/BF00389448

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00389448

Keywords

Navigation