Aneuploidy pp 433-444 | Cite as

Mechanisms and Detection of Chromosome Malsegregation Using Drosophila and the Yeast SaccharomycesCerevisiae

  • James M. Mason
  • Michael A. Resnick
Part of the Basic Life Sciences book series (BLSC, volume 36)


Chromosome aneuploidy in humans may have severe consequences in the individuals in which it occurs or in the following generation (35; Evans, this Volume). Approximately 15% of recognized pregnancies result in spontaneous abortion (78). Approximately half of these result from chromosome abnormalities (13,67). The rate of aneuploidy may actually be much higher than this because early fetal losses may go undetected (12) and certain types of aneuploidy are underrepresented in this sample (5). In fact, the frequency of aneuploids among human sperm is 1.5–5% (47; Martin, this Volume). Among livebirths the frequency of aneuploidy is roughly 0.3% (4). Most of these result from trisomy of one of three autosomes, primarily chromosome 21 (Down syndrome), or from trisomy or monosomy for the sex chromosomes. Although it is generally assumed that meiotic nondisjunction is responsible for the aneuploidy in these spontaneous abortions and birth defects, mitotic aneuploidy may contribute substantially to these incidences. Mason (49) and Vig (77) have pointed out that mitotic nondisjunction in the germline will mimic meiotic nondisjunction, which may serve to explain some otherwise anomalous observations such as the paucity of monosomies among early abortuses and the high frequency of apparent meiosis 2 errors.


Down Syndrome Chromosome Pairing Chromosome Segregation Synaptonemal Complex Meiotic Recombination 
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  1. 1.
    Baker, B.S., A.T.C. Carpenter, M.S. Esposito, R.E. Esposito, and L. Sandler (1976) The genetic control of meiosis. Ann. Rev. Genet. 10: 53–134.PubMedCrossRefGoogle Scholar
  2. 2.
    Bayliss, M.W., and R. Riley (1972) Evidence of premeiotic control of chromosome pairing in Triticum aestivum. Genet. Res. 20: 201–212.Google Scholar
  3. 3.
    Bloom, K.S., E. Amaya, J. Carbon, L. Clarke, A. Hill, and E. Yeh (1984) Chromatin conformation of yeast centromeres. J. Cell Biol. 99: 1559–1568.PubMedCrossRefGoogle Scholar
  4. 4.
    Bond, D.J., and A.C. Chandley (1983) Aneuploidy, Oxford University Press, Oxford, 198 pp.Google Scholar
  5. 5.
    Bou£, J.G., A Boud, and P. Lazar (1975) Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions. Teratology 12: 11 – 26.CrossRefGoogle Scholar
  6. 6.
    Boyd, J.B., M.D. Golino, T.D. Nguyen, and M.M. Green (1976) Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. Genetics 84: 485–506.PubMedGoogle Scholar
  7. 7.
    Boynton, A.L., and J. Whitfield (1981) Calmodulin and cyclic AMP- dependent protein kinases mediate calcium-induced stimulation of DNA synthesis in rat liver cells. Cyclic Nucleotide Res. 14: 411–419.Google Scholar
  8. 8.
    Bradley, M.O., and V.I. Taylor (1983) Repair-induced DNA double-strand breaks after ultraviolet-light and either aphidocolin or 1-3-D- arabinofuranosylcytosine/hydroxyurea. Carcinogenesis 4: 1513–1517.PubMedCrossRefGoogle Scholar
  9. 9.
    Bridges, C.G. (1916) Nondisjunction as proof of the chromosome theory of heredity. Genetics 1: 1–52, 107–163.Google Scholar
  10. 10.
    Campbell, D. (1980) Association of disomic chromosome loss with EMS- induced conversion in yeast. Genetics 96: 613–625.PubMedGoogle Scholar
  11. 11.
    Campbell, D.A., and S. Fogel (1977) Association of chromosome loss with centromere-adjacent mitotic recombination in a yeast disomic haploid. Genetics 85: 573–585.PubMedGoogle Scholar
  12. 12.
    Carr, D.H. (1971) Chromosomes and abortion. In Advances in Human Genetics, Vol. II, H. Harris and K. Hirshhorn, eds. Plenum Press, New York, pp. 201–257.Google Scholar
  13. 13.
    Carr, D.H., and M. Gedeon (1977) Population cytogenetics of human abortuses. In Population Cytogenetics: Studies in Humans, E.B. Hook and I.H. Porter, eds. Academic Press, New York, pp. 1–9.Google Scholar
  14. 14.
    Carpenter, A.T.C. (1973) A meiotic mutant defective in distributive disjunction in Drosophila melanogaster. Genetics 73: 393–428.PubMedGoogle Scholar
  15. 15.
    Carpenter, A.T.C. (1975) Electron microscopy of meiosis in Drosophila melanogaster females. II. The recombination nodule-a recombination- associated structure of pachytene? Proc. Natl. Acad. Sci., USA 72: 3186–3189.PubMedCrossRefGoogle Scholar
  16. 16.
    Carpenter, A.T.C. (1984) Recombination nodules and the mechanism of crossing-over in Drosophila. In Controlling Events in Meiosis, C.W. Evans and H.G. Dickinson, eds. Company of Biologists, Ltd., Cambridge press.Google Scholar
  17. 17.
    Chafouleas, J.G., W.E. Bolton, H. Hidaka, A.E. Boyd III, and A.R. Means (1982) Calmodulin and the cell cycle: Involvement in regulation of cell-cycle progression. Cell 28: 41–50.PubMedCrossRefGoogle Scholar
  18. 18.
    Chan, C.S.M., and B.-K. Tye (1983) Organization of DNA sequnces and replication origins at yeast telomeres. Cell 33: 563–573.PubMedCrossRefGoogle Scholar
  19. 19.
    Chandley, A.C. (1968) The effect of X-rays on female germ cells of Drosophila melanogaster. III. A comparison with heat treatment on crossing over in the X chromosome. Mut. Res. 5: 93–107.CrossRefGoogle Scholar
  20. 20.
    David, J.C., D. Vinson, and M. Loir (1982) Developmental changes of DNA ligase during ram spermatogenesis. Exptl. Cell Res. 141: 357–364.PubMedCrossRefGoogle Scholar
  21. 21.
    Davis, B.K. (1971) Genetic analysis of a meiotic mutant resulting in precocious sister-centromere separation in Drosophila melanogaster. Molec. Gen. Genet. 113: 251–272.PubMedCrossRefGoogle Scholar
  22. 22.
    de Serres, F.J. (1979) Aneuploidy as a human health problem of significance in environmental mutagenesis. Environ. Health Perspectives 31: 1–2.CrossRefGoogle Scholar
  23. 23.
    Dover, G.A., and R. Riley (1973) The effects of spindle inhibitors applied before meiosis on meiotic chromosome pairing. J. Cell Sci. 12: 143–161.PubMedGoogle Scholar
  24. 24.
    Driscoll, C.J., and N.L. Darvey (1970) Chromosome pairing: Effect of colchicine on an isochromosome. Science 169: 290–291.PubMedCrossRefGoogle Scholar
  25. 24.
    Driscoll, C.J., and N.L. Darvey (1970) Chromosome pairing: Effect of colchicine on an isochromosome. Science 169: 290–291.PubMedCrossRefGoogle Scholar
  26. 24.
    Driscoll, C.J., and N.L. Darvey (1970) Chromosome pairing: Effect of colchicine on an isochromosome. Science 169: 290–291.PubMedCrossRefGoogle Scholar
  27. 27.
    Game, J.C. (1983) Radiation sensitive mutants and repair in yeast. In Yeast Genetics, Fundamental and Applied Aspects, J.F.T. Spencer, D.M. Spencer, and A.R.W. Smith, eds. Springer-Verlag, New York, pp. 109– 137.Google Scholar
  28. 28.
    Game, J.C., T.J. Zamb, R.J. Braun, M.A. Resnick, and R.M. Roth (1980) The role of radiation (rad) genes in meiotic recombination in yeast. Genetics 94: 51–68.PubMedGoogle Scholar
  29. 29.
    Gelbart, W.M. (1974) A new mutant controlling mitotic chromosome disjunction in Drosophila melanogaster. Genetics 76: 51–63.PubMedGoogle Scholar
  30. 30.
    Goldstein, L.S.B. (1980) Mechanisms of chromosome orientation revealed by two meiotic mutants in Drosophila melanogaster. Chromosoma 78: 79–111.PubMedCrossRefGoogle Scholar
  31. 31.
    Grell, R.F. (1962) A new hypothesis on the nature and sequence of meiotic events in the female of Drosophila melanogaster. Proc. Natl. Acad. Sci., USA 48: 165–172.PubMedCrossRefGoogle Scholar
  32. 32.
    Grell, R.F. (1978) High frequency recombination in centromeric and histone regions of Drosophila genomes. Nature 272: 78–80.PubMedCrossRefGoogle Scholar
  33. 33.
    Hawley, R.S. (1980) Chromosomal sites necessary for normal levels of meiotic recombination in Drosophila melanogaster. I. Evidence for and mapping of the sites. Genetics 94: 625–646.PubMedGoogle Scholar
  34. 34.
    Haynes, R.M., and B.A. Kunz (1981) DNA repair and mutagenesis in yeast. In The Molecular Biology of the Yeast Saccharomyces, J. Strathern, E. Jones, and J. Broach, eds. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 371–414.Google Scholar
  35. 35.
    Hook, E.B. (1983) Perspectives in mutation epidemiology. III. Contribution of chromosome abnormalities to human morbidity and mortality and some comments upon surveillance of chromosome mutation rates. Mut. Res. 114: 389–423.Google Scholar
  36. 36.
    Hotta, Y., M.D. Bennett, L.A. Toledo, and H. Stern (1979) Regulation of R-protein and endonuclease activities in meiocytes by homologous chromosome pairing. Chromosoma (Berl.) 72: 191–201.Google Scholar
  37. 37.
    Kempf, C., M. Schmitt, J.-M. Danse, and J. Kempf (1984) Correlation of DNA repair synthesis with ageing in mice, evidenced by quantitative autoradiography. Mechanisms of Aging and Development 26: 183–194.CrossRefGoogle Scholar
  38. 38.
    Kemphues, K.J., T.C. Kaufman, R.A. Raff, and E.C. Raff (1982) The testis-specific 8-tubulin subunit in Drosophila melanogaster has multiple function in spermatogenesis. Cell 31: 655–670.PubMedCrossRefGoogle Scholar
  39. 39.
    Klapholz, S., and R.E. Esposito (1980) Recombination and chromosome segregation during the single division meiosis in spo12-l and spo13-l diploids. Genetics 96: 589–611.PubMedGoogle Scholar
  40. 40.
    Kofman-Alfaro, S., and A.C. Chandley (1971) Radiation-initiated DNA synthesis in spermatogenic cells of the mouse. Exptl. Cell Res. 69: 33–44.PubMedCrossRefGoogle Scholar
  41. 41.
    Kunz, B.A., and R.H. Haynes (1981) Phenomenology and genetic control of mitotic recombination in yeast. Ann. Rev. Genet. 15: 57–89.PubMedCrossRefGoogle Scholar
  42. 42.
    Kunz, B.A., and R.H. Haynes (1982) DNA repair and the genetic effects of thymidylate stress in yeast. Mut. Res. 93: 353–375.CrossRefGoogle Scholar
  43. 43.
    Lindahl, T. (1979) DNA glycosylases, endonucleases for apurinic/- apyrimidinic sites, and base excision-repair. In Progress in Nucleic Acid Research and Molecular Biology, Vol. 22, W.E. Cohn, ed. Academic Press, New York, pp. 135–192.Google Scholar
  44. 44.
    Malone, R.E. (1983) Multiple mutant analysis of recombination in yeast. Molec. Gen. Genet. 189: 405–412.CrossRefGoogle Scholar
  45. 45.
    Malone, R.E., and R.E. Esposito (1981) Recombinationless meiosis in Saccharomyces cerevisiae. Molec. Cell Biol. 1: 891–901.PubMedGoogle Scholar
  46. 46.
    Margolis, R.L., and D. Job (1984) Control of microtubule stability by calmodulin dependent and independent phosphorylation. Advances in Cyclic Nuc. Res. 17: 417–425.Google Scholar
  47. 47.
    Martin, R.H., W. Balkan, K. Burns, A.W. Rademaker, C.C. Lin, and N.L. Rudd (1983) The chromosome constitution of 1,000 human spermatozoa. Hum. Genet. 63: 305–309.PubMedCrossRefGoogle Scholar
  48. 48.
    Mason, J.M. (1976) Orientation disruptor (ord): A recombination– defective and disjunction-detective meiotic mutant in Drosophila melanogaster. Genetics 84: 545–572.PubMedGoogle Scholar
  49. 49.
    Mason, J.M. (1980) A mutant in Drosophila which increases the frequency of disomic eggs. Environ. Mutagen. 2: 276.Google Scholar
  50. 50.
    Mason, J.M., E. Strobel, and M.M. Green (1984) mu-2: Mutator gene in Drosophila that potentiates the induction of terminal deficiencies. Proc. Natl. Acad. Sci., USA 91: 6090–6094.Google Scholar
  51. 51.
    Mavor, J.W. (1923) Studies on the biological effects of X-rays. Am. J. Roentgenol. Radium Ther. 10: 968 – 974.Google Scholar
  52. 52.
    Merriam, J.R., and J.N. Frost (1964) Exchange and nondisjunction of the X chromosomes in temale Drosophila melanogaster. Genetics 49: 109–122.PubMedGoogle Scholar
  53. 53.
    Mortimer, R.K., R. Contopoulou, and D. Schild (1981) Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci., USA 78: 5778-5 /82.Google Scholar
  54. 54.
    Muller, H.J. (1925) The regionally differential effect of X-rays on crossing over in autosomes of Drosophila. Genetics 10: 470–507.PubMedGoogle Scholar
  55. 55.
    Muller, H.J. (1934) The nature of genetic ettects produced by radiation. In Radiation Biology, Vol. I, A. Hollaender, ed. McGraw-Hill, New York, pp. 351–473.Google Scholar
  56. 56.
    Neff, N.F., J.H. Thomas, P. Grisafi, and D. Botstein (1983) Isolation of the β-tubulin gene from yeast and demonstration of its essential function in vivo. Cell 33: 211–219.PubMedCrossRefGoogle Scholar
  57. 57.
    Nette, E.G., Y.-P. Xi, Y.-K. Sun, A.D. Andrews, and D.W. King (1984) A correlation between aging and DNA repair in human epidermal cells. Mechanisms of Aging and Development 24: 283–292.CrossRefGoogle Scholar
  58. 58.
    Orlando, P., P. Grippo, and R. Geremia (1984) DNA repair synthesis- related enzymes during spermatogenesis in the mouse. Exptl. Cell Res. 153: 499–305.PubMedCrossRefGoogle Scholar
  59. 59.
    Parker, D. (1970) Co-ordinated nondisjunction of Y and fourth chromosomes in irradiated compound-X female Drosophila. Mut. Res. 9:307– 322.Google Scholar
  60. 60.
    Prakash, L., and S. Prakash (1977) Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae. Genetics 86: 33–55.PubMedGoogle Scholar
  61. 61.
    Prakash, S., L. Prakash, W. Burke, and B.A. Monteleone (1980) Effects ot the RAD52 gene on recombination in Saccharomyces cerevisiae. Genetics 94: 31–50.PubMedGoogle Scholar
  62. 62.
    Resnick, M.A. (1976) The repair of double strand breaks in DNA: A model involving recombination. J. Theor. Biol. 59: 97–106.PubMedCrossRefGoogle Scholar
  63. 63.
    Resnick, M.A. (1979) The induction of molecular and genetic recombination in eukaryotic cells. Adv. Radiat. Biol. 8: 175–217.Google Scholar
  64. 64.
    Resnick, M.A., J.C. Game, and S. Stasiewicz (1983) Genetic effects of UV radiation on excision-proficient and -deficient yeast during meiosis. Genetics 104: 603 - 618.PubMedGoogle Scholar
  65. 64.
    Resnick, M.A., J.C. Game, and S. Stasiewicz (1983) Genetic effects of UV radiation on excision–proficient and -deficient yeast during meiosis. Genetics 104: 603 - 618.PubMedGoogle Scholar
  66. 66.
    Rockmill, B.M., S.G. Whittaker, M.A. Resnick, and S. Fogel (1985) The detection of mitotic and meiotic aneuploidy in yeast using a gene dosage selection system in prep.Google Scholar
  67. 67.
    Sankaranarayanan, K. (1979) The role of non-disjunction in aneuploidy in man: An overview. Mut. Res. 61: 1–28.CrossRefGoogle Scholar
  68. 68.
    Savontaus, M.-L. (1975) Relationship between effects of X-rays on non-disjunction and crossing over in Drosophila melanogaster. Hereditas 80: 195–204.PubMedCrossRefGoogle Scholar
  69. 69.
    Schumaker, V.N., G.E. Richards, and H.K. Schachman (1956) A study of the kinetics of the enzymatic digestion of deoxyribonucleic acid. J. Am. Chem. Soc. 78: 4230–4236.CrossRefGoogle Scholar
  70. 70.
    Shepard, J., E.R. Boothroyd, and H. Stern (1974) The effect of colchicine on synapsis and chiasma formation in microsporocytes of Lilium. Chromosoma 44: 423–437.CrossRefGoogle Scholar
  71. 71.
    Smith, P.D. (1976) Mutagen sensitivity on Drosophila melanogaster. III. X-linked loci governing sensitivity to methyl methanesulfonate. Molec. Gen. Genet. 149: 73–85.PubMedCrossRefGoogle Scholar
  72. 72.
    Sotomayor, R.E., G.A. Sega, and R.B. Cumming (1979) An autoradio-graphic study of unscheduled DNA synthesis in the germ cells of male mice treated with X-rays and methyl methanesulfonate. Mut. Res. 62: 293–309.CrossRefGoogle Scholar
  73. 73.
    Stern, H., and Y. Hotta (1978) Regulatory mechanisms in meiotic crossing-over. Ann. Rev. Plant Physiol. 29: 415–436.CrossRefGoogle Scholar
  74. 74.
    Stromnaes, O. (1968) Genetic changes in Saccharomyces cerevisiae grown on media containing DL-p-fluorophenylalanine. Hereditas 59: 197–220.CrossRefGoogle Scholar
  75. 75.
    Sturtevant, A.H., and G.W. Beadle (1936) The relations of inversions in the X chromosome of Drosophila melanogaster to crossing-over and disjunction. Genetics 21: 554–604.PubMedGoogle Scholar
  76. 76.
    Tsutsui, T., H. Maizumi, J.A. McLachlan, and J.C. Barrett (1983) Aneuploidy induction and cell transformation by diethylstilbestrol. A possible chromosomal mechanism in carcinogenesis. Cancer Res. 43: 3814–3821.PubMedGoogle Scholar
  77. 77.
    Vig, B.K. (1984) Sequence of centromere separation, another mechanism for the origin of nondisjunction. Hum. Genet. 66: 239–243.PubMedCrossRefGoogle Scholar
  78. 78.
    Warburton, D., and F.C. Fraser (1964) Spontaneous abortion risks in man: Data from reproductive histories collected in a medical genetics unit. Am. J. Human Genet .16: 1–25.Google Scholar
  79. 79.
    Zimmering, S. (1983) The mei-9a test for chromosome loss in Drosophila: A review of assays of 21 chemicals for chromosome breakage. Environ. Mutagenesis 5: 907–921.CrossRefGoogle Scholar
  80. 80.
    Zimmering, S., and J.M. Mason (1986) A comparison of assays for chemically-induced aneuploidy in Drosophila. In Proceedings of the Fourth International Conference on Environmental Mutagens (submitted for publication).Google Scholar
  81. 81.
    Zimmering, S., J.M. Mason, and C. Osgood (1985) Current status of aneuploidy testing in Drosophila. Mut. Res, (in press).Google Scholar
  82. 82.
    Zimmermann, F.K., V.W. Mayer, R.E. Taylor-Mayer, and M.A. Resnick (1985) Acetone, methyl ethyl ketone, ethyl acetate, acetonitrile and other polar aprotic solvents are strong inducers of aneuploidy in Saccharomyces cerevisiae. Mut. Res. (in press).Google Scholar
  83. 83.
    Zimmermann, F.K., U. Gröschel-Stewart, I. Scheel, and M.A. Resnick (1985) Genetic change may be caused by interference with protein-protein interactions. Mut. Res, (in press).Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • James M. Mason
    • 1
  • Michael A. Resnick
    • 1
  1. 1.Cellular and Genetic Toxicology BranchNational Institute of Environmental Health SciencesUSA

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