Trisomy 21

Molecular and Cytogenetic Studies of Nondisjunction
  • Gordon D. Stewart
  • Terry J. Hassold
  • David M. Kurnit
Part of the Advances in Human Genetics book series (AHUG, volume 17)


Chromosomal imbalance is the leading known cause of mental retardation (Smith and Berg, 1976), spontaneous abortion (Boué et al, 1975; Carr and Gedeon, 1978; Hassold et al, 1978), and congenital heart defects in man (Rowe and Uchida, 1961; Tandon and Edwards, 1973; Park et al, 1977). Our understanding of nondisjunction is at a crossroads. Recent advances in molecular genetics and cytogenetics have afforded glimpses into the mechanisms of nondisjunction in man, and these advances will soon enable us to determine how and why nondisjunction for chromosome 21 occurs. This review has an agnostic, but optimistic, outlook. We feel that few fundamental questions relevant to nondisjunction for chromosome 21 have been resolved, but that the protocols and techniques required to obtain fundamental answers are at hand.


Down Syndrome Parental Origin Pericentromeric Region Acrocentric Chromosome Chiasma Frequency 
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  1. Aldridge, J., Kunkel, L., Brans, G., Tantravahi, U., Lalande, M., Brewster, T., Moreau, E., Wilson, M., Bromley, W., Latt, S. A., and Lange, K., 1984, A strategy to reveal high frequency restriction fragment length polymorphisms along the human X chromosome, Am. J. Hum. Genet. 376:546–564.Google Scholar
  2. Alfi, O. S., Chang, R., and Azen, S. P., 1980, Evidence for genetic control of nondisjunction in man, Am. J. Hum. Genet. 32:477–483.PubMedGoogle Scholar
  3. Antonarakis, S. E., Kittur, S. D., Metaxotou, C., Watkins, P. C., and Patel, A. S., 1985, Analysis of DNA haplotypes suggests a genetic predisposition to trisomy 21 associated with DNA sequences on chromosome 21, Proc. Natl. Acad. Sci. USA 82:3360–3364.PubMedGoogle Scholar
  4. Antonarakis, S. E., Chakravarti, A., Warren, A. C., Slaugenhaupt, S. A., Wong, C., Halloran, S. L., and Metaxotou, C., 1986, Reduced recombination rate on chromosomes 21 that have undergone nondisjunction, Cold Spring Harbor Symp. Quant. Biol. 51:185–190.Google Scholar
  5. Ayme, S., and Lippman-Hand, A., 1982, Maternal-age effect in aneuploidy: Does altered embryonic selection play a role? Am. J. Hum. Genet. 34:558–565.PubMedGoogle Scholar
  6. Ayme, S., Baccichetti, C., Bricarelli, F. D., Dallapiccola, B., Lungarotti, D., Mikkelsen, M., and Nevin, M., 1986, Factors involved in chromosomal nondisjunc-tion: A European collaborative study, in: EEC 7th International Congress of Human Genetics, Abstracts, Part I:C IV. 19.Google Scholar
  7. Babu, A., Macera, M. J., and Verma, R. S., 1986, Intensity heteromorphisms of human chromosome 15p by DA/DAPI technique, Hum. Genet. 73:298–300.PubMedGoogle Scholar
  8. Bender, W., Akam, M., Karch, F., Beachy, P. A., Peifer, M., and Spierer, P., 1983, Molecular genetics of the bithorax complex in Drosophila melanogaster, Science 221:23–29.PubMedGoogle Scholar
  9. Biddle, F., Eates, B., and Oland, L., 1986, Strain difference in survival of XO embryos in the mouse, Am. J. Hum. Genet. 39:A104.Google Scholar
  10. Botstein, D., White, R. L., Skolnick, M., and Davis, R. W., 1980, Construction of a genetic linkage map in man using restriction fragment length polymorphisms, Am. J. Hum. Genet. 32:314–331.PubMedGoogle Scholar
  11. Bott, C. E., Sekhon, B. S., and Lubs, H. A., 1975, Unexpected high frequency of paternal origin of trisomy 21, Am. J. Hum. Genet. 27:20A.Google Scholar
  12. Boué, J. G., and Boué, A., 1973, Increased frequency of chromosomal anomalies after induced ovulation, Lancet i:679–680.Google Scholar
  13. Boué, J., Boué, A., and Lazar, P., 1975, Retrospective and prospective epidemiological studies of 1,506 karyotyped spontaneous abortions, Teratology 12:11–26.PubMedGoogle Scholar
  14. Bridges, C. B., 1916, Nondisjunction as proof of the chromosome theory of heredity, Genetics 1:1–52, 107–163.PubMedGoogle Scholar
  15. Carr, D. H., and Gedeon, M. M., 1978, Q-banding of chromosomes in human spontaneous abortions, Can. J. Genet. Cytol. 20:415–425.PubMedGoogle Scholar
  16. Carothers, A., 1987, Down syndrome and maternal age: The effect of erroneous assignment of parental origin, Am. J. Hum. Genet. 40:147–150.PubMedGoogle Scholar
  17. Caspersson, T., Zech, L., Johansson, C., and Modest, E. J., 1970, Identification of human chromosomes by DNA-binding fluorescent agents, Chromosoma 30:215–227.PubMedGoogle Scholar
  18. Cattanach, B. M., and Kirk, M., 1985, Differential activity of maternally and paternally derived chromosome regions in mice, Nature 315:496–498.PubMedGoogle Scholar
  19. Choo, K. H., Vissel, B., Brown, R., Filby, R. G., and Earle, E., 1988, Homologous alpha satellite sequences on human acrocentric chromosomes with selectivity of chromosomes 13, 14 and 21: Implications for recombination between nonhomologues and Robertsonian translocations, Nucleic Acids Res. 16:1273–1284.PubMedGoogle Scholar
  20. Cuckle, H. S., Wald, N. J., and Lindenbaum, R. H., 1984, Maternal serum alpha-fetoprotein measurement: A screening test for Down syndrome, Lancet i:926–929.Google Scholar
  21. Del Mazo, J., Castillo, A. M., and Abrisqueta, J. A., 1982, Trisomy 21: Origin of nondisjunction, Hum. Genet. 63:316–320.Google Scholar
  22. DiMaio, M. S., Baumgarten, A., Greenstein, R. M., Saal, H. M., and Mahoney, M. J., 1987, Screening for fetal Down’s syndrome in pregnancy by measuring maternal serum alpha-fetoprotein levels, N. Engl. J. Med. 317:342–346.PubMedGoogle Scholar
  23. Donlon, T. A., Lalande, M., Wyman, A., Bruns, G., and Latt, S. A., 1986, Isolation of molecular probes associated with the chromosome #15 instability in the Prader-Willi syndrome, Proc. Natl. Acad. Sci. USA 83:4409–4412.Google Scholar
  24. Erickson, J. D., 1981, Paternal age and Down syndrome, Am. J. Hum. Genet. 31:489–497.Google Scholar
  25. Evans, H. J., Buckland, R. A., and Pardue, M. L., 1974, Location of the genes coding for 18S and 28S ribosomal RNA in the human genome, Chromosoma 48:405–426.Google Scholar
  26. Ferguson-Smith, M. A., and Handmaker, S. D., 1986, Observations on the satellited human chromosomes, Lancet 1:638.Google Scholar
  27. Flannery, D. B., and Jackson-Cook, C. K., 1986, Thyroid antibodies are an independent risk factor for nondisjunction of chromosome 21, Am. J. Hum. Genet 39(Suppl.):A113.Google Scholar
  28. Ford, J. H., and Lester, P., 1978, Chromosomal variants on nondisjunction, Cytogenet. Cell Genet. 21:300–303.PubMedGoogle Scholar
  29. Gosden, J. R., Mitchell, A. R., Buckland, R. A., Clayton, R. P., and Evan, H. J., 1975, The location of four human satellite DNAs on human chromosomes, Exp. Cell Res. 92:148–158.PubMedGoogle Scholar
  30. Grell, R. F., 1979, Origin of meiotic nondisjunction in Drosophila females, Environ. Health Perspect. 31:33–39.PubMedGoogle Scholar
  31. Hamerton, J. L., 1971, Human Cytogenetics, Vol. II, Clinical Cytogenetics, Academic Press, New York.Google Scholar
  32. Hansson, A., and Mikkelsen, M., 1978, The origin of the extra chromosome 21 in Down syndrome. Studies of fluorescent variants and satellite association in 26 informative families, Cytogenet. Cell Genet. 20:194–203.PubMedGoogle Scholar
  33. Harlap, S., Shiono, P. H., Pellegrin, F., Golbus, M., Bachman, R., Mann, J., Schmidt, L., and Lewis, J. P., 1979, Chromosome abnormalities in oral contraceptive breakthrough pregnancies, Lancet i: 1342–1343.Google Scholar
  34. Hassold, T., 1986, Chromosome abnormalities in human reproductive wastage, Trends Genet. 2:105–110.Google Scholar
  35. Hassold, T. J., Matsuyama, A., Newlands, I. M., Matsuura, J. S., Jacobs, P. A., Manuel, B., and Tsuei, J. A., 1978, Cytogenetic study of spontaneous abortions in Hawaii, Ann. Hum. Genet. 41:443–454.PubMedGoogle Scholar
  36. Hassold, T., Jacobs, P. A., Kline, J., Stein, Z., and Warburton, D., 1980, Effect of maternal age on autosomal trisomies, Ann. Hum. Genet. 44:19–36.Google Scholar
  37. Hassold, T., Jacobs, P. A., and Pettay, D., 1987, Analysis of nucleolar organizing regions in patients of trisomic spontaneous abortions, Hum. Genet. 76:381–384.PubMedGoogle Scholar
  38. Henderson, A. S., Warburton, D., and Atwood, K. C., 1972, Location of ribosomal DNA in the human chromosome complement, Proc. Natl. Acad. Sci. USA 69:3394–3398.PubMedGoogle Scholar
  39. Henderson, S. A., and Edwards, R. G., 1968, Chiasma frequency and maternal age in mammals, Nature 218:22–28.PubMedGoogle Scholar
  40. Hook, E, B., and Regal, R. R., 1984, A search for a paternal-age effect upon cases of 47, + 21 in which the extra chromosome is of paternal origin, Am. J. Hum. Genet. 36:413–421.PubMedGoogle Scholar
  41. Hook, E. B., Cross, P. K., Lamson, S. H., Regal, R. R., Baird, P. A., and Uh, S. H., 1981, Paternal age and Down syndrome in British Columbia, Am. J. Hum. Genet. 33:123–128.PubMedGoogle Scholar
  42. Houghton, J. A., 1981, The study of chromosome nondisjunction in man, Irish J. Med. Sci. 150:357–366.PubMedGoogle Scholar
  43. Howell, W. M., Denton, T. E., and Diamond, J. R., 1975, Differential staining of the satellite regions of human acrocentric chromosomes, Experientia 31:260–262.PubMedGoogle Scholar
  44. Human Gene Mapping 8, 1985, Eighth International Workshop on Human Gene Mapping, Cytogenetic. Cell Genet. Vol. 40, Nos. 1–4.Google Scholar
  45. Jackson-Cook, C. K., Flannery, D. B., Corey, L. A., Nance, W. E., and Brown, J. A., 1985, Nucleolar organizer region variants as a risk factor for Down syndrome, Am. J. Hum. Genet. 37:1049–1061.PubMedGoogle Scholar
  46. Jacobs, P. A., and Mayer, M., 1981, The origin of human trisomy: A study of heteromorphisms and satellite associations, Ann. Hum. Genet. 45:49–57.Google Scholar
  47. Jacobs, P. A., and Morton, N. E., 1977, Origin of human trisomies and polyploids, Hum. Hered. 27:59–72.PubMedGoogle Scholar
  48. Jacobs, P. A., Szulman, A. E., Funkhouser, J., Matsuura, J., and Wilson, M. A., 1982, Human triploidy: Relationship between parental origin of the additional haploid complement and development of partial hydatidiform mole, Ann. Hum. Genet. 46:223–232.PubMedGoogle Scholar
  49. Jagiello, G., and Fang, J. S., 1979, Analyses of diplotene chiasma frequencies in mouse ooctyes and spermatocytes in relation to aging and sexual dimorphism, Cytogenet. Cell Genet. 23:53–60.PubMedGoogle Scholar
  50. John, B., and Miklos, G. L. G., 1979, Functional aspects of satellite DNA and heterochromatin, Int. Rev. Cytol. 58:1–114.PubMedGoogle Scholar
  51. Jorgensen, A. L., Jones, C., Bostock, C. J., and Bak, A. L., 1987, Different subfamilies of alphoid repetitive DNA are present on the human and chimpanzee homologous chromosomes 21 and 22, EMBO J. 6:1691–1696.PubMedGoogle Scholar
  52. Juberg, R. C., and Mowrey, P. N., 1983, Origin of nondisjunction in trisomy 21 syndrome. All studies compiled, parental age analysis, and external comparisons, Am. J. Med. Genet. 16:111–116.PubMedGoogle Scholar
  53. Kaufman, M., 1983, Ethanol-induced chromosomal abnormalities at conception, Nature 302:258–260.PubMedGoogle Scholar
  54. Kikuchi, Y., Oishi, H., Tonomura, A., Yamda, K., Tanaka, Y., Kurita, T., and Matsunaga, E., 1969, Translocation Down’s syndrome in Japan: Its frequency, mutation rate of translocation and parental age, Jpn. J. Hum. Genet. 14:93–106.Google Scholar
  55. Kishimoto, T. K., O’Connor, K., Lee, A., Roberts, T. M., and Springer, T. A., 1987, Cloning of the p subunit of the leukocyte adhesion proteins: Homology to an extracellular matrix receptor defines a novel supergene family, Cell 48:681–690.PubMedGoogle Scholar
  56. Kline, J., Levin, B., Shrout, P., Stein, Z., Susser, M., and Warburton, D., 1983, Maternal smoking and trisomy among spontaneously aborted conceptions, Am. J. Hum. Genet. 35:421–431.PubMedGoogle Scholar
  57. Krumlauf, R., Jeanpierre, M., and Young, B. D., 1982, Construction and characterization of genomic libraries from specific human chromosomes, Proc. Natl. Acad. Sci USA 79:2971–2975.PubMedGoogle Scholar
  58. Kurnit, D. M., 1979, Satellite DNA and heterochromatin variants: The case for unequal mitotic crossing over, Hum. Genet. 47:169–186.PubMedGoogle Scholar
  59. Kurnit, D. M., and Maio, J. J., 1974, Variable satellite DNA’s in the African green monkey, Cercopithecus aethiops, Chromosoma 45:387–400.PubMedGoogle Scholar
  60. Kurnit, D. M., Neve, R. L., Morton, C. C., Bruns, G. A. P., Ma, N. S. F., Cox, D. R., and Klinger, H. P., 1984, Recent evolution of DNA sequence homology in the pericentromeric region of human acrocentric chromosomes, Cytogenet. Cell Genet. 38:99–105.PubMedGoogle Scholar
  61. Kurnit, D. M., Roy, S., Stewart, G. D., Schwedock, J., Neve, R. L., Bruns, G. A. P., Van Keuren, M. L., and Patterson, D., 1986, The 724 family of DNA sequences is interspersed about the pericentromeric regions of human acrocentric chromosomes, Cytogenet. Cell Genet. 43:109–116.PubMedGoogle Scholar
  62. Lalande, M., Dryja, T. P., Schreck, R. R., Shipley, J., Flint, A., and Latt, S. A., 1984, Isolation of human chromosome 13-specific DNA sequences cloned from flow-sorted chromosomes and potentially linked to the retinoblastoma locus, Cancer Genet. Cytogenet. 13:283–296.PubMedGoogle Scholar
  63. Langenbeck, U., Hansmann, I., Hinney, B., and Honig, V., 1976, On the origin of the supernumerary chromosome in autosomal trisomies—With special reference to Down syndrome. A bias in tracing nondisjunction by chromosomal and biochemical polymorphisms, Hum. Genet. 33:89–102.PubMedGoogle Scholar
  64. Langlois, R. G., Yu, L. C., Gray, J. W., and Carrano, A. V., 1982, Quantitative karyotyping of human chromosomes by dual beam flow cytometry, Proc. Natl. Acad. Sci. USA 79:7876–7880.PubMedGoogle Scholar
  65. Lau, Y.-F., Pfeiffer, R. A., Arrighi, F. E., and Hsu, T. C., 1978, Combination of silver and fluorescent staining for metaphase chromosomes, Am. J. Hum. Genet. 30:76–79.PubMedGoogle Scholar
  66. Laurie, D. A., and Hulten, M. A., 1985, Further studies on bivalent chiasma frequency in human males with normal karyotypes, Ann. Hum. Genet. 49:189–201.PubMedGoogle Scholar
  67. Livingston, G. K., Lockey, J. E., Witt, K. S., and Rogers, S. W., 1985, An unstable giant satellite associated with chromosomes 21 and 22 in the same individual, Am. J. Hum. Genet. 37:553–560.PubMedGoogle Scholar
  68. Luthardt, F. W., 1977, Cytogenetic analyses of human oocytes, Am. J. Hum. Genet. 29:71A.Google Scholar
  69. Luthardt, F. W., Palmer, C. G., and Yu, P.-L., 1973, Chiasma and univalent frequencies in aging female mice, Cytogenet. Cell Genet. 12:68–79.PubMedGoogle Scholar
  70. Lutz, C. T., Hollifield, W. C., Seed, B., Davie, J. M., and Huang, H. V., 1987, Syrinx 2A: An improved X vector designed for screening DNA libraries by recombination in vivo, Proc. Natl Acad. Sci. USA 84:4379–4383.PubMedGoogle Scholar
  71. Magenis, R. E., Overton, K. M., Chamberlin, J., Brady, T., and Lovrien, E., 1977, Prenatal origin of the extra chromosome in Down’s syndrome, Hum. Genet. 37:7–16.PubMedGoogle Scholar
  72. Marlin, S. D., Morton, C. C., Anderson, D. C., and Springer, T. A., 1986, LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of a and b subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells, J. Exp. Med 164:855–867.PubMedGoogle Scholar
  73. Mattei, J. F., Ayme, S., Mattei, M. G., and Giraud, F., 1980, Maternal age and origin of nondisjunction in trisomy 21, J. Med. Genet. 17:368–372.PubMedGoogle Scholar
  74. McGrath, J., and Solter, D., 1984, Completion of mouse embryogenesis requires both the maternal and parental genomes, Cell 37:179–183.PubMedGoogle Scholar
  75. Merriam, J. R., and Frost, J. N., 1964, Exchange and nondisjunction of the X-chromosomes in female Drosophila melanogaster, Genetics 49:109–122.PubMedGoogle Scholar
  76. Mikkelsen, M., Hanne, P., Jorgen, G., and Aksel, L., 1980, Nondisjunction in trisomy 21: Study of chromosomal heteromorphisms in 110 families, Ann. Hum. Genet. Lond. 4:17–28.Google Scholar
  77. Morton, N. E., MacLean, C., and Lew, R., 1985, Tests of hypotheses on recombination frequencies, Genet. Res. 45:279–286.PubMedGoogle Scholar
  78. Mottironi, V. D., Hook, E. B., Willey, A. M., Porter, I. H., Swift, R. V., and Hatcher, N. H., 1983, Decreased HLA heterogeneity in parents of children with Down syndrome, Am. J. Hum. Genet. 35:1289–1296.PubMedGoogle Scholar
  79. Neve, R. L., and Kurnit, D. M., 1983, Comparison of sequence repetitiveness of human cDNA and genomic DNA using the recombination miniplasmid, piVX, Gene 23:355–367.PubMedGoogle Scholar
  80. Neve, R. L., Brans, G. A. P., Dryja, T. P., and Kurnit, D. M., 1983, Retrieval of human DNA from rodent-human libraries by a recombination process, Gene 23:343–354.PubMedGoogle Scholar
  81. Neve, R. L., Stewart, G. D., Newcomb, P., Van Keuren, M. L., Patterson, D., Drabkin, H. A., and Kurnit, D. M., 1986, Human chromosome 21-encoded cDNA clones, Gene 49:361–369.PubMedGoogle Scholar
  82. Nielsen, J., Freidrich, U., Hreidarsson, A. B., Noel, B., Quack, B., and Mottet, J., 1974, Brilliantly fluorescing enlarged short arms D or G, Lancet 1:1049–1050.PubMedGoogle Scholar
  83. Okamoto, E., Miller, D. A., Erlanger, B. F., and Miller, O. J., 1981, Polymorphism of 5-methylcytosine-rich DNA in human acrocentric chromosomes, Hum. Genet. 48:255–259.Google Scholar
  84. Ott, J., Under, D., McCaw, B. K., Lovrien, E., and Hecht, F., 1976, Estimating distances from the centromere by means of benign ovarian teratomas in man, Ann. Hum. Genet. 40:191–196.PubMedGoogle Scholar
  85. Park, S. C., Mathews, R. A., Zuberbuhler, J. R., Rowe, R. D., Neches, W. H., and Lenox, C. C., 1977, Down syndrome with congenital heart malformation, Am. J. Dis. Child. 131:29–33.PubMedGoogle Scholar
  86. Penrose, L. S., 1933, The relative effect of paternal age and maternal age in mongolism, Genet. 27:219–224.Google Scholar
  87. Perez-Castillo, A., Martin-Lucas, M. A., and Abrisqueta, J. A., 1986, New insights into the effects of extra nucleolus organizer regions, Hum. Genet. 72:80–82.PubMedGoogle Scholar
  88. Pinkerton, P. H., London, B., and Senn, J. S., 1984, Chronic myeloid leukemia with a Philadelphia chromosome involving a t(21;22), Cancer Genet. Cytogenet. 12:175–178.PubMedGoogle Scholar
  89. Polani, P. E., and Jagiello, G. M., 1976, Chiasmata, meiotic univalents and age in relationship to aneuploid imbalance in mice, Cytogenet. Cell Genet. 16:505–529.PubMedGoogle Scholar
  90. Pueschel, S. M., 1987, Maternal alpha-fetoprotein screening for Down’s syndrome, N. Engl. J. Med. 317:376–378.PubMedGoogle Scholar
  91. Reik, W., Collick, A., Norris, M. L., Barton, S. C., and Surani, M. A., 1987, Genomic imprinting determines methylation of parental alleles in transgenic mice, Nature 328:248–251.PubMedGoogle Scholar
  92. Roberts, D. F., and Callow, M. H., 1980, Origin of the additional chromosome in Down’s syndrome, J. Med. Genet. 39:68–78.Google Scholar
  93. Rothman, K. J., 1983, Spermicide use and Down’s syndrome, Am. J. Public Health 72:399–401.Google Scholar
  94. Rowe, R. D., and Uchida, I. A., 1961, Cardiac malformations in mongolism: A prospective study of 184 mongoloid children, Am. J. Med. 31:726.PubMedGoogle Scholar
  95. Sacchi, N., Gusella, J. F., Perroni, L., Dagna Bricarelli, F., and Papas, T. S., 1988, Lack of evidence for association of meiotic nondisjunction with particular DNA haplotypes on chromosome 21, Proc. Natl. Acad. Sci. USA (in press).Google Scholar
  96. Sandler, L., 1981, The meiotic nondisjunction of homologous chromosomes in Drosophila females, in: Trisomy 21 (Down Syndrome): Research Perspectives (F. de la Cruz and P. Gerald, eds.), pp. 181–197, University Park Press, Baltimore.Google Scholar
  97. Sapienza, C., Peterson, A. C., Rossant, J., and Balling, R., 1987, Degree of methylation of transgenes is dependent on gamete of origin, Nature 328:251–254.PubMedGoogle Scholar
  98. Schweizer, D., Ambros, P., and Andrle, M., 1978, Modification of DAPI banding on human chromosomes by prestaining with a DNA-binding oligopeptide antibiotic, distamycin A, Exp. Cell Res. 111:327–332.PubMedGoogle Scholar
  99. Searle, A. G., and Beechey, C., 1985, Noncomplementation phenomena and their bearing on nondisjunctional effects, in: Aneuploidy, Etiology and Mechanisms (V. L. Dellarco, P. E. Voytek, and A. Hollaender, eds.), pp. 363–276, Plenum Press, New York.Google Scholar
  100. Shahar, S., and Morton, N. E., 1986, Origin of teratomas and twins, Hum. Genet. 74:215–218.PubMedGoogle Scholar
  101. Shen, P., and Huang, H. V., 1986, Homologous recombination in Escherichia coli: Dependence on substrate length and homology, Genetics 11:441–457.Google Scholar
  102. Slaugenhaupt, S. A., and Chakravarti, A., 1986, Methods for studying recombination on chromosomes that have undergone nondisjunction, Am. J. Hum. Genet. 39:168A.Google Scholar
  103. Smith, G. E., and Berg, J. M., 1976, Down’s Anomaly, Churchill Livingstone, Edinburgh.Google Scholar
  104. Speed, R. M., 1977, The effects of aging on the meitoic chromosomes of male and female mice, Chromosoma 64:241–254.PubMedGoogle Scholar
  105. Speed, R. M., and Chandley, A. C., 1983, Meiosis in the foetal mouse ovary. II. Oocyte development and age-related aneuploidy. Does a production line exist? Chromosoma 88:184–189.PubMedGoogle Scholar
  106. Spinner, N. B., Eunpu, D. L., Schmickel, R. D., Zackai, E., Bunin, G., and Emanuel, B. S., 1986, The role of cytologic and molecular nor variants in trisomy 21, Am. J. Hum. Genet. 39(Suppl.):A133,392.Google Scholar
  107. Stein, Z., Stein, W., and Susser, M., 1986, Attrition of trisomies as a maternal screening device, Lancet i:944–946.Google Scholar
  108. Stewart, G. D., 1984, The isolation and characterisation of cloned DNA from a chromosome 21 enriched DNA library, Thesis, University of Glasgow, Scotland.Google Scholar
  109. Stewart, G. D., Harris, P., Gait, J., and Ferguson-Smith, M. A., 1985, Cloned DNA probes regionally mapped to human chromosome 21 and their use in determining the origin of nondisjunction, Nucleic Acids Res. 13:4125–4132.PubMedGoogle Scholar
  110. Stewart, G. D., Hassold, T. J., Berg, A., Watkins, P., Tanzi, R., and Kurnit, D. M., 1988, Down syndrome: Studying nondisjunction and meiotic recombination using cytogenetic and molecular polymorphisms that span chromosome 21, Am. J. Hum. Genet. 42:227–236.PubMedGoogle Scholar
  111. Strobino, B., Kline, J., Lai, A., Stein, Z., Susser, M., and Warburton, D., 1986, Vaginal spermicides and spontaneous abortion of known karyotype, Am. J. Epidemiol. 123:431–443.PubMedGoogle Scholar
  112. Sugawara, S., and Mikamo, K., 1983, Absence of correlation between univalent formation and meiotic nondisjunction in the aged female Chinese hamster, Cytogenet. Cell Genet. 35:34–40.PubMedGoogle Scholar
  113. Tandon, R., and Edwards, J. E., 1973, Cardiac malformations associated with Down syndrome, Circulation 47:1349.PubMedGoogle Scholar
  114. Tantravahi, U., Stewart, G. D., Roy, S., McNeil, G., Patterson, D., Van Keuren, M., Lalande, M., Kurnit, D. M., and Latt, S. A., 1988, Isolation of DNA sequences on chromosome 21 by application of a recombination-based assay to DNA from flow sorted chromosomes, Hum. Genet, (in press).Google Scholar
  115. Tanzi, R. E., Haines, J. L., Stewart, G. D., Watkins, P. C., Gibbons, K. T., Faryniarz, A. G., Wallace, M. R., Hallewell, R., Yount, E., Wexler, N. S., Conneally, P. M., and Gusella, J. F., 1988, Genetic linkage map of chromosome 21, manuscript submitted to Genomics.Google Scholar
  116. Therman, E., Otto, P. G., and Shahidi, N. T., 1981, Mitotic recombination and segregation of satellites in Bloom’s syndrome, Chromosoma 82:627–636.PubMedGoogle Scholar
  117. Uchida, I., 1979, Radiation-induced nondisjunction, Environ. Health Perspect. 31:13–18.Google Scholar
  118. Van Keuren, M. L., Watkins, P. C., Drabkin, H. A., Jabs, E. W., Gusella, J. F., and Patterson, D., 1986, Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids, Am. J. Hum. Genet. 38:793–804.PubMedGoogle Scholar
  119. Vekemans, M. J., and Trasler, D., 1985, Maternal genes control the extent of in utero selection against trisomic embryos in the mouse, Am. J. Hum. Genet. 37(Suppl.): A128,377.Google Scholar
  120. Waalwijk, C., and Flavell, R. A., 1978, DNA methylation at a CCGG sequence in the large intron of the rabbit beta-globin gene: Tissue specific variations, Nucleic Acids Res. 5:4631–4641.PubMedGoogle Scholar
  121. Wagenbicher, P., Killan, W., Aett, A., and Schnedl, W., 1976, Origin of the extra chromosome no. 21 in Down’s syndrome, Hum. Genet. 32:13–16.Google Scholar
  122. Warren, A. C., Chakravarti, AA, Wong, C., Slaugenhaupt, S. A., Halloran, S. L., Watkins, P. C., Metaxotou, C., and Antonarakis, S. E., 1987, Evidence for reduced recombination on the nondisjoined chromosomes 21 in Down syndrome, Science 237:652–654.PubMedGoogle Scholar
  123. Watkins, P. C., Tanzi, R. E., Gibbons, K. T., Tricoli, J. V., Landes, G., Eddy, R., Shows, T. B., and Gusella, J. F., 1985, Isolation of polymorphic DNA segments from chromosome 21, Nucleic Acids Res. 13:6075–6088.PubMedGoogle Scholar
  124. Watt, V. M., Ingles, C. J., Urdea, M. S., and Rutter, W. J., 1985, Homology requirements for recombination in Escherichia coli, Proc. Natl. Acad. Sci. USA 82:4768–4772.PubMedGoogle Scholar
  125. Willard, H. F., and Waye, J. S., 1987, Hierarchical order in chromosome-specific human alpha satellite DNA, Trends Genet. 3:192–198.Google Scholar

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© Plenum Press, New York 1988

Authors and Affiliations

  • Gordon D. Stewart
    • 1
  • Terry J. Hassold
    • 2
  • David M. Kurnit
    • 3
  1. 1.Department of Pediatrics Howard Hughes Medical InstituteUniversity of Michigan Medical CenterAnn ArborUSA
  2. 2.Division of Medical GeneticsEmory UniversityAtlantaUSA
  3. 3.Departments of Pediatrics and Human Genetics Howard Hughes Medical InstituteUniversity of Michigan Medical CenterAnn ArborUSA

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