Parental-Age Effects: Increased Frequencies of Genetically Abnormal Offspring

  • David Kram
  • Edward L. Schneider


In the previous chapters, the authors have discussed at length the effect of genotype on aging. In this chapter, we will focus on the effect of aging on human genotype—the increased risk faced by the older parent of having a child with a genetic disorder. This increased risk of genetically abnormal offspring with parental aging represents a sizable socioeconomical as well as clinical problem. The magnitude of this problem is reflected in the cost of one parental-age-related disorder, the Down syndrome. If the number of annual Down syndrome births (approximately 8000) is multiplied by the average life expectancy of a newborn with the Down syndrome (30 years) and by the average cost of specialized care for these persons ($5000 per year is a modest estimate), the staggering annual cost of 1.2 billion dollars is obtained (Swanson, 1970). In addition to the economic burden, one must consider the emotional and psychological problems that occur in a family with a Down syndrome child. The high frequency of parental-age-related disorders is also seen in institutions for the mentally retarded, where Down syndrome patients may comprise as much as one third of the entire patient population.


Down Syndrome Prenatal Diagnosis Meiotic Division Chiasma Frequency Syndrome Child 


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  1. Alberman, E., Polani, P. E., Roberts, J. A. F., Spicer C. C., Elliot, M., and Armstrong, E., 1972, Parental exposure to X-irradiation and Down’s syndrome, Ann. Hum. Genet. 36:195–208.PubMedGoogle Scholar
  2. Austin, C. R., 1967, Chromosome deterioration in ageing eggs of the rabbit, Nature (London) 213:1018–1019.Google Scholar
  3. Barrai, I., Cann, H. M., Cavalli-Sforza, L. L., and Nicola, P., 1968, The effect of parental age on rates of mutation for hemophilia and evidence for differing mutation rates for hemophilia A and B, Am. J. Human Genet. 20:175–196.Google Scholar
  4. Bell, A. G., and Cripps, M. H., 1974, Familial aneuploidy: What risk to sibs?, Can. J. Genet. Cytol. 16:113–119.PubMedGoogle Scholar
  5. Bennett, D., 1966, Non-random association of chromosomes during mitotic metaphase in tissue cells of the mouse, Cytologia 31:411–415.PubMedGoogle Scholar
  6. Berry, W. T. C., 1958, A study on the incidence of mongolism in relation to the fluoride content of water, Am. J. Ment. Defic. 62:634–636.PubMedGoogle Scholar
  7. Blank, C. E., 1960, Apert’s syndrome (a type of acrocephalosyndactyly)—Observations on a British series of thirty-nine cases, Ann. Hum. Genet. 24:151–164.PubMedGoogle Scholar
  8. Bodmer, W. F., 1961, Viability effects and recombination differences in a linkage test with pallid and fidget in the house mouse, Heredity 16:485–495.Google Scholar
  9. Bott, C. E., Sckhon, S. E. and Lubs, H. A., 1975, Unexpected high frequency of paternal origin of trisomy 21, Am. J. Hum. Genet. 27:20.Google Scholar
  10. Boyer, S. H., Ferguson-Smith, M. A., and Grumbach, M. M., 1961, The lack of influence on parental age and birth order in the aetiology of nuclear sex chromatin-negative Turner’s syndrome, Ann. Hum. Genet. 25:215–225.Google Scholar
  11. Branden, A. W. H., and Austin, C. R., 1954, Fertilization of the mouse egg and the effect of delayed coitus and hot-shock treatment, Aust. J. Biol. Sci. 7:552–565.Google Scholar
  12. Broustet, A., Serville, F., Roger, P., and Gachet, M., 1975, X monosomy and 21 trisomy in a sibship, Humangenetik 27:333–337.PubMedGoogle Scholar
  13. Burger, P. C., and Vogel, S. F., 1973, The development of the pathologic changes of Alzheimer’s disease and senile dementia in patients with Down’s syndrome, Am. J. Pathol. 73:457–476.PubMedGoogle Scholar
  14. Burgio, G. B., Severi, F., Rossoni, R., and Vaccaro, R., 1966, Auto-antibodies in Down’s syndrome, Lancet 1:497–498.PubMedGoogle Scholar
  15. Butcher, R. L., Blue, J. D., and Fugo, N. W., 1969, Overripeness and the mammalian ova. III. Fetal development at midgestation and at term, Fertil. Steril. 20:223–231.PubMedGoogle Scholar
  16. Butcher, R. L., and Fugo, N. W., 1967, Overripeness and the mammalian ova. II. Delayed ovulation and chromosome anomalies, Fertil. Steril. 18:297–304.PubMedGoogle Scholar
  17. Carter, C. O., and Evans, K. A., 1961, Risk of parents who have had one child with Down’s syndrome (mongolism) having another child similarly affected, Lancet 2:785–787.Google Scholar
  18. Carter, C. O., Evans, K. A., and Stewart, A. M., 1961, Maternal radiation and Down’s syndrome (mongolism), Lancet 2:1042.Google Scholar
  19. Chamberlain, J. G., and Kasahara, M., 1971, Influence of maternal age and parity on fetal mortality and congenital abnormalities induced in rats, Growth 35:213–220.PubMedGoogle Scholar
  20. Chrisman, C. L., 1974, Aneuploidy in mouse embryos induced by diethylstilbestrol diphosphate, Teratology 9:229–232.PubMedGoogle Scholar
  21. Cohen, B. L., and Lilienfeld, A. M., 1970, The epidemiological study of mongolism in Baltimore, Ann. N. Y. Acad. Sci. 171:320–327.Google Scholar
  22. Cohen, M. M., 1970, Drugs and chromosomes, Ann. N. Y. Acad. Sci. 171:467–477.Google Scholar
  23. Collman, R. D., and Stoller, A., 1962, A survey of mongoloid births in Victoria, Australia, 1942-1957, Am. J. Public Health 52:813–829.Google Scholar
  24. Cooke, P., 1972, Age-related variation in the number of secondary associations between acrocentric chromosomes in normal females and patients with Turner’s syndrome, Humangenetik 17:29–35.PubMedGoogle Scholar
  25. Craig-Holmes, A. P., Moore, F. B., and Shaw, M. W., 1975, Polymorphism of human C-band heterochromatin. II. Family studies with suggestive evidence for somatic crossing over, Am. J. Hum. Genet. 27:178–189.PubMedGoogle Scholar
  26. Crew, F., and Koller, P., 1926, The sex incidence of chiasma frequency and genetical crossing over in the mouse, J. Genet. 26:359–383.Google Scholar
  27. Dallaire, L., and Fraser, F. C., 1964, Two unusual cases of familial mongolism, Can. J. Genet. Cytol. 6:540–547.Google Scholar
  28. Dallaire, L., and Leboeuf, G., 1973, Maternal autoimmunity and its relationship to reproductive failure, in: INSERM Symposium: Les Accidents Chromosomiques de la Reproduction (A. Boué and C. Thibault, eds.), pp. 333-339, Institut National de la Santé et de la Recherche Médicale, Paris.Google Scholar
  29. Day, R. W., and Wright, S. W., 1964, Thyroid autoantibodies and sex-chromosome abnormalities, Lancet 2:667.Google Scholar
  30. de Capoa, A., Rocchi, A., and Gigliani, F., 1973, Frequency of satellite association in individuals with structural abnormalities of nucleolus organizer region, Humangenetik 18:111–115.PubMedGoogle Scholar
  31. Down, J. L. H., 1866, Observations on an ethnic classification of idiots, Clin. Lect. Rep, London Hosp. 3:259–262.Google Scholar
  32. Dunning, J. M., 1965, Current status of fluoridation, N. Engl. J. Med. 272:30–34.PubMedGoogle Scholar
  33. Edwards, J. H., Harnden, D. G., Cameron, A. H., Grosse, V. M., and Wolff, O. H., 1960, A new trisomie syndrome, Lancet 1:787–789.PubMedGoogle Scholar
  34. Edwards, R. G., 1970, Meiosis in males and females, in: Human Population Cytogenetics (P. A. Jacobs, W. H. Price, and P. Law, eds.), pp. 20-21, Williams and Wilkins Co., Baltimore.Google Scholar
  35. Engel, E., 1967, Autoantibodies and chromosomal aberrations, Lancet 1:1271–1272.PubMedGoogle Scholar
  36. Erickson, D., and Cohen, M. M., 1974, A study of parental effects on the occurrence of fresh mutations for the Apert syndrome, Ann. Hum. Genet. 38:89–96.PubMedGoogle Scholar
  37. Evans, H. J., 1967, The nucleolus, virus infection, and trisomy in man, Nature (London) 214:361–363.Google Scholar
  38. Fabricant, J. D., and Schneider, E. L., 1978, Studies of the genetic and immunologic components of the maternal age effect (in prep.).Google Scholar
  39. Fialkow, P. J., 1966, Autoimmunity and chromosomal aberrations, Am. J. Hum. Genet. 18:93–108.PubMedGoogle Scholar
  40. Fialkow, P. J., Thuline, H. C., Hecht, F., and Bryant, J., 1971, Familial predisposition to thyroid disease in Down’s syndrome: Controlled immunoclinical studies, Am. J. Hum. Genet. 23:67–86.PubMedGoogle Scholar
  41. Fitzgerald, P. H., Pickering, A. F., Mercer, J. M., and Miethke, P. M., 1975, Premature centromere division: A mechanism of nondisjunction causing X chromosome aneuploidy in somatic cells of man, Ann. Hum. Genet. 38:417–428.PubMedGoogle Scholar
  42. Freeman, M. E., Butcher, R. L., and Fugo, N. W., 1970, Alteration of oocytes and follicles by delayed ovulation, Biol. Reprod. 2:209–215.PubMedGoogle Scholar
  43. Furguson-Smith, M. A., Anderson, J. R., Froland, A., and Gray, K. G., 1966, Frequency of autoantibodies in patients with chromatin-positive Klinefelter’s syndrome and their parents, Lancet 2:566–568.Google Scholar
  44. Gates, A. H., and Beatty, R. A., 1954, Independence of delayed fertilization and spontaneous triploidy in mouse embryos, Nature (London) 174:356.Google Scholar
  45. German, J., 1968, Mongolism, delayed fertilization and human sexual behavior, Nature (London) 217:516–518.Google Scholar
  46. Giraud, F., Mattei, J. F. and Matei, M. G., 1975, Étude chromosomique chez les parents d’ enfants trisomiques 21: Chromosomes marquers, remaniements, cassures et aneuploidies, Lyon Med. 233:241–251.Google Scholar
  47. Glass, H. R., and Ritterhoff, R. K., 1961, Mutagenic effect of a 5-r dose of X-rays in Drosophila melanogaster, Science 133:1366.Google Scholar
  48. Golbus, M. S., 1977, The prenatal diagnosis of genetic defects, in: Advances in Obstetrics and Gynecology, Williams and Wilkins Co., Baltimore.Google Scholar
  49. Goodlin, R. C., 1965, Nondisjunction and maternal age in the mouse, J. Reprod. Fertil. 9:355–356.Google Scholar
  50. Gosden, R. G., 1973, Chromosomal anomalies of preimplantation mouse embryos in relation to maternal age, J. Reprod. Fertil. 35:351–354.PubMedGoogle Scholar
  51. Guerrero, R., and Rojas, O. I., 1975, Spontaneous abortion and aging of human ova and spermatozoa, N. Engl. J. Med. 293:573–574.PubMedGoogle Scholar
  52. Hamerton, J. L., Briggs, S. M., Giannelli, F., and Carter, C. O., 1961, Chromosome studies in detection of parents with high risk of second child with Down’s syndrome, Lancet 2: 788–791.PubMedGoogle Scholar
  53. Hara, Y. and Sasaki, M., 1975, A note on the origin of extra chromosomes in trisomies 13 and 21, Proc. Jpn. Acad. 51:295–299.Google Scholar
  54. Harlap, S., 1974, A time-series analysis of the incidence of Down’s syndrome in West Jerusalem, Am. J. Epidemiol. 99:210–217.PubMedGoogle Scholar
  55. Hauschka, T. S., Hasson, J. E., Goldstein, M. N., Koepe, G. E., and Sandberg, A. A., 1962, an XYY man with progeny indicating familial tendency to nondisjunction, Am. J. Hum. Genet. 14:22–30.PubMedGoogle Scholar
  56. Heindrichs, E. H., Allen, S. W., and Nelson, P. S., 1963, Simultaneous 18-trisomy and 21-trisomy cluster, Lancet 2:468.Google Scholar
  57. Henderson, S. A., and Edwards, R. G., 1968, Chiasma frequency and maternal age in mammals, Nature (London) 218:22–28.Google Scholar
  58. Herrmann, J., 1966, Der Einfluss des Zeugungsalters auf die Mutationen zu Haemophile A, Humangenetik 3:1–16.PubMedGoogle Scholar
  59. Heilig, A. T., 1967, The overall problem in man, in: Comparative Aspects of Reproductive Failure (K. Benirschke, ed.), pp. 11–41, Springer-Verlag, Berlin.Google Scholar
  60. Hsia, D. Y. Y., Justice, P., Smith, G. F., and Dowben, R. M., 1971, Down’s syndrome: A critical review of the biochemical and immunological data, Am. J. Dis. Child. 121:153–161.PubMedGoogle Scholar
  61. Hutton, E. M., and Thompson, M. W., 1970, Parental age and mutation rate in Duchene muscular dystrophy, Am. J. Hum. Genet. 22: 26a.Google Scholar
  62. Israsena, T., Quatrale, A. C., and Becker, K. L., 1967, Autoimmune disease and chromosomal instability, Lancet 2:1226–1227.PubMedGoogle Scholar
  63. Jagiello, G., and Lin, J. S., 1973, An assessment of the effects of mercury on the meiosis of mouse ova, Mutat. Res. 17:93–99.PubMedGoogle Scholar
  64. James, W. H., 1968, Mongolism, delayed fertilization and sexual behavior, Nature (London) 219:279–280.Google Scholar
  65. Jones, J. L., Smith, D. W., Harvey, M. A. S., Hall, B. D., and Quan, L., 1975, Older paternal age and fresh gene mutation: Data on additional disorders, J. Pediatr. 86:84–88.PubMedGoogle Scholar
  66. Jongbloet, P. H., 1975, The effects of preovulatory overripeness of human eggs on development, in: Aging Gametes (R. J. Blandau, ed.), pp. 300–329, S. Karger, Basel.Google Scholar
  67. Juberg, R. C., and Davis, L. M., 1970, Etiology of nondisjunction: Lack of evidence for genetic control, Cytogenetics 9:284–293.PubMedGoogle Scholar
  68. Klinefelter, H. F., Reifenstein, E. C., and Albright, F., 1942, Syndrome characterized by gynecomastia, aspermatogenesis without α-Leydigism, and increased excretion of follicle-stimulating hormone, J. Clin. Endocrinol. 2:615–627.Google Scholar
  69. Kochupillai, N., Verma, I. C., Grewal, M. S., and Ramalingaswami, V., 1976, Down’s syndrome and related abnormalities in an area of high background radiation in coastal Kerala, Nature (London) 262:60–61.Google Scholar
  70. Kogan, A., Kronmal, R., and Peterson, D. R., 1967, Viral hepatitis and Down’s syndrome, Lancet 1:615.Google Scholar
  71. 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’s syndrome, Hum. Genet. 33:89–102.PubMedGoogle Scholar
  72. Leek, I., 1966, Incidence and epidemicity of Down’s syndrome, Lancet 2:457–460.Google Scholar
  73. Lejeune, J., Gautier, M., and Turpin, R., 1959, Étude des chromosomes somatiques de neuf enfants mongoliens, C. R. Acad. Sci. 248: 1721–1722.Google Scholar
  74. Lieznerski, R. L., and Lindsten, J., 1972, Trisomy 21 in man due to maternal nondisjunction during the first meiotic division, Hereditas 70:153–154.Google Scholar
  75. Lilienfeld, A. M., 1969, Epidemiology of Mongolism, Johns Hopkins University Press, Baltimore.Google Scholar
  76. Lowry, R. B., Jones, D. C., Renwick, D. G. H., and Trimble, B. K., 1976, Teratology 14:29–34.PubMedGoogle Scholar
  77. Lunn, J. E., 1959, A survey of mongol children in Glasgow, Scott. Med. J. 4:368–372.PubMedGoogle Scholar
  78. 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
  79. Lynas, M. A., 1958, Marfan’s syndrome in Northern Ireland: An account of thirteen families, Ann. Hum. Genet. 22:289-301. Lyon, M. R., 1961, Gene action in the X-chromosome of the mouse, Nature (London) 190:372–373.Google Scholar
  80. Magenis, R. E., Hecht, F., and Milham, S., 1968, Trisomy 13 (D1) syndrome: Studies on parental age, sex ratio, and survival, J. Pediatr. 73: 222–228.PubMedGoogle Scholar
  81. Mariona, F. G., 1975, Is pregnancy a risk in the elderly woman?, in: Aging and Reproductive Physiology (E. S. E. Hafez, ed.), pp. 167–192, Ann Arbor Press, Ann Arbor, Michigan.Google Scholar
  82. Marmol, J. G., Scriggins, A. L., and Vollman, R. F., 1969, Mothers of mongoloid infants in the collaborative project, Am. J. Obstet. Gynecol. 104:533–543.PubMedGoogle Scholar
  83. Matsunaga, E., and Maruyama, T., 1969, Human sexual behavior, delayed fertilization and Down’s syndrome, Nature (London) 221:642–644.Google Scholar
  84. Mikamo, K., and Hamaguchi, H., 1975, Chromosomal disorder caused by preovulatory overripeness of oocytes, in: Aging Gametes (R. J. Blandau, ed.), pp. 72–97, S. Karger, Basel.Google Scholar
  85. Mikkelsen, M., Hallberg, A., and Poulsen, H., 1976, Maternal and paternal origin of extra chromosome in trisomy 21, Hum. Genet. 32:17–21.PubMedGoogle Scholar
  86. Miller, R. W., 1970, Neoplasia and Down’s syndrome, Ann. N. Y. Acad. Sci. 171:637–644.Google Scholar
  87. Murdoch, J. L., Walker, A. A., Hall, J. G., Abbey, H., Smith, K. K., and McKusick, V. A., 1970, Achondroplasia: A genetic and statistical survey, Ann. Hum. Genet. 33:227–244.PubMedGoogle Scholar
  88. Murdoch, J. L., Walker, B. A., and McKusick, V. A., 1972, Parental age effects on the occurrence of new mutations of the Marfan syndrome, Ann. Hum. Genet. 35:331–336.PubMedGoogle Scholar
  89. Needleman, H. L., Pueschel, S. M., and Rothman, K. J., 1974, Fluoridation and the occurrence of Down’s syndrome, N. Engl. J. Med. 291:821–823.PubMedGoogle Scholar
  90. Nichols, W. W., 1970, Virus induced chromosome abnormalities, Annu. Rev. Microbiol. 24:479–500.PubMedGoogle Scholar
  91. Nielsen, J., 1972, Immunological aberrations in patients with aneuploid chromosome abnormalities and their parents, Humangenetik 16:171–176.PubMedGoogle Scholar
  92. Nielsen, J., Brunn Petersen, G., and Therkelsen, A. J., 1973, Seasonal variation in the birth of children with aneuploid chromosome abnormalities, Humangenetik 19:67–74.PubMedGoogle Scholar
  93. Ohno, S., Kaplan, W. D., and Kinosita, R., 1959, Do XY and O sperm occur in Mus musculus?, Exp. Cell Res. 18:382–384.Google Scholar
  94. Patau, K., Smith, D. W., Therman, E., Inhorn, S. L., and Wagner, H. P., 1960, Multiple congenital anomaly caused by an extra autosome, Lancet 1:790–793.PubMedGoogle Scholar
  95. Pellie, C., Feingold, J., and Demos, J., 1973, Age parental et mutation a propos d’une enquéte sur la myopathie de Duchene deBoulogne, J. Genet. Hum. 21:33–41.PubMedGoogle Scholar
  96. Penrose, L. S., 1933, The relative effects of paternal and maternal age in mongolism, J. Genet. 27:219–224.Google Scholar
  97. Penrose, L. S., 1955, Parental age and mutation, Lancet 2:312–313.Google Scholar
  98. Race, R. R., and Sanger, R., 1969, Xg and sex chromosome abnormalities, Br. Med. Bull. 25:99–103.PubMedGoogle Scholar
  99. Rapaport, I., 1956, Contribution a l’étude due mongolisme: Rôle pathogenique du fluor, Bull. Acad. Natl. Med. 140:529–531.PubMedGoogle Scholar
  100. Reid, D. H., and Parsons, P. A., 1963, Sex of parent and variation of recombination with age in the mouse, Heredity 18:107–108.PubMedGoogle Scholar
  101. Robinson, A., and Puck, T. T., 1967, Studies on chromosomal nondisjunction in man. II. Am. J. Hum. Genet. 19:112–129.PubMedGoogle Scholar
  102. Robinson, J. A., 1973, Origin of the extra chromosome in trisomy 21, Lancet 1:131–133.PubMedGoogle Scholar
  103. Rodman, T. C., 1971, Chromatid disjunction of unfertilized ageing oocytes, Nature (London) 233:191–193.Google Scholar
  104. Rohrborn, G., and Hansmann, I., 1971, Induced chromosome aberrations in unfertilized oocytes of mice, Humangenetik 18:184–198.Google Scholar
  105. Rowe, R. D., and Uchida, I. A., 1961, Cardiac malformation in mongolism: A prospective study of 184 mongoloid children, Am. J. Med. 31:726–735.PubMedGoogle Scholar
  106. Sandier, L., Lindsley, D. L., Nicoletti, B., and Trippa, G., 1968, Mutants affecting meiosis in natural populations of Drosophila melanogaster, Genetics 60:525–558.Google Scholar
  107. Schedl, W., 1971, Unterschiedliche Fluoreszenz der beiden homologen Chromosomen Nr. 3 beim Menschen, Humangenetik 12:59–63.Google Scholar
  108. Schneider, E. L., Stanbridge, E. J., Epstein, C. J., Golbus, M., Abbo-Halbasch, G., and Rodgers, G., 1974, Mycoplasma contamination of cultured amniotic fluid cells: Potential hazard to prenatal diagnosis, Science 184:477–479.PubMedGoogle Scholar
  109. Searle, A. G., and Beechey, C. V., 1974, Cytogenetic effects of X-rays and fission neutrons in female mice, Mutat. Res. 24:171–186.PubMedGoogle Scholar
  110. Shaver, E. L., and Carr, D. H., 1967, Chromosome abnormalities in rabbit blastocysts following delayed fertilization, J. Reprod. Fertil. 14:415–420.PubMedGoogle Scholar
  111. Shaver, E. L., and Carr, D. H., 1969, The chromosome complement of rabbit blastocyte in relation to the time of mating and ovulation, Can. J. Genet. Cytol. 11:287–293.PubMedGoogle Scholar
  112. Smith, C. A. B., 1972, Note on the estimation of parental age effects, Ann. Hum. Genet. 35:337–342.PubMedGoogle Scholar
  113. Smith, D. J., and Joffe, J. M., 1975, Increased neonatal mortality in offspring of male rats treated with methadone or morphine before mating, Nature (London) 253:202–203.Google Scholar
  114. Smith, D. W., 1970, in: Recognizable patterns of human malformation, p. 129, W. B. Saunders and Co., Philadelphia.Google Scholar
  115. Smith, S. W., and Wilson, A. A., 1973, What is a child with Down’s syndrome like? in: The Child with Down’s Syndrome (D. W. Smith and A. A. Wilson, eds.), p. 24, W. B. Saunders and Co., Philadelphia.Google Scholar
  116. Smith, G. F., and Sachdeva, S., 1973, Paternal origin of the extra chromosome in trisomy 21, Lancet 1:487.PubMedGoogle Scholar
  117. Stevenson, A. C., Mason, R., and Edwards, K., 1970, Maternal diagnostic X-irradiation before conception and the frequency of mongolism in children subsequently born, Lancet 2:1335–1337.PubMedGoogle Scholar
  118. Stoller, A., and Collman, R. D., 1965, Virus aetiology of Down’s syndrome (mongolism), Nature (London) 208:903–904.Google Scholar
  119. Swanson, T. E., 1970, Economics of mongolism, Ann. N. Y. Acad. Sci. 171:679–682.Google Scholar
  120. Szemere, G., and Chandley, A. C., 1975, Trisomy and triploidy induced by X-irradiation of mouse spermatocytes, Mutat. Res. 33:229–238.PubMedGoogle Scholar
  121. Tijo, J. H., and Levan, A., 1956, The chromosome number of man, Hereditas 42:1–6.Google Scholar
  122. Tunte, W., 1972, Human mutations and paternal age, Humangenetik 16:77–82.PubMedGoogle Scholar
  123. Tunte, W., Becker, P. E., and Von Knorre, G., 1967, Zur Genetik der Myositis ossificans progressiva, Humangenetik 4:320–351.PubMedGoogle Scholar
  124. Uchida, I. A., 1962, The effect of maternal age and radiation on the rate of nondisjunction in Drosophila melanogaster, Can. J. Genet. Cytol. 4:402–408.Google Scholar
  125. Uchida, I. A., and Curtis, E. J., 1961, A possible association between maternal radiation and mongolism, Lancet 2:848–850.PubMedGoogle Scholar
  126. Uchida, I. A., Ray, M., McRae, K. N., and Besant, D. F., 1968, Familial occurrence of trisomy 21, J. Hum. Genet. 20:107–118.Google Scholar
  127. Vanhaelst, L., Hayez, F., Bonnyns, M., and Bastenie, P. A., 1970, Thyroid autoimmune disease and thyroid function in families of subjects with Down’s syndrome, J. Clin. Endocrinol. 30:792–797.Google Scholar
  128. Vickers, A. D., 1969, Delayed fertilization and chromosomal anomalies in mouse embryos, J. Reprod. Fertil. 20:69–76.PubMedGoogle Scholar
  129. Wagenbichler, P., Killian, W., Rett, A., and Schnedl, W., 1976, Origin of the extra chromosome No. 21 in Down’s syndrome, Hum. Genet. 32:13–16.PubMedGoogle Scholar
  130. Witschi, E., 1952, Overripeness of the egg as a cause of twinning and teratogenesis: A review, Cancer Res. 12:763–786.PubMedGoogle Scholar
  131. Witschi, E., and Laguens, R., 1963, Chromosomal aberrations in embryos from overripe eggs, Dev. Biol. 7:605–616.PubMedGoogle Scholar
  132. Wren, P. J., Evans, D. A. P., Vetters, J. M., and Chew, A., 1967, Autoimmune antibodies in mongol families, Lancet 2:186–188.PubMedGoogle Scholar
  133. Yamamoto, M., Endo, A., and Watanabe, G., 1973, Maternal age dependence of chromosome anomalies, Nature (London) New Biol. 241:141–142.Google Scholar
  134. Zellweger, H., and Simpson, J., 1973, Is routine prenatal karyotyping indicated in pregnancies of very young women?, J. Pediatr. 82:675–677.PubMedGoogle Scholar
  135. Zuppinger, E., Engel, E., Forbes, A. P., Mantooth, L., and Claffey, J., 1967, Klinefelter’s syndrome: A clinical and cytogenetic study in twenty-four cases, Acta Endocrinol. (Copenhagen) Suppl. 113:5–48.Google Scholar

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© Plenum Press, New York 1978

Authors and Affiliations

  • David Kram
    • 1
  • Edward L. Schneider
    • 1
    • 2
  1. 1.Laboratory of Cellular and Comparative PhysiologyGerontology Research CenterBaltimoreUSA
  2. 2.National Institute on Aging, National Institutes of Health, Public Health ServiceU.S. Department of Health, Education and WelfareBaltimoreUSA

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