Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

To err (meiotically) is human: the genesis of human aneuploidy

Key Points

  • Aneuploidy (trisomy or monosomy) is the most commonly identified chromosome abnormality in humans, occurring in at least 5% of all clinically recognized pregnancies.

  • About 1 in 300 liveborn infants are aneuploid, most commonly with a missing or additional sex chromosome or an additional chromosome 21 (Down syndrome).

  • About 1 in 3 miscarriages are aneuploid, with sex chromosome monosomy (45,X) and trisomy 16 being the most common.

  • Most 45,X conceptions involve loss of the paternal X chromosome; most trisomies arise from errors at maternal meiosis I (MI).

  • Abnormal levels or positioning of meiotic recombinational events (cross-overs) have been implicated in the origin of human trisomies.

  • Reductions in recombination have been observed in maternal MI-derived trisomies 15, 16, 18, and 21 and sex-chromosome trisomies, and in paternal MI-derived XXYs and trisomy 21.

  • Increases in recombination have been observed for maternal meiosis-II (MII)-derived trisomy 21, which indicates that the precipitating event for these cases probably occurred at MI.

  • Abnormally positioned recombinational events (too close to, or too far from, the centromere) have been reported for trisomies 16 and 21.

  • Increasing maternal age is the most important aetiological agent associated with aneuploidy: for women in their 40s, as many as one-third of all clinically recognized pregnancies might be trisomic. The basis of the age effect is unclear, although for certain trisomies it might be associated with abnormal recombination.

  • Genetic and/or environmental contributors to human aneuploidy are unknown, although recent reports indicate a possible association with maternal folate polymorphisms and with maternal smoking habits.

Abstract

Aneuploidy (trisomy or monosomy) is the most commonly identified chromosome abnormality in humans, occurring in at least 5% of all clinically recognized pregnancies. Most aneuploid conceptuses perish in utero, which makes this the leading genetic cause of pregnancy loss. However, some aneuploid fetuses survive to term and, as a class, aneuploidy is the most common known cause of mental retardation. Despite the devastating clinical consequences of aneuploidy, relatively little is known of how trisomy and monosomy originate in humans. However, recent molecular and cytogenetic approaches are now beginning to shed light on the non-disjunctional processes that lead to aneuploidy.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Meiotic 'timelines' for humans.
Figure 2: Meiotic non-disjunction.
Figure 3: Genetic maps of normal and trisomic meioses.
Figure 4: Recombination and meiosis-II-derived trisomies.
Figure 5: Molecular cytogenetic approaches to studying gametes.
Figure 6: Maternal age and trisomy.

Similar content being viewed by others

References

  1. Sears, D. D., Hegemann, J. H. & Hieter, P. Meiotic recombination and segregation of human-derived artificial chromosomes in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 89, 5296–5300 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Koehler, K. E., Hawley, R. S., Sherman, S. & Hassold, T. Recombination and nondisjunction in humans and flies. Hum. Mol. Genet. 5, 1495–1504 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  3. Sandler, L. in Trisomy 21 (Down Syndrome): Research Perspectives (eds de la Cruz, F. & Gerald, P.) 181–197 (Academic, New York, 1981).

    Google Scholar 

  4. Bond, D. & Chandley, A. in Aneuploidy 86– 91 (Oxford Univ. Press, Oxford, 1983).

    Google Scholar 

  5. Smith, K. N. & Nicolas, A. Recombination at work for meiosis . Curr. Opin. Genet. Dev. 8, 200– 211 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Hassold, T. et al. Human aneuploidy: incidence, origin, and etiology. Environ. Mol. Mutagen. 28, 167–175 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Warburton, D. & Fraser, C. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am. J. Hum. Genet. 16, 1–27 (1964).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Angell, R. R., Sandison, A. & Bain, A. D. Chromosome variation in perinatal mortality: a survey of 500 cases. J. Med. Genet. 21, 39– 44 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jamieson, M. E., Coutts, J. R. & Connor, J. M. The chromosome constitution of human preimplantation embryos fertilized in vitro. Hum. Reprod. 9, 709–715 (1994).

    Article  CAS  PubMed  Google Scholar 

  10. Delhanty, J. D. Chromosome analysis by FISH in human preimplantation genetics. Hum. Reprod. 12, 153–155 (1997).

    CAS  PubMed  Google Scholar 

  11. Hassold, T. J. Nondisjunction in the human male. Curr. Top. Dev. Biol. 37, 383–406 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Jacobs, P. A. The chromosome complement of human gametes. Oxf. Rev. Reprod. Biol. 14, 47–72 ( 1992).

    CAS  PubMed  Google Scholar 

  13. Marquez, C., Cohen, J. & Munne, S. Chromosome identification in human oocytes and polar bodies by spectral karyotyping. Cytogenet. Cell Genet. 81, 254–258 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Volarcik, K. et al. The meiotic competence of in-vitro matured human oocytes is influenced by donor age: evidence that folliculogenesis is compromised in the reproductively aged ovary. Hum. Reprod. 13, 154–160 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Jacobs, P. et al. Turner syndrome: a cytogenetic and molecular study. Ann. Hum. Genet. 61, 471–483 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Bugge, M. et al. Non-disjunction of chromosome 18. Hum. Mol. Genet. 7, 661–669 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  17. Hassold, T., Merrill, M., Adkins, K., Freeman, S. & Sherman, S. Recombination and maternal age-dependent nondisjunction: molecular studies of trisomy 16. Am. J. Hum. Genet. 57, 867–874 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Lamb, N. E. et al. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21. Hum. Mol. Genet. 6, 1391–1399 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. Lamb, N. E. et al. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nature Genet. 14, 400–405 (1996).Study that links errors scored as arising at meiosis II, as well as those originating at meiosis I, to the genesis of trisomy 21.

    Article  CAS  PubMed  Google Scholar 

  20. Robinson, W. P. et al. Nondisjunction of chromosome 15: origin and recombination . Am. J. Hum. Genet. 53, 740– 751 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. MacDonald, M. et al. The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination. Hum. Mol. Genet. 3, 1365–1371 ( 1994).

    Article  CAS  PubMed  Google Scholar 

  22. Zaragoza, M. V. et al. Nondisjunction of human acrocentric chromosomes: studies of 432 trisomic fetuses and liveborns. Hum. Genet. 94, 411–417 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Zaragoza, M. V., Millie, E., Redline, R. W. & Hassold, T. J. Studies of non-disjunction in trisomies 2, 7, 15, and 22: does the parental origin of trisomy influence placental morphology? J. Med. Genet. 35, 924–931 ( 1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Roeder, G. S. Meiotic chromosomes: it takes two to tango. Genes Dev. 11, 2600–2621 (1997).

    Article  CAS  PubMed  Google Scholar 

  25. Ross, L. O., Maxfield, R. & Dawson, D. Exchanges are not equally able to enhance meiotic chromosome segregation in yeast. Proc. Natl Acad. Sci. USA 93, 4979–4983 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sears, D. D., Hegemann, J. H., Shero, J. H. & Hieter, P. Cis-acting determinants affecting centromere function, sister-chromatid cohesion and reciprocal recombination during meiosis in Saccharomyces cerevisiae . Genetics 139, 1159– 1173 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Koehler, K. E. et al. Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories . Nature Genet. 14, 406– 414 (1996).Comprehensive analysis of X-chromosome non-disjunction in female flies, demonstrating an association between recombination and non-disjunction that is remarkably similar to that observed in humans.

    Article  CAS  PubMed  Google Scholar 

  28. Rasooly, R. S., New, C. M., Zhang, P., Hawley, R. S. & Baker, B. S. The lethal(1)TW-6cs mutation of Drosophila melanogaster is a dominant antimorphic allele of nod and is associated with a single base change in the putative ATP-binding domain. Genetics 129, 409–422 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Moore, D. P., Miyazaki, W. Y., Tomkiel, J. E. & Orr-Weaver, T. L. Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males. Genetics 136 , 953–964 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Krawchuk, M. D. & Wahls, W. P. Centromere mapping functions for aneuploid meiotic products: analysis of rec8, rec10 and rec11 mutants of the fission yeast Schizosaccharomyces pombe. Genetics 153, 49–55 ( 1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zetka, M. C. & Rose, A. M. Mutant rec-1 eliminates the meiotic pattern of crossing over in Caenorhabditis elegans. Genetics 141, 1339–1349 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chakravarti, A. et al. Gene-Centromere Mapping and the Study of Non-Disjunction in Autosomal Trisomies and Ovarian Teratomas (eds Hassold, T. & Epstein, C.) (Alan R. Liss, New York City, 1989).

    Google Scholar 

  33. Savage, A. R. et al. Elucidating the mechanisms of paternal non-disjunction of chromosome 21 in humans. Hum. Mol. Genet. 7, 1221–1227 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. Hassold, T. J., Sherman, S. L., Pettay, D., Page, D. C. & Jacobs, P. A. XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region . Am. J. Hum. Genet. 49, 253– 260 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Thomas, N. S., Collins, A. R., Hassold, T. J. & Jacobs, P. A. A reinvestigation of non-disjunction resulting in 47,XXY males of paternal origin. Eur. J. Hum. Genet. 8, 805– 808 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Robinson, W. P. et al. Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination. Hum. Mol. Genet. 7, 1011–1019 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  37. Thomas, N. et al. The origin of maternal sex chromosome non-disjunction. Hum. Mol. Genet. 10, 243–250 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Angell, R. R. Aneuploidy in older women. Higher rates of aneuploidy in oocytes from older women. Hum. Reprod. 9, 199– 200 (1994).

    Google Scholar 

  39. Angell, R. R. Predivision in human oocytes at meiosis I: a mechanism for trisomy formation in man. Hum. Genet. 86, 383– 387 (1991).

    Article  CAS  PubMed  Google Scholar 

  40. Angell, R. First-meiotic-division nondisjunction in human oocytes. Am. J. Hum. Genet. 61, 23–32 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Angell, R. R., Xian, J. & Keith, J. Chromosome anomalies in human oocytes in relation to age. Hum. Reprod. 8, 1047–1054 ( 1993).

    Article  CAS  PubMed  Google Scholar 

  42. Wolstenholme, J. & Angell, R. R. Maternal age and trisomy — a unifying mechanism of formation. Chromosoma 109, 435–438 ( 2000).This paper describes a model linking maternal-age-dependent trisomy and premature separation of sister chromatids at meiosis I.

    Article  CAS  PubMed  Google Scholar 

  43. Mahmood, R., Brierley, C. H., Faed, M. J., Mills, J. A. & Delhanty, J. D. Mechanisms of maternal aneuploidy: FISH analysis of oocytes and polar bodies in patients undergoing assisted conception. Hum. Genet. 106, 620– 626 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Dailey, T., Dale, B., Cohen, J. & Munne, S. Association between nondisjunction and maternal age in meiosis-II human oocytes. Am. J. Hum. Genet. 59, 176–184 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Penrose, L. The relative effects of paternal and maternal age in mongolism. J. Genet. 27, 219–224 ( 1933).

    Article  Google Scholar 

  46. Morton, N. E., Jacobs, P. A., Hassold, T. & Wu, D. Maternal age in trisomy. Ann. Hum. Genet. 52, 227 –235 (1988).

    Article  CAS  PubMed  Google Scholar 

  47. Risch, N., Stein, Z., Kline, J. & Warburton, D. The relationship between maternal age and chromosome size in autosomal trisomy. Am. J. Hum. Genet. 39, 68–78 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Ayme, S. & Lippman-Hand, A. Maternal-age effect in aneuploidy: does altered embryonic selection play a role? Am. J. Hum. Genet. 34, 558–565 ( 1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kline, J., Kinney, A., Levin, B. & Warburton, D. Trisomic pregnancy and earlier age at menopause. Am. J. Hum. Genet. 67 , 395–404 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Freeman, S. B., Yang, Q., Allran, K., Taft, L. F. & Sherman, S. L. Women with a reduced ovarian complement may have an increased risk for a child with Down syndrome. Am. J. Hum. Genet. 66, 1680–1683 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zheng, C. J. & Byers, B. Oocyte selection: a new model for the maternal-age dependence of Down syndrome. Hum. Genet. 90, 1–6 (1992).

    Article  CAS  PubMed  Google Scholar 

  52. Henderson, S. A. & Edwards, R. G. Chiasma frequency and maternal age in mammals. Nature 217, 22–28 (1968).

    Article  Google Scholar 

  53. Hawley, R. S., Frazier, J. A. & Rasooly, R. Separation anxiety: the etiology of nondisjunction in flies and people. Hum. Mol. Genet. 3, 1521 –1528 (1994).

    Article  CAS  PubMed  Google Scholar 

  54. Warburton, D. The effect of maternal age on the frequency of trisomy: change in meiosis or in utero selection? Prog. Clin. Biol. Res. 311, 165–181 (1989). Thoughtful review of possible mechanisms leading to the generation of the maternal-age effect, with a description of a 'limited oocyte pool' hypothesis to explain it.

    CAS  PubMed  Google Scholar 

  55. Hassold, T., Sherman, S. & Hunt, P. Counting cross-overs: characterizing meiotic recombination in mammals. Hum. Mol. Genet. 9, 2409– 2419 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Battaglia, D., Goodwin, P. & Klein, N. Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Hum. Reprod. 11, 2217–2222 (1996). Study that demonstrates an effect of increasing maternal age on meiotic spindle morphology.

    Article  CAS  PubMed  Google Scholar 

  57. Shonn, M. A., McCarroll, R. & Murray, A. W. Requirement of the spindle checkpoint for proper chromosome segregation in budding yeast meiosis. Science 289, 300–303 (2000). Study demonstrating that in yeast, spindle-checkpoint mutations preferentially affect meiosis I chromosome segregation, and indicating that checkpoint defects might contribute to Down syndrome.

    Article  CAS  PubMed  Google Scholar 

  58. Yuan, L. et al. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol. Cell 5, 73–83 (2000). Generation and phenotypic analysis of mice in which a component of the lateral element of the synaptonemal complex has been knocked out.

    Article  CAS  PubMed  Google Scholar 

  59. Uchida, I. & Curtis, E. A possible association between maternal radiation and mongolism. Lancet 2, 848– 850 (1961).

    Article  CAS  PubMed  Google Scholar 

  60. Harlap, S. et al. Chromosome abnormalities in oral contraceptive breakthrough pregnancies. Lancet 1, 1342– 1343 (1979).

    Article  CAS  PubMed  Google Scholar 

  61. Torfs, C. P., van den Berg, B. J., Oechsli, F. W. & Christianson, R. E. Thyroid antibodies as a risk factor for Down syndrome and other trisomies . Am. J. Hum. Genet. 47, 727– 734 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kaufman, M. H. The teratogenic effects of alcohol following exposure during pregnancy, and its influence on the chromosome constitution of the pre-ovulatory egg. Alcohol Alcohol. 32, 113–128 (1997).

    Article  CAS  PubMed  Google Scholar 

  63. Jongbloet, P. H., Mulder, A. & Hamers, A. J. Seasonality of pre-ovulatory non-disjunction and the aetiology of Down syndrome. A European collaborative study. Hum. Genet. 62, 134–138 (1982).

    Article  CAS  PubMed  Google Scholar 

  64. Schimmel, M. S., Eidelman, A. I., Zadka, P., Kornbluth, E. & Hammerman, C. Increased parity and risk of trisomy 21: review of 37,110 live births. Br. Med. J. 314, 720–721 (1997).

    Article  CAS  Google Scholar 

  65. Narchi, H. & Kulaylat, N. High incidence of Down's syndrome in infants of diabetic mothers. Arch. Dis. Child. 77 , 242–244 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Alfi, O. S., Chang, R. & Azen, S. P. Evidence for genetic control of nondisjunction in man . Am. J. Hum. Genet. 32, 477– 483 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Avramopoulos, D., Mikkelsen, M., Vassilopoulos, D., Grigoriadou, M. & Petersen, M. B. Apolipoprotein E allele distribution in parents of Down's syndrome children. Lancet 347, 862–865 (1996).

    Article  CAS  PubMed  Google Scholar 

  68. Jackson-Cook, C. K., Flannery, D. B., Corey, L. A., Nance, W. E. & Brown, J. A. Nucleolar organizer region variants as a risk factor for Down syndrome. Am. J. Hum. Genet. 37, 1049–1061 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Verger, P. Down syndrome and ionizing radiation. Hlth Phys. 73 , 882–893 (1997).

    Article  CAS  Google Scholar 

  70. Hassold, T. J. & Jacobs, P. A. Trisomy in man . Annu. Rev. Genet. 18, 69– 97 (1984).

    Article  CAS  PubMed  Google Scholar 

  71. Sayee, R. & Thomas, I. M. Consanguinity, non-disjunction, parental age and Down's syndrome. J. Indian Med. Assoc. 96, 335–337 (1998).

    CAS  PubMed  Google Scholar 

  72. Morris, J. K., Alberman, E. & Mutton, D. Is there evidence of clustering in Down syndrome? Int. J. Epidemiol. 27, 495–498 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Pelz, J. & Kunze, J. Down's syndrome in infants of diabetic mothers. Arch. Dis. Child. 79, 199– 200 (1998).

    Article  CAS  PubMed  Google Scholar 

  74. Stolwijk, A. M., Jongbloet, P. H., Zielhuis, G. A. & Gabreels, F. J. Seasonal variation in the prevalence of Down syndrome at birth: a review. J. Epidemiol. Commun. Hlth 51, 350– 353 (1997).

    Article  CAS  Google Scholar 

  75. Ezquerra, M. et al. Apolipoprotein E ɛ4 alleles and meiotic origin of non- disjunction in Down syndrome children and in their corresponding fathers and mothers. Neurosci. Lett. 248, 1– 4 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Hassold, T., Jacobs, P. A. & Pettay, D. Analysis of nucleolar organizing regions in parents of trisomic spontaneous abortions. Hum. Genet. 76, 381–384 (1987).

    Article  CAS  PubMed  Google Scholar 

  77. Rubin, R. Folic acid might reduce risk of Down syndrome. USA Today Sept 29, D1 (1999).

    Google Scholar 

  78. James, S. J. et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am. J. Clin. Nutr. 70, 495–501 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. van der Put, N. M. et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am. J. Hum. Genet. 62, 1044–1051 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hobbs, C. A. et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am. J. Hum. Genet. 67, 623–630 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wilson, A. et al. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol. Genet. Metab. 67, 317–323 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Petersen, M., Grigoriadou, M. & Mikkelsen, M. A common mutation in the methylenetetrahydrofolate reductase gene is not a risk factor for Down syndrome. Am. J. Hum. Genet. 67, S141 (2000).

    Google Scholar 

  83. Chen, C. L., Gilbert, T. J. & Daling, J. R. Maternal smoking and Down syndrome: the confounding effect of maternal age. Am. J. Epidemiol. 149, 442–446 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Yang, Q. et al. Risk factors for trisomy: maternal cigarette smoking and oral contraceptive use in a population-based case-control study. Genet. Med. 1, 80–88 ( 1999).Combined epidemiological and molecular analysis of trisomy 21, in which potential aetiological agents can be linked to the parent and meiotic stage of origin of the extra chromosome.

    Article  CAS  PubMed  Google Scholar 

  85. Hassold, T. & Chiu, D. Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy. Hum. Genet. 70, 11–17 ( 1985).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Research conducted in the T. Hassold and P. Hunt laboratories and discussed in this article was supported by the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Related links

Related links

DATABASE LINKS

trisomy 21

nod

Axs

Dub

ncd

Klinefelter syndrome

MTHFR

MTRR

SCP3

MLH1

FURTHER INFORMATION

Terry Hassold's lab

Patricia Hunt's lab

Glossary

ATRESIA

Apoptotic death of follicles.

POLAR BODY

Oogenesis results in only one functional gamete; the remaining products of MI or MII are the polar bodies, which contain chromosomes but virtually no cytoplasm.

GAMETE INTRA-FALLOPIAN TRANSFER (GIFT).

Assisted reproduction technique in which oocytes and sperm are mixed and placed into the fallopian tubes, where fertilization might occur.

SPECTRAL KARYOTYPING

Fluorescence in situ hybridization technique in which differentially labelled DNA probes to all chromosomes are used, making it possible to identify every chromosome in the complement in a single hybridization.

GENE CONVERSION

Non-reciprocal recombination event, in which genetic information at one allele is copied into the complementary allele.

BIVALENT

Synapsed pair of homologous chromosomes in meiosis I.

SYNAPTONEMAL COMPLEX

A tripartite, meiosis-specific structure that binds the homologous chromosomes together during meiosis I.

ANTRAL FOLLICLE

Final stage in the growth of the oocyte, when the follicle develops a fluid-filled cavity — the antrum.

PERIOVULATORY FOLLICLE

The follicle around the time of ovulation; at this stage, the oocyte, which has been suspended in prophase, will resume and complete meiosis I in response to the preovulatory surge of gonadotrophins ('LH surge').

FOLIC ACID

One of the B-vitamins; folic acid is essential for cellular methylation reactions and for de novo synthesis of nucleotide precursors in DNA synthesis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hassold, T., Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2, 280–291 (2001). https://doi.org/10.1038/35066065

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35066065

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing