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A chiasma–hormonal hypothesis relating Down's syndrome and maternal age

Nature volume 280, pages 417–419 (1979)Cite this article

Abstract

THE incidence of the human congenital abnormality known as Down's syndrome (or mongolism) has been observed to increase with maternal age1. The trend of sharply increased incidence beyond the age of 30 has been well documented2, and various hypotheses have been formulated to explain it. These include cumulative ovum or uterine dysfunction (radiation3, chemicals4, disease5), acute effects of radiation and chemicals, hormonal effects6, the ‘production line’ hypothesis7,8 and changes in sexual behaviour9. We describe here our hypothesis that there is an interaction between the hormonally governed rate of meiosis and the timing of chiasma terminalisation. We propose that changing hormone levels during the menstrual cycle not only trigger resumption of meiosis in the ovum10, but also control the rate of meiosis through the availability of a limiting substance11. As hormone levels and the length of the cycle change with advancing age of the mother, meiosis slows down, and chiasma frequencies decline7,12. Meiotic chromosome bivalents are held together by their chiasmata against strong mutual repulsion during late dictyotene and diakinesis13, making smaller bivalents with fewer chiasmata, such as 21, the most vulnerable to premature separation during terminalisation14,15; premature separation can lead to trisomy 21, by far the most frequent cytological manifestation of Down's syndrome16.

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Authors and Affiliations

  1. Thomas Hunt Morgan School of Biological Sciences, University of Kentucky, Lexington, Kentucky, 40506

    PHILIP H. CROWLEY & DUSHYANT K. GULATI

  2. Department of Mathematics, University of Kentucky, Lexington, Kentucky, 40506

    THOMAS L. HAYDEN & PENELOPE LOPEZ

  3. Biomedical Engineering Program, Department of Mechanical Engineering, University of Kentucky, Lexington, Kentucky, 40506

    RUTH DYER

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  1. PHILIP H. CROWLEY
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  2. DUSHYANT K. GULATI
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  5. RUTH DYER
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CROWLEY, P., GULATI, D., HAYDEN, T. et al. A chiasma–hormonal hypothesis relating Down's syndrome and maternal age. Nature 280, 417–419 (1979). https://doi.org/10.1038/280417a0

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