Adaptive-filtering of trisomy 21: risk of Down syndrome depends on family size and age of previous child |
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Authors: | Markus Neuhäuser Sven Krackow |
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Institution: | (1) Department of Mathematics and Technique, RheinAhrCampus Remagen, Südallee 2, 53424 Remagen, Germany;(2) Institute for Biology, Humboldt University Berlin, Invalidenstrasse 43, 10115 Berlin, Germany |
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Abstract: | The neonatal incidence rate of Down syndrome (DS) is well-known to accelerate strongly with maternal age. This non-linearity
renders mere accumulation of defects at recombination during prolonged first meiotic prophase implausible as an explanation
for DS rate increase with maternal age, but might be anticipated from chromosomal drive (CD) for trisomy 21. Alternatively,
as there is selection against genetically disadvantaged embryos, the screening system that eliminates embryos with trisomy
21 might decay with maternal age. In this paper, we provide the first evidence for relaxed filtering stringency (RFS) to represent
an adaptive maternal response that could explain accelerating DS rates with maternal age. Using historical data, we show that
the proportion of aberrant live births decrease with increased family size in older mothers, that inter-birth intervals are
longer before affected neonates than before normal ones, and that primiparae exhibit elevated levels of DS incidence at higher
age. These findings are predicted by adaptive RFS but cannot be explained by the currently available alternative non-adaptive
hypotheses, including CD. The identification of the relaxation control mechanism and therapeutic restoration of a stringent
screen may have considerable medical implications. |
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Keywords: | In utero screening Aberrant embryos Spontaneous abortion Maternal age Menopause Chromosomal drive |
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