Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21 |
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Authors: | Lamb NE; Feingold E; Savage A; Avramopoulos D; Freeman S; Gu Y; Hallberg A; Hersey J; Karadima G; Pettay D; Saker D; Shen J; Taft L; Mikkelsen M; Petersen MB; Hassold T; Sherman SL |
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Institution: | Department of Genetics, Emory University School of Medicine, Atlanta, GA, USA. |
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Abstract: | Recent studies of trisomy 21 have shown that altered levels of
recombination are associated with maternal non-disjunction occurring at
both meiosis I (MI) and meiosis II (MII). To comprehend better the
association of recombination with nondisjunction, an understanding of the
pattern of meiotic exchange, i.e. the exchange of genetic material at the
four-strand stage during prophase, is required. We examined this underlying
exchange pattern to determine if specific meiotic configurations are
associated with a higher risk of non-disjunction than others. We examined
the crossover frequencies of chromosome 21 for three populations: (i)
normal female meiotic events; (ii) meiotic events leading to MI
non-disjunction; and (iii) those leading to MII non-disjunction. From these
crossover frequencies, we estimated the array of meiotic tetrads that
produced the observed crossovers. Using this approach, we found that nearly
one-half of MI errors were estimated to be achiasmate. The majority of the
remaining MI bivalents had exchanges that clustered at the telomere. In
contrast, exchanges occurring among MII cases clustered at the
pericentromeric region of the chromosome. Unlike the single exchange
distributions, double exchanges from the non-disjoined populations seemed
to approximate the distribution in the normal population. These data
suggest that the location of certain exchanges makes a tetrad susceptible
to non- disjunction. Specifically, this susceptibility is associated with
the distance between the centromere and closest exchange. This result
challenges the widely held concept that events occurring at MII are largely
independent of events occurring at MI, and suggests that all
non-disjunction events may be initiated during MI and simply resolved at
either of the two meiotic stages.
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