Abstract
We have previously examined characteristics of maternal chromosomes 21 that exhibited a single recombination on 21q and proposed that certain recombination configurations are risk factors for either meiosis I (MI) or meiosis II (MII) nondisjunction. The primary goal of this analysis was to examine characteristics of maternal chromosomes 21 that exhibited multiple recombinant events on 21q to determine whether additional risk factors or mechanisms are suggested. In order to identify the origin (maternal or paternal) and stage (MI or MII) of the meiotic errors, as well as placement of recombination, we genotyped over 1,500 SNPs on 21q. Our analyses included 785 maternal MI errors, 87 of which exhibited two recombinations on 21q, and 283 maternal MII errors, 81 of which exhibited two recombinations on 21q. Among MI cases, the average location of the distal recombination was proximal to that of normally segregating chromosomes 21 (35.28 vs. 38.86 Mb), a different pattern than that seen for single events and one that suggests an association with genomic features. For MII errors, the most proximal recombination was closer to the centromere than that on normally segregating chromosomes 21 and this proximity was associated with increasing maternal age. This pattern is same as that seen among MII errors that exhibit only one recombination. These findings are important as they help us better understand mechanisms that may underlie both age-related and nonage-related meiotic chromosome mal-segregation.
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Acknowledgments
We would like to thank our lab personnel, recruiters and the families that participated in this study. This work was supported by the National Institutes of Health (1T32MH087977, R01 HD057029, R01 HD38979, R01 HL083300, R01-DE 014899 and U01-DE018903); the Center for Inherited Disease Research (HHSN268200782096C); and the Children’s Healthcare of Atlanta Cardiac Research Committee.
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Oliver, T.R., Tinker, S.W., Allen, E.G. et al. Altered patterns of multiple recombinant events are associated with nondisjunction of chromosome 21. Hum Genet 131, 1039–1046 (2012). https://doi.org/10.1007/s00439-011-1121-7
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DOI: https://doi.org/10.1007/s00439-011-1121-7