title: Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21.
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.
authors.affiliation: Department of Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Lamb
authors.forename: E
authors.initials: E
authors.lastname: Feingold
authors.forename: A
authors.initials: A
authors.lastname: Savage
authors.forename: D
authors.initials: D
authors.lastname: Avramopoulos
authors.forename: S
authors.initials: S
authors.lastname: Freeman
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: A
authors.initials: A
authors.lastname: Hallberg
authors.forename: J
authors.initials: J
authors.lastname: Hersey
authors.forename: G
authors.initials: G
authors.lastname: Karadima
authors.forename: D
authors.initials: D
authors.lastname: Pettay
authors.forename: D
authors.initials: D
authors.lastname: Saker
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Taft
authors.forename: M
authors.initials: M
authors.lastname: Mikkelsen
authors.forename: M B
authors.initials: MB
authors.lastname: Petersen
authors.forename: T
authors.initials: T
authors.lastname: Hassold
authors.forename: S L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D003434:Crossing Over, Genetic; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008423:Maternal Age; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D009630:Nondisjunction, Genetic; D011418:Prophase / Q000235:genetics; D016615:Telomere
chemical_list: D005819:Genetic Markers