title: New insights into human nondisjunction of chromosome 21 in oocytes.
abstract: Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2) a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America. toliver@genetics.emory.edu
authors: Tiffany Renee
authors: TR
authors: Oliver
authors: Eleanor
authors: E
authors: Feingold
authors: Kai
authors: K
authors: Yu
authors: Vivian
authors: V
authors: Cheung
authors: Stuart
authors: S
authors: Tinker
authors: Maneesha
authors: M
authors: Yadav-Shah
authors: Nirupama
authors: N
authors: Masse
authors: Stephanie L
authors: SL
authors: Sherman
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008423:Maternal Age; D008540:Meiosis / Q000235:genetics; D018895:Microsatellite Repeats; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000378:metabolism*; D011247:Pregnancy; D011995:Recombination, Genetic; D012307:Risk Factors