title: Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21.
abstract: In oocytes with nondisjoined chromosomes 21 due to a meiosis I (MI) error, recombination is significantly reduced along chromosome 21; several lines of evidence indicate that this contributes to the nondisjunction event. A pilot study found evidence that these oocytes also have reduced recombination genome-wide when compared with controls. This suggests that factors that act globally may be contributing to the reduced recombination on chromosome 21, and hence, the nondisjunction event. To identify the source of these factors, we examined two levels of recombination count regulation in oocytes: (i) regulation at the maternal level that leads to correlation in genome-wide recombination across her oocytes and (ii) regulation at the oocyte level that leads to correlation in recombination count among the chromosomes of an oocyte. We sought to determine whether either of these properties was altered in oocytes with an MI error. As it relates to maternal regulation, we found that both oocytes with an MI error (N = 94) and their siblings (N = 64) had reduced recombination when compared with controls (N = 2723). At the oocyte level, we found that the correlation in recombination count among the chromosomes of an oocyte is reduced in oocytes with MI errors compared with that of their siblings or controls. These results suggest that regulation at the maternal level predisposes MI error oocytes to reduced levels of recombination, but additional oocyte-specific dysregulation contributes to the nondisjunction event.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Candace D
authors.initials: CD
authors.lastname: Middlebrooks
authors.forename: Nandita
authors.initials: N
authors.lastname: Mukhopadhyay
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Tinker
authors.forename: Emily Graves
authors.initials: EG
authors.lastname: Allen
authors.forename: Lora J H
authors.initials: LJ
authors.lastname: Bean
authors.forename: Ferdouse
authors.initials: F
authors.lastname: Begum
authors.forename: Reshmi
authors.initials: R
authors.lastname: Chowdhury
authors.forename: Vivian
authors.initials: V
authors.lastname: Cheung
authors.forename: Kimberly
authors.initials: K
authors.lastname: Doheny
authors.forename: Marcia
authors.initials: M
authors.lastname: Adams
authors.forename: Eleanor
authors.initials: E
authors.lastname: Feingold
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008540:Meiosis / Q000235:genetics; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000378:metabolism*; D011995:Recombination, Genetic