title: Inefficient Crossover Maturation Underlies Elevated Aneuploidy in Human Female Meiosis.
abstract: Meiosis is the cellular program that underlies gamete formation. For this program, crossovers between homologous chromosomes play an essential mechanical role to ensure regular segregation. We present a detailed study of crossover formation in human male and female meiosis, enabled by modeling analysis. Results suggest that recombination in the two sexes proceeds analogously and efficiently through most stages. However, specifically in female (but not male), ∼25% of the intermediates that should mature into crossover products actually fail to do so. Further, this "female-specific crossover maturation inefficiency" is inferred to make major contributions to the high level of chromosome mis-segregation and resultant aneuploidy that uniquely afflicts human female oocytes (e.g., giving Down syndrome). Additionally, crossover levels on different chromosomes in the same nucleus tend to co-vary, an effect attributable to global per-nucleus modulation of chromatin loop size. Maturation inefficiency could potentially reflect an evolutionary advantage of increased aneuploidy for human females.
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, PR China; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Shunxin
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Hassold
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hunt
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: White
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Zickler
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: kleckner@fas.harvard.edu.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kleckner
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, PR China. Electronic address: zhangliangran@sdu.edu.cn.
authors.forename: Liangran
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000782:Aneuploidy; D002467:Cell Nucleus / Q000235:genetics; D002877:Chromosomes, Human; D005260:Female; D005718:Gametogenesis; D006801:Humans; D008297:Male; D008540:Meiosis; D011995:Recombination, Genetic; D012727:Sex Characteristics