title: Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates.
abstract: Crossover recombination reshuffles genes and prevents errors in segregation that lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Here we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses. Genotyping >4 million informative SNPs from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns of 529 chromosome pairs. We uncover a new reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germ line by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings show that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II.
authors.affiliation: The Bridge Centre, London, UK.|School of Biosciences, University of Kent, Canterbury, UK.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Ottolini
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Newnham
authors.affiliation: G.E.N.E.R.A., Centers for Reproductive Medicine, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Capalbo
authors.affiliation: Illumina, Capital Park CPC4, Fulbourn, Cambridge, UK.
authors.forename: Senthilkumar A
authors.initials: SA
authors.lastname: Natesan
authors.affiliation: Illumina, Capital Park CPC4, Fulbourn, Cambridge, UK.
authors.forename: Hrishikesh A
authors.initials: HA
authors.lastname: Joshi
authors.affiliation: G.E.N.E.R.A., Centers for Reproductive Medicine, Rome, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Cimadomo
authors.affiliation: School of Biosciences, University of Kent, Canterbury, UK.
authors.forename: Darren K
authors.initials: DK
authors.lastname: Griffin
authors.affiliation: The Bridge Centre, London, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Sage
authors.affiliation: The Bridge Centre, London, UK.|School of Biosciences, University of Kent, Canterbury, UK.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Summers
authors.affiliation: Illumina, Capital Park CPC4, Fulbourn, Cambridge, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Thornhill
authors.affiliation: Department of Mathematics and Statistics, University of Indiana, Bloomington, Indiana, US.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Housworth
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Herbert
authors.affiliation: G.E.N.E.R.A., Centers for Reproductive Medicine, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rienzi
authors.affiliation: G.E.N.E.R.A., Centers for Reproductive Medicine, Rome, Italy.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Ubaldi
authors.affiliation: The Bridge Centre, London, UK.|School of Biosciences, University of Kent, Canterbury, UK.|Illumina, Capital Park CPC4, Fulbourn, Cambridge, UK.|Institute of Integrative and Comparative Biology, University of Leeds, Leeds, UK.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Handyside
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Hoffmann
mesh_terms: D002478:Cells, Cultured; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D003434:Crossing Over, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D008540:Meiosis; D009865:Oocytes / Q000502:physiology; D059705:Polar Bodies; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA