Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates

Christian S Ottolini; Louise J Newnham; Antonio Capalbo; Senthilkumar A Natesan; Hrishikesh A Joshi; Danilo Cimadomo; Darren K Griffin; Karen Sage; Michael C Summers; Alan R Thornhill; Elizabeth Housworth; Alex D Herbert; Laura Rienzi; Filippo M Ubaldi; Alan H Handyside; Eva R Hoffmann

doi:10.1038/ng.3306

Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates

Christian S Ottolini, Louise J Newnham, Antonio Capalbo, Senthilkumar A Natesan, Hrishikesh A Joshi, Danilo Cimadomo, Darren K Griffin, Karen Sage, Michael C Summers, Alan R Thornhill, Elizabeth Housworth, Alex D Herbert, Laura Rienzi, Filippo M Ubaldi, Alan H Handyside, Eva R Hoffmann

140 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	47
Issue number	7
Pages (from-to)	727-35
Number of pages	9
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.3306
Publication status	Published - 26 Jun 2015
Externally published	Yes

Keywords

Cells, Cultured
Chromosome Mapping
Chromosome Segregation
Crossing Over, Genetic
Female
Genome, Human
Humans
Meiosis
Oocytes
Polar Bodies
Polymorphism, Single Nucleotide
Recombination, Genetic
Sequence Analysis, DNA
Journal Article
Research Support, Non-U.S. Gov't

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Ottolini, C. S., Newnham, L. J., Capalbo, A., Natesan, S. A., Joshi, H. A., Cimadomo, D., Griffin, D. K., Sage, K., Summers, M. C., Thornhill, A. R., Housworth, E., Herbert, A. D., Rienzi, L., Ubaldi, F. M., Handyside, A. H., & Hoffmann, E. R. (2015). Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. Nature Genetics, 47(7), 727-35. https://doi.org/10.1038/ng.3306

Ottolini, CS, Newnham, LJ, Capalbo, A, Natesan, SA, Joshi, HA, Cimadomo, D, Griffin, DK, Sage, K, Summers, MC, Thornhill, AR, Housworth, E, Herbert, AD, Rienzi, L, Ubaldi, FM, Handyside, AH & Hoffmann, ER 2015, 'Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates', Nature Genetics, vol. 47, no. 7, pp. 727-35. https://doi.org/10.1038/ng.3306

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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.",

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AU - Ottolini, Christian S

AU - Newnham, Louise J

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AU - Joshi, Hrishikesh A

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AU - Summers, Michael C

AU - Thornhill, Alan R

AU - Housworth, Elizabeth

AU - Herbert, Alex D

AU - Rienzi, Laura

AU - Ubaldi, Filippo M

AU - Handyside, Alan H

AU - Hoffmann, Eva R

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AB - 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.

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KW - Chromosome Segregation

KW - Crossing Over, Genetic

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KW - Humans

KW - Meiosis

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KW - Polar Bodies

KW - Polymorphism, Single Nucleotide

KW - Recombination, Genetic

KW - Sequence Analysis, DNA

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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EP - 735

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JF - Nature Genetics

IS - 7

ER -

Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates

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Keywords

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