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

TY - JOUR

T1 - Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates

AU - Ottolini, Christian S

AU - Newnham, Louise J

AU - Capalbo, Antonio

AU - Natesan, Senthilkumar A

AU - Joshi, Hrishikesh A

AU - Cimadomo, Danilo

AU - Griffin, Darren K

AU - Sage, Karen

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

PY - 2015/6/26

Y1 - 2015/6/26

N2 - 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.

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.

KW - Cells, Cultured

KW - Chromosome Mapping

KW - Chromosome Segregation

KW - Crossing Over, Genetic

KW - Female

KW - Genome, Human

KW - Humans

KW - Meiosis

KW - Oocytes

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

U2 - 10.1038/ng.3306

DO - 10.1038/ng.3306

M3 - Journal article

C2 - 25985139

SN - 1061-4036

VL - 47

SP - 727

EP - 735

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -