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

Received 11 November 2014; accepted 23 April 2015; published online 18 May 2015; doi:10.1038/ng.3306

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 ,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.