TY - JOUR T1 - Insights about variation in meiosis from 31,228 human sperm genomes JF - bioRxiv DO - 10.1101/625202 SP - 625202 AU - Avery Davis Bell AU - Curtis J. Mello AU - James Nemesh AU - Sara A. Brumbaugh AU - Alec Wysoker AU - Steven A. McCarroll Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/02/625202.abstract N2 - Meiosis, while critical for reproduction, is also highly variable and error prone: crossover rates vary among humans and individual gametes, and chromosome nondisjunction leads to aneuploidy, a leading cause of miscarriage. To study variation in meiotic outcomes within and across individuals, we developed a way to sequence many individual sperm genomes at once. We used this method to sequence the genomes of 31,228 gametes from 20 sperm donors, identifying 813,122 crossovers, 787 aneuploid chromosomes, and unexpected genomic anomalies. Different sperm donors varied four-fold in the frequency of aneuploid sperm, and aneuploid chromosomes gained in meiosis I had 36% fewer crossovers than corresponding non-aneuploid chromosomes. Diverse recombination phenotypes were surprisingly coordinated: donors with high average crossover rates also made a larger fraction of their crossovers in centromere-proximal regions and placed their crossovers closer together. These same relationships were also evident in the variation among individual gametes from the same donor: sperm with more crossovers tended to have made crossovers closer together and in centromere-proximal regions. Variation in the physical compaction of chromosomes could help explain this coordination of meiotic variation across chromosomes, gametes, and individuals. ER -