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Wysoker, Alec

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Wysoker, Alec

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Author's Publications: search.filters.isAuthorOfPublication.6f765751-5785-4697-89b9-d132f3e3f379

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    Insights about variation in meiosis from 31,228 human sperm genomes
    (Springer Nature, 2019-05-02) Bell, Avery; Mello, Curtis; Nemesh, James; Brumbaugh, Sara A; Wysoker, Alec; McCarroll, Steven
    Meiosis, while critical for reproduction, is also variable and error-prone: crossover rates vary among gametes, between the sexes, and among humans of the same sex, and chromosome mis-segregation leads to aneuploidy1-8. To study diverse meiotic outcomes and how they co-vary across chromosomes, gametes, and humans, we developed Sperm-seq, a way to simultaneously sequence the genomes of thousands of individual sperm. We analyzed the genomes of 31,228 human gametes from 20 sperm donors, identifying 813,122 crossovers and 787 aneuploid chromosomes. Sperm donors had aneuploidy rates ranging from 0.01 to 0.05 aneuploidies per gamete; crossovers partially protected chromosomes from nondisjunction at meiosis I. Some chromosomes and donors underwent more-frequent non-disjunction during the meiosis I cell division, while other chromosomes and donors showed more segregation failures during meiosis II; many genomic anomalies that could not be explained by simple nondisjunction also occurred. Diverse recombination phenotypes – from crossover rates to crossover location and separation (a measure of crossover interference) – co-varied strongly across individuals and cells. Our results can be incorporated with earlier observations into a unified model in which a core mechanism – the variable physical compaction of meiotic chromosomes – generates inter-individual and cell-to-cell variation in diverse meiotic phenotypes.