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High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice

View ORCID ProfileY. Yin, View ORCID ProfileY. Jiang, J. B. Berletch, View ORCID ProfileC. M. Disteche, W. S. Noble, F. J. Steemers, View ORCID ProfileA. C. Adey, View ORCID ProfileJ. A. Shendure
doi: https://doi.org/10.1101/338053
Y. Yin
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
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Y. Jiang
2Unaffiliated
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J. B. Berletch
3Department of Pathology, University of Washington, Seattle, Washington, USA
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C. M. Disteche
3Department of Pathology, University of Washington, Seattle, Washington, USA
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W. S. Noble
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
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F. J. Steemers
4Illumina, San Diego, California, USA
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A. C. Adey
5Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.
6Knight Cardiovascular Institute, Portland, Oregon, USA
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  • For correspondence: adey@ohsu.edu shendure@uw.edu
J. A. Shendure
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
7Brotman Baty Institute for Precision Medicine, Seattle, WA 98195
8Howard Hughes Medical Institute, Seattle, Washington, USA
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  • For correspondence: adey@ohsu.edu shendure@uw.edu
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Abstract

We developed “sci-LIANTI”, a high-throughput, high-coverage single-cell DNA sequencing method that combines single-cell combinatorial indexing (“sci”) and linear amplification via transposon insertion (“LIANTI”). To characterize rare chromosome mis-segregation events in male meiosis and their relationship to the landscape of meiotic crossovers, we applied sci-LIANTI to profile the genomes of 6,928 sperm and sperm precursors from infertile, interspecific F1 male mice. From 1,663 haploid and 292 diploid cells, we mapped 24,672 crossover events and identified genomic and epigenomic contexts that influence crossover hotness. Surprisingly, we observed frequent mitotic chromosome segregation during meiosis. Moreover, segregation during meiosis in individual cells was highly biased towards either mitotic or meiotic events. We anticipate that sci-LIANTI can be applied to fully characterize various recombination landscapes, as well as to other fields requiring high-throughput, high-coverage single-cell genome sequencing.

One Sentence Summary Single-cell genome sequencing maps crossover and non-meiotic chromosome segregation during spermatogenesis in interspecific hybrid mice.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 12, 2018.
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High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice
Y. Yin, Y. Jiang, J. B. Berletch, C. M. Disteche, W. S. Noble, F. J. Steemers, A. C. Adey, J. A. Shendure
bioRxiv 338053; doi: https://doi.org/10.1101/338053
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High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice
Y. Yin, Y. Jiang, J. B. Berletch, C. M. Disteche, W. S. Noble, F. J. Steemers, A. C. Adey, J. A. Shendure
bioRxiv 338053; doi: https://doi.org/10.1101/338053

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