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Efficient allelic-drive in Drosophila

Author

Listed:
  • Annabel Guichard

    (University of California, San Diego)

  • Tisha Haque

    (University of California, San Diego)

  • Marketta Bobik

    (University of California, San Diego)

  • Xiang-Ru S. Xu

    (University of California, San Diego)

  • Carissa Klanseck

    (University of California, San Diego)

  • Raja Babu Singh Kushwah

    (University of California, San Diego
    Tata Institute for Genetics and Society-India (TIGS), TIGS Center at inStem)

  • Mateus Berni

    (Universidade Federal do Rio de Janeiro
    Federal University of Rio de Janeiro (PCM/UFRJ))

  • Bhagyashree Kaduskar

    (University of California, San Diego
    Tata Institute for Genetics and Society-India (TIGS), TIGS Center at inStem)

  • Valentino M. Gantz

    (University of California, San Diego)

  • Ethan Bier

    (University of California, San Diego
    Tata Institute for Genetics and Society-UCSD)

Abstract

Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this “active genetic” approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as “shadow-drive”, have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox.

Suggested Citation

  • Annabel Guichard & Tisha Haque & Marketta Bobik & Xiang-Ru S. Xu & Carissa Klanseck & Raja Babu Singh Kushwah & Mateus Berni & Bhagyashree Kaduskar & Valentino M. Gantz & Ethan Bier, 2019. "Efficient allelic-drive in Drosophila," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09694-w
    DOI: 10.1038/s41467-019-09694-w
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    Cited by:

    1. Gerard Terradas & Jared B. Bennett & Zhiqian Li & John M. Marshall & Ethan Bier, 2023. "Genetic conversion of a split-drive into a full-drive element," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Sebald A. N. Verkuijl & Estela Gonzalez & Ming Li & Joshua X. D. Ang & Nikolay P. Kandul & Michelle A. E. Anderson & Omar S. Akbari & Michael B. Bonsall & Luke Alphey, 2022. "A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Zhiqian Li & Lang You & Anita Hermann & Ethan Bier, 2024. "Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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