Efficient allelic-drive in Drosophila.
Title | Efficient allelic-drive in Drosophila. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Guichard A, Haque T, Bobik M, Xu X-RS, Klanseck C, Kushwah RBabu Singh, Berni M, Kaduskar B, Gantz VM, Bier E |
Journal | Nat Commun |
Volume | 10 |
Issue | 1 |
Pagination | 1640 |
Date Published | 2019 04 09 |
ISSN | 2041-1723 |
Keywords | Agriculture, Alleles, Animals, Animals, Genetically Modified, CRISPR-Cas Systems, DNA End-Joining Repair, DNA Mutational Analysis, Drosophila, Female, Gene Drive Technology, Gene Editing, Inheritance Patterns, Male, Mosaicism, RNA, Guide |
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. |
DOI | 10.1038/s41467-019-09694-w |
Alternate Journal | Nat Commun |
PubMed ID | 30967548 |
PubMed Central ID | PMC6456580 |
Grant List | DP5 OD023098 / OD / NIH HHS / United States P30 NS047101 / NS / NINDS NIH HHS / United States R01 GM117321 / GM / NIGMS NIH HHS / United States |