PT  - JOURNAL ARTICLE
AU  - Douglas W. Drury
AU  - Dylan J. Siniard
AU  - Gabriel E. Zentner
AU  - Michael J. Wade
TI  - CRISPR/Cas9 gene drives in genetically variable and non-randomly mating wild populations
AID  - 10.1101/071670
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 071670
4099  - http://biorxiv.org/content/early/2016/08/25/071670.short
4100  - http://biorxiv.org/content/early/2016/08/25/071670.full
AB  - Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of CRISPR/Cas9-based synthetic gene. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many diseasevectoring arthropods. We conclude that designing such a drive will require characterization of genetic variability and the mating system within and among targeted populations.