Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
119-328 |
DRI_Challenge |
denotes |
he sequence polymorphisms underlying complex trait variation is a key goal of genetics research, since knowing the precise causative molecular events allows insight into the pathways governing trait variation. |
T2 |
329-489 |
DRI_Background |
denotes |
Genetic analysis of complex traits in model systems regularly starts by constructing QTL maps, but generally fails to identify causative sequence polymorphisms. |
T3 |
490-708 |
DRI_Approach |
denotes |
Previously we mapped a series of QTL contributing to resistance to nicotine in a Drosophila melanogaster multiparental mapping resource, and here use a battery of functional tests to resolve QTL to the molecular level. |
T4 |
709-942 |
DRI_Background |
denotes |
One large-effect QTL resided over a cluster of UDP-glucuronosyltransferases, and quantitative complementation tests using deficiencies eliminating subsets of these detoxification genes revealed allelic variation impacting resistance. |
T5 |
943-1122 |
DRI_Outcome |
denotes |
RNAseq showed that Ugt86Dd had significantly higher expression in genotypes that are more resistant to nicotine, and anterior midgut-specific RNAi of this gene reduced resistance. |
T6 |
1123-1332 |
DRI_Approach |
denotes |
We discovered a segregating 22-bp frameshift deletion in Ugt86Dd, and accounting for the InDel during mapping largely eliminates the QTL, implying the event explains the bulk of the effect of the mapped locus. |
T7 |
1333-1532 |
DRI_Background |
denotes |
CRISPR/Cas9 editing a relatively resistant genotype to generate lesions in Ugt86Dd that recapitulate the naturally-occurring putative loss-of-function allele leads to a large reduction in resistance. |
T8 |
1533-1720 |
DRI_Outcome |
denotes |
Despite this major effect of the deletion, the allele appears to be very rare in wild-caught populations, and likely explains only a small fraction of the natural variation for the trait. |
T9 |
1721-1856 |
DRI_Challenge |
denotes |
Nonetheless, this putatively causative coding InDel can be a launchpad for future mechanistic exploration of xenobiotic detoxification. |