Data from: Fine-mapping nicotine resistance loci in Drosophila using a multiparent advanced generation inter-cross population

Animals in nature are frequently challenged by toxic compounds, from those that occur naturally in plants as a defense against herbivory, to pesticides used to protect crops. On exposure to such xenobiotic substances, animals mount a transcriptional response, generating detoxification enzymes and transporters that metabolize and remove the toxin. Genetic variation in this response can lead to variation in the susceptibility of different genotypes to the toxic effects of a given xenobiotic. Here we use Drosophila melanogaster to dissect the genetic basis of larval resistance to nicotine, a common plant defense chemical and widely used addictive drug in humans. We identified quantitative trait loci (QTL) for the trait using the DSPR (Drosophila Synthetic Population Resource), a panel of multiparental advanced intercross lines. Mapped QTL collectively explain 68.4% of the broad-sense heritability for nicotine resistance. The two largest-effect loci—contributing 50.3 and 8.5% to the genetic variation—map to short regions encompassing members of classic detoxification gene families. The largest QTL resides over a cluster of ten UDP-glucuronosyltransferase (UGT) genes, while the next largest QTL harbors a pair of cytochrome P450 genes. Using RNA-seq we measured gene expression in a pair of DSPR founders predicted to harbor different alleles at both QTL and showed that Ugt86Dd, Cyp28d1, and Cyp28d2 had significantly higher expression in the founder carrying the allele conferring greater resistance. These genes are very strong candidates to harbor causative, regulatory polymorphisms that explain a large fraction of the genetic variation in larval nicotine resistance in the DSPR.R script for QTL analysis (B population)This R script allows a user to read in genotype data for the DSPR (Drosophila Synthetic Population Resource, FlyRILs.org) and nicotine resistance phenotype data, and recapitulate the QTL mapping results presented in Marriage et al. for the "B" population of DSPR RILs.Nicotine_pB_AnalysisCode.RR script for QTL analysis (A population)This R script allows a user to read in genotype data for the DSPR (Drosophila Synthetic Population Resource, FlyRILs.org) and nicotine resistance phenotype data, and recapitulate the QTL mapping results presented in Marriage et al. for the "A" population of DSPR RILs.Nicotine_pA_AnalysisCode.RNicotine Resistance Phenotypes (A population)This file contains nicotine resistance measures for a large number of A lines from the Drosophila Synthetic Population Resource (DSPR, www.FlyRILs.org). Line identifiers are presented in the "patRIL" column, and phenotypes are presented in the "NicotineViability" column. Together with genotype data and analytical R code this file allows users to generate the QTL mapping results presented in Marriage et al. for the A population of DSPR RILs.NicotinePheno_A.txtNicotine Resistance Phenotypes (B population)This file contains nicotine resistance measures for a large number of B lines from the Drosophila Synthetic Population Resource (DSPR, www.FlyRILs.org). Line identifiers are presented in the "patRIL" column, and phenotypes are presented in the "NicotineViability" column. Together with genotype data and analytical R code this file allows users to generate the QTL mapping results presented in Marriage et al. for the B population of DSPR RILs.NicotinePheno_B.txtDSPR Genotypes (A population)This file contains genotypes for the population A RILs (Recombination Inbred Lines) of the DSPR (Drosophila Synthetic Population Resource). The genotypes were originally published in King et al. (Genome Research 2012, 22:1558-66) and are also available at www.FlyRILs.org (Data Release 2 - HMM Results for pA RILs at regularly spaced 10 kb intervals). The genotypes are derived from a Hidden Markov Model (HMM) at regularly spaced 10KB positions along the Drosophila melanogaster genome. There are no column headers in the file. Columns are: chromosome, genome position, line identifier, 36 columns of founder genotype probabilities, and 8 columns of additive probabilities. The precise names for each of the columns are listed in the analysis R code file for population A. Together with this code, and the nicotine resistance phenotype scores, a user can recapitulate the QTL mapping from Marriage et al.HMMregA_R2.tgzDSPR Genotypes (B population)This file contains genotypes for the population B RILs (Recombination Inbred Lines) of the DSPR (Drosophila Synthetic Population Resource). The genotypes were originally published in King et al. (Genome Research 2012, 22:1558-66) and are also available at www.FlyRILs.org (Data Release 2 - HMM Results for pB RILs at regularly spaced 10 kb intervals). The genotypes are derived from a Hidden Markov Model (HMM) at regularly spaced 10KB positions along the Drosophila melanogaster genome. There are no column headers in the file. Columns are: chromosome, genome position, line identifier, 36 columns of founder genotype probabilities, and 8 columns of additive probabilities. The precise names for each of the columns are listed in the analysis R code file for population B. Together with this code, and the nicotine resistance phenotype scores, a user can recapitulate the QTL mapping from Marriage et al.HMMregB_R2.tg