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Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster

Nature Genetics volume 39, pages 264268 (2007) | Download Citation

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Abstract

Although most genetic association studies are performed with the intention of detecting nucleotide polymorphisms that are correlated with a complex trait, transcript abundance should also be expected to associate with diseases or phenotypes. We performed a scan for such quantitative trait transcripts in adult female heads of the fruit fly (Drosophila melanogaster) that might explain variation for nicotine resistance. The strongest association was seen for abundance of ornithine aminotransferase transcripts, implicating detoxification and neurotransmitter biosynthesis as mediators of the quantitative response to the drug. Subsequently, genetic analysis and metabolite profiling confirmed a complex role for ornithine and GABA levels in modification of survival time upon chronic nicotine exposure. Differences between populations from North Carolina and California suggest that the resistance mechanism may be an evolved response to environmental exposure.

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Acknowledgements

We thank S. Nuzhdin for providing the California inbred lines and R. Carrillo for initial sampling of nicotine resistance. This paper is dedicated to the memory of R. Rose, who first pointed out the lindane connection in our data. This work was supported by US National Institutes of Health grant P01-GM45344 to G.G.

Author information

Affiliations

  1. Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.

    • Gisele Passador-Gurgel
    • , Priscilla Hunt
    •  & Greg Gibson
  2. Department of Statistics, National Tsing Hua University, Hsinchu 30013, Taiwan.

    • Wen-Ping Hsieh
  3. Metabolomics and Proteomics Laboratory, North Carolina State University, Raleigh, North Carolina, 27695 USA.

    • Nigel Deighton

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Contributions

G.P.-G. performed all of the data analysis and experimental components, with the exception of the genetic complementation test (P.H.) and metabolite profiling (N.D.). She was assisted by W.-P.H. in the statistical analysis. G.G. conceived the experiment and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Greg Gibson.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Schematic of OAT function.

  2. 2.

    Supplementary Fig. 2

    Regression of nicotine concentration on survival time.

  3. 3.

    Supplementary Fig. 3

    qRT-PCR of Gad1.

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    Supplementary Table 1

    Expression on nicotine correlated to survival time.

  5. 5.

    Supplementary Table 2

    Expression on control food correlated to survival time.

  6. 6.

    Supplementary Table 3

    Primers.

  7. 7.

    Supplementary Methods

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DOI

https://doi.org/10.1038/ng1944

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