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Originally published as Genetics Published Articles Ahead of Print on February 19, 2006.

Genetics, Vol. 173, 197-205, May 2006, Copyright © 2006
doi:10.1534/genetics.105.054098

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High-Resolution Quantitative Trait Locus Mapping Reveals Sign Epistasis Controlling Ovariole Number Between Two Drosophila Species

Virginie Orgogozo*,1, Karl W. Broman{dagger} and David L. Stern*

* Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544 and {dagger} Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland 21205

1 Corresponding author: Princeton University, EEB Department, 106A Guyot Hall, Princeton, NJ 08544.
E-mail: virginie.orgogozo{at}normalesup.org

Identifying the genes underlying genetically complex traits is of fundamental importance for medicine, agriculture, and evolutionary biology. However, the level of resolution offered by traditional quantitative trait locus (QTL) mapping is usually coarse. We analyze here a trait closely related to fitness, ovariole number. Our initial interspecific mapping between Drosophila sechellia (8 ovarioles/ovary) and D. simulans (15 ovarioles/ovary) identified a major QTL on chromosome 3 and a minor QTL on chromosome 2. To refine the position of the major QTL, we selected 1038 additional recombinants in the region of interest using flanking morphological markers (selective phenotyping). This effort generated approximately one recombination event per gene and increased the mapping resolution by approximately seven times. Our study thus shows that using visible markers to select for recombinants can efficiently increase the resolution of QTL mapping. We resolved the major QTL into two epistatic QTL, QTL3a and QTL3b. QTL3a shows sign epistasis: it has opposite effects in two different genetic backgrounds, the presence vs. the absence of the QTL3b D. sechellia allele. This property of QTL3a allows us to reconstruct the probable order of fixation of the QTL alleles during evolution.







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