Consequences of Recombination Rate Variation on Quantitative Trait Locus Mapping Studies: Simulations Based on the Drosophila melanogaster Genome

Corresponding author: Mohamed A. F. Noor, Department of Biological Sciences, Life Sciences Bldg., Louisiana State University, Baton Rouge, LA 70803., mnoor{at}lsu.edu (E-mail)

Communicating editor: Z-B. ZENG

We examine the effect of variation in gene density per centimorgan on quantitative trait locus (QTL) mapping studies using data from the Drosophila melanogaster genome project and documented regional rates of recombination. There is tremendous variation in gene density per centimorgan across this genome, and we observe that this variation can cause systematic biases in QTL mapping studies. Specifically, in our simulated mapping experiments of 50 equal-effect QTL distributed randomly across the physical genome, very strong QTL are consistently detected near the centromeres of the two major autosomes, and few or no QTL are often detected on the X chromosome. This pattern persisted with varying heritability, marker density, QTL effect sizes, and transgressive segregation. Our results are consistent with empirical data collected from QTL mapping studies of this species and its close relatives, and they explain the "small X-effect" that has been documented in genetic studies of sexual isolation in the D. melanogaster group. Because of the biases resulting from recombination rate variation, results of QTL mapping studies should be taken as hypotheses to be tested by additional genetic methods, particularly in species for which detailed genetic and physical genome maps are not available.

This article has been cited by other articles:

				K. Bullaughey, M. Przeworski, and G. Coop No effect of recombination on the efficacy of natural selection in primates Genome Res., April 1, 2008; 18(4): 544 - 554. [Abstract] [Full Text] [PDF]

				C. Lee Selection Bias in Quantitative Trait Loci Mapping J. Hered., July 1, 2005; 96(4): 363 - 367. [Abstract] [Full Text] [PDF]

				J. G. Mezey, D. Houle, and S. V. Nuzhdin Naturally Segregating Quantitative Trait Loci Affecting Wing Shape of Drosophila melanogaster Genetics, April 1, 2005; 169(4): 2101 - 2113. [Abstract] [Full Text] [PDF]

				A. J. Betancourt, Y. Kim, and H. A. Orr A Pseudohitchhiking Model of X vs. Autosomal Diversity Genetics, December 1, 2004; 168(4): 2261 - 2269. [Abstract] [Full Text] [PDF]

				M. Slotman, A. della Torre, and J. R. Powell The Genetics of Inviability and Male Sterility in Hybrids Between Anopheles gambiae and An. arabiensis Genetics, May 1, 2004; 167(1): 275 - 287. [Abstract] [Full Text] [PDF]

				M. I. Jensen-Seaman, T. S. Furey, B. A. Payseur, Y. Lu, K. M. Roskin, C.-F. Chen, M. A. Thomas, D. Haussler, and H. J. Jacob Comparative Recombination Rates in the Rat, Mouse, and Human Genomes Genome Res., April 1, 2004; 14(4): 528 - 538. [Abstract] [Full Text] [PDF]

				C. K. Griswold and M. C. Whitlock The Genetics of Adaptation: The Roles of Pleiotropy, Stabilizing Selection and Drift in Shaping the Distribution of Bidirectional Fixed Mutational Effects Genetics, December 1, 2003; 165(4): 2181 - 2192. [Abstract] [Full Text] [PDF]

				K. L. Montooth, J. H. Marden, and A. G. Clark Mapping Determinants of Variation in Energy Metabolism, Respiration and Flight in Drosophila Genetics, October 1, 2003; 165(2): 623 - 635. [Abstract] [Full Text] [PDF]