Permutation Tests for Multiple Loci Affecting a Quantitative Character

INVESTIGATIONS

Permutation Tests for Multiple Loci Affecting a Quantitative Character

R. W. Doerge and G. A. Churchill
Biometrics Unit, Cornell University, Ithaca, New York 14853

The problem of detecting minor quantitative trait loci (QTL) responsible for genetic variation not explained by major QTL is of importance in the complete dissection of quantitative characters. Two extensions of the permutation-based method for estimating empirical threshold values are presented. These methods, the conditional empirical threshold (CET) and the residual empirical threshold (RET), yield critical values that can be used to construct tests for the presence of minor QTL effects while accounting for effects of known major QTL. The CET provides a completely nonparametric test through conditioning on markers linked to major QTL. It allows for general nonadditive interactions among QTL, but its practical application is restricted to regions of the genome that are unlinked to the major QTL. The RET assumes a structural model for the effect of major QTL, and a threshold is constructed using residuals from this structural model. The search space for minor QTL is unrestricted, and RET-based tests may be more powerful than the CET-based test when the structural model is approximately true.

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				P. D. Holler, T. Yamagata, W. Jiang, M. Feuerer, C. Benoist, and D. Mathis The same genomic region conditions clonal deletion and clonal deviation to the CD8{alpha}{alpha} and regulatory T cell lineages in NOD versus C57BL/6 mice PNAS, April 24, 2007; 104(17): 7187 - 7192. [Abstract] [Full Text] [PDF]

				N. H. Martin, A. C. Bouck, and M. L. Arnold The Genetic Architecture of Reproductive Isolation in Louisiana Irises: Flowering Phenology Genetics, April 1, 2007; 175(4): 1803 - 1812. [Abstract] [Full Text] [PDF]

				B. Foley, S. F. Chenoweth, S. V. Nuzhdin, and M. W. Blows Natural Genetic Variation in Cuticular Hydrocarbon Expression in Male and Female Drosophila melanogaster Genetics, March 1, 2007; 175(3): 1465 - 1477. [Abstract] [Full Text] [PDF]

				B. E. Stranger, M. S. Forrest, M. Dunning, C. E. Ingle, C. Beazley, N. Thorne, R. Redon, C. P. Bird, A. de Grassi, C. Lee, et al. Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes Science, February 9, 2007; 315(5813): 848 - 853. [Abstract] [Full Text] [PDF]

				N. Grarup, M. K. Andersen, C. H. Andreasen, A. Albrechtsen, K. Borch-Johnsen, T. Jorgensen, J. Auwerx, O. Schmitz, T. Hansen, and O. Pedersen Studies of the Common DIO2 Thr92Ala Polymorphism and Metabolic Phenotypes in 7342 Danish White Subjects J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 363 - 366. [Abstract] [Full Text] [PDF]

				S. M. Rogers, N. Isabel, and L. Bernatchez Linkage Maps of the dwarf and Normal Lake Whitefish (Coregonus clupeaformis) Species Complex and Their Hybrids Reveal the Genetic Architecture of Population Divergence Genetics, January 1, 2007; 175(1): 375 - 398. [Abstract] [Full Text] [PDF]

				T. E. Scheetz, K.-Y. A. Kim, R. E. Swiderski, A. R. Philp, T. A. Braun, K. L. Knudtson, A. M. Dorrance, G. F. DiBona, J. Huang, T. L. Casavant, et al. Regulation of gene expression in the mammalian eye and its relevance to eye disease PNAS, September 26, 2006; 103(39): 14429 - 14434. [Abstract] [Full Text] [PDF]

				M. Buresova, V. Zidek, A. Musilova, M. Simakova, A. Fucikova, V. Bila, V. Kren, L. Kazdova, R. Di Nicolantonio, and M. Pravenec Genetic relationship between placental and fetal weights and markers of the metabolic syndrome in rat recombinant inbred strains Physiol Genomics, September 14, 2006; 26(3): 226 - 231. [Abstract] [Full Text] [PDF]

				K. W. Jordan, T. J. Morgan, and T. F. C. Mackay Quantitative Trait Loci for Locomotor Behavior in Drosophila melanogaster Genetics, September 1, 2006; 174(1): 271 - 284. [Abstract] [Full Text] [PDF]