Advances in Statistical Methods to Map Quantitative Trait Loci in Outbred Populations

INVESTIGATIONS

Advances in Statistical Methods to Map Quantitative Trait Loci in Outbred Populations

I. Hoeschele, P. Uimari, F. E. Grignola, Q. Zhang and K. M. Gage
Interdepartmental Genetics Program and Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0315

Statistical methods to map quantitative trait loci (QTL) in outbred populations are reviewed, extensions and applications to human and plant genetic data are indicated, and areas for further research are identified. Simple and computationally inexpensive methods include (multiple) linear regression of phenotype on marker genotypes and regression of squared phenotypic differences among relative pairs on estimated proportions of identity-by-descent at a locus. These methods are less suited for genetic parameter estimation in outbred populations but allow the determination of test statistic distributions via simulation or data permutation; however, further inferences including confidence intervals of QTL location require the use of Monte Carlo or bootstrap sampling techniques. A method which is intermediate in computational requirements is residual maximum likelihood (REML) with a covariance matrix of random QTL effects conditional on information from multiple linked markers. Testing for the number of QTLs on a chromosome is difficult in a classical framework. The computationally most demanding methods are maximum likelihood and Bayesian analysis, which take account of the distribution of multilocus marker-QTL genotypes on a pedigree and permit investigators to fit different models of variation at the QTL. The Bayesian analysis includes the number of QTLs on a chromosome as an unknown.

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				G. Freyer, P. Sorensen, C. Kuhn, R. Weikard, and I. Hoeschele Search for Pleiotropic QTL on Chromosome BTA6 Affecting Yield Traits of Milk Production J Dairy Sci, March 1, 2003; 86(3): 999 - 1008. [Abstract] [Full Text] [PDF]

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				T. H. E. Meuwissen, A. Karlsen, S. Lien, I. Olsaker, and M. E. Goddard Fine Mapping of a Quantitative Trait Locus for Twinning Rate Using Combined Linkage and Linkage Disequilibrium Mapping Genetics, May 1, 2002; 161(1): 373 - 379. [Abstract] [Full Text] [PDF]

				R. D. Ball Bayesian Methods for Quantitative Trait Loci Mapping Based on Model Selection: Approximate Analysis Using the Bayesian Information Criterion Genetics, November 1, 2001; 159(3): 1351 - 1364. [Abstract] [Full Text] [PDF]

				O. Carlborg, L. Andersson-Eklund, and L. Andersson Parallel Computing in Interval Mapping of Quantitative Trait Loci J. Hered., September 1, 2001; 92(5): 449 - 451. [Abstract] [Full Text] [PDF]

				N. Yi and S. Xu Bayesian Mapping of Quantitative Trait Loci Under Complicated Mating Designs Genetics, April 1, 2001; 157(4): 1759 - 1771. [Abstract] [Full Text]

				R. Wu and Z.-B. Zeng Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations Genetics, February 1, 2001; 157(2): 899 - 909. [Abstract] [Full Text]

				S. Xu and N. Yi Mixed model analysis of quantitative trait loci PNAS, December 8, 2000; (2000) 250235197. [Abstract] [Full Text]

				A. W. George, P. M. Visscher, and C. S. Haley Mapping Quantitative Trait Loci in Complex Pedigrees: A Two-Step Variance Component Approach Genetics, December 1, 2000; 156(4): 2081 - 2092. [Abstract] [Full Text]

				M. Pérez-Enciso and L. Varona Quantitative Trait Loci Mapping in F2 Crosses Between Outbred Lines Genetics, May 1, 2000; 155(1): 391 - 405. [Abstract] [Full Text]

				T. H. E. Meuwissen and M. E. Goddard Fine Mapping of Quantitative Trait Loci Using Linkage Disequilibria With Closely Linked Marker Loci Genetics, May 1, 2000; 155(1): 421 - 430. [Abstract] [Full Text]

				R. L. Wu Mapping Quantitative Trait Loci by Genotyping Haploid Tissues Genetics, August 1, 1999; 152(4): 1741 - 1752. [Abstract] [Full Text]

				M. J. Sillanpää and E. Arjas Bayesian Mapping of Multiple Quantitative Trait Loci From Incomplete Outbred Offspring Data Genetics, April 1, 1999; 151(4): 1605 - 1619. [Abstract] [Full Text]

				K. Demarest, J. McCaughran Jr, E. Mahjubi, L. Cipp, and R. Hitzemann Identification of an Acute Ethanol Response Quantitative Trait Locus on Mouse Chromosome 2 J. Neurosci., January 15, 1999; 19(2): 549 - 561. [Abstract] [Full Text] [PDF]

				M. C. A. M. Bink and J. A. M. Van Arendonk Detection of Quantitative Trait Loci in Outbred Populations With Incomplete Marker Data Genetics, January 1, 1999; 151(1): 409 - 420. [Abstract] [Full Text]

				Q. Zhang, D. Boichard, I. Hoeschele, C. Ernst, A. Eggen, B. Murkve, M. Pfister-Genskow, L. A. Witte, F. E. Grignola, P. Uimari, et al. Mapping Quantitative Trait Loci for Milk Production and Health of Dairy Cattle in a Large Outbred Pedigree Genetics, August 1, 1998; 149(4): 1959 - 1973. [Abstract] [Full Text] [PDF]