Originally published as Genetics Published Articles Ahead of Print on June 11, 2007.

Genetics, Vol. 176, 2551-2560, August 2007, Copyright © 2007
doi:10.1534/genetics.107.070953

Multipoint Identity-by-Descent Prediction Using Dense Markers to Map Quantitative Trait Loci and Estimate Effective Population Size

Theo H. E. Meuwissen*,1 and Mike E. Goddard{dagger},{ddagger}

* IHA, Norwegian University of Life Sciences, 1432 Ås, Norway, {dagger} Department of Primary Industry, Attwood, 3049 Australia and {ddagger} University of Melbourne, Melbourne, 3052 Australia

1 Corresponding author: IHA, Norwegian University of Life Sciences, Box 5003, 1432 Ås, Norway.
E-mail: theo.meuwissen{at}umb.no

A novel multipoint method, based on an approximate coalescence approach, to analyze multiple linked markers is presented. Unlike other approximate coalescence methods, it considers all markers simultaneously but only two haplotypes at a time. We demonstrate the use of this method for linkage disequilibrium (LD) mapping of QTL and estimation of effective population size. The method estimates identity-by-descent (IBD) probabilities between pairs of marker haplotypes. Both LD and combined linkage and LD mapping rely on such IBD probabilities. The method is approximate in that it considers only the information on a pair of haplotypes, whereas a full modeling of the coalescence process would simultaneously consider all haplotypes. However, full coalescence modeling is computationally feasible only for few linked markers. Using simulations of the coalescence process, the method is shown to give almost unbiased estimates of the effective population size. Compared to direct marker and haplotype association analyses, IBD-based QTL mapping showed clearly a higher power to detect a QTL and a more realistic confidence interval for its position. The modeling of LD could be extended to estimate other LD-related parameters such as recombination rates.




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