Genetical Research



Use of randomization testing to detect multiple epistatic QTLs


ÖRJAN  CARLBORG  a1 c1 and LEIF  ANDERSSON  a1
a1 Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, BMC, Box 597, S-751 24 Uppsala, Sweden

Abstract

Here, we describe a randomization testing strategy for mapping interacting quantitative trait loci (QTLs). In a forward selection strategy, non-interacting QTLs and simultaneously mapped interacting QTL pairs are added to a total genetic model. Simultaneous mapping of epistatic QTLs increases the power of the mapping strategy by allowing detection of interacting QTL pairs where none of the QTL can be detected by their marginal additive and dominance effects. Randomization testing is used to derive empirical significance thresholds for every model selection step in the procedure. A simulation study was used to evaluate the statistical properties of the proposed randomization tests and for which types of epistasis simultaneous mapping of epistatic QTLs adds power. Least squares regression was used for QTL parameter estimation but any other QTL mapping method can be used. A genetic algorithm was used to search for interacting QTL pairs, which makes the proposed strategy feasible for single processor computers. We believe that this method will facilitate the evaluation of the importance at epistatic interaction among QTLs controlling multifactorial traits and disorders.

(Received May 8 2001)
(Revised September 28 2001)
(Revised December 10 2001)


Correspondence:
c1 Corresponding author. Tel: +46 18 471 4589. Fax: +46 18 471 4833. e-mail: orjan.carlborg@hgen.slu.se


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