Do epistatic modules exist in the genetic control of blood pressure in Dahl rats? A critical perspective

IN THE INITIAL DISSECTIONS of blood pressure (BP) into its genetic components using hypertensive inbred Dahl salt-sensitive rats (SS/Jr, referred to hereafter as S rats), gene-gene interactions and genetic background effects were evident. The effects of alleles at different genetic loci on a quantitative trait such as BP can be additive (plus or minus), or the combined effects can be higher or lower than the sum of the individual alleles alone (genetic interaction known as epistasis). As the techniques for the analysis of quantitative trait loci (QTL) became available, followed by the use of congenic strains, the importance of powerful genetic interactions was recognized in the Dahl S rat model, as early as 1998 and 2002 (5, 7). More recently Moreno et al. (6) showed, using a series of overlapping contiguous congenic strains involving S and Brown Norway rats, that chromosome 13 contains four highly interacting regions influencing BP.