Effect of within-strain sample size on QTL detection and mapping using recombinant inbred mouse strains

Increasing the number of mice used to calculate recombinant inbred (RI) strain means increases the accuracy of determining the phenotype associated with each genotype (strain), which in turn enhances quantitative trait locus (QTL) detection and mapping. The purpose of this paper is to examine quantitatively the effect of within-strain sample size (n) on additive QTL mapping efficiency and to make comparisons with F-2 and backcross (BC) populations, where each genotype is represented by only a single mouse. When 25 RI strains are used, the estimated equivalent number of F-2 mice yielding the same power to detect QTLs varies inversely as a function of the heritability of the trait in the RI population (h(RI)(2)). For example, testing 25 strains with n = 10 per strain is approximately equivalent to 160 F-2 mice when h(RI)(2) = 0.2, but only 55 when h(RI)(2) = 0.6. While increasing n is always beneficial, the gain in power as n increases is greatest when h(RI)(2) is low and is much diminished at high h(RI)(2) values. Thus, when h(RI)(2) is high, there is little advantage of large n, even when n approaches infinity. A cost analysis suggested that RI populations are more cost-effective than conventional selectively genotyped F-2 populations at h(RI)(2) values likely to be seen in behavioral studies. However, with DNA pooling, this advantage is greatly reduced and may be reversed depending on the values of h(RI)(2) and n.