Where are all of the QTL that are so consistently detected in pedigrees and in experimental crosses, when we transition to outbred populations? Why is it that 10 loci can each explain 5% of the genetic variance and most of the heritability in a cross between two strains, but in no case has GWAS yet found more than one locus with an effect size that large? Two explanations can be forwarded immediately: first, the QTL are actually rare variants that only contribute in that cross, and so are precisely the rare variants predicted by the rare allele theory; or second, each cross captures just a small fraction of the genetic variance in a population, so QTL with relatively large effects in one cross will be expected to be diluted in their contribution relative to other QTL when measured in the entire population. In many cases as well, the effect size estimated in the cross will be an overestimate due to the Beavis effect/winner’s curse101,102, while in an unknown proportion of cases, QTL will turn out to be due to multiple
