The genetics of quantitative traits: challenges and prospects

Key Points Most phenotypic variation in natural populations is attributable to multiple interacting loci, with allelic effects that are sensitive to the exact environmental conditions each individual experiences. The underlying quantitative trait loci (QTLs) can be mapped by linkage to polymorphic marker loci with clear Mendelian segregation such as molecular polymorphisms. QTLs can be mapped in families or segregating progeny of crosses between genetically divergent strains (linkage mapping) or in unrelated individuals from the same population (association mapping). In both cases, large numbers of individuals are needed to detect and localize QTLs; the number of individuals and genotypes per individual needed increases as the QTL effect size decreases and the precision of localization increases. Positional cloning is the gold standard of identifying genes that correspond to QTLs. Corroborating evidence that a gene causes the variation in the trait of interest includes replication in independent studies, identifying potentially functional DNA polymorphisms between alternative alleles of one of the candidate genes, showing a difference in mRNA expression levels between genotypes, showing that mRNA or protein is expressed in tissues that are thought to be relevant to the trait, and showing that mutations in candidate genes affect the trait or fail to complement QTL alleles. Results of QTL mapping efforts in many species over the past 20 years have showed that there are key common features of the genetic architecture of quantitative traits: many loci with small effects are responsible for most quantitative genetic variation, these loci are often unexpected based on prior knowledge of the trait or correspond to computationally predicted genes; the effects of QTL alleles are highly context-dependent and vary depending on genetic background, environment and sex; and pleiotropic QTL effects are widespread. Despite 20 years of intensive effort, we have fallen short of our long-term goal of explaining genetic variation for quantitative traits in terms of the underlying genes, the effects of segregating alleles in different genetic backgrounds and in a range of ecologically relevant environments, as well as their effects on other traits, the molecular basis of functional allelic effects and the population frequency of causal variants. The challenge of dissecting quantitative traits into individual genes and their causal molecular polymorphisms will be solved in the