Genetic architecture of quantitative traits in mice, flies, and humans

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Abstract
We compare and contrast the genetic architecture of quantitative phenotypes in two genetically well-characterized model organisms, the laboratory mouse, Mus musculus, and the fruit fly, Drosophila melanogaster, with that found in our own species from recent successes in genome-wide association studies. We show that the current model of large numbers of loci, each of small effect, is true for all species examined, and that discrepancies can be largely explained by differences in the experimental designs used. We argue that the distribution of effect size of common variants is the same for all phenotypes regardless of species, and we discuss the importance of epistasis, pleiotropy, and gene by environment interactions. Despite substantial advances in mapping quantitative trait loci, the identification of the quantitative trait genes and ultimately the sequence variants has proved more difficult, so that our information on the molecular basis of quantitative variation remains limited. Nevertheless, available data indicate that many variants lie outside genes, presumably in regulatory regions of the genome, where they act by altering gene expression. As yet there are very few instances where homologous quantitative trait loci, or quantitative trait genes, have been identified in multiple species, but the availability of high-resolution mapping data will soon make it possible to test the degree of overlap between species.