Previous work by CGD faculty has established two critical properties of quantitative trait loci (QTL). First, they represent only a sub-set of the totality of genes functionally required for a complex trait such as the regulation of blood pressure or relative susceptibility to atherosclerosis. And second, the same sub-set of genes determine QTLs across mammalian species. QTLs for a given trait are often located at homologous chromosomal locations in human, mouse and rat. A probable explanation for these findings is that QTLs represent key regulatory functions whose role has been conserved over the course of mammalian evolution. Given that the QTLs for various phenotypes are responsible for most of the population variation on which evolution can act and that the identity of these QTL is an ancient property of mammals, genome dynamics predicts that the QTLs for fundamental physiological properties are likely to be genetically linked to promote the co-inheritance of favorable allelic combinations. The hypothesis of this project is that functional domains are a general feature of mammalian chromosomal organization and will be revealed by the clustering of QTLs affecting a phenotype. Rigorously testing this hypothesis requires that we efficiently locate QTLs at a resolution of a few Mb or less across the diversity of Mus subspecies.
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