David Kingsley

Although the genomes of many organisms have now been sequenced, we still know relatively little about the specific DNA sequence changes that underlie important traits and diseases. My laboratory has developed an innovative combination of genetic and genomic approaches to identify the detailed molecular mechanisms that control key vertebrate traits. We use genetic crosses in mice, stickleback fish, and pluripotent stem cells to identify key chromosome regions controlling phenotypic traits. We use comparative genomics and  gene expression analysis in different populations, species, and hybrids to identify particular genomic changes with these key regions.  And we use transgenic and genome editing approaches to test the phenotypic effect of specific genomic changes, thus providing a direct functional link  between DNA sequence changes and classic phenotypes.  By combining genetics and genomics we have been able to identify the detailed molecular basis of major changes in skeletal structures, limb development, pigmentation, and neural functions across a range of populations and species.  We are currently extending these approaches to genetic and genomic mapping of human traits and diseases using experiments with chimp and human stem cells.    We are still a long way from knowing the genomic mechanisms that have made us human. However, we believe that molecular mechanisms contributing to human  traits can now be studied, and that progress in this area will lead to important new insights into both human health and human disease.