An example how intersection of genomics and evolution can generate novel approaches for macroevolutionary reconstruction is our recent development of genomic phylostratigraphy. As the application of evolutionary theory in biomedical research has proven to have substantial explanatory potential, it is tempting to test this novel approach on biomedical data. Indeed, by applying phylostratigraphy on human genome data we were able to show that evolutionary origin of disease genes is not random. Clear bias towards old genes led us to propose that genetic diseases are an inescapable component of life. These regularities will allow easier identification of novel disease genes in the future, in particular those involved in multi-factorial diseases. We believe that similar evolutionary and systems biology approaches could further inform future biomedical research strategies and bring quite novel and unexpected perspectives on the distal causes of human diseases. Accordingly, an important extension of our work on evolutionary patterns of human genetic diseases would be to incorporate gene expression as another level of analysis. Within the scope of the proposed project we plan to explore, using phylostratigraphic approach, relationship among evolutionary age of the genes, full ontogenetic timing of their expression and their disease status. We plan to generate a genome-wide microarray expression dataset which covers full ontogeny of zebrafish in high resolution. Proposed project objectives represent a quite unique and novel macroevolutionary-developmental view on genetic diseases and we anticipate that expected project results carry potential to substantially enlighten our understanding of distal causes of the genetic diseases. Proposed project represents up to date joint efforts in evolutionary genetics of the Ruđer Bošković Institute, Zagreb and the Max-Planck-Institute for Evolutionary Biology, Plön and will allow knowledge and technology transfer in Croatia.