Developmental gene expression differences between humans and mammalian models

Identifying the molecular programs underlying human organ development and how they differ from those in model species will advance our understanding of human health and disease. Developmental gene expression profiles provide a window into the genes underlying organ development as well as a direct means to compare them across species. We use a transcriptomic resource for mammalian organ development to characterize the temporal profiles of human genes associated with distinct disease classes and to determine, for each human gene, the similarity of its spatiotemporal expression with its orthologs in rhesus macaque, mouse, rat and rabbit. We find that half of human genes differ from their mouse orthologs in their temporal trajectories. These include more than 200 disease genes associated with brain, heart and liver disease, for which mouse models should undergo extra scrutiny. We provide a new resource that evaluates for every human gene its suitability to be modeled in different mammalian species.