The Deep Genome Project
K. C. Kent Lloyd, David J. Adams, Gareth Baynam, Arthur L. Beaudet, Fátima Bosch, Kym M. Boycott, Robert E. Braun, Mark J. Caulfield, Ronald D. Cohn, Mary E. Dickinson, Michael S. Dobbie, Ann M. Flenniken, Paul Flicek, Sanjeev Galande, Xiang Gao, Anne Grobler, Jason D. Heaney, Yann Hérault, Martin Hrabě de Angelis, James R. Lupski, Stanislas Lyonnet, Ann‐Marie Mallon, Fabio Mammano, Calum A. MacRae, Roderick R. McInnes, Colin McKerlie, Terrence F. Meehan, Stephen A. Murray, Lauryl M. J. Nutter, Yuichi Obata, Helen Parkinson, Michael S. Pepper, Radislav Sedláček, Je Kyung Seong, Toshihiko Shiroishi, Damian Smedley, Glauco P. Tocchini‐Valentini, David Valle, Chi‐Kuang Leo Wang, Sara Wells, Jacqueline K. White, Wolfgang Wurst, Ying Xu, Steve D. M. Brown
Abstract
In vivo research is critical to the functional dissection of \nmulti-organ systems and whole organism physiology, and \nthe laboratory mouse remains a quintessential animal model \nfor studying mammalian, especially human, pathobiology. \nEnabled by technological innovations in genome sequencing, \nmutagenesis and genome editing, phenotype analyses, and \nbioinformatics, in vivo analysis of gene function and dysfunction \nin the mouse has delivered new understanding of the \nmechanisms of disease and accelerated medical advances. \nHowever, many significant hurdles have limited the elucidation \nof mechanisms underlying both rare and complex, \nmultifactorial diseases, leaving significant gaps in our scientific \nknowledge. Future progress in developing a functionally \nannotated genome map depends upon studies in model organisms, \nnot least the mouse. Further, recent advances in \ngenetic manipulation and in vivo, in vitro, and in silico phenotyping \ntechnologies in the mouse make annotation of the \nvast majority of functional elements within the mammalian \ngenome feasible. The implementation of a Deep Genome \nProject—to deliver the functional biological annotation of all human orthologous genomic elements in mice—is an essential \nand executable strategy to transform our understanding \nof genetic and genomic variation in human health and disease \nthat will catalyze delivery of the promised benefits of \ngenomic medicine to children and adults around the world.