The vertebrate genome contains a predicted 20,000+ genes, many of unknown biological role(s). In addition, a large fraction of these molecules have distinct functions in diverse processes. The functional annotation of genes is one of the major next steps in understanding the vertebrate genome. Indeed, despite over a decade after the completion of the human genome effort, the diversity of genes undergoing active research has not substantially changed. We have developed a collection of gene-break transposon (GBT) alleles for use in phenotypic annotation of the vertebrate genome using the preeminent non-mammalian model organism, the zebrafish (Danio rerio). GBTs represent an innovative methodology to ask current questions while also serving as a platform for new scientific query. We will use our ongoing 500 GBT collection as a platform of candidate gene mutations for assessment of the vertebrate phenome. In this competitive renewal, we will focus on the annotation of biological function to identify new players in development as well as a set of clinically relevant biological processes. We will accomplish this goal through the following specific aims:
Specific Aim I. We will conduct phenotypic annotation of 500+ GBT lines for genes required for zebrafish embryonic and early larval development.
Specific Aim II. We will conduct phenotypic annotation of skin-expressed proteins required for formation of the integument during development and for genes required for the skin's wound healing response.
Specific Aim III : We will identify cardiac mutants for annotation of gene functions in either cardiogenesis or adult cardiomyopathy.
Specific Aim I V. We will identify genes required for digestive organ formation, lipid metabolism and lipid signaling.
Specific Aim V. Recording of GBT gene function annotation using PATO-compliant phenotypic assessment description and integration into ongoing zebrafish functional databases including zfishbook and ZFIN. We selected embryonic development due to the advantages of external development of the zebrafish, cardiac biology and function due to the critical role of heart disease as the leading cause of death in the US, integument biology due to the strong impact of skin disease on one in three Americans, and lipid biology in development and physiology due to its critical role(s) in development, heart disease and obesity. Together, this project will annotate a panel of new genes for the better understanding of human health and disease.

Public Health Relevance

This proposal is to phenotypically annotate 500+ vertebrate genes using an ongoing mutant resource of new conditional protein trap mutations for the zebrafish (Danio rerio), the preeminent non-mammalian system for the study of core vertebrate biology and for modeling of human disease. This program will identify new genes involved in development, skin biology including regeneration, heart development and disease, and GI organ formation and lipid biochemistry.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Genomics, Computational Biology and Technology Study Section (GCAT)
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Hoodbhoy, Tanya
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Mayo Clinic, Rochester
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Pogoda, Hans-Martin; Riedl-Quinkertz, Iris; Löhr, Heiko et al. (2018) Direct activation of chordoblasts by retinoic acid is required for segmented centra mineralization during zebrafish spine development. Development 145:
Richardson, Rebecca; Hammerschmidt, Matthias (2018) The role of Rho kinase (Rock) in re-epithelialization of adult zebrafish skin wounds. Small GTPases 9:230-236
Löhr, Heiko; Hess, Simon; Pereira, Mafalda M A et al. (2018) Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit. Cell Rep 23:1728-1741
Sæle, Øystein; Rød, Kari Elin L; Quinlivan, Vanessa H et al. (2018) A novel system to quantify intestinal lipid digestion and transport. Biochim Biophys Acta Mol Cell Biol Lipids 1863:948-957
Quinlivan, Vanessa H; Farber, Steven A (2017) Lipid Uptake, Metabolism, and Transport in the Larval Zebrafish. Front Endocrinol (Lausanne) 8:319
Anderson, Jennifer L; Mulligan, Timothy S; Shen, Meng-Chieh et al. (2017) mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces unexpected transcripts that escape nonsense-mediated decay. PLoS Genet 13:e1007105
Wang, Lei; Ma, Xiao; Xu, Xiaolei et al. (2017) Systematic identification and characterization of cardiac long intergenic noncoding RNAs in zebrafish. Sci Rep 7:1250
Stainier, Didier Y R; Raz, Erez; Lawson, Nathan D et al. (2017) Guidelines for morpholino use in zebrafish. PLoS Genet 13:e1007000
El-Rass, Suzan; Eisa-Beygi, Shahram; Khong, Edbert et al. (2017) Disruption ofpdgfraalters endocardial and myocardial fusion during zebrafish cardiac assembly. Biol Open 6:348-357
Otis, Jessica P; Shen, Meng-Chieh; Quinlivan, Vanessa et al. (2017) Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels. Dis Model Mech 10:283-295

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