Discovering the functions of the tens of thousands of genes in the human genome is a required step for understanding human biology and disease. Genetic model organisms, including zebrafish, play a critical role in this discovery process, because genetic analysis can connect gene sequence and function. Model organism databases, like ZFIN, provide tools required to make this connection. The zebrafish has emerged as a premier organism to study vertebrate biology. Powerful techniques allow rapid efficient generation and recovery of mutations affecting genes that orchestrate developmental patterning, organogenesis, physiology, and behavior. It is easy to study gene function by generating transgenic zebrafish, by knocking down gene function with morpholino antisense oligonucleotides, or by altering gene function by genome editing. The genome has been sequenced and about 50% of the protein coding genes have been mutated by targeted gene knockout technology. Large-scale projects are underway or planned that will produce functional data about almost all the genes and sequence-based functional elements in the genome. Multiple mutations and gene knockdowns can be combined in the same individual to study gene modifiers and other genetic interactions. The functions of most of these genes are conserved among vertebrate groups. Thus, analysis of zebrafish mutations provides insights into gene functions in other vertebrates, including humans. The long term goals for ZFIN are a) to be the community database resource for the laboratory use of zebrafish, b) to develop and support integrated zebrafish genetic, genomic, developmental, and physiological information, c) to maintain the definitive reference data sets of zebrafish research information, d) to link this information extensively to corresponding data in other model organism and human databases, e) to facilitate the use of zebrafish as a model for human biology, and f) to help serve the broad needs of the biomedical research community. This project will continue and expand curation of zebrafish research data, develop expanded support for zebrafish models of human disease, expand and integrate links to other databases, and maintain and update the zebrafish reference genome. This work will provide a powerful means for researchers to associate gene sequence and function, thus facilitating studies of human gene function and disease as well as cross-species analyses of genome organization and evolution.

Public Health Relevance

Zebrafish are widely used to study vertebrate gene function including human biology and disease. ZFIN is the centralized database of zebrafish research information and will provide efficient means to identify gene candidates and animal models of human disease, which may shorten the lengthy path to identification and understanding of the genetic basis of human disease.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Biotechnology Resource Cooperative Agreements (U41)
Project #
5U41HG002659-15
Application #
9270034
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Pillai, Ajay
Project Start
2003-07-11
Project End
2021-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
15
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Oregon
Department
Neurosciences
Type
Organized Research Units
DUNS #
City
Eugene
State
OR
Country
United States
Zip Code
97403
Van Slyke, Ceri E; Bradford, Yvonne M; Howe, Douglas G et al. (2018) Using ZFIN: Data Types, Organization, and Retrieval. Methods Mol Biol 1757:307-347
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Howe, Douglas G; Bradford, Yvonne M; Eagle, Anne et al. (2017) The Zebrafish Model Organism Database: new support for human disease models, mutation details, gene expression phenotypes and searching. Nucleic Acids Res 45:D758-D768
Bradford, Yvonne M; Toro, Sabrina; Ramachandran, Sridhar et al. (2017) Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN. ILAR J 58:4-16
Huntley, Rachael P; Sitnikov, Dmitry; Orlic-Milacic, Marija et al. (2016) Guidelines for the functional annotation of microRNAs using the Gene Ontology. RNA 22:667-76
Edmunds, Richard C; Su, Baofeng; Balhoff, James P et al. (2016) Phenoscape: Identifying Candidate Genes for Evolutionary Phenotypes. Mol Biol Evol 33:13-24
Howe, D G; Bradford, Y M; Eagle, A et al. (2016) A scientist's guide for submitting data to ZFIN. Methods Cell Biol 135:451-81
Diehl, Alexander D; Meehan, Terrence F; Bradford, Yvonne M et al. (2016) The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability. J Biomed Semantics 7:44
Van Slyke, Ceri E; Bradford, Yvonne M; Westerfield, Monte et al. (2014) The zebrafish anatomy and stage ontologies: representing the anatomy and development of Danio rerio. J Biomed Semantics 5:12
Haendel, Melissa A; Balhoff, James P; Bastian, Frederic B et al. (2014) Unification of multi-species vertebrate anatomy ontologies for comparative biology in Uberon. J Biomed Semantics 5:21

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