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Characterizing the Zebrafish Genome


Zebrafish is an excellent genetic and developmental system for studying vertebrate biology and disease. One of the most important foundations for the success of a model organism is to have an accurate genome assembly available. The zebrafish genome sequencing project has involved a consortium of laboratories, mostly being led by the Sanger Center. Our laboratory has provided a necessary, independent, and comprehensive radiation hybrid (RH) map to assist and quality control the genome sequence assembly. BAG clones in fingerprinted contigs and whole genome shotgun sequences are used for the genome assembly. This RH map now contains 17,301 markers, including genes, mutant locations, BAG ends, and CA repeat markers useful for genotyping. The current assembly is a wonderful resource, but requires "finishing" with the correction of gaps and mis-assemblies. These problems are likely caused by in-strain polymorphisms and gene duplications associated with zebrafish. We plan to use RH mapping, physical walking and annotation tools to correct these assembly defects. We will help research projects in less-well assembled genomic regions. A half-YAC library with 900 primary clones has been collected and we plan to continue the clone collection to increase the coverage of telomeric and centromeric regions. Our major goal is to insure high quality sequence assembly of the zebrafish genome. We will increase the polymorphic marker coverage of the genome by identifying new and polymorphic simple repeat markers and update the "Positional Cloning Guide" to expedite mutant mapping and cloning. We plan to create bioinformatics resources to relate zebrafish genes to other model organisms, including human diseases. For instance, our laboratory has developed an annotation repository with quality assurance by lab scientists that establishes orthology of zebrafish genes on microarray platforms with human genes. This accelerates comparisons to human diseases, and allows a better understanding of conserved genetic pathways. The repository will soon include genes from other species such as mouse. This annotation project will integrate zebrafish map, genetic mutants, and human OMIM genes and diseases to create the first zebrafish genome map annotated by human diseases. Our efforts in zebrafish genomic and bioinformatic studies are required for the genome sequencing project and provide with effective genomic tools for using zebrafish to improve human health. Lay language: Zebrafish studies have advanced our understanding of vertebrate development and human disease. We plan to improve the zebrafish genome assembly and to create bioinformatics tools for promoting interactions between the zebrafish and other research communities, including those studying human disease. A well assembled zebrafish genome will lead to discoveries impacting human health and disease.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.