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Welcome to the Zebrafish component of our cardiovascular research.

The zebrafish (Danio rerio) is a powerful model well suited to both developmental and genetic analysis. Large-scale genetic screens have allowed scientists to identify hundreds of mutant phenotypes, many of which resemble human clinical disorders. The creation of critical genetic reagents, coupled with the rapid progress of the zebrafish genome initiative are bringing this model system to its full potential for the study of the vertebrate biology, physiology and human diseases.

Genetic screens in the zebrafish have also isolated mutation in hundreds of genes essential for vertebrate development, physiology, and behaviour. We plan to localize zebrafish genes and various expressed sequence tags (ESTs) , proposing to use this genetic system to address fundamental questions of vertebrate developmental physiology. As an example, we focus on zebrafish mutations that reveal single genes essential for normal development of the cardiovascular system. These single gene mutations disrupt specific aspects to heart rate, rhythm, conduction, and/or contractility of the developing heart.

Comparative analysis of map positions between zebrafish and human has identified that gene orthologs that are syntenic in mammals are also syntenic in zebrafish (Postletwaith et al. 1998). This discovery of extensive sharing of chromosome segments between zebrafish and humans has practical significance to the Human Genome Project. For example, synteny between zebrafish and humans will enable researchers to identify human ortholog from a gene's position in the zebrafish genome. Reciprocally, and more importantly, the phenotype of a zebrafish mutation can suggest function for the human gene (Postlethwait and Talbot, 1997).

The generation of expressed sequence tags (ESTs) has proven to be a rapid and economical approach to identify and characterize expressed genes.  To date, we have generated more than 11,000 ESTs from embryonic, adult heart and skeletal muscle zebrafish cDNA libraries.  Virtually all of these were generated from the 5’-ends of cDNA clones while a 500 EST subset was taken from the 3’-end (these ESTs serve as candidates for chromosome mapping).  From our EST database, approximately 61% matched to known genes from other organisms, though the vast majority of these have not been characterized in the zebrafish.  Interestingly, a relatively large proportion of ESTs (28%) did not match to any other ESTs or known sequence and thus represent novel genes, while only 11% exhibited similarity to other ESTs.  A total of approximately 5,000 unique genes and gene clusters were identified from the 11,000 ESTs generated.  To help identify candidate genes in our data set for developmental mutants, radiation hybrid mapping was performed for 150 ESTs.Comparison of map positions between zebrafish and human identified several new synteny groups which will be useful in defining the boundaries of conserved chromosome segments between zebrafish and humans, and facilitate the transfer of genetic information between the two organisms. This resource of EST data and clones will also provide a rich collection of cDNA clones for the generation of cDNA microarrays.

To view genes which have been mapped, follow the link here.

To view a nonredundant list of genes accumulated in our zebrafish cDNA libraries, follow the link here.

To view our zebrafish cDNA microarray project, please follow the link here.

To view our list of zebrafish hypoxia-induced gene, please follow the link here.