| The Cardiovascular Genomics Unit at Harvard University and Brigham and Women's Hopsital | NCBI |
|
|
| Human Cardiovascular Projects | Mouse Project | Zebrafish Project | Contact | Search | Links | Home | Harvard Medical School | Brigham and Women's Hospital |

|
|
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 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.