PUBLICATION
Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome
- Authors
- Pickart, M.A., Klee, E.W., Nielsen, A.L., Sivasubbu, S., Mendenhall, E.M., Bill B.R., Chen, E., Eckfeldt, C.E., Knowlton, M., Robu, M.E., Larson, J.D., Deng, Y., Schimmenti, L.A., Ellis, L.B., Verfaillie, C.M., Hammerschmidt, M., Farber, S.A., and Ekker, S.C.
- ID
- ZDB-PUB-070122-38
- Date
- 2006
- Source
- PLoS One 1(1): e104 (Journal)
- Registered Authors
- Ekker, Stephen C., Farber, Steven, Hammerschmidt, Matthias, Klee, Eric W., Knowlton, Michelle, Larson, Jon D., Pickart, Michael, Sivasubbu, Sridhar
- Keywords
- Embryos, Zebrafish, Protein sequencing, Phenotypes, Vertebrates, Comparative genomics, Veins, Sequence alignment
- MeSH Terms
-
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/physiology
- Antisense Elements (Genetics)/genetics
- Genome
- PubMed
- 17218990 Full text @ PLoS One
Abstract
BACKGROUND: Understanding the functional role(s) of the more than 20,000 proteins of the vertebrate genome is a major next step in the post-genome era. The approximately 4,000 co-translationally translocated (CTT) proteins - representing the vertebrate secretome - are important for such vertebrate-critical processes as organogenesis. However, the role(s) for most of these genes is currently unknown. RESULTS: We identified 585 putative full-length zebrafish CTT proteins using cross-species genomic and EST-based comparative sequence analyses. We further investigated 150 of these genes (Figure 1) for unique function using morpholino-based analysis in zebrafish embryos. 12% of the CTT protein-deficient embryos resulted in specific developmental defects, a notably higher rate of gene function annotation than the 2%-3% estimate from random gene mutagenesis studies. CONCLUSION: This initial collection includes novel genes required for the development of vascular, hematopoietic, pigmentation, and craniofacial tissues, as well as lipid metabolism, and organogenesis. This study provides a framework utilizing zebrafish for the systematic assignment of biological function in a vertebrate genome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping