ZFIN ID: ZDB-PUB-070122-38
Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome
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.
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:
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Antisense Elements (Genetics)/genetics
  • Base Sequence
  • Blood Vessels/embryology
  • Computational Biology
  • Genome
  • Genomics
  • Hematopoiesis
  • Lipid Metabolism/genetics
  • Molecular Sequence Data
  • Proteome
  • Proteomics
  • Sequence Alignment
  • Vertebrates/genetics*
  • Vertebrates/growth & development
  • Vertebrates/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
PubMed: 17218990 Full text @ PLoS One
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.