Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome
Pickart, Michael A × Klee, Eric W Nielsen, Aubrey L Sivasubbu, Sridhar Mendenhall, Eric M Bill, Brent R Chen, Eleanor Eckfeldt, Craig E Knowlton, Michelle Robu, Mara E Larson, Jon D Deng, Yun Schimmenti, Lisa A Ellis, Lynda B M Verfaillie, Catherine Hammerschmidt, Matthias Farber, Steven A Ekker, Stephen C #
Public Library of Sciene
PLoS One vol:1 issue:1
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#ENTITYSTARTX00028;S#ENTITYSTARTX00029;: 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.