Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome.

<h4>Background</h4>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 fo...

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Main Authors: Michael A Pickart, Eric W Klee, Aubrey L Nielsen, Sridhar Sivasubbu, Eric M Mendenhall, Brent R Bill, Eleanor Chen, Craig E Eckfeldt, Michelle Knowlton, Mara E Robu, Jon D Larson, Yun Deng, Lisa A Schimmenti, Lynda B M Ellis, Catherine M Verfaillie, Matthias Hammerschmidt, Steven A Farber, Stephen C Ekker
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-12-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000104&type=printable
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Summary:<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
ISSN:1932-6203