Functional Characterization in Caenorhabditis Elegans of Transmembrane Worm-Human Orthologs

Resource type
Date created
2004
Authors/Contributors
Abstract
Background: The complete genome sequences for human and the nematode Caenorhabditiselegans offer an opportunity to learn more about human gene function through functionalcharacterization of orthologs in the worm. Based on a previous genome-wide analysis of wormhumanorthologous transmembrane proteins, we selected seventeen genes to exploreexperimentally in C. elegans. These genes were selected on the basis that they all have highconfidence candidate human orthologs and that their function is unknown. We first analyzed theirphylogeny, membrane topology and domain organization. Then gene functions were studiedexperimentally in the worm by using RNA interference and transcriptional gfp reporter genefusions.Results: The experiments gave functional insights for twelve of the genes studied. For example,C36B1.12, the worm ortholog of three presenilin-like genes, was almost exclusively expressed inhead neurons, suggesting an ancient conserved role important to neuronal function. We proposea new transmembrane topology for the presenilin-like protein family. sft-4, the worm ortholog ofsurfeit locus gene Surf-4, proved to be an essential gene required for development during the larvalstages of the worm. R155.1, whose human ortholog is entirely uncharacterized, was implicated inbody size control and other developmental processes.Conclusions: By combining bioinformatics and C. elegans experiments on orthologs, we providefunctional insights on twelve previously uncharacterized human genes.
Document
Published as
BMC Genomics 2004, 5:85 doi:10.1186/1471-2164-5-85
Publication title
BMC Genomics
Document title
Functional Characterization in Caenorhabditis Elegans of Transmembrane Worm-Human Orthologs
Date
2004
Volume
5
Issue
85
Publisher DOI
10.1186/1471-2164-5-85
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Copyright is held by the author(s).
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Peer reviewed?
Yes
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Member of collection
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