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Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs
BACKGROUND: The complete genome sequences for human and the nematode Caenorhabditis elegans offer an opportunity to learn more about human gene function through functional characterization of orthologs in the worm. Based on a previous genome-wide analysis of worm-human orthologous transmembrane prot...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2004
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC533873/ https://www.ncbi.nlm.nih.gov/pubmed/15533247 http://dx.doi.org/10.1186/1471-2164-5-85 |
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author | Henricson, Anna Sonnhammer, Erik LL Baillie, David L Gomes, Ana Vaz |
author_facet | Henricson, Anna Sonnhammer, Erik LL Baillie, David L Gomes, Ana Vaz |
author_sort | Henricson, Anna |
collection | PubMed |
description | BACKGROUND: The complete genome sequences for human and the nematode Caenorhabditis elegans offer an opportunity to learn more about human gene function through functional characterization of orthologs in the worm. Based on a previous genome-wide analysis of worm-human orthologous transmembrane proteins, we selected seventeen genes to explore experimentally in C. elegans. These genes were selected on the basis that they all have high confidence candidate human orthologs and that their function is unknown. We first analyzed their phylogeny, membrane topology and domain organization. Then gene functions were studied experimentally in the worm by using RNA interference and transcriptional gfp reporter gene fusions. 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 in head neurons, suggesting an ancient conserved role important to neuronal function. We propose a new transmembrane topology for the presenilin-like protein family. sft-4, the worm ortholog of surfeit locus gene Surf-4, proved to be an essential gene required for development during the larval stages of the worm. R155.1, whose human ortholog is entirely uncharacterized, was implicated in body size control and other developmental processes. CONCLUSIONS: By combining bioinformatics and C. elegans experiments on orthologs, we provide functional insights on twelve previously uncharacterized human genes. |
format | Text |
id | pubmed-533873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-5338732004-11-26 Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs Henricson, Anna Sonnhammer, Erik LL Baillie, David L Gomes, Ana Vaz BMC Genomics Research Article BACKGROUND: The complete genome sequences for human and the nematode Caenorhabditis elegans offer an opportunity to learn more about human gene function through functional characterization of orthologs in the worm. Based on a previous genome-wide analysis of worm-human orthologous transmembrane proteins, we selected seventeen genes to explore experimentally in C. elegans. These genes were selected on the basis that they all have high confidence candidate human orthologs and that their function is unknown. We first analyzed their phylogeny, membrane topology and domain organization. Then gene functions were studied experimentally in the worm by using RNA interference and transcriptional gfp reporter gene fusions. 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 in head neurons, suggesting an ancient conserved role important to neuronal function. We propose a new transmembrane topology for the presenilin-like protein family. sft-4, the worm ortholog of surfeit locus gene Surf-4, proved to be an essential gene required for development during the larval stages of the worm. R155.1, whose human ortholog is entirely uncharacterized, was implicated in body size control and other developmental processes. CONCLUSIONS: By combining bioinformatics and C. elegans experiments on orthologs, we provide functional insights on twelve previously uncharacterized human genes. BioMed Central 2004-11-08 /pmc/articles/PMC533873/ /pubmed/15533247 http://dx.doi.org/10.1186/1471-2164-5-85 Text en Copyright © 2004 Henricson et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Henricson, Anna Sonnhammer, Erik LL Baillie, David L Gomes, Ana Vaz Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs |
title | Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs |
title_full | Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs |
title_fullStr | Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs |
title_full_unstemmed | Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs |
title_short | Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs |
title_sort | functional characterization in caenorhabditis elegans of transmembrane worm-human orthologs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC533873/ https://www.ncbi.nlm.nih.gov/pubmed/15533247 http://dx.doi.org/10.1186/1471-2164-5-85 |
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