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Comparative Study
. 2006;7(12):R126.
doi: 10.1186/gb-2006-7-12-r126.

Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics

Nansheng Chen  1 , Allan Mah, Oliver E Blacque, Jeffrey Chu, Kiran Phgora, Mathieu W Bakhoum, C Rebecca Hunt Newbury, Jaswinder Khattra, Susanna Chan, Anne Go, Evgeni Efimenko, Robert Johnsen, Prasad Phirke, Peter Swoboda, Marco Marra, Donald G Moerman, Michel R Leroux, David L Baillie, Lincoln D Stein
Affiliations
Comparative Study

Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics

Nansheng Chen et al. Genome Biol. 2006.

Abstract

Background: The recent availability of genome sequences of multiple related Caenorhabditis species has made it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditis elegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C. elegans, some of which may be orthologs of unidentified human ciliopathy genes.

Results: By screening for genes possessing canonical X-box sequences in promoters of three Caenorhabditis species, namely C. elegans, C. briggsae and C. remanei, we identified 93 genes (including known X-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subject to the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cells was confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative transcriptional profiling of different tissue types and of daf-19(+) and daf-19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5(mn400) animals, which is indicative of compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5.

Conclusion: Our comparative genomics-based predictions may be useful for identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome (BBS), since the C. elegans orthologs of known human BBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.

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Figures

Figure 1
Figure 1
Procedure and searching results. (a) Procedure for identifying genes that are expressed in ciliated neurons in C. elegans. Known X-boxes used in this procedure are listed in Additional data file 1. The program hmmb was used to build an HMM profile, which was then used to search the promoter sequences using the program hmmfs. (b) The Generic Genome Browser and Bio::DB::GFF database [49] were used for finding candidate X-boxes and X-box regulated genes.
Figure 2
Figure 2
The X-box-containing genes Y69A2AR.2a, C02H7.1, F41E7.9, F32A6.2 and M04C9.5 are expressed exclusively within ciliated cells. Shown are green fluorescent protein (GFP) fluorescence images of the head (for example, amphid cell region) and tail (for example, phasmid cell region) regions of worms expressing transcriptional GFP reporters to the indicated genes. In all cases, expression is observed only within ciliated neuronal cells such as the amphid head cells and the phasmid tail cells.
Figure 3
Figure 3
The candidate gene dataset (Additional data file 2) is enriched with genes whose SAGE tag expression profile positively correlates with that of daf-19. 'Random genes' (black line) represents the correlation profile in gene expression between daf-19 and a random set of 1,000 genes in C. elegans; 'before filtration' (blue line) represents the correlation profile between DAF-19 and a raw list of genes that contain all putative X-box motifs in their promoters; and 'after comparative filtration' (green line) represents the correlation profile between DAF-19 and the set of filtered genes that contain X-box motifs in orthologous genes in three Caenorhabditis species.
Figure 4
Figure 4
Identification of X-box regulated genes facilitated the cloning of the C. elegans dye filling defective gene, dyf-5. M04C9.5 in C. elegans and its orthologs in C. briggsae (CBG22182) and C. remanei (Cr_M04C9.5) all have X-box motifs in their promoters. The C. elegans candidate gene M04C9.5 matches the genetic position of dyf-5. Sequencing of M04C9.5 in the dyf-5 strain revealed that it carries a G→A point mutation in its second coding exon, which generates a nonsense mutation and, therefore, causes a premature termination in translation. Numbers next to X-box motifs are their HMM scores. This figure was drawn using the Generic Genome Browser [49].
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References

    1. Badano JL, Mitsuma N, Beales PL, Katsanis N. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet. 2006;7:125–148. doi: 10.1146/annurev.genom.7.080505.115610. - DOI - PubMed
    1. Kozminski KG, Forscher P, Rosenbaum JL. Three flagellar motilities in Chlamydomonas unrelated to flagellar beating. Video supplement. Cell Motil Cytoskeleton. 1998;39:347–348. - PubMed
    1. Scholey JM. Intraflagellar transport. Annu Rev Cell Dev Biol. 2003;19:423–443. doi: 10.1146/annurev.cellbio.19.111401.091318. - DOI - PubMed
    1. Barr MM. Caenorhabditis elegans as a model to study renal development and disease: sexy cilia. J Am Soc Nephrol. 2005;16:305–312. doi: 10.1681/ASN.2004080645. - DOI - PubMed
    1. Inglis PN, Boroevich KA, Leroux MR. Piecing together a ciliome. Trends Genet. 2006;22:491–500. doi: 10.1016/j.tig.2006.07.006. - DOI - PubMed

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