Research

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

Nansheng Chen^1,2 , Allan Mah² , Oliver E Blacque^2,3 , Jeffrey Chu² , Kiran Phgora² , Mathieu W Bakhoum² , C Rebecca Hunt Newbury⁴ , Jaswinder Khattra⁴ , Susanna Chan⁴ , Anne Go⁴ , Evgeni Efimenko⁵ , Robert Johnsen² , Prasad Phirke⁵ , Peter Swoboda⁵ , Marco Marra⁶ , Donald G Moerman⁴ , Michel R Leroux² , David L Baillie² and Lincoln D Stein¹

¹Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

²Department of Molecular Biology and Biochemistry, Simon Fraser University, University Drive, Burnaby, British Columbia, Canada V5A 1S6

³School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland

⁴Department of Zoology, University of British Columbia, West Mall, Vancouver, British Columbia, Canada V6T 1Z4

⁵Karolinska Institute, Department of Biosciences and Nutrition, Södertörn University College, School of Life Sciences, S-14189 Huddinge, Sweden

⁶British Columbia Cancer Agency, Genome Sciences Centre, Vancouver, British Columbia, Canada V5Z 4S6

author email corresponding author email

Genome Biology 2006, 7:R126doi:10.1186/gb-2006-7-12-r126

Published:	22 December 2006

Subject areas: Genome studies, Bioinformatics

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.