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


CONCLUSIONS
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.
Chen
Nansheng
N
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. chenn@sfu.ca
Mah
Allan
A
Blacque
Oliver E
OE
Chu
Jeffrey
J
Phgora
Kiran
K
Bakhoum
Mathieu W
MW
Newbury
C Rebecca Hunt
CR
Khattra
Jaswinder
J
Chan
Susanna
S
Go
Anne
A
Efimenko
Evgeni
E
Johnsen
Robert
R
Phirke
Prasad
P
Swoboda
Peter
P
Marra
Marco
M
Moerman
Donald G
DG
Leroux
Michel R
MR
Baillie
David L
DL
Stein
Lincoln D
LD
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D002923:Cilia / Q000378:metabolism*; D017931:DNA Primers; D020869:Gene Expression Profiling; D005816:Genetic Complementation Test; D023281:Genomics; D049452:Green Fluorescent Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic
D017931:DNA Primers; D049452:Green Fluorescent Proteins