Background: Primary ciliary dyskinesia (PCD) is a severe inherited disorder characterised by chronic respiratory disease, male infertility, and, in ∼50% of affected individuals, a left-right asymmetry defect called situs inversus. PCD is caused by defects in substructures of the ciliary and flagellar axoneme, most commonly loss of the outer dynein arms. Although PCD is believed to involve mutations in many genes, only three have been identified.
Methods: To facilitate discovery of new PCD genes, we have used database searching and analysis to systematically identify the human homologues of proteins associated with the Chlamydomonas reinhardtii outer dynein arm, the best characterised outer arm of any species.
Results: We find that 12 out of 14 known Chlamydomonas outer arm subunits have one or more likely orthologues in humans. The results predict a total of 24 human genes likely to encode outer dynein arm subunits and associated proteins possibly necessary for outer arm assembly, plus 12 additional closely related human genes likely to encode inner dynein arm subunits.
Conclusion: These genes, which have been located on the human chromosomes for easy comparison with known or suspected PCD loci, are excellent candidates for screening for disease-causing mutations in PCD patients with outer and/or inner dynein arm defects.
- AK, adenylate kinase
- DC, docking complex
- HC, heavy chains, IC, intermediate chains, LC, light chains
- PCD, primary ciliary dyskinesia
- immotile cilia syndrome
- Kartagener’s syndrome
- primary ciliary dyskinesia
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Published Online First 3 June 2005
This work was supported by grants from the NIH (GM-60992 to GJP and GM30626 to GBW), by a Worcester Foundation for Biomedical Research Foundation Scholar Award (to GJP), and by the Robert W. Booth Fund at the Greater Worcester Community Foundation (to GBW)
Competing interests: none declared