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Investigation of the Possible Role of a Novel Gene, DPCD, in Primary Ciliary Dyskinesia

Departments of Medicine, Pathology, and Pediatrics, and the Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Address correspondence to: Lawrence E. Ostrowski, Ph.D., University of North Carolina at Chapel Hill School of Medicine, Cystic Fibrosis/Pulmonary Research and Treatment Center, CB# 7248, 6123A Thurston-Bowles Bldg., Chapel Hill, NC 27599-7248. E-mail: ostro{at}med.unc.edu

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by mutations that affect the proper function of cilia. Recently, deletion of DNA polymerase (Poll) in mice produced a phenotype characteristic of PCD (Kobayashi et al., 2002, Mol. Cell. Biol. 22:2769–2776). Because it is unclear how a mutation in a DNA polymerase would result in a specific defect in axonemes, the targeting construct was examined further. Analysis of the genomic region surrounding the Poll gene revealed an uncharacterized gene, named Dpcd, that is predicted to be transcribed from the opposite strand relative to Poll. The deletion of Poll would also remove the first exon of Dpcd. Because it is possible that the PCD phenotype observed is due to the absence of either gene, the expression of these genes during ciliogenesis of human airway epithelial cells was examined. Northern analysis demonstrated that DPCD expression increases during ciliated cell differentiation; the expression of POLL decreases. To examine directly whether DPCD is mutated in cases of human PCD, the complete coding sequence of DPCD was sequenced from 51 unrelated PCD patients. No disease-causing mutations were confirmed; however, one variant could not be excluded. Therefore, DPCD remains a novel candidate gene for PCD.

Abbreviations: deleted in a mouse model of PCD, Dpcd • human bronchial epithelial cells, HBE cells • inner dynein arm, IDA • outer dynein arm, ODA • primary ciliary dyskinesia, PCD • DNA polymerase , Poll