title: Ciliary genes are down-regulated in bronchial tissue of primary ciliary dyskinesia patients.
abstract: Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis and male infertility. The pulmonary phenotype in PCD is caused by the impaired motility of cilia in the respiratory epithelium, due to ultrastructural defects of these organelles. We hypothesized that defects of multi-protein ciliary complexes should be reflected by gene expression changes in the respiratory epithelium. We have previously found that large group of genes functionally related to cilia share highly correlated expression pattern in PCD bronchial tissue. Here we performed an explorative analysis of differential gene expression in the bronchial tissue from six PCD patients and nine non-PCD controls, using Illumina HumanRef-12 Whole Genome BeadChips. We observed 1323 genes with at least 2-fold difference in the mean expression level between the two groups (t-test p-value <0.05). Annotation analysis showed that the genes down-regulated in PCD biopsies (602) were significantly enriched for terms related to cilia, whereas the up-regulated genes (721) were significantly enriched for terms related to cell cycle and mitosis. We assembled a list of human genes predicted to encode ciliary proteins, components of outer dynein arms, inner dynein arms, radial spokes, and intraflagellar transport proteins. A significant down-regulation of the expression of genes from all the four groups was observed in PCD, compared to non-PCD biopsies. Our data suggest that a coordinated down-regulation of the ciliome genes plays an important role in the molecular pathomechanism of PCD.
authors: International Institute of Molecular and Cell Biology, Warsaw, Poland ; Genetics Department, University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands ; Complex Genetics Group, Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Maciej
authors: M
authors: Geremek
authors: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Poznan, Poland.
authors: Ewa
authors: E
authors: Ziętkiewicz
authors: Genetics Department, University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands.
authors: Marcel
authors: M
authors: Bruinenberg
authors: Genetics Department, University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands.
authors: Lude
authors: L
authors: Franke
authors: Institute of Tuberculosis and Lung Diseases, Rabka, Poland.
authors: Andrzej
authors: A
authors: Pogorzelski
authors: Genetics Department, University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands ; Complex Genetics Group, Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Cisca
authors: C
authors: Wijmenga
authors: International Institute of Molecular and Cell Biology, Warsaw, Poland ; Department of Molecular and Clinical Genetics, Institute of Human Genetics, Poznan, Poland.
authors: Michał
authors: M
authors: Witt
mesh_terms: D001980:Bronchi / Q000473:pathology*; D016022:Case-Control Studies; D002923:Cilia / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics* / Q000473:pathology; D058977:Molecular Sequence Annotation; D009154:Mutation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics