Gene expression studies in cells from primary ciliary dyskinesia patients identify 208 potential ciliary genes
Gene expression studies in cells from primary ciliary dyskinesia patients identify 208 potential ciliary genes
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DOI：
10.1007/s00439-010-0922-4
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发表时间：
2011-03-01
期刊：
影响因子：
5.3
通讯作者：
Wijmenga, Cisca
中科院分区：
文献类型：
--
作者：
Geremek, Maciej;Bruinenberg, Marcel;Wijmenga, Cisca
纤毛是小的细胞突起，其充当传感器（初级纤毛）或将流体推动到各种器官的上皮上（运动纤毛）。最近，由于其与一组称为纤毛病的人类疾病有关，该细胞器获得了广泛的关注。原发性纤毛运动障碍（PCD）是由纤毛运动基因突变引起的常染色体隐性遗传性纤毛病。该疾病的特征在于由于缺乏有效的粘膜纤毛清除而引起的反复呼吸道感染。我们在PCD患者的支气管活检中进行了全基因组基因表达谱分析。我们使用质量阈值聚类算法来识别在活检中揭示高度相关的RNA表达模式的基因组。最大的簇包含372个基因，并且显著富集了与纤毛相关的基因。数据库和文献检索显示，该簇中有164个基因是已知的纤毛基因，强烈表明其余208个基因可能是新的纤毛基因。208个新纤毛基因和164个已知基因的组织表达模式与给定组织中存在运动纤毛一致。上游启动子序列的分析揭示了RFX转录因子结合位点基序在两个亚组中的证据。根据PCD影响组织中的相关表达模式，我们确定了208个基因，我们预测参与纤毛生物学。我们的预测是直接基于人体材料，而不是模型生物。该基因列表提供了PCD和其他纤毛病的候选基因。
Cilia are small cellular projections that either act as sensors (primary cilia) or propel fluid over the epithelia of various organs (motile cilia). The organellum has gained much attention lately because of its involvement in a group of human diseases called ciliopathies. Primary ciliary dyskinesia (PCD) is an autosomal recessive ciliopathy caused by mutations in cilia motility genes. The disease is characterized by recurrent respiratory tract infections due to the lack of an efficient mucociliary clearance. We performed whole-genome gene expression profiling in bronchial biopsies from PCD patients. We used the quality threshold clustering algorithm to identify groups of genes that revealed highly correlated RNA expression patterns in the biopsies. The largest cluster contained 372 genes and was significantly enriched for genes related to cilia. The database and literature search showed that 164 genes in this cluster were known cilia genes, strongly indicating that the remaining 208 genes were likely to be new cilia genes. The tissue expression pattern of the 208 new cilia genes and the 164 known genes was consistent with the presence of motile cilia in a given tissue. The analysis of the upstream promotor sequences revealed evidence for RFX transcription factors binding site motif in both subgroups. Based on the correlated expression patterns in PCD-affected tissues, we identified 208 genes that we predict to be involved in cilia biology. Our predictions are based directly on the human material and not on model organisms. This list of genes provides candidate genes for PCD and other ciliopathies.