Laboratory of Cytoskeleton and Cilia Biology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.
University of Warsaw, Faculty of Chemistry, 1 Pasteura Street, 02-093 Warsaw, Poland.
Cells. 2019 Dec 11;8(12):1614. doi: 10.3390/cells8121614.
Primary ciliary dyskinesia (PCD) is a recessive heterogeneous disorder of motile cilia, affecting one per 15,000-30,000 individuals; however, the frequency of this disorder is likely underestimated. Even though more than 40 genes are currently associated with PCD, in the case of approximately 30% of patients, the genetic cause of the manifested PCD symptoms remains unknown. Because motile cilia are highly evolutionarily conserved organelles at both the proteomic and ultrastructural levels, analyses in the unicellular and multicellular model organisms can help not only to identify new proteins essential for cilia motility (and thus identify new putative PCD-causative genes), but also to elucidate the function of the proteins encoded by known PCD-causative genes. Consequently, studies involving model organisms can help us to understand the molecular mechanism(s) behind the phenotypic changes observed in the motile cilia of PCD affected patients. Here, we summarize the current state of the art in the genetics and biology of PCD and emphasize the impact of the studies conducted using model organisms on existing knowledge.
原发性纤毛运动障碍(PCD)是一种隐性的纤毛运动障碍的异质性疾病,影响每 15000-30000 个人中的 1 人;然而,这种疾病的频率可能被低估了。尽管目前有 40 多个基因与 PCD 相关,但在大约 30%的患者中,表现出的 PCD 症状的遗传原因仍然未知。由于纤毛在蛋白质组学和超微结构水平上都是高度进化保守的细胞器,因此在单细胞和多细胞模式生物中的分析不仅有助于鉴定对纤毛运动至关重要的新蛋白(从而鉴定新的潜在 PCD 致病基因),还可以阐明已知 PCD 致病基因编码的蛋白的功能。因此,涉及模式生物的研究可以帮助我们了解 PCD 患者的活动纤毛中观察到的表型变化背后的分子机制。在这里,我们总结了 PCD 的遗传学和生物学的最新进展,并强调了使用模式生物进行的研究对现有知识的影响。