CiliaCarta: An integrated and validated compendium of ciliary genes

Teunis J. P. van Dam*, Julie Kennedy, Robin van der Lee, Erik de Vrieze, Kirsten A. Wunderlich, Suzanne Rix, Gerard W. Dougherty, Nils J. Lambacher, Chunmei Li, Victor L. Jensen, Michel R. Leroux, Rim Hjeij, Nicola Horn, Yves Texier, Yasmin Wissinger, Jeroen van Reeuwijk, Gabrielle Wheway, Barbara Knapp, Jan F. Scheel, Brunella FrancoDorus A. Mans, Erwin van Wijk, Francois Kepes, Gisela G. Slaats, Grischa Toedt, Hannie Kremer, Heymut Omran, Katarzyna Szymanska, Konstantinos Koutroumpas, Marius Ueffing, Thanh-Minh T. Nguyen, Stef J. F. Letteboer, Machteld M. Oud, Sylvia E. C. van Beersum, Miriam Schmidts, Philip L. Beales, Qianhao Lu, Rachel H. Giles, Radek Szklarczyk, Robert B. Russell, Toby J. Gibson, Colin A. Johnson, Oliver E. Blacque, Uwe Wolfrum, Karsten Boldt, Ronald Roepman, Victor Hernandez-Hernandez, Martijn A. Huynen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Web of Science)

Abstract

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

Original languageEnglish
Article number0216705
Number of pages32
JournalPLOS ONE
Volume14
Issue number5
DOIs
Publication statusPublished - 16 May 2019

Keywords

  • RETINAL PHOTORECEPTOR CELLS
  • LEBER CONGENITAL AMAUROSIS
  • SOLUTE-CARRIER-PROTEIN
  • PRIMARY CILIUM
  • INTRAFLAGELLAR TRANSPORT
  • TRANSITION ZONE
  • EXPRESSION
  • MUTATIONS
  • DIFFERENTIATION
  • IDENTIFICATION

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