CiliaCarta: An integrated and validated compendium of ciliary genes
Teunis J. P. Van Dam
(1, 2)
,
Julie Kennedy
(3, 4)
,
Robin van Der Lee
(1)
,
Erik De Vrieze
(1, 5)
,
Kirsten A. Wunderlich
(6)
,
Suzanne Rix
(7)
,
Gerard W. Dougherty
(8)
,
Nils J. Lambacher
(3, 9)
,
Chunmei M. Li
(9)
,
Victor L. Jensen
(9)
,
Michel R. Leroux
(9)
,
Rim Hjeij
(8)
,
Nicola Horn
(10)
,
Yves Texier
(10)
,
Yasmin Wissinger
(10)
,
Jeroen Van Reeuwijk
(11)
,
Gabrielle Wheway
(12)
,
Barbara Knapp
(13)
,
Jan F. Scheel
(13)
,
Brunella Franco
(14, 15)
,
Dorus A. Mans
(11)
,
Erwin Van Wijk
(1, 5)
,
François Kepes
(16, 17)
,
Gisela G. Slaats
(18)
,
Grischa Toedt
(19)
,
Hannie Kremer
(1, 5, 20)
,
Heymut Omran
(8)
,
Katarzyna Szymanska
(12)
,
Konstantinos Koutroumpas
(16, 17)
,
Marius Ueffing
(10)
,
Thanh-Minh T. Nguyen
(20, 11)
,
Stef J. F. Letteboer
(20, 11)
,
Machteld M. Oud
(20, 11)
,
Sylvia E. C. Van Beersum
(20, 11)
,
Miriam Schmidts
(20, 11, 21)
,
Philip L. Beales
(7)
,
Qianhao H. Lu
(22, 23, 24)
,
Rachel H. Giles
(18)
,
Radek Szklarczyk
(1)
,
Robert B. Russell
(23)
,
Toby J. Gibson
(19)
,
Colin A. Johnson
(12)
,
Olivier E. Blacque
(3)
,
Uwe Wolfrum
(13)
,
Karsten Boldt
(10)
,
Ronald Roepman
(20, 11)
,
Victor Hernandez-Hernandez
(7)
,
Martijn A. Huynen
(1)
1
Radboud University Medical Center [Nijmegen]
2 Universiteit Utrecht / Utrecht University [Utrecht]
3 UCD - University College Dublin [Dublin]
4 School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
5 Donders Institute for Brain, Cognition and Behaviour
6 University Medical Center of the Johannes Gutenberg-University Mainz
7 UCL - Great Ormond Street Institute of Child Health
8 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
9 SFU.ca - Simon Fraser University = Université Simon Fraser
10 Eberhard Karls Universität Tübingen = University of Tübingen
11 Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands]
12 University of Leeds
13 JGU - Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University
14 TIGEM - Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina
15 University of Naples Federico II = Università degli studi di Napoli Federico II
16 ISSB - Institut de biologie systémique et synthétique
17 Génopole [Evry]
18 UMCU - University Medical Center [Utrecht]
19 EMBL - European Molecular Biology Laboratory [Heidelberg]
20 Department of Human Genetics [Nijmegen]
21 University Hospital Freiburg
22 BZH - Biochemie-Zentrum / Biochemistry-Center
23 Universität Heidelberg [Heidelberg] = Heidelberg University
24 Bioquant
2 Universiteit Utrecht / Utrecht University [Utrecht]
3 UCD - University College Dublin [Dublin]
4 School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
5 Donders Institute for Brain, Cognition and Behaviour
6 University Medical Center of the Johannes Gutenberg-University Mainz
7 UCL - Great Ormond Street Institute of Child Health
8 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
9 SFU.ca - Simon Fraser University = Université Simon Fraser
10 Eberhard Karls Universität Tübingen = University of Tübingen
11 Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands]
12 University of Leeds
13 JGU - Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University
14 TIGEM - Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina
15 University of Naples Federico II = Università degli studi di Napoli Federico II
16 ISSB - Institut de biologie systémique et synthétique
17 Génopole [Evry]
18 UMCU - University Medical Center [Utrecht]
19 EMBL - European Molecular Biology Laboratory [Heidelberg]
20 Department of Human Genetics [Nijmegen]
21 University Hospital Freiburg
22 BZH - Biochemie-Zentrum / Biochemistry-Center
23 Universität Heidelberg [Heidelberg] = Heidelberg University
24 Bioquant
Résumé
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/.
Domaines
Sciences du Vivant [q-bio]Licence |
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