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An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

Van Dam, Teunis J.P.; Letteboer, Stef J.F.; Nguyen, Thanh Minh T.; Wheway, Gabrielle; Schmidts, Miriam; Mans, Dorus A.; Szymanska, Katarzyna; Nguyen, Thanh-Minh T.; Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; Van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J. F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toome...


Teunis J.P. Van Dam

Stef J.F. Letteboer

Thanh Minh T. Nguyen

Gabrielle Wheway
Occasional Associate Lecturer - CHSS - DAS

Miriam Schmidts

Dorus A. Mans

Katarzyna Szymanska

Thanh-Minh T. Nguyen

Hilary Racher

Ian G. Phelps

Grischa Toedt

Julie Kennedy

Kirsten A. Wunderlich

Nasrin Sorusch

Zakia A. Abdelhamed

Subaashini Natarajan

Warren Herridge

Jeroen Van Reeuwijk

Nicola Horn

Karsten Boldt

David A. Parry

Stef J. F. Letteboer

Susanne Roosing

Matthew Adams

Sandra M. Bell

Jacquelyn Bond

Julie Higgins

Ewan E. Morrison

Darren C. Tomlinson

Gisela G. Slaats

Teunis J. P. van Dam

Lijia Huang

Kristin Kessler

Andreas Giessl

Clare V. Logan

Evan A. Boyle

Jay Shendure

Shamsa Anazi

Mohammed Aldahmesh

Selwa Al Hazzaa

Robert A. Hegele

Carole Ober

Patrick Frosk

Aizeddin A. Mhanni

Bernard N. Chodirker

Albert E. Chudley

Ryan Lamont

Francois P. Bernier

Chandree L. Beaulieu

Paul Gordon

Richard T. Pon

Clem Donahue

A. James Barkovich

Louis Wolf

Carmel Toomes

Christian T. Thiel

Kym M. Boycott

Martin McKibbin

Chris F. Inglehearn

Fiona Stewart

Heymut Omran

Martijn A. Huynen

Panagiotis I. Sergouniotis

Fowzan S. Alkuraya

Jillian S. Parboosingh

A. Micheil Innes

Colin E. Willoughby

Rachel H. Giles

Andrew R. Webster

Marius Ueffing

Oliver Blacque

Joseph G. Gleeson

Uwe Wolfrum

Philip L. Beales

Toby Gibson

Dan Doherty

Hannah M. Mitchison

Ronald Roepman

Colin A. Johnson


© 2015 Macmillan Publishers Limited. Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.


Van Dam, T. J., Letteboer, S. J., Nguyen, T. M. T., Wheway, G., Schmidts, M., Mans, D. A., …Johnson, C. A. (2015). An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nature Cell Biology, 17(8), 1074-1087.

Journal Article Type Article
Acceptance Date Jun 5, 2015
Publication Date Jan 1, 2015
Deposit Date Jun 7, 2016
Journal Nature Cell Biology
Print ISSN 1465-7392
Electronic ISSN 1476-4679
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 17
Issue 8
Pages 1074-1087
Keywords cilia, ciliogenesis, RNAi
Public URL
Publisher URL