@article {159,
	title = {Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome.},
	journal = {Elife},
	volume = {4},
	year = {2015},
	month = {2015 May 30},
	pages = {e06602},
	abstract = {<p>Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content genome-wide small interfering RNA (siRNA) screen to identify genes regulating ciliogenesis as candidates for JS. We analyzed results with a supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, a centriole siRNA screen and the GTex project, identifying 591 likely candidates. Intersection of this data with whole exome results from 145 individuals with unexplained JS identified six families with predominantly compound heterozygous mutations in KIAA0586. A c.428del base deletion in 0.1\% of the general population was found in trans with a second mutation in an additional set of 9 of 163 unexplained JS patients. KIAA0586 is an orthologue of chick Talpid3, required for ciliogenesis and Sonic hedgehog signaling. Our results uncover a relatively high frequency cause for JS and contribute a list of candidates for future gene discoveries in ciliopathies. </p>},
	keywords = {Abnormalities, Multiple, Cell Cycle Proteins, Cerebellum, Eye Abnormalities, Gene Frequency, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Heterozygote, Humans, Kidney Diseases, Cystic, Mutant Proteins, Retina, RNA, Small Interfering},
	issn = {2050-084X},
	doi = {10.7554/eLife.06602},
	author = {Roosing, Susanne and Hofree, Matan and Kim, Sehyun and Scott, Eric and Copeland, Brett and Romani, Marta and Silhavy, Jennifer L and Rosti, Rasim O and Schroth, Jana and Mazza, Tommaso and Miccinilli, Elide and Zaki, Maha S and Swoboda, Kathryn J and Milisa-Drautz, Joanne and Dobyns, William B and Mikati, Mohamed A and {\.I}ncecik, Faruk and Azam, Matloob and Borgatti, Renato and Romaniello, Romina and Boustany, Rose-Mary and Clericuzio, Carol L and D{\textquoteright}Arrigo, Stefano and Str{\o}mme, Petter and Boltshauser, Eugen and Stanzial, Franco and Mirabelli-Badenier, Marisol and Moroni, Isabella and Bertini, Enrico and Emma, Francesco and Steinlin, Maja and Hildebrandt, Friedhelm and Johnson, Colin A and Freilinger, Michael and Vaux, Keith K and Gabriel, Stacey B and Aza-Blanc, Pedro and Heynen-Genel, Susanne and Ideker, Trey and Dynlacht, Brian D and Lee, Ji Eun and Valente, Enza Maria and Kim, Joon and Gleeson, Joseph G}
}
@article {148,
	title = {An siRNA-based functional genomics screen for the~identification of regulators of ciliogenesis and ciliopathy~genes.},
	journal = {Nat Cell Biol},
	volume = {17},
	year = {2015},
	month = {2015 Aug},
	pages = {1074-1087},
	abstract = {<p>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. </p>},
	keywords = {Abnormalities, Multiple, Animals, Caenorhabditis elegans, Cerebellar Diseases, Cerebellum, Cilia, Ciliary Motility Disorders, Databases, Genetic, Ellis-Van Creveld Syndrome, Eye Abnormalities, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Genomics, HEK293 Cells, High-Throughput Nucleotide Sequencing, Humans, Kidney Diseases, Cystic, Membrane Proteins, Mice, Inbred C57BL, Mice, Knockout, Mutation, Phenotype, Photoreceptor Cells, Pregnancy Proteins, Proteins, Reproducibility of Results, Retina, RNA Interference, Suppressor Factors, Immunologic, Transfection, Zebrafish},
	issn = {1476-4679},
	doi = {10.1038/ncb3201},
	author = {Wheway, Gabrielle and Schmidts, Miriam and Mans, Dorus A and Szymanska, Katarzyna and Nguyen, Thanh-Minh T and Racher, Hilary and Phelps, Ian G and Toedt, Grischa and Kennedy, Julie and Wunderlich, Kirsten A and Sorusch, Nasrin and Abdelhamed, Zakia A and Natarajan, Subaashini and Herridge, Warren and van Reeuwijk, Jeroen and Horn, Nicola and Boldt, Karsten and Parry, David A and Letteboer, Stef J F and Roosing, Susanne and Adams, Matthew and Bell, Sandra M and Bond, Jacquelyn and Higgins, Julie and Morrison, Ewan E and Tomlinson, Darren C and Slaats, Gisela G and van Dam, Teunis J P and Huang, Lijia and Kessler, Kristin and Giessl, Andreas and Logan, Clare V and Boyle, Evan A and Shendure, Jay and Anazi, Shamsa and Aldahmesh, Mohammed and Al Hazzaa, Selwa and Hegele, Robert A and Ober, Carole and Frosk, Patrick and Mhanni, Aizeddin A and Chodirker, Bernard N and Chudley, Albert E and Lamont, Ryan and Bernier, Francois P and Beaulieu, Chandree L and Gordon, Paul and Pon, Richard T and Donahue, Clem and Barkovich, A James and Wolf, Louis and Toomes, Carmel and Thiel, Christian T and Boycott, Kym M and McKibbin, Martin and Inglehearn, Chris F and Stewart, Fiona and Omran, Heymut and Huynen, Martijn A and Sergouniotis, Panagiotis I and Alkuraya, Fowzan S and Parboosingh, Jillian S and Innes, A Micheil and Willoughby, Colin E and Giles, Rachel H and Webster, Andrew R and Ueffing, Marius and Blacque, Oliver and Gleeson, Joseph G and Wolfrum, Uwe and Beales, Philip L and Gibson, Toby and Doherty, Dan and Mitchison, Hannah M and Roepman, Ronald and Johnson, Colin A}
}
