دورية أكاديمية
Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome
العنوان: | Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome |
---|---|
المؤلفون: | Roosing, Susanne, Hofree, Matan, Kim, Sehyun, Scott, Eric, Copeland, Brett, Romani, Marta, Silhavy, Jennifer L, Rosti, Rasim O, Schroth, Jana, Mazza, Tommaso, Miccinilli, Elide, Zaki, Maha S, Swoboda, Kathryn J, Milisa-Drautz, Joanne, Dobyns, William B, Mikati, Mohamed A, İncecik, Faruk, Azam, Matloob, Borgatti, Renato, Romaniello, Romina, Boustany, Rose-Mary, Clericuzio, Carol L, D'Arrigo, Stefano, Strømme, Petter, Boltshauser, Eugen, Stanzial, Franco, Mirabelli-Badenier, Marisol, Moroni, Isabella, Bertini, Enrico, Emma, Francesco, Steinlin, Maja, Hildebrandt, Friedhelm, Johnson, Colin A, Freilinger, Michael, Vaux, Keith K, Gabriel, Stacey B, Aza-Blanc, Pedro, Heynen-Genel, Susanne, Ideker, Trey, Dynlacht, Brian D, Lee, Ji Eun, Valente, Enza Maria, Kim, Joon, Gleeson, Joseph G |
المصدر: | Roosing, S., M. Hofree, S. Kim, E. Scott, B. Copeland, M. Romani, J. L. Silhavy, et al. 2015. “Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome.” eLife 4 (1): e06602. doi:10.7554/eLife.06602. http://dx.doi.org/10.7554/eLife.06602Test. |
بيانات النشر: | eLife Sciences Publications, Ltd, 2015. |
سنة النشر: | 2015 |
المجموعة: | HMS Scholarly Articles |
مصطلحات موضوعية: | Joubert syndrome, ciliopathy, siRNA, high-content screen, KIAA0586, Talpid3, human |
الوصف: | 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. DOI: http://dx.doi.org/10.7554/eLife.06602.001Test |
نوع الوثيقة: | Journal Article |
اللغة: | English |
تدمد: | 2050-084X |
العلاقة: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477441/pdfTest/; eLife |
DOI: | 10.7554/eLife.06602 |
الوصول الحر: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295778Test |
حقوق: | open |
رقم الانضمام: | edshld.1.17295778 |
قاعدة البيانات: | Digital Access to Scholarship at Harvard (DASH) |