Marcogliese, Paul C., Deal, Samantha L., Andrews, Jonathan ORCID: 0000-0002-3086-7225, Harnish, J. Michael, Bhavana, V. Hemanjani, Graves, Hillary K., Jangam, Sharayu ORCID: 0000-0001-7389-0890, Luo, Xi, Liu, Ning, Bei, Danqing, Hull, Brooke, Pan, Hongling, Bhadane, Pradnya, Longley, Colleen M., Haelterman, Nele A., Kanca, Oguz, Manivannan, Sathiya N., Rossetti, Linda Z., German, Ryan J., Gerard, Amanda, Schwaibold, Eva Maria Christina, Fehr, Sarah, Guerrini, Renzo ORCID: 0000-0002-7272-7079, Vetro, Annalisa, England, Eleina, Murali, Chaya N., Barakat, Tahsin Stefan, van Dooren, Marieke F., Wilke, Martina, van Slegtenhorst, Marjon, Lesca, Gaetan, Sabatier, Isabelle, Chatron, Nicolas, Brownstein, Catherine A., Madden, Jill A., Agrawal, Pankaj B., Keren, Boris, Courtin, Thomas, Perrin, Laurence, Brugger, Melanie, Roser, Timo, Leiz, Steffen, Mau-Them, Frederic Tran, Delanne, Julian, Sukarova-Angelovska, Elena, Trajkova, Slavica, Rosenhahn, Erik, Strehlow, Vincent, Platzer, Konrad, Keller, Roberto, Pavinato, Lisa ORCID: 0000-0002-7630-8365, Brusco, Alfredo, Rosenfeld, Jill A., Marom, Ronit, Wangler, Michael F. and Yamamoto, Shinya (2022). Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases. Cell Reports, 38 (11). CAMBRIDGE: CELL PRESS. ISSN 2211-1247

Full text not available from this repository.

Abstract

Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through humanizationrescue and overexpression-based strategies. We examine 79 ASD variants in 74 genes identified in the Simons Simplex Collection and find 38% of them to cause functional alterations. Moreover, we identify GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in 13 previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes points to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Marcogliese, Paul C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deal, Samantha L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrews, JonathanUNSPECIFIEDorcid.org/0000-0002-3086-7225UNSPECIFIED
Harnish, J. MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bhavana, V. HemanjaniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graves, Hillary K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jangam, SharayuUNSPECIFIEDorcid.org/0000-0001-7389-0890UNSPECIFIED
Luo, XiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, NingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bei, DanqingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hull, BrookeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pan, HonglingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bhadane, PradnyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Longley, Colleen M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haelterman, Nele A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kanca, OguzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manivannan, Sathiya N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossetti, Linda Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
German, Ryan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerard, AmandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwaibold, Eva Maria ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fehr, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerrini, RenzoUNSPECIFIEDorcid.org/0000-0002-7272-7079UNSPECIFIED
Vetro, AnnalisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
England, EleinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murali, Chaya N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barakat, Tahsin StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Dooren, Marieke F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilke, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Slegtenhorst, MarjonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesca, GaetanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabatier, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatron, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brownstein, Catherine A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madden, Jill A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agrawal, Pankaj B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keren, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Courtin, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perrin, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brugger, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roser, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leiz, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mau-Them, Frederic TranUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delanne, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sukarova-Angelovska, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trajkova, SlavicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenhahn, ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strehlow, VincentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platzer, KonradUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keller, RobertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pavinato, LisaUNSPECIFIEDorcid.org/0000-0002-7630-8365UNSPECIFIED
Brusco, AlfredoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenfeld, Jill A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marom, RonitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wangler, Michael F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamamoto, ShinyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-698576
DOI: 10.1016/j.celrep.2022.110517
Journal or Publication Title: Cell Reports
Volume: 38
Number: 11
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATIONS; GENE; GENERATION; FRAMEWORK; RESOURCE; ANNOTATION; COLLECTION; VERSATILE; INSERTION; REVEALSMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69857

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item