Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster

Janani Iyer, Mayanglambam Dhruba Singh, Matthew Jensen, Payal Patel, Lucilla Pizzo, Emily Huber, Haley Koerselman, Alexis T. Weiner, Paola Lepanto, Komal Vadodaria, Alexis Kubina, Qingyu Wang, Abigail Talbert, Sneha Yennawar, Jose Badano, J. Robert Manak, Melissa M. Rolls, Arjun Krishnan and Santhosh Girirajan ()
Additional contact information
Janani Iyer: The Pennsylvania State University
Mayanglambam Dhruba Singh: The Pennsylvania State University
Matthew Jensen: The Pennsylvania State University
Payal Patel: The Pennsylvania State University
Lucilla Pizzo: The Pennsylvania State University
Emily Huber: The Pennsylvania State University
Haley Koerselman: University of Iowa
Alexis T. Weiner: The Pennsylvania State University
Paola Lepanto: Institut Pasteur de Montevideo
Komal Vadodaria: The Pennsylvania State University
Alexis Kubina: The Pennsylvania State University
Qingyu Wang: The Pennsylvania State University
Abigail Talbert: The Pennsylvania State University
Sneha Yennawar: The Pennsylvania State University
Jose Badano: Institut Pasteur de Montevideo
J. Robert Manak: University of Iowa
Melissa M. Rolls: The Pennsylvania State University
Arjun Krishnan: Michigan State University
Santhosh Girirajan: The Pennsylvania State University

Nature Communications, 2018, vol. 9, issue 1, 1-19

Abstract: Abstract As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We test 565 pairwise knockdowns in the developing eye, and identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways are also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for pervasive genetic interactions within CNVs towards cellular and developmental phenotypes.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04882-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04882-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04882-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().