Phenotypic Landscape of Schizophrenia-Associated Genes Defines Candidates and Their Shared Functions
| Autor: | Shristi Pandey, Owen Randlett, Lindsey M. Pieper, Joel Greenwood, Steven A. McCarroll, Summer B. Thyme, Steven Zimmerman, Eric Li, Edward R. Soucy, Yiqun Wang, Joo Won Choi, Carrie Sha, Alexander F. Schier, Nathan S. Morris |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Candidate gene Mechanism (biology) Computational biology Biology biology.organism_classification Phenotype 03 medical and health sciences 0302 clinical medicine Forebrain Gene Transcription factor Zebrafish Prepulse inhibition 030217 neurology & neurosurgery 030304 developmental biology Genetic association |
| Zdroj: | SSRN Electronic Journal. |
| ISSN: | 1556-5068 |
| Popis: | SummaryGenomic studies have identified hundreds of candidate genes near loci associated with risk for schizophrenia. To define candidates and their functions, we mutated zebrafish orthologues of 132 human schizophrenia-associated genes and created a phenotype atlas consisting of whole-brain activity maps, brain structural differences, and profiles of behavioral abnormalities. Phenotypes were diverse but specific, including altered forebrain development and decreased prepulse inhibition. Exploration of these datasets identified promising candidates in more than 10 gene-rich regions, including the magnesium transportercnnm2and the translational repressorgigyf2, and revealed shared anatomical sites of activity differences, including the pallium, hypothalamus or tectum. Single-cell RNA sequencing uncovered an essential role for the understudied transcription factorznf536in the development of forebrain neurons implicated in social behavior and stress. This phenotypic landscape of schizophrenia-associated genes prioritizes more than 30 candidates for further study and provides hypotheses to bridge the divide between genetic association and biological mechanism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|