Window of Susceptibility for Zika-Induced Microcephaly Identified by Temporal Gene Analysis

No Thumbnail Available
Authors
Bennett, Kristin P.
Brown, Elisabeth
De Los Santos, Hannah
Poegel, Matt
Kiehl, Thomas
Patton, Evan
McGuinness, Deborah L.
Temple, Sally
Boles, Nathan
Issue Date
2017-04-10
Type
Language
Keywords
CHEAR (Child Health Exposure Analysis Repository)
Research Projects
Organizational Units
Journal Issue
Alternative Title
Abstract
Increased understanding of developmental disorders of the brain has shown that genetic mutations, environmental toxins and biological insults typically act during developmental windows of susceptibility. Through analysis of developmental time-course gene expression data derived from human pluripotent stem cells, with disease association, pathway, and protein interaction databases, we identify windows of developmental time that appear most vulnerable to a specific insult, and therefore, the time periods for productive interventions. The results are displayed as interactive Susceptibility Windows Ontological Transcriptome (SWOT) Clocks illustrating disease susceptibility over developmental time. Using this method, we determine the likely windows of susceptibility for multiple neurological disorders, including Zika-induced microcephaly. We find that genes impacted by Zika infection are most active in the earliest stages of neural development, prior to cerebral cortex layer formation.
Description
Full Citation
Publisher
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
EISSN