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EVENT DESCRIPTION  
 
Event Type:  Seminar (This is an NIH Science event)
 
Title:  Translating Genetics into Molecular Mechanisms of Neuropsychiatric Disorders.
 
Description:  Three-dimensional (3D) physical interactions within chromosomes dynamically regulate gene expression in a tissue specific manner. However, the detailed 3D structural organization of chromosomes in human brain development and its role in regulating gene expression networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are not understood. We generated high-resolution 3D maps of chromatin contacts during the peak of human corticogenesis, permitting large-scale annotation of previously uncharacterized gene regulatory relationships relevant to the evolution of human cognition and disease. Our analyses identify hundreds of genes that physically interact with human-gained enhancers during human brain development, many of which we show are under purifying selection and associated with human cognitive function. By integrating chromatin contacts with non-coding variants identified in schizophrenia genome-wide association studies (GWAS), we highlight multiple candidate risk schizophrenia genes and pathways, including transcription factors involved in neurogenesis, cortical lamination and patterning, as well as cholinergic receptors. We characterize several novel putative schizophrenia risk genes identified by their physical interaction during brain development with a credible GWAS locus, and supported by independent eQTL and gene expression analyses in post mortem brain. Genome editing in primary human neural progenitors (phNPC) suggests that one of these distal schizophrenia GWAS loci regulates FOXG1 expression, suggesting a mechanistic basis for its potential role as a novel schizophrenia risk gene. This work provides a framework for understanding the impact of non-coding regulatory elements on human brain development and the evolution of cognition, and highlights novel genetic mechanisms underlying neuropsychiatric disorders.
 
Videocast:  Event will not be videocast
 
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EVENT DATE/TIME  
 
Date/Time: 
Thursday, March 23, 2017   11:00am - 12:00pm Add To Outlook Calendar     Add To iCal Calendar     Add To Entourage Calendar
 
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EVENT SPEAKER(S)  
 
Name:   Hyejung Won, Ph.D.
Title:   Postdoctoral Fellow
Organization:   University of California, Los Angeles
City/Province:   Los Angeles
State:   California
Country:   USA
 

EVENT SPONSOR(S)  
 
Organization(s):  Cellular & Developmental Neurobiologist, NICHD
 

EVENT LOCATION  
 
Location:  On the main NIH Campus
Building:  John Edward Porter Neuroscience Research Center
Room:  Building 35, Room GG607
 
Street Address:  35 Convent Drive
City:  Bethesda
State:  Maryland
Zip Code:  20892
 

EVENT CONTACT(S)  
 
Name:   Katrina Matthews
E-mail:   mattheka@mail.nih.gov
Phone:   301-496-5039
Fax:   301-402-9319
 
 
 
 
 
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