Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk
Program in Bioinformatics and Integrative Biology
Bioinformatics | Computational Biology | Genetic Phenomena | Genomics | Integrative Biology | Mental Disorders | Nervous System | Nervous System Diseases | Neuroscience and Neurobiology | Structural Biology | Systems Biology
To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type-specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type-specific disease risk vulnerabilities in spatial genome organization.
DOI of Published Version
Science. 2018 Dec 14;362(6420). pii: eaat4311. doi: 10.1126/science.aat4311. Link to article on publisher's site
Science (New York, N.Y.)
Rajarajan, Prashanth; Borrman, Tyler M.; Weng, Zhiping; and Akbarian, Schahram, "Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk" (2018). Program in Bioinformatics and Integrative Biology Publications and Presentations. 145.