Title

Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk

UMMS Affiliation

Program in Bioinformatics and Integrative Biology

Publication Date

2018-12-14

Document Type

Article

Disciplines

Bioinformatics | Computational Biology | Genetic Phenomena | Genomics | Integrative Biology | Mental Disorders | Nervous System | Nervous System Diseases | Neuroscience and Neurobiology | Structural Biology | Systems Biology

Abstract

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

10.1126/science.aat4311

Source

Science. 2018 Dec 14;362(6420). pii: eaat4311. doi: 10.1126/science.aat4311. Link to article on publisher's site

Journal/Book/Conference Title

Science (New York, N.Y.)

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30545851

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