Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec;59:112-119.
doi: 10.1016/j.conb.2019.05.007. Epub 2019 Jun 27.

Spatial Genome Exploration in the Context of Cognitive and Neurological Disease

Affiliations
Free PMC article
Review

Spatial Genome Exploration in the Context of Cognitive and Neurological Disease

Prashanth Rajarajan et al. Curr Opin Neurobiol. .
Free PMC article

Abstract

The 'non-linear' genome, or the spatial proximity of non-contiguous sequences, emerges as an important regulatory layer for genome organization and function, including transcriptional regulation. Here, we review recent genome-scale chromosome conformation mappings ('Hi-C') in developing and adult human and mouse brain. Neural differentiation is associated with widespread remodeling of the chromosomal contact map, reflecting dynamic changes in cell-type-specific gene expression programs, with a massive (estimated 20-50%) net loss of chromosomal contacts that is specific for the neuronal lineage. Hi-C datasets provided an unexpected link between locus-specific abnormal expansion of repeat sequences positioned at the boundaries of self-associating topological chromatin domains, and monogenic neurodevelopmental and neurodegenerative disease. Furthermore, integrative cell-type-specific Hi-C and transcriptomic analysis uncovered an expanded genomic risk space for sequences conferring liability for schizophrenia and other cognitive disease. We predict that spatial genome exploration will deliver radically new insights into the brain nucleome in health and disease.

Conflict of interest statement

Conflicts of Interest: The authors report no conflict.

Similar articles

See all similar articles

Publication types

LinkOut - more resources

Feedback