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dc.contributor.authorRajarajan, Prashanth
dc.contributor.authorBorrman, Tyler M.
dc.contributor.authorLiao, Will
dc.contributor.authorEspeso-Gil, Sergio
dc.contributor.authorChandrasekaran, Sandhya
dc.contributor.authorJiang, Yan
dc.contributor.authorWeng, Zhiping
dc.contributor.authorBrennand, Kristen J.
dc.contributor.authorAkbarian, Schahram
dc.date2022-08-11T08:07:59.000
dc.date.accessioned2022-08-23T15:38:05Z
dc.date.available2022-08-23T15:38:05Z
dc.date.issued2019-12-01
dc.date.submitted2019-09-25
dc.identifier.citation<p>Curr Opin Neurobiol. 2019 Dec;59:112-119. doi: 10.1016/j.conb.2019.05.007. <a href="https://doi.org/10.1016/j.conb.2019.05.007">Link to article on publisher's site</a></p>
dc.identifier.issn0959-4388 (Linking)
dc.identifier.doi10.1016/j.conb.2019.05.007
dc.identifier.pmid31255842
dc.identifier.urihttp://hdl.handle.net/20.500.14038/25861
dc.description.abstractThe '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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31255842&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.conb.2019.05.007
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectBioinformatics
dc.subjectComputational Biology
dc.subjectGenetics and Genomics
dc.subjectIntegrative Biology
dc.subjectMental Disorders
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.titleSpatial genome exploration in the context of cognitive and neurological disease
dc.typeJournal Article
dc.source.journaltitleCurrent opinion in neurobiology
dc.source.volume59
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/bioinformatics_pubs/154
dc.identifier.contextkey15424794
html.description.abstract<p>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.</p>
dc.identifier.submissionpathbioinformatics_pubs/154
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.source.pages112-119


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