Is Aberrant Genome Organization a Cause or Consequence of Specific Diseases?

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Background

The genome is specifically organized in healthy cells. Disruption of such genome organization has been observed in most of a class of inherited diseases linked to mutations in nuclear envelope proteins collectively termed laminopathies and also in a wide variety of other heritable disorders ranging from developmental defects to metabolic syndromes to cancer. Genome organization also changes in response to environmental stimuli, upon cellular senescence and at different stages in differentiation; so it is possible that the observed altered genome organization in many of these disorders is a consequence of other changes from a distinct root cause as opposed to the primary defect underlying the disorder. To determine appropriate treatments it is critical to ascertain whether the aberrant genome organization is cause or consequence.

Thus, this Research Topic invites papers addressing not just the core question of whether aberrant genome organization is cause or consequence of disease, but also studies addressing the other issues raised above potentially linking disease changes to other functional genome states, finding the best controls to partner assessment of diseased cells, new models to study disease — especially developing transitional states from health to compromised cells on a path to disease or immortalization and that better recapitulate the in vivo environment, and most importantly the mechanisms by which the genome is changed in a disease state. Furthermore, we need to take a more global view of nuclear and genomic health and develop assays and tests that circumvent the need to sequence and map the whole genome, perform mass spectrometry and high resolution imaging on every cell type or sick person. When we have this clearer picture of genome organization in disease compared to health, then we may be able to decide whether cells displaying aberrant genome organization should be targeted for disposal, treated to restore more normal genome behavior or addressed in other ways.
We encourage creative submissions including theory papers. For research studies, we would encourage those submitting on the same disease to liaise with one another to generate some unified standards to enable better comparison of studies; however, we will also accept papers from those who do not want to participate in this novel approach. For those interested, we would request permission to share your contact details with other participants. The editors will also be happy to discuss potential submissions with any interested parties. For both research and theory papers the core question addressed should interrogate the idea that genome mis-organization is the direct cause of a particular disease, but we encourage a wide range of approaches: for example, one could test indirect effects through nucleoskeleton defects disrupting mechanosignaling or one could investigate wide-ranging aspects of genome organization from gene and regulatory element mispositioning to phase separation or nuclear body disruption.

Keywords: Genome, Genome Organization, Nuclear Envelope, Inherited Disease, Cellular Senescence

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