Novel open reading frames in human accelerated regions and transposable elements reveal new leads to understand schizophrenia and bipolar disorder.
Authors
Erady, Chaitanya
Onilogbo, Temiloluwa OAE
Jukes-Jones, Rebekah
Umrania, Yagnesh
Bahn, Sabine
Publication Date
2022-03Journal Title
Mol Psychiatry
ISSN
1359-4184
Publisher
Springer Science and Business Media LLC
Volume
27
Issue
3
Pages
1455-1468
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Erady, C., Amin, K., Onilogbo, T. O., Tomasik, J., Jukes-Jones, R., Umrania, Y., Bahn, S., & et al. (2022). Novel open reading frames in human accelerated regions and transposable elements reveal new leads to understand schizophrenia and bipolar disorder.. Mol Psychiatry, 27 (3), 1455-1468. https://doi.org/10.1038/s41380-021-01405-6
Description
Funder: Ms. Chaitanya Erady was funded by Dr Manmohan Singh scholarship
Funder: Dr. Jakub Tomasik was funded by the Stanley Medical Research Institute (grant number: 07R-1888).
Funder: Prof. Sabine Bahn was funded by the Stanley Medical Research Institute (grant number: 07R-1888).
Abstract
Schizophrenia (SCZ) and bipolar disorder are debilitating neuropsychiatric disorders arising from a combination of environmental and genetic factors. Novel open reading frames (nORFs) are genomic loci that give rise to previously uncharacterized transcripts and protein products. In our previous work, we have shown that nORFs can be biologically regulated and that they may play a role in cancer and rare diseases. More importantly, we have shown that nORFs may emerge in accelerated regions of the genome giving rise to species-specific functions. We hypothesize that nORFs represent a potentially important group of biological factors that may contribute to SCZ and bipolar disorder pathophysiology. Human accelerated regions (HARs) are genomic features showing human-lineage-specific rapid evolution that may be involved in biological regulation and have additionally been found to associate with SCZ genes. Transposable elements (TEs) are another set of genomic features that have been shown to regulate gene expression. As with HARs, their relevance to SCZ has also been suggested. Here, nORFs are investigated in the context of HARs and TEs. This work shows that nORFs whose expression is disrupted in SCZ and bipolar disorder are in close proximity to HARs and TEs and that some of them are significantly associated with SCZ and bipolar disorder genomic hotspots. We also show that nORF encoded proteins can form structures and potentially constitute novel drug targets.
Keywords
Article, /631/208, /631/378, /38/91, /101/58, article
Identifiers
s41380-021-01405-6, 1405
External DOI: https://doi.org/10.1038/s41380-021-01405-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337090
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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