Journal article
RNA sequencing analysis reveals increased expression of interferon signaling genes and dysregulation of bone metabolism affecting pathways in the whole blood of patients with osteogenesis imperfecta
BMC Medical Genomics, Vol.13(1)
2020
Abstract
Background
Osteogenesis imperfecta (OI) is a rare genetic disorder in which the patients suffer from numerous fractures, skeletal deformities and bluish sclera. The disorder ranges from a mild form to severe and lethal cases. The main objective of this pilot study was to compare the blood transcriptional landscape of OI patients with COL1A1 pathogenic variants and their healthy relatives, in order to find out different gene expression and dysregulated molecular pathways in OI.
Methods
We performed RNA sequencing analysis of whole blood in seven individuals affected with different OI severity and their five unaffected relatives from the three families. The data was analyzed using edgeR package of R Bioconductor. Functional profiling and pathway analysis of the identified differently expressed genes was performed with g:GOSt and MinePath web-based tools.
Results
We identified 114 differently expressed genes. The expression of 79 genes was up-regulated, while 35 genes were down-regulated. The functional analysis identified a presence of dysregulated interferon signaling pathways (IFI27, IFITM3, RSAD12, GBP7). Additionally, the expressions of the genes related to extracellular matrix organization, Wnt signaling, vitamin D metabolism and MAPK-ERK 1/2 pathways were also altered.
Conclusions
The current pilot study successfully captured the differential expression of inflammation and bone metabolism pathways in OI patients. This work can contribute to future research of transcriptional bloodomics in OI. Transcriptional bloodomics has a strong potential to become a major contributor to the understanding of OI pathological mechanisms, the discovery of phenotype modifying factors, and the identification of new therapeutic targets. However, further studies in bigger cohorts of OI patients are needed to confirm the findings of the current work.
Details
- Title
- RNA sequencing analysis reveals increased expression of interferon signaling genes and dysregulation of bone metabolism affecting pathways in the whole blood of patients with osteogenesis imperfecta
- Authors/Creators
- L. Zhytnik (Author/Creator) - Tartu University HospitalK. Maasalu (Author/Creator) - Tartu University HospitalE. Reimann (Author/Creator) - University of TartuA. Märtson (Author/Creator) - Tartu University HospitalS. Kõks (Author/Creator) - Murdoch University
- Publication Details
- BMC Medical Genomics, Vol.13(1)
- Publisher
- BioMed Central Ltd as part of Springer Nature
- Identifiers
- 991005541505807891
- Copyright
- © 2020 The Authors.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.132 Extracellular Matrix & Cell Differentiation
- 1.132.1065 Collagen Disorders
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics