Extreme context specificity in differential allelic expression
Open accessAbstract
Variability in cis-regulation of gene expression has been implicated in the phenotypic manifestation of complex traits including common, multifactorial diseases. The differential expression of alleles due to polymorphism in cis-regulatory elements is common in the human genome, but there is a paucity of information about the context specificity of these control elements. In this study, we examined the differential allelic expression (DAE) of BMP5 in human mesenchymal tissues obtained from 16 donors undergoing joint replacement for treatment of osteoarthritis. We observed significant differences in BMP5 allelic output, with allelic ratios greater than 4:1 (P < 10(-20)) in the tissues of some donors. We also discovered a significant variability in allelic expression within the different tissues of donors. For 12 of our donors, we examined the allelic expression of BMP5 in two different regions of cartilage: cartilage adjacent to the site of the osteoarthritic lesion and cartilage distal from the lesion. Five of these 12 donors demonstrated highly significant differences (P < or = 10(-8)) in allelic expression between the different regions of their cartilage. Using DAE as a phenotype, we attempted to map tissue-specific cis-regulatory polymorphisms, and we identified a single nucleotide polymorphism located downstream of BMP5, which was significantly associated with DAE in some but not all of the examined tissues. These findings suggest that allelic expression can be highly context specific and that when interrogating the cis-regulatory control of a particular gene, one cannot necessarily assume that allelic expression is conserved across different tissues or even across different regions of the same tissue.
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Allelic imbalance is commonly observed in a tissue-specific manner.
“Allelic imbalance is commonly observed in a tissue-specific manner (51, 52).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [51]
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“Allelic imbalance is commonly observed in a tissue-specific manner (51, 52).”
- Authors
- Wilkins, J. M., Southam, L., Price, A. J., Mustafa, Z., Carr, A., & Loughlin, J.
- Affiliations
- Nuffield Orthopaedic Centre (GB)
- Corresponding author
- Wilkins, James M.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-12
- Volume
- 16
- Issue
- 5
- Pages
- 537-546
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2150674712
- Cited by
- 53
- References
- 31
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Marshall Aid Commemoration Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- differential allelic expression, BMP5, cis-regulatory polymorphisms, context specificity, single nucleotide polymorphisms, mesenchyme, cartilage, osteoarthritis, joint replacement, tissue-specific gene regulation, allelic ratio
- MeSH terms
- Alleles, Heterozygote, Homozygote, Humans, Mesoderm, Organ Specificity, Regulatory Sequences, Nucleic Acid, Tissue Donors, Genetic Variation, Bone Morphogenetic Proteins, Gene Expression Profiling, Bone Morphogenetic Protein 5
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