The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
A Regulatory SNP Causes a Human Genetic Disease by Creating a New Transcriptional Promoter
Abstract
We describe a pathogenetic mechanism underlying a variant form of the inherited blood disorder α thalassemia. Association studies of affected individuals from Melanesia localized the disease trait to the telomeric region of human chromosome 16, which includes the α-globin gene cluster, but no molecular defects were detected by conventional approaches. After resequencing and using a combination of chromatin immunoprecipitation and expression analysis on a tiled oligonucleotide array, we identified a gain-of-function regulatory single-nucleotide polymorphism (rSNP) in a nongenic region between the α-globin genes and their upstream regulatory elements. The rSNP creates a new promoterlike element that interferes with normal activation of all downstream α-like globin genes. Thus, our work illustrates a strategy for distinguishing between neutral and functionally important rSNPs, and it also identifies a pathogenetic mechanism that could potentially underlie other genetic diseases.
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Self-citationCis-Acting Regulatory Variation in the Human Genome
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Cited by
Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning
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Ishigaki, K., Akiyama, M., Kanai, M., Takahashi, A., Kawakami, E., Sugishita, H., Sakaue, S., Matoba, N., Low, S.-K., Okada, Y., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0640-3 · Cited by 508
Topology of mammalian developmental enhancers and their regulatory landscapes
de Laat, W., & Duboule, D. (2013) · Nature · doi:10.1038/nature12753 · Cited by 521
Metadata
- Authors
- De Gobbi, M., Viprakasit, V., Hughes, J. R., Fisher, C., Buckle, V. J., Ayyub, H., Gibbons, R. J., Vernimmen, D., Yoshinaga, Y., de Jong, P., Cheng, J.-F., Rubin, E. M., Wood, W. G., Bowden, D., & Higgs, D. R.
- Venue
- Science
- Published
- 2006-05-26
- Volume
- 312
- Issue
- 5777
- Pages
- 1215-1217
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1553587640
- Cited by
- 278
- References
- 15
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- closed
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- De Gobbi, M., Viprakasit, V., Hughes, J. R., Fisher, C., Buckle, V. J., Ayyub, H., Gibbons, R. J., Vernimmen, D., Yoshinaga, Y., de Jong, P., Cheng, J.-F., Rubin, E. M., Wood, W. G., Bowden, D., & Higgs, D. R. (2006). A Regulatory SNP Causes a Human Genetic Disease by Creating a New Transcriptional Promoter. Science. https://doi.org/10.1126/science.1126431
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