The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Defining functional DNA elements in the human genome
Open accessAbstract
With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.
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Cites
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The Human Transcription Factors
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Self-citationPartitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases
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Metadata
- Authors
- Kellis, M., Wold, B., Snyder, M. P., Bernstein, B. E., Kundaje, A., Marinov, G. K., Ward, L. D., Birney, E., Crawford, G. E., Dekker, J., Dunham, I., Elnitski, L. L., Farnham, P. J., Feingold, E. A., Gerstein, M., Giddings, M. C., Gilbert, D. M., Gingeras, T. R., Green, E. D., Guigo, R., Hubbard, T., Kent, J., Lieb, J. D., Myers, R. M., Pazin, M. J., Ren, B., Stamatoyannopoulos, J. A., Weng, Z., White, K. P., & Hardison, R. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2014-04-21
- Volume
- 111
- Issue
- 17
- Pages
- 6131-6138
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2007203150
- Cited by
- 696
- References
- 26
- FWCI
- 35.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kellis, M., Wold, B., Snyder, M. P., Bernstein, B. E., Kundaje, A., Marinov, G. K., Ward, L. D., Birney, E., Crawford, G. E., Dekker, J., Dunham, I., Elnitski, L. L., Farnham, P. J., Feingold, E. A., Gerstein, M., Giddings, M. C., Gilbert, D. M., Gingeras, T. R., Green, E. D., . . . Hardison, R. C. (2014). Defining functional DNA elements in the human genome. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1318948111
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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