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Defining functional DNA elements in the human genome.

Publication ,  Journal Article
Kellis, M; Wold, B; Snyder, MP; Bernstein, BE; Kundaje, A; Marinov, GK; Ward, LD; Birney, E; Crawford, GE; Dekker, J; Dunham, I; Elnitski, LL ...
Published in: Proc Natl Acad Sci U S A
April 29, 2014

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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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 29, 2014

Volume

111

Issue

17

Start / End Page

6131 / 6138

Location

United States

Related Subject Headings

  • Software
  • Regulatory Sequences, Nucleic Acid
  • Humans
  • Genome, Human
  • Disease
  • DNA
  • Biological Evolution
 

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Kellis, M., Wold, B., Snyder, M. P., Bernstein, B. E., Kundaje, A., Marinov, G. K., … Hardison, R. C. (2014). Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A, 111(17), 6131–6138. https://doi.org/10.1073/pnas.1318948111
Kellis, Manolis, Barbara Wold, Michael P. Snyder, Bradley E. Bernstein, Anshul Kundaje, Georgi K. Marinov, Lucas D. Ward, et al. “Defining functional DNA elements in the human genome.Proc Natl Acad Sci U S A 111, no. 17 (April 29, 2014): 6131–38. https://doi.org/10.1073/pnas.1318948111.
Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, et al. Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6131–8.
Kellis, Manolis, et al. “Defining functional DNA elements in the human genome.Proc Natl Acad Sci U S A, vol. 111, no. 17, Apr. 2014, pp. 6131–38. Pubmed, doi:10.1073/pnas.1318948111.
Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos JA, Weng Z, White KP, Hardison RC. Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6131–6138.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 29, 2014

Volume

111

Issue

17

Start / End Page

6131 / 6138

Location

United States

Related Subject Headings

  • Software
  • Regulatory Sequences, Nucleic Acid
  • Humans
  • Genome, Human
  • Disease
  • DNA
  • Biological Evolution