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Published August 19, 2014 | Published
Journal Article Open

Reply to Brunet and Doolittle: Both selected effect and causal role elements can influence human biology and disease


We agree with Brunet and Doolittle (1) on the utility of distinguishing the evolutionarily selected effects (SE) of some genomic elements from the causal roles (CR) of other elements that lack signatures of selection (1⇓⇓–4). DNA sequences identified by biochemical approaches include both SE and CR elements, and genetic variation in both has been implicated in human traits and disease susceptibility. We thus view the Encyclopedia of DNA Elements (ENCODE) catalog and similar data resources as important foundations for understanding the DNA elements and molecular mechanisms underlying human biology and disease.

Additional Information

© 2014 2014 National Academy of Sciences. Published online before print August 8, 2014. Author contributions: M.K., B.W., M.P.S., B.E.B., and R.C.H. designed research; M.K., B.W., M.P.S., B.E.B., A.K., G.K.M., L.D.W., and R.C.H. performed research; M.K., B.W., M.P.S., B.E.B., A.K., G.K.M., L.D.W., and R.C.H. analyzed data; and M.K., B.W., M.P.S., B.E.B., A.K., G.K.M., L.D.W., E.B., G.E.C., J.D., I.D., L.L.E., P.J.F., E.A.F., M.G., M.C.G., D.M.G., T.R.G., E.D.G., R.G., T.H., J.K., J.D.L., R.M.M., M.J.P., B.R., J.S., Z.W., K.P.W., and R.C.H. wrote the paper. The authors declare no conflict of interest.

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August 20, 2023
October 17, 2023