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

Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

doi:10.1073/pnas.1410434111

Letter

Biological Sciences

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

August 8, 2014

111 (33) E3366

https://doi.org/10.1073/pnas.1410434111

Perspective

April 21, 2014

Defining functional DNA elements in the human genome

Letter

August 8, 2014

Getting “function” right

Tyler D. P. Brunet, W. Ford Doolittle

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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.

References

1

TDP Brunet, WF Doolittle, Getting “function” right. Proc Natl Acad Sci USA 111, E3365 (2014).

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2

M Kellis, et al., Defining functional DNA elements in the human genome. Proc Natl Acad Sci USA 111, 6131–6138 (2014).

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3

PL Germain, E Ratti, F Boem, Junk or functional DNA? ENCODE and the function controversy. Biol Philos, 2014).

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WF Doolittle, TDP Brunet, S Linquist, TR Gregory, Distinguishing between “function” and “effect” in genome biology. Genome Biol Evol 6, 1234–1237 (2014).

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Information & Authors

Information

Published in

Proceedings of the National Academy of Sciences

Vol. 111 | No. 33
August 19, 2014

PubMed: 25275169

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Published online: August 8, 2014

Published in issue: August 19, 2014

Authors

Affiliations

Manolis Kellis¹ [email protected]

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;

Broad Institute, Cambridge, MA 02139;

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Barbara Wold

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;

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Michael P. Snyder

Department of Genetics, Stanford University, Stanford, CA 94305;

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Bradley E. Bernstein

Broad Institute, Cambridge, MA 02139;

Harvard Medical School and

Massachusetts General Hospital, Boston, MA 02114;

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Anshul Kundaje

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;

Broad Institute, Cambridge, MA 02139;

Department of Genetics, Stanford University, Stanford, CA 94305;

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Georgi K. Marinov

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;

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Lucas D. Ward

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;

Broad Institute, Cambridge, MA 02139;

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Ewan Birney

European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom;

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Gregory E. Crawford

Medical Genetics, Duke University, Durham, NC 27708;

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Job Dekker

Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605;

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Ian Dunham

European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom;

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Laura L. Elnitski

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;

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Peggy J. Farnham

Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089;

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Elise A. Feingold

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;

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Mark Gerstein

Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520;

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Morgan C. Giddings

Marketing Your Science, LLC, Boise, ID 83702;

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David M. Gilbert

Department of Biological Science, Florida State University, Tallahassee, FL 32306;

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Thomas R. Gingeras

Functional Genomics Group, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;

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Eric D. Green

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;

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Roderic Guigo

Bioinformatics and Genomics Program, Center for Genome Regulation, E-08003 Barcelona, Catalonia, Spain;

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Tim Hubbard

Medical and Molecular Genetics, King's College London and Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SD, United Kingdom;

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Jim Kent

Biomolecular Engineering, University of California, Santa Cruz, CA 95064;

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Jason D. Lieb

Department of Human Genetics, University of Chicago, Chicago, IL 60637;

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Richard M. Myers

HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806;

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Michael J. Pazin

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;

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Bing Ren

Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093;

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John Stamatoyannopoulos

Genome Sciences and Medicine, University of Washington, Seattle, WA 98195; and

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Zhiping Weng

Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605;

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Kevin P. White

Department of Human Genetics, University of Chicago, Chicago, IL 60637;

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Ross C. Hardison¹ [email protected]

Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802

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Notes

1

To whom correspondence may be addressed. Email: [email protected] or [email protected].

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.

Competing Interests

The authors declare no conflict of interest.

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Cite this article

M. Kellis,
B. Wold,
M.P. Snyder,
B.E. Bernstein,
A. Kundaje,
G.K. Marinov,
L.D. Ward,
E. Birney,
G.E. Crawford,
J. Dekker,
I. Dunham,
L.L. Elnitski,
P.J. Farnham,
E.A. Feingold,
M. Gerstein,
M.C. Giddings,
D.M. Gilbert,
T.R. Gingeras,
E.D. Green,
R. Guigo,
T. Hubbard,
J. Kent,
J.D. Lieb,
R.M. Myers,
M.J. Pazin,
B. Ren,
J. Stamatoyannopoulos,
Z. Weng,
K.P. White,
& R.C. Hardison,

Reply to Brunet and Doolittle: Both selected effect and causal role elements can influence human biology and disease, Proc. Natl. Acad. Sci. U.S.A. 111 (33) E3366-E3366, https://doi.org/10.1073/pnas.1410434111 (2014).

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Further reading in this issue

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