Modularity and interactions in the genetics of gene expression

Oren Litvin; Helen C. Causton; Bo-Juen Chen; Dana Pe'er

doi:10.1073/pnas.0810208106

journal article Apr 21, 2009

Modularity and interactions in the genetics of gene expression

Oren Litvin Helen C. Causton Bo-Juen Chen Dana Pe'er

Proceedings of the National Academy of Sciences Vol. 106 No. 16 pp. 6441-6446 · Proceedings of the National Academy of Sciences

View at Publisher Save 10.1073/pnas.0810208106

Abstract

Understanding the effect of genetic sequence variation on phenotype is a major challenge that lies at the heart of genetics. We developed GOLPH (GenOmic Linkage to PHenotype), a statistical method to identify genetic interactions, and used it to characterize the landscape of genetic interactions between gene expression quantitative trait loci. Our results reveal that allele-specific interactions, in which a gene only exerts an influence on the phenotype in the presence of a particular allele at the primary locus, are widespread and that genetic interactions are predominantly nonadditive. The data portray a complex picture in which interacting loci influence the expression of modules of coexpressed genes involved in coherent biological processes and pathways. We show that genetic variation at a single gene can have a major impact on the global transcriptional response, altering interactions between genes through shutdown or activation of pathways. Thus, different cellular states occur not only in response to the external environment but also result from intrinsic genetic variation.

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References

30

[1]

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Paul R. Burton, David G. Clayton, Lon R. Cardon et al.

Nature 10.1038/nature05911

[2]

10.1126/science.1069516

[3]

10.1038/ng1094

[4]

10.1038/nature01434

[5]

10.1038/ng1222

[6]

10.1073/pnas.0408709102

[7]

10.1371/journal.pbio.0060083

[8]

10.1371/journal.pbio.0030267

[9]

10.1038/nature03865

[10]

10.1038/ng.167

[11]

10.1038/ng1991

[12]

From molecular to modular cell biology

Leland H. Hartwell, John J. Hopfield, Stanislas Leibler et al.

Nature 10.1038/35011540

[13]

10.1038/ng1165

[14]

10.1016/s0092-8674(00)00015-5

[15]

10.1242/jeb.201.8.1177

[16]

10.1074/jbc.273.48.32042

[17]

An improved map of conserved regulatory sites for Saccharomyces cerevisiae

Kenzie D MacIsaac, Ting Wang, D Benjamin Gordon et al.

BMC Bioinformatics 10.1186/1471-2105-7-113

[18]

Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families

E. H. Corder, A. M. Saunders, W. J. Strittmatter et al.

Science 10.1126/science.8346443

[19]

10.1038/ng.215

[20]

10.1101/gr.068692.107

[21]

10.1371/journal.pgen.1000024

[22]

10.1101/gr.075622.107

[23]

10.1038/msb.2008.4

[24]

Using Bayesian Networks to Analyze Expression Data

Nir Friedman, Michal Linial, Iftach Nachman et al.

Journal of Computational Biology 10.1089/106652700750050961

[25]

10.1073/pnas.0601852103

[26]

10.1371/journal.pcbi.0030069

[27]

Variations in DNA elucidate molecular networks that cause disease

Yanqing Chen, Jun Zhu, Pek Yee Lum et al.

Nature 10.1038/nature06757

[28]

Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results

Eric Lander, Leonid Kruglyak

Nature Genetics 10.1038/ng1195-241

[29]

10.1093/biomet/29.3-4.350

[30]

Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

Yoav Benjamini, Yosef Hochberg

Journal of the Royal Statistical Society Series B:... 1995 10.1111/j.2517-6161.1995.tb02031.x

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Details

Published: Apr 21, 2009
Vol/Issue: 106(16)
Pages: 6441-6446

Authors

O

Oren Litvin

Department of Biological Sciences, Columbia University, New York, NY 10027;; Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032; and

H

Helen C. Causton

Department of Biological Sciences, Columbia University, New York, NY 10027;

B

Bo-Juen Chen

Department of Biological Sciences, Columbia University, New York, NY 10027;; Department of Biomedical Informatics, Columbia University, New York, NY 10032

D

Dana Pe'er

Department of Biological Sciences, Columbia University, New York, NY 10027;; Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032; and

Cite This Article

Oren Litvin, Helen C. Causton, Bo-Juen Chen, et al. (2009). Modularity and interactions in the genetics of gene expression. Proceedings of the National Academy of Sciences, 106(16), 6441-6446. https://doi.org/10.1073/pnas.0810208106

Modularity and interactions in the genetics of gene expression

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