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Epistatic and Environmental Control of Genome-Wide Gene Expression

Published online by Cambridge University Press:  21 February 2012

Timothy P. York ,
Michael F. Miles ,
Kenneth S. Kendler ,
Colleen Jackson-Cook ,
Melissa L. Bowman  and
Lindon J. Eaves
Timothy P. York*
Affiliation:
Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Human Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America. [email protected]
Michael F. Miles
Affiliation:
Departments of Pharmacology/Toxicology, Neurology and the Center for Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Kenneth S. Kendler
Affiliation:
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Colleen Jackson-Cook
Affiliation:
Department of Human Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Melissa L. Bowman
Affiliation:
Departments of Pharmacology/Toxicology, Neurology and the Center for Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Lindon J. Eaves
Affiliation:
Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Human Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
*
*Address for correspondence: Timothy P. York, Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, PO Box 980003, Richmond, VA 23298-0003, USA.

Abstract

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All etiological studies of complex human traits focus on analyzing the causes of variation. Given this complexity, there is a premium on studying those processes that mediate between gene products and cellular or organismal phenotypes. Studies of levels of gene expression could offer insight into these processes and are likely to be especially useful to the extent that the major sources of their variation are known in normal tissues. The classical study of monozygotic (MZ) and dizygotic (DZ) twins was employed to partition the genetic and environmental influences in gene expression for over 6500 human genes measured using microarrays from lymphoblastoid cell lines. Our results indicate that mean expression levels are correlated about .3 in monozygotic (MZ) and .0 in dizygotic (DZ) twins suggesting an overall epistatic regulation of gene expression. Furthermore, the functions of several of the genes whose expression was most affected by environmental effects, after correction for measurement error, were consistent with their known role in mediating sensitivity to environmental influences.

Type
Articles
Information
Twin Research and Human Genetics , Volume 8 , Issue 1 , 01 February 2005 , pp. 5 - 15
Copyright
Copyright © Cambridge University Press 2005