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Intra- and inter-individual genetic differences in gene expression

Mark J. Cowley¹, Chris J. Cotsapas¹, Rohan B. H. Williams², Eva K. F. Chan¹, Jeremy N. Pulvers¹, Michael Y. Liu¹, Oscar J. Luo¹, David J. Nott³, & Peter F. R. Little¹

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1. School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
2. The Clive and Vera Ramaciotti Centre for Gene Function Analysis, The University of New South Wales, Sydney, NSW, Australia
3. School of Mathematics and Statistics, The University of New South Wales, Sydney, NSW, Australia

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Document Type:

Manuscript

Date:

Received 15 April 2008 01:17 UTC; Posted 15 April 2008

Subjects:

Genetics, Bioinformatics

Tags:

• gene expression
• genetic variation
• genetical genomics
• Genetics
• tissue
• mouse
• microarray

Abstract:

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Cowley, Mark, Cotsapas, Chris, Williams, Rohan, Chan, Eva, Pulvers, Jeremy, Liu, Michael, Luo, Oscar, Nott, David, and Little, Peter. Intra- and inter-individual genetic differences in gene expression. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1799.1> (2008)

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