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Genetics of gene expression surveyed in maize, mouse and man

Abstract

Treating messenger RNA transcript abundances as quantitative traits and mapping gene expression quantitative trait loci for these traits has been pursued in gene-specific ways. Transcript abundances often serve as a surrogate for classical quantitative traits in that the levels of expression are significantly correlated with the classical traits across members of a segregating population. The correlation structure between transcript abundances and classical traits has been used to identify susceptibility loci for complex diseases such as diabetes1 and allergic asthma2. One study recently completed the first comprehensive dissection of transcriptional regulation in budding yeast3, giving a detailed glimpse of a genome-wide survey of the genetics of gene expression. Unlike classical quantitative traits, which often represent gross clinical measurements that may be far removed from the biological processes giving rise to them, the genetic linkages associated with transcript abundance affords a closer look at cellular biochemical processes. Here we describe comprehensive genetic screens of mouse, plant and human transcriptomes by considering gene expression values as quantitative traits. We identify a gene expression pattern strongly associated with obesity in a murine cross, and observe two distinct obesity subtypes. Furthermore, we find that these obesity subtypes are under the control of different loci.

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Figure 1: Murine gene expression quantitative trait loci (eQTL) distributions and the molecular basis for fat pad mass (FPM) in a murine F2 cross.
Figure 2: Cis-acting eQTL identified for several DNA polymorphisms known to induce transcription polymorphisms.
Figure 3: Clinical QTL (cQTL) for obesity-related traits localize together with eQTL.
Figure 4: Genes with no overall correlation with respect to expression demonstrate interesting patterns of genetic interaction.

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Acknowledgements

Rosetta Inpharmatics is a wholly owned subsidiary of Merck & Co., Inc.

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Correspondence to Eric E. Schadt or Stephen H. Friend.

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Stephen Friend is a Senior Vice President of Merck Research Laboratories.

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Schadt, E., Monks, S., Drake, T. et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003). https://doi.org/10.1038/nature01434

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