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Natural variation in human gene expression assessed in lymphoblastoid cells

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Abstract

The sequencing of the human genome has resulted in greater attention to genetic variation among individuals, and variation at the DNA sequence level is now being extensively studied. At the same time, it has become possible to study variation at the level of gene expression by various methods. At present, it is largely unknown how widespread this variation in transcript levels is over the entire genome and to what extent individual differences in expression level are genetically determined. In the present study, we used lymphoblastoid cells to examine variation in gene expression and identified genes whose transcript levels differed greatly among unrelated individuals. We also found evidence for familial aggregation of expression phenotype by comparing variation among unrelated individuals, among siblings within families and between monozygotic twins. These observations suggest that there is a genetic contribution to polymorphic variation in the level of gene expression.

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Figure 1: Scatter plot of variance in expression level between individuals and between replicates for 813 genes.
Figure 2: Genomic locations and functions of genes with highly variable expression level.
Figure 3: The expression levels measured using microarrays for five highly variable genes in 35 individuals.
Figure 4: Variance in expression level for five genes.

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Acknowledgements

We thank W.J. Ewens for discussion and A. Bruzel, K. Ewens and H.H. Kazazian for comments. This work was supported by grants from the U.S. National Institutes of Health (to V.G.C. and R.S.S.) and from the W.W. Smith Endowed Chair in Pediatric Genomics (to V.G.C.).

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Authors and Affiliations

  1. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Vivian G. Cheung, Laura K. Conlin & Kuang-Yu Jen

  2. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Vivian G. Cheung, Kuang-Yu Jen & Richard S. Spielman

  3. The Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA

    Vivian G. Cheung, Teresa M. Weber, Melissa Arcaro & Michael Morley

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  1. Vivian G. Cheung
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  2. Laura K. Conlin
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  3. Teresa M. Weber
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  4. Melissa Arcaro
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  5. Kuang-Yu Jen
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  7. Richard S. Spielman
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Correspondence to Vivian G. Cheung.

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Cheung, V., Conlin, L., Weber, T. et al. Natural variation in human gene expression assessed in lymphoblastoid cells. Nat Genet 33, 422–425 (2003). https://doi.org/10.1038/ng1094

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