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Cis-acting variation in the expression of a high proportion of genes in human brain

Human Genetics volume 113, pages 149–153 (2003)Cite this article

Abstract

Much of the genetic component of human phenotypic diversity, including susceptibility to disease, is proposed to be the result of cis-acting influences on gene expression. If this hypothesis is correct, it implies that cis-acting regulatory variation is a common phenomenon. However, direct evidence in support of this view is scarce. We have applied highly quantitative measures of allele-specific expression in order to screen an average of 19 informative subjects (range 8–26) for the presence of common cis-acting influences on the expression of 15 genes by using RNA derived from human brain. We found that, in seven of the 15 assayed genes, at least one individual exhibited relative differences in allelic expression of 20% or more and, in one gene (DTNBP1), allelic expression differences exceeded 50%. These results suggest that cis-acting variation in gene expression commonly occurs in native tissue and hence provide empirical support for the hypothesis that this is potentially an important mechanism underlying human phenotypic diversity.

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Acknowledgements

We are grateful to the Department of Clinical Neuroscience at the Karolinska Institute (Stockholm, Sweden), to the Stanley Medical Research Institute (Bethesda, USA) and to the MRC London Neurodegenerative Diseases Brain Bank (UK) for donating brain tissue. This work was funded by the Medical Research Council (UK).

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  1. Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK

    Nicholas J. Bray, Paul R. Buckland, Michael J. Owen & Michael C. O'Donovan

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  1. Nicholas J. Bray
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  2. Paul R. Buckland
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  3. Michael J. Owen
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  4. Michael C. O'Donovan
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Correspondence to Michael C. O'Donovan.

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Bray, N.J., Buckland, P.R., Owen, M.J. et al. Cis-acting variation in the expression of a high proportion of genes in human brain. Hum Genet 113, 149–153 (2003). https://doi.org/10.1007/s00439-003-0956-y

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  • DOI: https://doi.org/10.1007/s00439-003-0956-y

Keywords

  • Allelic Expression
  • Allele Ratio
  • Differential Allelic Expression
  • Stanley Medical Research Institute
  • Detectable Polymerase Chain Reaction Product