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Genome-wide analysis of transcript isoform variation in humans

Nature Genetics volume 40, pages 225231 (2008) | Download Citation

Abstract

We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternative splice site use, intron retention), differential 5′ UTR (initiation of transcription) use, and differential 3′ UTR (alternative polyadenylation) use. These results demonstrate that the regulatory effects of genetic variation in a normal human population are far more complex than previously observed. This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility.

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Acknowledgements

The authors would like to thank D. Serre, T. Pastinen, E. Harmsen and H. Zuzan for helpful discussions and D. Sinnett for technical assistance. This work is supported by Genome Canada, Genome Québec and the Canadian Institutes of Health Research (CIHR). T.J.H. is the recipient of a Clinician-Scientist Award in Translational Research by the Burroughs Wellcome Fund and an Investigator Award from CIHR. J.M. is a recipient of a Canada Research Chair.

Author information

Affiliations

  1. Department of Human Genetics, McGill University, 740 Dr. Penfield, Room 7210, Montréal, Québec H3A 1A4, Canada.

    • Tony Kwan
    • , David Benovoy
    • , Christel Dias
    • , Thomas J Hudson
    • , Rob Sladek
    •  & Jacek Majewski
  2. McGill University and Génome Québec Innovation Centre, 740 Dr. Penfield, Room 7210, Montréal, Québec H3A 1A4, Canada.

    • Tony Kwan
    • , David Benovoy
    • , Scott Gurd
    • , Cathy Provencher
    • , Thomas J Hudson
    • , Rob Sladek
    •  & Jacek Majewski
  3. Division of Hematology-Oncology, Research Centre, Sainte-Justine Hospital, Montréal, Québec H3T 1C5, Canada.

    • Patrick Beaulieu
  4. Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College Street, Suite 800, Toronto, Ontario M5G 1L7, Canada.

    • Thomas J Hudson

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Corresponding author

Correspondence to Jacek Majewski.

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DOI

https://doi.org/10.1038/ng.2007.57

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