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Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma

Nature Genetics volume 34, pages 181–186 (2003)Cite this article

Abstract

Atopic or immunoglobulin E (IgE)-mediated diseases include the common disorders of asthma, atopic dermatitis and allergic rhinitis1. Chromosome 13q14 shows consistent linkage to atopy and the total serum IgE concentration2,3,4,5,6. We previously identified association between total serum IgE levels and a novel 13q14 microsatellite (USAT24G1; ref. 7) and have now localized the underlying quantitative-trait locus (QTL) in a comprehensive single-nucleotide polymorphism (SNP) map. We found replicated association to IgE levels that was attributed to several alleles in a single gene, PHF11. We also found association with these variants to severe clinical asthma. The gene product (PHF11) contains two PHD zinc fingers and probably regulates transcription. Distinctive splice variants were expressed in immune tissues and cells.

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Figure 1: LD map of the locus associated with atopy.
Figure 2: Domain architectures of SETDB2, PHF11 and related proteins, drawn approximately to scale.
Figure 3: Expression of PHF11.

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Acknowledgements

We thank D. Gordon for support and advice, the people of Busselton and the many individuals who helped with their clinical testing and the subjects in the other panels of families for their participation. The study was funded by the Wellcome Trust and the National Asthma Campaign. Individuals with severe asthma were recruited with support from the Asmarley Trust.

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Author notes

  1. Nicholas I Leaves and Gavin G Anderson: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Youming Zhang, Nicholas I Leaves, Gavin G Anderson, John Broxholme, Richard Holt, Pauline Edser, Sumit Bhattacharyya, Gonçalo Abecasis, Lon Cardon, Melanie White, Richard Mott, Roger Cox, Miriam F Moffatt & William O C M Cookson

  2. Department of Human Anatomy and Genetics, Medical Research Council Functional Genetics Unit, University of Oxford, UK

    Chris P Ponting

  3. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

    Andy Dunham, John Burton, Lucy Matthews & Mark Ross

  4. Department of Thoracic Medicine, National Heart and Lung Institute, London, UK

    Ian M Adcock, Louise Pulleyn & Peter J Barnes

  5. Great Ormond Street Hospital and the Institute for Child Health, London, UK

    John I Harper

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Correspondence to William O C M Cookson.

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The University of Oxford holds a patent protecting the diagnostic and therapeutic consequences of the research described in the paper. Commercialization of the patent may result in financial benefits to the authors affiliated with University of Oxford.

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Zhang, Y., Leaves, N., Anderson, G. et al. Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet 34, 181–186 (2003). https://doi.org/10.1038/ng1166

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