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Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy

Genes & Immunity volume 7, pages 169–178 (2006)Cite this article

Abstract

A genome-wide screen for asthma and atopy susceptibility alleles conducted in the Hutterites, a founder population of European descent, reported evidence of linkage with a short tandem repeat polymorphism (STRP) within the type I interferon (IFN) gene cluster on chromosome 9p21. The goal of this study was to identify variation within the IFN gene cluster that influences susceptibility to asthma and atopic phenotypes. We screened approximately 25 kb of sequence, including the flanking sequence of all 15 functional genes and the single coding exon in 12, in Hutterites representing different IFNA-STRP genotypes. We identified 78 polymorphisms, and genotyped 40 of these (in 14 genes) in a large Hutterite pedigree. Modest associations (0.003<P<0.05) with asthma, bronchial hyper-responsiveness (BHR), and atopy were observed with individual variants or genes, spanning the entire 400 kb region. However, pairwise combinations of haplotypes between genes showed highly significant associations with different phenotypes (P<10−5) that were localized to specific pairs of genes or regions of this cluster. These results suggest that variation in multiple genes in the type I IFN cluster on 9p22 contribute to asthma and atopy susceptibility, and that not all genes contribute equally to all phenotypes.

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Acknowledgements

We acknowledge Harvey Dytch, Emma Thompson, and D'Anne Duncan for technical assistance. This work was supported by NIH Grants HL56399 and HL66533.

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Author notes

  1. A Chan

    Present address: Department of Pediatrics, Weill Medical College, Cornell University, New York, NY, USA

  2. D L Newman

    Present address: Department of Biological Sciences, Rochester Institute of Technology, Rochester, NY, USA

  3. A Chan and D L Newman: These authors contributed equally.

Authors and Affiliations

  1. Department of Human Genetics, The University of Chicago, Chicago, IL, USA

    A Chan, D L Newman, A M Shon, D H Schneider, S Kuldanek & C Ober

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  1. A Chan
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Correspondence to C Ober.

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Chan, A., Newman, D., Shon, A. et al. Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy. Genes Immun 7, 169–178 (2006). https://doi.org/10.1038/sj.gene.6364287

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