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Linkage of atopic dermatitis to chromosomes 4q22, 3p24 and 3q21

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Abstract

Atopic dermatitis (AD) is a common, itchy skin disease of complex inheritance characterized by dermal and epidermal inflammation. The heritability is considerable and well documented. To date, four genome scans have examined the AD phenotype, showing replicated linkage at 3p26-22, 3q13-21 and 18q11-21. Our previous AD scan showed evidence of linkage to loci at 3p and 18q, and furthermore at 4p15-14. In order to further investigate the genetic basis of AD, we collected and analysed a new Danish family sample consisting of 130 AD sib pair families (555 individuals including 295 children with AD). AD was diagnosed after clinical examination, AD severity was scored and specific IgE was determined. A linkage scan of chromosome 3, 4 and 18 was performed using 91 microsatellite markers. Linkage analyses were performed of dichotomous phenotypes and semi-quantitative traits including the AD severity score. We analysed the novel AD sample alone and together with the previously examined sample. AD severity showed a maximum Z-score of 3.7 at 4q22.1 suggesting the localization of a novel gene for AD severity. A maximum MOD score of 4.6 was obtained at 3p24 for the AD phenotype, providing the first significant linkage of AD at this locus. A maximum MLS score of 3.3 was obtained at 3q21 for IgE-associated AD, and evidence of linkage was also obtained at 3p22.2-21.31, 3q13, 4q35, and 18q12. The results presented should provide a firm basis for gene-targeting studies of AD and related disorders.

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Abbreviations

AD:

Atopic dermatitis

LOD:

Logarithm of odds

MLS:

Maximum likelihood score

NIgE:

Number of positive IgEs

IAD:

IgE-associated AD

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Acknowledgments

We thank the families for participating in the project. The study was supported by grants from The Faculty of Health Sciences, University of Aarhus, The Aarhus University Research Foundation, ALK Abello, The Danish Lung Association, The Danish Asthma-Allergy Association, the Ville Heise, the Hørslev, the Mimi and Victor Larsen, the Aage Bang, the Ellen Pedersen, the Marie Dorthea and Holger From, Haderslev, and the Augustinus Foundation.

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Authors and Affiliations

  1. Institute of Human Genetics, University of Aarhus, The Bartholin Building, Wilhelm Meyers Allé, 8000, Århus C, Denmark

    Ulla Christensen, Steffen Møller-Larsen, Mette Nyegaard, Annette Haagerup, Anne Hedemand, Thomas Juhl Corydon & Anders D. Børglum

  2. Department of Paediatrics, Skejby Sygehus, Aarhus University Hospital, Århus, Denmark

    Annette Haagerup

  3. Department of Clinical Biochemistry and Genetics, Odense University Hospital, Odense, Denmark

    Charlotte Brasch-Andersen & Torben A. Kruse

  4. Department of Dermatology, Aarhus University Hospital, Århus, Denmark

    Mette Deleuran

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  1. Ulla Christensen
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  2. Steffen Møller-Larsen
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  3. Mette Nyegaard
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Correspondence to Anders D. Børglum.

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Christensen, U., Møller-Larsen, S., Nyegaard, M. et al. Linkage of atopic dermatitis to chromosomes 4q22, 3p24 and 3q21. Hum Genet 126, 549–557 (2009). https://doi.org/10.1007/s00439-009-0692-z

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  • DOI: https://doi.org/10.1007/s00439-009-0692-z

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