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. 2005 Jan 5:5:1.
doi: 10.1186/1471-2466-5-1.

Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families

Janine Altmüller  1 , Corinna Seidel, Young-Ae Lee, Sabine Loesgen, Dieter Bulle, Frank Friedrichs, Heidemarie Jellouschek, Julika Kelber, Angela Keller, Antje Schuster, Michael Silbermann, Wolfgang Wahlen, Peter Wolff, Gerhard Schlenvoigt, Franz Rüschendorf, Peter Nürnberg, Matthias Wjst
Affiliations

Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families

Janine Altmüller et al. BMC Pulm Med. .

Abstract

Background: Asthma is a complex genetic disease with more than 20 genome-wide scans conducted so far. Regions on almost every chromosome have been linked to asthma and several genes have been associated. However, most of these associations are weak and are still awaiting replication.

Methods: In this study, we conducted a second-stage genome-wide scan with 408 microsatellite markers on 201 asthma-affected sib pair families and defined clinical subgroups to identify phenotype-genotype relations.

Results: The lowest P value for asthma in the total sample was 0.003 on chromosome 11, while several of the clinical subsets reached lower significance levels than in the overall sample. Suggestive evidence for linkage (p = 0.0007) was found for total IgE on chromosomes 1, 7 and again on chromosome 11, as well as for HDM asthma on chromosome 12. Weaker linkage signals could be found on chromosomes 4 and 5 for early onset and HDM, and, newly described, on chromosome 2 for severe asthma and on chromosome 9 for hay fever.

Conclusions: This phenotypic dissection underlines the importance of detailed clinical characterisations and the extreme genetic heterogeneity of asthma.

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Figures

Figure 1
Figure 1
Multipoint linkage results for all traits. Chromosomes are arranged with increasing numbers with orientation from p-ter to q-ter. Distance is given in centimorgans (cM) on a linear scale. A = asthma all, B = asthma German families, C = extrinsic asthma, D = HDM RAST positive, E = HDM SPT positive, F = severe asthma, G = early onset asthma, H = winter-type, I = summer-type, J = LnIgE continuous, K = LnLgE categorical.
See this image and copyright information in PMC

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