Chapter

Dawn of the genomic age for asthma

Ian M Adcock

in Landmark Papers in Allergy

Published on behalf of Oxford University Press

Published in print February 2013 | ISBN: 9780199651559
Published online April 2013 | e-ISBN: 9780191754241 | DOI: http://dx.doi.org/10.1093/med/9780199651559.003.0088

Series: Landmark Papers

Dawn of the genomic age for asthma

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Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log10 of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 – 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.

Chapter.  1728 words. 

Subjects: Public Health and Epidemiology ; Immunology ; Respiratory Medicine and Pulmonology

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