Research
Expression analysis of asthma candidate genes during human and murine lung development
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* Corresponding author: Erik Melén erik.melen@ki.se
1 Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
2 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
3 Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
4 Children's Hospital Informatics Program, Boston, MA, USA
5 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA
6 Division of Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA
7 Division of Neonatology and Center for Pediatric Biomedical Research, University of Rochester, Rochester NY, USA
8 Partners Center for Personalized Genetic Medicine, Boston, MA, USA
Respiratory Research 2011, 12:86 doi:10.1186/1465-9921-12-86
Published: 23 June 2011Abstract
Background
Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function.
Objective
To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma.
Methods
Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6.
Results
In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. NOD1, EDN1, CCL5, RORA and HLA-G. Among the asthma genes identified in genome wide association studies, ROBO1, RORA, HLA-DQB1, IL2RB and PDE10A were differentially expressed during human lung development.
Conclusions
Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.