The genomic origins of asthma

Abstract

Lung function tracks from the earliest age that it can be reliably measured. Genome wide association studies suggest that most variants identified for common complex traits are regulatory in function and active during fetal development. Fetal programming of gene expression during development is critical to the formation of a normal lung. An understanding of how fetal developmental genes related to diseases of the lungs and airways is a critical area for research. This review article considers the developmental origins hypothesis, the stages of normal lung development and a variety of environmental exposures that might influence the developmental process: in utero cigarette smoke exposure, vitamin D and folate. We conclude with some information on developmental genes and asthma.

Keywords: Asthma; Asthma Genetics.

Figure 1. Stages of Human Lung Development

This figure from Kajekar and colleagues depicts the known histologic stages of human fetal lung development.(76)

Figure 2. Novel Developmental Growth Stage Identified by Genomics

In this figure from Kho et al., the transcriptome profile of the 38-sample developing human fetal lung time series is show in the first two principal components . While age correlates well with PC1, inflection points in PC2 indicate a novel molecular transition at day 94, which is independent of histologic stage.(13)

Figure 3. Cotinine Distribution in Human Fetal Lung Tissue

This histogram from Vylidahl and colleagues, demonstrates the distribution of cotinine, a known nicotine metabolite, in human fetal lung tissue samples.(41)

Figure 4. Tracking of Lung Function Growth

This figure from the Harvard Six Cities Study, this plots FEV₁ against height (surrogate for age) with each blue dot representing a repeated measure of FEV₁ for a given individual. Lung function tracks along percentile curves over time.(77)