Gene Mapping in Asthma-Related Traits

In asthma, as in many other common multifactorial diseases, the identification of the susceptibility genes has been challenging because consistent results at the genome-wide significance level have been scarce. So far, genome-wide scans have been reported in 17 study populations. By means of genome-wide linkage and hierarchical association analysis, six positional candidate genes (ADAM33, PHF11, DPP10, GPR154, HLA-G , and CYFIP2 ) for asthma-related traits have been cloned. The interactions of the proteins encoded by these genes and the biological relevance of these signaling pathways in the development of asthma are still poorly understood. Also, the disease mechanisms resulting from the genetic variance in the genes identified remain largely unknown. Although this information is gradually accumulating, we can examine the statistical robustness of each genetic finding in combination with the limited data available on the functional properties of the corresponding proteins to estimate the strengths and weaknesses in the chains of evidence.