New approaches to understanding the genetics of asthma.

Several key conditions that are necessary to identify disease susceptibility genes in common diseases such as asthma are now available, including (1) increasingly comprehensive genomic information on gene location, genomic structure, and sequence variants, from the Human Genome Project (and from other species); (2) better understanding of the biologic functions of relevant genes and inflammatory and immunity pathways important in asthma; (3) newer high throughput and accurate technologies for DNA sequencing and SNP genotyping; (4) improved statistical methods for analyzing genetic data from families and populations; and (5) availability of methods to characterize function of sequence variants and study biologic responses. Collectively, these conditions will allow the prioritization of candidate genes based on available knowledge of map position and biologic relevance; obtain genomic structure of these genes; and study sequence variants in these genes in populations to facilitate the identification of genes that are important in the development and expression (severity) of asthma and associated phenotypes. Although, it is still a labor-intensive and expensive project to identify susceptibility genes in common diseases such as asthma, the new techniques that are now being used will greatly facilitate gene mapping. The techniques discussed in this article include genome-by-genome analysis in family data, such as those listed in Box 2. This analysis has already been shown to be a powerful too in mapping genes for another common disease (prostate cancer) with interesting preliminary results for asthma. Second, the use of man-mouse homology mapping that has proven very useful in cardiovascular studies is beginning to be applied to asthma and related phenotypes. finally with new available technology, genome-wide screens using very dense SNP maps are now a reality and a significant new development in family linkage and case-control association studies. In summary, these new approaches should be considered in designing studies to detect genes that are important in asthma and allergy.