Once linkage is confirmed in complex genetic disorders such as asthma or clinical allergic disease, identification of the actual gene is a complex process, although significant progress has been made during the last decade (Fig. 5). Fine-mapping studies include further clinical analyses and additional statistical analyses using techniques such as linkage disequilibrium and molecular and physical mapping with detection of mutations. It needs to be determined whether single mutations have a major effect on genetic susceptibility to asthma or whether, even within a major gene, there are multiple common sequence variants. Clearly, multiple genes influence development and expression of asthma, which is expected given the frequency of the disease and the failure to detect a strong major gene effect from initial family studies. Several regions of the genome have been identified for susceptibility loci to asthma and BHR. Future research will be focused in five major areas: (1) completion of genome-wide screens in different populations, (2) replication of previously reported linkages, (3) development of multilocus models to investigate the role of multiple susceptibility loci, (4) fine mapping of all the regions of interest, and (5) candidate-gene association studies. Determining the specific role of each gene in the development of asthma and BHR and correlations of phenotype to genotype will become important areas of research. These combined genetic, molecular, and clinical studies will lead to improved therapies and better techniques for early diagnosis of these disorders. By understanding the basic genetic mechanisms that lead to the development of allergy and asthma, new therapeutic interventions can be developed that modify the development and clinical progression of these disorders.
ASJC Scopus subject areas
- Immunology and Allergy