Genome-Wide Search for Asthma Genes

In addition to important environmental factors, it is now well established that genetic factors contribute significantly to the development of asthma and atopy, accounting for between 30 and 60% of the predisposition (1 -3 ). This genetic predisposition is likely to result from the inheritance of a multiple number of polymorphic or mutant genes (4 ). Over the past decade, numerous researchers have conducted genetic linkage and/or association studies that aimed to identify such genes. These two types of studies are fundamentally different. A linkage study compares the inheritance pattern of the disease phe-notype to the inheritance pattern of a particular genetic marker in pedigrees, looking for coinheritance, and thus linking that particular marker locus to the disease. The association study, on the other hand, identifies candidate genes by comparing particular gene variant (allele) frequency in cases and controls, and therefore implicating that particular allele in the predisposition to the disease. Detecting genetic linkage usually indicates the presence of a gene within a genetic distance of approx 10 centimorgans (cM ) around the linked locus. Genetic association tends to operate within a much shorter genetic distance (1 cM ), but this distance varies, depending on the structure of the study population (relating to the ancestor founder effect).