GENOME-WIDE SEARCH FOR ASTHMA SUSCEPTIBILITY LOCI IN A FOUNDER POPULATION

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heteroge neous. To identify genes that influence asthma and asthma-associated p henotypes, we conducted a genome-wide screen in the Hutterites, a reli gious isolate of European ancestry. A primary sample of 361 individual s and a replication sample of 292 individuals were evaluated for asthm a phenotypes according to a standardized protocol. A genome-wide scree n has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi(2) test and t he transmission-disequilibrium test, we identified 12 markers in 10 re gions that showed possible linkage to asthma or an associated phenotyp e (likelihood ratio P < 0.01), Markers in four regions (5q23-31, 12q15 -24.1, 19q13 and 21q21) showed possible linkage in both the primary an d replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24 .2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility allel es at many loci may influence asthma phenotypes and that these suscept ibility alleles are likely to be common polymorphisms in the populatio n.