Fine-scale mapping of type I allergy candidate loci suggests central susceptibility genes on chromosomes 3q, 4q and Xp

Background:  Type I allergy globally affects an increasing number of individuals with the consequence of considerable personal morbidity and socio-economic costs. Identification of disease susceptibility genes would render enormous medical perspectives in terms of improved diagnosis, treatment and prevention. Like for other complex disorders, achievement of the knowledge necessary depends on confirmation of reported genomic candidate regions. Methods:  We performed a two-stage fine-scale linkage analysis in 11 selected candidate regions on chromosome 3p, 3q, 4p, 4q, 5q, 6p, 9p, 12q, 12qter, 18q and Xp. We analysed 97 polymorphic markers in 424 individuals from 100 sib-pair families and evaluated the data for five phenotypes: Allergic asthma, atopic dermatitis, allergic rhinitis and total and specific immunoglobulin E. Results:  The highest maximum likelihood scores (MLS) were obtained on chromosomes 3q (MLS = 2.69), 4p (MLS = 2.34), 4q (MLS = 2.75), 6p (MLS = 2.22), 12qter (MLS = 2.15) and Xp (MLS = 2.23). All five phenotypes showed MLS ≥ 2 in one or more of the candidate regions. Conclusions: Susceptibility genes in the 3q, 4q and Xp regions may play a central role in the inheritance of allergic disease, as positive results were obtained for all five phenotypes in these three regions.