The Hereditary Basis of Allergic Diseases

Allergic diseases are complex and involve a range of environmental factors interacting with a susceptible genotype. The familial clustering of diseases, such as asthma and hay fever, has been recognised for over two centuries, but identification of the genetic basis to this had to await the molecular biological revolution. Estimates of the contribution that genetic factors make to asthma susceptibility range from 35% to 70%. For the majority of allergic diseases, segregation analysis has not identified a consistent Mendelian pattern of inheritance, which, when combined with multiple phenotypes and environmental interactions, has made identifying candidate genes especially difficult and, at times, controversial. Part of the difficulty has been lack of agreement over phenotype definitions, reduced power of studies to predict linkage and association, and, importantly, lack of true heterogeneity between populations. Despite these difficulties, the last decade has witnessed enormous progress in this field.

Contenu

Heredity of allergy and asthma 1.- Genome scans for asthma.- The role of founder populations in mapping complex disease genes: Studies in the South Dakota Hutterites.- Genetic regulation of specific IgE responsiveness.- Genetic variation at the HLA and TCR loci and the development of allergy and asthma.- Chromosome 11q13, FccRI13 and atopic asthma.- Genetic regulation of interleukin-13 production.- The role of interleukin-9 and the interleukin-9 receptor gene candidates in asthma.- Genetics of the nitric oxide synthetic pathway in asthma.- Genetic regulation of leukotriene production and activity.- Genetics of asthma severity.